FitSugar

Get in Gear: Strider Hydration Waistpack

FitSugar — Tue, 24 Jul 2007 14:30:00 -0700

This hot weather makes exercising outdoors tough. I used to go for a run and then come back and drink water, but because I'm sweating so much, I need to rehydrate while I workout.

One of my new favorite finds is this water waistpack known as Strider made by Ultimate Direction.

It is a waistpack so obviously you wear it around your waist, and the straps are adjustable so you can get it to fit as snug as you like it. The water bottle fits right into the curve of your lower back and the little zippered pouch rests on your left hip. The small amount of weight from the water bottle pressing on my lower back feels really comfortable.

It comes with a water bottle and the pack is so lightweight, I hardly feel it when I'm running or bike riding. The tiny pouch is 8 inches long, so it's big enough to fit some money, keys, cellphone, and a pack of tissues (or whatever other small items you like to have when exercising outside).

You can order it online from Rei.com for $30. It comes in black, as shown, or sage gray.

Get in Gear: Ultimate Direction Access 2x

FitSugar — Wed, 11 Apr 2007 10:15:00 -0700

Especially now that the weather is getting warmer, it is really important to keep hydrated on long walks, runs or hikes. The problem is, most of us don't want to deal with carrying the water in our hands and a backpack does not always make for a comfortable outing.

The Ultimate Direction Access 2x ($27.95) water bottle carry features two
insulted bottle holsters and 20 oz. bottles, an ultra wicking hydrophilic interlock back panel for maximum ventilation with anti-microbial finish against skin and a zippered storage pocket. Which means you can bring a snack or pick me up (such as Sport Beans) along too. The pack is much less bulky than a lot of water bottle holsters out there, which means you'll be able to really go the distance.

Want it? Then buy it from RunningWarehouse.com. How much water should you be drinking anyway? Find out with the Fit Calculator.

Attention deficit hyperactivity disorder

FitSugar — Wed, 08 Oct 2008 17:35:28 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration (FDA) approved lisdexamfetamine (Vysvanse), a new stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). The active ingredient in lisdexamfetamine is similar to dextroamphetamine, the drug used in Dexedrine and Adderall.

Drug Warning

In 2007, the FDA instructed the manufacturers of all ADHD drugs to include drug warning labels describing the risks for heart and psychiatric side effects. Doctors should carefully evaluate patients for any risk factors. Reports have linked ADHD drugs to sudden death in patients with serious heart problems. There is also a slightly increased risk for auditory hallucinations, paranoia, and manic behavior even in patients with no history of psychiatric problems. The FDA warning applies to all stimulant ADHD drugs and to the non-stimulant drug atomoxetine (Strattera).

Ritalin Can Stunt Growth

After 3 years of methylphenidate (Ritalin) treatment, children are about an inch shorter and 6 pounds lighter than their peers who do not take this drug, according to a 2007 study in the Journal of the American Academy of Child and Adolescent Psychiatry.

ADHD Improves Over Time

ADHD symptoms may improve over time regardless of the treatment approach, indicates a 2007 study in the Journal of the American Academy of Child and Adolescent Psychiatry. Researchers found that medication, behavioral therapy, or a combination of the two all helped produce improvement after 3 years. There appeared to be no significant difference between children who took medication and those who did not.

Neurofeedback May Help ADHD

Neurofeedback (also known as biofeedback) is a non-drug treatment that may help improve attention and behavior problems associated with ADHD. This treatment approach involves teaching children to control their brain wave activity.

Introduction

According to the U.S. National Institute of Mental Health, attention deficit hyperactivity disorder (ADHD) is a legitimate psychologic condition.

ADHD is a syndrome generally characterized by the following symptoms:

Inattention
Distractibility
Impulsivity
Hyperactivity

Some experts categorize ADHD into three subtypes:

Behavior marked by hyperactivity and impulsivity, but not inattentiveness
Behavior marked by inattentiveness, but not hyperactivity and impulsivity
A combination of the above two

There is some debate over these criteria. Some argue the condition is over-diagnosed. Others say it's underdiagnosed. (See Difficulties in Identifying Children with ADHD later in this article.) One-third of cases are accompanied by learning disabilities and other neurologic or emotional problems, making an ADHD diagnosis particularly difficult. It is likely that the term attention-deficit hyperactivity disorder will eventually give way to subgroups of problems that include some of these general symptoms.

In the United States, about 4.7 million children ages 3 - 17 have been diagnosed at some point with ADHD. This accounts for 7.4% of all American children in this age range.

ADHD is a genuine disorder, but it is telling that the U.S. accounts for 90% of worldwide prescriptions for stimulants for ADHD. It is not known whether this reflects a real increase in ADHD, or a better ability to recognize it. Some say it may be an indication of a culture that places excessive value on normalcy and academic achievement at the expense of more frequent diagnoses.

Symptoms of ADHD usually occur before the age of 7. Studies indicate that ADHD symptoms in preschool children with ADHD do not differ significantly from older children.

The classic ADHD symptoms do not always adequately describe the child's behavior, nor do they describe what is actually happening in the child's mind. Some experts are focusing on deficits in "executive functions" of the brain to understand and describe all ADHD behaviors. Such impaired executive functions in ADHD children can cause the following problems:

Inability to hold information in short-term memory
Impaired organization and planning skills
Difficulty in establishing and using goals to guide behavior, such as selecting strategies and monitoring tasks
Inability to keep emotions from becoming overpowering
Inability to shift efficiently from one mental activity to another

Hyperactivity. The term hyperactive is often confusing since, for some, it suggests a child racing around non-stop. A boy with ADHD playing a game, for instance, may have the same level of activity as another child without the syndrome. But when a high demand is placed on the ADHD child's attention, his brain motor activity intensifies beyond the levels of the other children. In a busy environment, such as a classroom or a crowded store, ADHD children often become distracted and react by pulling items off the shelves, hitting people, or spinning out of control into erratic, silly, or strange behavior.

Impulsivity and Temper Explosions. Even before the "terrible twos," impulsive behavior is often apparent. The toddler may gleefully make erratic and aggressive gestures, such as hair pulling, pinching, and hitting. Temper tantrums, normal in children after age 2, are usually exaggerated and not necessarily linked to a specific negative event in the life of an ADHD child. One of the most painful events a parent may experience is an abrupt and aggressive attack that may occur after cuddling a young ADHD child. Often this reaction seems to be caused not by anger, but by the child's apparent inability to endure overstimulation or displays of physical affection.

Attention and Concentration. ADHD children are usually distracted and made inattentive by an overstimulating environment (such as a large classroom). They are also inattentive when a situation is low-key or dull. Some experts believe that certain parts of the brain in ADHD children may be underactive, so the children fail to be aroused by nonstimulating activities. In contrast, they may exhibit a kind of "super concentration" to a highly stimulating activity (such as a video game or a highly specific interest). Such children may even become over-attentive -- so absorbed in a project that they cannot modify or change the direction of their attention.

Impaired Short-Term Memory. Many experts now believe that an essential feature in ADHD, as well as in learning disabilities, is an impaired working (also called short-term) memory. People with ADHD can't hold groups of sentences and images in their mind long enough to extract organized thoughts. They are not necessarily inattentive. Instead, a patient with ADHD may be unable to remember a full explanation (such as a homework assignment), or unable to complete processes that require remembering sequences, such as model building. In general, children with ADHD are often attracted to activities (television, computer games, or active individual sports) that do not tax the working memory, or produce distractions. Children with ADHD have no differences in long-term memory compared with other children.

Inability to Manage Time. Studies suggest that children with ADHD have difficulties being on time and planning the correct amount of time to complete tasks. (This may coincide with short-term memory problems.) In one study, although children with probable ADHD were able to self-report many ADHD symptoms, they tended to believe they used their time wisely, in contrast to reports by their teacher.

Lack of Adaptability. ADHD children have a very difficult time adapting to even minor changes in routines, such as getting up in the morning, putting on shoes, eating new foods, or going to bed. Any shift in a situation can precipitate a strong and noisy negative response. Even when they are in a good mood, they may suddenly shift into a tantrum if met with an unexpected change or frustration. In one experiment, ADHD children could closely focus their attention when directly cued to a specific location, but they had difficulty shifting their attention to an alternative location.

Hypersensitivity and Sleep Problems. ADHD children are often hypersensitive to sights, sounds, and touch. They usually complain excessively about stimuli that seem low key or bland to others. Sleeping problems usually occur well after the point when most small children sleep through the night. In one study, 63% of children with ADHD had trouble sleeping.

A. Either 1 or 2 should be present:

1. Should have 6 or more of the following symptoms of inattention, persisting for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:

Often fails to give close attention to detail, makes careless mistakes

Often has difficulty sustaining attention in tasks or play

Often does not seem to listen when spoken to directly

Often does not follow through and fails to finish tasks

Has difficulty organizing tasks and activities

Avoids or dislikes tasks requiring sustained mental effort

Often loses things necessary for tasks or activities

Is often easily distracted by extraneous stimuli

Is often forgetful in daily activities

2. Should have 6 or more of the following symptoms of hyperactivity-impulsivity that lasts for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:

Often fidgets or squirms when sitting

Has difficulty remaining seated when required to do so

Often runs about or climbs excessively in inappropriate situations

Has difficulty playing quietly

Is often "on the go"

Often talks excessively

Often blurts out answers to questions before they have been completed

Has difficulty waiting for his or her turn

Often interrupts or intrudes on others

Note: Patients with A1 symptoms are diagnosed with ADHD, predominantly inattentive type. Those with A2 are diagnosed with ADHD, predominantly hyperactive-impulsive type. Those with both A1 and A2 are diagnosed as ADHD, combined-type.

B. Onset of some symptoms before the age of 7. However, children with the inattentive subtype are not often diagnosed until they are above 7 years of age.

C. Symptoms occur in two or more settings. For example, at home and at school.

D. Clear evidence of significant impairment in social or academic functioning.

E. Not caused by a pervasive developmental disorder, schizophrenia, or any other psychotic disorder, and is not better accounted for by another mental disorder, including anxiety or depression.

Source: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Ed. (Text Revision). Washington, DC: 2000.

Risk Factors

ADHD is most often diagnosed in boys. However, there is some evidence that it is underdiagnosed in girls. Until recently, all major studies were conducted using boys as subjects. Important studies on girls with ADHD are now underway. A major study reported that girls with the condition experience the same multiple impairments as boys do.

Although ADHD is primarily thought of as a childhood disorder, diagnoses of attention-deficit disorder in adults are on the rise. Methylphenidate (Ritalin) was prescribed for nearly 800,000 adults in the U.S. in 1997, nearly three times the number in 1992. As of 2005, experts estimated that ADHD affects about 4.1% of adults ages 18 - 44 years in a given year.

How Is ADHD Identified in Adults?

Research suggests that ADHD affects 2 - 6% of the adult population, assuming that one- to two-thirds of cases persist into adulthood. ADHD in adults always occurs as a continuum of the childhood condition. Adult-onset symptoms are likely due to other factors. Diagnosing adult ADHD can be a difficult problem since hyperactivity typically wanes as children get older, while attention and organizational problems may develop in older people. Some experts believe, then, that the number of adults with ADHD is underestimated.

A rating scale using four factors may be useful in identifying adults with ADHD:

Inattention and memory problems. (Examples: losing or forgetting things, being absent-minded, not finishing things, misjudging time, depending on others for order, having trouble getting started, changing jobs or projects in the middle.)
Hyperactivity and restlessness. (Examples: always being on the go, fidgety, easily bored, taking risks, liking active and fast paced jobs and activities, such as being a sales representative or stockbroker.)
Impulsivity and emotional instability. (Examples: saying things without thinking first, interrupting others, being annoying to others, easily frustrated, easily angered, having unpredictable moods, driving recklessly, having high relationship and job turnover.)
Problems with self worth. (Examples: Avoids new challenges, appears confident to others but not to oneself.)

Doctors use adult reports of their childhood behaviors and experiences when searching for clues for a diagnosis. Interestingly, the disorder seems to be distributed equally between adult women and men.

How Serious Is Attention Deficit Disorder in Adults?

Accompanying Emotional, Personality, and Learning Disorders. Between 19 - 37% of adults with ADHD have depression or bipolar disorder. Between 25 - 50% have an anxiety disorder. Bipolar disorder plus ADHD, in fact, may be very difficult to differentiate from ADHD alone in adults.

Accompanying Learning Disorders. About 20% of adults with ADHD have learning disorders, usually dyslexia and auditory processing problems. These problems should be considered in any treatment plan.

Effect on Work. Compared to adults without ADHD, those with the condition tend to reach lower educational levels, earn less money, and be fired more often. In fact, one article reported that by the time they are in their 30s, about 35% of ADHD adults are self-employed.

Substance Abuse. About 1 in 5 adults with ADHD also contend with substance abuse. Studies indicate that adolescents with ADHD are twice as likely to smoke cigarettes as their peers who do not have ADHD. Cigarette smoking during adolescence is a risk factor for the development of substance abuse in adulthood.

Sleep Disorders. Sleep disorders, especially restless legs syndrome and sleep apnea, are common in adults and children with ADHD. Sleep apnea is a disorder in which a person temporarily stops breathing during sleep, perhaps hundreds of times. In most cases the person is unaware of it, although sometimes they awaken and gasp for breath. It is usually accompanied by snoring. One report suggested that treating sleep apnea in adults with both conditions may help reduce ADHD symptoms. [For more information, see In-Depth Report #65: Sleep apnea.]

Causes

Brain Structures. Research using advanced imaging techniques shows there is a difference in the size of certain parts of the brain in children with ADHD compared to children who do not have ADHD. The areas showing change include the prefrontal cortex, the caudate nucleus and globus pallidus, and the cerebellum:

The prefrontal cortex is located in the front of the brain. It is thought to be the brain's command center. It regulates the brain’s ability to block certain responses. Numerous imaging studies have indicated that the prefrontal cortex of the brain in people with ADHD may be less active than in those without the disorder.
The caudate nucleus and globus pallidus, located near the center of the brain, speed up or stop orders coming from the prefrontal cortex. In some reports, these areas have been smaller than average in young children with ADHD, but tended to become normal as the children got older. Abnormalities in these areas may impair a person's ability to stop certain actions, resulting in the impulsivity typical of people with ADHD.
The cerebellum is the area above the brain stem. This area helps control muscle tone and balance, and synchronizes muscle activity. This has been found to be smaller in children with ADHD compared to those without the condition.

Brain Chemicals. Abnormal activity of certain brain chemicals in the prefrontal cortex may contribute to ADHD. The chemicals dopamine and norepinephrine are of special interest. Dopamine and norepinephrine are neurotransmitters, or chemical messengers, that affect both mental and emotional functioning. They also play a role in the "reward response." This response occurs when a person experiences pleasure in response to certain stimuli (such as food or love). Studies suggest that increased levels of the brain chemicals glutamate, glutamine, and GABA -- collectively called Glx -- interact with the pathways that transport dopamine and norepinephrine.

Nerve Pathways. Another area of interest is a network of nerves called the basal-ganglia thalamocortical pathways. Abnormalities along this neural route have been associated with ADHD, Tourette syndrome, and obsessive-compulsive disorders, all of which share certain symptoms.

Genetic factors may play the most important role in ADHD. The relatives of ADHD children (both boys and girls) have much higher rates of ADHD, antisocial, mood, anxiety, and substance abuse disorders than the families of non-ADHD children. A study reported that 90% of children with a diagnosis of ADHD shared it with their twin.

Genetic Factors Regulating Dopamine and Advantages in Early Man. Most of the research on the underlying genetic mechanisms targets the neurotransmitter dopamine. Variations in genes that regulate specific dopamine receptors have been identified in a high proportion of people with addictions and ADHD. Such genes have been associated with novelty seeking and extroversion. Some experts theorize that the genetic variants may have first appeared thousands of years ago, and affect as many as half of ADHD children. Furthermore, the genetic variations may have offered some benefits to their early carriers. In such people, a genetic predilection for novelty-seeking and risk-taking may have supplied an advantage in reproduction, mating, hunting, and achieving dominance.

Genetic Resistance to Thyroid Hormone. About 50% of adults and 70% of children with a genetic resistance to thyroid hormone, essential for normal brain development, have ADHD. People who have this condition appear to have a more severe form of ADHD. The thyroid disorder is not a common cause of ADHD. Only those with a family history of thyroid disease are at risk.

Infant malnutrition is a strong risk indicator of ADHD. Even if children receive enough food later on, infants who suffer from malnutrition may develop behavior problems, the most prevalent being attention-deficit disorder.

Deficiencies in Zinc and Essential Fatty Acids. Several dietary factors have been researched in association with ADHD, including sensitivities to certain food chemicals, deficiencies in fatty acids (compounds that make up fats and oils) and zinc, and sensitivity to sugar.

Some studies have found an association between deficiencies in certain fatty acids and ADHD. Other research reports an association between zinc deficiencies and ADHD. Zinc aids in the breakdown of fatty acids, which affects dopamine, the neurotransmitter likely to be involved with ADHD.

No clear evidence has emerged, however, that implicates any of these nutritional factors in ADHD.

Research suggests that prenatal exposure to tobacco, alcohol, environmental lead, and other toxins may increase the risk for ADHD and conduct disorders.

Diagnosis

Important factors for making a diagnosis of attention-deficit hyperactivity disorder (ADHD) include:

Children between ages 6 - 12 should first be evaluated for ADHD if they show symptoms of inattention, hyperactivity, impulsivity, academic underachievement, or behavior problems in at least two settings. Such behaviors should have been harmful for the child academically or socially for at least 6 months.
The child should meet the official symptom guidelines.
A diagnosis requires detailed reports by parents or caregivers. It should be noted that a mother's description of her child's behavior is a very accurate and reliable guide for diagnosing ADHD. Parents should not be shy about insisting on further evaluation if their experience does not match a doctor's single observation of their child.
Guidelines for primary care doctors emphasize the importance of obtaining direct evidence from the classroom teacher or other school-based professionals about the child's symptoms and their duration, and evidence of functional impairment in the school setting.
The child should be assessed for accompanying conditions (such as learning difficulties).

No laboratory or imaging tests exist to reliably diagnose ADHD. A diagnosis relies only on behavioral symptoms and ruling out other disorders. Many experts believe that the disorder is both over- and underdiagnosed. Diagnosis of attention-deficit hyperactivity disorder is difficult for some of the following reasons:

Factors Leading to the Over-Diagnosis of ADHD:

The popularity methylphenidate (Ritalin) has encouraged some parents and teachers to pressure doctors into prescribing this standard ADHD drug for children who are aggressive or who have poor grades. Often with careful testing many of these children do not meet the criteria for the illness. Children may have other diagnoses, other behavioral or emotional problems, or no problems at all.
Other factors that may contribute to misdiagnosis include children who are young for their grade and therefore socially and intellectually immature, and social and economic problems such as single parent households.

Factors Leading to the Under-Diagnosis of ADHD:

Some evidence suggests that many girls with ADHD may go underdiagnosed. Research indicates that girls with ADHD are often inattentive but not hyperactive or impulsive. In fact, older girls with ADHD tend to have social problems due to withdrawal and internalized emotions, showing symptoms of anxiety and depression. The inattentive subtype, in any case, may first show up in older children and adolescents.
Doctors may fail to diagnose children with ADHD because they often behave normally in the quiet doctor's office where there are no distractions to trigger symptoms. In addition, doctors may be unfamiliar with how to diagnose the condition.
In spite of the fact that there seems to be no differences in response to treatment among population groups, African-American, Hispanic, and Asian children with ADHD are half as likely to be diagnosed and treated as Caucasian children. By high school, the racial disparity increases to the level that the medication rate for blacks is one-fifth of that for whites.

The doctor will first require a detailed history of the child's behavior. Doctors will match this against a standardized checklist to define the disorder.

The parents should describe the following:

Specific problems, beginning as early as possible, they have encountered during the child's development -- school reports are very helpful
Sibling relationships
Recent life changes
A family history of ADHD
Eating habits
Sleep patterns
Speech and language development
Any problems during the mother's pregnancy or during delivery
Any history of medical or physical problems, particularly allergies, chronic ear infections, and hearing difficulties

The health professional will want to know how the parents handle different situations, and may want to observe them interacting with the child.

The child should also be given a general physical examination to determine if any medical conditions are present. The child should be given a hearing test to rule out hearing abnormalities as a source of behavioral problems.

Various tests are available to test neurologic, intellectual, and emotional development problems. Most involve learning and problem solving tasks that help define the particular areas that are most disabling. Blood or other laboratory tests are currently recommended only if the doctor suspects lead toxicity or other medical problems.

Although some doctors use a trial of a psychostimulant (usually Ritalin) to facilitate diagnosis, most experts strongly recommend against this method of diagnosis, because it is not always accurate. An improvement in symptoms is considered suggestive of ADHD, while in non-ADHD children the stimulant often increases agitation and hyperactivity. Many children and adults without the disorder have a similar response, and such a diagnostic trial may lead to unnecessary prescriptions of this drug.

Other Disorders Associated with ADHD

Several disorders may mimic or accompany attention-deficit disorder. ADHD exists alone in only about one-third of children. Many professionals object to the use of the single term "attention-deficit hyperactivity disorder" to encompass such a wide spectrum of behaviors, which they believe should be categorized into subgroups. Many of these problems require other modes of treatment and should be diagnosed separately, even if they accompany ADHD.

Attention-deficit disorder can appear without hyperactivity, in which case the child's primary symptoms are distractibility and an inability to persist in tasks.

About 14% of children diagnosed with ADHD also have oppositional-defiant disorder (ODD). The most common symptom for this disorder is a pattern of negative, defiant, and hostile behavior toward authority figures that lasts more than 6 months. In addition to displaying inattentive and impulsive behavior, these children demonstrate aggression, have frequent temper tantrums, and display antisocial behavior. A significant number of children with ODD also have anxiety disorders and depression, which should be treated separately. Many children who develop ODD at an early age go on to develop conduct disorder.

Some children with ADHD also have conduct disorder, which describes a complex group of behavioral and emotional disturbances seen in children. It includes aggression towards people and animals, destruction of property, deceitfulness, lying, or stealing, and general violation of rules.

Pervasive developmental disorder (PDD) is rare and usually marked by autistic-type behavior, hand-flapping, repetitive statements, slow social development, and speech and motor problems. If a child who has been diagnosed with ADHD does not respond to treatment, the parents might inquire about PDD, which often responds to antidepressants. Some children with PDD may also benefit from stimulants.

Children with ADHD often have difficulties with tasks that involve listening or hearing. Research is indicating that symptoms of the two disorders often overlap but may actually be two distinct disorders. Hearing problems themselves may cause ADHD symptoms.

Children diagnosed with attention-deficit disorder may also have bipolar disorder, commonly called manic depression. Indications of this problem include episodes of depression and mania (with symptoms of irritability, rapid speech, and disconnected thoughts), sometimes occurring at the same time. [For more information, see In-Depth Report #66: Bipolar disorder.] Both disorders often cause inattention and distractibility and may be difficult to distinguish, particularly in children. Children with mania and ADHD may have more aggression, behavioral problems, and emotional disorders than those with ADHD alone. In some cases, ADHD in children or adolescents can even be a marker for an emerging bipolar disorder. The primary way to differentiate bipolar disorder from ADHD is by the presence of a manic or hypomanic episode, which occurs in patients with bipolar disorder but not with ADHD. Most children with bipolar will also respond to the drug valproate, which does not typically work for ADHD in children.

Anxiety disorders commonly accompany ADHD. Obsessive-compulsive disorder is a specific anxiety disorder that shares many characteristics with ADHD and may share a genetic component. Young children who have experienced traumatic events, including sexual or physical abuse or neglect, exhibit characteristics of ADHD, including impulsivity, emotional outbursts, and oppositional behavior.

Sleep disorders or disturbances are very common with ADHD patients. Insomnia is common. In addition, specific sleep disorders -- restless legs syndrome and sleep-disordered breathing -- have been identified with hyperactivity and conduct disorder.

Restless Legs Syndrome (RLS). Some experts believe RLS and periodic limb movement disorder are strongly associated with ADHD in some children. One theory is that the two are linked by a common mechanism. The disorders have much in common, including poor sleep habits, twitching, and the need to get up suddenly and walk about frequently. They may even be genetically linked. For example, both have been associated with lower levels of dopamine in the brain, which is associated with faulty motor control, a common problem in both disorders.

Sleep-Disorder Breathing and Sleep Apnea. Some research has shown an association between mild symptoms of ADHD and sleep-disordered breathing, including snoring and obstructive sleep apnea in children and adults. Treating the sleep-related breathing disorders may improve the attention disorder in some children. (One study indicated that such problems are unlikely to be associated with children with moderate to severe ADHD.) [For more information, see In-Depth Report #65: Sleep apnea.]

Tourette Syndrome and Other Genetic Disorders. Several genetic disorders cause symptoms resembling ADHD, including fragile X and Tourette syndrome. About 50% of those with Tourette syndrome also have ADHD, and some of the treatments are similar.

Other Medical Conditions. A number of medical conditions, including hyperthyroidism and vision problems, can produce ADHD-like symptoms.

Lead. Children who ingest even low amounts of lead may manifest symptoms similar to those of ADHD. A child may be easily distractible, disorganized, and have trouble thinking logically. The major cause of lead toxicity is exposure to leaded paint, particularly in homes that are old and in poor repair.

Complications

More than half of children with attention-deficit disorder have accompanying disorders, including anxiety, depression, and conduct disorders. Children with ADHD who experience anxiety or depression are also more likely to suffer from low self-esteem.

Anti-Social Behavior. Even if these emotional disorders are absent in childhood, the ADHD child's relationship with others is volatile, and they are often unhappy from a very young age. Research indicates that any boy or girl with ADHD, particularly an aggressive child, has trouble getting along with others, and is less liked by his or her peers.

Children with the inattentive subtype of ADHD are more likely to be picked on and to spend time alone.
Children with the combined subtypes tend to have different problems. Boys with ADHD are less likely than others to empathize with people in difficult circumstances. A best friend can turn into an enemy overnight when, for example, a boy with ADHD does not perceive his friend's fearful response to over-aggressive roughhousing and fails to let up. The next day the child with ADHD has forgotten the event; the ex-friend hasn't. When a child with ADHD hurts someone, the child either may go into a state of denial or blame himself excessively. As ostracism, fear, and ridicule from peers persist from year to year, the unstable behavior, originally neurologic, becomes emotionally based. Unless this cycle is broken, serious adult problems can evolve.

Substance Abuse in Young People. Studies consistently report that young people with ADHD -- in particular those with conduct or mood disorders -- have a higher than average risk for substance abuse and that it starts in younger ages. In one study, for example, by age 11 nearly 20% of children with ADHD had tried smoking cigarettes, drinking alcohol, or both. Biologic factors associated with ADHD may make these individuals susceptible to substance abuse. Many of these young people are self-medicating their condition. In fact, according to a major analysis, Ritalin or other stimulants used to treat ADHD may help protect such patients against substance abuse. (Boys with ADHD and conduct disorder, however, still face a high risk for substance abuse. Girls with ADHD and emotional disorders may also still have a higher risk.)

High-Risk Behavior. Impulsivity in young people with ADHD can certainly cause them to take chances before thinking them through, putting them in situations where the consequences become clear only after the action has been taken. Children with ADHD and high levels of aggression are at higher risk for delinquent behavior in adolescents and criminal activity in adulthood. However, children with ADHD who are not aggressive have a lower and even normal risk for dangerous activities. Even in aggressive children with ADHD, close parental attention and early treatment can limit the risk considerably.

Although speech and learning disorders are common in children with ADHD, the disorder does not affect intelligence. People with ADHD span the same IQ range as the general population.

Many children with ADHD are underachievers, and half are held back in school at least once. Some evidence suggests that inattention may be a major factor in low academic performance in these children. About 20% also have reading difficulties, and 60% have serious handwriting problems. Adults with ADHD are also at very high risk for these conditions.

Some research suggests that ADHD persists in one- to two-thirds of those diagnosed with the condition in childhood. Many researchers describe the pattern of ADHD as they would a chronic illness, with remission and periods of worsening.

The time and attention needed to deal with a child with ADHD can change internal family relationships and have devastating effects on parents and siblings.

Effect on Parents. Studies indicate that any intervention for the child must include the parents. Parents who are responsive to their child in a positive way can help reduce the chances for oppositional behaviors. But it can be very difficult. A child with ADHD is wonderful one day and terrible the next, for no apparent reason. The parent can feel betrayed and hurt, and believe they have no control over their child. Parents must protect themselves and their child by establishing tough but kind rules about where their space ends and the child's begins. The are many effects on parents:

Mothers generally get the brunt of the emotional and physical abuse that a child with ADHD can produce.
Parents may have to give up on the idea of an immaculate house and a hot meal every night. Parents must learn that striving for perfection is among the most counterproductive goals to pursue in raising a child with ADHD, or any child.
Parents must face the hostility and anger of other parents and see their own child rejected. It is very easy to fall into an emotional black hole, and feel alone, inadequate, and helpless.
Marriages are often stressed to the breaking point because of exhaustion and disagreements between the husband and wife on how to respond to the child.

Effect on Siblings. Siblings of children with ADHD have particular difficulties, and are also at risk for psychologic impairment, depression, drug abuse, and language disorders. The non-ADHD sibling does not have the control a parent does in the management of the ADHD child's behavior and is very likely to feel alienated and alone. Children without ADHD are often victimized by siblings with ADHD who may be demanding or bullying.

A sibling who does not receive attention in their own right may begin to imitate undesirable behaviors or to act out negatively in other ways. It is very important to make the brothers and sisters equally vital to the family's functioning. However, they should never be made to feel that their value in the family is as caregivers of the ADHD sibling.

Treatment

A combination of a psychostimulant, most commonly methylphenidate (Ritalin), and cognitive-behavioral therapy is proving to be the best option for treatment of children with ADHD. Although medication can be helpful during the initial years of treatment, some research indicates that the benefits of medication eventually wear off. It appears that for ADHD symptoms may improve naturally over time, regardless of the treatment approach.

Signs that ADHD may be easing include not having to adjust medication dosages during growth spurts, no deterioration when a drug dose is missed, or new abilities to concentrate during “drug holidays.” (School vacation times are a good period to test the effectiveness of temporarily stopping medication.) The American Academy of Child and Adolescent Psychiatry suggests that parents evaluate whether medication can safely be withdrawn when children with ADHD have been free of symptoms for at least 1 year. If a child’s condition worsens after medication withdrawal, the drug should be resumed.

Developing a Treatment Approach. The following guidelines may be useful in determining a treatment approach for children with ADHD:

Behavioral techniques, possibly including dietary changes, should be tried first, if possible.
If the symptoms are severe or do not respond, a trial using medication (usually psychostimulants), in conjunction with behavior modification therapy, is advisable.

Cognitive behavioral therapy (CBT) is often administered by mental health providers, with both primary care physicians and psychiatrists prescribing medications. Unfortunately, many children do not have access to behavioral therapies, either because of lack of time or available resources.

Specific Patient Populations. Unfortunately, such guidelines do not address the following specific patient groups:

There are no definite guidelines for treating preschool children with severe ADHD. Some parents have reported very good long-term results with behavioral interventions at this age.
There are no reliable guidelines on how to treat the inattentive subtype of ADHD, which might be more common in girls.
There are no defined treatments for ADHD patients with accompanying conditions, including impaired working memory and deficits in language processing.
There are no defined treatments for children with ADHD and accompanying emotional problems, such as bipolar or anxiety disorders. (There is some evidence, for example, that children with ADHD plus anxiety disorders do worse on psychostimulants.)

Determining a Medication Regimen. Doctors still have a difficult time predicting which medications will produce beneficial results, so treatment is individualized and performed on a trial and error basis, which requires close observation and cooperation between all participants. In developing an effective medication plan, the following steps may be helpful:

Before any drug is administered, a child should be given a thorough examination for any medical problems to be sure there are no medical conditions that interfere with the medication.
Both the doctor and the parents should be very clear about the specific behaviors they hope the medication will target.
The goal is to use the lowest possible dosage that produces improved behavior.
If an initial regimen doesn't work, changing the dosage, or changing to a different medication often brings improvement.
Frequent follow-up visits should be scheduled to assess the response and to detect possible side effects.

Arguments For and Against Psychostimulants. Many parents are very disturbed by the idea of putting their children on intensive stimulant drug regimens, possibly for years, particularly given the uncertainties in diagnosis and the negative publicity surrounding the use of these drugs. Although the decision to use these drugs should not be made lightly, the negative social and emotional effects of the disorder itself for many children with ADHD are far more severe and long-lasting than the use of these drugs. For some parents and children, medication seems like a miracle and can provide desperate families with a quality of life for which they had almost given up hope. Whether or not psychostimulants are used, children and families should understand that ongoing efforts around behavior control will be necessary.

Of great concern is the dramatic increase in prescriptions for psychostimulants among preschool children. Although low doses of methylphenidate (Ritalin) may help preschoolers (ages 3 - 5 years) with ADHD, the drug can cause considerable side effects in many children. These side effects include insomnia, nervousness, anxiety, loss of appetite and weight, and slowed growth. Children in one large study grew about an inch less and weighed about 6 pounds less than normal after 3 years of methylphenidate treatment. Doctors must carefully consider the risks versus benefits when prescribing ADHD drugs to preschoolers. Children who do receive these drugs need to be carefully monitored by their doctors.

Treatment for Adult ADHD. As with children, adults with ADHD are treated with a combination of medication and psychotherapy. For medication, stimulant drugs or the non-stimulant drug atomoxetine (Strattera) are usually first-line treatments, with antidepressants a secondary option. Atomoxetine is approved specifically for adults with ADHD. Adults who have heart problems or heart condition risk factors should be aware of the cardiovascular risks associated with ADHD medication. There have been ADHD medication-associated incidents of sudden death in patients with underlying serious heart problems, and reports of stroke and heart attack in adults with cardiac risk factors.

Research increasingly supports the view that interventions for the ADHD child must also include the parents if they are to be successful. Teachers and school officials should also be educated and involved in the process.

Parents who feel they have the most control over their child's situation experience the least psychological stress and depression. Parents who are responsive in a positive way also help reduce the chances for their child developing oppositional behaviors. But it can be very difficult, particularly for parents who have ADHD themselves. In fact, parents who have severe ADHD symptoms are less likely to respond to parent training programs unless they get help for themselves.

In addition to behavioral therapy for the child, family therapy may help ADHD children and their parents and siblings cope with the emotional conflicts that nearly always arise in the lifelong process of managing the condition. Separate psychological therapies for specific family members might be needed, particularly in light of the high incidence of psychiatric and other emotional problems in families with ADHD children.

Medications

Several types of medication are available to treat ADHD.

Psychostimulants are the primary drugs used to treat ADHD. Although these drugs stimulate the central nervous system, they have a calming effect on people with ADHD.

These drugs include:

Methylphenidate (Ritalin, Concerta, Metadate, Daytrana)
Dexmethylphenidate (Focalin)
Amphetamine-Dextroamphetamine (Adderall)
Dextroamphetamine (Dexedrine, Dextrostat)
Lisdexamfetamine (Vyvanse)

Pemoline (Cylert), another stimulant drug, was withdrawn from the U.S. market in 2005 after several reports of liver failure.

Methylphenidate and Dexmethylphenidate. Methylphenidate drugs (Ritalin, Metadate, Concerta, Daytrana) are the most commonly used psychostimulants for treating ADHD in both children and adults. Dexmethylphenidate (Focalin) is a similar drug. These drugs increase dopamine, a neurotransmitter important for cognitive functions such as attention and focus.

With the exception of Daytrana, all of these drugs are pills taken by mouth. Daytrana, approved in 2006, is the first skin patch drug for ADHD. A patch is applied to the hip each day and delivers a 9-hour dose of methylphenidate.

These drugs are available in short-acting and long-acting dosage forms. The short-acting forms need to be taken several times a day, including during school hours. As the drug wears off, a rebound effect can occur, and ADHD symptoms can intensify. For this reason, the long-acting dosage forms have become popular.

Amphetamine, Dextroamphetamine, and Lisdexamfetamine. Amphetamine-dextroamphetamine (Adderall), dextroamphetamine (Dexedrine, Dextrostat), and lisdexamfetamine (Vyvanse) work by blocking the reabsorption of the brain chemicals dopamine and norepinephrine. Side effects can include stomach problems and mood changes, including sadness, anxiety, and irritability.

Psychostimulant medications are associated with some significant risks. All ADHD stimulant drugs carry warnings that they should not be used by patients with structural heart problems or pre-existing heart conditions (high blood pressure, heart failure, or heart rhythm disturbances). These drugs have been associated with sudden death in children with heart problems. They have also been associated with sudden death, stroke, and heart attack in adults with a history of heart disease. In addition, these drugs may slightly increase the risk for auditory hallucinations, paranoia, and manic behavior even in patients who do not have a history of psychiatric problems. The FDA has directed manufacturers of ADHD medications to warn all patients taking these medicines of their potential cardiovascular and psychiatric risks.

Stimulant drugs may also:

Worsen behavior and thought disturbance in patients with a pre-existing psychotic disorder.
Cause a mixed or manic episode in patients who have both ADHD and bipolar disorder.
Increase aggressive behavior or hostility. Patients beginning stimulant drug treatment should be monitored for worsening of these behaviors.
Slow growth and weight gain in children. Children who take stimulant drugs should have their growth monitored. If they do not gain height or weight at a normal rate, they may need to stop taking the drug.

Side Effects. All stimulants have a number of side effects:

The most common side effects of any stimulant are nervousness and sleeplessness, although some parents have reported improved sleep patterns in their children after taking stimulants.
Tics or jerky, disordered movements occur in about 9% of children.
Other side effects include irritability, stomach pain, headache, depression, hair loss, and lack of spontaneity.

Symptoms of Overdose. Symptoms of overdose include changes in heart rhythm and rate, hypertension, confusion, breathing difficulties, sweating, vomiting, and muscle twitches. If they occur, parents should call the doctor immediately. Even among young people who abuse Ritalin, however, less than 1% experience severe side effects (rapid heart rate, hypertension), and outcomes are generally good. Side effects may be very severe, however, if Ritalin is overused and taken with other drugs. A 2006 study reported that over 3,000 people are treated in hospital emergency rooms due to side effects from ADHD drugs. Sixty-one percent of these visits involved accidental ingestion or overdose.

Concerns for Abuse. Studies on both animals and humans suggest that Ritalin lacks the properties that create addiction, particularly in doses used for treating ADHD. Although methylphenidates have properties similar to amphetamines, their drug levels rise very slowly in the brain at the oral doses given for ADHD. This slow rise prevents a so-called "high" and subsequent addiction to the drug. Some stimulant drugs, such as lisdexamfetamine, may pose a lower risk for abuse than others.

The primary danger for drug abuse from stimulants appears to occur in non-ADHD young people who purchase these drugs illegally. In one study, for instance, 16% of children with ADHD reported pressure from their fellow students to sell or give them their medication. While people ages 18 - 25 are more likely to use ADHD drugs for non-medical uses, children ages 12 - 17 are more likely to suffer adverse effects from medication misuse and to require treatment at an emergency room. If a child abuses another drug (alcohol, prescription medication) along with the ADHD medication, the chance for serious side effects is even greater.

Atomoxetine (Strattera) was the first non-stimulant approved for ADHD in children and the first treatment approved for adult ADHD. The drug works by increasing levels of both norepinephrine and dopamine, which are generally lower than normal in ADHD. The most common side effect is decreased appetite. A few cases of atomoxetine-associated liver injury have been reported, and the FDA has warned doctors that the drug should be discontinued at the first signs of jaundice or liver problems. Long-term effects, such as any impact on growth, are still unknown. Atomoxetine may cause suicidal thinking in children and adolescents, especially during the first few months of treatment. Parents should monitor children taking atomoxetine for any changes in mood or behavior, and immediately contact their doctor if changes occur.

Antidepressants are not FDA-approved for ADHD treatment, but may be helpful in certain circumstances. Because antidepressants appear to work about as well as behavioral therapy, doctors recommend that patients first try psychotherapy before using antidepressants.

Bupropion (Wellbutrin) and tricyclics are the types of antidepressants used for ADHD. Bupropion affects the reuptake of the serotonin, norepinephrine, and dopamine neurotransmitters. Side effects include restlessness, agitation, sleeplessness, headache, and stomach problems. Bupropion should not be used by patients who have a seizure disorder.

Tricyclics are an older type of antidepressant that are effective but have many side effects. Imipramine (Tofranil) and nortriptyline (Pamelor, Aventil) are the tricyclics most commonly prescribed for ADHD. A third tricyclic, desipramine (Norpramin) should only be used if patients are not helped by other tricyclics. (Desipramine has caused sudden death in some children and adolescents.)

Tricyclic antidepressants can cause disturbances in heart rhythm. Children should have an electrocardiogram when they first begin to take this drug, and after any dose increase.

[For more information, see In-Depth Report #8: Depression ].

Alpha-2 agonists stimulate the neurotransmitter norepinephrine, which appears to be important for concentration. They include clonidine (Catapres) and guanfacine (Tenex). They are used for Tourette syndrome and may be beneficial when other drugs have failed for ADHD children with tics or those whose primary symptoms are severe impulsivity and aggression. These drugs are mainly prescribed in combination with a stimulant.

These drugs have a number of side effects. Sedation is the most common. A clonidine skin patch, which gradually releases the medication, helps reduce the sedative effect. Because clonidine slows the heart down, it can have adverse effects in some children. Going off too quickly or missing doses can cause rapid heartbeats and other symptoms that may lead to severe problems. Doctors strongly recommend that no child be given this medication without a preliminary examination for heart problems, and no child with existing heart, kidney, or circulatory problems should take it.

Behavioral Management

Behavioral techniques for managing the child with ADHD are not intuitive for most parents and teachers. To learn them, caregivers may need help from qualified health care professionals or from ADHD support groups. At first, the idea of changing the behavior of a highly energetic, obstinate child is daunting. It is futile and damaging to try to force a child with ADHD to be like most children. It is possible, however, to limit destructive behavior and to instill a sense of self-worth that will help overcome negativity toward life, which is one of the great dangers of the disorder.

Bringing up a child with ADHD, like bringing up any child, is a process. No single point is ever reached where the parent can sit back and say, "That's it. My child is now OK, and I don't have to do anything more." The child's self worth will evolve with an increasing ability to step back and consider the consequences of an action and then to control that action before taking it. But this does not happen overnight. A growing child with ADHD is different from other children in very specific ways, presenting challenges at every age.

Setting Priorities for the Parent. Parents must first establish their own levels of tolerance. Some parents are easygoing and can accept a wide range of behaviors, while others cannot. To help a child achieve self-discipline requires empathy, patience, affection, energy, and toughness. Some tips to help the parents include:

Parents should prepare a list giving priority to those behaviors they think are the most negative, such as fighting with other children or refusing to get up in the morning. The least negative behaviors on the bottom of the list should be ignored temporarily or even permanently (refusing to wear anything but red T-shirts).
Certain odd behaviors that are not hurtful to the child or to others may be an indication of creative or humorous attempts to adapt (making up silly songs or drawing violent pictures). These should be accepted as part of the child's unique and positive development, even if they seem peculiar to the parent.
It is important to keep in mind that no one is a saint. Loving parents who occasionally lose their tempers will not damage their children forever. In fact, non-abusive open disapproval or dismay is far less destructive to both parent and child than harboring resentment beneath a false calm.

Establishing Consistent Rules for the Child. Parents must be as consistent as possible in their approach to the child, which should reward good behavior and discourage destructive behavior. Rules should be well-defined but flexible enough to incorporate harmless idiosyncrasies. It is very important to understand that children with ADHD have much more difficulty adapting to change than do children without the condition. (For example, the child should do homework every day but might choose to start it after a TV show or computer game.)

Managing Aggression. Some useful tips for managing aggression include:

Parents should try to give little attention to mildly disruptive behaviors that allow this energetic child to let off some harmless steam. The parent will also be wasting energy that will be needed when the negative behavior becomes destructive, abusive, or intentional.
The use of "time-out," isolating the child immediately for a short period of time, is an effective measure for allowing both the caregiver and the child to cool down. The child should immediately (and without emotion) be removed from a situation in which they are endangered or endangering others. The child should view time out as a way of cooling off and getting a distance on their behavior, not as isolation from others.
To channel physical aggression and impulsivity in the ADHD toddler, the parents must teach them to use verbal responses. (A parent may need to allow verbal responses that would be unacceptable in another child.)
When the ADHD child becomes older and if the verbal responses become intentionally abusive and socially undesirable, the parent must redirect this form of aggression into more acceptable activities, such as competitive one-on-one sports, energetic music, video games, or big colorful paintings. Competitive video games, such as sports games, may also be an option.
Sometimes a parent can anticipate situations when an ADHD child is likely to misbehave, but all too often the child explodes for no apparent reason. If the blow-up occurs in public, the parents should complete their activities and leave as quickly as possible.

Establishing a Reward System. Children with ADHD respond particularly well to reward systems. One study reported that they performed equally well when encouraged either by a direct reward for a correct response or with the use of a system called response-cost. With this system, the child is given the reward first and allowed to keep it if their behavior remains appropriate.

Some suggested tips for rewarding the ADHD child are:

Create charts with points or stars for good behavior or for completed tasks. It is important to give points for even simple positive behaviors, which may be taken for granted in other children (responding happily to a change in plans, changing an obscenity to a more acceptable expletive).
Rewards for any child can include playing a favorite game with the child, extending bedtime by an hour, or allowing an extra half-hour of TV.
Rewards of food or gifts should be used infrequently, if at all. They can create other problems, such as being overweight, having a bad diet, or making continuous demands for objects.
A reward system should rotate different types of rewards, because such children are easily bored.
Children with ADHD respond better with small rewards promised in the short-term than large rewards offered in the future. One approach that employs both short- and long-term rewards uses a system that gives the child points for specific positive behaviors. As the children accumulate points, they can use them for larger tangible rewards, such as a favorite video game or CD.
Rewards should be promised only when caregivers are fairly certain they can follow through. ADHD children respond with much greater frustration than non-ADHD children to disappointment, and are likely to have a strong (and noisy) negative reaction. A parent must remember that this response is part of the ADHD child's make-up and not necessarily in their control.

Improving Concentration and Attention. Research indicates that ADHD children perform significantly better when their interest is engaged. Parents should be on the lookout for activities that hold the child's concentration. Some options that may help an ADHD child to focus include:

Many ADHD children are particularly lured by the computer, which is a very promising tool. A number of non-violent computer games are available that offer problem-solving techniques using characters, narrative, and humor.
Swimming, tennis, and other sports that focus attention and limit peripheral stimuli are often appealing. ADHD children often do not do well with team sports, although they are interested. Children with ADHD are less likely to become distracted in sports that require constant alertness, such as football or basketball. In baseball, positions such as pitching or catching are preferable to the outfield, where attention easily wanders. Finding a coach that understands the child’s difficulties is very helpful.
Some experts are enthusiastic about martial arts, such as Tae Kwon Do, which can offer an appropriate and controlled emotional outlet, help to focus attention, and teach self-restraint, self-discipline, and tolerance. Care should be taken to select an instructor who makes such goals a priority.
Learning an instrument may be one of the best ways for an ADHD child to develop a more rhythmic and balanced sense of self. Music, even simply listening to it, is often very important for these children. (Parents may have to tolerate music that does not please them.)

Even if a parent is successful in managing the child at home, difficulties often arise at school. The ultimate goal for any educational process should be the happy and healthy social integration of the ADHD child with their peers.

Preparing the Teacher. Although teachers can expect at least one student in every classroom to have ADHD, there is currently little training that prepares them for managing these children. The teacher should be prepared for the certain behaviors in the child with ADHD:

Students with ADHD are often demanding, talkative, and highly visible.
Inattention is a major factor in low academic performance. It causes them to frequently forget homework or miss assignments. Children with ADHD often require frequent reminders or visual cues (such as posters) for rules and regulations. Having the child sit in the front of the classroom may be helpful for both increasing attention and reducing noisy activity.
Lack of fine motor control makes taking notes very difficult, and handwriting is often poor. Using a typewriter or computer can compensate for this. One useful skill that has helped some children is learning to type at an early age, around the third or fourth grade.
Rote memorization and math computation, which require following a set of ordered steps, are often difficult. (Children with ADHD may do better with math concepts.)
Many children with ADHD respond well to school tasks that are rapid, intense, novel, or of short duration (such as spelling bees or competitive educational games), but they almost always have problems with long-term projects where there is no direct supervision.

The Role of the Parent in the School Setting. The parent can help the child by talking to the teacher before the school year starts about their child's situation:

The first priority for the parent is to develop a positive, not adversarial, relationship with the child's teacher.
The parent must acknowledge the teacher's situation, for the teacher must deal not only with the ADHD child's behavior but also with the needs of all the other children.
Frequent brief and sympathetic conversations with the teacher can be helpful and can lead to coordination of efforts, particularly if they provide reciprocal information about progress or setbacks.
Finding a tutor to help after school may be helpful. It is not clear, however, if tutoring offers significant benefits for children whose academic problems stem from inattention unless it is structured specifically to address this problem.

Special Education Programs. The Individuals with Disabilities Education Act (IDEA) requires the school to identify and evaluate children who may need help and to provide special services. However, parents sometimes report pressure by the school to put their children on medication or force them into special classrooms without clear educational justification. The schools, in these cases, may be acting illegally.

High-quality special education can be extremely helpful in improving learning and developing a child's sense of self worth. Many families, however, may not have appropriate programs available for them. Programs vary widely in their ability to provide quality education. Parents must be aware of certain limitations and problems with special education:

Special education programs within the normal school setting often increase the child's feelings of social alienation.
If the educational strategy focuses only on abnormal behavior, it will fail to take advantage of the creative, competitive, and dynamic energy that often accompanies ADHD behavior.
There is no federally funded special education category specifically targeted to ADHD.

If, in fact, ADHD is as common as studies are indicating, the best approach may be to treat the syndrome as a variant of the norm and train teachers to manage these children within the context of a normal classroom.

Special programs are also required under the Rehabilitation Act and by the Americans with Disabilities Act (ADA) for students at institutions of higher learning. It is the student's responsibility, however, to inform the administration at their college or university that they need such services. Unfortunately, many college students are reluctant to do this, although such programs can provide important and beneficial assistance in improving their academic performance.

Other Treatments

A number of diets have been suggested for people with ADHD. Several well-conducted studies have failed to support dietary effects of sugar and food additives on behavior, except possibly in a very small percentage of children. Still various studies have reported behavioral improvement with diets that restrict possible allergens in the diet. Parents may want to discuss with their doctor implementing an elimination diet of certain foods that would not be harmful and that might help.

Food Allergies. Evidence suggests that children with behavioral difficulties may be sensitive to certain chemicals in foods. Studies vary widely, however, on how many cases of ADHD may be associated with sensitivities or allergies to food chemicals or additives, with results ranging widely from 5 - 62%. Among the suspected additives and foods that parents and studies report as inciting behavioral changes are the following:

Any artificial colorings (particularly yellow, red, or green)
Other chemical additives -- for example, BHT or BHA
Milk
Chocolate
Eggs
Wheat
Foods containing salicylates, including all berries, chili powder, apples and cider, cloves, grapes, oranges, peaches, peppers (bell & chili), plums, prunes, tomatoes

In one small study, 62% of children who were given only rice, turkey, pears, and lettuce to eat for 2 weeks experienced at least a 50% improvement in symptoms. Nevertheless, about a quarter of the children pulled out because they could not stick with the diet or they became ill.

Feingold Diet. The most well-known diet for ADHD is the Feingold diet, a salicylate- and additive-free diet, which requires rigorous vigilance over a child's eating habits. This diet also prohibits aspirin, which contains salicylates. Some parents report great success with this diet, although it may be difficult to impose. One study that reported the diets efficacy suggested that it might not provide enough nutritive value, although the diet provides a wide range of healthy foods to select from. It is certainly wise, in any case, to avoid food with artificial colors and flavors and to provide a healthy balance of fresh, natural foods.

Essential Fatty Acids. Omega-3 fatty acids, found in fatty fish and certain vegetable oils, are important for normal brain function and may have some benefits for people with ADHD. It is not clear if supplements of fatty acid compounds, such as docosahexaenoic acid (DHA) and eicosapentaneoic acid (EPA), provide any advantages.

Zinc. Zinc is important for the metabolism of certain neurotransmitters that play a role in ADHD, and deficiencies have been associated with some cases of ADHD. Long-term use of zinc, however, can cause anemia and other side effects in people without deficiencies and it has no effect on ADHD in these patients. In any case, testing for trace minerals, such as zinc, is not standard procedure when evaluating children suspected to have ADHD.

Sugar. Although parents often blame sugar for causing children to become impulsive or hyperactive, a number of studies strongly indicate that sugar plays no role in hyperactivity. One study reported, in fact, that ADHD children had fewer problems after a high-carbohydrate breakfast than after a high-protein one. Another reported that children actually moved more slowly after a high-sugar meal, suggesting the carbohydrates may have a sedative effect. (Still, it's probably always wise for any child to cut down on sugar.)

Techniques that use biologic or auditory feedback are proving to be effective tools for increasing children's attention -- a primary factor in low academic performance.

Neurofeedback. Neurofeedback is an approach that uses electronic devices to help the child control their own brain wave activity. Electrodes are pasted to the child's head and pick up signals from the brain. The child watches images, such as moving graphs, on a computer monitor that reflect the child's brain wave activity. Children are then taught certain high-level mental activities at the point when feedback information on the screen indicates that they are fully concentrating. Children usually attend forty 50-minute sessions, usually twice a week. Small studies have reported significant improvement in inattention, impulsivity, and response time.

Interactive Metronome and Musical Therapy. Interactive metronome uses feedback from sound to improve attention, motor control, and certain academic skills. In this technique study, children wear headphones and sensors on their hands and feet. They perform a number of exercises to a rhythmic computer-beat. Training sessions are completed in 3 - 5 weeks. Some small studies have reported improvement in attention, motor control, language processing, and behavior. (In support of this, some parents report that learning a musical instrument helped their children significantly.)

Procedures and Non-Drug Therapies. A number of alternative approaches are used for children and adults with mild ADHD symptoms. For example, daily massage therapy may help people with ADHD feel happier, fidget less, be less hyperactive, and focus on tasks. Other alternative approaches that may be helpful include relaxation training, meditation, and music therapy. Based on existing evidence, these treatments may be helpful for symptom management but are not proven to benefit the underlying disorder.

Natural Remedies. A number of parents resort to alternative remedies as an alternative to psychostimulants and other drugs. Small trials have found some herbs and supplements -- such as oral flower essence, ginkgo biloba, panax ginseng, melatonin, and pine bark extract (Pycnogenol) --may possibly have benefits for ADHD. Based on existing evidence, however, none can be recommended, particularly for children.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for attention-deficit disorders:

Melatonin. High doses of melatonin have been associated with an increased risk for seizures in children with existing neurologic disorders.
Gingko. The risk for side effects from gingko appear to be low, but there is an increased risk for bleeding and interaction with anti-clotting medications at high doses.
Ginseng. There have been contaminated forms of imported ginseng. Ginseng also has been associated with low blood sugar and a higher risk for bleeding. In addition, a great number of ginseng products have been found to contain little or no ginseng.

Resources

www.aap.org -- American Academy of Pediatrics
www.nimh.nih.gov -- National Institute of Mental Health
www.chadd.org -- Children and Adults with Attention-Deficit Disorder
www.add.org -- Attention Deficit Disorder Association
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.psych.org -- American Psychiatric Association
www.parentsmedguide.org -- Medication Guide for Treating ADHD
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.nichcy.org -- National Dissemination Center for Children with Disabilities
www.ncld.org -- National Center for Learning Disabilities
www.ldaamerica.org -- Learning Disabilities Association of America

References

Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect. 2006 Dec;114(12):1904-9.

Heinrich H, Gevensleben H, Strehl U. Annotation: neurofeedback - train your brain to train behaviour. J Child Psychol Psychiatry. 2007 Jan;48(1):3-16.

Jensen PS, Arnold LE, Swanson JM, et al. 3-year follow-up of the NIMH MTA study. J Am Acad Child Adolesc Psychiatry. 2007 Aug;46(:989-1002.

Nigg JT, Breslau N. Prenatal smoking exposure, low birth weight, and disruptive behavior disorders. J Am Acad Child Adolesc Psychiatry. 2007 Mar;46(3):362-9.

Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007 Jul;46(7):894-921.

Steiner H, Remsing L; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with oppositional defiant disorder. J Am Acad Child Adolesc Psychiatry. 2007 Jan;46(1):126-41.

Swanson JM, Elliott GR, Greenhill LL, et al. Effects of stimulant medication on growth rates across 3 years in the MTA follow-up. J Am Acad Child Adolesc Psychiatry. 2007 Aug;46(:1015-27.

Valera EM, Faraone SV, Murray KE, Seidman LJ. Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Psychiatry. 2007 Jun 15;61(12):1361-9. Epub 2006 Sep 1.

Wilens TE, Upadhyaya HP. Impact of substance use disorder on ADHD and its treatment. J Clin Psychiatry. 2007 Aug;68(:e20.

Williams JH, Ross L. Consequences of prenatal toxin exposure for mental health in children and adolescents: a systematic review. Eur Child Adolesc Psychiatry. 2007 Jun;16(4):243-53. Epub 2007 Jan 2.

Review Date:
12/27/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

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Immunizations

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights
Introduction
Diphtheria, Tetanus, and Pe...
Measles, Mumps, and Rubella...
Varicella-Zoster Virus (Chi...
Varicella-Zoster Virus (Shi...
Hepatitis A
Hepatitis B
Pneumococcal Pneumonia
Poliomyelitis
Viral Influenza
Haemophilus Influenzae Type...
Human Papillomavirus (HPV)...
Rotavirus
Smallpox
Other Vaccinations
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Vaccines

The Centers for Disease Control and Prevention now recommends that children receive 2 doses of the varicella-zoster (Chickenpox) vaccine: the initial vaccine between ages 12 - 15 months, and a booster between 4 - 6 years. Children aged 12 and older and adults who have not had the vaccine should receive 2 doses. Immunization guidelines were changed following research that indicated the effectiveness of the vaccine declines over time. A 2007 study indicated that children who were vaccinated 5 or more years earlier were 2.6 times more likely to have a moderate-to-severe breakthrough case of chickenpox than those who had been vaccinated more recently.
A study finds that the conjugate pneumococcal vaccine, which was introduced for children in 2000, has reduced hospital admissions for pneumonia in children under age 2 by about 39%. The vaccine has also caused hospital admissions to drop 26% among adults aged 18 - 39. Another study found that recurrent ear infections have fallen by 28% since the introduction of the vaccine.
In April 2007, the U.S. Food and Drug Administration approved the first vaccine against the avian flu virus. The avian flu vaccine is designed for people ages 18 - 64 who are at risk for exposure to the virus. The vaccine is given in 2 shots, spaced about 1 month apart. The U.S. government is stockpiling the vaccination in case of an avian influenza outbreak, but the vaccine is not available to the general public.
Research finds that the human papillomavirus (HPV) vaccine (Gardisil) is 100% effective against cervical, vaginal, and vulvar diseases caused by 4 types of HPV (6, 11, 16, and 18).

Introduction

Immunizations against childhood diseases have saved millions of lives. American vaccination rates are now at an all-time high. Disease and death from diphtheria, pertussis, tetanus, measles, mumps, rubella, and Haemophilus influenzae (H. influenzae) type b are at or near record lows. In adults, immunizations against influenza (the flu), pneumococcal pneumonia, hepatitis, and other ailments have likewise saved many lives and prevented many more cases of serious illness. A new vaccine has been shown to be highly effective for preventing the virus that leads to cervical cancer.

More than 70 bacteria, viruses, parasites, and other infectious microbes cause major human disease. Fortunately, vaccines are either available or being developed against many of them. With the advent of new or newly feared biological threats, emerging infections, and bacterial resistance to common antibiotics, immunizations are assuming an increasingly important role in maintaining the health of billions of people worldwide.

Immunizations (vaccinations) are given to initiate or augment resistance to an infectious disease. Immunizations provide a specialized form of immunity that provides long-lasting protection against specific antigens, which cause disease.

Routine Childhood Vaccines. Experts recommend that all children be routinely vaccinated against the following diseases:

Measles
Mumps
Rubella (German measles)
Diphtheria
Tetanus
Pertussis (whooping cough)
Poliomyelitis (polio)
Varicella (chickenpox)
Hepatitis B
Hepatitis A
H. influenzae type B (a cause of meningitis)
Influenza (children aged 6 - 59 months)
Pneumococcal disease
Meningococcal disease (for selected populations)
Rotavirus (children aged 6 - 32 weeks)

Many vaccinations are first given during infancy. Even premature infants can, in most cases, be given vaccinations on a normal schedule. There is even some evidence that doing so may offer some slight protection against sudden infant death syndrome. Note: These facts pertain to children in the United States. Children from other countries have not been well studied. Parents who adopt internationally may want to have their children's immunity assessed by a physician. Some evidence suggests that their medical records may not correctly reflect immunization status and that many adopted children, such as those from China, have not had many important vaccinations.

Click the icon to see an animation about vaccines.

Common Adult Vaccines. Vaccinations against the following disorders are also recommended routinely for certain adults:

Influenza (flu). Every year in high-risk adults under 49 and everyone over 50. When supplies are limited, as with the 2004 - 2005 flu season, the vaccine should be administered preferentially to adults only over age 65 and to individuals with heart disease, lung disease, and other significant chronic illnesses. Health care providers with direct patient contact, child care providers, and residents of long-term care facilities should also be vaccinated.
Pneumococcal pneumonia. One dose in high-risk adults under 64 and a first dose or a revaccination in everyone over 65.
Hepatitis A and B and Meningococcal vaccine. Given to high-risk individuals.
Tetanus. Adults need a booster shot every 10 years.
Measles, mumps, rubella. Typically given to adults under 56 who are unsure of their vaccination history. High-risk individuals may receive two doses.
Diphtheria and pertussis are now recommended with tetanus (Tdap vaccine) booster every 10 years until age 65.
Herpes zoster (shingles) vaccine. One dose for adults 60 and older.
Human papillomavirus (HPV). Three doses in young women aged 11 - 26.

Vaccines are currently taken by mouth (orally) or given by a shot (injection). Vaccines are usually made of one of two agents that cause the body to produce antibodies that attack a specific disease. A vaccine may contain:

A live but weakened virus. Live-virus vaccines provide longer immunity than inactivated ones, but they can cause serious infection in people with weakened immune systems and have also been associated with severe medical disorders in rare instances.
Inactivated bacteria, viruses, or toxoids. Inactivated vaccines are safe even in people with impaired immune systems.

Click the icon to see an image of antibodies.

The weakened or inactivated agent in the vaccine teaches the immune system to recognize the real, harmful substance and attack it when the person becomes exposed to the infection. The antibodies remain in the body, preventing future illness from the disease. This is called immunity.

Combination Vaccines. The American Academy of Pediatrics and American Academy of Family Physicians recommend that health care providers use, whenever possible, combination vaccines instead of individual components. Combination shots containing vaccines for diphtheria, tetanus, and pertussis (DTaP), and for measles, mumps, and rubella (MMR), have been available for years. New combinations that cover up to 5 vaccinations are being developed and are proving to be safe and well tolerated in infants as young as 2 months. For example, one that combines DTaP, hepatitis B, and the polio vaccine (Pediarix) has been approved and should simplify the immunization process.

There is some concern that increasing use of combinations may reduce the potency of some of the vaccines. Some parents are also worried about increased side effects. Studies to date, however, are reporting that combinations are effective and safe.

Passive Immunity. Another form of protection against disease is called passive immunity. This approach uses immune globulin, which are blood products containing antibodies. Immune globulin is generally used for people who cannot be vaccinated, when immediate protection is required, or to prevent severe complications of the disease. In some circumstances, passive immunity can interfere with active vaccinations, particularly live-virus vaccines, so, if possible, they should not be administered within weeks or even months of each other.

General Information on Side Effects. Vaccines can have side effects, such as swelling at the injection site or fever, which are nearly always mild. There have been a number of reports in the popular press about alarming side effects in many vaccines. Anti-vaccine groups vocally oppose immunizations in children. Although it is true that no vaccine is 100% safe, childhood infections have not been wiped out. Without immunization, children risk diseases that have in the past killed millions of young children.

Thimerosal is a preservative used in many vaccines. It has been in use since the 1930s. The preservative contains small amounts of mercury. Some people are concerned about possible neurologic consequences from cumulative doses of mercury contained in vaccines given to infants. A 2003 study did report an association between thimerosal in DTaP vaccines and a higher risk for problems in neurologic development, including autism and speech problems.

In 2004, the Institute of Medicine (IOM) Safety Review Committee reported the results of studies in the U.S. and several European countries evaluating a possible association between thimerosal and autism. They concluded that scientific studies did not find that thimerosal caused autism.

In any case, manufacturers have been removing this preservative from vaccines. At the time of this report, all vaccines recommended for children age 6 or younger contain either no thimerosal or only trace amounts, with the exception of the inactivated influenza vaccine (although a limited supply of a version of the vaccine containing only trace amounts of thimerosal is available for use in infants, children, and pregnant women). A trace amount means that a given dose of vaccine contains less than 1 part per million.

Inactivated-virus and toxoid vaccines are usually safe in pregnant women, although any vaccination should be delayed, if possible, until the second or third trimester. Because of a possible risk to the fetus, live-virus vaccines should not be given to pregnant women or those likely to become pregnant within 28 days unless such women need immediate protection against life-threatening diseases, such as yellow fever, that are only prevented using live-virus vaccines. The live-virus MMR combination, which vaccinates against measles, mumps, and rubella, is not given to pregnant women because of the theoretical risk of the live-rubella vaccine on the fetus.

Click the icon to see an image of rubella syndrome.

Live-virus vaccines are not usually given to people whose immune system has been compromised by illness or the use of medication such as long-term corticosteroids. They include:

Click the icon to see an image of HIV.

Persons who have immune deficiency diseases (such as HIV or AIDS).
Patients with active leukemia or lymphoma.
Patients who are taking treatments that suppress the immune system, such as corticosteroids, alkylating drugs, antimetabolites, or radiation. (There are important exceptions, however, which are noted in the discussion of individual vaccinations below.) Short-term corticosteroids (given for less than 2 weeks) do not suppress the immune system and so should not affect any live-virus vaccination. It should be noted that some topical corticosteroids are suppressive. Patients who need vaccinations and who take long-term or high-dose topical steroids should check with their physicians.

In general, vaccines are not completely effective for patients whose immune systems are compromised by disease or medications. Often, such patients are given immune globulin if they are exposed to infection. It may take 3 months to 1 year before a person who has stopped taking immunosuppressant drugs regains the full ability to be successfully immunized against disease.

People who are traveling to developing countries should check with the US Centers for Disease Control (www.cdc.gov/travel) for up-to-date information on immunization requirements for their destination.

Below are some general guidelines for vaccinations, immunizations, and other preventive steps for travel:

Everyone should be up-to-date on any recommended vaccinations for childhood diseases, regardless of their age. Booster shots may be required for travelers to developing countries even if they have completed the initial series. Vaccinations may include polio, H. influenzae, the series for diphtheria, pertussis, and tetanus (DTaP), hepatitis B, rotavirus, measles, and varicella-zoster (chickenpox). If children have not completed their DTaP series, parents should consider having it completed while overseas.
Pregnant women should have vaccinations that are appropriate to their trimester. Not all vaccinations are safe during pregnancy.
Older adults may not respond to a vaccination as quickly as younger people or they may have a higher risk for side effects. They should check with their physicians.
Upper respiratory infections are very common after foreign travel. The flu vaccine may be recommended when traveling to any country during flu season, particularly for the elderly and people at risk for serious illness. This group may also need the pneumococcal vaccine.
Travelers to areas where there are tuberculosis (TB) outbreaks should have skin tests before traveling; those with negative tests should have a repeat test 2 - 4 months after they return.
Vaccination against hepatitis A is recommended for all travelers to developing countries. Some expert groups believe that such travelers should have hepatitis B vaccinations as well, but the CDC does not generally recommend them at this time except under certain circumstances.
Travelers to countries with malaria should take preventive agents.
Some countries may require vaccinations against yellow fever, meningitis, typhoid, cholera, Japanese encephalitis, and rabies under certain circumstances. Some of these vaccinations are covered in this report.
Studies indicate that multiple vaccines may be given at the same time to most adults without significantly increasing adverse effects.

[For more information, see In-Depth Report #1: Travel to developing countries.]

Childhood Immunization Schedule**
Age	Chickenpox (Varicella Zoster)	Diphtheria, Tetanus, Pertussis (DTaP)*	Haemophilus influenzae type (Hib)	Hepatitis A	Rotavirus
Birth
2 months		DTaP*	Hib		Rotavirus
4 months		DTaP*	Hib		Rotavirus
6 months		DTaP*	Hib (Depending on brand. For example, no third dose is required for PedvaxHIB or ComVax.)		Rotavirus
12 to 15 months	Varicella	DTaP* (Typically between 15 and 18 months. May be given as early as 12 months in high-risk children as long as 6 months have passed since the third dose.)	Hib (Sometime between 12 and 15 months.)	HepA (In 2 does, between 12 and 23 months)
2 years old				In children who have not been fully vaccinated.
4 to 6 years	Varicella	DTaP
11 to 12 years	Varies. (If previously missed, two doses should be given at least four weeks apart.)			In adolescents through age 18 in selected areas.

Age	Hepatitis B (Hep-B)*	Measles, Mumps, Rubella (MMR)	Pneumococcal Vaccine (PCV7)	Polio (Inactive virus) (IPV)*	Human Papillomavirus (HPV)
Birth	Hep-B immediately after birth. (This is very important when mothers are infected.) No later than 2 months in children of noninfected mothers. *
2 months	Hep-B some time between 1 and 4 months depending on risk. *		PCV7	IPV*
4 months			PCV7	IPV*
6 months	Hep-B some time between 6 and 18 months. *		PCV7	IPV* (Advised at some point between 6 and 18 months.) *
12 to 15 months	Varies.	MMR (Some time between 12 and 15 months.)
2 years old			PCV7 -- 1 dose for children not previously vaccinated.
4 to 6 years		MMR	PCV7 -- 1 dose in high-risk children.	IPV*
11 to 12 years	Hep-B (If vaccinations were previously missed). Two or 3 doses a few months apart.	MMR (If vaccinations were previously missed).			HPV (Females)
* A one-shot combination vaccine (Pediarix) has been approved that covers polio, hepatitis B, diphtheria, pertussis, and tetanus (DTaP) and should simplify the immunization process. It would be given as a single injection at 2, 4, and 6 months with booster shots given at 12 to 15 months and 4 to 6 years. **All children aged 6 - 59 months should receive an annual flu shot. Children older than 5 years of age who have chronic medical conditions should also receive the influenza vaccination. The flu shot is not approved for children younger than 6 months of age.

Of great concern are anti-immunization organizations and websites, which were formed mostly because of unsubstantiated reports linking small numbers of serious problems to some vaccines. The following watchdog systems are now in effect to monitor side effects from vaccination:

VAERS (Vaccine Adverse Event Reporting System) is a government service that registers all adverse events reported after vaccination, including those not related to the vaccine. It is useful for surveillance but has limitations. For example, the service may record the same case more than once. In addition, more serious events that occur after a vaccination are more likely to be reported than later and milder events, and such events are not necessarily linked to the vaccine.
VSD (Vaccine Safety Datalink) is a linked database that analyzes the records of more than 5 million patients each year. It is more accurate than VAERS, although the information it contains is not as timely.
The CDC has established the national network of Clinical Immunization Safety Assessment (CISA) Centers. It will provide services to physicians to help them evaluate and manage patients who may have had a side effect.

Studies using these systems are ongoing and none to date have confirmed reports of any significant association between most vaccines and severe side effects that would outweigh the benefits of these important and lifesaving agents.

No vaccine is 100% safe. Allergic and serious reactions are possible. In 2 cases, the early polio vaccine and the rotavirus vaccine, problems did occur, and some were serious. It is important to note, however, that even in these cases, the vaccines were withdrawn and the severe events still were far fewer than the number of lives saved.

The focus on vaccination side effects is ironic due to the fact that reports of such adverse effects outnumber the number of actual infections. Because vaccinations have been in existence for so long, today's parents have no direct knowledge of the consequences of these dreaded infections, which killed or severely sickened millions of children in the past.

It should be noted that studies are reporting that the risk for infection increases significantly in children who are not vaccinated. There is also a rise in infections among immunized children, suggesting resistance to the vaccines.

Infants often accept the first injection easily, since they are not expecting it. It gets more difficult, however, with each additional shot. Simply providing love and warmth can help children of all ages tolerate immunizations.

Additional tips:

Do not lie and tell an older child that a shot will be painless. Some health care providers suggest telling them that it stings a little and to count to 5 while it is being administered.
Ask the doctor if it is OK to give the child a dose of acetaminophen (Tylenol) before or after a shot. Ibuprofen (Motrin, Advil) or other non-aspirin pain relievers may be acceptable alternatives. (Children should NEVER take aspirin after vaccinations.)
Ask the doctor about EMLA cream, a topical anesthetic containing lidocaine and prilocaine. This product can be applied about an hour before the injection. (Note: EMLA may interact with acetaminophen and certain vaccinations, so be sure to check with the doctor first.)
A cooling spray may work as well as EMLA and have fewer side effects.
Longer needles, rather than shorter ones, may help reduce pain. One study reported that using longer needles decreased redness at the injection site by about two-thirds. Parents may want to ask their doctor about this study.
Have your child take a deep breath right before the shot and blow out very hard while it is being given. One study reported very good results with this breathing technique.
Give a sweet fluid before the shot and a little reward, such as a lollipop, immediately after the shot. Sugar actually has mild pain relieving properties for infants.

Diphtheria, Tetanus, and Pertussis

Diphtheria. Diphtheria is caused by the bacterium Corynebacterium diphtheriae, which can occur as either a toxic or nontoxic strain. When only the skin is involved, it is known as cutaneous diphtheria, and is likely to be a nontoxic strain. If the toxic strain affects the mucus linings in the body, such as the throat, diphtheria becomes life threatening. Between 1900 and 1925, diphtheria infected 200,000 people every year and killed between 5 - 10% of them, mostly the very young and very old. Because of immunizations, only one case was reported in 2000.

Tetanus. Tetanus is a disease that causes severe muscular contractions and convulsions. It is caused by a powerful toxin secreted by the bacterium Clostridium tetani. The bacterium is anaerobic, which means it lives without oxygen. People become infected by this dangerous bacterium through wounds in the skin. It is fatal in 15 - 40% of cases. Only 35 cases were reported in the U.S. in 2000, mostly in adults. One case, however, occurred in a 12-year-old boy whose parents refused to vaccinate him.

Pertussis. Pertussis (whooping cough) was a very common childhood illness throughout the first half of the 1900s. The disease is very easily spread from one person to another, and it is most severe in babies. Because of immunizations, which began in the 1940s, cases of whooping cough reached an all-time low of 1,010 in 1976 in the U.S. The incidence has risen recently, with almost 25,837 cases reported in 2004. Many more cases are reported worldwide. Nearly half of pertussis cases now occur in people 10 years of age or older, perhaps due to waning immunity in adolescents and adults. Such cases may be greatly underreported. One study suggested that as many as 25% of adults who see a doctor for persistent cough may actually have pertussis, but it may go undiagnosed because symptoms are usually mild and adults are unlikely to have the classic whooping cough. This is of some concern, because such adults may unknowingly infect unvaccinated children. The younger the patient, the higher the risk for severe complications, including pneumonia, seizures, and even death. Children younger than 6 months are at particular risk because even with vaccination, protection is incomplete.

The Initial Vaccination. Diphtheria, tetanus, and pertussis (DTaP) are very different disorders, but a combination injection has been routinely given to children since the 1940s. Since the early 1990s, the standard vaccine is DTaP, which uses a form of the pertussis component known as acellular pertussis that consists of a single weakened toxoid. (The older vaccine, DTP, includes a pertussis vaccine that contains multiple toxins against different variants of the disease. DTaP is just as effective but has fewer side effects than DTP.)

Pertussis is increasing among adults; the Centers for Disease Control data indicate that there were more than 25,000 cases of pertussis in 2004.

The Booster. Protection against diphtheria and tetanus from the vaccine lasts about 10 years. At that point a booster may be given against tetanus and diphtheria (Td). The Td vaccine contains the standard dose against tetanus and a less potent one against diphtheria and does not contain the pertussis component. In April 2005, the FDA approved the first pertussis booster shot ("Boostrix") for kids aged 10 - 18. Boostrix is a lower dose of infant pertussis vaccine. The infant pertussis vaccine can start to wear off after about 5 years, and some previously immunized teens and adults can get a mild form of the disease. The booster shot may help reduce the number of pertussis cases in adolescents and adults. The FDA also approved in 2005 another novel booster vaccine called Adacel for protection against tetanus, diphtheria and pertussis from adolescence through adulthood.

DTaP Schedule in Childhood. All children younger than 7 years old should receive the DTaP vaccine. In general, the vaccinations are given as follows:

Infants receive a series of three vaccinations at 2, 4, and 6 months of age (doctors may delay a vaccination in infants with suspected neurologic problems until their neurologic situation is clarified, but no later than their first birthday). Children with neurologic problems that have been corrected can be vaccinated.
A fourth dose is given between 15 and 18 months. (Infants at higher risk, such as those exposed to an outbreak of pertussis, may be given this vaccination earlier.) Of note, children who receive their third shot late in the schedule are at higher risk for skipping the fourth dose than children who were on schedule. Parents should be sure to adhere to a schedule that includes the fourth shot, even if they were late on the third.
A fifth dose is given at 4 - 6 years. This fifth shot now usually includes a vaccine against H. influenzae as well.
Children between the ages of 11 and 15 years old should receive a tetanus and diphtheria (Td) booster shot.
Boostrix is a single-dose booster that can be given to children age 10 - 18 years.
Adacel is a single-dose booster Tdap for people age 11 - 64 years.

If a child has a moderate or severe current or recent fever-related illness, vaccinations should be postponed until after recovery. Colds or other mild respiratory infections are no cause for delay. Parents should not be unduly concerned if the interval between shots is longer than that recommended. The immunity from any previous vaccinations persists, and the doctor does not have to start a new series from scratch.

Recommendations for Adults. All vaccinated adults should have a Td booster at least every 10 years throughout their lifetimes. One study reported that fewer than half of adult Americans ages 20 and older were protected against both tetanus and diphtheria, and immunity rates were even lower in those over 70. The results indicate that many people are not getting routine boosters.

Other recommendations for adults are as follows:

Adults who did not receive the primary childhood vaccinations should have the tetanus, diphtheria, and pertussis (Tdap) vaccine, approved in 2005, every 10 years.
Unvaccinated pregnant women should receive two doses of Td, properly spaced, and previously vaccinated women should have a booster.

Preventing Tetanus in Individuals with Wounds. Wounds that put patients at highest risk for tetanus are puncture wounds or wounds contaminated with dirt, feces, or saliva. However, any patient who requires medical care for any wound is a candidate for tetanus immunity.

Some considerations for tetanus vaccinations in wounded people are as follows:

A booster is needed if the last shot was 5 or more years before the injury.
Children under 7 are usually given DTP if they are not fully vaccinated.
Most individuals are given the Td vaccination if they have been vaccinated.
Older patients who had experienced an allergic response to a previous tetanus booster may be given the tetanus immune globulin (TIG).

Allergic Reactions. In rare cases, people may be allergic to the older diphtheria, tetanus, and pertussis vaccine, DTP. Parents should tell their doctor if their children have any allergies. The newer vaccine, DTaP, may pose a slightly higher risk for an allergic reaction than the older vaccine, DTP. Children who have severe responses should not be given further vaccinations. A rash that occurs after a dose of DTP is of little consequence. In fact, it does not usually indicate an allergic response but only a temporary immune reaction and does not usually recur with subsequent shots. It should be noted that no deaths have been reported from allergic reactions, even severe (anaphylactic) ones, to the DTP vaccine.

Pain and Swelling at the Injection Site. Children may feel pain at the injection site. In some cases, a small lump may remain at the site for several weeks. Placing a clean, cool washcloth over any swollen, hot, or red area can help. Children should not be covered or wrapped tightly in clothes or blankets.

The risk for swelling, including of the whole arm or leg, increases with subsequent injections, particularly the fourth and fifth doses. If possible, parents should request that their children receive the same vaccine brand each time to help reduce the risk of side effects.

Feverand Other Symptoms. A child may develop a mild fever, irritability, drowsiness, and loss of appetite after a shot.

The following remedies may be helpful:

Acetaminophen (for example, Children's Tylenol) and a sponge bath in lukewarm -- NOT cold -- water may help relieve fever and pain.
The doctor may suggest that children who have had previous high fevers or other reactions to the shot be given acetaminophen at the time of the vaccination and every 4 hours afterward for 24 hours. (The doctor will determine the dosage according to the weight of the child.)
Children should NEVER be given aspirin.

Fevers that should cause concern include the following:

The older DTP vaccine posed some risk for fever-related seizures on the day of vaccination. The newer DTaP has significantly reduced this side effect. Any very high fever in children (over 105° F) that causes convulsions should be reported immediately to the doctor. Although frightening, such fever-related seizures are uncommon and rarely have any long-term effect, and a recurrence after a subsequent vaccination is very unlikely.
A new fever that develops 24 hours after the vaccination, a fever that persists for longer than 24 hours, or seizures without fever are most likely due to other causes.

Hypotonic-Hyporesponsive Episode (HHE). HHE is an uncommon response to the pertussis component and occurs within 48 hours of the injection in children under 2. The child usually starts out feverish and irritable and then becomes pale, limp, and unresponsive. Breathing is shallow, and the child's skin may turn bluish. The reaction lasts an average of 6 hours and, although it is frightening, virtually all children return to normal. This side effect is less common since the introduction of the DTaP vaccine, but it can still occur.

Neurologic Effects in Pertussis Component. Of concern have been a few reports of permanent neurologic abnormalities that have occurred after children have been vaccinated. Such reports include attention deficit disorder, learning disorders, autism, brain damage (encephalopathy), and even death.

It is well known that the diphtheria and tetanus components cause no adverse neurologic effects, so some people suspect the pertussis component. However, many major studies, including an important statistically sound analysis in 2002, found no causal relationship between neurologic problems and the pertussis vaccination. In fact, one study indicated that children who received pertussis vaccine had fewer problems in school than those who were not vaccinated, regardless of family income levels. Studies on the newer DTaP have reported no safety concerns to date.

There may be some exceptions. Studies now suggest that in cases where neurologic problems have been strongly linked to the vaccination, high fevers -- not immunization -- are responsible. Children with known neurologic abnormalities may also be at risk for an outbreak of symptoms 2 or 3 days after the vaccination. Such a temporary worsening of their disease rarely poses a danger to the child. (Some experts suggest that children who have new neurologic events following their shot may already have a preexisting impairment, such as epilepsy, which is revealed -- but not caused -- by the vaccine.) To date, there is no proof that the pertussis vaccine causes these neurologic events, which, in any case, are so infrequent as to be nearly statistically unmeasurable.

Important Note: Unwarranted fears of side effects from vaccinations can be dangerous. In England such fears have caused a significant decline in immunization rates since the 1970s. Outbreaks of whooping cough have occurred as a result, causing a number of deaths and brain damage in many children. Small babies are particularly endangered if they become infected from older unvaccinated children (who usually have a mild disease).

Call the doctor immediately if a child has any of the following symptoms.

Extremely High Fever. A rectal temperature of 105° F or higher. (Temperatures taken under the arm or by mouth often register lower than actual temperatures.)
Inconsolable Crying. The child has been crying for over 3 hours without stopping or has a cry that isn't normal, such as being high-pitched.
Convulsions. The child's body starts shaking, twitching, or jerking. This is usually in response to a high fever. Place the child face down with the head to one side, protecting the head from hitting anything hard. Be sure the child can breathe freely. Seizures caused by fevers usually last less than 15 minutes.
Shock. The child collapses, turns pale, and becomes unresponsive.
Severe Allergic (Anaphylactic) Reaction. Swelling in the mouth and throat, wheezing and breathing difficulties, dizziness. The child collapses or is pale and limp.

Call the doctor if the following symptoms persist for more than 24 hours:

The injection site is still red and tender.
Fever does not go down.
The child is still fussy.

Measles, Mumps, and Rubella

Measles. Measles, one of the most contagious of all human infections, used to be a very common childhood disease. Most cases go away without serious complications. In severe cases, however, measles can cause pneumonia, and in about 1 out of 1,000 cases it can lead to encephalitis (inflammation in the brain) or death. The risk for these severe complications is highest in the very young and very old. In pregnant women, measles increases the rates for miscarriage, low birth weight, and birth defects.

Measles outbreaks still occur in the United States, usually among groups of people who do not believe in immunizations or in areas where immunization levels have fallen below the critical level. It is a fairly serious childhood infection that is recognized by the rash (as seen here), Koplik spots (small white spots on red background), red eyes, photophobia (sensitivity to light), and coughing.

Aggressive vaccination programs have reduced the incidence of measles in the U.S., to a low of 86 cases in 2000, most imported from other countries. Full-blown measles cases among unvaccinated children still remain a serious international problem, with 42 million cases and over 1 million deaths in small children each year.

Mumps. Mumps is at record lows in the US, with only 338 cases reported in 2000. In about 15% of cases, mumps affects the lining of the brain and spinal cord, although this is usually not ultimately harmful. Swelling of the testicles occurs in between 20 - 30% of males who have reached puberty, although sterility is rare. Deafness in one ear occurs in one patient out of 20,000 with mumps.

Click the icon to see an image of the meninges of the brain.

Rubella (German Measles). When rubella, commonly known as German measles, infects children or adults, it causes a mild illness that includes a rash, enlarged lymph nodes, and sometimes a fever. If a pregnant woman is infected during her first trimester, however, her baby has a 80% chance for developing birth defects, including heart abnormalities, cataracts, mental retardation, and deafness.

Click the icon to see an image of a cataract.

Before the vaccine became available, about 56,000 cases of rubella occurred annually in the U.S. Vaccination programs have dramatically reduced the number of cases to a low of 176 in 2000, but between 6 - 11% of adults are still susceptible, particularly unvaccinated Hispanic Americans who were born outside of the U.S.

Click the icon to see an image of rubella.

Safe and effective live-virus vaccines for measles, mumps, and rubella have been developed over recent decades. They are usually combined in children as the measles, mumps, and rubella (MMR) vaccine. Individual live-virus vaccines or the combined MMR may be given to adults, depending on their risk factors.

Measles-Mumps-Rubella (MMR) Vaccine in Early Childhood. The combined MMR vaccine should be given in two doses:

Between ages 12 and 15 months for the first dose. (Some doctors believe that the vaccine may be effective and safe in children younger than 9 months who are in areas of measles outbreaks. It should be noted that there were only 86 reported cases of measles in the U.S. in 1999.)
Between ages 4 and 6 years for the second dose. (Children who receive only one dose at 15 months or older have five times the risk of measles compared to those who had two doses.)

Measles-Mumps-Rubella (MMR) Vaccine in Adolescents and Adults. The general recommendations for adult MMR vaccinations are as follows:

Most people born before 1957 have experienced these once-common childhood diseases and do not require vaccination.
All unvaccinated people born after 1956 who did not already have measles and mumps should be given two doses of the live MMR vaccine administered at least 1 month apart.
Many people received an inactivated measles-virus vaccine in the early 1960s or an inactivated mumps-virus vaccine between 1950 and 1978; such people need revaccination with two doses of the live MMR vaccine. (This will cause no harm even if someone had a previous live-virus-mumps vaccination.)
The American Academy of Pediatrics now recommends the live-virus MMR vaccine for HIV-infected children, teenagers, and young adults, except for those who are severely immunocompromised. At this time, however, the vaccine appears to be safe in HIV-infected children, and it should be stressed that measles is very dangerous in this population.

Rubella Vaccinations During Pregnancy. It is particularly important for any unvaccinated nonpregnant woman who wants children to be vaccinated against rubella. It is recommended that women wait at least 28 days after vaccination to start trying to conceive. Except under very special circumstances, no live-virus vaccine, especially MMR, is given to an already pregnant woman, since there is a theoretical risk for birth defects from the rubella vaccine. Fortunately, the risk is low. In fact, studies have reported no increase in birth defects in women who were inadvertently vaccinated for rubella early in their pregnancy.

Common side effects from the MMR vaccination include fever, rash, and joint pain. Children are more likely to experience such side effects from the second dose (at 10 - 12 years) than from the first (at 4 - 6 years).

Fever. About 5 - 15% of people who are vaccinated with any live measles virus vaccine develop a fever of 103° F or greater, usually between 5 and 15 days after the vaccination. It usually lasts 1 or 2 days but can persist up to 5 days. In very young children, seizures can occur from high fever 8 - 14 days after vaccination, but they are rare and almost never have any long-term effects.

Swollen Glands. The live-mumps vaccine can cause mild swelling in the glands that are situated near the ears.

Joint Pain. Up to 25% of women have joint pain 1 - 3 weeks after a vaccination with a live-rubella virus; it lasts for 1 day to 3 weeks. Such pain does not usually interrupt daily activities. Rarely, it recurs or becomes persistent.

Allergic Reaction. People who have known anaphylactic allergies (very severe reactions) to eggs or neomycin are at high risk for a severe allergic response to the MMR vaccine. People with allergies that do not cause anaphylactic shock to these substances are not at higher risk for a serious allergic reaction to the vaccine. Mild allergic reactions may occur in some people, including rash and itching. A rash occurs in about 5% of people who are vaccinated with a live-measles vaccine. A live-mumps vaccination has caused rash and itching, but these symptoms are usually mild.

Interaction with Tuberculosis Test. The live-measles vaccine may interfere with a tuberculosis test, so the two should be administered at least 4 - 6 weeks apart. No evidence exists that the vaccine has an adverse effect on tuberculosis itself.

Mild Infection. One study suggests that a mild form of measles that has no symptoms may develop in previously immunized people who are exposed to the virus, although this mild infection may not be significant.

Idiopathic Thrombocytopenic Purpura (ITP). In about 1 in 22,300 doses, MMR can cause a rare bleeding disorder called idiopathic thrombocytopenic purpura (ITP). This can cause a purple, bruise-like discoloration that can spread across the body, nose bleeds, or tiny red spots. It is nearly always mild and temporary. (Of note, the risk for ITP is much higher with the actual infections, particularly rubella.)

Note: Unsubstantiated Reports of Neurologic Side Effects and Decline in Immunization. Much controversy has arisen over unsubstantiated reports of neurologic side effects attributable to MMR. This is of great concern since such reports have resulted in a decline in immunizations in certain areas, notably affluent areas in England where the vaccination rate has dropped from 92% in 1996 to 84% currently. Here, measles outbreaks are now climbing, and doctors fear that unless immunization rates increase rapidly, case numbers will significantly increase. In these and other regions, some parents mistakenly believe that the dangers of immunization outweigh a dangerous childhood illness that only older people remember. It should be strongly noted that measles still cause about 745,000 deaths in unvaccinated children who live in underdeveloped countries, primarily in Africa.

Most publicity has centered on a possible link between the MMR vaccine, which was introduced in 1988, and a variant of autism that includes inflammatory bowel disease (IBD) and impaired behavioral development. Such findings have been rigorously reviewed and refuted in a number of well-conducted studies. Of special note, a 2002 analysis of vaccination records of children born between 1979 and 1998 found no higher incidence in autism, with or without behavioral problems and gastrointestinal disorders. In the study, there was a link between impaired behavioral development and bowel problems, but they were not related to the vaccine.

Despite considerable publicity, there is no evidence linking MMR vaccination with the development of autism. The Centers for Disease Control & Prevention website provides extensive information on this matter. The popular media has incorrectly reported the possible link between autism and MMR as causing a split in the scientific community, but virtually all experts refute any association. In fact, reports of symptoms related to autism increased only after widespread publicity of this supposed side effect.

The potential benefits from receiving the MMR vaccine far outweigh the potential adverse effects. Measles, mumps, and rubella are all very serious illnesses and each may have complications resulting in lifetime disabilities or even death. The incidence of such complications, related to having the actual diseases, is far greater than the potential of developing serious, or even moderate, adverse effects due to the MMR vaccine.

Click the icon to see an image of inflammatory bowel disease.

Varicella-Zoster Virus (Chickenpox)

Chickenpox (caused by the varicella-zoster virus) is one of the most contagious childhood diseases. Nearly every unvaccinated child becomes infected with it. The affected child or adult may develop hundreds of itchy, fluid-filled blisters that burst and form crusts.

The infection rarely causes complications in healthy children, but it is not always harmless. Five out of every 1,000 children are hospitalized and, in rare cases, it can be fatal. Before the vaccination became widespread, chickenpox resulted in about 11,000 hospitalizations and 100 deaths a year.

This is a close-up picture of chickenpox. Early chickenpox lesions consist of small red papules that quickly fill with a yellowish or straw colored fluid to form small blisters (vesicles), as seen in this photograph. Later, these vesicles will rupture, forming shallow erosions that crust over and then ultimately heal.

Click the icon to see an x-ray of pneumonia following exposure to chickenpox.

Chickenpox can be especially severe in adults and very serious in anyone with a compromised immune system. In addition, the varicella virus (which persists after the childhood disease) erupts as a painful and distressing condition called herpes zoster (shingles) in about 20% of adults with a history of chickenpox. Chickenpox itself usually occurs only once, although a few cases of mild second infections, marked by the telltale rash, have been reported in older children years after their first infection.

Click the icon to see an image of the shingles.

A live-virus vaccine (Varivax) produces persistent immunity against chickenpox. Data show that the vaccine can prevent chickenpox or reduce the severity of the illness even if it is used within 3 days, and possibly up to 5 days, after exposure to the infection.

Recommendations for the Vaccine in Children. The vaccine against chickenpox is now recommended in the U.S. for all children between the ages of 18 months and adolescence who have not yet had chickenpox. Children are given one dose of the vaccine. Two doses 1 - 2 months apart are given to people over 13 years of age. To date, more than 75% of children have been vaccinated.

Doctors recommend that the chickenpox vaccine be given at the same time as the measles-mumps-rubella (MMR) vaccine or that there is a delay of at least 1 month between the two vaccinations. (If the chickenpox vaccination is given within that 30-day period -- but not at the same time -- there is a higher risk for a breakthrough infection later on.)

A chickenpox vaccine is part of the routine immunization schedule. It is about 100% effective against moderate or severe illness, and 85 - 90% effective against mild chickenpox. Parents often express concern that the immunity from the vaccine might not last. The chickenpox vaccine, though, is the only routine vaccine that does not require a booster.

Recommendations for the Vaccine in Adults.

Some doctors suggest that every healthy adult without a known history of chickenpox be vaccinated. In general, however, the following adults should consider vaccinations:

Older people without a history of chickenpox and who are at high risk of exposure or transmission (such as hospital or day care workers and parents of young children)
People who live or work in environments in which viral transmission is likely
Nonpregnant women of childbearing age
Adolescents and adults living in households with children
International travelers

As with other live-virus vaccines, the chickenpox vaccine is not recommended for the following:

Pregnant women (including the 3 months prior to pregnancy). Of note, an encouraging study suggested that pregnant women who were inadvertently vaccinated did not face a higher risk for birth defects in their offspring.
People whose immune systems are compromised by disease or drugs (such as after organ transplantation). The vaccine is being studied, however, for its safety in some of these patients, particularly children with cancer or other high-risk conditions. Experts report that it is safe in children with acute lymphoblastic leukemia (ALL), who should receive two doses. Certain children who are HIV positive may be candidates for the vaccine. An inactivated varicella vaccine may be safe and effective in patients undergoing bone marrow transplants, when given before and after the operation.
Most patients who cannot be vaccinated but are exposed to chickenpox are given immune globulin antibodies against varicella virus. This helps prevent complications of the disease if they become infected.

Discomfort at the Injection Site. About 20% of vaccine recipients have pain, swelling, or redness at the injection site.

Mild Rash and Risk of Transmission. The vaccine may produce a mild rash within about a month of the vaccination, which has been known to transmit chickenpox to others. Individuals who have recently been vaccinated should avoid close contact with anyone who might be susceptible to severe complications from chickenpox until the risk for a rash has passed.

Severe Side Effects. Between 1995 and 2001, 759 serious adverse effects were reported. Such events included seizures, pneumonia, anaphylactic reaction, encephalitis, Stevens-Johnson syndrome, neuropathy, herpes zoster, and blood abnormalities. Anecdotal reports have found a higher association of side effects when varicella vaccine is given at the same time as the measles, mumps, and rubella (MMR) vaccination. Because combined vaccinations are being developed, such effects should be closely studied.

There is intense debate over the long-term protection of the vaccine. The incidence of breakthrough infections after vaccination stimulates the controversy. It should be noted, however, that evidence is showing improvements in quality of life and better survival rates since the introduction of the vaccine. Any negative studies to date on long-term effectiveness simply raise the question of the need for booster or higher doses -- not the elimination of the vaccine altogether.

Long-Term Protection in Vaccinated Children. Most studies suggest that the vaccine is not wholly effective in up to 30% of vaccinated children. However, they also report if chickenpox occurs, more than 95% of the cases are mild. It is also usually less contagious. In such people, the infection appears to be caused by a wild virus, not a reactivation of the vaccine. (Of concern was a 2002 study of a day care center reporting a much higher rate -- 56% -- of break-through infection, with only 86% of cases being mild. The implications of this study are unclear.) The longer the interval since vaccination occurs, the higher the risk for a breakthrough infection.

This does not necessarily mean, however, that children who are vaccinated eventually lose total immunity. A breakthrough infection is often due to issues with the primary vaccine (improper storage, low potency, the duration between the chickenpox and measles, mumps, and rubella vaccines being less than a month) or the child's history (having asthma, being less than 14 months at the time of vaccination). Nevertheless, there is also some evidence that either having the vaccination or even having chickenpox itself is not as protective against a later infection as experts have thought.

Long-Term Protection in Vaccinated Adults. The protective effects for adults are even less clear. An encouraging 2002 study of adults vaccinated between 1979 and 1999 reported that 9% developed chickenpox months to years after their last vaccination. The length of time since the vaccination did not seem to affect whether the adults would catch chickenpox or not. (Nearly half of those had been exposed to the disease in their homes.) In all cases, infection was mild, with none of the serious complications of adult chickenpox.

Vaccine's Effect on Shingles. A primary concern is whether the vaccine protects against shingles later on, particularly in people who have breakthrough infections -- however mild. As more and more children get vaccinated, the actual protection of the vaccine and the implication of the breakthrough infection will become clearer.

[For more information, see In-Depth Report #82: Shingles and chickenpox (Varicella-zoster virus).]

In September, 2005, the Food and Drug Administration approved a combination vaccine to protect against measles, mumps, rubella, and chickenpox. Proquad, produced by Merck & Co., protects against all four infections with one shot, thus sparing young children from multiple painful injections. Proquad is approved for use in children from 12 months to 12 years of age. Proquad was studied in four randomized trials involving 5,446 healthy children aged 12 - 23 months received Proquad. Proquad’s immune response rates were 97.4% for measles, 95.8 - 98.8% for mumps, 98.5% for rubella, and 91.2% for chickenpox, similar to the rates induced by the concomitant administration of single doses of M-M-R II and Varviax at separate injection sites in 2,038 children.

Varicella-Zoster Virus (Shingles)

Shingles is a painful infection caused by the varicella zoster virus, the same virus responsible for chickenpox. Once a person has chickenpox, the virus lies dormant in the body. It can emerge years later as shingles.

Shingles causes a painful, red, and sometimes blistery rash to form on the body or face. The disease can cause intense pain, called post herpetic neuralgia. Other symptoms include fever, headache, and chills. In rare cases, complications, such as pneumonia, blindness, and brain inflammation (encephalitis), can occur. Shingles is most common in adults over age 50.

In May 2006, the U.S. Food and Drug Administration licensed the herpes zoster vaccine (Zostavax) for the prevention of shingles. The vaccine can reportedly cut the incidence of shingles in half for adults over age 60.

Recommendations for the Vaccine in Adults. All adults age 60 or older should get a single dose of the herpes zoster vaccine, regardless of whether they have previously had shingles.

The following people should not receive the herpes zoster vaccine:

Anyone who has a weakened immune system due to HIV/AIDS or cancer of the lymph, bone, or blood, or due to treatments such as radiation or corticosteroid drugs
Women who are pregnant, or anyone who is in close contact with a pregnant woman who has not had chickenpox
Children -- they should receive only the chickenpox vaccine

Redness, pain, and swelling. About 1 out of every 3 people who get the vaccine have mild redness, soreness, swelling, or itching at the injection site.

Headache. About 1 in 70 people experience headache after taking the vaccine.

There have been no serious side effects reported with the shingles vaccine.

Research has found that the herpes zoster vaccine reduces the incidence of shingles by about 50%. The benefit is as high as 64% in people ages 60 - 69. In people who are vaccinated but still develop shingles, the vaccine reduces the duration of the pain involved with the disease.

One 2007 study found that doing tai chi might boost the immune response to the vaccine. According to the study, people aged 59 - 86 who took part in a 16-week tai chi program had immunity similar to that of 30- and 40-year-old adults who had been vaccinated. Combining tai chi with the vaccine increased the effects of the vaccine by about 40%.

Hepatitis A

The hepatitis A virus infected an estimated 56,000 people in 2004. Hepatitis A, formerly called infectious hepatitis, is always acute and never becomes chronic. The virus is excreted in feces and transmitted by contaminated food and water. Eating shellfish taken from sewage-contaminated water is a common means of contracting hepatitis A. It can also be acquired by close contact with individuals infected with the virus. It is estimated that 11 - 16% of reported cases occur among children or employees in daycare centers or among their contacts. The hepatitis A virus does not directly kill liver cells, and experts do not yet know how the virus actually injures the liver.

A fly may act as a mechanical vector of diseases such as hepatitis A. The fly may carry the infective organism on its feet or mouth parts and contaminate food or water, which a person then consumes. A biological vector actually develops an infective organism in its body and passes it along to its host, usually through its saliva. A fly can be a biological vector, as in the transmission of leishmaniasis by the sandfly.

All children should get 2 doses of the hepatitis A vaccine starting at 1 year, according to CDC recommendations. The doses should be given at least 6 months apart. Others who should be vaccinated against hepatitis A include travelers to developing countries, people living in communities where outbreaks occur, people with blood-clotting disorders, sexually active homosexual men, and health care workers exposed to the virus. People with chronic liver disease, including those with hepatitis C, should also be vaccinated, particularly if they have not been exposed to hepatitis A, since the infection can cause liver failure in these patients.

The hepatitis A vaccine can be given along with immune globulin and other vaccines. Individuals should also receive immune globulin if they are exposed within 4 weeks of the vaccination. A combined vaccine against both hepatitis A and B is now available as well for those at high risk for both these infections. People should get 3 doses of this vaccine, and the last dose should be given 6 months after the first dose.

Side Effects. The vaccine is very safe and effective, although allergies can occur. The most common side effects reported are soreness at the injection site, headache, and general malaise.

Click the icon to see an image about hepatitis A immunization.

Hepatitis B

About 2 billion people have been infected with the hepatitis B virus (HBV) worldwide, and each year 1 million people die, mostly due to cirrhosis and liver cancers that develop in the chronic form of this disease. In the U.S., about 1.25 million people have chronic hepatitis B.

Hepatitis B is also known as serum hepatitis. It spreads through blood and sexual contact. The infection is seen with increased frequency among intravenous drug users who share needles and among the homosexual population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Courtesy of the CDC.)

Pregnant women with hepatitis B can transmit the virus to their babies. Even if they are not infected at birth, unvaccinated children of infected mothers run a 60% risk of developing hepatitis B before age 5. Although hepatitis B infections have dropped 95% since routine immunization began in the early 1990s, there are still children who aren't immunized, and the disease persists. Universal vaccination against this disease during childhood is very important.

Several inactivated virus vaccines, including Recombivax HB, GenHevac B, Hepagene, and Engerix-B, can prevent hepatitis B. Twinrix is a vaccine against both hepatitis A and B. They are safe, even for infants and children. Vaccination programs are proving to reduce the risk for liver cancer.

Click the icon to see an image of hepatitis B.

Hepatitis B Vaccine for Early Childhood. Experts now recommend that all infants and children not previously vaccinated be immunized by the time they reach seventh grade. Typical schedules for hepatitis B vaccinations in childhood are as follows:

All infants should receive the hepatitis B vaccine soon after birth and before hospital discharge. (The first dose may be delayed if the mother has no evidence of infection, but only with the doctor's permission.) The second dose should be given at 1 - 2 months; and the third between 6 and 18 months (at least 16 weeks after first dose and 8 weeks after second dose). (A fourth dose may also be given if any of the previous doses was a combination vaccine.) This is a safe vaccine, even in newborns, and parents should be sure their infants are immunized.
Infants of mothers infected with hepatitis B should be treated with immune globulin plus the hepatitis vaccine within 12 hours of birth. The second dose should be given at 1 - 2 months and the third at 6 months. Infants should be tested for antibody status at 9 - 18 months to see if they are chronic virus carriers or need to be revaccinated. Immunization rates are still too low in this group.
When it is not known if a mother is infected, the infant should receive the vaccine within 12 hours of birth. The mother's blood should then be tested right away. If she is infected, the infant should receive immune globulin within 1 week of birth.
Children who are 11 - 12 and who have not been immunized should receive 2 or 3 doses of the vaccine (depending on the brand) given over a few months.

Hepatitis B vaccine protection may wane over time. According to a 2007 study, 40% of adolescents who had received a first dose of the vaccine as newborns had declining immunity to the disease by age 14. As of now, routine booster shots are not recommended because more research is needed on the subject. Booster shots may be recommended for those at risk, such as from sexual exposure.

Hepatitis B Vaccine for Adults. The following adults are at very high risk and should be vaccinated:

Health care and public safety workers who may be exposed to blood products. Such individuals have a risk for hepatitis B that ranges from 15 - 30%.
People in the same household ashepatitis B-infected individuals. (Unvaccinated people who have had intimate exposure to people with hepatitis B may be protected with immune globulin, which is sometimes administered with the vaccine.)
Travelers to countries with a high incidence of hepatitis B infection.
Patients who require transfusions and have not been infected with hepatitis B. (Those with blood clotting disorders should have the vaccination administered under the skin, not injected in the muscle.)
Sexually active individuals with multiple partners.
People with any sexually transmitted diseases.

Other people at risk who would benefit from vaccinations include:

Patients and workers in mental institutions
Morticians
Patients undergoing hemodialysis. (These people may need larger doses or boosters; they also may need to be revaccinated if blood tests indicate they are losing immunity.)
People who use injected drugs
Pregnant women at risk for the virus. (There is no evidence that the vaccine is dangerous to the fetus.)
People receiving treatments or who have conditions that suppress the immune system may need the vaccination, although its benefits for this group are unclear except for those at high risk, such as people with HIV or spleen abnormalities.

Click the icon to see an image of the immune system structures.

The regimen in adults is typically 3 doses given over 6 months. One study reported that older adults would benefit from a fourth dose without incurring serious side effects. People who abuse alcohol may need higher doses.

A small percentage of people do not develop immunity, even after a vaccine has been given repeatedly. A more potent vaccine is proving to be effective for these people; it loses its effect after 5 years in about one-third of those who receive it.

Soreness. Soreness at the injection site is the most common side effect.

Nerve Inflammation. There have been some reports of nerve inflammation after vaccinations for hepatitis B, and some questions about multiple sclerosis. A review article published in 2006 found no evidence that hepatitis B vaccine is associated with multiple sclerosis, sudden infant death syndrome, or chronic fatigue syndrome. Earlier studies also found no evidence linking the vaccine to multiple sclerosis. A 2007 study found that the vaccine doesn't increase the risk for rheumatoid arthritis.

Because of even a small theoretical risk of nerve damage in infants, some groups oppose the vaccination in children who are not in high-risk groups. Worldwide, 65 million people with chronic hepatitis are expected to die from liver disease and vaccinations are saving lives. For example, in Taiwan, where infection rates are high and infants are at risk for hepatitis B from infected mothers, vaccination programs have significantly reduced the risk for liver cancer. [For more information see In-Depth Report #59: Hepatitis.]

Pneumococcal Pneumonia

The pneumococcal bacterium (also called Streptococcus pneumoniae or S. pneumoniae ) is responsible for many respiratory infections in the upper and lower airways. This bacterium is dangerous for people with serious underlying chronic medical conditions and illnesses and is the leading cause of ear infections and sinusitis in children. The most serious complication is pneumonia.

More than 200,000 people in the U.S. are hospitalized each year for pneumonia-related complications. Although the majority of pneumonias respond well to treatment, the infection can still be a very serious problem. It kills approximately 36,000 people each year. Together with influenza, pneumonia is the eighth leading cause of death in the U.S.

Of particular concern is the increasing prevalence of pneumococcal bacteria that are resistant to many standard antibiotics. This has created a great sense of urgency in the medical community to find effective measures for preventing infection.

This picture shows the organism pneumococci. These bacteria are usually paired (diplococci) or appear in chains. Pneumococci are typically associated with pneumonia, but may cause infection in other organs, such as the brain (pneumococcal meningitis) and bloodstream (pneumococcal septicemia). (Courtesy of the CDC.)

The pneumococcal vaccine protects against S. pneumoniae (also called pneumococcal) bacteria, the most common cause of respiratory infections. There are 2 effective vaccines available: The 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults and the 7-valent conjugate vaccine Prevnar (PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria.

The 7-valent conjugate vaccine Prevnar (PCV7) is very effective in children. Research finds that the vaccine, which was introduced in 2000, has reduced hospital admissions for pneumonia in children under age 2 by about 39%. The vaccine has even lowered hospital admissions 26% among adults aged 18 - 39 the study found, likely because they are parents of young children who might otherwise have developed the disease. Another study found that the vaccine also has benefited children who regularly get ear infections. Recurrent ear infections have fallen by 28% since the introduction of the vaccine.

Click the icon to see an image of pneumococcal pneumonia.

The pneumococcal vaccine is now recommended by many experts for the following groups:

Children up to age 2. The vaccine is very effective in children. In one study, a similar vaccine under investigation not only protected children in day care from serious respiratory infections, but their younger unvaccinated siblings had fewer infections as well.
Children up to age 5 who are at risk for pneumonia or complications of influenza, such as children with sickle cell disease, those with immune deficiencies, a damaged spleen or no spleen, or children with chronic medical conditions. One study has found that the rate of pneumococcal disease among children with sickle cell disease has dropped 90% since the vaccine was introduced.
Other children ages 2 - 5 who are at higher risk for serious pneumococcal infections should be considered for vaccinations. They include African- or Native Americans, children in group child care, socially or economically disadvantaged children, or those who have had frequent or complicated acute middle ear infections within the past year.

Pneumococcal Vaccine in Older Children and Adults. The vaccine is proving to be effective in reducing the rate of pneumonia in young adults, although not to the degree that it protects young children. The benefit for the elderly -- other than protection against bloodstream infection -- is unclear. Still, pneumonia is declining among adults, which may be due to fewer infections being transmitted from vaccinated young children. Many experts now recommend the vaccine for the following older children or adults:

All people over 65 years old. Some experts believe that all adults 50 - 64 should also be vaccinated. Unfortunately, although the vaccination is protective against pneumococcal bacteremia (invasive infection) in people over 65, evidence suggests that it does not appear to protect against community-acquired pneumonia.
Adults with any chronic condition that increases the risk for pneumonia. This includes patients with heart disease (such as congestive heart failure), chronic lung disease (COPD or emphysema, but not asthma), or diabetes.
Individuals with immune deficiencies (such as HIV) or those undergoing treatments that suppress the immune system.
Patients with autoimmune diseases, such as rheumatoid arthritis and lupus. Unfortunately, studies show the vaccine may not be as effective in these patients as in those with healthy immune systems. Nevertheless, they are at high risk for serious respiratory infections and should be vaccinated.
Patients with kidney disease or kidney transplants. Older people who have had transplant operations or those with kidney disease may require a revaccination after 6 years.
Patients with problems in the spleen.
Alcoholics, especially those with cirrhosis.
People living in long-term care facilities.
Alaska Natives or American Indians, who may be at increased risk for pneumonia.

The safety of the pneumococcal vaccine hasn't been proven during the first trimester of pregnancy; however, there have been no adverse effects reported. When the vaccine is administered to pregnant women, it may actually protect their infants against certain respiratory infections.

Protection lasts for more than 6 years in most people, although the protective value may be lost at a faster rate in elderly people than in younger adults. Anyone at risk for serious pneumonia should be revaccinated 6 years after the first dose, including those who were vaccinated before age 65. Subsequent booster doses, however, are not recommended.

The recommended schedule of immunization for Prevnar (PCV7) is 4 doses, given at 2, 4, 6, and 12 - 15 months of age. Infants starting immunization between 7 and 11 months should have 3 doses. Children starting their vaccinations between 12 and 23 months only need 2 doses. Those who are over 2 years old need only 1 dose.

Side effects include pain and redness at the injection site, fever, and joint aches. Children are more likely to have fever within 48 hours if they receive other vaccines at the same time, and also after the second dose. Fortunately, severe reactions are very rare, even if a person is mistakenly revaccinated before the effects of the first vaccination have worn off. Allergic reactions are also very rare.

Poliomyelitis

Poliomyelitis, more commonly known as polio, is a disorder caused by a virus and marked by potentially paralyzing nerve-related damage, which can be fatal. Fifty years ago it was a major killer of children, and it remains a threat in parts of Asia and Africa today. Vaccination programs eliminated the disease in the Americas in 1994, with the last case of wild poliovirus in the U.S. reported in 1979. As of 2004, polio has been eradicated in the Americas, the Western Pacific, and Europe.

Poliomyelitis is a communicable disease caused by viral infection and occurs through direct contact with infected secretions. Polio is found worldwide, but immunization has reduced the incidence. Clinical polio affects the central nervous system (brain and spinal cord). Disability is more common than death.

Two poliovirus vaccines have been available in the U.S.: oral poliovirus vaccine (OPV), a live-virus vaccine, and inactivated poliovirus vaccine (IPV), a killed vaccine that is administered by a shot. Both produce immunity in more than 95% of people. The live-virus used in the vaccine, however, has, in some cases, reverted to a form that can cause polio in unvaccinated people. This is a particular danger in developing countries where vaccination rates are low. The Centers for Disease Control and Prevention now recommends only the inactivated IPV vaccine for children. The schedule is 4 doses of IPV at ages 2 months, 4 months, 6 - 18 months, and 4 - 6 years.

Poliovirus Vaccine in Older Children and Adults. The poliovirus vaccine is not usually recommended for people over 18. Exceptions are unvaccinated health care workers, laboratory technicians, or others exposed to polioviruses. Travelers to developing countries where outbreaks of poliovirus have been reported should be vaccinated. Adults should also be given the inactivated poliovirus vaccine (IPV).

Allergic Reactions. The inactivated poliovirus vaccine (IPV) contains small amounts of streptomycin and neomycin, so people allergic to these antibiotics can also have an allergic response to this vaccine. Patients should report any allergies to their physician.

Paralysis. Rare cases of paralysis have occurred in people taking the oral live poliovirus vaccine or in those exposed to recipients of this vaccine. It should be stressed the risk is very small, with only 1 case occurring out of 2.4 million doses. Since the introduction of the current recommended series that uses only IPV, no cases have been reported.

Contamination by Simian Virus 40. The public was alarmed by reports of contamination of polio vaccines given between 1955 and 1963 by a virus known as SV40. The virus has been detected in certain rare cancers, including mesothelioma (a lung cancer normally associated with asbestos exposure), osteosarcoma, some brain tumors, and non-Hodgkin's lymphoma.

Click the icon to see an image of a brain tumor.

Still, about 98 million people may have been exposed, and most of these cancers are very rare (although some, including non-Hodgkin's lymphoma, are increasing). At least 40 years of observation have raised no red flags that indicate any serious problem. However, polio, once a major killer of children, has nearly been wiped out worldwide.

Viral Influenza

Influenza, commonly called the flu, is always caused by a virus.

Influenza, also known as the flu, is caused by a virus.

There are different strains of influenza:

Influenza A is the most widespread and most severe strain. It can affect both animals and humans. Influenza A is the cause of the worldwide epidemics (pandemics) of the flu that have occurred. More than 200,000 hospitalizations per year are due to this strain of the flu. Influenza A is usually further categorized by 2 subtypes based on 2 substances that occur on the surface of the viruses: hemagglutinin (H) and neuraminidase (N).
Avian Influenza A (called “bird flu”) was first detected in humans in 1997 in China and the region of Hong Kong. Bird flu is spread easily from bird to bird. Humans usually contract the flu from contact with infected domesticated birds, such as chickens, turkeys, and ducks. The World Health Organization confirms that there were, as of the publishing of this report, 331 cases of bird flu in humans and 203 deaths. The greatest number of cases have occurred in Indonesia, followed by Vietnam, Egypt, Thailand, and China. In April 2007, the U.S. Food and Drug Administration approved the first vaccine against the avian flu virus.
Influenza B infects only humans. It is less common than type A, but is often associated with specific outbreaks, such as in nursing homes. Flu caused by this strain tends to be milder than that caused by Influenza A.

Based on a final analysis of the 2005 - 2006 flu season, nearly 80% were type A and about 20% were type B. Influenza A usually causes more severe disease than type B. However, because influenza B has been less common in the past few years, there is concern that some people -- particularly small children -- may have fewer antibodies to it and so may be at higher risk for severe infection. (See Flu Vaccines in this report.)

Complications of the Flu. In general, the flu is usually self-limited and not serious. It is responsible, however, for 15 - 30% of the excess number of hospitalizations that occur in winter. More than 200,000 people who contract the flu end up in the hospital, and an estimated 36,000 people currently die each year of flu-related complications. The highest risks for serious complications occur in people age 65 and older and in those who are already sick with another disease. There have also been reports of flu-related deaths in very young children.

Pneumonia is the major serious complication of the flu and can be very serious. It can develop about 5 days after viral influenza. It is an uncommon event, however. It nearly always occurs in high-risk individuals, such as the very young or very old, and hospitalized or immunocompromised patients.

Note on Pandemics. Every year, flu strikes millions of people worldwide. Influenza epidemics are most serious when they involve a new strain against which most people are not immune. Such so-called pandemics can infect more than one fourth of the world's population within a 3-month period. For example, the Spanish flu in 1918 and 1919 killed 20 million people in the U.S. and Europe, and 17 million people in India. Although pandemics are still of great concern, there have been major improvements in private and public health since then, including the discovery of antibiotics to treat bacterial complications, new antiviral agents and vaccines, and intensive worldwide surveillance of outbreaks.

Description of Vaccines. Vaccines against the flu use inactivated (not live) viruses. The influenza vaccine is commonly called a "flu shot." It is designed to provoke the immune system to attack antigens contained on the surface of the virus. (Antigens are foreign molecules that the immune system specifically recognizes as alien and so targets for attack.)

Click the icon to see an image of antigens.

Unfortunately, the antigens in these influenza viruses undergo genetic alterations (called antigenic drift ) over time, so they are likely to become resistant to a vaccine that worked in the previous year. Vaccines are redesigned annually to match the current strain.

Influenza A. The influenza A virus is further categorized by primary molecular antigens (hemagglutinin and neuraminidase), which serve as the targets for the vaccines. Influenza A is a particular problem because it can infect other species, such as pigs or chickens, and undergo major genetic changes.
Influenza B viruses tend to be more stable than influenza A viruses, but they, too, vary. Although influenza B has been far less common than A, a vaccine for type B is important because experts are concerned that small children will not have developed any immunity to the virus and will experience severe flu if they are exposed to type B.

Until recently the vaccine has been administered only by injection. A vaccine (FluMist) that can be delivered in a nasal spray has now been approved for people aged 5 - 49. The vaccine contains live viruses that have been engineered to replicate in the cool temperatures of the nasal passages, but not in the warmer lungs and lower airways. Its presence in the nasal passages boosts the specific immune factors in the mucous membranes that fight off the epidemic viruses. Studies in 2003 reported protection against the flu that ranged from 66 - 92%, depending on whether the flu was type A or type B. (The lower rates were those observed for influenza B, particularly a new variant.) A 2007 study found that children aged 6 months - 5 years who had the nasal spray had 55% fewer cases of the flu than those given the injection. However, the vaccine is not approved for children in this age group. A preservative-free intramuscular injectable vaccine (Fluzone) is also now available.

The avian flu vaccine is designed for people aged 18 - 64 who are at risk for exposure to the avian H5N1 virus. The vaccine is given as 2 shots, spaced about 1 month apart. In studies, the vaccine appeared to be effective and well tolerated. Currently, the government is stockpiling the vaccination in case of an avian influenza outbreak. The vaccine is not available to the general public.

Ideally, appropriate candidates should be vaccinated every October or November. However, it may take longer for a full supply of the vaccine to reach certain locations. In such cases, the high-risk groups should be served first.

Antibodies to the flu virus usually develop within 2 weeks of vaccination, and immunity peaks within 4 - 6 weeks, then gradually wanes.

Because children under age 9 do not develop strong immune responses to 1 dose, the CDC recommends 2 vaccinations given 1 month apart.
Early research also suggests that it may be equally effective to administer children’s vaccinations in the spring and fall, rather than 1 month apart; further study is ongoing.
It should be noted that if an individual develops flu symptoms and is accurately diagnosed in time, vaccination of the other members of the household within 36 - 48 hours affords effective protection to those individuals, according to a 2004 Canadian analysis of multiple studies.

In healthy adults, immunization typically reduces the chance of getting the flu by about 70 - 90%. The current flu vaccines may be slightly less effective in certain patients, such as the elderly and those with certain chronic diseases. Some evidence suggests, however, that even in people with a weaker response, the vaccine is usually protective against serious flu complications, particularly pneumonia. The major outstanding question is whether the vaccination prevents complications of serious illness. One 2003 study, for instance, reported no reduction in severity of chronic lung diseases among vaccinated patients with asthma, emphysema, or chronic bronchitis. Some evidence suggests, on the other hand, that among the elderly, a flu shot may help protect against stroke, adverse heart events, and death from all causes.

Children Who Should Be Vaccinated. The following children over 6 months should be vaccinated against the flu:

The American Academy of Pediatrics (AAP) and the CDC recommend flu shots for all healthy children ages 6 - 23 months. In addition, any child over age 2 years who has a condition that requires regular medical care or who has been hospitalized for a serious illness (particularly lung or kidney disease, diabetes, sickle cell disease, or immune deficiencies).
Children who are receiving long-term aspirin therapy should also receive a flu shot. Children who get the flu are at higher risk for Reye syndrome, a life-threatening disease.
Some doctors now advocate flu shots for all school-age children. Research indicates that children are responsible for transmitting the vast majority of cases of the flu, and that routine vaccination of school-age children would considerably reduce transmission rates throughout communities.

There has been some question concerning flu shots because of some reports that vaccines may worsen asthma. Recent and major studies have been reporting, however, that the vaccination is safe for children with asthma. It is also very important for these patients to reduce their risk for respiratory diseases. Yet many children with asthma are not vaccinated. One study by the CDC found that fewer than one-third of children with asthma were vaccinated during the 2004-2005 flu season.

Older Children and Adults Who Should Be Vaccinated. The following, in order of priority, are the population groups who should be vaccinated each year. The first 2 groups have the highest need for flu shots and are given top priority:

All adults 65 years and older. Older adults who get a flu shot have lower hospitalization rates than those who do not. Evidence now suggests that vaccination may help protect against adverse heart events (including after heart surgeries), stroke, and death from all causes in the elderly. Still, studies suggest that only two-thirds of people in this group are vaccinated, mostly because of unwarranted fears of ineffectiveness or adverse effects.
People of any age at high risk for serious complications from the flu. Such people include those with heart disease, lung problems, immune deficiencies, diabetes, kidney disease, or chronic blood disease. Those with any condition that may compromise respiratory function or the handling of respiratory secretions, including people with cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders, are included in this group. (There have been concerns about the safety of the vaccinations in certain high-risk patients, such as those with HIV or asthma. Studies now suggest that the vaccine is generally safe in these patient groups. Furthermore, their risk for serious complications from the flu outweighs any potential adverse effects from the vaccines.)
Adults aged 50 - 64 who have chronic medical conditions. The U.S. Advisory Committee on Immunization Practices (ACIP) suggests that all adults over age 50 should be vaccinated, although this is not a recommendation of the CDC.
All health care workers should be vaccinated, according to the ACIP’s 2005 recommendations.
Household members in contact with individuals who are at high risk for complications from the flu should be vaccinated.

Other adults who should consider flu shots include:

People at risk for complications of the flu who are traveling to the tropics at any time or to the Southern Hemisphere between April and September.
Pregnant women who are at risk for complications of the flu and who will be in their second or third trimester during flu season. Women who are pregnant should receive only the inactivated flu vaccine. (Vaccinations should usually be given after the first trimester. Exceptions may be women who are in their first trimester during flu season, because their risk from complications of the flu is higher than any theoretical risk to the baby from the vaccine.)
People such as firemen or policemen who are critical for public safety.

Possible side effects of the flu vaccine include:

Allergic Reaction. Newer vaccines contain very little egg protein, but an allergic reaction still may occur in people with strong allergies to eggs.
Soreness at the Injection Site. Up to two-thirds of people who receive the influenza vaccine develop redness or soreness at the injection site for 1 or 2 days afterward.
Flu-like Symptoms. Some people actually experience flu-like symptoms, called oculo-respiratory syndrome, which include conjunctivitis, cough, wheeze, tightness in the chest, sore throat, or a combination. Such symptoms tend to occur 2 - 24 hours after the vaccination and generally last for up to 2 days. It should be noted that these symptoms are not the flu itself but an immune response to the virus proteins in the vaccine. (Anyone with a fever at the time the vaccination is scheduled, however, should wait to be immunized until the ailment has subsided.)
Guillain-Barre Syndrome. Isolated cases of a paralytic illness known as Guillain-Barre syndrome have occurred, but if there is any higher risk, it is very small (one additional case per 1 million people), and does not outweigh the benefits of the vaccine.

Haemophilus Influenzae Type B

Haemophilus influenzae (H. influenzae) type B is a bacterium, which, despite its name, is entirely different from the viruses that cause influenza (the flu). Before vaccination, H. influenzae type B (Hib) was the most common cause of childhood bacterial meningitis, killing 600 American children every year and leaving others deaf, mentally retarded, or epileptic. It is rarely troublesome for adults, although it can be dangerous for anyone with chronic lung disease and those susceptible to infections.

This is a Gram stain of spinal fluid from a person with meningitis. The rod-like organisms seen in the fluid are Haemophilus influenza, one of the most common causes of childhood meningitis (prior to the widespread use of the H. influenza vaccine). The large red-colored objects are cells in the spinal fluid. A vaccine to prevent infection by Haemophilus influenza type B is available as one of the routine childhood immunizations (Hib), typically given at 2, 4, and 12 months.

Three equally effective inactivated bacterial vaccines (commonly called Hib vaccines) are available for H. influenzaetype B. All children under 5 should be vaccinated against H. influenzae type B. The vaccine is administered as an injection at 2 and 4 months. Depending on the vaccination preparation, a third shot in the series is administered at 6 months. A booster is required at some time between 12 and 15 months of age.

Click the icon to see an image of Hib immunization.

In children older than 12 months, the Hib and DTaP vaccines are being combined in a single injection. This combined injection can be given as a booster, but not as the initial Hib immunization.

Evidence suggests that in infants, this combined vaccine using acellular pertussis (the current DTaP standard) is less effective in protecting against Hib than one that uses the older form with whole-cell pertussis. The booster at 1 year should help maintain protection, however.

The Hib vaccine may benefit older people who have had their spleen removed or illnesses that put them at risk for pneumonia, including sickle cell disease, leukemia, and HIV infection.

Click the icon to see an image of sickle cells.

Side effects of the Hib vaccine include redness and pain at the injection site, moderate fever, and, in rare cases, weakness, nausea, and dizziness.

Human Papillomavirus (HPV)

In 2006, the U.S. Advisory Committee on Immunization Practices( ACIP) voted to recommend the use of the first vaccine (Gardasil) to protect against human papillomavirus (HPV). This group of 100 viruses includes some 40 sexually transmitted viruses. Some HPV viruses can significantly increase the risks of cervical cancer, as well as cancers of the vulva, vagina, anus, and penis.

HPV is a very common virus; an estimated 20 million people in the U.S. have it. At least half of all sexually active men and women will eventually develop the virus.

A 2007 study indicated that the Gardasil vaccine is 100% effective against cervical, vaginal, and vulvar diseases caused by 4 types of HPV (6, 11, 16, and 18); however, it does not protect against the other types of the virus. It is less effective in women who were exposed to the virus before they were vaccinated. A 2007 study indicated that the vaccine is effective for 5 years after women receive the initial dose. The manufacturer has applied to the FDA for approval of the vaccine to also help prevent cancers of the vagina and vulva.

A new experimental vaccine, called Cervarix, has been shown in research to be effective for 5 1/2 years against the 2 most prevalent strains of HPV. Research is also indicating that the vaccine might be effective against more types of infections than the Gardasil vaccine. Researchers are studying the vaccine further, and they're looking at whether Cervarix is effective in women over age 25.

Girls ages 11 - 12 should get the vaccine, but they can get it as early as age 9. Adolescents and women ages 13 - 26 also should get the vaccine if they haven't already received it. Young women should ideally get the vaccine before they are sexually active, but it is still effective in sexually active women who haven't yet been infected with HPV. Currently there is no research to confirm the vaccine's effectiveness in women over 26, so there is no recommendation yet for this age group. Gardasil is not recommended for pregnant women.

Young women should get 3 doses of the vaccine. They should get the second dose 2 months after the first dose, and the third dose 6 months after the first dose.

Studies have shown no significant side effects from the HPV vaccine. The most common side effect was soreness at the injection site.

Rotavirus

Rotavirus is the most common cause of diarrhea, cramps, and vomiting in infants, and affects about 3.5 million children in the U.S. each year. As many as 80% of small children become infected with the virus. Although most cases in this country are mild, more than 50,000 American children are hospitalized and as many as 125 die from severe diarrhea every year. Worldwide the virus can be devastating, causing more than 600,000 infant deaths annually. There is also some strong evidence that the virus can lead to childhood diabetes.

An oral vaccine (Rotashield) has been withdrawn after reports of a severe and even life-threatening condition called intussusception following use of the vaccine. Intussusception occurs when the bowel slips inside itself like a telescope and obstructs the intestine. The risk was very small and occurred within a week or two of the vaccination. Any child who previously had the vaccination no longer incurs any increased risk. Preliminary reports suggest that newer rotavirus vaccines may be highly effective in preventing infection among infants, although more research is needed to confirm these findings and to determine their safety record in a large number of children. The association between diabetes and the virus itself raises some alarm that the vaccine might also increase the risk in children who are genetically susceptible to type 1 diabetes.

The U.S. Food and Drug Administration (FDA) approved a new oral rotavirus vaccine (Rotavirus, Live, Oral, Pentavalent vaccine -- trade name RotaTeq) early in 2006, and the Advisory Committee on Immunization Practices (ACIP) recommended that all infants should be immunized (3 liquid doses by mouth at 2, 4, and 6 months of age). In February 2007, the FDA announced there had been 28 reports of intussusception in infants who received the vaccine. After carefully monitoring cases of intussusception and other adverse effects associated with RotaTeq the FDA announced in March 2007 that the vaccine does not pose an increased risk of intussusception.

Because this is a deadly virus for many children worldwide, international groups believe that the few cases of intussusception do not warrant withdrawing its use, at least for countries where the infection is so common and deadly.

Click the icon to see an x-ray of intussusception.

Smallpox

Vaccination against smallpox used to be routine in the U.S. until 1972, and most older Americans bear the telltale small round smallpox vaccination scar on their upper arms. Immunity may last 10 years or longer. The last case of smallpox, a highly contagious and deadly disease caused by the variola virus, occurred in a laboratory worker in the U.K. in 1978.

However, the growing threat of bioterrorism has raised fears that smallpox could be used as a biological weapon, and in 2002 the US government issued plans for vaccinating every citizen against the disease in the event of an outbreak. The vaccination, however, carries some risks. Currently, then, vaccination continues to be recommended only for laboratory workers and scientists who work with the virus.

If an outbreak occurs, guidelines from the CDC call for a so-called "ring vaccination" approach. This involves identifying anyone who comes into contact with an infected person and vaccinating them and their contacts with a single dose of vaccine. This includes people of all ages and even those at risk for vaccine complications. The vaccine may work even if given within the first few days of infection.

Those at increased risk of vaccine complications but who should still be immunized if they are actually exposed to an outbreak include the following:

Children younger than a year. About 42 infants out of a million will develop brain swelling that may result in retardation or death. A severe, body-wide rash may also occur, especially if children touch the vaccination site.
Pregnant women. There is a small risk of miscarriage or premature delivery, although smallpox itself in pregnant mothers has more serious implications.
People with skin conditions, particularly eczema. They may develop a widespread blistering rash called eczema vaccinatum, which is fatal in 1 - 6% of cases, and they should not be vaccinated unless they've been exposed to the disease. They should also avoid others who have been vaccinated until those persons' vaccination scabs heal and fall off. People with non-chronic skin conditions, such as allergic rashes, severe burns, or chickenpox, may be vaccinated once their skin condition clears up.
People with suppressed immunity due to HIV, organ transplants, high-dose steroids, cancer chemotherapy, or other conditions.
Should a severe rash or other complication develop, patients should notify their doctors immediately. Two investigational medications, vaccine immune globulin (derived from the blood of people who have been vaccinated against smallpox) and an antiviral drug called cidofovir (Vistide), may be administered intravenously in the hospital should serious complications arise.
In the event of an outbreak, current plans specify that vaccination against smallpox will remain voluntary, although unvaccinated people who are exposed to the disease may be quarantined for 18 days to help contain the spread of disease.

Other Vaccinations

Many other types of vaccinations are available.

Rabies is a frequently fatal, acute viral infection that is transmitted to humans by infected animals (often dogs or bats) via a bite or exposing broken skin to an infected animal's saliva. In the past, human cases in the U.S. usually resulted from a dog bite, but more cases of human rabies have been linked to bats. Meanwhile, there have not been any rabies cases caused by dog bites for a number of years. Few cases occur in the U.S. because of extensive animal vaccination programs.

Anyone who is exposed to bats or to secretions of an animal suspected of having rabies should receive the rabies vaccine. Exposed individuals should also receive immune globulin unless they were previously vaccinated. Veterinarians and animal handlers should be vaccinated. This does not eliminate the need for treatment if they are exposed to rabies, but it reduces the intensity of the treatment.

Side effects include pain, redness, swelling at the injection site, headache, nausea, stomach pain, muscle aches, and dizziness. Allergic response can occur after the first shot and as many as 21 days after a booster shot. Rare cases of neurologic disorders that cause pain and paralysis in the legs and arms have also been reported. These neurologic disorders usually clear up in about 12 weeks.

Click the icon to see an image of rabies.

Plague is a severe, and potentially deadly, infection. It is caused by the organism Yersinia pestis. Wild rodents, like rats, spread the disease to humans. Plague is spread among rodents by a flea bite. Humans may get the plague when they touch or eat the infected animal, or when they come in contact with its feces. Certain forms of the plague can be spread from human to human. Plague is rare in the United States, but has been known to occur in parts of California, Utah, Arizona, Nevada, and New Mexico.

Veterinarians and assistants in the western U.S. or anyone who works with potentially plague-infected animals and travelers to developing countries where outbreaks have occurred should be vaccinated. The plague vaccine is not 100%y protective; it may only lessen severity of the disease. Preventive antibiotics are needed for anyone exposed. Side effects include headache, malaise, fever, swollen lymph nodes, and, occasionally, non-infected abscesses. Allergic reactions may occur, particularly in those sensitive to beef, soy, milk, and phenol.

Anthrax is an infectious disease caused by the spore-forming bacteria called Bacillus anthracis. Infection in humans most often involves the skin, the gastrointestinal tract, or the lungs.

Anthrax commonly affects hoofed animals such as sheep and goats, but humans who come in contact with the infected animals can get sick from anthrax, too. Historically, the populations most at risk for anthrax included farm workers, veterinarians, and tannery and wool workers. Anthrax is a potential agent for use as a biological weapon or for bioterrorism. In 2001, bioterrorist activities involving the U.S. Postal Service infected 22 people with anthrax; 7 survivors had confirmed cutaneous anthrax disease.

Military personnel and vaccine researchers, as well as people who work with imported animal hides, furs, bone meal, wool, animal hair (especially goat hair), and bristles, should receive an anthrax vaccine. The anthrax vaccine appears to be safe and effective, even after exposure, but requires 6 shots over 18 months. Up to half of recipients develop temporary soreness; some develop fever. Pregnant women should not get the anthrax vaccine.

Click the icon to see an image of cutaneous anthrax.

Click the icon to see an image of tuberculosis.


Disease	Who Should Get It?	Additional Information
Adenovirus	Military personnel.	Vaccine given orally for the prevention of respiratory illness.
Yellow Fever	Travelers to developing countries where outbreaks have occurred, currently parts of Africa and Central and South America. Residents of these areas, particularly children.	Vaccinations safe and effective for the prevention of jaundice and kidney and liver failure. Anaphylactic reactions in those allergic to eggs. Very rarely, may cause a potentially fatal illness resembling yellow fever, with fever and diarrhea, particularly in seniors. Lower immunity when given with cholera vaccine; the vaccines should be given three weeks apart.
Cholera	Travelers to developing countries where outbreaks have occurred.	Recently developed vaccines (Dukoral, Mutacol) are more effective than previous ones, which provided little protection. Not recommended or available, however, in the US.
Typhoid	Travelers to developing countries where outbreaks have occurred.	Oral vaccines include: (Ty21a, Vivotif). The oral vaccines are not effective against parathyroid fever. One-shot vaccine (Typhim Vi). Can be taken as early as two weeks before travel. Vi-rEPA is a newer injected vaccine that is safe in children and may be more effective-than other vaccines to date. No vaccine is 100% effective. The response to the typhoid vaccine tends to be lower in older people.
Tuberculosis	Individuals exposed to infected people.	Bacille Calmette-Guerin vaccine has been the standard vaccine, but its effectiveness has been questioned. No longer recommended in US except for certain high-risk children. A new recombinant BCG vaccine, shown in early trials to be more effective, is now licensed for use and is undergoing continued study.
Meningitis caused by meningococcal bacteria	U.S. Advisory Committee on Immunization Practices (ACIP) recommendations now call for routine vaccination of all young adolescents (aged 11 - 12) as well as those previously defined as at increased risk: People exposed to single cases or outbreaks; freshmen college students living in dorms; military recruits; travelers to developing countries where outbreaks have occurred; patients with problems in the spleen.	Vaccines are available against four subtypes of meningococcal bacteria but not for serogroup B, which causes up to 40% of meningococcal disease in the U.S. Among young people, fatalities have been higher in 15- to 24-year-olds than those younger than 15.

Resources

www.immunize.org -- Immunization Action Coalition
www.cdc.gov/vaccines/ -- The National Immunization Program
www.fda.gov/cber/vaers/vaers.htm -- Vaccine Adverse Event Reporting System
www.909shot.com/Issues/Injury_Compensation.htm -- National Vaccine Injury Compensation Program
www.immunizationinfo.org -- The National Network for Immunization Information
www.vaccine.chop.edu -- Vaccine Education Center, Children's Hospital of Philadelphia
www.vaccinesafety.edu -- Institute for Vaccine Safety, Johns Hopkins School of Public Health
www.whathealth.com -- National Partnership for Immunization
www.immunofacts.com -- Information on vaccinations
www.vaccines.org -- The Vaccine Page

References

American Academy of Pediatrics Committee on Infectious Diseases. Recommended childhood and adolescent immunization schedule: United States, 2005. Pediatrics. 2005 Jan;115(1):182.

Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). Mor Mortal Wkly Rep. June 2007;56:1-40.

Centers for Disease Control and Prevention. Recommended Immunization Schedule for Ages 0-6 Years, United States, 2007.

Chaves SS, Gargiullo P, Zhang JX, Civen R, Guris D, Mascola L. Loss of vaccine-induced immunity to varicella over time. NEJM. March 15, 2007;356:1121-1129.

Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. NEJM. May 10, 2007;356:1928-1943.

Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet. April 7, 2007;369:1179-1186.

Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges CB. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2005 Jul 29;54(RR-8):1-40.

Poehling KA, Szilagyi PG, Crijalva CG, Martin SW, LaFleur B, Mitchel E, et al. Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine. Pediatrics. April 4, 2007;119:707-715.

Prevention of influenza in the general population: Recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ. 2004;171:10.

American Academy of Pediatrics Committee on Infectious Diseases. Prevention and control of meningococcal disease: recommendations for use of meningococcal vaccines in pediatric patients. Pediatrics. 2005 Aug;116(2):496-505.

Pneumococcal vaccine cuts severe bacterial disease in US. Mor Mortal Wkly Rep CDC Surveill Summ 2005;54:893-896.

Wise R, Iskander J, Pratt D, et al. Postlicensure Safety Surveillance for 7-Valent Pneumococcal Conjugate. JAMA. 2004; 292:1702-1710.

Krym VF, MacDonald RD. Global efforts to eradicate polio. CMAJ. 2004 Jan 20;170(2):189-90.

Zuckerman JN. Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines. J Med Virol. 2006 Feb;78(2):169-77.

Review Date:
10/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Asthma in children and adolescents

FitSugar — Wed, 08 Oct 2008 17:35:28 -0700

In This Report

Highlights
Introduction
Causes
Prognosis
Risk Factors
Symptoms
Diagnosis
Treatment
Quick-Relief Medications...
Long-Term Relief Medication...
Other Treatments
Managing Asthma
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

In 2007, the FDA requested the manufacturers of omalizumab (Xolair) to include a “boxed warning” emphasizing that this drug may cause a severe and life-threatening allergic reaction (anaphylaxis). Health care providers need to carefully observe patients for 2 hours after they receive an omalizumab injection. However, because an allergic reaction can occur up to 24 hours after the injection, patients need to know the signs and symptoms of anaphylaxis and how to self-administer emergency treatment. Omalizumab is approved for patients ages 12 and older who have moderate-to-severe asthma related to allergies.

Drug Approval

In 2006, budesonide/formoterol (Symbicort) was approved for patients age 12 years and older. Symbicort combines a corticosteroid and a long-acting beta2-agonist into a single inhaler.

Inhaled Corticosteroids

Inhaled corticosteroids may help reduce wheezing in young children with breathing problems, but they do not help prevent the development of asthma, according to several 2006 studies in the New England Journal of Medicine.
Inhaled corticosteroids work better than a corticosteroid/long-acting beta2-agonist combination or a leukotrine receptor antagonist drug in treating children with mild-to-moderate asthma, suggests a 2007 study in the Journal of Allergy and Clinical Immunology.

Long-Acting Beta2-Agonists

Long-acting beta2-agonist drugs such as salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer) may worsen asthma symptom severity and increase the risk for asthma-related death, indicates a 2006 review in the Annals of Internal Medicine.
Products that contain salmeterol and formoterol now have strengthened warning labels detailing these risks.

Childhood Asthma Statistics

Asthma death rates among children have largely declined since 1999 while doctors’ office visits for asthma treatment have more than doubled, indicates a recent report from the U.S. Centers for Disease Control and Prevention.

Introduction

The word asthma originates from an ancient Greek word meaning panting. Essentially, asthma is an inability to breathe properly. When any person inhales, the air travels through the following structures:

Air passes into the lungs and flows through progressively smaller airways called bronchioles. The lungs contain millions of these airways.
All bronchioles lead to alveoli, which are microscopic sacs where oxygen and carbon dioxide are exchanged.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Asthma is a chronic condition in which these airways undergo changes when stimulated by allergens or other environmental triggers. Such changes appear to be two specific responses:

The hyperreactive response (also called hyperresponsiveness)
The inflammatory response

These actions in the airway cause patients to cough, wheeze, and experience shortness of breath (dyspnea), the classic symptoms of asthma.

In the hyperreactive response, smooth muscles in the airways constrict and narrow excessively in response to inhaled allergens or other irritants. Airways in everyone's lungs respond by constricting when exposed to allergens or irritants but there are major differences in the hyperreactive response that occurs in people with asthma:

When people without asthma breathe in and out deeply, the airways relax and open in order to rid the lungs of the irritant.
When people with asthma try to take those same deep breaths, their airways do not relax but instead narrow, causing the patients to pant for breath. Smooth muscles in the airways of people with asthma may have a defect, perhaps a deficiency in a critical chemical that prevents the muscles from relaxing.

The hyperreactive stage is followed by the inflammatory response, which generally contributes to asthma in the following way:

The immune system responds to allergens or other environmental triggers by delivering white blood cells and other immune factors to the airways.
These so-called inflammatory factors cause the airways to swell, fill with fluid, and produce a thick sticky mucus.

Click the icon to see an image of a normal versus asthmatic bronchiole.

This combination of events results in wheezing, breathlessness, inability to exhale properly, and a phlegm-producing cough.

Inflammation appears to be present in the lungs of all patients with asthma, even those with mild cases, and plays a key role in all forms of the disease.

Causes

Asthma occurs in about 5 million American children. Each year about 200,000 of them are hospitalized. It is the most common chronic childhood illness. About half of all cases of asthma develop before the age of 10, and about 80% of patients develop symptoms before they are 5 years old.

The mechanisms that cause asthma are complex and vary among population groups and even individuals. For example, asthma in children is highly associated with allergies. However, only a minority of children with allergies have asthma, and allergic response cannot explain all cases of asthma. Other factors, such as genetics or environmental conditions are probably involved in the development of asthma. Most likely, several genes combine to make a child susceptible to environmental triggers, not only allergens but also possibly infections, dietary patterns, or air pollution. Physical factors, particularly having smaller lungs, affect the chances for later asthma.

Asthma and allergies often coexist, and the allergic response plays a strong role in childhood asthma. About 70 - 85% of children with asthma also have allergies. Some studies suggest that children who have allergies are also at greater risk for developing asthma as adults. A 2006 study found that children who are allergic to dust mites are three times more likely to later develop asthma than children who were not allergic.

However, the evidence is clearly mixed. Several other 2006 studies suggested that avoiding dust mites does not help prevent asthma and, in fact, early exposure to dust mites may even protect children from developing asthma and allergic responses. Some experts think that giving immunotherapy (“allergy shots”) to children with allergies may help prevent asthma development.

An asthma attack can be induced or aggravated by direct irritants to the lungs. Studies indicate that the more indoor allergens a child is allergic to, the higher the risk for severe asthma. Important irritants or allergens include the following:

Dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. These are the primary allergens in the home.
Animal dander. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems.
Molds.
Cockroaches. Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
Pollen. An asthma attack from an allergic response to pollen is more likely to occur during extreme air changes, such as thunderstorms. Major weather changes, such as El Nino, can affect the timing of allergy seasons because they cause seasonal changes (and pollen) to start earlier.
Food allergies. About 8 - 10% of children with asthma also have food allergies. These children also appear to have a high risk for very serious reactions to such foods. In infants and toddlers, allergy to eggs appears to be a predictor of asthma.
Fossil Fuels. Certain chemicals may trigger allergic rhinitis. Some experts believe that refined fossil fuels, such as diesel fuel and particularly kerosene, may be important triggers for allergic rhinitis. In people who already have allergies or asthma, exposure to such fossil fuels may worsen symptoms.

The Allergic Response. The allergic process, called atopy, and its connection to asthma are not completely understood. It involves various airborne allergens or other triggers that set off a cascade of events in the immune system leading to inflammation and hyperreactivity in the airways. One description is as follows:

The conductor in an orchestra of immune factors that contribute to allergies and asthma appears to be a category of white blood cells known as helper T cells, in particular a subgroup called Th2 cells.
Th2 cells overproduce interleukins (ILs), immune factors that are molecular members of a family called cytokines, which are involved in the inflammatory process.
Interleukins 4, 9, and 13, for example, may be responsible for a first-phase asthma attack. These interleukins stimulate the production and release of antibody groups known as immunoglobulin E (IgE). (People with both asthma and allergies appear to have a genetic predisposition for overproducing IgE.)
During an allergic attack, these IgE antibodies can bind to special cells in the immune system called mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of a number of active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, overproduce mucus, and activate nerve endings in the airway lining.
Another cytokine, interleukin 5, appears to contribute to a late-phase inflammatory response. This interleukin attracts white blood cells known as eosinophils. These cells accumulate and remain in the airways after the first attack. They persist for weeks and mediate the release of other damaging particles that remain in the airways.

Researchers are investigating the role that T cells play in asthma. T cells are white blood cells that are involved in the immune response. Researchers had focused on the T cell called type 2 helper (ThH2) cells. However, a 2006 breakthrough study in the New England Journal of Medicine suggested that a different type of T cell may play a stronger role in asthma than previously thought.

Researchers discovered that these cells, called natural killer T cells, are far more common in the lungs of people with asthma than in the lungs of healthy people. Natural killer T cells are very rare, but researchers found them in 60% of people with moderate-to-severe persistent asthma. While this research is preliminary, it may explain why corticosteroid drugs do not work well for some patients with asthma: Steroid drugs target Th2 and other inflammatory cells, not natural killer T cells. Researchers think that further investigation of natural killer T cells may lead the way to new types of asthma drugs. If these cells prove to be involved in asthma, then drugs that eliminate them might become an important new treatment.

Over the course of years the repetition of the inflammatory events involved in asthma can cause irreversible structural and functional changes in the airways, a process called remodeling. The remodeled airways are persistently narrow and can cause chronic asthma. Researchers are trying to determine how this process occurs:

Interleukins. Some researchers are looking at potent immune factors, including interleukins 11 and 13. They have been linked to a number of processes possibly involved in remodeling, including scarring in the airways and overgrowth of cells in the smooth muscles that line the airways.

Growth Factors. Compounds known as vascular endothelial growth factor (VEGF) have been observed in the airways of patients with asthma. VEGF is a powerful promoter of cell growth in blood vessel linings and some researchers believe it may be major factor in remodeling.

About one-third of all persons with asthma share this condition with another member of their immediate family. Asthma may be more likely to be passed to children from the mother than from the father. Both allergies and asthma are strongly associated with hereditary factors, sharing certain genetic markers, but they are not always inherited together.

Research on the genetics of these conditions is confusing. Of some significant promise, researchers have identified a gene (ADAM33), which has been linked to asthma. The gene regulates one of the enzymes called metalloproteases, which are involved with the smooth muscle in the airway. A mutation of this gene could play a role in airway changes that occur after inflammation.

The role of early childhood respiratory and intestinal infections is very complex. Viral respiratory infections certainly worsen existing asthma, but the most common ones are unlikely to be causes of childhood asthma. In fact, early respiratory and intestinal infections may offer some protection against asthma.

Early Respiratory Infections as Causes of Asthma. Studies suggest that most respiratory infections are not important causes of asthma in children, except in certain cases. An important exception is the respiratory syncytial virus (RSV), which has been implicated in the development of asthma. RSV is the major viral cause of infant pneumonia. Studies also indicate that infants who have reduced lung function within a few days after birth are at increased risk of developing asthma by the time they are 10 years old.

Common Respiratory Infections Worsen Asthma. Common respiratory infections viruses that cause colds (such as the rhinovirus) may in some cases be associated with the development of asthma. A 2007 study suggested that children who have a wheezing rhinovirus during infancy are at increased risk for developing asthma by age 6. Even if these viruses do not directly cause asthma, they can worsen asthma in children who already have it. Rhinovirus has been reported to be the most common infection associated with asthma attacks. In one study, it was associated with 61% of asthma worsening in children. Some research suggests that colds promote inflammation in patients with existing asthma and increase the intensity of airway responsiveness for weeks.

The Hygiene Theory: Early Infections as Protection Against Asthma. Another blames the dramatic increase in asthma on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. The basic theory rests on the idea that infections stimulate production of specific immune factors called Th1 cells. As these cells build up, they replace other immune factors called Th2 cells, which react to allergens -- a less serious threat to the body. Without infections to stimulate the production of the Th1 infection fighters, the Th2 allergen fighters are not replaced, and they persist at high levels, making the growing child more susceptible to allergies and asthma.

A number of different studies support this theory:

Some studies suggest that being part of a large family or attending day care increases the risk for early respiratory infections but reduces the risk of childhood asthma. The occasional cold, then, may be protective.
In one study, researchers measured levels of bacterial byproducts called endotoxins in the mattress dust of 812 children. Those with the highest levels had 80% lower rates in allergies and asthma.
Another study further found a strong association between allergy development and the absence of certain beneficial bacteria (called probiotics) carried in the infant's intestines. Infants who were born in more hygienic environments tended to lack these bacteria. Antibiotic overuse and modern hygiene may be reducing these helpful organisms. (Probiotics can be obtained in active yogurt cultures and in supplements, which are being studied for protection.)

The standard vaccinations against serious childhood infections, according to several important studies, pose no risk for asthma. One of the studies even reported some lower risk for asthma and allergies in the second and third years after vaccinations. Infections killed thousands of children every year before immunization became widespread. Asthma, although serious, is rarely fatal in children. No one should stop giving their children vaccinations against childhood killers.

GERD. At least half of patients with asthma also have gastroesophageal reflux disease (GERD), the cause of heartburn. It is not entirely clear which condition causes the other or whether they are both due to common factors.

Heartburn is a condition where the acidic stomach contents back up into the esophagus causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux which causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

Some theories for the causal connection between GERD and asthma are:

Acid leaking from the lower esophagus in GERD stimulates the vagus nerve, which runs through the gastrointestinal tract. This stimulated nerve, in turn, triggers the nearby airways in the lung to constrict, causing asthma symptoms.
Acid back-up that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that cause asthma symptoms.

GERD is sometimes hard to detect and might be suspected as a contributor in the following patients:

Those who do not respond to asthma treatments.
Those whose asthma attacks follow episodes of heartburn.
Those whose attacks are worse after eating or exercise.
Those whose coughs follow episodes of acid reflux. (One study found that GERD was associated with about half of the episodes of coughs and wheezes in patients with asthma.)

Treating GERD symptoms with anti-acid drugs may resolve asthma in some (but not all) patients who share both conditions. A small 2005 observational study found that while GERD was common in patients with asthma, treatment of GERD had no effect on asthma symptoms. [See In-Depth Report #85: Heartburn and gastroesophageal reflux disease.]

Sinusitis. Almost half of children and adults with allergic asthma have sinus abnormalities, and in various studies, between 17 - 30% of patients with asthma develop true sinusitis. The presence of sinusitis, however, does not appear to increase the severity of asthma.

Click the icon to see an image of sinusitis.

Parental Migraines and Childhood Asthma. Some studies have reported a link between childhood asthma and parental migraines, with one small study suggesting that children are about five times more likely to develop asthma if their parents have a history of migraines.

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath.

About 10% of adults and some fewer children have aspirin-induced asthma (AIA). With this condition, asthma gets worse when patients take aspirin. Aspirin is one of the drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs). Although aspirin is used to reduce inflammation in other disorders, it appears to have the opposite effect in many asthma cases. It is not wholly known why this occurs. AIA often develops after a viral infection. It is a particularly severe asthmatic condition and is associated with up to 25% of asthma-related hospitalizations. In about 5% of cases, aspirin is responsible for a syndrome that involves multiple attacks of asthma, sinusitis, and nasal congestion. Such patients also often have polyps (small benign growths) in the nasal passages.

Patients with aspirin-induced asthma (AIA) should avoid aspirin and most likely NSAIDs, including ibuprofen (Advil) and naproxen (Aleve).

Acetaminophen (Tylenol) has been the traditional alternative for relief of minor pain for patients who are aspirin-sensitive. Unfortunately, recent evidence has muddied these recommendations. Moreover, some asthmatic episodes have been linked to high consumption of acetaminophen among adults. And a study of children with asthma reported that those who took ibuprofen were less likely to be hospitalized for asthma than those taking acetaminophen. This is of particular concern, since acetaminophen is the pain reliever of choice in small children.

Asthma occurs primarily at night (nocturnal asthma) in as many as 75% of patients with the condition. Attacks often occur between 2 - 4 a.m. Factors that might play role in nocturnal asthma may include one or more of the following:

Chemical and temperature changes in the body during the night that increase inflammation and narrowing of the airways
Delayed allergic responses from exposure to allergens during the day
The wearing off of inhaled medications toward the early morning
An increase in acid reflux (back up of stomach acid) that causes airways to narrow
Postnasal drip that occurs during sleep
Conditions relating to sleep, such as sleep apnea or sleeping on one's back, which may worsen any asthma attack that occurs at night

Some experts believe that nocturnal asthma may actually be a unique form of asthma with its own specific biologic mechanisms that occur only at night and which reduce natural steroid hormones (which block inflammation).

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath. This condition generally occurs in children and young adults, most often during intense exercise in cold dry air. Symptoms are generally most intense about 10 minutes after exercising and then gradually resolve.

EIA is triggered only by exercise and is distinct from ordinary allergic asthma in that it does not produce a long duration of airway activity, as allergic asthma does. (However, some people have both forms of asthma.) People who have only EIA do not appear to require long-term maintenance therapy. A study of military recruits with EIA also reported that the condition does not hinder a person's overall physical performance.

Medications. Cromolyn, a mild anti-inflammatory drug, or short-acting beta2-agonists have been the treatments of choice for preventing EIA. Newer approaches for people who work out regularly include pretreatment with long-acting beta2-agonists, such as salmeterol (Serevent) or the regular use of inhaled corticosteroids.

Hints for Reducing EIA. EIA occurs only after exercise and is more likely to occur with regular paced activities in cold, dry air. The following are some suggestions for reducing its impact:

Warm-up and cool-down periods are important.
Patients with EIA might do better with activities that involve short bursts of exercise (tennis, football) than with exercises involving long-duration regular pacing (cycling, soccer, and distance running).
Breathing through a scarf or through the nose helps warm up the airways.
Restricting dietary salt might help reduce EIA.

Click the icon to see an image of exercise-induced asthma.

Prognosis

Asthma is the third major cause of hospitalization in children under age 15. The condition can be very serious in children, particularly those younger than age 5, because their airways are very narrow.

The severity of asthma is graded as mild intermittent and mild, moderate, and severe persistent. A patient in any of these categories, even mild intermittent, can still experience a severe and even life-threatening attack. According to one report, 30% of asthma deaths occur in patients with mild asthma.

Asthma is rarely fatal in children, with only 187 asthma deaths reported in 2002 in children under age 18. In fact, a 2006 study from the U.S. Centers for Disease Control and Prevention reported that asthma death rates for children have steadily declined since 1999. (During the same time, the number of doctor visits for asthma treatment more than doubled.) Even low mortality numbers are unacceptable, however, since asthma deaths are largely preventable.

Factors associated with an increased risk of death from asthma in children include:

Previous life-threatening episodes of asthma
Lack of adequate and ongoing health care. (Most likely the reason for the higher fatalities rates in minority children.)
Significant behavioral problems
Underestimating the severity of an acute attack poses the greatest threat. Unfortunately, one study of children found that nearly 40% of them were unaware of asthmatic symptoms when they occurred.

African American children have more than six times the death rate of Caucasians in the age groups of 4 years and younger and 15 - 24 years. Hispanic children also have a higher risk.

The following signs and symptoms may indicate a life-threatening situation:

As the chest labors to bring enough air into the lungs, breathing often becomes shallow.
Lacking sufficient oxygen, the skin becomes bluish.
The flesh around the ribs of the chest appears to be sucked in.
The patient may begin to lose consciousness.

Asthma often progresses very slowly to a serious condition or may develop to a fatal or near-fatal attack within a few minutes. It is very difficult to predict when an attack will become very serious. Early symptoms or lack thereof do not always reflect the ultimate severity of an attack. Some studies even suggest that people at high risk for fatal or near-fatal asthma attacks are those with poor awareness of their own reduced ability to breathe and who are slow in seeking help. Monitoring peak flow rates is, therefore, an important management component, since it provides a more accurate assessment of lung function than symptoms alone.

In a 2003 study, researchers followed people with asthma for longer than 30 years. About a third of children had outgrown their asthma in adulthood. In general, the more severe the childhood asthma, the greater the likelihood that it will persist. For example, only 23% of children who experienced wheezy bronchitis (wheezing during respiratory infections) suffered from frequent or persistent asthma in adulthood.

There is evidence that severe asthma can cause long-lasting damage and possibly permanent scarring in some patients. The risk for such injury is highest, however, when asthma strikes children in the first 3 - 5 years. There does not appear to be any significant risk for long-term lung damage for children who develop mild-to-moderate persistent asthma between ages 5 - 12. Children adapt well to living with asthma, and even with severe asthma they can function as well as healthy children in virtually all areas of life.

Studies are mixed over the effects of emotional disorders on the severity of asthma. One study indicated that parents of children with asthma may suffer greater psychological stress than their children. A 2000 study reported that mild-to-moderate asthma does not significantly affect the psychological well-being of most children ages 5 - 12. Teenagers and preteens may have particular difficulty coping with what they perceive as the social stigma of asthma. Parents and older children should not hesitate to seek help from support groups, doctors, friends, or family members. Support programs may help children to better manage their asthma and even reduce hospitalization.

Although there have been few studies on the effects of asthma on schooling, a 2000 study reported that nocturnal (nighttime) asthma affected school attendance and performance in children and work attendance in their parents.

Risk Factors

Asthma affects about 5 million American children between the ages of 5 - 14. Asthma has dramatically increased worldwide over the last few decades, in both developed and developing countries. From 1980 - 1994, asthma increased 160% in American children younger than 4 years and has also dramatically risen worldwide. Experts are puzzling over the cause of this phenomenon. Possible causes and risk factors that are suspects in the dramatic rise in asthma in children include:

Survival rates are now higher in low-birth-weight babies, who may be more susceptible to asthma.
Declining rates in nursing may be a contributor. Breast milk contains important anti-inflammatory substances, such as omega-3 fatty acids, which might protect against asthma.
Western dietary habits (which commonly include more fast foods and less fruits, vegetables, fiber, minerals, and other nutrients) may contribute to the development of childhood asthma.
Children are spending more time indoors watching television, playing video games, or using the computer and are, therefore, overexposed to indoor allergens.
The trend of making homes more energy-efficient may result in dust mites being trapped inside them.

Among younger children, asthma develops twice as frequently in boys as in girls, but after puberty it may be more common in girls.

Urban Life. Urban life is strongly associated with a higher risk. Although poverty plays a significant role, urban life has been associated with a higher risk for asthma in any income group and among both children and adults. In some urban areas, as many as 25% of children have asthma or show signs of wheezing. In fact, it may be greatly underdiagnosed in city children. A 1999 study reported that almost a third of children in inner-city kindergartens had asthma symptoms without a diagnosis of the disorder; 10% had actually been diagnosed with asthma, mainly because their symptoms were severe.

Ethnicity. Since 1980, asthma rates have risen the most dramatically among African American children, and they have significantly higher rates of asthma than Caucasian children. Hispanic children are also at higher risk. Both groups of minority children are more likely to have fatal asthma than Caucasian children.

Some studies indicate that the difference in risk exists simply because African Americans and other minority groups are more likely to live in urban areas. Poverty and lack of access to health care also play a role. However, Caucasian children who live in cities also face a high risk for asthma, and rural African American children do not.

Urban life and socioeconomic factors, however, may not fully explain the ethnic disparity.

Low Birth Weight. Infants of low birth weight are at higher risk for lung problems and asthma.

Winter Birth. Children born in the winter may have a greater risk for asthmatic allergies to cockroaches than children born at other times of the year.

Vitamin D. A 2006 study suggested a link between vitamin D intake during pregnancy and development of early childhood asthma. Pregnant women who had a higher intake of vitamin D were less likely to give birth to children who developed asthma.

Breast Feeding. Most studies on breastfeeding report some protection against wheezing and asthma in the first year of life. Breastfeeding has many other benefits for the child as well. The American Academy of Pediatrics recommends exclusively breastfeeding for the child's first 6 months of life.

Complications of Pregnancy. According to a 2000 study, complications of pregnancy, specifically those involving the mother's uterus (such as post-birth hemorrhage, pre-term contractions, insufficient placenta, and restricted growth of the uterus), are associated with an increased risk of childhood asthma. Another study reported that delivery procedures such as Cesarean section, the use of vacuum extraction or forceps also raised the risk of childhood asthma.

In both adults and children, the incidence of obesity and asthma has been increasing over recent years. Studies report a strong association between the two conditions. Some experts suggest that excess weight pressing on the lungs may trigger the hyperreactive response in the airways typical of asthma. Others believe that asthma leads to obesity by inhibiting physical activity, although several studies have found no difference in activity levels between people with or without asthma. Some studies suggest that many obese people may be misdiagnosed as having asthma when they are simply short of breath, possibly because of the increased effort required for breathing.

In any case, there is evidence that losing weight can relieve asthma symptoms. Some evidence also suggests that people who are overweight (body mass index greater than 25) have more difficulty getting their asthma under control. Weight loss in anyone who is obese and has asthma or shortness of breath reduces airway obstruction and improves lung function. [See In-Depth Report #53: Weight control and diet.].

Damp Homes. Studies suggest that children who live in damp homes have a much higher risk for asthma.

Mental Health. Research indicates that poor mental health of parents and children are significant predictors of more severe symptoms in childhood asthma. A 2000 study suggested that high stress levels can predict the onset and severity of asthma in children genetically at risk for the condition.

Symptoms

In children with asthmatic symptoms, it is important to first consider as a possible cause inhaled foreign objects such as peanuts; viral infections such as croup; and bacterial infections, which may be accompanied by high fever and progress rapidly. Any child who has frequent coughing or respiratory infections should be checked for asthma.

The classic symptoms of an asthma attack include:

Wheezing when breathing out is nearly always present during an attack. Usually the attack begins with wheezing and rapid breathing, and, as it becomes more severe, all breathing muscles become visibly active.
Shortness of breath (dyspnea). Shortness of breath is a major source of distress in patients with asthma, although severe dyspnea does not always reflect a serious attack or reduced lung function.
Coughing. In some people, the first symptom of asthma is a nonproductive cough.
Chest tightness or pain. Initial chest tightness without any other symptoms may be an early indicator of a serious attack.
Neck muscles may tighten, and talking may become difficult or impossible.
Rapid heart rate
Sweating
Chest pain occurs in about 75% of patients. It can be very severe, although its intensity is not necessarily related to the severity of the asthma attack itself.

The end of an attack is often marked by a cough that produces thick, stringy mucus. After an initial acute attack, inflammation persists for days to weeks, often without symptoms. (The inflammation itself must still be treated, however, because it usually causes relapse.)

Diagnosis

The doctor will consider a diagnosis of asthma if a child has a history of periodic attacks of shortness of breath, coughing, and wheezing, perhaps accompanied by tightness in the chest. The parent should describe the pattern of symptoms and possible precipitating factors, including:

Whether symptoms are more frequent during the spring or fall (allergy seasons)
Whether exercise, a respiratory infection, or exposure to cold air has ever triggered an attack
Any family history of asthma or allergic disorders such as eczema, hives, or hay fever

A number of disorders may cause some or all of the symptoms of asthma. Panic disorder can coincide with asthma or be confused with it. Other diseases that must be considered during diagnosis are pneumonia, bronchitis, severe allergic reactions, psychosomatic illnesses, and certain rare disorders (such as tapeworm and trichomoniasis).

If symptoms and a patient's history are indicative of asthma, the doctor will usually perform tests known as pulmonary function tests to confirm the diagnosis and determine the severity of the disease.

Using a spirometer, an instrument that measures the air taken into and exhaled from the lungs, the doctor will determine several values:

Vital capacity (VC), which is the maximum volume of air that can be inhaled or exhaled.
Peak expiratory flow rate (PEFR), commonly called the peak flow rate, which is the maximum flow rate that can be generated during a forced exhalation.
Forced expiratory volume (FEV1), the maximum volume of air expired in 1 second.

If the airways are obstructed, these measurements will fall. Depending on the results, the doctor will take the following steps:

If measurements fall, the doctor typically asks the patient to inhale a bronchodilator. This drug is used in asthma to open the air passages. The measurements are taken again. If the measurements are more normal, the drug has most likely cleared the airways, and a diagnosis of asthma is strongly suspected.
If measurement results fail to show airway obstruction, but asthma is still suspected, the doctor may perform a challenge test. It involves administering a specific drug (histamine or methacholine) that usually increases airway resistance only when asthma is present.

The patient may be given skin or blood allergy tests, particularly if a specific allergen is suspected and available for testing. Allergy skin tests may be the best predictive test for allergic asthma, although they are not recommended for people with year-round asthma.

One of the most common methods of allergy testing is the scratch test or skin prick test. The test involves placing a small amount of the suspected allergy-causing substance (allergen) on the skin (usually the forearm, upper arm, or the back), and then scratching or pricking the skin so that the allergen is introduced under the skin surface. The skin is observed closely for signs of a reaction, which usually includes swelling and redness of the site. With this test, several suspected allergens can be tested at the same time, and results are usually available within about 20 minutes.

Tests that either rule out other diseases or obtain more information about the causes of asthma include the following:

A complete blood count
Chest and sinus x-rays
Computed tomography (CT) scans. CT scans may be helpful in certain cases, such as for determining wall thickness in airways in patients who are difficult to treat, which could signify a higher risk for lung damage.
Examination of the patient's sputum for eosinophils (white blood cells that in high levels are associated with severe allergic asthma).
Researchers are investigating measurements of certain chemicals in sputum or exhaled air that indicate airway inflammation. Such chemical markers include nitric oxide and hydrogen peroxide. For example, high levels of nitric oxide may prove to be a simple and noninvasive way of diagnosing asthma.

Treatment

Treating an Acute Attack in the Hospital. An acute attack may require hospitalization. Laboratory tests, an electrocardiogram (ECG), and a chest x-ray are performed to determine lung function, oxygen levels, and other indications of severity or rule out other causes. Depending on the results, the following treatments may be given:

Beta2-agonists are the standard therapy. They are typically administered with a nebulizer (a device that administers the drug in a fine spray). Studies suggest, however, that even very small children may be able to use metered-dose inhalers (MDIs), which are just as effective and more convenient than nebulizers. (Intravenous delivery is not recommended in most cases.)
An anticholinergic drug (ipratropium) is sometimes added to improve symptoms.
A corticosteroid (commonly called a steroid) given within the first hour helps reduce the need for hospitalization. Steroids may be administered intravenously, as a shot, or orally. Children may respond well to oral steroids.
Oxygen is usually administered, and can be life saving in severe cases.
Infusions of magnesium sulfate open airways and are an important emergency treatment for adults. Its benefits for children need to be further demonstrated.
In life-threatening situations, the patient may require mechanical ventilation.

Antibiotics are not useful for asthma attacks if there is no strong evidence of the presence of a bacterial infection. Viral infections, most often colds and the flu, are more likely to trigger an asthma attack. In such cases, antibiotics are not helpful and may have adverse effects.

Discharge and Relapse After Hospitalization. It typically takes about 3 - 4 hours to determine if a patient can be safely sent home or if they need to stay. Patients are generally discharged when:

Symptoms are gone or minimal, and
The peak expiratory flow rate is 70% or more of the predicted rate

Despite reasonable precautions, between 12 - 16% of patients relapse within 2 weeks of leaving the hospital. Receiving a steroid shot at discharge or taking an oral corticosteroid for a few days can reduce this risk.

Avoiding allergens, following appropriate drug treatments, and home monitoring are key elements in preventing dangerous asthma attacks and hospitalization. In addition, good communication between the doctor and patient is a key factor in a successful management program.

Medications for asthma fall into two categories:

Rescue Medications. Medications that open the airways (bronchodilators, or inhalers) are used to quickly relieve any moderate or severe asthma attack. These drugs are usually short-acting beta-adrenergic agonists (beta2-agonists). Other drugs used in special cases include corticosteroids taken by mouth and anticholinergic drugs. None of these drugs have any effect on the disease process itself. They are only useful for treating symptoms.
Maintenance Medications. Simply coping with asthma symptoms without also controlling the damaging inflammatory response is a common and serious error. For adults and children over age 5 with moderate-to-severe persistent asthma, experts now recommend inhaled corticosteroids and long-acting beta2-agonists.

Parents can greatly reduce the frequency and severity of their children’s asthma attacks by understanding the difference between coping with asthma attacks and controlling the disease over time. Unfortunately, many patients do not understand the difference between medications that provide rapid, short-term relief and those that are used for long-term symptom control. Many patients with moderate or severe asthma overuse their short-term medications and underuse their corticosteroid medications. The overuse of bronchodilators can have serious consequences; not using steroids can lead to permanent lung damage.

Patients need to understand that asthma symptoms can change quickly over time and that treatment strategies may need to change in response. In 2005, the two leading U.S. allergy associations published joint guidelines on controlling asthma. The guidelines emphasize that asthma treatment decisions need to be made on an individual basis. It is important that patients have a close relationship with their doctor. The doctor needs to evaluate a patient’s asthma symptoms at each visit to determine any need for changes in medication. According to the guidelines, asthma management is classified as either “well-controlled” or “not well-controlled.” The doctor may need to change some medications, or increase or decrease the dosage, depending on whether a child’s asthma is well-controlled or not well-controlled.

These are the signs of well-controlled asthma:

Asthma symptoms occur twice a week or less
Rescue bronchodilator medication is used twice a week or less
Symptoms do not cause nighttime or early morning awakening
Symptoms do not limit work, school, or exercise activities
Peak flow meter readings are normal or the patient’s personal best
Both the doctor and the patient consider the asthma to be well controlled


Classification	Symptom Frequency	Children Age 5 Years and Younger: Recommended Treatment	Children Older Than 5 Years: Recommended Treatment
Mild intermittent	At least 2 days per week. At least 2 nights per month.	No daily medication.	No daily medication. If severe attacks occur, systemic corticosteroids recommended.
Mild Persistent	More than 2 days per week, but less than once per day. More than 2 nights per month.	Preferred treatment: Low-dose inhaled corticosteroids with nebulizer, or MDI with holding chamber with or without face mask. Alternative treatment: Cromolyn or leukotriene-antagonist.	Preferred treatment: Low-dose corticosteroids. Alternative treatment: Cromolyn, leukotriene modifier, nedocromil, OR sustained release theophylline.
Moderate Persistent	Daily daytime symptoms. More than 1 night per week.	Preferred treatment: Low-dose inhaled corticosteroids and long-acting beta2-agonists OR medium-dose inhaled corticosteroids. Alternative treatment: Low-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline. If needed (especially if severe attacks occur): Medium-dose inhaled corticosteroids and long-acting beta2-agonists; medium-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline.	Preferred treatment: Low-to-medium dose inhaled corticosteroids and long-acting beta2-agonists. Alternative treatment: Low-to-medium dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline, or increased medium dose inhaled corticosteroids. If needed (especially if severe attacks occur): Increase dosage of medium-dose inhaled corticosteroids with add-on long-acting beta2-agonists. Alternatively, increase dosage of medium-dose inhaled corticosteroids plus either leukotriene receptor antagonist or theophylline.
Severe Persistent	Continual daytime symptoms. Frequent nighttime symptoms.	Preferred treatment: High-dose inhaled corticosteroids and long-acting beta2-agonists plus (if needed) oral corticosteroids.	Preferred treatment: High-dose inhaled corticosteroids combined with long-acting inhaled beta2-agonists. Add, if needed: Oral corticosteroids. Repeat attempts should be made to reduce use of systemic corticosteroid and maintain control with inhaled corticosteroid.
Adapted from National Asthma Education and Prevention Program (NAEPP) Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma – Update on Selected Topics 2002 (EPR-2 Update).

Most asthma drugs are inhaled using various forms of inhalers or nebulizers. Inhaled drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. Studies suggest that many children fail to use the devices properly, although newer devices are easier to use than others. The basic devices are the metered-dose inhaler (MDI), breath-actuated inhalers, dry powder inhalers, and nebulizers.

MDIs have used chlorofluorocarbons (CFCs) as their propellants. CFCs are damaging to the environment and are now being replaced with other propellants (hydrofluoroalkane) that are more environmentally safe, and do not chill the device as CFCs do. Devices that don't use any propellants are also now available.

Metered-Dose Inhaler. The standard device for administering any asthma medication is the metered-dose inhaler (MDI). This device, particularly when used with a spacer, allows precise doses to be delivered directly to the lungs. (The spacer is a tube that is attached to the inhaler. It serves as a holding chamber for the medication that is sprayed by the inhaler.) MDI-delivered drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. Some patients hold the MDI too close to their mouths, or even inside them. Others may exhale too forcefully before inhalation.

The spacer helps improve medication delivery by allowing the patient additional time to inhale. They vary, however, in their effectiveness. It should be noted that MDIs can continue to deliver propellant even after the drug has been used up. Patients should track their medicine and throw the device away when the last dose has been administered.

Nebulizers (not MDIs) are typically used in very small children, both at home and in the emergency room. However, recent studies suggest spacers may be better than nebulizers for children and shorten the time spent in emergency rooms. Studies also indicate that with the use of a face mask and a spacer, the MDI works well even for infants in the emergency room and may prove to be useable at home.

Click the icon to see an illustrated series detailing a metered dose inhaler.

Breath-Actuated Inhalers. Breath-actuated rotary inhalers (Easi-Breathe and Autohaler) deliver the drug directly to the back of the throat as the user inhales. Their primary advantage over the MDI is their ease of use. They also do not use CFCs as propellants. In comparison studies, patients have been very successful with the breath-actuated inhalers. They are not recommended for children under 8 years old.

Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of beta2-agonists or corticosteroids directly into the lungs. Such devices include Rotahaler, Spinhaler, Turbohaler, Clickhaler, Easyhaler, Diskhaler, Discus, Twisthaler, Spiros, and others. DPIs are as effective as the older devices, and generally have a better taste and are easier to manage. They may differ among themselves, however, in their ability to deliver drugs into the airways. In one study, for example, the Turbohaler was easier to use than the Diskhaler and so achieved better delivery.

Humidity or extreme temperatures can affect DPIs' performance, so they should not be stored in humid places (bathroom cabinets) or locations subject to high temperatures (glove compartments during summer months).

Dry-powder may cause tooth erosion. Children are advised to rinse their mouths out right after using these inhalers and to brush twice a day with a fluoride toothpaste.

Other Hand-Held Inhalers. Respimat delivers a fine-mist spray that is created by forcing the liquid medication through nozzles. It does not use any propellant.

Nebulizers. A nebulizer is a machine that delivers a fine spray of medication-containing liquid. Nebulizers are often used for children younger than 3 years and sometimes for older children who have difficulty using the MDI. It takes 5 - 10 minutes to administer medication using a nebulizer. Because the spray is less targeted than with the inhaler, it must deliver large amounts of the drug. This increases the risk for toxicity and severe side effects. Nebulizers should not be used by children who can manage an inhaler. Their use has been associated with a higher rate of hospitalizations and longer duration of symptoms than inhalers. A 2007 study also suggested that the misuse of home nebulizers may be an important factor in asthma deaths in children and young adults. If children must use an albuterol nebulizer, parents should be sure that it does not contain the preservative benzalkonium, which actually narrows the airways.

Click the icon to see an illustrated series detailing the use of a nebulizer.

Asthma triggers a vicious emotional-physical cycle:

Breathlessness and wheezing incite a fear of suffocation and death, even in very small children.
This anxiety produces further constriction on the muscles surrounding the airways, which makes breathing even more difficult.

Caregivers must first focus on alleviating their own anxiety, which can heighten a child's own fears. The next step is to help the child relax. One method for this is as follows:

The child sits comfortably, bending slight forward with the eyes closed.
The hands are placed gently over the navel.
The child is then told to pretend the stomach is a balloon.
The "balloon" must be "blown up" by inhalation, not exhalation. The child can tell if this working because the hands will move slightly apart.
When the child breathes out, the "balloon" will be made flat.

This exercise both relaxes the child and discourages shallow, oxygen-poor breathing. Massaging the child in gentle circles on the chest is relaxing and may also loosen mucus.

Other recommendations include:

A child may also find relief by lying stomach-down on several pillows so that the head is slightly lower than the chest while the caregiver gently pats the back between the shoulder blades.
Warm liquids, such as soup or hot cider, are effective in loosening mucus and may also relax bronchial muscles. Cold fluids, like cold air, should be avoided.
Overhydration (too much liquid) can be harmful, however, so these drinks should not be forced on the child.
Warm, moist air from vaporizers can greatly ease and moderate asthma attacks.
Daily massages and breathing and relaxation techniques to reduce stress can be very helpful.

Many adults self-manage their asthma using daily monitoring of peak air flow with adjustments of the medications as needed. This involves the use of a peak flow meter, which measures peak expiratory flow rate (PEFR).

Click the icon to see an image of a peak flow meter.

Studies suggest, however, that for most children with asthma, an educational program is just as effective for managing the condition as monitoring. Most children do not need to monitor their peak air flow on any regular basis.

Quick-Relief Medications

These medications quickly control acute asthma attacks.

Beta2-agonists do not reduce inflammation or airway responsiveness but serve as bronchodilators, relaxing and opening constricted airways during an acute asthma attack. A short-acting inhaled beta2-agonist, taken as needed, is often the only medication used by children with chronic mild asthma.

Asthma is a disease in which inflammation of the airways causes airflow into and out of the lungs to be restricted. When an asthma attack occurs, mucus production is increased, muscles of the bronchial tree become tight, and the lining of the air passages swells, reducing airflow and producing the characteristic wheezing sound.

Specific short-acting beta2-agonists include:

Albuterol (Proventil, Ventolin), called salbutamol outside the U.S., is the standard short-acting beta2-agonist in America. Other similar beta2-agonists are isoproterenol (Isuprel, Norisodrine, Medihaler-Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair), terbutaline (Brethine, Brethaire, Bricanyl), and bitolterol (Tornalate). Isoetharine (Bronkometer, Bronkosol) is available in nebulizers.
Newer beta2-agonists, including levalbuterol (Xopenex), have more specific actions than the standard drugs. Xopenex is administered with a nebulizer, and studies have indicated that it is as effective as albuterol with fewer side effects. The original formulation of Xopenex was administered with a nebulizer. A new metered-dose inhaler formulation was launched at the end of 2005. It is approved for children age 4 years and older.

Short-acting bronchodilators are generally administered through inhalation and are effective for 3 - 6 hours. They relieve the symptoms of acute attacks, but they do not control the underlying inflammation. If asthma continues to worsen with the use of these drugs, a doctor may prescribe corticosteroids or other drugs to treat underlying inflammation.

Side Effects of Beta2-Agonists. Side effects of all beta2-agonists may include:

Anxiety
Tremor
Restlessness
Headache
Fast and irregular heartbeats. A doctor should be notified immediately if this side effect occurs.
These drugs should be taken with caution by children with diabetes or a history of seizures.
Beta2-agonists have serious interactions with certain drugs and parents should tell the doctor about any other medications their child is taking.

Loss of Effectiveness and Overdose. There has been some concern that short-acting beta2-agonists become less effective when taken regularly over time, increasing the risk for overuse. Over time, some patients may become tolerant to many effects of short-acting beta2-agonists. The degree to which this affects the airways is uncertain. In some studies, the duration of action has declined but the peak effect appears to be preserved, making these drugs still useful for acute attacks. Regular use of long-acting beta2-agonists may increase the chances of a reduced effect from the short-acting forms.

A 2005 landmark study suggested that patients’ differing clinical response to albuterol may be based on their genotype. Albuterol targets the beta-adrenergic receptor. In the Beta-Adrenergic Response by Genotype (BARGE) trial, researchers studied the effects of albuterol on patients with two different forms of this receptor. The results suggested that patients with the arginine form of the receptor did not respond to albuterol. These patients’ asthma symptoms actually improved when albuterol was not used. By contrast, patients with the glycine form of the receptor had improved asthma control with albuterol.

Inhaled ipratropium bromide (Atrovent) acts as a bronchodilator over time. Ipratropium bromide alone is only modestly beneficial for acute asthma attacks. In fact, the drug is not approved specifically for asthma. Some parents report benefit for treating wheezing in infants. It is also sometimes used in the emergency room to treat children with severe asthma to enhance the effects of intravenous beta2-agonists.

Common oral corticosteroids include prednisone/prednisolone, dexamethasone, methylprednisolone, and hydrocortisone. They reduce inflammation very effectively. A 2006 study indicated that oral prednisolone worked better than inhaled fluticasone for treating mild-to-moderate asthma attacks in children in emergency rooms. However, children often have difficulty taking these drugs because they have a bitter taste and can cause vomiting. Taking oral dexamethasone for 2 days may be as effective and more tolerable than the standard 5-day regimen of prednisone/prednisolone. Prolonged use of oral steroids has widespread and sometimes serious side effects, so they are not generally give to children for longer than a few days.

[See In-Depth Report #4: Asthma in adults.]

Long-Term Relief Medications

These medications are taken on a regular basis to prevent asthma attacks and control chronic symptoms.

Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs. Steroids are not bronchodilators (they do not relax the airways) and have little effect on symptoms. Instead, they work over time to reduce inflammation and prevent permanent injury in the lungs. They can also help prevent asthma attacks from occurring. Many studies have shown that the use of inhaled corticosteroids in patients with moderate-to-severe asthma significantly reduces the rate of rehospitalizations and deaths from asthma.

Inhalation of corticosteroids makes it possible to provide effective local anti-inflammatory activity in the lungs with minimal systemic effects. (By contrast, oral steroids have considerable side effects throughout the body.) Inhaled corticosteroids are recommended as the primary therapy under the following circumstances:

For any asthmatic condition more serious than occasional episodes of mild asthma. (Low-doses of inhaled steroids may even be safe and effective for some people with mild asthma, particularly those who find themselves using beta2-agonists daily.)
When treatment with bronchodilators is not effective.

Examples of inhaled corticosteroids:

Inhaled steroids include fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, the newer drugs are more powerful than the older generation of inhaled drugs. Budesonide (Pulmicort Respules) is available in a jet nebulizer for children from 12 months to 8 years. It is the first such medication to be approved for children in this age group.
The FDA approved a new inhaled corticosteroid, mometasone furoate (Asmanex) was approved in 2005 for patients age 12 and older.
The older corticosteroid inhalants are beclomethasone (Beclovent, Vanceril) and dexamethasone (Decadron Phosphate Respihaler and others). They are less powerful than the newer steroids when delivered with standard inhalers. New inhalers that use very fine sprays (QVAR, Autohaler) to deliver the drugs deep into the lungs may prove to be as effective as the newer, more potent steroids.
Inhalers that combine both long-acting beta2-agonists and corticosteroids are also available. These include Symbicort (budesonide/formoterol), which was approved in 2006 for patients ages 12 years and older.

Expert guidelines recommend inhaled corticosteroids as the preferred first-line therapy for children with mild-to-moderate asthma. Nevertheless, they are still significantly underprescribed in the patients who need them most. An important 2007 study of 6 - 14 year old children with asthma compared inhaled corticosteroid therapy (fluticasone) with an inhaled corticosteroid/long-term beta2 agonist (fluticasone/salmeterol) and a leukotrine receptor antagonist (montelukast). The results indicated that fluticasone alone worked better than the other two treatments.

Researchers have been investigating whether early treatment with corticosteroids can help prevent the development of asthma in at-risk children. Two important 2006 studies in the New England Journal of Medicine suggested that while inhaled corticosteroids helped ease symptoms and reduce breathing problems in pre-school children at risk for asthma, they did not help protect against asthma development.

For now, experts caution against corticosteroids for infants and toddlers with mild asthma and urge close monitoring especially for children under age 5 with severe asthma who are receiving high doses. Because the newer potent drugs, particularly fluticasone, may produce major side effects similar to oral steroids, it is important when treating all children to aim for the lowest effective dose possible. Fortunately, studies suggest that low doses of fluticasone may achieve the same benefits as with high ones, thus reducing risks for serious side effects. Better delivery methods may also allow lower doses.

Side effects of inhaled steroids may include:

The most common side effects are throat irritation, hoarseness, and dry mouth. These effects can be minimized or prevented by using a spacer device and rinsing the mouth after each treatment.
Rashes, wheezing, facial swelling (edema), fungal infections (thrush) in the mouth and throat, and bruising are also possible but not common with inhalators.
Some children experience changes in mood, memory, and behavior. These changes are not permanent.
Some studies have suggested a higher risk for gum inflammation.
Oral steroids reduce bone density. Research reports that inhaled steroids -- both older and newer drugs -- may also affect bone growth and density. However, a number of studies report only a slight effect (about half an inch) on children's growth, which may be only temporary. It is still unknown if these drugs have any significant long-term effect on bone density. Calcium supplements may help prevent bone loss that is due to inhaled steroids.
It is not yet known whether inhaled steroids affect lung growth in very young children. Steroids administered using nebulizers are of particular concern.
There is also some concern that the stronger drugs, particularly fluticasone, suppress the adrenal system to a greater degree than other steroid inhalants. This effect, in turn, reduces levels of natural steroids -- notably cortisol, the major stress hormone. (This is a serious side effect of oral steroids).

Long-acting beta2-agonists are used in combination with inhaled corticosteroids for treating children with moderate-to-severe asthma. These drugs include include salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer). A single inhaler (Advair Diskus) that combines both salmeterol and the corticosteroid fluticasone is available for children age 4 years and older, and an inhaler (Symbicort) combining formoterol and the corticosteroid budesonide is approved for children age 12 years and older.

Long-acting beta2-agonists are used for preventing an asthma attack (not for treating attack symptoms). The effects of one dose of a long-acting beta2-agonist last for about 12 hours, so they are particularly effective during the night. These drugs also may be used for prevention of exercise-induced asthma in people and to protect against aspirin-induced asthma.

However, research indicates that long-acting beta2-agonists can worsen asthma by increasing symptom severity. These drugs may also increase the risk for asthma-related deaths. Experts are still trying to determine when long-acting beta2-agonists should be added to an asthma treatment plan. If a child’s symptoms do not improve or if symptoms worsen with this type of drug, the doctor will recommend discontinuing it. Patients should not, however, stop taking this drug or other asthma medications without first talking with their doctors.

Side Effects. Side effects of long-acting beta2-agonists are similar to the short-acting drugs.

Specific Warning on Salmeterol and Formoterol. In 2003 a "black box" warning was added to product packaging for drugs that contain salmeterol, including Serevent Diskus, and Advair Diskus. Serevent and Advair are approved for patients age 12 years and older. The warning was based on a study that demonstrated more serious and even fatal asthma episodes in patients who used the drug than in patients who used a placebo.

In 2006, the FDA updated the warning to include formoterol (Foradil Aerolizer, approved for patients 5 years and older). Warnings for salmeterol and formoterol products emphasize that these medicines can increase the risk of severe asthma episodes. Long-acting beta2-agonists require up to 20 minutes to achieve effectiveness, and there is a danger of overdose if a patient is not aware of this delay and takes additional doses to achieve faster relief. The FDA recommends that patients:

Use long-acting beta2-agonists only if other medicines (such as steroids) have not helped control asthma.
Use a short-acting bronchodilator, not a long-acting beta2-agonist, to treat sudden wheezing.
Do not use long-acting beta2-agonists to treat wheezing that is getting worse. Call your doctor if this situation occurs.
Do not stop using any asthma medicines without first talking to your doctor.

Cromolyn sodium (Intal) is both an anti-inflammatory drug and has antihistamine properties that block asthma triggers such as allergens, cold, or exercise. Cromolyn has been the anti-inflammatory drug of choice for prevention of asthma attacks in children over age 4 with chronic moderate asthma. It is not as effective as inhaled corticosteroids, however, for reducing hospitalization rates, improving symptoms, and reducing the use of beta2-agonists in children with persistent asthma. Still, cromolyn has a well-known long-term safety record, while the long-term adverse effects of corticosteroids in children are still not fully known. Many children who need asthma maintenance therapy will still do well on cromolyn. (It may not provide any real benefit for children under age 4.)

Nedocromil (Tilade) is similar to cromolyn and needs to be taken only once a day. It also prevents asthmatic reactions to cold and exercise. It is not used in very young children. A cromolyn nasal spray called Nasalcrom has been approved for over-the-counter purchase, but only to relieve nasal congestion caused by allergies. Patients should not use it for self-medication without the advice of a doctor.

Side Effects. Side effects of cromolyn include nasal congestion, coughing, sneezing, wheezing, nausea, nosebleeds, and dry throat. Nedocromil has an unpleasant taste, and some people have complained of nausea, headache, and spasms in the airways, but no serious side effects have been reported.

Leukotriene-antagonists (also called anti-leukotrienes or leukotriene modifiers) are oral medications that block leukotrienes. Leukotrienes are powerful immune system factors that, in excess, produce a battery of damaging chemicals that can cause inflammation and spasms in the airways of people with asthma. As with other anti-inflammatory drugs, leukotrienes are used for prevention and not for treating acute asthma attacks.

Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are proving helpful for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID) -induced asthma. However, most studies to date have reported better success with inhaled corticosteroids than with the leukotriene-antagonists. A 2006 study of children with mild-to-moderate persistent asthma indicated that the corticosteroid fluticasone worked better than the leukotriene-antagonist montelukast in controlling symptoms. Nevertheless, some studies suggest that montelukast, which comes in a chewable tablet, may be particularly useful for managing asthma in small children (ages 2 - 5), since they have trouble with inhaled steroids.

Side Effects and Complications. Gastrointestinal distress is the most common side effect of leukotriene-antagonists. Very few other side effects have been reported. In general, these drugs appear to be safe and well-tolerated.

Of some concern are reports of Churg-Strauss syndrome in a few people taking zafirlukast or montelukast. Churg-Strauss syndrome is very rare, but it causes blood vessel inflammation in the lungs and can be life threatening. Oral steroids quickly resolve the problem. In fact, usually the syndrome has occurred in patients who were tapering off steroids and changing over to the leukotriene-antagonists. Some experts believe that, in such cases, the steroids may simply have masked the presence of the disorder, which then developed when the steroid drugs were withdrawn. Symptoms include severe sinusitis, flu-like symptoms, rash, and numbness in the hands and feet.

Other concerns are indications of liver injury in patients taking zileuton and zafirlukast when taken at higher than standard doses. No adverse effects on the liver have been reported to date with montelukast.

Theophylline (Theo-Dur, Theolair, Slo-Phyllin, Slo-bid, Constant-T, Respbid) is a mild-to-moderate bronchodilator that has been used to treat childhood asthma for more than 30 years. It is useful for treating nocturnal asthma and may also have anti-inflammatory qualities even in low doses.

Available in tablet, liquid, and injectable forms, some theophylline sustained-release tablets and capsules have a long duration of action and can therefore be taken once or twice a day with good results.

Side effects may include changes in behavior, mood, and memory. If theophylline is not taken exactly as prescribed, an overdose can easily occur. Toxicity can cause nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in heart rhythm and convulsions. Contact a doctor immediately if any of these side effects occur.

The risks for these adverse effects are small if the drug is taken exactly as prescribed but the following precautions should be noted:

Infants tend to metabolize the drug extremely slowly and, therefore, should receive very low doses.
By the time children reach age 1, however, they metabolize the drug faster than adults. There is a risk, therefore, of toxic effects.
Fever and certain antibiotics may slow down the rate at which theophylline is eliminated from the body. In such cases, the doctor may want to reduce the dosage of theophylline.

If a child is taking theophylline on an ongoing basis, the doctor should monitor the drug level at the start of therapy and at regular intervals thereafter.

Omalizumab (Xolair) is FDA-approved for patients age 12 and older who have moderate-to-severe persistent asthma related to allergies. The first drug of this type to be approved for asthma, omalizumab is a monoclonal antibody (MAb), a genetically developed drug designed to attack very specific targets. Omalizumab is administered by injection every 2 - 4 weeks. It is used only to treat patients whose symptoms are not controlled by inhaled corticosteroids.

Omalizumab prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to asthmatic attacks. Studies have shown excellent benefits of the drug, including a reduced need for corticosteroids, fewer hospitalizations, and significant symptomatic improvements.

However, about 1 in 1,000 patients who take omalizumab develop anaphylaxis (a life-threatening allergic reaction). In 2007 the FDA requested the manufacturers of omalizumab to put a “boxed warning” on the medicine’s label emphasizing the drug’s risk for anaphylaxis. The boxed warning notes that patients can develop anaphylaxis after any dose of omalizumab, even if they had no reaction to a first dose. Anaphylaxis may occur up to 24 hours after the dose is given.

The FDA recommends that healthcare providers observe patients for at least 2 hours after an injection. Patients should also carry emergency self-treatment for anaphylaxis (such as an Epi-Pen) and know how to administer it. With an Epi-Pen, or similar auto-injector device, patients can quickly give themselves a life-saving dose of epinephrine.

Anaphylaxis symptoms include:

Difficulty breathing
Chest tightness
Dizziness
Fainting
Itching and hives
Swelling of the mouth and throat

[See In-Depth Report #4: Asthma in adults.]

Other Treatments

Alternative therapies are widely used by children, adolescents, and adults with asthma. In one study, nearly half of asthma or allergy sufferers resorted to alternative treatments. To date, however, evidence does not support most alternative therapies, including high-dose vitamins, urine injections, homeopathic remedies, and most herbal remedies.

Relaxation and Stress-Reduction Techniques. Patients report benefits from many stress reduction and physical techniques, such as acupuncture, hypnosis, breathing relaxation techniques, the Alexander technique, massage therapy, and meditation practices. There have been very few well-conducted studies supporting their use, however.

Acupuncture, hypnosis, and biofeedback are alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Breathing Exercises. Some studies have suggested that breathing exercises or training may be helpful. A number of different methods are available. One example is the Buteyko breathing method, an experimental approach designed to increase levels of carbon dioxide in the body. To do this, patients are trained to reduce their volume of breath and to avoid hyperventilation (over-breathing). Some studies report that patients using this method reduce their use of medications and improve their quality of life. The system originated in Australia and is not yet widely available in the U.S.

Probiotics. Probiotics are beneficial bacteria that may possibly help protect against allergies and asthma. Antibiotic overuse and modern hygiene may specifically be reducing these helpful organisms. Look for probiotics in active yogurt cultures and in supplements, which are being studied for protection.

Herbal Remedies. Butterbur (also known as Petasites hybridus, butter dock, blatterdock, bog rhubarb, and exwort), is a traditional herbal remedy used for seasonal allergies and asthma. In a 2002 study, it was as effective and less sedating than a commonly prescribed antihistamine for treating seasonal allergies over a 2-week period. However, little research exists on its effect on asthma. Overall, there is scant evidence supporting the benefits of herbs and nutritional supplements for asthma control.

Managing Asthma

The more allergies a child has, the more severe the asthma. Making lifestyle changes to reduce allergy attacks and other triggers is extremely important.

House dust is a reservoir for pollen and dust mites. Some experts believe that reducing household allergens and pollutants in the home could reduce asthma in children by 40%.

Controlling for Dust. Spray furniture polish is very effective for reducing both dust and allergens. Air cleaners, filters for air conditioners, and vacuum cleaners with High Efficiency Particular Air (HEPA) filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo, however, is effective in removing mites in house dust. Vacuuming actually stirs up both mites and cat allergens. If possible, avoid carpets and rugs.

Click the icon to see an image of a HEPA air filter.

Bedding and Curtains. Many experts recommend reducing exposure to dust mites by enclosing mattresses and pillows in semipermeable coverings. (Vinyl mattress covers limit airflow and may also worsen, or even cause, asthma in children. Synthetic pillows may pose a significantly higher risk for severe asthma attacks in children than feather or no pillows.) However, several 2005 studies suggested that such covers do not prevent asthma or allergies. Replace curtains with shades or blinds, and wash bedding using the highest temperature setting.

Click the icon to see an image of dust mite prevention.

One study found that children sleeping in bottom bunk beds are significantly more likely to develop asthma than siblings occupying the upper bunks. Families with children who have asthma or allergies should avoid bunk beds or be sure that children with asthma sleep in the top bunk. Even with standard beds, it may be useful to have them sleep as high off the floor as possible.

Exterminating Pests (Cockroaches and Mice). Use professional exterminators to eliminate cockroaches. (One study reported that ridding a home of cockroaches and cleaning the house using standard housecleaning techniques failed to eliminate the cockroach allergens themselves.) Exterminate mice, and attempt to remove all dust, which might contain mouse urine and dander.

Reducing Humidity in the House. Although warm, moist air from vaporizers can greatly ease and moderate asthma attacks, living in a damp house is counterproductive. Dust mites thrive in humidity and damp houses increase the risk for mold, so on-going humidifiers can be unhelpful. If they are used, humidity levels should not exceed 40%, and humidifier should be cleaned daily with a vinegar solution.

Controlling Pets. People with asthma who already have pets and are not allergic to them probably have a low risk for developing such allergies later on. When children are exposed to more than one dog or cat during their first year, they have a much lower risk for allergies and asthma.

For children who have an existing allergy to pets, however, the pets should be given away or kept outside. If this isn't possible, they should at least be confined to carpet-free areas outside the bedroom. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems. Washing animals once a week can reduce allergens. Dry shampoos, such as Allerpet, are now available for both cats and dogs to remove allergens from skin and fur and are easier to administer than wet shampoos.

Many of the same substances trigger both allergies and asthma. Common allergens include pollen, dust mites, mold and pet dander. Other asthma triggers include irritants like smoke, pollution, fumes, cleaning chemicals, and sprays. Asthma symptoms can be substantially reduced by avoiding exposure to known allergens and respiratory irritants.

Preventing Exposure to Cigarette and Cooking Smoke. Parents who smoke are strongly urged to quit. Studies indicate that exposure to second-hand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children. Even smoky cooking can worsen asthma.

Parental smoking has been shown to increase the airway responsiveness of infants as early as the first 2 - 10 weeks of life. This extends even to the fetus of pregnant women who smoke. Such mothers tend to have babies born at a low birth weight, which affects lung function and increases babies' risks for asthma.

Avoiding Outdoor Allergens. The following are some recommendations for avoiding allergens outside:

Avoid scheduling camping and hiking trips during times of high pollen count (generally, May and June for grass pollen and mid-August to October for ragweed).
Patients should avoid strenuous activity when ozone levels are highest, which usually occur in early afternoon, particularly on hot hazy summer days. Levels are lowest in early morning and at dusk.
Asthma attacks are often higher during thunderstorms. Some evidence points to a build-up of ozone that accompanies such storms. Other evidence suggests that the changing airflow patterns bring a sudden downdraft of air containing concentrations of pollens, small particles and allergens.
Patients who are allergic to mold should avoid barns, hay, raking leaves, and mowing grass.
Exposure to automobile fumes may worsen asthma. Fungi in car air conditioners can also be a problem.

Reducing Exposure to Air Pollution. Children breathe faster than adults, taking in more pollutants, and therefore are particularly susceptible to soot and other small particles in the air. A 2001 study found an association between higher rates of asthma and other health problems in children who were exposed to high levels of specific pollutants (particularly sulfur dioxide and nitrogen dioxide). Diesel fuel exhaust has also been associated with worsening asthma in children.

Some experts point out that asthma rates in North America have increased over recent years while the prevalence of many common air pollutants have declined. So pollution is unlikely to be a primary cause of asthma. Regardless of whether pollution is an important cause of asthma, evidence strongly suggests that it can affect existing asthma.

Patients with asthma and chronic allergic rhinitis may require daily medications. Patients with severe seasonal allergies may be advised to start medications a few weeks before the pollen season, and to continue it until the season is over.

Immunotherapy ("allergy shots") may help reduce asthma symptoms, and the use of asthma medications, in patients with known allergies. They may also help prevent the development of asthma in children with allergies. Immunotherapy poses some risk for severe allergic reactions, especially for children with poorly controlled asthma, so it is important that the doctor carefully evaluates the child’s asthma condition.

[See In-Depth Report #77: Allergic rhinitis.]

Weight Loss. Children who are both asthmatic and overweight may reduce asthma symptoms simply with weight loss.

Fruits, Vegetables, and Whole Grains. Healthy foods are important for lung function. Specific foods that may be important for healthy lungs contain antioxidants (deep green and yellow-orange fruits and vegetables), selenium (fish, red meat, grains, eggs, chicken, liver, garlic), plant chemicals called flavonoids (apples, onions), and magnesium (green leafy vegetables, nuts, whole grains, milk, and meats).

Fish Oil. Omega-3 fatty acids, found in cold water oily fish and in supplements (preferably DHA-EPA, the important compounds in fish oil) have anti-inflammatory effects. Some evidence suggests they may be helpful for people with asthma.

Caffeine. Caffeine has properties that are similar to the asthma drug theophylline. A major analysis of studies reported that caffeine improved lung function for up to 4 hours after consumption. Although tea and coffee are the major sources of caffeine, some sodas contain it and should be avoided when children have an asthma attack. (People who are going to have their lung function tested should avoid drinking coffee, tea, or other caffeinated beverages for at least 4 hours beforehand.)

Food Allergies. Although about 70% of people with asthma believe their symptoms are aggravated by food allergies, studies indicate that this belief may be true in only 5% of cases. If young children show signs of or test positive for food allergies, however, parents should be extra cautious in preventing exposure to any asthma trigger. Some doctors now counsel all children with asthma to avoid nuts entirely, and, of course, children who experience reactions to any foods should avoid them.

Chemicals that may pose some risk for an allergic reaction are monosodium glutamate, or MSG (found in some canned soups, cheese, and certain vegetables), and sulfites (preservatives in foods, such as frozen potatoes and tuna). Contrary to what many believe, dairy products do not appear to worsen asthma symptoms in people who are not already allergic to them.

Asthma is no reason to avoid exercise. Historically, about 10% of Olympic athletes have asthma. Some studies indicate that long-term exercise may help control asthma and reduce hospitalization.

Encourage children with asthma to swim and play sports, such as baseball, that will present less difficulty for them. Intense activities lasting less than 2 minutes, such as sprinting or competitive swimming, may cause fewer problems than longer-lasting exercises.

Young people who enjoy running should probably choose an indoor track to avoid pollutants. Swimming is excellent for people with asthma. Yoga practice, which uses both stretching, breathing, and meditation techniques, may have particular benefits. One study reported that two-thirds of patients who practiced yoga regularly were able to reduce or stop taking their asthma medications.

Patients should consult their doctors before starting any exercise program. Exercise-induced asthma is a limited condition that has specific recommendations.

People with asthma should try to minimize their risk for respiratory tract infections. Washing hands is a very simple but effective preventive measure.

Patients with asthma should ask their doctor about getting the influenza ("flu") vaccine and also whether they should receive the vaccination against pneumococcal pneumonia.

Zanamivir, a new drug used for treating influenza, is considered safe for patients with asthma 12 years of age or older. In one study, patients with asthma treated with zanamivir experienced fewer flu symptoms, and their lung function improved.

People with asthma have no higher rate of anxiety or depression than the general population. However, such emotions interact with the effects of asthma and its treatments in important ways:

Negative emotions can discourage compliance with medication and the ability to cope.
Poor control of asthma symptoms, in turn, increases the risk for negative emotions.
Stress and depression have been associated with more severe symptoms and even an increased risk of fatal asthma attacks.

Some evidence suggests that stress reduction techniques, a positive attitude, and relaxation techniques may be very helpful in the long-term management of asthma.

Resources

www.lungusa.org -- The American Lung Association
www.acaai.org -- American College of Allergy, Asthma & Immunology
www.aaaai.org -- American Academy of Allergy, Asthma, and Immunology
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.asthma-carenet.org -- Childhood Asthma Research and Education Network
www.njc.org -- National Jewish Center for Immunology and Respiratory Medicine
www.aafa.org -- Asthma and Allergy Foundation of America
www.aanma.org -- Allergy and Asthma Network, Mothers of Asthmatics

References

Akinbami L; Centers for Disease Control and Prevention National Center forHealth Statistics. The state of childhood asthma, United States, 1980-2005. Adv Data. 2006 Dec 12;(381):1-24.

Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med. 2006 May 11;354(19):1998-2005.

Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000052.

Douwes J, van Strien R, Doekes G, Smit J, Kerkhof M, Gerritsen J, et al. Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study. J Allergy Clin Immunol. 2006 May;117(5):1067-73.

Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006 May 11;354(19):1985-97.

Haland G, Carlsen KC, Sandvik L, Devulapalli CS, Munthe-Kaas MC, Pettersen M, et al. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med. 2006 Oct 19;355(16):1682-9.

Marks GB, Mihrshahi S, Kemp AS, Tovey ER, Webb K, Almqvist C, et al. Prevention of asthma during the first 5 years of life: a randomized controlled trial. J Allergy Clin Immunol. 2006 Jul;118(1):53-61.

National Asthma Education and Prevention Program Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics -- 2002. Rockville, MD. National Heart, Lung, and Blood Institute, US Dept of Health and Human Services; 2003. NIH publications 02-5074.

O'Byrne PM, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, et al. Effects of early intervention with inhaled budesonide on lung function in newly diagnosed asthma. Chest. 2006 Jun;129(6):1478-85.

Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006 Jun 20;144(12):904-12.

Schuh S, Dick PT, Stephens D, Hartley M, Khaikin S, Rodrigues L, Coates AL. High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma. Pediatrics. 2006 Aug;118(2):644-50.

Sorkness CA, Lemanske RF Jr, Mauger DT, Boehmer SJ, Chinchilli VM, Martinez FD, et al. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. J Allergy Clin Immunol. 2007 Jan;119(1):64-72.

Review Date:
3/26/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Healthy Eating Tip: When to Buy Groceries

FitSugar — Tue, 06 Jan 2009 16:00:00 -0800

Going to the grocery store when you're hungry is the ultimate test in temptation and it's a given that you shouldn't run this errand on an empty stomach. It's good to go when when you've had some food, but an even better time to go is right after you've exercised. Working out can actually decrease your appetite.

Next time you're in need of a grocery-store run, try and go after you've pushed yourself at the gym or taken a challenging bike ride. Just slip your grocery list into your wallet and go directly to the store after your workout (well, maybe after taking a quick rinse to keep the sweat from clogging up your pores). Remember to pack a small snack for after your workout so that your hunger pangs don't distract you from what's on the list.

The dark chocolate-covered cookies will still make your mouth water, but your mind will remember how hard you just worked and it won't take long to walk away from the junk food empty-handed.

Source

Cataracts

FitSugar — Wed, 08 Oct 2008 17:35:39 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Prognosis
Risk Factors
Prevention
Diagnosis
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Medical Societies Issue Tamsulosin (Flomax) Warning

In August 2006, the American Society of Cataract and Refractive Surgery (ASCRS), the American Academy of Ophthalmology, and the American Urological Association (AUA) issued a joint warning concerning Tamsulosin (Flomax). The societies advised patients to be sure to inform their eye surgeons if they are taking this drug. Tamsulosin is frequently prescribed to treat prostate enlargement.

The ACSRS has developed specific cataract surgery techniques for cataract patients who take this drug. Recent research suggests that these new techniques produce successful surgical outcomes.
The AUA warns that while men are primarily at risk, more women may be at risk in the future as Tamsulosin is increasingly being prescribed for urinary retention.

Cost of Cataracts

Cataracts cost the United States nearly $7 billion a year in medical services and pharmaceutical costs, according to a 2006 report in the Archives of Ophthalmology.

Can Statins Reduce Cataract Risk?

Statin drugs, which are used to manage cholesterol levels, are associated with a lower risk of nuclear cataract -- the most common type of age-related cataract -- according to a 2006 study in the Journal of the American Medical Association. Researchers think that the antioxidant properties of statins may account for this association.

Cataract Surgery

A new surgical technique, phacoviscocanalostomy, works well for patients who have both glaucoma and cataracts, suggests a 2006 study in the Journal of Cataract and Refractive Surgery.
Newer methods of administering local anesthesia are resulting in fewer complications than older methods, indicates a 2006 study in the British Journal of Ophthalmology.

Intraocular Lenses (IOLs)

The Tecnis ZM001 IOL helped produce better reading clarity and reading speed than several other newer multifocal IOLs, according to a 2006 comparison study. Multifocal IOLs are used for patients who need correction for both farsightedness and nearsightedness.

Introduction

A cataract is an opacity, or clouding, of the lens of the eye.

The lens of an eye is normally clear. If the lens becomes cloudy or is opacified, it is called a cataract.

The prevalence of cataracts increases dramatically with age. It typically occurs in the following way:

The lens is an elliptical structure that sits behind the pupil and is normally transparent. The function of the lens is to focus light rays into images on the retina (the light-sensitive tissue at the back of the eye).
In young people, the lens is elastic and changes shape easily, allowing the eyes to focus clearly on both near and distant objects.
As people reach their mid-40s, biochemical changes occur in the proteins within the lens, causing them to harden and lose elasticity. This causes a number of vision problems. For example, loss of elasticity causes presbyopia, or far-sightedness, requiring reading glasses in almost everyone as they age.
In some people, the proteins in the lens, notably those called alpha crystallins, may also clump together, forming cloudy (opaque) areas called cataracts. They usually develop slowly over several years and are related to aging. In some cases, depending on the cause of the cataracts, loss of vision progresses rapidly.
Depending on how dense they are and where they are located, cataracts can block the passage of light through the lens and interfere with the formation of images on the retina, causing vision to become cloudy.

Click the icon to see an image of eye anatomy.

Cataracts can form in any of three parts of the lens and are named by their location.

Nuclear cataracts. These form in the nucleus (the inner core) of the lens. This is the most common variety of cataract associated with the aging process.
Cortical cataracts. These form in the cortex (the outer section of the lens).
Posterior subcapsular cataracts. These form toward the back of a cellophane-like capsule that surrounds the lens. They are more frequent in people with diabetes, who are overweight, or those taking steroids.

Causes

Although older age is the primary risk factor for cataracts, experts are still not certain about the exact biologic mechanisms that tie cataracts to aging.

Researchers have been focusing on particles called oxygen-free radicals as a major factor in the development of cataracts. They cause harm in the following way:

Oxygen free radicals (also called oxidants) are molecules produced by natural chemical processes in the body. Toxins, smoking, ultraviolet radiation, infections, and many other factors can create reactions that produce excessive amounts of these oxygen free radicals.
Oxidants are missing an electron, so they are unstable and tend to chemically bind with other molecules in the body. When oxidants are overproduced, these chemical reactions can be very harmful to nearly any type of cell in the body. At times these reactions can even effect genetic material in cells.
Cataract formation is one of many destructive changes that can occur with overproduction of oxidants, possibly in concert with deficiencies of an important protective anti-oxidant called glutathione.
Glutathione occurs in high levels in the eye and helps clean up these free radicals. One theory posits that in the aging eye, barriers develop that prevent glutathione and other protective antioxidants from reaching the nucleus in the lens, thus making if vulnerable to oxidation.

Sunlight and Ultraviolet Radiation. Sunlight consists of ultraviolet (referred to as UVA or UVB) radiation, which penetrates the layers of the skin. Both have destructive properties that can promote cataracts. The eyes are protected from the sun by eyelids and the structure of the face (overhanging brows, prominent cheekbones, and the nose). Long-term exposure to sunlight, however, can overcome these defenses.

UVB radiation produces the shorter wavelength, and primarily affects the outer skin layers. It is the primary cause of sunburn. It is also the UV radiation primarily responsible for cataracts. Long-term exposure to even low levels of UVB radiation can eventually cause changes in the lens, including pigment changes, which contribute to cataract development. (UVB also appears to be responsible for macular degeneration, an age-related disorder of the retina.) Some scientists suggest that global warming and ozone depletion may increase people’s exposure to UVB, leading to a greater incidence of cataracts.
UVA radiation is composed of longer wavelengths. They penetrate more deeply and efficiently into the inner skin layers and are responsible for tanning. The main damaging effect of UVA appears to be the promotion of the release of oxidants.

Radiation Treatments. Cataracts are common side effects of total body radiation treatments, which are administered for certain cancers.

Electromagnetic Waves. Questions have been raised about the hazards of low-level radiation from computer screens. To date, no study has demonstrated an association between cataract development and video display terminals. It is a good idea, in any case, to sit at least a foot away from the front of a screen.

Cataracts are one of the many ill effects caused by smoking. Many studies have implicated smoking in the development of nuclear cataracts. The major damaging effects of cigarette smoke appear to be enhancement of free oxygen radicals, the chemical byproducts in the body that can damage cells, including those in the eye.

Corticosteroids. Long-term use of oral steroids is a well-known cause of cataracts. Studies have been conflicting, however, over whether inhaled and nasal-spray steroids increase the risk for cataracts. Information on cataract risk from inhaled steroids is important because they are commonly used by asthma patients, and steroid spray use is increasing among allergy sufferers. Studies have suggested a higher risk for cataracts among middle-aged and elderly patients treated with beclomethasone (Beclovent, Vanceril). However, newer inhaled steroids are available, and their effects on the eye are unclear. In children, cataracts are rare, and the benefits of inhaled steroids for asthma far outweigh any small additional risk.

Other Medications Associated with Cataracts.

Psoralens, a class of drugs used along with light therapy to treat skin disorders, such as psoriasis
Antipsychotic medications such as chlorpromazine (Thorazine)
Glaucoma medications

Many others drugs have been weakly associated with cataracts, including allopurinol, tamoxifen, amiodarone, tricyclic antidepressants, potassium-sparing diuretics (but not other diuretics), thyroid hormone, tetracyclines, sulfamidase, and mepacrine. According to a 2006 study in the Journal of the American Medical Association, statin drugs (used for managing cholesterol) may possibly reduce the risk for nuclear cataracts.

Click the icon to see an animation about cataracts.

Glaucoma. Glaucoma and its treatments, including certain drugs (notably miotics) and filtering surgery, pose a high risk for cataracts. The glaucoma drugs posing a particular risk for cataracts including demecarium (Humorsol), isoflurophate (Floropryl), and echothiophate (Phospholine).

Uveitis. Uveitis is chronic inflammation in the eye, which is often caused by an autoimmune disease or response. Often the cause is unknown. It is a rare condition that carries a high risk for cataracts.

A number of medical conditions appear to be associated with a higher risk for cataracts either because of a direct effect or because of the medications used for them, or both. They include the following:

Diabetes. Cataracts in patients with diabetes appear to form when high levels of blood sugar react with proteins in the eye to form byproducts that accumulate in the lens (sugar cataracts).
High blood pressure (hypertension).
Autoimmune diseases including rheumatoid arthritis, psoriasis, multiple sclerosis, systemic lupus erythematosus, Behcet's disease, and others.

Rarely, about 1 in every 10,000 births, a baby is born with cataracts (called congenital cataracts).

Inherited disorders are often involved in the development of congenital cataracts in children. Such cataracts are most often due to inborn abnormalities in the structure or shape of the lens, including its capsule. Dozens of variations can affect the lens causing, susceptibility to cataracts. Researchers are also investigating genetic factors that may cause mutations in alpha crystallins -- major proteins in the lens, which form cataracts. (Genetic factors also may play a role in some adult cataract cases. The exact hereditary predispositions have yet to be established.)
Infection during pregnancy can lead to cataracts.
Pregnant women who abuse alcohol or drugs increase the risk for cataracts (along with other more serious birth defects) in their infants.

Surgery in children with early-onset cataracts can help correct this problem in many cases, but it should be performed as soon as possible for full benefit. Experts recommend routine examination of the face of a fetus during ultrasound for abnormalities.

Symptoms

During the early stages, cataracts have little effect on vision. The symptoms of a cataract may include:

Cloudy vision, double vision, or both may be the first signs.
Images may take on a yellowish tint as color vibrancy diminishes.
Reading may become difficult over time because of a reduced contrast between letters and their background.
Sensitivity to bright lights may make it difficult or impossible to drive at night because of glare from the headlights of oncoming cars. (People with diffuse cataracts in the rear walls of their lenses are particularly prone to glare sensitivity because bright light tends to scatter in their lenses.)
In very advanced cases, the pupil, which is normally black, looks milky or yellowish. The patient's vision is reduced to being able only to distinguish light from dark.

This photograph shows a cloudy white lens (cataract) over the pupil. Cataracts are a leading cause of decreased vision in older individuals, but children may have congenital cataracts. With new surgical techniques, the cataract can be removed, a new lens implanted, and the person can usually return home the same day.

Nuclear Cataracts. Cataracts of the lens nucleus are most commonly associated with aging. Symptoms include:

Hazy distance vision and increasing glare.
Progressive nearsightedness and the need for frequent changes in eyeglass prescriptions. This effect may even temporarily counteract age-related farsightedness and provide a temporary improvement in overall vision in some people. The improvement fades when the cataract advances sufficiently to overwhelm the inherent farsightedness. Eventually, as the cataracts grow worse, stronger glasses can no longer correct the patient's vision.

Click the icon to see an image of normal, near, and farsighted vision.

Cortical Cataracts. Cortical cataracts usually start on the outside of the cortex (the outer area of the lens).

They have very little initial effect on vision.
Glare can develop as these cataracts increase and approach the center of the lens.
Problems with distance vision, contrast sensitivity, and clarity may occur as the cataracts progress further.

Posterior Subcapsular Cataracts. Posterior subcapsular cataracts typically start near the center of the back part of the capsule surrounding the lens. These cataracts often advance rapidly. For many patients, major impairment of eyesight, including near-vision problems and glare, develops within several months.

Prognosis

Some cataracts stop progressing after a certain point. Cataracts are never reversible, however, even after eliminating factors, (such as drugs or illnesses), which might have promoted their development. If extensive and progressive cataracts are left untreated they can cause blindness. In fact, cataracts are the leading cause of blindness among adults age 55 and older. About 20.5 million Americans have at least one cataract. By 2020, that number is expected to jump to 30.1 million.

Fortunately, cataracts nearly always can be successfully removed with surgery. However, surgery is unavailable in certain parts of the world, leaving millions at risk for vision loss. Even in the U.S., where surgery has greatly reduced the risk of blindness, tens of thousands still lose their sight and millions more have poor vision because of cataracts. Cataracts also exact a financial burden. According to 2006 data, cataracts cost the U.S. nearly $7 billion each year in medical services and drug treatments.

In a 2001 study, cataracts were associated with a significantly higher mortality rate in older women, although not older men. These higher rates did not seem to be caused by certain health risks (for example, diabetes) that are often associated with both cataracts and lower survival rates. A 2004 study published by scientists in Italy appears to confirm the association between shortened lifespan and cataracts, especially cataracts confined to the lens nucleus and those that had already required surgery. A few other studies have also linked cataracts and vision impairment with poorer survival, regardless of accompanying health problems. One study reported that even middle-aged people with cataracts, particularly those in ethnic minority groups, had lower survival rates than their peers, perhaps because of premature aging.

Effect on Survival by Location of the Cataract. Some studies have suggested poorer survival specifically in patients with nuclear or mixed cataracts but not in those with cataracts in the cortex or capsule. Not all studies have found these differences. In any case, nuclear cataracts are highly associated with smoking and diabetes, although some studies have found lower survival rates in patients with nuclear cataract regardless of these health risks.

A 2002 study reported twice the rate of automobile accidents in patients who do not have cataract surgery compared to those who had surgery. This finding, however, is obscured by the possibility that patients who choose not to have surgery may have other health problems that put them at risk for accidents. Also, driving skills decline with age in nearly everyone. Cataract surgery, then, is no insurance against age-related accidents.

Reduced vision ranks third only behind arthritis and heart disease as a cause of impaired function in older people. Extensive cataracts can compromise the ability to earn a living, read, drive, or live independently. Although vision loss has been associated with a number of major adverse effects, few studies have reported on the effect of vision on daily activities.

Both blurred vision and problems in seeing contrasts contribute to impaired activity. The degree of these impairments, however, may have different effects on disability depending on individual tasks and needs. For example, even a slight loss in vision sharpness and contrast can impair the ability to recognize faces or slow down reading speed. For those who read very quickly, this may not be significant, but it could be very disabling for slower readers. In one study, people under age 65 rated blurred vision as reducing their quality of life more than any other chronic medical problem except shortness of breath.

Nevertheless some people who have small cataracts can see well enough around the clouded areas to live normally. But for many people, cataracts are extensive enough to interfere greatly with daily activities.

Risk Factors

Aging is the primary risk factor for cataracts, but other factors are also involved.

Nearly everyone who lives long enough will develop cataracts to some extent. A major study reported that:

About 40% of people age 55 - 64 years had some opaque areas in their lenses, and 5% had fully-developed cataracts.
About 70% of people age 65 - 74 years had opaque areas, and 18% had cataracts.
More than 90% of people age 75 - 84 years had opaque areas, and almost 50% had cataracts.

One study indicated that posterior subcapsular cataracts are the most common type in people under 70 years old, while nuclear and mixed cataracts are most common in people over age 80. The risk for nuclear cataracts also increases with age.

Women face a higher risk than men. Women who started menstruating late are at an even higher risk.

Eye Features. People who are nearsighted and those with brown eyes may be at higher than average risk. (Not all studies, however, report a higher risk in people with darker eyes.)

Obesity and Height. Studies are now reporting obesity as a risk factor for cataracts, notably posterior subcapsular cataracts, which form toward the back of the lens. A study of 17,150 people found a specifically higher rate of cataracts in overweight people who are tall and whose fat distribution is primarily in the abdomen.

A 9-year population study, published in 2004, revealed that African Americans have nearly twice the risk of developing cataracts than do Caucasians. Analysis of the 3,000 participants also demonstrated for the first time that the risk of cortical cataracts is 3 times higher in African Americans than Caucasians. Earlier studies also identified a higher cataract risk in the black population, suggesting that it may be due to other medical illnesses, particularly diabetes. It has long been known that African Americans are much more likely to become blind from cataracts and glaucoma than Caucasians, mostly due to lack of treatment.

Hispanic Americans are also at increased risk for cataracts. In fact, cataracts are the leading cause of visual impairment among Hispanics. A 2005 study found that cataracts were about 3 times more common in Hispanic patients age 65 - 84 years than in similarly aged white or African Americans. (The study evaluated Hispanic patients of Mexican descent.) As with African Americans, Hispanic patients often face barriers to access to care.

People with certain medical conditions, notably diabetes, are at high risk for cataracts, either because of a direct effect of the disease, its treatments, or both.

Autoimmune Diseases and Conditions Requiring Steroid Use. Medical conditions requiring high use of corticosteroids (commonly called steroids) pose a particularly high risk. Many of these medical conditions are autoimmune diseases, including rheumatoid arthritis, psoriasis, multiple sclerosis, systemic lupus erythematosus, Behcet's disease, and others.

Diabetes and People with High Blood Glucose Levels. People with diabetes type 1 or 2 are at very high risk for cataracts and are much more likely to develop them at a younger age. They also have a higher risk for nuclear cataracts than nondiabetics. Cataract development is significantly related to high levels of blood sugar (called glycemia), and cataracts in people with diabetes are sometimes referred to as so-called sugar cataracts. Even people without diabetes but with higher-than-normal blood sugar levels are at high risk for cataracts. Some doctors now recommend that children with diabetes undergo an eye exam to check for cataracts at the time they are diagnosed.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Exposure to even low-level UVB radiation from sunlight increases the risk for cataracts. A 2003 study published provided new evidence supporting the link between sun exposure and nuclear cataracts. The risk was highest among those who had significant sun exposure at a young age. Additional studies suggesting risk associated with sunlight exposure report:

The closer people live to the equator the greater the chance for cataracts. As suggested by a study in Southern France, sunlight exposure in these climates also increases the risk for severe cortical or mixed cataracts. In this study, even wearing sunglasses did not reduce the risk for these cataracts, although it did for posterior subcapsular cataracts.
People whose jobs expose them to sunlight for prolonged periods are at higher risk. People in southern climates whose occupations, such as fishing or oyster farming, exposed them to very intense sunlight were at high risk for all cataracts, including posterior subcapsular cataracts. (People in more northern climates with similar occupations may not have as high a risk.)
Occupational exposure to very intense artificial light, such as arc welding, increases the risk for cataracts.

Smokers. A study of nearly 18,000 doctors showed that those who smoked 20 or more cigarettes a day had approximately twice the risk of developing cataracts. Smokers are at particular risk for cataracts located in the nuclear portion of the lens, which limit vision more severely than cataracts in other sites. Quitting smoking may reverse some of this damage.

Alcohol Users. Chronic drinkers are at high risk for a number of eye disorders, including cataracts. Alcohol has been implicated in cataract development in a number of studies. Wine provided the least risk, and the more moderate the drinking the lower the risk. Alcohol may work directly on the proteins in the lens itself and indirectly by affecting absorption of nutrients important to the lens.

Long-term environmental lead exposure may increase the risk of developing cataracts according to a study published in the Journal of the American Medical Association. Researchers assessed bone lead levels in 795 men aged 60 years and older. Because lead tends to accumulate over time in the skeleton, the researchers measured lead levels in the men’s shin bones. Men with the highest levels of lead were three times more likely to have cataracts than men with the least amount of lead.

A poor diet may deprive the body of amino acids and B vitamins that are essential for eye health. A French study of elderly adults found that lower blood levels of the protein albumin were associated with an increased risk of cataracts.

Other conditions that can trigger the process leading to cataracts include:

Physical injury to the eye (such as a hard blow, cut, or puncture)
Chemical burns
Electrical shock injuries
Chronic exposure to intense heat or cold

Prevention

Although cataracts are not completely preventable, their occurrence can be delayed. Quitting smoking, avoiding overexposure to sunlight, drinking alcohol in moderation, and eating plenty of fresh fruits and vegetables can delay the formation of cataracts. No evidence exists that using eye drops or ointments or performing eye exercises will stem the onset of cataracts.

The simplest and most effective way to protect against ultraviolet (UV) radiation is to stay out of the sun. A hat and cover-up should be worn outside, particularly when the sun is most intense (10 AM - 3 PM). A wide-brimmed hat can reduce eye exposure to UVB radiation by 30 - 50%. Because the sun's rays are highly reflective, sitting in the shade or under an umbrella by itself does not guarantee protection.

Clothing that blocks or screens the harmful rays of the sun (UVA and UVB), in combination with wide-brimmed hats, sunglasses, and sunscreen, all help prevent damage to the eyes and skin. Any one of these by itself, even the sunscreen, may not be enough to prevent sun damage.

Note: Avoidance of the sun should not be taken to extremes. Some sunshine is desirable. Moderate sun exposure provides an important source of vitamin D, which is essential for healthy bones. There is a link between lack of sun exposure and depression (known as seasonal affective disorder, or SAD).

Click the icon to see an image of vitamin D.

Sunglasses. Protective sunglasses do not have to be expensive. Sunglasses are classified into three categories based on UVA and UVB protection:

Cosmetic purpose sunglasses block at least 70% UVB and up to 60% UVA. People should avoid these glasses if they have any risk for cataracts or eye problems.
General purpose sunglasses block at least 95% UVB and a minimum of 60% UVA. At the very least, people should purchase general purpose sunglasses that are labeled "Meets ANSI Z80.3 General Purpose UV Requirements." Labels should indicate that sunglasses block UV radiation up to 400 nm.
Special purpose sunglasses block at least 99% UVB and a minimum of 60% UVA rays. These are the optimal sunglasses for people at risk for cataracts. Ideally they should have the Skin Cancer Foundation's Seal of Recommendation for Sunglasses. Special purpose glasses should wrap around the head and block light coming from above, below, and both sides of the glasses. They should also fit snugly on the nose.
Lenses that are simply dark but not coated with UV-absorbing material may actually increase the risk of cataracts because the pupil widens to compensate for the shaded glass. This may allow more harmful ultraviolet waves to enter. Polarized glasses cut glare but have no effect on UV radiation. Mirror finishes without additional processing for UV blockage are also not fully protective. There is some controversy over whether blue light is harmful to the eyes. Some people prefer amber lenses, which block out the blue spectrum.

Antioxidant vitamins C and E. Because of the role oxidants may play in cataract formation, researchers are investigating the benefits of antioxidant vitamins and other food chemicals. Vitamins C, E, and riboflavin (a B vitamin), for example, are helpful in preserving levels of glutathione, an enzyme that helps protect against oxidation in the eye. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. Some evidence also suggests that ultraviolet B radiation interacts with deficiencies in certain antioxidants, such as vitamin E and zinc, to increase damage in the corneas and lenses of the eye.

Evidence on the benefits of supplements of vitamin E or C, or vitamin-rich foods, is conflicting. For example, in two identically constructed trials in the US and Britain, the American group derived apparent benefits from vitamins E, C, and beta carotene while the British group reported very little cataract protection. A 2005 study suggested that long-term use of vitamin E supplements may slow cataract development. However, in a major on-going American study called the Age-Related Eye Disease Study (AREDS), researchers reported no difference in the incidence of cataracts after 7 years in people who took the antioxidant vitamins compared to those who took sham vitamins.

High doses of vitamins may have harmful effects. It is always wise, in any case, to pursue a healthy diet that is low in fats, high in complex carbohydrates, and rich in fruits and vegetables.

B vitamins. Some studies report some protection from a number of B vitamins, including vitamins B1 (thiamin) B2 (riboflavin), B3 (niacin) and B12 (folate). Riboflavin, for example, plays a critical role in the production of glutathione, an enzyme that helps protect against oxidation in the eye. All forms of vitamin B are widely available in dairy products, fortified grains, and meat.

Carotenoids. Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Different carotenoids may be more beneficial then others. They include:

Xanthophylls are compounds that form a particular category of carotenoids. The xanthophylls lutein and zeaxanthin are found in the lenses of the eye and may be of significant importance for people at risk for cataracts. Some evidence indicates supplements of xanthophyll-rich foods may help retard the aging process in the eye and protect against cataracts. In fact, some experts suggest that the higher risk of cataracts in women compared to men may be partly due to a lesser ability to transport these carotenoids from the blood into the eye. Xanthophylls can be obtained from dark green leafy vegetables (such as spinach), broccoli, and eggs.
Lycopene is an important carotenoid that may also play an important role in eye health as a person ages. Tomatoes are the importance sources of lycopene.
Beta carotene is the most widely studied carotenoid and is a powerful antioxidant. It has been specifically studied for cataract protection. Most studies, however, have found little or no benefits. A 2003 study did suggest that beta carotene may protect against cataracts in smokers, although it is important to note that other studies report a higher risk for lung cancer in smokers who take beta carotene.

Click the icon to see an image of folate sources.

Click the icon to see an image of vitamin B12 sources.

Click the icon to see an image of riboflavin sources.

Phytochemicals. Phytochemicals are substances in plants that have beneficial effects. Dark colored (green, red, purple, and yellow) fruits and vegetables usually have high levels of important plant chemicals and have been associated with a lower risk for cataracts. Tea contains certain plant chemicals called polyphenols that have been associated with protection against cataracts.

Click the icon to see an image of phytochemicals.

Diagnosis

Either an ophthalmologist or an optometrist can examine patients for cataracts, but only ophthalmologists are qualified to treat cataracts.

An ophthalmologist is a doctor who specializes in the medical and surgical care of the eye.
An optometrist is engaged in the practice of eye care, but is not a doctor and cannot prescribe medication or perform surgery.

The eye professional can observe cloudy areas on the lenses with a direct physical examination, even before the cataracts begin to interfere with vision. Cameras can measure the cataract density. Various vision tests are also performed.

Snellen Eye Chart. To determine how clearly a person can actually see, the Snellen eye chart is used, with rows of letters decreasing in size:

From a specified distance, usually 20 feet, a person reads the letters using one eye at a time.
If a person can read down to the small letters on the line marked 20 feet, then vision is 20/20 (normal vision).
If a person can read only down through the line marked 40 feet, vision is 20/40; that is, from 20 feet the patient can read what someone with normal vision can read from 40 feet.
If the large letters on the line marked 200 feet cannot be read with the better eye, even with glasses, the patient is considered legally blind.

The visual acuity test can be performed in many different ways. It is a quick way to detect vision problems and is frequently used in schools or for mass screening. Driver license bureaus often use a small device that can test the eyes individually and then together.

Other Tests. A number of other tests are used to diagnose cataracts or to determine if surgery is needed.

A chart similar to the Snellen chart, which has the same size letters, but in different contrasts with background, is used to test contrast sensitivity,
Glare sensitivity is tested by having the patient read a chart twice, with and without bright lights.
Tests of macular function, which evaluate the eye's acute vision center, can help the ophthalmologist determine the expected improvement from surgery.
The corneal endothelium, a layer of cells lining the cornea, is sensitive to surgical trauma and should be evaluated before any intraocular operation.
Patients with other eye disorders may require a number of other pre-operative tests.

Although eye tests aid in making a diagnosis for cataracts, results do not always reflect the quality of life and how effectively people function at home:

Some people with cataracts perform poorly on the tests yet appear to have no difficulty functioning normally day-to-day.
Others perform well on the tests but insist that their eyesight is bad enough to curtail ordinary activities, such as driving.

Standard eye tests, therefore, may not be useful for determining whether a patient actually needs cataract surgery.

In general, even if cataracts are diagnosed, the decision to remove them should be based on the patient's own perception of vision difficulties and needs and the effect of vision loss on normal activity. The patient should also be aware of all the risks and costs of surgery. In order to determine the quality of life, the patient may be given a questionnaire such as National Eye Institute Visual Function Questionnaire, which asks 39 questions related to vision and daily activities. This test or others may be useful for determining if eye disease is actually impairing the ability to function.

Treatment

Although surgery is the only remedy for cataracts, it is almost never an emergency. Most cataracts cause no problem other than reducing a person's ability to see, so there is no harm in delaying surgery.

Early cataracts may be managed with the following measures:

Stronger eyeglasses or contact lenses
Use of a magnifying glass during reading
Strong lighting
Medication that dilates the pupil. (May help some people with capsular cataracts, although glare might be a problem with this treatment.)

It is important to note, however, that no treatments will prevent cataract formation or progression or make a cataract disappear.

Progression of Cataracts. Patients and their families usually have plenty of time to consider options carefully and discuss them with an ophthalmologist. There is no constant rate at which cataracts progress:

Some develop to a certain point and then stop.
Even if a cataract does progress, it may be years before it interferes with vision.
Only in a very few, very rare circumstances is it necessary that cataract surgery be performed immediately.

Each year about 2.8 million cataract operations are performed, making it the most common operation in the U.S. for people over age 65. Cataract surgery may be the oldest procedure in the world, having been introduced to Europe from India by Alexander the Great's army.

In the past, cataract surgery was not performed until the cataract had become well developed. Newer techniques, however, have made it safer and even more efficient to operate in earlier stages. In fact, modern cataract techniques not only remove cataracts but are also becoming important procedures for correcting astigmatism. Cataract surgery improves vision in up to 95% of cases and prevents millions of Americans from going blind.

Nevertheless, considerable evidence suggests that, because of the ease and relative safety of the procedure, it may be performed more often than needed. Patients having operations now tend to have better preoperative vision than those operated on 10 or 20 years ago. In a study of 800 cataract operations, 25% of the patients said that clouding had had no obvious effect on their lives before the procedure.

Cataract surgery is very successful. It has the following advantages:

Nearly all patients enjoy better vision after surgery. Advanced procedures in lens development are allowing correction of astigmatism as well as cataract removal. (Patients with significant eye disease, such as glaucoma or corneal or retinal disease, may not experience the same degree of improvement.)
Many people experience significant improvement in quality of life after the operation.
Some studies indicate that better vision might even help slow down age-related health problems unrelated to the eyes.

In general, surgery is indicated for people with cataracts under the following circumstances:

The Snellen eye test reports 20/40 or worse, with the cataract being responsible for vision loss and glasses or visual aids no longer being helpful.
Everyday activities have become difficult to perform to the point that independence is threatened. Questionnaires that assess the effects of cataracts on quality of life have been developed.
The patient is at risk for falling in low light.

These guidelines are general, however. Whether surgery is appropriate or not further depends on the cataract patient's specific condition and needs. Some examples include the following:

Even if the criteria for surgery are met, a very sick, very elderly person in a nursing home may have less need for sharp vision than an active younger adult. Among very elderly patients (85 years and older), especially those with serious health problems, there are also higher risks for complications during surgery and poor outcomes afterward. Nevertheless, these cautions should not prevent the very elderly from having this procedure; vision improvement rates are still over 85%.
Even if the criteria for surgery are not met, some people with eye tests of 20/40 or better might want surgery because of problems with glare, double vision, or the need to have an unrestricted driver's license.
Even if the criteria for surgery are not met, if retinal disease is also suspected (usually a complication of diabetes), the doctor may perform cataract surgery in order to have a clear view of the eye.

Because of the risks, albeit small ones, of poorer vision or blindness, no one should be forced to have cataract surgery if they don't want it or are not strong enough to undergo the procedure. If there are any doubts about whether or not to undergo cataract surgery, a second opinion should be considered.

The patient should ask the ophthalmologist the following questions before agreeing to cataract surgery:

Is my cataract surgery an emergency?
Are the cataracts the only cause of my poor vision?
How much experience do you have with this procedure?
Do I have other eye diseases that might complicate surgery or reduce my benefit?
Do I have other health problems that might further complicate eye surgery?
Will you be able to implant an intraocular lens?
What type of procedure will you use?
Will I have to stay in the hospital overnight?
Afterwards, what are my chances of having poorer vision or becoming totally blind in that eye?
How well should I ultimately be able to see out of the operated eye?
How long will it take to heal?
How long will it take to achieve my best eyesight?
Will I have to wear glasses or contact lenses after surgery?
When will I get my final eyeglass prescription?
How soon after surgery will I be able to see well enough to go back to work? Drive a car? Return to full activity?
What will the surgery cost?

Cataract surgery is now usually done as an outpatient procedure under local anesthesia and takes less than an hour. Preoperative preparations may include:

Having a general physical examination is important for patients with medical problems such as diabetes. Diabetes can cause damage to the blood vessels of the eye’s retina, a condition called diabetic retinopathy. Recent research suggests that patients who have diabetic retinopathy and poor blood sugar control should not have their blood sugar rapidly corrected before cataract surgery. Correcting blood sugar too quickly before surgery can cause vision problems after surgery.
The ophthalmologist will use a painless ultrasound test to measure the length of the eye and determine the type of replacement lens that will be needed after the operation.
Topical application of so-called fluoroquinolone antibiotics (such as ofloxacin or ciprofloxacin) may be applied preoperatively to protect against postoperative infection.
Most healthy patients are given either a local injection or topical anesthetic. The patients who report the least pain during the operation are those given a sedative followed by a local injection rather than just the topical drug.
Some patients may require a general anesthetic, such as those who are very anxious, those who are unable to cooperate with the surgeon, and those who are allergic to local anesthetics.

All cataract procedures involve removal of the cataract-affected lens and replacing it with an artificial lens.

Phacoemulsification. Phacoemulsification (phaco means lens, emulsification means to liquefy) is now the most common cataract procedure in the United States and accounts for 85% of cases. Benefits are greater than with standard extracapsular surgery, and it may be particularly helpful for people with diabetes.

The procedure generally involves:

The surgeon makes an incision, which is much smaller than with standard cataract extraction.
Ultrasound is then used to break up the clouded lens into small fragments.
The tiny pieces are sucked out with a vacuum-like device.
A replacement lens is then usually inserted into the capsular bag where the natural lens used to be. In most cases, this is an intraocular lens (IOL), which is foldable and slips in through the tiny incision.
Because the incision is so small, it is often watertight and does not require a suture afterward, particularly if a foldable lens has been used. A suture may be needed if a tear or break occurs during the procedure or the surgeon inserts a rigid lens that requires a wider incision.

Click the icon to see an illustrated series detailing cataract surgery.

Phacoemulsification requires only local anesthesia. Newer methods for administering local anesthesia produce few complications. Most phacoemulsification procedures now take about 15 minutes, and the patient is usually out of the operating room in about an hour. There is little discomfort afterward and visual rehabilitation takes about 1 - 3 weeks.

Phacoemulsification is sometimes combined with viscocanalostomy, a glaucoma surgical procedure, for patients who have both glaucoma and cataracts. Recent research suggests that phacoviscocanalostomy (as this combined procedure is called) is safe and effective for this group of patients.

Surgeons in the U.S. and Europe are currently investigating Microphaco, a new approach to cataract surgery that uses two smaller (micro) incisions. The smaller incisions measure about 1.6 mm compared to the traditional 3 mm. Experts say this procedure is expected to revolutionize refractive and cataract surgery.

Other Lens Removal Techniques. The AquaLase device uses pulses of fluid to wash away the clouded lens. Some experts believe this approach causes less trauma to the eye, and allows for a quicker recovery time for the patient, than the ultrasound used in phacoemulsification.

Extracapsular or Intracapsular Cataract Extraction. Extracapsular cataract extraction was the original standard procedure, but is now generally used only in patients who have an extremely hard lens. It typically involves the following steps:

The ophthalmologist works under an operating microscope to make a small incision in the cornea of the eye.
The surgeon then extracts the clouded lens through this incision.
The capsule is left in place, which adds structural strength to the eye and enhances the healing process. (Less commonly, in intracapsular cataract extraction, the surgeon removes the lens and the entire capsule. There are greater risks with this procedure for swelling and retinal detachment.)
A replacement lens is then usually inserted.
A small suture is needed to stitch the incision together.

It takes about 2 - 4 weeks to completely restore vision.

With the clouded lens removed, the eye cannot focus a sharp image on the retina. A replacement lens or eyeglass are therefore needed:

Intraocular Lenses (IOL). In about 90% of cataract operations, an artificial lens, known as an intraocular lens (IOLs), is inserted. Until recently, IOLs used a pair of little spring-loaded loops to hold the lens in place. Most IOLs are now foldable, which makes insertion easier. In fact, a prefolded lens is now available that unrolls to fit the eye as body temperature warms it.

IOLs are available as monofocal or multifocal. Monofocal lenses correct only one type of vision range (such as distance vision). Multifocal lenses are designed for patients who need correction for a range of vision. A 2006 study suggested that the Tecnis IOL works particularly well for patients who require a multifocal IOL.

Although all the lens materials are presumably chemically inert, there are some reports of specific problems, notably a risk for causing a reaction that leads to the development of secondary cataracts, a condition called posterior capsular opacification. IOLs include the following materials:

Acrylic: The majority of IOLs are made from acrylic, which allows a controlled unfolding of the lens. Evidence indicates that this material provides a better visual outcome and fewer complications than other standard IOLs.
Polymethylmethacrylate (PMMA): Has the longest safety record. A PMMA IOL coated with heparin, a blood thinner drug, helps protect against the development of a secondary cataract after surgery.
Silicone: Can be inserted through a smaller incision than other materials. It has the highest rates of secondary cataracts. Newer forms of silicon IOLs may pose a lower risk.

Other materials are under investigation.

IOL brands include:

Crystalens: The FDA approved the Crystalens IOL in 2003. It is made from a form of silicone called Biosil. The Crystalens uses "hinges" that allow the lens to move, mimicking the eye's natural ability to focus automatically and seamlessly at all distances. Studies indicate that when used along with standard cataract removal methods, the Crystalens can restore a full range of functional vision, from distance to reading vision, without total dependence on glasses or contact lenses.
Array: The Array lens also uses silicon. It is one of a number of so-called second-generation IOLs that is available as a multifocal lens to help correct presbyopia (nearsightedness).
Tecnis: The Tecnis foldable IOL was specifically designed to improve functional vision of cataract surgery patients. Tecnis has a patented surface that reduces light scattering (spherical aberration) of the cornea, which can negatively affect vision. In April 2004, The FDA approved new labeling claims for Tecnis, stating the lens may help improve driving safety for senior cataract patients. In clinical trials, simulated night driving and visual acuity (20/20, 20/40) results were significantly better in eyes implanted with the Tecnis IOL. In addition, spherical aberrations were significantly less when compared to the traditional lens with the spherical optic.
AcrySof Natural: Approved in 2003, the yellow-tinted Acrysof Natural IOL was the first foldable lens to filter ultraviolet and blue-light. Eliminating both UV and portions of the high-energy blue light help prevent retinal damage. This lens also conforms to the natural shape of the human lens capsule so it remains centered over the eye.
AcrySof ReSTOR: The AcrySof ReSTOR IOL is approved in the U.S. for patients with and without presbyopia. The lens enhances vision at near, intermediate, and distant ranges. In clinical trials, 80% of patients who received the lens did not require glasses after cataract surgery. The FDA approved the AcrySof ReSTOR in March 2005.

IOLs are designed to improve specific aspects of vision. The choices include:

Lenses that address a single fixed focal point. Such lenses are suitable either for reading or for distance vision, but not both. If a distance lens is implanted, the surgeon prescribes glasses or contact lenses for reading. If a reading lens is implanted, lenses for seeing distances will be prescribed.
Lenses that address multifocal points. Multifocal lenses can focus at different points for both reading and distance vision. One study reported that more than 80% of patients with multifocal lenses were able to see 20/40 or better without correction. However, contrast may be reduced and some patients experience glare and halos, particularly at night.
Lenses are available that will correct astigmatism after cataract surgery.

The patients and the doctor must make these decisions based on specific visual needs.

Contact Lenses or Cataract Glasses. A few patients do not receive a new lens and rely solely on corrective eyeglasses or contact lenses. Such patients may include:

Patients who are extremely near-sighted
Patients with other eye disorders

In such cases, the patient typically returns to the ophthalmologist for a check up the day after surgery, and three additional check-ups are scheduled over a 2-month period. The ophthalmologist can usually give a final prescription for eyeglasses or contact lenses about three months after surgery.

Choosing Contact Lenses. Contact lenses allow clear vision but do not magnify, so those who choose contact lenses after surgery may have to wear reading glasses. Contacts can be prescribed either for use only during the day or for extended-wear. Occasionally contact lenses cause problems, such as infection. Those who wear them should call their eye doctor if they have red or watery eyes, pain, or sensitivity to light.
Cataract Glasses. Until the advent of contact lenses, people who had cataract surgery had no choice but to wear glasses with thick lenses, sometimes called Coke-bottle glasses. These glasses have gotten thinner and lighter in recent years, but they may still be cumbersome. Cataract glasses are different from ordinary glasses and are sometimes difficult to adjust to. Images can seem distorted and may appear suddenly within the peripheral vision. Distances may be hard to judge.

Sometimes a patient has two cataracts and needs to wear glasses between the first and second operation. They are particularly troublesome during this period. The treated eye will see images magnified while the other eye will view them as they actually are, and the brain cannot blend the two images. This is a temporary state that is resolved by the second operation.

Modern cataract surgery is one of the safest of all surgical procedures. Most complications, even if they occur, are not serious. They can include the following:

Swelling and inflammation. Risk is about 1%. This complication is particularly harmful for patients with existing uveitis (chronic inflammation in the eye, which can be due to various conditions).
Glare. Patients may experience glare after surgery from light scattering at the edges of the new lens, particularly with square-edged IOLs, which are typically used with posterior capsular cataracts. In most cases, this is a temporary problem that resolves after a few weeks. Sometimes, the problem persists, and the patient requires another operation. Some research suggests that glare can be significantly reduced by texturizing the edges of the square lens.
Materials used in some lenses trigger an immune response in about half of patients. This causes inflammation and tiny deposits of tissue in the eye that lead to secondary cataracts -- called posterior capsule opacification. Studies suggest that silicone implants pose the highest rates for inflammation and secondary cataracts, particularly in patients with other eye diseases. Newer silicon IOLs pose less risk. In one study, the lowest rates were with IOLs made of acrylic and heparin-coated PMMA.
Retinal detachment. In rare cases, the retina at the rear of the eye can become detached. Risk is very low (0.1%), and phacoemulsification poses less of a risk for this than standard surgery.
Atonia (loss of muscle tone that results in a disturbing glare). (Phacoemulsification poses less of a risk than standard surgery.)
Glaucoma. This is an eye condition in which the pressure of fluids inside the eye rises dangerously. Risk is very low, but patients should be sure to avoid activities after surgery that increase pressure.

Glaucoma is a condition of increased fluid pressure inside the eye. The increased pressure causes compression of the retina and the optic nerve which can eventually lead to nerve damage. Glaucoma can cause partial vision loss, with blindness as a possible eventual outcome.

Infection. This is very rare (0.2%), but is devastating if it does develop.
Blisters on the cornea. There is a higher risk of rupture with phacoemulsification, but the risk is extremely low, particularly for experienced eye surgeons. In 2004, the FDA approved the StabilEyes Capsular Tension Ring (CTR) to help support the eye's capsular bag during cataract surgery, especially in those with weak or broken eye fibers (zonules). A CTR is an open ring made of polymethylmethacrylate (PMMA). The ring goes into the capsular bag itself, stabilizing the eye.
Bleeding can develop inside the eye. Risk is about 1% for minor bleeding and 1 in 10,000 for severe bleeding.
An implanted IOL can become damaged or dislocated. Risk is very low.
The surgery itself can produce vision loss or impairment. The risk for this is 1 in 1,000. (Phacoemulsification poses less of a risk than standard surgery.)
Macular degeneration. Macular degeneration, in which the retina breaks down, is a common cause of vision loss in the elderly. In a 5-year study, people who underwent cataract surgery had twice the risk for progression of age-related macular degeneration. Interestingly, another study reported that cataract surgery significantly helped patients who had existing macular degeneration. More research is needed to refute or confirm this finding.

Click the icon to see an image of macular degeneration.

Phacoemulsification does have some specific complications, although they are rare, particularly with experienced eye surgeons. They include:

Rupture of the lens capsule.
Loss of the lens nucleus into the eye fluid. (This will require removal by a specialist and may result in poorer vision.)
Flying fragments of the lens can damage the cornea or threaten the retina.
Pre- and postoperative changes in blood pressure, which are generally not a problem, should be observed carefully, since in some cases the changes may be extreme.

In about 30% of cases patients develop secondary cataracts within 1 - 5 years after either procedure, which require different treatment choices.

Preventing Infection and Reducing Swelling. The ophthalmologist may prescribe the following medications:

A topical antibiotic (neomycin or, more effectively, gentamicin). This drug protects against infection.
Corticosteroid eyedrops or ointments are often used to reduce swelling. Corticosteroids (commonly called steroids) are potent anti-inflammatory drugs. However, they also pose a risk for pressure in the eye and infection. One study reported less visual sharpness with the use of steroids compared to antibiotics. Some newer steroids such as rimexolone, loteprednol, and fluorometholone may pose a lower risk for abnormal pressure.
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, ketorolac, naproxen, and voltaren, also reduce swelling and do not pose the same risks as steroids. Newer NSAIDS that have been approved to treat pain and swelling after cataract surgery include bromfenac (Xibrom) and nepafenac (Nevanac).

In one study, applying an ice pack for 2 hours immediately after phacoemulsification improved comfort level and reduced inflammation, even days after the operation. This simple procedure has no adverse effects and patients should discuss it with their surgeons before the operation.

Factors That Increase Risk for Complications. The risks of complications are greater for the following people:

Patients who have other eye diseases.
People with diabetes. Intracapsular and extracapsular cataract extraction are known to pose a high risk for the development or worsening of retinopathy, a known eye complication of diabetes. Experts have hoped that phacoemulsification would pose a lower risk, but a 2001 study reported a high percentage of retinopathy progression after this procedure. The amount of experience a surgeon has plays a role in whether or not a patient has this complication.
People who have taken tamsulosin (Flomax) or other alpha-1 blocker drugs. Tamsulosin is a muscle relaxant prescribed for treatment of several urinary conditions including benign prostatic hyperplasia (BPH). In 2005, a leading ophthalmologic association and the FDA warned that tamsulosin may cause intraoperative floppy iris syndrome (IFIS), a loss of muscle tone in the iris that can cause complications during eye surgery. Problems have been reported both for patients who were taking the drug during surgery as well as those who had stopped taking the drug weeks or months before surgery. Men who have taken tamsulosin or similar drugs should inform their eye surgeon. The surgeon may need to use different techniques to minimize the risk of IFIS. A 2006 study indicated that patients can have safe and successful surgeries with these modified techniques.

Returning Home and Follow-up Visits.

Patients usually leave the surgical site within an hour of surgery. Cataract surgery almost never requires an overnight hospital stay.
They need to have someone drive them home and stay with them for a few days until their vision is acclimated.
The patient is usually examined the day after surgery and then during the following month. Additional visits are made as required.
Vision usually remains blurred for a while but gradually clears, usually over a 2 - 6 week period. (It can take longer.)
When the doctor decides the condition has stabilized, the patient will receive a final prescription for glasses or contacts.

Protecting the Eye. Postoperative protection of the eye typically involves:

The ophthalmologist usually tapes a bandage over the eye to protect it during the healing process.
When changing the bandage, the eye can be cleaned gently using a washcloth dipped in warm water without soap. A new bandage can then be positioned and taped.
It is very important not to press or rub the eye during this procedure.
An eye shield may be placed over the bandage at night.

Avoiding Glaucoma. Cataract surgery can cause glaucoma, a condition in which the pressure of fluids inside the eye rises dangerously. It is very important to minimize any activity that increases internal eye pressure. Postoperative cataract patients take the following precautions:

Minimize vigorous exercise.
Put on shoes while sitting and without lifting up the feet.
Kneel instead of bending over to pick something up.
Avoid lifting.
Limit reading since it requires eye movement (watching television is all right).
Sleep on the back or on the unoperated side.

Cataracts and Glaucoma. For patients with both glaucoma and cataracts, experts recommend:

In patients with cataracts and poorly controlled glaucoma, a two-step procedure for both eye conditions is needed. The patient first receives a trabeculectomy for glaucoma, followed by cataract surgery. Fluid leakage and the presence of blood in the back chamber of the eye are potential complications of this combined procedure. Phacoemulsification has improved success rates and reduced high complication rates of the double procedure compared with extracapsular cataract extraction. New advances that replace trabeculectomy with nonpenetrating glaucoma surgery may prove to be beneficial.
In patients who have cataracts plus either closed-angle glaucoma or open angle glaucoma that is stabilized with medication, the cataract may be able to be extracted and medication continued for the glaucoma.
A major 2002 analysis suggested that the combined approach generally offers better control over eye pressure for patients with both cataracts and glaucoma. The best surgical procedure, however, is still uncertain.

Cataracts and Corneal Disease. Patients who have both cataracts and corneal disease may undergo one of the following:

Combination Procedure. A single operation that combines three procedures. The combined procedure has been used since the late 1970s and employs extracapsular cataract extraction and intraocular lens insertion with corneal transplantation (called penetrating keratoplasty).
Sequential Procedure. An operation that uses two procedures sequentially. The sequential option performs the cataract procedures and the corneal transplantation separately.

Recovery of vision is usually much more rapid after the combined procedure than after the sequential procedures. Performing the procedures sequentially may also carry a higher rejection rate of the implant, although a 2003 study found no differences in failure rates between the two approaches after a year.

In any case, many experts recommend that for most patients the sequential procedures may be the better option because it appears to have fewer of the following complications than with the combined procedure:

Posterior capsule rupture
Eye fluid loss
Postoperative refractive errors, which result in abnormal distribution of light patterns

The rate of these errors still depends on the skill of the surgeon and the power of the implanted lens no matter what approach is used.

About 30% of patients who undergo extracapsular cataract surgery develop a secondary "after-cataract" called posterior capsular opacification. Posterior capsular opacification generally occurs because of the following events:

After surgery, there are still some natural lens cells left behind that proliferate on the back of the capsule.
The capsule gradually becomes cloudy and interferes with clear vision the same way the original cataract did.

According to a 2001 study, the probability of developing a secondary cataract was 6% at 1 year, 15% at 2 years, 23% at 3 years, and 38% at 9 years. The risk is lower with phacoemulsification. Secondary cataracts are more likely to occur in younger patients, in those with diabetes, or when cataract surgery is combined with vitrectomy (clearance of debris from the fluid in the eye).

Preventing Posterior Capsular Opacification. Studies suggest that acrylic lenses pose the lowest risk for posterior capsular opacification. A number of substances to prevent posterior capsular opacification are under investigation, including tranilast eyedrops, new lens materials, special capsular rings inserted during phacoemulsification, and new coatings on the implanted lens.

Treatment Decisions for Cataracts in the Second Eye. If a person has a cataract in a second eye, the issues for decision making are the same as for the first eye. The time of the procedure in the case of two cataracts is unclear. Doctors have long recommended that surgery on the second eye should be postponed until the first eye has healed and the results known (about a year).

One study has called this recommendation into question. It was conducted in England, where for budgetary reasons, there are long waits for second-eye cataract surgeries. In the study, patients who waited 7 - 12 months for the second-eye surgery reported significant difficulty in reading and performing ordinary tasks during the waiting period. Only 1% of patients who had the second surgery within 6 weeks reported having trouble seeing. In addition, 70% of those who waited experienced problems in depth perception, which can cause difficulty in walking and driving; only 12% who didn't wait reported this problem. Patients with double cataracts should discuss all options with their surgeon.

Treatment for Posterior Capsular Opacification. The standard treatment is laser surgery known as a YAG capsulotomy. (Capsulotomy means cutting into the capsule, and YAG is an abbreviation of yttrium aluminum garnet, the laser most often used for this procedure.)

This is an outpatient procedure and involves no incision.
Using the laser beam, the ophthalmologist makes an opening in the clouded capsule to let light through.
After the procedure the patient should remain in the doctor's office for an hour to be sure that pressure in the eye is not elevated.
An eye examination for any complications should follow within 2 weeks.

Complications. Laser surgery has become so commonplace that some ophthalmologists use it after cataract surgery to prevent later clouding. However, laser surgery carries its own risks and possible complications, similar to those of cataract surgery itself, and can also lead to poorer vision or blindness. About 1% of laser surgery patients develop a detached retina, which is much higher than the risk from the original cataract surgery.

Click the icon to see an image of a detached retina.

In some people, particularly those with glaucoma or who are severely nearsighted, the pressure in the eye may spike after laser surgery. Certain drugs used for treating glaucoma, such as dorzolamide (Trusopt) or apraclonidine (Iopidine), may helpful for preventing this occurrence. It is strongly recommended, however, that this surgery not be performed to prevent a secondary cataract, but only if the lens capsule clouds up again.

Infants. Treatment of infants first depends on whether one or both eyes are affected:

For infants born with cataracts in one eye, the American Academy of Ophthalmology recommends surgery as soon as possible, by 4 months or ideally even earlier. The procedure is followed by contact lens correction and patching of the unaffected eye. Although this approach is successful in many cases, some children still become blind in the affected eye. There is also a high risk for glaucoma after surgery.
In infants with cataracts in both eyes, surgery is not always an option. In some cases, it may be performed sequentially, with the second eye operated on a few days after the first. Phacoemulsification appears to pose a much higher risk for secondary cataracts than standard lens removal.

Toddlers and Older Children. Intraocular lens replacement is now becoming standard treatment for children 2 years and older.

Resources

www.ascrs.org -- The American Society of Cataract and Refractive Surgery
www.aao.org -- American Academy of Ophthalmology
www.nei.nih.gov -- National Eye Institute
www.eyesurgeryeducation.com -- Eye Surgery Education Council
www.lighthouse.org -- Lighthouse International
www.aao.org/aao/find_eyemd.cfm -- Find an ophthalmologist

References

Eke T, Thompson JR. Serious complications of local anaesthesia for cataract surgery: a one-year national survey in the United Kingdom. Br J Ophthalmol. 2006 Nov 23; [Epub ahead of print]

Hutz WW, Eckhardt HB, Rohrig B, Grolmus R. Reading ability with 3 multifocal intraocular lens models. J Cataract Refract Surg. 2006 Dec;32(12):2015-21.

Klein BE, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. JAMA. 2006 Jun 21;295(23):2752-8.

Rein DB, Zhang P, Wirth KE, Lee PP, Hoerger TJ, McCall N, et al. The economic burden of major adult visual disorders in the United States. Arch Ophthalmol. 2006 Dec;124(12):1754-60.

Wishart MS, Dagres E. Seven-year follow-up of combined cataract extraction and viscocanalostomy. J Cataract Refract Surg. 2006 Dec;32(12):2043-9.

Review Date:
3/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M. Copyright

adam.com

Heart failure

FitSugar — Wed, 08 Oct 2008 17:35:10 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Medications
Surgery and Devices
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Permanent Implantable Heart Approved

In 2006, the FDA approved the first permanent artificial heart. The AbiCor is intended for patients who are not eligible for heart transplants and who are only expected to survive about a month without medical treatment. Patients who received the AbiCor have survived, on average, about 5 months.

Statin Drug Approved for Heart Failure

In 2006, the FDA approved the cholesterol drug atorvastatin (Lipitor) to reduce the risks of hospitalization for heart failure in patients with heart disease.

Drug Research

The investigational drug tolvaptan improved symptoms in patients hospitalized with severe heart failure and fluid build-up in the lungs, according to several 2007 Journal of the American Medical Association (JAMA) studies. However, the drug did not reduce the risks of re-hospitalization and death.

Preserved Versus Reduced Ejection Fraction

Heart failure with preserved left-ventricular ejection fraction (LVEF) is becoming more common, suggests several 2006 studies published in JAMA and the New England Journal of Medicine. Unfortunately, this type of heart failure is less well studied than reduced LVEF. Experts are urging that more studies be conducted to determine better treatment options for preserved LVEF. Both types of heart failure have high mortality rates.

Systolic Blood Pressure Predictor of Mortality

Patients who are admitted to the hospital with heart failure and low systolic blood pressure have a poorer chance of survival than patients admitted with high blood pressure, indicates a 2006 JAMA study.

Diet and Lifestyle Factors

Daily consumption of whole-grain breakfast cereals may reduce the risk for heart failure, suggests research presented at a 2007 American Heart Association conference on heart disease prevention.
A drink or two a day is associated with lower risk of heart failure, indicates a 2006 Journal of the American College of Cardiology study. However, heavy alcohol consumption can increase the risk for heart failure.

Introduction

To understand what occurs in heart failure, it is useful to be familiar with the anatomy of the heart and how it works. The heart is composed of two independent pumping systems, one on the right side, and the other on the left. Each has two chambers, an atrium and a ventricle. The ventricles are the major pumps in the heart.

The external structures of the heart include the ventricles, atria, arteries, and veins. Arteries carry blood away from the heart while veins carry blood into the heart. The vessels colored blue indicate the transport of blood with relatively low content of oxygen and high content of carbon dioxide. The vessels colored red indicate the transport of blood with relatively high content of oxygen and low content of carbon dioxide.

The Right Side of the Heart. The right system receives blood from the veins of the whole body. This is "used" blood, which is poor in oxygen and rich in carbon dioxide.

The right atrium is the first chamber that receives blood.
The chamber expands as its muscles relax to fill with blood that has returned from the body.
The blood enters a second muscular chamber called the right ventricle.
The right ventricle is one of the heart's two major pumps. Its function is to pump the blood into the lungs.
The lungs restore oxygen to the blood and exchange it with carbon dioxide, which is exhaled.

The Left Side of the Heart. The left system receives blood from the lungs. This blood is now oxygen rich.

The oxygen-rich blood returns through veins coming from the lungs (pulmonary veins) to the heart.
It is received from the lungs in the left atrium, the first chamber on the left side.
Here, it moves to the left ventricle, a powerful muscular chamber that pumps the blood back out to the body.
The left ventricle is the strongest of the heart's pumps. Its thicker muscles need to perform contractions powerful enough to force the blood to all parts of the body.
This strong contraction produces systolic blood pressure (the first and higher number in blood pressure measurement). The lower number ( diastolic blood pressure) is measured when the left ventricle relaxes to refill with blood between beats.
Blood leaves the heart through the ascending aorta, the major artery that feeds blood to the entire body.

The Valves. Valves are muscular flaps that open and close so blood will flow in the right direction. There are four valves in the heart:

The tricuspid regulates blood flow between the right atrium and the right ventricle.
The pulmonary valve opens to allow blood to flow from the right ventricle to the lungs.
The mitral valve regulates blood flow between the left atrium and the left ventricle.
The aortic valve allows blood to flow from the left ventricle to the ascending aorta.

Click the icon to see an image of the internal structures of the heart.

The Heart's Electrical System. The heartbeats are triggered and regulated by the conducting system, a network of specialized muscle cells that form an independent electrical system in the heart muscles. These cells are connected by channels that pass chemically caused electrical impulses.

Click the icon to see an image of the conduction system of the heart.

Heart failure is not a disease. It is a condition or process in which the heart is unable to pump enough blood to meet the needs of the body's tissues. The heart doesn't "fail" in the sense of ceasing to beat (as occurs during a heart attack). Rather, it weakens, usually over the course of months or years, so that it is unable to pump out all the blood that enters its chambers. As a result, fluids tend to build up in the lungs and tissues, causing congestion. This condition used to be called "congestive heart failure," but the name was officially changed to heart failure in 2005.

Ways the Heart Can Fail. Heart failure can occur in several ways:

The muscles of the heart pumps (ventricles) become thin and weakened. They stretch (dilate) to the extent that they cannot pump the blood with enough force to reach all the body's tissues.
The heart muscles stiffen or thicken. Here, they lose elasticity and cannot relax. Insufficient blood enters the chamber, so not enough blood is pumped out into the body to serve its needs.
Sometimes the valves of the heart are abnormal. (Valves open or close to control the flow of blood entering or leaving the heart). They may narrow, such as in aortic stenosis, causing a back up of blood, or they may close improperly so that blood leaks back into the heart. The mitral valve (which regulates blood flow between the two chambers on the left side of the heart) often becomes leaky in severe heart failure -- a condition called mitral regurgitation.

Click the icon to see an image of the valves of the heart.

The very mechanisms that the body uses to compensate for inefficient heart pumping can, over time, change the architecture of the heart (called remodeling) and finally lead to irreversible problems.

The specific effects of heart failure on the body depend on whether it occurs on the left or right side. Over time, however, in either form of heart failure, the organs in the body do not receive enough oxygen and nutrients, and the body's wastes are removed slowly. Eventually, vital systems break down.

Failure on the Left Side (Left-Ventricular Heart Failure). Failure on the left side of the heart is more common than failure on the right side. The failure can be a result of abnormal systolic (contraction) or diastolic (relaxation) action:

Systolic. Systolic heart failure is a pumping problem. In systolic failure, the heart muscles weaken and cannot pump enough blood throughout the body. The left ventricle is usually stretched (dilated). Fluid backs up and accumulates in the lungs (pulmonary edema). Systolic heart failure typically occurs in men between the ages of 50 - 70 years who have had a heart attack.
Diastolic. Diastolic heart failure is a filling problem. When the left ventricle muscle becomes stiff and cannot relax properly between heartbeats, the heart cannot fill fully with blood. When this happens, fluid entering the heart backs up. This causes the veins in the body and tissues surrounding the heart to swell and become congested. Patients with diastolic failure are typically women, overweight, and elderly, and have high blood pressure and diabetes.

Failure on the Right Side (Right-Ventricular Heart Failure). Failure on the right side of the heart is most often a result of failure on the left. Because the right ventricle receives blood from the veins, failure here causes the blood to back up. As a result, the veins in the body and tissues surrounding the heart to swell. This causes swelling in the feet, ankles, legs, and abdomen.

Ejection Fraction. To help determine the severity of left-sided heart failure, doctors use an ejection fraction (EF) calculation, also called a left-ventricular ejection fraction (LVEF). This is the percentage of the blood pumped out from the left ventricle during each heartbeat. An ejection fraction of 50 - 75% is considered normal. Patients with left-ventricular heart failure are classified as either having a preserved ejection fraction (greater than 50%) or a reduced ejection fraction (less than 50%).

In general, systolic heart failure has been thought to be associated with a reduced ejection fraction, whereas diastolic heart failure was associated with a preserved (normal) ejection fraction. However, several 2006 studies indicated that diastolic heart failure can occur regardless of the ejection fraction, although it is more common in patients with a preserved ejection fraction. Mortality rates among patients with reduced LVEF and preserved LVEF are similar.

Although reduced LVEF heart failure is better studied, and its treatment goals more clearly defined, several important 2006 studies suggest that preserved LVEF heart failure is becoming increasingly common. The studies, published in the Journal of the American Medical Association and the New England Journal of Medicine, indicated that patients with preserved LVEF heart failure are more likely to be female and older, and have a history of high blood pressure and atrial fibrillation (a disturbance in heart rhythm). Experts are now urging that more studies focus on patients with preserved LVEF so that better treatment options can be established.

Causes

Heart failure has many causes and can evolve in different ways.

It can be a direct, last-stage result of heart damage from one or more of several heart or circulation diseases.
It can occur over time as the heart tries to compensate for abnormalities caused by these conditions, a condition called remodeling.

In all cases, the weaker pumping action of the heart means that less blood is sent to the kidneys. The kidneys respond by retaining water and salt. This in turn increases edema (fluid buildup) in the body, which causes widespread damage.

Uncontrolled high blood pressure (hypertension) is also a major cause of heart failure even in the absence of a heart attack. In fact, about 75% of cases of heart failure start with hypertension. It generally develops as follows:

The heart muscles thicken to make up for increased blood pressure.
The force of the heart muscle contractions weaken over time, and the muscles have difficulty relaxing. This prevents the normal filling of the heart with blood.

[See In-Depth Report #14:High blood pressure.]

Hypertension is a disorder characterized by consistently high blood pressure. Generally, high blood pressure consists of systolic blood pressure (the "top" number, which represents the pressure generated when the heart beats) higher than 140, or diastolic blood pressure (the "bottom" number, which represents the pressure in the vessels when the heart is at rest) over 90.

Coronary artery disease is the end result of a complex process called atherosclerosis (commonly called "hardening of the arteries"). It is the most common cause of heart attack and involves the build-up of unhealthy cholesterol in the arteries, with inflammation and injury in the cells of the blood vessels. The arteries narrow and become brittle. Heart failure in such cases most often results from a pumping defect in the left side of the heart. [See In-Depth Report #3: Coronary artery disease and angina ; and In-Depth Report #23: Cholesterol.]

Click the icon to see an image of atherosclerosis.

People now often survive heart attacks, but eventually many develop heart failure from the physical damage done to the heart muscles by the attack. Ironically, heart attack recovery is probably one of the major factors in the dramatic increase in heart failure cases over the past decade. On an encouraging note, however, new therapies that are reducing the severity of heart attacks may help stabilize heart failure rates. [See In-Depth Report #12: Heart attack.]

The valves of the heart control the flow of blood leaving and entering the heart. Abnormalities can cause blood to back up or leak back into the heart.

Click the icon to see an image of the heart valves.

In the past, rheumatic fever, which scars the heart valves and prevents them from closing, was a major cause of death from heart failure. Fortunately, antibiotics have relegated this disease to a minor cause of heart failure. Birth defects may also cause abnormal valvular development. Although more children born with heart defects are now living to adulthood, they still face a higher than average risk for heart failure as they age.

Cardiomyopathy is disease that damages the heart muscles and leads to heart failure. There are several different types. Injury to the heart muscles may cause the heart muscles to thin out (dilate) or become too thick (become hypertrophic). In either case, the heart doesn't pump correctly.

Dilated Cardiomyopathy. Dilated cardiomyopathy involves an enlarged heart ventricle. The muscles thin out, reducing the pumping action, usually on the left side. Although this condition is associated with genetic factors, the direct cause often is not known. (This is called idiopathic dilated cardiomyopathy.) Research strongly indicates that viruses, such as Coxsackie virus, or other infections may be at the base of this condition. Experts think that an autoimmune response occurs in which infection-fighting antibodies attack a person's own proteins in the heart, mistaking them for foreign substances.

Click the icon to see an image of dilated cardiomyopathy.

Hypertrophic Cardiomyopathy. In hypertrophic cardiomyopathy, the heart muscles become thick and contract with difficulty. Some research indicates that this occurs because of a genetic defect that causes a loss of power in heart muscle cells and, subsequently, lower pumping strength. To compensate for this power loss, the heart muscle cells grow. This condition, rare in the general population, is often the cause of sudden death in young athletes.

Click the icon to see an image of hypertrophic cardiomyopathy.

High blood pressure, heart attacks, or other initial processes that impair the pumping actions of the heart trigger a number of hormonal and neurochemical mechanisms to correct imbalances in pressure and blood flow. Unfortunately, while these corrective responses help in the short term, they increase the work of the heart. The mechanisms are now viewed as major contributors to the end stages of heart failure. Some are described briefly in the following sections.

Remodeling. The heart responds to high blood pressure and overload by enlarging in order to increase blood input. This leads to structural damage called remodeling:

In order to accommodate the increased blood input, the heart muscle cells elongate. The muscular walls of the heart that they form become thinner and inefficient.
The muscle cells undergo other changes that result in calcium loss. Calcium is a mineral that is crucial for healthy heart contractions.
The thinner heart muscles and the impaired heart contractions further weaken the heart's pump.
Mitral valve regurgitation is a possible outcome of remodeling. The mitral valve regulates blood flow between the two chambers on the left side of the heart. In response to remodeling, the structural changes in the heart may distort the mitral valve so that the blood leaks backward into the left atrium of the heart instead of flowing out into the body's circulation.
These changes are generally irreversible, although heart pacemakers and certain drugs, including beta-blockers and ACE inhibitors, may reverse some of the remodeling in some patients.

Activation of the Sympathetic Nervous System. The sympathetic nervous system consists of the nerve cells that automatically govern and regulate the beating heart.

This nervous system responds to the failing heart pump by signaling the release of stress hormones, in particular a powerful one called norepinephrine.
These hormones flood the heart, causing it to beat even faster.
These rapid heart beats, although intended to accommodate the weakened pumping actions, only accelerate the damage.

The Renin-Angiotensin-Aldosterone System (RAAS). The renin-angiotensin-aldosterone system (RAAS) is a group of hormones that are responsible for the opening and narrowing of blood vessels and retention of fluids. They also affect cell development in the heart.

The RAAS hormones are called into action by the failing heart.
They respond to the lower blood volume of the weakened heart by constricting the blood vessels and retaining fluids and sodium.
The heart then works harder to pump blood through these narrowed vessels. Blood pressure, then, is forced to increase, which creates a vicious cycle.

Immune System Response. The immune system may also compound the damage. In response to injury in the heart muscle cells or in other parts of the body that occurs as the heart fails, the immune system releases factors intended to protect these areas.

In excess, however, they can cause inflammation and damage.

The most important of these factors are called cytokines. Active cytokines include tumor necrosis factor (TNF) and possibly interleukins 1 and 6.
High levels of these cytokines have been observed in patients with the most severe classes of heart failure.
They may play an important role in the process leading to remodeling. High levels of these cytokines may actually trigger muscle cell growth and enlargement of the heart.

Other Players. Other molecules or compounds have been identified that might play a positive or negative role in the process of the failing heart.

Natriuretic peptides are a family of compounds released to counterbalance the effects of RAAS. Atrial natriuretic peptide (ANP) is a specific member of this family that opens blood vessels and counteracts the sodium-retaining properties of aldosterone (one of the RAAS hormones). It is of particular interest to researchers looking for new treatments.
Endothelin is a powerful protein involved in blood vessel constriction, cell proliferation and build-up, and other negative effects on the heart.
Nitric oxide is important for blood vessel dilation and elasticity.

Symptoms

Many symptoms of heart failure result from the congestion that develops as fluid backs up into the lungs and leaks into the tissues. Other symptoms result from inadequate delivery of oxygen-rich blood to the body's tissues. Since heart failure can progress rapidly, it is essential to consult a doctor immediately if any of the following symptoms are detected.

Fatigue and shortness of breath (dyspnea) are the first symptoms. They are caused by fluid in the lungs. Patients typically report that they feel out of breath after mild exertion. It is unlike the breathlessness of angina, which feels like a heavy weight pressing on the chest.

Fluid retention. Patients may complain of leg or abdominal swelling.
Wheezing or cough. Patients may have asthma-like wheezing or a dry hacking cough that occurs a few hours after lying down, but then stops after the patient sits up.
Central sleep apnea. This disorder results when the brain fails to signal the muscles to breathe during sleep. It occurs in up to half of people with heart failure. Sleep apnea causes disordered breathing at night. If heart failure progresses, the apnea may be so acute that a person, unable to breathe, may awaken from sleep in panic.
Loss of muscle mass. Over time, patients may lose muscle weight due to low cardiac output.

Ultimately, fluid in the lungs may build up. This is called pulmonary edema. When this happens, symptoms become more severe.

In addition to shortness of breath, patients sometimes have a cough that produces a pinkish froth.
Patients may experience a bubbling sensation in the lungs and feel as if they are drowning.
Typically, the skin is clammy and pale, sometimes nearly blue. This is a life-threatening situation, and the patient must go immediately to an emergency room.

Fatigue. As with left-side heart failure, an early symptom of right-side (right-ventricular) failure is extreme tiredness.
Fluid accumulation. This first occurs in the feet, then the ankles and legs, and finally in the abdomen. The liver may also be enlarged.
Weight gain. Although appetites are often depressed, patients with heart failure gain weight because they retain salt and water.
Loss of muscle mass.

Risk Factors

Nearly 5 million Americans currently suffer from heart failure. About 550,000 new cases of heart failure are now diagnosed each year. In 1970 there were only 250,000 new cases, so the annual numbers have risen dramatically. Such numbers represent an increasingly older population. Although there has been a dramatic increase over the last several decades in the number of people who suffer from heart failure, survival rates have been improving greatly.

Coronary artery disease and high blood pressure are the main causes of heart failure. Other diseases that damage or weaken the heart muscle or heart valves can also cause heart failure. Heart failure is most common in people over age 65, African-Americans, and women.

Heart failure is the most common reason for hospitalization in the elderly, and as the population ages, the incidence of heart failure is rising dramatically. According to one report, it occurs at a rate of about 10 in 1,000 people after age 65. The positive implication is, however, that people are living longer with heart failure.

Men are at higher risk for heart failure than women, although the difference narrows with age. Women also have a better survival rate than men do when heart failure is caused by valvular heart disease, high blood pressure, or alcohol abuse. (Some studies indicate that this is because men may be more susceptible to the process of heart muscle-cell remodeling, a damaging effect of hypertension.)

The survival rates of women and men are more similar, however, when heart failure evolves from coronary artery disease or heart attack. Women are much more likely to develop heart failure after a heart attack than men. In such cases, some evidence suggests that the reasons for this may include less aggressive approach to treatment for the initial heart conditions.

African-Americans are at higher risk for heart failure than Caucasians, and studies have reported that they tend to do much worse. In a 2003 study, however, in which Caucasians and African-Americans had comparable treatment, African-Americans actually had lower 1-year mortality rates (with slightly higher rates of rehospitalizations). Some evidence suggests that African-Americans are more often likely than Caucasians to develop diastolic heart failure (a failure of the heart muscle to relax normally), which is often a precursor to systolic heart failure (impaired ability to pump blood). Caucasians tend to develop systolic heart failure first.

According to a 2006 New England Journal of Medicine study, people whose parents had heart failure have a greatly increased risk of developing heart failure, particularly left-ventricular systolic heart failure. Earlier studies have suggested that a family history of early heart failure caused by cardiomyopathies (diseases that damage the heart muscle) may also predispose people to the disease. Researchers are looking for changes in specific genes that might regulate systems involved in heart failure and so increase susceptibility in certain populations.

Chronic alcohol abuse can damage the heart muscles, can cause hypertension, and may prove to be one cause of idiopathic dilated cardiomyopathy. Moderate alcohol consumption, on the other hand (generally defined as 2 drinks a day for men and 1 drink for women), may protect against heart failure. Non-drinkers, though, are not advised to begin drinking.

Coronary artery disease. More than 60% of heart failure cases may be due to coronary artery disease and its risk factors (smoking, sedentary living, obesity).
Heart attack. The injured heart after an attack is at high risk for failure. The improved survival rates from heart attack over the past decades have actually been responsible for the dramatic increase in heart failure rates.
High blood pressure. Hypertension is a significant risk factor and is present in 75% of patients with heart failure.
Diabetes. People with diabetes are at high risk for heart failure, particularly if they also have coronary artery disease. Even blood sugar abnormalities that precede diabetes increase the risk.
Obesity. Obesity is associated with both hypertension and type 2 diabetes, conditions that place people at risk for heart failure. Evidence strongly suggests that obesity itself is a major risk factor for heart failure, particularly in women. In a major 2002 study, about 14% of heart failure cases in women and 11% in men could be attributed to obesity. Both overweight and obese women had a significantly higher than normal risk for heart failure. Only obesity led to a significant risk in men.
Valvular heart disease. Specific valvular conditions that are common in patients with heart failure include aortic stenosis and mitral regurgitation.
Severe emphysema. Chronic obstructive pulmonary disease is a major risk factor for right-side heart failure.

Emphysema is a lung disease involving damage to the air sacs (alveoli).There is progressive destruction of alveoli and the surrounding tissue that supports them. As the disease gets worse, large air cysts take the place of normal lung tissue. Air is trapped in the lungs.

Cardiomyopathies due to various causes, including birth defects, HIV infection, and other infections.
In rare cases, heart failure can occur in women around the time of childbirth, a condition called peripartum cardiomyopathy.

Click the icon to see an image of peripartum cardiomyopathy.

An overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism) can have severe effects on the heart and increase the risk for heart failure.
Amyloidosis. A starchy protein (amyloid) that builds up in tissues and organs can lead to heart failure.
Surviving childhood cancers. Survivors face a risk for developing heart failure in later years, particularly those treated with chemotherapies such as doxorubicin. Newer cancer advances may reduce this risk.
Acute myocarditis. This rare viral infection involves the heart muscle and can produce temporary but potentially life-threatening heart failure.

Long-term use of anabolic steroids (male hormones used to build muscle mass) increases the risk for heart failure. The drug itraconazole (Sporanox), used to treat skin, nail, or other fungal infections, has been linked to heart failure. In 2006, the FDA warned that the cancer drug imatinib (Gleevec) has been associated with heart failure cases. Most patients who took imatinib and developed heart failure had a history of diabetes, high blood pressure, or heart disease.

Complications

At least 20% of hospitalizations in older adults are due to heart failure. For people over age 65, it is the number one cause of death, with nearly 290,000 people dying from this disease each year. Nevertheless, although heart failure produces very high mortality rates, treatment advances in hypertension, heart surgeries, and heart pacemakers are improving survival rates.

The most serious and life-threatening complications of heart failure are:

Arrhythmias (irregular beatings of the heart)
Acute pulmonary edema (fluid in the lungs)

Left-side heart failure tends to be more severe than right-side heart failure, particularly when it is associated with the following conditions:

Coronary artery disease
HIV infection
Amyloidosis (a metabolic disorder than can lead to organ failure)
Chemotherapy that uses the drug doxorubicin

The outlook is better in patients with left-side heart failure associated with:

Idiopathic cardiomyopathy (the cause is unknown)
Heart failure due to childbirth

Weight Issues. If patients with heart failure are overweight to begin with, their condition tends to be more severe. Once heart failure develops, however, an important indicator of a worsening condition is the occurrence of cardiac cachexia, which is unintentional rapid weight loss (a loss of at least 7.5% of normal weight within 6 months).

Impaired Kidney Function. Heart failure weakens the heart’s ability to pump blood. This can affect other parts of the body including the kidneys (which in turn can lead to fluid build-up). Decreased kidney function is common in patients with heart failure, both as a complication of heart failure and as a complication of other diseases associated with heart failure (such as diabetes). Studies suggest that in patients with heart failure, impaired kidney function increases the risks for heart complications including hospitalization and death.

Congestion (Fluid Buildup). In left-sided heart failure, fluid builds up first in the lungs. Later, as right-sided heart failure develops, fluid builds up in the legs, feet, and abdomen. According to one study, patients with severe symptoms who had congestion (fluid buildup) had poorer survival rates than those without fluid build up. Two-year survival rates were 87% in those who were congestion-free compared to 41 - 67% in patients with various signs of congestion (such as swelling, difficulty breathing when lying down, and weight gain from fluid buildup). Fluid buildup is treated with lifestyle measures, such as reducing salt in the diet, as well as drugs, such as diuretics. Sometimes, for hospitalized patients, an ultrafiltration device is used to remove excess water and salt from the body (see Surgery and Devices).

Atrial Fibrillation. This abnormal rhythm is a rapid quivering beat in the upper chambers of the heart. It is a major cause of stroke and very dangerous in people with heart failure.

Left Bundle Branch Block. Left bundle-branch block is an abnormality in electrical conduction in the heart. It develops in about 30% of patients with heart failure and is a major risk factor for serious adverse heart events.

Systolic Blood Pressure. An important 2006 study indicated that patients who arrive at the hospital with heart failure and low systolic blood pressure have a poorer prognosis than those who arrive with high systolic blood pressure. Researchers think that high systolic blood pressure may be a signal for unique clinical characteristics.

Sleep Apnea. With this disorder, a person stops breathing during the night, perhaps hundreds of times, usually for periods of 10 seconds or longer. It is a very strong risk factor for heart failure, and patients with apnea have a higher mortality rate than those who do not.

Depression. The presence of depression indicates a poorer outlook for the heart. Studies indicate that depression may have adverse biologic effects on the immune and nervous systems, blood clotting, blood pressure, blood vessels, and heart rhythms.

Seasonal and Daily Patterns. Studies have shown that more emergency room visits and higher mortality rates occur during winter months and on Mondays in patients with heart failure. One factor in this higher risk may be sudden and strenuous exertion, particularly snow-shoveling, which is associated with a risk for heart attack in people with heart problems.

Diagnosis

Doctors can often make a preliminary diagnosis of heart failure by medical history and careful physical examination.

The medical history risks for heart failure include:

High blood pressure
Diabetes
Poor cholesterol levels
Heart or peripheral vascular disease
Sleep apnea
Thyroid problems
Obesity
Lifestyle factors (smoking, alcohol use)

The following physical signs, along with medical history, strongly suggest heart failure:

Enlarged heart
Irregular heart sounds
Abnormal sounds in the lungs
Swelling or tenderness of the liver
Fluid retention in legs and abdomen
Elevation of pressure in the veins of the neck

Both blood and urine tests are used to check for problems with the liver and kidneys and to detect signs of diabetes. Lab tests can measure:

Cholesterol and lipid levels
Blood sugar (glucose)
Red blood cell count (to rule out anemia)
Blood sugar levels
Thyroid function

Urine tests can be used to assess the presence of a protein called albumin. Albumin in the urine is usually a sign of kidney disease, but even tiny amounts (microalbumin) signal an increased risk for heart failure in people with and without diabetes.

The exercise stress test measures heart rate, blood pressure, and oxygen consumption while a patient is performing physically, usually walking on a treadmill. It is an important diagnostic component in determining heart failure symptoms. Doctors also use exercise tests to gauge long-term outlook and the effects of particular treatments.

An electrocardiogram (ECG) cannot diagnose heart failure, but it can indicate underlying heart problems. It is sometimes called an EKG. The test is simple and painless to perform. It may be used to diagnose:

Enlargement of the heart muscle, which may help to determine long-term outlook
The presence of coronary artery disease
Abnormal cardiac rhythms. A rhythm pattern called a prolonged QT interval, for example, might predict people with heart failure who are at risk for severe complications and would need more aggressive therapies.

The major benefit of an ECG is that it can help determine which patients do not need an echocardiogram, a more accurate (but more expensive) diagnostic test.

The electrocardiogram (ECG, EKG) is used extensively to diagnose heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. There are several different types of electrocardiograms.

The best diagnostic test for heart failure is echocardiography. Echocardiography is a noninvasive, entirely safe test that uses ultrasound to image the heart as it is beating. Cardiac ultrasounds provide the following information:

Accurate indications of valve function
The amount of blood flow through the heart's chambers
The location of the failure and where it has occurred

Doctors use information from the echocardiogram for calculating the ejection fraction (how much blood is pumped out during each heartbeat), which is important for determining the severity of heart failure.

Radionuclide Ventriculography. Radionuclide ventriculography is an imaging technique that uses a tiny amount of radioactive material (called a trace element). The substance is injected into a patient. As it passes through the bloodstream it is picked up on x-rays. This is a very important imaging technique for patients with heart failure. It is very sensitive in revealing heart enlargement or evidence of fluid accumulation around the heart and lungs. It is typically used in concert with angiography.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) scans that use contrast dyes to improve resolution are proving helpful for identifying patients with irreversible heart damage. Damage appears as very bright areas on the scan.

Doctors may recommend angiography if they suspect that blockage of the arteries is contributing to heart failure. This procedure is invasive.

A thin tube called a catheter is inserted into one of the large arteries in the arm or leg.
It is gently guided through the artery until it reaches the heart.
The catheter measures internal blood pressure at various locations, giving the doctor a comprehensive picture of the extent and nature of the heart failure.
Dye is then injected through the tube into the heart.
X-rays called angiograms are taken as the dye moves through the heart and arteries.
These images help locate problems in the heart's pumping action or blockage in the arteries.

Major complications of angiography are rare (about 0.1%) but can occur. They include stroke, heart attacks, and kidney damage. The more experienced the medical center in this procedure, the lower the risk.

Click the icon to see an image of cardiac catheterization.

Researchers are looking for biologic factors (called biomarkers) that will confirm a diagnosis or suggest a better or worse prognosis. Many are under investigation.

Tumor Necrosis Factor. Elevated levels of tumor necrosis factor (TNF) may be a very strong and accurate predictor of a poor outlook. This immune substance is known to be a potent substance in the inflammatory process.

Natriuretic Peptides. Natriuretic peptides are substances that help regulate salt and water balance in the body. Levels of these peptides increase as heart failure symptoms worsen. Blood tests for brain natriuretic peptide (BNP) are now used to help diagnose heart failure. There are two types of BNP tests: The enzyme-linked immunosorbent assay (ELISA) and the radioimmunosorbent assay (RIA). Research from 2006 suggested that the ELISA test may be more accurate, but it is also more expensive.

BNP testing can be very helpful in correctly diagnosing heart failure in patients who come to the emergency room complaining of shortness of breath (dyspnea). A 2006 study indicated that this test can also help predict which patients with dyspnea are at greatest risk of dying within a year from heart failure.

Brain Metabolites. High levels of a compound called N-acetylaspartate, generated as a byproduct of chemical processes in the brain, may indicate a poor outlook.

Treatment

Guidelines for evaluating the severity of heart failure and determining treatments use a staging system that is similar to the one used for major cancers:

Stage A: Patients are at high risk for heart failure, but there is no evidence of structural damage to the heart. Risk factors include high blood pressure, heart diseases, diabetes, obesity, metabolic syndrome, and previous use of medications that damage the heart (such as some chemotherapy).
Stage B: Patients have a structural heart abnormality but no symptoms of heart failure. Abnormalities include left ventricular hypertrophy and low ejection fraction, asymptomatic valvular heart disease, and a previous heart attack.
Stage C: Patients have a structural abnormality and current or previous symptoms of heart failure, including shortness of breath, fatigue, and difficulty exercising.
Stage D: Patients have end-stage symptoms that do not respond to standard treatments.

According to expert guidelines, the first step in managing heart failure is to treat the primary conditions causing or complicating heart failure. These include:

Coronary artery disease. Treatment includes a healthy diet, exercise, smoking cessation, medications, and, possibly, bypass or angioplasty. [See In-Depth Report #3: Coronary artery disease and angina.]
Cholesterol and lipid problems. Treatments include lifestyle management and medications, especially statins. [See In-Depth Report #23: Cholesterol.]
High blood pressure. A normal systolic blood pressure is considered below 120 mm Hg, and a normal diastolic blood pressure is below 80 mm Hg. Patients with diabetes or chronic kidney disease should maintain blood pressure readings of 130/80 or less, while other patients with high blood pressure should aim for readings no higher than 140/90. Effective reduction of blood pressure reduces the risk of heart failure by 30 - 50%. [See In-Depth Report #14: High blood pressure.]
Diabetes. Treating diabetes is extremely important for reducing the risk for heart disease. ACE inhibitors are especially beneficial, particularly for people with diabetes. Recent research suggests that metformin, a drug used to treat diabetes, may also help prevent heart failure. [See In-Depth Report #60: Diabetes - type 2; and In-Depth Report #9: Diabetes - type 1.]
Valvular abnormalities such as aortic stenosis and mitral regurgitation. Surgery may be required.
Abnormal health rhythms (arrhythmias). Ventricular assisted devices, notably biventricular pacers (BVPs), are proving to be important in preventing hospitalizations for patients with these conditions.
Anemia. Giving erythropoietin (EPO) and iron injections to patients with heart failure and underlying anemia not only reverses the anemia, but may markedly improve heart symptoms as well. [See In-Depth Report #57: Anemia.]
Thyroid function. Various medications are used to treat overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism). [See In-Depth Report #38: Hypothyroidism.]
Sleep apnea. Continuous positive airway pressure (CPAP) is an effective treatment for sleep apnea. CPAP may help reduce systolic blood pressure and improve left ventricular systolic function. [See In-Depth Report#65:Sleep apnea.]

Click the icon to see an image of CPAP treatment.

Treatments for patients with Stage B risk for heart failure include all of the treatments recommended in Stage A. In addition, the following types of drugs and devices may be recommended for some patients. These include:

Angiotensin-converting enzyme (ACE) inhibitors for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack if they have a low left ventricular ejection fraction (LVEF) and no heart failure symptoms. A reduced LVEF indicates that the heart’s left ventricle is not pumping blood efficiently.
Beta blockers for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack but who do have reduced LVEF without heart failure symptoms.
Angiotensin-receptor blockers (ARBs) for patients who have had a heart attack or have low LVEF, but who cannot take ACE inhibitors.
Implantable defibrillators for patients who have weakened heart pumps (ischemic cardiomyopathy), who had a heart attack more than 40 days prior, and who have low LVEF.

Treat conditions as recommended in Stage A plus:

Restrict dietary salt. Lowering salt in the diet can help diuretics work better.
ACE inhibitors, beta blockers, and diuretics are recommended for most patients.
ARBs are recommended for patients who cannot tolerate ACE inhibitors.
Aldosterone inhibitors or digitalis may be used for some patients.
A hydralazine and nitrate combination (BiDil) may be used for African-American patients who are taking an ACE inhibitor and beta blocker and who still have heart failure symptoms.
Avoid drugs that can worsen heart failure symptoms. These include nonsteroidal anti-inflammatory drugs (NSAIDs), most calcium channel blockers, and most drugs used to treat irregular heart rhythms (arrhythmia).
Exercise training for appropriate patients.
Biventricular pacemakers and implantable defibrillators for some patients.

Treatment includes appropriate measures used for Stages A, B, and C plus:

Heart transplantation referral for appropriate patients.
Left-ventricular assist devices (LVADs) as permanent therapy for patients who are not candidates for heart transplants. LVADs are surgically implanted to help pump blood through the body.
Hospice and end-of-life care information for patients and families.

Medications

Many different medications are used in the treatment of heart failure. They include:

Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin-receptor blockers (ARBs)
Beta blockers
Diuretics
Aldosterone blockers
Digitalis
Hydralazine and nitrates
Statins
Nesiritide (Natrecor)
Aspirin

Angiotensin-converting enzyme (ACE) inhibitors are among the most important drugs for treating patients with heart failure. ACE inhibitors open blood vessels and decrease the workload of the heart. They are used to treat high blood pressure but can also help improve heart and lung muscle function. Major studies suggest that ACE inhibitors may reduce the risk of death, heart attack, and hospital admissions by 28% in patients with existing heart failure.

ACE inhibitors are particularly important for patients with diabetes. A large study reported that patients with diabetes who took these drugs had fewer heart attacks and lower overall mortality rates than patients who took other types of high blood pressure medications. ACE inhibitors may also help slow progression of kidney disease, in addition to controlling blood pressure.

Doctors sometimes avoid giving aspirin to patients who are taking ACE inhibitors due to concerns that this drug combination can cause kidney problems. A 2005 study of patients with both coronary artery disease and heart failure indicated that an aspirin and ACE inhibitor combination is not harmful, and that aspirin can significantly reduce mortality risk for these patients.

Choosing an ACE inhibitor. ACE inhibitors treat Stage A high-risk conditions such as high blood pressure, heart disease, and diabetic nerve disorders (neuropathy). They also treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands and stages include:

Benazepril (Lotrel) -- (Stage A)
Captopril (Capoten) -- (Stages A, B, C)
Enalapril (Vasotec) -- (Stages A, B, C)
Fosinopril (Monopril) -- (Stages A, C)
Lisinopril (Prinivil, Zestril) -- (Stages A, B, C)
Moexipril (Univasc) -- (Stage A)
Perindopril (Aceon) -- (Stage A)
Quinapril (Accupril) -- (Stages A, C)
Ramipril (Altace) -- (Stages A, B, C)
Trandolapril (Mavik) -- (Stages A, B, C)

Side Effects of ACE Inhibitors:

Low blood pressure is the main side effect of ACE inhibitors. This can be severe in some patients, especially at the start of therapy.
Irritating cough is a common side effect, which some people find intolerable. Although all ACE inhibitors can have this side effect, sometimes switching to another brand will reduce this symptom.
Although ACE inhibitors can protect against kidney disease, they also increase potassium retention in the kidneys. This increases the risk for cardiac arrest if potassium levels become too high. Because of this action, they are not generally given with potassium-sparing diuretics or potassium supplements.
A rare but severe side effect is granulocytopenia, which is an extreme reduction in infection-fighting white blood cells.
In very rare cases, patients suffer a sudden and severe allergic reaction called angioedema that causes swelling in the eyes and mouth and may close off the throat.

Patients who have difficulty tolerating ACE inhibitor side effects are usually switched to an angiotensin-receptor blocker (ARB).

ARBs, also known as angiotensin II receptor antagonists, are similar to ACE inhibitors in their ability to open blood vessels and lower blood pressure. They may have fewer or less-severe side effects than ACE inhibitors, especially coughing, and are sometimes prescribed as an alternative to ACE inhibitors. Some patients with heart failure take an ACE inhibitor along with an ARB.

Brands and Indications. ARBs are used to treat Stage A high-risk conditions such as high blood pressure and diabetic nerve disorders (neuropathy). They are also used to treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands, and the stage of heart failure they are used for, are listed below.

Candesartan (Atacand) -- (Stages A, C)
Eprosartan (Teveten) -- (Stage A)
Irbesartan (Avapro) -- (Stage A)
Losartan (Cozaar) -- (Stages A, B)
Olmesartan (Benicar) -- (Stage A)
Telmisartan (Micardis) -- (Stage A)
Valsartan (Diovan) -- (Stages A, B, C)

Common Side Effects

Low blood pressure
Dizziness and lightheadedness
Raised potassium levels
Drowsiness

Beta blockers are almost always used in combination with other drugs, such as ACE inhibitors and diuretics. They help slow heart rate and lower blood pressure. Research presented at the 2006 American College of Cardiology meeting indicated that beta-blockers are an important treatment for most patients with left ventricular heart failure. Data from the study found that the beta blocker carvedilol (Coreg) significantly lowered the risk of death or rehospitalization within 3 - 6 months after hospital discharge.

Beta blockers can help patients with heart failure by:

Treating high blood pressure, angina, arrhythmias, and preventing heart attack in high-risk patients.
Preventing left ventricular remodeling in patients with enlarged heart chambers and weakened heart muscles (dilated cardiomyopathy), and in those who have suffered a first heart attack.
Blocking inflammatory immune factors called cytokines, including tumor necrosis factor (TNF). TNF may play a key role in the process leading to heart failure.
Preventing norepinephrine (adrenaline) from binding to heart cells. Elevated levels of norepinephrine, a stress hormone, can overstimulate the failing heart and are associated with severe heart failure.

Brands and Indications. Beta blockers treat Stage A high blood pressure. They are also treat Stage B patients (both those who have had a heart attack and those who have not had a heart attack but who have heart damage). Recent guidelines identify three drugs best for treating Stage C patients with heart failure. Specific brands and stages include:

Acebutolol (Sectral) -- (Stage A)
Atenolol (Tenormin) -- (Stages A, B)
Betaxolol (Kerlone) -- (Stage A)
Bisoprolol (Zebeta) -- (Stages A, C)
Cartelol (Cartrol) -- (Stage A)
Carvedilol (Coreg) -- (Stages A, B, C)
Labetalol (Trandate) -- (Stage A)
Metoprolol succinate (Toprol XL) -- (Stages A, C)
Metoprolol tartrate (Lopressor) -- (Stages A, B)
Nadolol (Corgard) -- (Stage A)
Penbutolol (Levatol) -- (Stage A)
Pindolol (Visken) -- (Stage A)
Propranolol (Inderal) -- (Stages A, B)
Timolol (Blocadren, Timolide) -- (Stages A, B)

Beta Blocker Concerns

Do not abruptly stop taking these drugs. The sudden withdrawal of beta blockers can rapidly increase heart rate and blood pressure. Your doctor may want you to slowly decrease the dose before stopping completely.
Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol can narrow bronchial airways. Patients with asthma, emphysema, or chronic bronchitis should not use these beta blockers.
Beta blockers can lower HDL (“good”) cholesterol.
These drugs can hide warning signs of low blood sugar (hypoglycemia) in patients with diabetes.
Beta blockers are usually used in combination with ACE inhibitors, but the two drugs are not started at the same time. Research presented at the 2005 European Society of Cardiology meeting indicates that either a beta blocker or an ACE inhibitor can be prescribed at first, and the other drug added on later.

Common Side Effects

Fatigue and lethargy
Vivid dreams and nightmares
Depression
Memory loss
Dizziness and lightheadedness
Reduced ability to exercise
Coldness in extremities (legs, toes, arms, hands)

Check with your doctor about any side effects. Do not stop taking these drugs on your own.

Diuretics cause the kidneys to rid the body of excess salt and water. Fluid retention is a major symptom of heart failure. Aggressive use of diuretics can help eliminate excess body fluids, while reducing hospitalizations and improving exercise capacity. These drugs are also important to help prevent heart failure in patients with high blood pressure. In addition, certain diuretics, notably spironolactone (Aldactone), block aldosterone, a hormone involved in heart failure. This drug class is beneficial for patients in late stages of heart failure (Stages C and D).

Diuretic Types and Brands. Diuretics come in many brands and are generally inexpensive. Some need to be taken once a day, some twice a day. Treatment is usually started at a low dose and gradually increased. Diuretics are virtually always used in combination with other drugs, especially ACE inhibitors and beta blockers. There are three main types of diuretics:

Potassium-sparing diuretics. These include amiloride (Midamor), spironolactone (Aldactone), and triamterene (Dyrenium).
Thiazide diuretics. These include chlorothiazide (Diuril), chlorthalidone (Hygroton), indapamide (Lozol), hydrochlorothiazide (Esidrix, HydroDiuril), and metolazone (Mykrox, Zaroxolyn).
Loop diuretics. Because loop diuretics act faster than other diuretics it is important to avoid dehydration and potassium loss. Loop diuretics include bumentanide (Bumex), furosemide (Lasix), and torsemide (Demadex).

Problems with Diuretics. Loop and thiazide diuretics deplete the body's supply of potassium, which, if left untreated, increases the risk for arrhythmias. Arrhythmias are heart rhythm disturbances that can, in rare instances, lead to cardiac arrest. In such cases, doctors will prescribe lower doses of the current diuretic, recommend potassium supplements, or use potassium-sparing diuretics either alone or in combination with a thiazide. Potassium-sparing drugs have their own risks, which include dangerously high levels of potassium in people with existing elevated levels of potassium or in those with damaged kidneys. However, all diuretics are generally more beneficial than harmful.

Common Side Effects

Fatigue
Depression and irritability
Urinary incontinence
Reduced sexual drive

Aldosterone is a hormone that is critical in controlling the body's balance of salt and water. Excessive levels may play important roles in hypertension and heart failure. Drugs that block aldosterone are prescribed for some patients with Stage C heart failure.

Spironolactone (Aldactone, Spirinol) is both a potassium-sparing diuretic and an aldosterone blocker. A major study of patients with heart failure found that spironolactone reduced death rate by 30%. Like all medications for heart failure, it must be used with care; elevated potassium levels are a potential risk of therapy.
Eplerenone (Inspra), a newer aldosterone blocker, has been specifically approved for treatment of heart failure. It is prescribed for patients who have heart failure following a heart attack. Its actions are similar to potassium-sparing diuretics and, like these drugs, it poses some risk for high potassium levels.

Digitalis is derived from the foxglove plant. It has been used to treat heart disease since the 1700s. Digoxin (Lanoxin) is the most commonly prescribed digitalis preparation. Digoxin decreases heart size and reduces certain heart rhythm disturbances (arrhythmias).

Unfortunately, digitalis does not reduce mortality rates, although it does reduce hospitalizations and worsening of heart failure. Controversy has been ongoing for more than 100 years over whether the benefits of digitalis outweigh its risks and adverse effects.

Digitalis may be useful for patients with left-ventricular systolic dysfunction who do not respond to other drugs (diuretics, ACE inhibitors). It is also used for patients who have atrial fibrillation.

Digitalis does not appear to help patients with left-ventricular diastolic heart failure. It may be harmful in patients with right-ventricular heart failure and those who stop taking digoxin after using it in combination with ACE inhibitors.

Side Effects and Problems. While digitalis is generally a safe drug, it can have toxic side effects due to overdose or other accompanying conditions. The most serious side effects are arrhythmias (abnormal heart rhythms that can be life-threatening). Early signs of toxicity may be irregular heartbeat, nausea and vomiting, stomach pain, fatigue, visual disturbances (such as yellow vision, seeing halos around lights, flickering or flashing of lights), and emotional and mental disturbances.

Many factors increase the chance for side effects.

Advanced age
Low blood potassium levels (which may be caused by diuretics)
Hypothyroidism
Anemia
Valvular heart disease
Impaired kidney function

Digitalis also interacts with many other drugs, including quinidine, amiodarone, verapamil, flecainide, amiloride, and propafenone.

A blood test that monitors drug levels in patients taking the drug can limit the rate of toxicity to about 2%. For most patients with mild-to-moderate heart failure, low-dose digoxin may be as effective as higher doses. If side effects are mild, patients should still consider continuing with digitalis if they experience other benefits.

Hydralazine and nitrates are two older drugs that help relax arteries and veins, thereby reducing the heart's workload and allowing more blood to reach the tissues. In 2005, the FDA approved BiDil, a drug that combines isosorbide dinitrate and hydralazine. BiDil is approved to specifically treat heart failure in African-Americans. African-Americans have a particularly high risk for heart failure. BiDil is the first drug approved for a specific racial group. The Food and Drug Administration (FDA) based its approval on a landmark 2004 study published in the New England Journal of Medicine, which showed that African-Americans who took the drug were 43% more likely to survive heart failure than patients who took placebo. Some experts suggest that BiDil could also benefit other racial groups.

Statins are important drugs used to lower cholesterol and to prevent heart disease leading to heart failure. These drugs include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). In 2007, the FDA approved atorvastatin to reduce the risks for hospitalization for heart failure in patients with heart disease.

In a 2006 Journal of the American Medical Association study, patients with heart failure who began taking a statin drug had a 24% lower relative risk of death and a 21% lower relative risk of hospitalization for heart failure than patient who did not take a statin. Statins appeared to help these patients regardless of whether or not they had co-existing coronary heart disease.

Aspirin is a type of non-steroid anti-inflammatory (NSAID). A 2005 study in the Journal of the American College of Cardiology indicated that aspirin is important for preventing heart failure death in patients with heart disease, and can safely be used with ACE inhibitors. However, some research has suggested that NSAIDs may increase the risk of heart failure for patients with a history of heart disease, especially when used in combination with ACE inhibitors or diuretics. Patients with heart disease should ask their doctor which NSAIDs are right for them.

Nesiritide treats patients who have arrived at a hospital with decompensated heart failure. Decompensated heart failure is a life-threatening condition in which the heart fails over the course of minutes or a few days, often as the result of a heart attack or sudden and severe heart valve problems. However, nesiritide may cause serious kidney damage.

In 2005, the FDA released recommendations from an expert panel concerning the appropriate and inappropriate use of nesiritide. The panel emphasized that nesiritide should be used to treat only patients with decompensated heart failure who have shortness of breath (dyspnea) and trouble breathing. The drug should not be a replacement for diuretics.

Despite these warnings, some doctors have prescribed nesiritide “off-label” to treat patients with severe heart failure outside of a hospital setting. Research presented at the 2007 American College of Cardiology annual conference criticized this practice by demonstrating that nesiritide plus standard treatment does not reduce the risk of heart- or kidney-related death or hospitalization. In addition, the research suggested some concerns about nesiritide’s overall safety.

Tolvaptan. Tolvaptan is an investigational drug that is being studied in combination with standard therapy for treatment of heart failure. It is especially being investigated for acute decompensated heart failure, a type of heart failure categorized by fluid build-up in the lungs (pulmonary edema) for which there are few available treatments. In patients hospitalized with heart failure, tolvaptan plus standard drugs improved breathing problems (dyspnea) and reduced fluid accumulation (edema) and body weight, according to two studies published in 2007 in the Journal of the American Medical Association. However, the drug did not appear to reduce the risk of re-hospitalization or death.

Levosimendan. Levosimendan is an experimental inotropic drug that is being investigated as a treatment for severely ill patients with heart failure. It belongs to a new class of drugs called calcium sensitizers that may help improve heart contractions and blood flow. Clinical trials suggest that levosimendan may improve survival in patients hospitalized for heart failure. The drug also appears to reduce levels of BNP (brain natriuretic peptide), a chemical marker for heart failure severity.

Prograf. Tacrolimus (Prograf) was approved in 2006 to help prevent organ rejection in patients who have received a heart transplant. The drug suppresses the immune system. Patients who receive this drug are at increased risk of developing lymphoma (a cancer of the immune system).

Surgery and Devices

Revascularization surgery helps to restore blood flow to the heart. It can treat blocked arteries in patients with coronary artery disease and may help selected patients with heart failure. Surgery types include coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). CABG is a traditional type of open heart surgery. PCI, also called angioplasty, uses a catheter to inflate a balloon inside the artery. A metal stent may also be inserted during a PCI procedure. [See In-Depth Report#03:Coronary artery disease.]

A 2006 study suggested that early treatment with revascularization surgery may be particularly important for patients with systolic heart failure, a condition that occurs when the heart does not pump out enough blood. This condition has a very high death rate. Researchers found that CABG or PCI surgery halved the risk of dying compared to standard drug therapy. Patients in the study first underwent a positron emission tomography (PET) test to determine if they would be good candidates for surgery.

Click the icon to see an illustrated series detailing coronary artery balloon angioplasty.

Click the icon to see an illustrated series detailing heart bypass surgery.

In appropriate patients, mitral valve surgery may significantly reduce the severity of heart failure. In a study of 92 patients with late-stage heart failure and faulty valves, reconstruction of the heart's mitral valve drastically improved heart function.

An experimental mesh "heart sock" is being investigated as an adjunct to mitral valve repair surgery. Research presented at the 2004 American Heart Association Scientific Sessions suggested that the device reduced the progression of heart failure and halved the need for transplant surgery. The "sock" helps realign the shape of the heart and improve heart function. To date, it has been tested in patients with dilated cardiomyopathy.

Ventricular Remodeling. Ventricular remodeling (also called partial left ventriculectomy or the Batista procedure, after its inventor) may allow some patients with dilated cardiomyopathy to avoid a heart transplant.

The procedure involves the following:

The surgeon first performs ventriculectomy, which is the removal of a section of healthy heart muscle weighing about 3 ounces.
The surgeon then reshapes the heart to a more normal size and form.
Any faulty heart valves are repaired.

Ventricular remodeling is still relatively new, and mortality rates are very high. Studies on long-term improvement are mixed. More research is needed to target the patients who would most benefit.

Patients who suffer from severe heart failure and whose symptoms do not improve with drug therapy or mechanical assistance may be candidates for heart transplantation. Some 3,600 people are awaiting a transplant, although only about 2,000 operations are performed each year.

The most important factor for heart transplant eligibility is overall health. Chronological age is less important. Most heart transplant candidates are between the ages of 50 – 64 years. About 72% of transplant patients are male, and 70% are white.

While the risks of this procedure are high, the 1-year survival rate is about 86% for men and 84% for women. The 3-year survival rate is 78% for men and 75% for women. Five years after a heart transplant, about 71% of men and 67% of women remain alive. In general, the highest risk factors for death 3 or more years after a transplant operation are coronary artery disease and the adverse effects (infection and certain cancers) of immunosuppressive drugs used in the procedure. The rejection rates in older people appear to be similar to those of younger patients.

In 2004, the FDA approved a temporary artificial heart (Syncardia) intended to keep patients alive in the hospital while they waited for a heart transplant. In 2006, the FDA approved the first permanent implantable artificial heart (AbiCor). The AbiCor is available only for patients who are not eligible for a heart transplant and who are not expected to live more than a month without medical treatment. The device requires a large chest cavity, which means that most women will not be eligible for it. Of the 14 men who have received the AbiCor, the average survival was less than 5 months after surgery. Only one patient was discharged from the hospital. The device’s manufacturer is working on a new model that it hopes will extend survival by as long as 5 years.

A growing array of heart devices and machines are changing the face of heart failure treatment. They have gained widespread acceptance for use as a bridge to transplant in patients who are on medications but still have severe symptoms and are awaiting a donor heart. Increasingly, though, doctors are exploring the possibility that such devices may be satisfactory treatments themselves, forestalling the need for a transplant altogether in some patients.

Ventricular Assist Devices (VADs). Ventricular assist devices are machines that help improve pumping actions. Several models with slightly different features are in use or under investigation. Some include the following:

Left ventricular assist device (LVAD) are used for patients whose heartbeat has slowed dangerously (a condition called bradycardia) to help take over the pumping action of the failing heart. Studies suggest that in some people the use of an LVAD may allow some of the damaged heart muscle to heal, perhaps even helping some patients avoid heart transplants. These devices are also being studied in combination with drug therapy to help recover heart function and improve patients’ chances for survival. Until recently, these machines required remaining in the hospital. Smaller battery-powered LVAD units, however, are allowing many patients to leave the hospital and are proving to be effective bridges to heart transplants in adults. The HeartMate, for example, a portable LVAD about the size of a portable CD player (2 in. by 4 in.), is implanted in the upper abdomen. The implanted device plugs into an external power base, which is used when the patient is at rest to recharge the battery and provide continuous power.
Fully implanted miniature artificial pumps that assist the heart (not replace it) are also being tested. The DeBakey ventricular assist device (VAD) for example, is a tiny heart pump that weighs less than 4 ounces. It has been approved in Europe and is being tested in the United States. The Jarvik 2000 heart pump is also showing promise.
The intra-aortic balloon pump (IABP) is helpful for maintaining heart function in people with left-side failure waiting for transplants and in those who develop a sudden and severe deterioration of heart function. The IABP is an implanted thin balloon that is usually inserted into the artery in the leg and threaded up to the aorta leading from the heart. Its pumping action is generated by inflating and deflating the balloon at certain rates. Usually, it is used only for short periods, but some studies indicate that patients may be able to use it safely for somewhat longer periods (an average duration of 23 days in one study).

There are risks involved with many of these devices, including bleeding, blood clots, and right-side heart failure. Infections are a particular hazard.

Pacers (Pacemakers). Pacers, or pacemakers, help regulate the heart’s beating action, especially when the heart beats too slowly. Biventricular pacers (BVPs) are a special type of pacemaker used for patients with heart failure. Because BVPs help the heart’s left and right chambers beat together, this treatment is called cardiac resynchronization therapy (CST). BVPs may particularly help heart failure patients who have left bundle branch block, a condition in which the electrical impulses in the heart do not follow their normal pattern. In general, BVPs are recommended for patients with moderate-to-severe heart failure. A small 2006 study suggested that a defibrillator may be better suited for patients with moderate heart failure, while indicating a BVP might be best for patients with severe heart failure.

Implantable Cardioverter-Defibrillators. Devices called implantable cardioverter-defibrillators (ICDs), which are sometimes combined with pacemakers, work well for preventing arrhythmias (abnormal heart rhythms) in heart failure patients. Studies have also found them effective in preventing sudden death from severe rhythm disturbances in patients with weakened hearts from previous arrhythmias and in patients with genetic hypertrophic cardiomyopathy. Patients who have an ICD should avoid taking fish oil supplements. A 2005 Journal of the American Medical Association study found that omega-3 fatty acid supplements may increase the risk of rapid heart beat (ventricular tachycardia) or irregular heart rhythm (ventricular fibrillation) in some of these patients.

ICDs have many benefits, and recent expert guidelines recommend that they be used in more patients with heart failure. However, in June 2005, certain ICD models and biventricular pacemaker-defibrillators were recalled by the manufacturer because of a circuitry flaw that prevents the devices from delivering therapeutic electrical shocks when needed. The problem may result in patient death. Although the FDA did not make any specific recommendations, the agency encourages patients who may have such a device to ask their doctor if they should have it removed or replaced.

In April 2006, two studies published in the Journal of the American Medical Association evaluated data concerning the safety and reliability of implantable pacemakers and defibrillators. The studies found that from 1990 – 2002, pacemakers became increasingly reliable. From 1998 – 2002, ICDs had a significantly higher rate of malfunction than pacemakers, although the reliability of ICDs appeared to improve from 2003 – 2004.

In October 2006, the U.S. Heart Rhythm Society issued recommendations for doctors, manufacturers, and the FDA to help improve communication concerning performance and recalls of ICDs and pacemakers. Experts stress that the chance of an ICD or pacemaker saving a person’s life far outweigh the possible risks of these devices failing.

Ultrafiltration devices are used in hospitals to pump excess water and salt from the body. Catheters are inserted into several of the patient’s veins. The catheters are connected to a blood filter device. Blood is withdrawn through one of the catheters and filtered in the device to remove excess fluid. The filtered blood is then returned to the patient through another catheter. A 2006 study reported that ultrafiltration devices may work better than diuretic drugs for patients with acute decompensated heart failure (ADHF). ADHF is heart failure that has rapidly deteriorated so that patients require immediate hospitalization.

Lifestyle Changes

Between 30 - 47% of patients who require hospitalization for heart failure are back in the hospital within 6 months. Many people return because of lifestyle factors such as poor diet, failure to comply with medications, and social isolation.

In one study, elderly people who had no emotional support at home had triple the risk of a heart attack after hospitalization for heart failure than those who did have such support. (Women had eight times the risk.) In another study, the greatest risk factor for death and readmission to the hospital after a first hospitalization was being single, regardless of the health of the patient at discharge. A third study confirmed that a strong marriage predicted long-term survival. Evidence continues to mount that programs that offer intensive follow-up to ensure that the patient complies with lifestyle changes and medication regimens at home are reducing rehospitalization rates and improving survival. Patients without available rehabilitation programs should seek support from local and national heart associations and groups.

Patients should weigh themselves each morning and keep a record. Any changes are important:

A sudden increase in weight of more than 2 - 3 pounds may indicate fluid accumulation and should prompt an immediate call to the doctor.
Rapid wasting weight loss over a few months is a very serious sign and may indicate the need for surgical intervention.

Whole Grains. Evidence suggests that daily consumption of whole grain foods may help prevent heart failure. In research presented at a 2007 American Heart Association conference, people who ate whole-grain breakfast cereals seven or more times a week had a 28% lower risk of developing heart failure than those who never ate these cereals.

Mediterranean Diet. Evidence suggests that the Mediterranean diet helps protect the heart and may even reduce the risk for heart failure after a first heart attack. The diet emphasizes whole grains, fish, olive oil, garlic, and moderate daily intake of wine. There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet. However, patients who have an implantable defibrillator should not take fish oil supplements. A 2005 study suggested that these supplements may worsen heart rhythm problems in some patients.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Daily glass or two of wine. Light-to-moderate alcohol use may reduce the risk for heart failure, (but heavy alcohol consumption is a risk factor).
Plenty of fresh fruits and vegetables, as well as nuts, legumes, beans, and whole grains.

DASH Diet. The Dietary Approaches to Stop Hypertension (DASH) diet is an important lifestyle step in managing blood pressure. It may also be useful for many patients with heart failure. This diet is not only rich in important nutrients and fiber but also includes foods that contain two and a half times the amounts of electrolytes, potassium, calcium, and magnesium found in the average American diet.

Potassium-rich foods, which are important for patients with heart failure, include bananas, oranges, prunes, cantaloupes, carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli. However, patients who take potassium-sparing diuretics or ACE inhibitors, and those with kidney dysfunction, may have to restrict their potassium intake.

The DASH diet is rich in whole grains and fresh fruits and vegetables. It stresses avoiding saturated fats, as any healthy diet does, although it includes calcium-rich dairy products that are non- or low-fat. When choosing fats, the diet recommends monounsaturated oils such as olive or canola oil.

Salt Restriction. People with high blood pressure are generally urged to restrict salt, although certain people may be more susceptible to its effects. For example, a high intake of salt may be an independent risk factor for the development of heart failure in people who are overweight. All patients with heart failure should limit their salt intake, and in severe cases, very stringent salt restriction may be necessary. Patients should not add salt to their cooking and their meals. They should also avoid foods high in sodium. These salty foods include ham, bacon, hot dogs, lunch meats, prepared snack foods, dry cereal, cheese, canned soups, soy sauce, and condiments. Some patients may need to reduce their water intake as well. People with high cholesterol levels or diabetes require additional dietary precautions. [See In-Depth Report #43: Heart-healthy diet. ]

People with heart failure used to be discouraged from exercising. Now, experts think that exercise, when performed under medical supervision, is extremely important for many patients with stable conditions. Studies have reported that patients with stable conditions who engage in regular moderate exercise (three times a week) experience a better quality of life and lower mortality rates than those who do not exercise.

The following guidelines are critical:

Experts warn that exercise is not appropriate for all patients with heart failure. If you have heart failure, always consult your doctor before starting an exercise program.
People who are approved for, but not used to, exercise should start with 5 - 15 minutes of easy exercise with frequent breaks. Although the goal is to build up to 30 - 45 minutes of walking, swimming, or low-impact aerobic exercises three to five times every week, even shorter times spent exercising are useful.

Studies report benefits from specific exercises:

Progressive strength training may be particularly useful for patients with heart failure since it strengthens muscles, which commonly deteriorate in this disorder. Strength training typically uses light weights, weight machines, or even the body's weight (leg raises or sit-ups, for example). Even performing daily handgrip exercises can improve blood flow through the arteries.
Patients who exercise regularly using supervised treadmill and stationary-bicycle exercises can increase their exercise capacity by 14 - 36%. In one study, patients as old as 91 years increased their oxygen consumption significantly after 6 months of supervised treadmill and stationary bicycle exercises. Exercising the legs may help correct problems in heart muscles. In one study, patients who did leg extension exercises for 8 weeks had higher levels of an enzyme involved in forming new blood vessels. Exercise has also been associated with reduced inflammation in blood vessels.
Dancing may be a fun and beneficial alternative to standard aerobic exercise, according to research presented at the 2006 annual meeting of the American Heart Association. In a study of patients with stable chronic heart failure, dancing helped improve cardiopulmonary fitness, arterial elasticity, and quality of life. Patients in the study danced fast and slow waltzes for 21 minutes, three times a week.

Bed rest may be required in cases of severe heart failure. To reduce congestion in the lungs, the patient's upper body should be elevated. For most patients, resting in an armchair is better than lying in bed. Relaxing and contracting leg muscles is important to prevent clots. As the patient improves, a doctor will progressively recommend more activity.

Experts have traditionally recommended that people with heart failure avoid warm baths, which can increase the heart rate. Some studies now report that carefully controlled bathing for short periods may not be harmful and may actually be beneficial, reducing irregular heart beats and increasing cardiac output and ejection fraction. Warm water may behave like a vasodilating drug, opening up the vessels gently and improving circulation. In clinical trials, patients sat in warm water or a dry sauna for 10 minutes, with their bodies tilted at a 45 degree angle.

Warning Note: Prolonged periods in hot or even warm conditions can be dangerous. Any patient with heart failure should consult their doctor first, not bathe unaccompanied, and be sure that the temperature does not go above 106° Fahrenheit for water bathing or 140° Fahrenheit for dry saunas.

Stress reduction techniques, such as meditation and relaxation response methods, may have direct physical benefits for lowering stress hormones. These hormones include cortisol, which suppresses the immune system, and norepinephrine (also known as adrenaline), the chemical messenger associated with heart dysfunction.

Patients with heart failure may resort to alternative remedies. Such remedies are often ineffective and may have severe or toxic effects. Of particular note for patients with heart failure is an interaction between St. John's wort (an herbal medicine used for depression) and digoxin (a heart drug). St. John's wort can significantly interfere with this drug.

Arginine. Some evidence suggests that arginine (also called L-arginine) may have some benefit. This amino acid appears to reduce endothelin, a protein that causes blood vessel constriction and is found in high amounts in patients with heart failure. It can have adverse effects, however, including gastrointestinal problems. It can also lower blood pressure and change levels of certain chemicals and electrolytes in the body. It may increase the risk for bleeding. Some people have an allergic reaction to it, which in same cases may be severe. It may worsen asthma.

Coenzyme Q10 and Vitamin E. Small studies have suggested that coenzyme Q10 (CoQ10) may help patients with heart failure, particularly when combined with vitamin E. CoQ10 is a vitamin-like substance found in organ meats and soybean oil. More recent studies, however, have found that CoQ10 and vitamin E do not help the heart or prevent heart disease. According to a 2005 Journal of the American Medical Association study, vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases.

Crataegus Extract. An herbal remedy, Crataegus Extract WS1442, which is made from the leaves of the Crataegus tree, may have antioxidant properties that can help patients with heart failure. In a study presented at the 2007 American College of Cardiology annual meeting, over 2,000 patients with severe heart failure were randomized to receive either Crataegus Extract or placebo (plus standard drug treatment) for 2 years. The researchers noted a 20% reduction in heart-related deaths among patients who received the extract, and suggested that the herb extended patients’ lives by 4 months during the first 18 months of the study.

Other Vitamins and Supplements. A wide variety of other vitamins (thiamin, B6, and C), minerals (calcium, magnesium, zinc, manganese, copper, selenium), nutritional supplements (carnitine, creatine), and herbal remedies (hawthorn) have been proposed as treatments for heart failure. None have been adequately tested. There is no evidence that a particular vitamin or supplement can cure heart failure. In any case, vitamins are best consumed through the food sources contained in a healthy diet.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology
www.hfsa.org -- Heart Failure Society of America
www.heartfailure.org -- Heart Failure Online
www.unos.org -- United Network for Organ Sharing
www.organdonor.org -- National Transplant Society
www.organdonor.gov -- US government organ donor site

References

Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006 Aug 1;114(5):397-403.

Battaglia M, Pewsner D, Juni P, Egger M, Bucher HC, Bachmann LM. Accuracy of B-type natriuretic peptide tests to exclude congestive heart failure: systematic review of test accuracy studies. Arch Intern Med. 2006 May 22;166(10):1073-80.

Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006 Jul 20;355(3):260-9.

Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006 Nov 2;355(18):1873-84.

Bryson CL, Mukamal KJ, Mittleman MA, Fried LP, Hirsch CH, Kitzman DW, et al. The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study. J Am Coll Cardiol. 2006 Jul 18;48(2):305-11.

Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, et al. Systolic and diastolic heart failure in the community. JAMA. 2006 Nov 8;296(18):2209-16.

Carlson MD, Wilkoff BL, Maisel WH, Carlson MD, Ellenbogen KA, Saxon LA, et al. Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines Endorsed by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) and the International Coalition of Pacing and Electrophysiology Organizations (COPE). Heart Rhythm. 2006 Oct;3(10):1250-73.

Davis BR, Piller LB, Cutler JA, Furberg C, Dunn K, Franklin S, et al. Role of diuretics in the prevention of heart failure: the Antihypertensive andLipid-Lowering Treatment to Prevent Heart Attack Trial. Circulation. 2006 May 9;113(18):2201-10. Epub 2006 May 1.

Gheorghiade M, Abraham WT, Albert NM, Greenberg BH, O'Connor CM, She L, et al. Systolic blood pressure at admission, clinical characteristics, and outcomes inpatients hospitalized with acute heart failure. JAMA. 2006 Nov 8;296(18):2217-26.

Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heartfFailure: the EVEREST clinical status trials. JAMA. 2007 Mar 25; [Epub ahead of print]

Go AS, Lee WY, Yang J, Lo JC, Gurwitz JH. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA. 2006 Nov 1;296(17):2105-11.

Hildebrandt P. Systolic and nonsystolic heart failure: equally serious threats. JAMA. 2006 Nov 8;296(18):2259-60.

Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007 Mar 25; [Epub ahead of print]

Lee DS, Pencina MJ, Benjamin EJ, Wang TJ, Levy D, O'Donnell CJ, et al. Association of parental heart failure with risk of heart failure in offspring. N Engl J Med. 2006 Jul 13;355(2):138-47.Maisel WH. Pacemaker and ICD generator reliability: meta-analysis of device registries. JAMA. 2006 Apr 26;295(16):1929-34.

Maisel WH, Moynahan M, Zuckerman BD, Gross TP, Tovar OH, Tillman DB, et al. Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA. 2006 Apr 26;295(16):1901-6.

Mueller C, Laule-Kilian K, Schindler C, Klima T, Frana B, Rodriguez D, et al. Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea. Arch Intern Med. 2006 May 22;166(10):1081-7.

Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9.

Review Date:
4/11/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Non-small cell lung cancer

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Lifestyle Changes
Diagnostic Tests
Staging Systems
Surgical Procedures
Radiation Treatments
Treatment Options by Stages...
Chemotherapy Treatments
Investigative Agents
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Research News:

About 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke, according to a 2006 Surgeon General report.
Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Advexin is in Phase II clinical trials for NSCLC.
Studies are finding that NSCLC tumors in people who never smoked have a much higher rate of epithelial growth-factor receptor (EGFR) mutations. EGFR helps new blood vessels grow to feed tumors. This discovery may help tailor future treatments to specific patient populations. It also helps explain why some newer treatments seem effective mostly in patients who never smoked.

Treatment News:

Video-assisted thoracic surgery (VATS) is a new, less-invasive surgical technique that uses a thin tube containing a miniature camera and surgical instruments. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients, in the treatment of early stage non-small cell lung cancer (NSCLC).
Bevacizumab, a monoclonal antibody, was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.
Gefitinib (Iressa), a drug that targets EGFR, proved disappointing in final clinical trials. However, erlotinib (Tarceva), a drug that targets a different part of the EGFR molecule, has shown benefits. Erlotinib is now approved as a second-line chemotherapy to treat patients with locally advanced or metastatic NSCLC after a previous course of chemotherapy failed.

Introduction

Although lung cancer accounts for only 13% of all cancers, it is among the most lethal, accounting for over 28% of all cancer deaths. It is more deadly than colon, breast, and prostate cancers combined. An estimated 160,390 people will die from lung cancer in 2007. Death rates have been declining in men over the past decade, and they have now stabilized in women.

The lungs are two spongy organs surrounded by a thin moist membrane called the pleura. Each lung is composed of smooth, shiny lobes: the right lung has three lobes, and the left has two. About 90% of the lung is filled with air; only 10% is solid tissue.

Air is carried from the trachea (the windpipe) into the lung through flexible airways called bronchi.
Like the branches of a tree, the bronchi in turn divide into over a million smaller airways called bronchioles.
The bronchioles lead to grape-like clusters of microscopic sacs called alveoli.
In each adult lung, there are about 300 million of these tiny alveoli. A thin membrane makes up the alveoli sacs. Oxygen and carbon dioxide pass through this membrane to and from capillaries.
Capillaries, the smallest of our blood vessels, carry blood throughout the body.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.

The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues).

Some experts believe all primary lung cancers come from a single common malignant (cancerous) stem cell that, as it copies itself, can develop into any one of these cancer types in different individuals.

In addition, cancers in the lung may have spread from other primary sites, such as the breast, thyroid, or colon. In these cases, doctors name the cancer after its original location; for example, "breast cancer with lung metastases."

Non-small cell lung cancers are categorized into three types: squamous cell carcinoma (also called epidermoid carcinoma), adenocarcinoma, and large cell carcinoma. These separate types are grouped together because, in early stages before the cancers have spread, they all can be treated surgically.

Squamous Cell Carcinoma. Squamous cells are formed from reserve cells, which are round cells that replace injured or damaged cells in the lining (the epithelium) of the bronchi, the major airways. Tumors formed from squamous cells are usually found in the center of the lung, either in a major lobe or in one of the main airway branches. They may grow to large sizes and form cavities in the lungs.

Click the icon to see an image of squamous cell carcinoma.

When squamous cell cancer metastasizes, it may travel to the bone, adrenal glands, liver, small intestine, and brain.

Squamous cell carcinoma is nearly always caused by smoking and used to be the most common cancer. It still makes up 25 - 40% of all lung cancers.

Adenocarcinoma. Adenocarcinomas usually arise from the mucus-producing cells in the lung. About two-thirds of adenocarcinomas develop in the outer regions of the lung, while one-third develop in the center of the lung. In 1965, 12% of lung cancers were adenocarcinomas. They are now estimated to account for 30 - 50% of all lung cancers and are the most common lung cancers in many countries. They are also the most common lung cancers in women. In fact, a 2000 European study showed that nearly 34% of the women with lung cancer under investigation had adenocarcinoma, compared to 26.4% who had squamous cell carcinoma, and 22.3% with small cell lung cancer. Adenocarcinoma is also increasing dramatically in men. Until recently, adenocarcinoma was only weakly linked to smoking. Experts now suggest, however, that the dramatic increase in recent decades in this lung cancer type may be due to low-tar, filtered cigarettes. People who smoke them draw tiny particles deeper into the lungs, thereby possibly increasing the risk for adenocarcinoma.

The course of this cancer varies widely. Most often, it develops slowly and causes few or no symptoms until it is far advanced. In some cases, however, it can be extremely aggressive and rapidly fatal. In 50% of cases in which this cancer spreads, it spreads only to the brain. Other common locations it spreads to include the other lung, the liver, the adrenal glands, and bone.

Click the icon to see an image of adenocarcinoma.

Bronchoalveolar Lung Cancer. Bronchoalveolar lung cancer is actually a subtype of adenocarcinoma. It develops as a layer of column-like cells on the lung and spreads through the airways, causing great volumes of sputum. This cancer also is increasing in incidence.

Large Cell Carcinoma. Large cell carcinoma, which makes up about 10 - 20% of lung cancers, includes cancers that cannot be identified under the microscope as squamous cell cancers or adenocarcinomas.

Click the icon to see an image of large cell carcinoma.

Small cell lung cancer may, like squamous cells, be derived from reserve cells or other cells in the epithelium. It causes 15 - 25% of all lung cancers; without chemotherapy, it is very aggressive and usually rapidly fatal. It requires a different treatment approach from non-small cell lung cancer, so it is not discussed in this report.

Click the icon to see an image of small cell carcinoma.

Causes

Cigarette Smoke. Smoking causes 87% of lung cancer deaths, accounting for 30% of all cancer deaths. Cigarettes, nicotine, or both may contribute to lung cancer in one or more of the following ways:

In general, chronic exposure to nicotine may cause an acceleration of coronary artery disease, peptic ulcer disease, reproductive disturbances, esophageal reflux, hypertension, fetal illnesses and death, and delayed wound healing.

The smoke is the most dangerous component of the cigarette. Chemicals formed during smoking trigger genetic mutations that lead to cancer. When people inhale cigarette smoke, they bring into their lungs tar that includes over 4,000 chemicals, some of which are carcinogenic (cancer-causing). Other inhaled chemicals in cigarette smoke that may increase the risk for cancer include cyanide, benzene, formaldehyde, methanol (wood alcohol), acetylene (the fuel used in torches), and ammonia. Smoke also contains nitrogen oxide and carbon monoxide, both of which are harmful gases.
Nicotine itself may be a hazard. A 2000 laboratory study suggested that the human body might be converting inhaled nicotine into a chemical called aminoketone, which has been linked to the formation of tobacco-related lung cancer. A 2001 study reported that nicotine triggered new blood vessel growth, which could, in theory, promote growth of any existing tumors. A study published in 2005 found that nicotine was responsible for disabling a gene that induces the death of cancer cells in lung tumors. Whether or not these studies apply to long-term use of nicotine replacement products (such as patches), or to cigarette smoking, is still unclear. The studies should certainly not discourage people from using nicotine replacement methods for quitting. However, these studies may indicate that people should not use these devices on a long-term basis.

Radon. Radon is a gas produced naturally by the breakdown of uranium. It is often present in the soil and in water and can seep into any dwelling. Radon may be responsible for between 10% and 14% of lung cancer deaths, making it, after smoking, the second leading cause of this cancer.

Other Contributors. Toxic particles leading to precancerous changes in the lung are also found in marijuana. In one study, 53.8% of cigarette smokers, 66.7% of marijuana smokers, and all of those subjects who smoked both substances showed evidence of precancerous changes in the lungs.

There is considerable debate over the lung cancer risk posed by depleted uranium used in military weapons (such as in the Gulf and Balkan conflicts). A 2001 study estimated that it would cause an additional 8 deaths from lung cancer out of every 10,000 people or soldiers who were highly exposed to this substance. The study was based on a mathematical model, however, and the issue is not settled.

Other lung carcinogens include asbestos, arsenic, certain petrochemicals (materials made from crude oil or natural gas), and other airborne (carried through the air) byproducts of various mining and manufacturing processes.

Click the icon to see an image of the tobacco plant.

Genetic mutations that cause cancer generally occur in two types of genes:

Tumor-suppressor genes, which prevent cells from endlessly copying themselves
Proto-oncogenes, which encourage cells to keep making copies of themselves [when a proto-oncogene changes (becomes mutated), it is then called an oncogene]

Damage to either type of gene can cause a mutation that results in an uncontrolled division of cells. This uncontrolled division forms tumors.

It is unlikely that a single specific abnormality causes all lung cancer. It probably takes a variety of mutations to start the devastating chain of events leading to cancer. The following mutations are among those under investigation:

BPDE-caused mutations: The chemical BPDE, a byproduct of tobacco smoke, is involved with a number of genetic mutations, including those to an oncogene called K-ras and to three tumor-suppressor genes known as p53, PPP2R1B, and p16. When normal, the tumor-suppressor genes are involved in cell repair and healthy copying of the cell. When they are damaged or blocked, out of control cell production can occur, leading to cancer. About 10% of the population may carry a gene that protects against lung cancer, by reducing levels of BPDE.
Chemotherapy resistance genes: Tumors that contain the p53 mutation may also be more resistant to chemotherapy.
Rb Mutations: Another important contributor to lung cancer is a genetically defective protein called retinoblastoma (Rb), which is associated with very aggressive tumors. Low levels of the normal Rb gene may sometimes predict aggressive cancer, especially in patients with small cell lung cancer.
Mutations to the FHIT gene: Another potentially important mutation may be an abnormality in the FHIT gene. This mutation causes the cells lining the lung to become more vulnerable to the effects of tobacco smoke and other carcinogens.

Symptoms

Lung cancer is unlikely to produce symptoms until the disease is advanced. When symptoms develop, they may result from the lung tumor itself, from its effects on tissues outside the lung, or from the spread of malignant cells to other organs.

Early symptoms may include the following:

Frequent bouts of pneumonia, or pneumonia that does not clear up in a normal period of time
Coughing (particularly coughing up blood)
Weight loss
Fever
Shortness of breath
Chest pain

Later-stage symptoms include the following:

Shortness of breath: This common symptom is the result of cancer that has spread in the lung and the pleura, the membrane covering the lung.
Superior vena cava syndrome: In some cases, tumor growth or spreading of the cancer presses against the superior vena cava, a large vein that returns blood from the upper part of the body to the heart. When this happens, a condition called superior vena cava syndrome may occur, leading to obvious swelling in the arms and face.
Trouble swallowing: The esophagus is the pipe that takes food from the mouth to the stomach. The cancer may spread to or press against the esophagus, interfering with swallowing and nutrition.
Hoarseness: Cancer can damage the nerves that control the voice box, causing hoarseness.
Pancoast syndrome: Damage to the brachial plexus, a group of nerves branching from the neck, can cause pain, weakness, or numbness in the arm or hand (Pancoast syndrome).
Bronchoalveolar lung cancer may produce very large amounts of mucus.
Hypercalcemia: Some lung cancers produce substances that remove calcium from bone and release it into the bloodstream, causing a condition called hypercalcemia. Patients with this disorder can experience nausea, vomiting, constipation, weakness, and fatigue.

Other lung cancers (usually small cell cancer) cause the body to retain water, lowering the blood's sodium levels. This condition, called hyponatremia, can produce confusion, weakness, and even seizures.

Risk Factors

Before cigarettes became popular in the beginning of the 20th century, lung cancer was rare. In 2007, lung cancer is expected to strike up to 213,380 Americans, and about 160,390 are expected to die from it.The disease usually occurs in people over 50 years old. Men have a significantly greater incidence of lung cancer compared to women. On the encouraging side, the rate of lung cancer in men has been declining significantly over the past decade. While lung cancer rates have been increasing dramatically in women (by 600% from 1950 to 2000), they now appear to be stabilizing.

Smoking appears to be the primary risk factor in 85 - 90% of lung cancers. About 15% of all people who smoke develop lung cancer. The risk depends on the duration of the addiction and the number of pack years. (One pack year equals the number of packs of cigarettes smoked per day, multiplied by the number of years that the person has smoked.) Genetic damage in the lung occurs in nearly all chronic smokers, even if cancer has not developed.

An elevated risk for lung cancer can persist for more than 20 years after quitting smoking, although the risk drops significantly even in the first year after quitting. And, there are benefits to quitting smoking even for people who are well into middle age.


Quitting Age	Percentage
30	2%
40	3%
50	6%
60	10%

Second-Hand Smoke. The Environmental Protection Agency has classified second-hand smoke as a carcinogen (cancer-causing chemical). Exposure to second-hand tobacco smoke increases the risk of lung cancer in the nonsmoker by about 20 - 30%. A 2006 Surgeon General report found that about 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke.

There may be some ethnic differences in lung cancer risk. For example, African-Americans face a risk that is two to four times higher than that in Caucasians, regardless of smoking status. It is not clear what factors are responsible for this higher risk. Some African-Americans appear to have a genetic vulnerability to the harmful chemicals in cigarette smoke.

In China, an estimated one third of all young male smokers will eventually die because of tobacco-related illnesses. Their risk for lung cancer, however, is much less than it is for chronic lung disease, the opposite of the Western trend. A 2001 study reported that the lower rate of lung cancer among Chinese people might be due to a slow rate of clearing nicotine, which results in smoking fewer cigarettes.

People with High Exposure to Radon. Studies have shown that radon raises the risk of lung cancer in underground miners by 40%. It is unclear whether the results of these studies would apply to people exposed to radon in their homes One study suggests that people with intense or prolonged exposure to radon in their homes do indeed face the same risk as miners exposed to similar levels of radon. A cumulative long-term exposure to radon and smoking also increases the danger. Most people move an average of 10 or 11 times over their lifetime, so the risk of developing lung cancer through radon exposure is very low in most individuals, even for those who lived for awhile in areas with high radon levels. People with homes that have high radon levels and those who sleep or spend many hours to days in basements with detectable but moderate levels should consider taking protective measures.

Workers Highly Exposed to Carcinogens. An estimated 9,000 - 10,000 men and 900 - 1,900 women develop lung cancer each year because of occupational exposure to carcinogens. More than half of these cases are attributable to past exposure to asbestos, which has long been known to be a risk factor for mesothelioma (cancer of the pleura, the lining around the lung) and can increase the risk of lung cancer in smokers. With better protective measures, these rates are expected to fall in the future.

Other chemicals that put workers at risk for lung cancer include:

Arsenic (insecticide and herbicide sprayers, tanners, oil refinery workers)
Chloromethyl methyl ether (workers exposed to certain polymers, water repellents, or products using chloride and formaldehyde)
Chromium compounds (workers using certain alloys, paints, pigments, and preservatives)
Depleted uranium (soldiers exposed to weapons during battlefield conditions)
Crystalline silica

By contrast, agricultural workers seem to have a lower lung cancer rate, despite their possible occupational exposures to risky chemicals. While this rate has traditionally been attributed to good health habits, including low tobacco use, a 2000 study suggests that agricultural workers' exposure to endotoxin may be responsible. Endotoxin is a component of common bacteria found in soil and animals and may have cancer-preventing effects on the immune system.

Exposure to Smoke from Grills. Grilling and high-heat frying emit chemicals called heterocyclic amines, which are known to be carcinogenic. A 2000 study of Chinese women found that smokers who stir-fried meat daily and inhaled cooking fumes had a higher risk of lung cancer than did those who stir-fried meat less frequently. No higher risk was found among nonsmokers.

Air Pollution. Although any risk from air pollution is very small, it nevertheless may be a contributor to those lung cancers not obviously related to smoking. Some studies, including a major analysis of vital statistics in 2002, have found an association between increased risk for lung cancer and long-term exposure to very small particulates, especially sulfates, present in polluted air. The risk, if any, is very small.

A family history of lung cancer may play a role in increasing susceptibility to this disease. In one study, people who had parents or siblings with respiratory tract cancers had a 30% higher risk for lung cancer, compared to people without a family history. Women with mothers or sisters with lung cancer had triple the risk. A higher risk occurred in both smokers and nonsmokers. There was no association between a history of other cancers and lung cancer. Both genetic factors and secondhand smoke appeared to contribute to the danger in these individuals.

Smokers with emphysema or chronic inflammatory lung diseases, such as asthma, are at increased risk for lung cancer. Both smokers and nonsmokers whose lungs are scarred from recurrent lung diseases, such as pneumonia or tuberculosis, are also at increased risk, particularly for bronchoalveolar lung cancer.

Lifestyle Changes

Quitting improves lung function almost immediately. Some evidence suggests that the benefits for the lungs are even more significant for women who quit than for men. It should be noted, however, that it can take 20 years or longer, particularly in heavy smokers, for the lungs to be restored to a fully healthy condition in which the risk for lung cancer is as low as for nonsmokers. Quitting is extremely difficult. No one should be discouraged if they relapse. Everyone should keep trying to quit. With continued efforts, many people succeed.

The many methods of quitting smoking include counseling and support groups, nicotine patches, gums and sprays, and incremental reduction.

At this time perhaps the most effective method for quitting is a combination of the following:

Nicotine replacement products that reduce withdrawal symptoms and cravings.
The antidepressants bupropion (Zyban) or nortriptyline (Pamelor, Aventyl), which reduce emotional effects and cravings associated with withdrawal, and improve abstinence rates.
Professional counseling or support organizations that may be effective, in addition to the medication, in helping people maintain abstinence.

[See In-Depth Report #41: Smoking.]

While people are in the process of quitting (and afterwards), they should maintain as healthy a lifestyle as possible.

Phytochemicals. Some data suggest that diets rich in fresh fruits and vegetables may be protective against lung cancer in both smokers and non-smokers. Some studies have reported protection from specific plant chemicals (phytochemicals), such as the following:

Isothiocyanates. These chemicals are found in cruciferous vegetables (broccoli, cauliflower, and Brussels sprouts). They may help block the effects of carcinogens in smoke, suppress tumor growth, and inhibit growth-promoting steroid hormones.
Flavonoids. Major sources are apples, grapefruit, onions, red wine, and tea. In one study on flavonoids, apple eaters had the lowest cancer risk, 68% less than those who ate fruit infrequently. In another, those who ate relatively more onions, apples, and white grapefruit had less than half the lung cancer risk as people who ate relatively small amounts of these foods. Flavonoids are also found in soybeans, berries, broccoli, carrots, citrus fruits, eggplant, peppers, squash, and tomatoes. Specific flavonoids in dark chocolate may be protective against lung cancer (but not other cancers).
Lycopene. Lycopene is found in tomatoes, which have been associated with a lower risk for lung cancer. Cooking the tomatoes appears to increase the potency of lycopene.
Cryptoxanthin. Some studies suggest that eating foods rich in cryptoxanthin, a yellow-orange pigment, reduces the risk for lung cancer. Foods with high amounts of cryptoxanthin include pumpkin, corn, papaya, red bell peppers, tangerines, oranges, and peaches. More research is needed in this area, however.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Some evidence suggests the genistein (a type of isoflavone) in soy may have properties that are protective against lung cancer.

Click the icon to see an image of phytochemicals.

Note: Studies on these chemicals are not consistent. It is unlikely that individual phytochemicals offer protection, but rather that the benefits come from a collection of vitamins and plant chemicals contained in fruits and vegetables. Fruit, especially, appears to be protective.

Fats and Oils. Some studies have indicated that diets high in animal fats increase the risk for lung cancer. Others have suggested some protection from cod liver oil, which contains omega-3 fatty acids (found in fatty fish), omega-6 fatty acids (found in flax and in soybean and canola oils), and monounsaturated oils (found in olive and canola oils). Of interest was a 2002 study reporting that women who had a high intake of cheese had a lower risk of lung cancer. Despite these intriguing pieces of information, the ability of these substances to protect against lung cancer remains controversial, and discontinuation of smoking remains the best advice.

Click the icon to see an image of fats and oils.

Vitamin Supplements. Even with a healthful diet, smoking reduces the levels of a number of vitamins, importantly vitamin C. There is no evidence, however, to support any protection from antioxidant supplements, including vitamins E, A, or beta carotene.

In fact, evidence is now suggesting that high doses of vitamin C, vitamin E, and beta carotene supplements may have harmful effects. A 2000 study, for example, reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. The strongest studies to date on negative effects of antioxidant supplements have reported an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. In other words, antioxidants may actually be harmful in people who already harbor cancer cells. This is particularly important information for smokers, who may carry precancerous or cancerous cells for years prior to developing the disease. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see the benefits of vitamin A.

Click the icon to see dietary sources of vitamin A.

Trace Element Supplements. Trace elements may be important in cancer risk and prevention.

Selenium appears to inhibit cell production and may have other anti-cancer properties. A few studies have reported some protection with selenium. However, a major 2002 analysis supports previous work, indicating that taking selenium helps only people who are deficient to begin with.

Click the icon to see the benefits of selenium.

Zinc may prove to be more important than selenium. Some research suggests that zinc may help protect smokers by blocking cadmium. Smokers have higher levels of cadmium in their body, and there may be a link between cadmium and a higher risk for lung cancer. Some laboratory studies have indicated that zinc might help protect against tumor progression. There is no evidence that taking zinc supplements will reduce the risk for lung cancer, however.

A 2003 study reported a lower risk in lung cancer in men and women who were physically active. Both moderate and intensive exercises were associated with protection.

People concerned about radon in their home or area can purchase a test approved by the Environmental Protection Agency. Methods for removing radon include installing a soil suction system. It should be noted, however, that home prevention measures rarely reduce radon levels to zero. Simply sleeping by an open window reduces the risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (coxibs) both block cyclooxygenase (COX) enzymes. NSAIDs block COX-1 and 2, and coxibs selectively block COX-2. Evidence now strongly suggests that the COX-2 enzyme plays a role in blood vessel growth (angiogenesis) that can feed lung cancers.

NSAIDs. NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). These agents inhibit COX-2, but they also target another COX enzyme. Studies are now reporting an association between regular use of aspirin or other NSAIDs and a reduced risk for non-small cell lung cancer.

COX-2 Inhibitors. The COX-2 inhibitors are more recent forms of NSAIDs. Currently, only celecoxib (Celebrex) is still on the market. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the market due to their high risk of causing strokes and heart attacks. Because they target the COX-2 enzyme specifically, researchers are focusing on these drugs for a possible role in treating lung cancer and preventing recurrence.

Diagnostic Tests

Chest X-Rays. In a small percentage of cases, a routine chest x-ray reveals the first signs of lung cancer. Usually, however, symptoms of existing lung cancer, such as coughing, chest pain, and blood in the sputum, will lead to a chest x-ray. If non-small cell lung cancer is present, chest x-rays may show lesions (damaged or abnormal tissue) in the center of the lung, cavities formed by squamous cell carcinoma, or lace-like pattern of cells spreading through the lungs. By the time lung cancer is diagnosed by chest x-rays, however, it has often spread so far that it cannot be surgically cured. Four major studies found no survival benefits in early detection from chest x-rays and sputum screening. Regular screening for lung cancer using x-rays is therefore not currently recommended.

Computed Tomography. Computed tomography (CT), particularly the specific technique called low-dose spiral (or helical) CT, is more effective than x-rays for detecting cancer in patients with suspected lung cancer. It is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Surgeons also use CT scans to evaluate patients before lung surgery.

CT stands for computerized tomography. In this procedure, a thin x-ray beam is rotated around the area of the body to be visualized. Using very complicated mathematical processes called algorithms, the computer is able to generate a 3-D image of a section through the body. CT scans are very detailed.

The use of helical CT for early screening is still controversial. Studies of CT scans in smokers suggest that early screening will detect about 2% of lung cancers, most of these in early stages. In the studies, 62 - 82% of the patients with stage 1A cancer (when the tumor has not spread yet) were still alive at 5 years. Neither study, however, was controlled (compared with other groups, such as non-smokers). The survival figures were likely to be higher than in actual practice.

Click the icon to see an image of a CT scan of the chest.

Evidence regarding the survival benefits of early detection is not clear. Many experts are highly opposed to widespread screening for lung cancer. Some evidence, for example, suggests that lung cancer cells in non-small cell lung cancer are often very aggressive at microscopic levels (before a tumor is formed). If this were true, the cancer would be highly likely to have already spread, long before it was visible with CT scans. Moreover, some studies have found no association between tumor size at the time of diagnosis and survival times. On the other hand, some suspicious areas detected by CT scans may actually be innocent, and these patients might be more likely to die from aggressive treatments than from the disorder itself.

It should also be noted that about 98% of suspicious areas seen on CT scans turn out to be benign. Even after rescreening, many scans will show suspicious areas that turn out to be harmless but will require invasive and expensive biopsies. Additional experience with CT scans, however, may allow experts to better determine which abnormalities are likely to be benign.

High-risk individuals who are still interested in early screening with CT scans should ask their doctor about available clinical trials.

Computed tomography is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Other imaging tests, however, may be useful for staging and tracking lung cancers (staging means finding out how advanced the cancer is).

Positron Emission Tomography. Positron emission tomography (PET), specifically a technique known as FDG/PET, is the most accurate noninvasive test for detecting early lung cancer. It is also the best imaging technique for staging lung cancers, not only those located in the lungs, but also those that have spread, particularly into the space between the two lungs (the mediastinum). With this imaging test, the patient is first injected with a specially formulated liquid sugar (called FDG), and then viewed with a machine that records energy given off by tumor cells.

PET is expensive and not widely available. However, its supporters suggest that it may prevent many unnecessary surgeries by identifying patients whose cancer has advanced past the stage at which surgery is helpful. There is some evidence that FDG/PET scan can detect a metabolic (processing) response to treatments that may help predict the outlook for the patient.

Scintigraphy. Scintigraphy is an imaging procedure in which patients are administered low-level radioactive agents that bind to cancer cells, which then can be tracked by special cameras to reveal the cancer cells' location and intensity. Agents selected are those that can best bind successfully with specific tumor types. For example, a 2001 study of the binding agent 111In-DOTA-LAN demonstrated excellent results in identifying non-small cell lung tumors. This study further suggests the possibility of using such highly-targeted binding agents as lung cancer treatments.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI), an imaging procedure that uses radio wave energy, is frequently used instead of CT scanning to locate brain and bone metastases that can be associated with lung cancer.

Biopsies of lung tissue are needed to confirm lung cancer. This requires invasive procedures that may vary from simple needle aspiration to chest surgery.

Needle Aspiration. Sometimes, a biopsy specimen is obtained by inserting a needle between the ribs, and then guiding it with the use of computed tomography scans, ultrasound, or fluoroscopy (a device allowing an x-ray view). Specific techniques include transbronchial or transthoracic needle aspiration (TBNA or TTNA) or endoscopic ultrasound-guided needle aspiration (EUS-NA). Their use depends on how much of the area can be observed with less invasive imaging methods. There is a 5 -10% risk for bleeding or collapsed lung with needle aspiration.

Thoracoscopy. Thoracoscopy is usually very effective for diagnosing cancer in the outer areas of the lungs, or those involving the pleura (membrane surrounding the lungs). This is a surgical procedure that uses a fiber-optic tube to view the area:

The procedure requires general anesthesia.
The surgeon passes surgical instruments and a fiber-optic tube through a small incision in the chest. The tube has a camera in it, which allows the surgeon to look at the lungs on a video screen.

Bronchoscopy. To locate cancer that develops in the central areas and major airways of the lung (usually squamous or small cell cancer), bronchoscopy is typically performed. The procedure is done as follows:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The doctor inserts a bronchoscope, a hollow flexible tube often containing a fiber-optic light source, into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the doctor to see the windpipe and major airways. In a procedure called fluorescence bronchoscopy, the doctor injects the patient with a drug that makes cancer tissue appear red when exposed to laser light from the bronchoscope.
The surgeon removes specimens for biopsy, ideally combining techniques to include cutting tissue, brushings, and a washing process called bronchoalveolar lavage (BAL). BAL involves injecting saline through the bronchoscope into the lung and then immediately suctioning the fluid back through the hollow tube of the bronchoscope; the fluid is then analyzed in the laboratory. Both brushing and washing procedures may be very valuable additions.

Advances in this procedure, such as laser-induced fluorescence endoscopic bronchoscopy, may improve early detection of cancer.

Bronchoscopy is usually very safe, but complications can occur; they include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Click the icon to see an image of bronchoscopy procedure.

Click the icon to see an image of a bronchoscope.

Mediastinoscopy. Mediastinoscopy uses a tube inserted between the lungs to locate the appropriate areas for biopsy. It is performed if the physician suspects that cancer has spread to nearby lymph nodes but has not yet metastasized.

Sputum Analysis for Presence of Cancer Cells. Some experts are now recommending an analysis of coughed-up sputum as a useful and cost-effective measure for identifying cancer cells, particularly those located in central areas of the lung. However, although sputum analysis appears to be as accurate as any other screening test currently conducted, it may miss cancers such as adenocarcinoma, which form in mucus-producing cells typically in the outer portion of the lungs. If a sputum analysis does not show cancer cells, but other signs of lung cancer are present, including blood in the sputum and suspicious areas on x-rays, other tests are performed.

Biomarkers. Biologic markers, called biomarkers, are high levels of substances that are released by tumors and indicate the presence of specific cancers. Biomarkers can be found in sputum, blood, and tissue samples. They can include enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some biomarkers may prove to reveal the presence of cancer cells before they are evident on CT scans or other imaging tests. For example, genetic mutations, notably K-ras and p53, can now be detected in cells found in sputum, or cells taken during bronchoscopy. Such mutations occur only with cancerous changes and may enable early detection. Other markers that prove to be important for predicting aggressive cancers are high levels of matrix metalloproteinase (MMP9) and vascular endothelial growth factor (VEGF), which are compounds involved with angiogenesis (the process in which blood vessels serving the tumor develop).

As part of the doctor's initial examination, patients may have a pulmonary function test to evaluate lung health and capacity. In addition, since the heart and lungs are often involved in complications following lung cancer surgery, the doctor may be especially interested in taking a complete history of those systems in patients who might need surgery.

Staging Systems

Tests to Determine Cancer Stage. After diagnosing non-small cell lung cancer, the doctor makes treatment choices by determining the cancer's stage (how large the tumor is and how far the cancer has spread). To stage the cancer and determine other aspects of the disease, a number of tests are conducted:

The cancer cells are examined microscopically for size, shape, and other configurations.
Computer tomography (CT), magnetic resonance imaging (MRI), or both, are used to scan the lung and perhaps other locations, such as the liver, upper abdomen, and brain, to determine the extent of the disease.

Physical Examination. A detailed physical examination of the whole body is very important to identify or rule out the spread of cancer to other areas, and to determine the general condition of the patient. For example, questions about dizziness or headaches can help the doctor determine if the cancer has spread to the brain, while bone or joint pain might suggest that the cancer has spread to the bone. The doctor will also look for head and neck symptoms that might reveal the presence of other tumors. Also, according to a 2000 review, the patient's weight loss and ability to function are two very important factors for predicting survival following treatment. Patients who are mobile and have lost less than 10% of their pre-treatment weight tend to have better survival rates.

In lung cancer, the stage of the disease at the time of diagnosis is a major factor in determining how to treat the cancer, and how long the patient can expect to live. In general, survival is longest for patients with very early-stage disease and shortest for patients with very advanced disease that has spread to several regions of the body. Staging is based on the results of physical and surgical examinations, and laboratory and imaging tests, including biopsies.

To determine the stage, medical professionals first categorize each tumor by size and by how far it has extended. This identification method is called the TNM system.

The TNM categories then determine the stage (numbered 0 to IV), indicating how advanced the cancer is.

TNM stands for Tumor, regional lymph Nodes, and Metastasis (cancer spread beyond the original tumor).

T refers to the size and extension of the tumor itself. In TX and T0, the tumor is indicated by cancer cells in sputum or lung samples but cannot be seen. Tis: Carcinoma in situ. The cells are cancerous, but the tumor does not show evidence of spreading. In T1, the tumor is 3 cm or less in size, is still contained in the lung or the membrane covering the lung, and has not reached the main airway.

In T2, the tumor has one or more of the following features:

It is greater than 3 cm
It involves the main airway
It is 2 cm or more away from the ridge (the carina) at the lowest part of the windpipe
It has invaded the pleura
It is associated with collapsed lung tissue (atelectasis) or swelling that blocks part (but not all) of the lung

In T3, a tumor of any size has directly invaded any of the following:

Chest wall
Diaphragm
The membrane covering organs and structures in the chest
The outer wall of the membrane around the heart (pericardium)

In addition, one or more of the following conditions are present:

The tumor is in the main airway, less than 2 cm away from the carina, but is not in the trachea (windpipe).
The tumor is associated with a collapsed lung or swelling that blocks the entire lung.

In T4, the tumor has invaded any of the following:

The area between the lungs (mediastinum)
The heart
The great vessels (the blood vessels that carry blood from the heart)
Carina, trachea, or esophagus
Main portion of the spine

In addition, one or both of the following occurs: separate tumors are present in the same lobe; the tumor is accompanied by an increased amount of fluid between the pleural membrane and the lung.

N followed by a number from 0 to 3 refers to whether the cancer has reached regional (in the area of tumor) lymph nodes. In stage N0, the regional lymph nodes are still cancer-free.

In N1, the cancer has spread to the nearest lymph nodes around the airways, to the hilum (a central zone in the lung where blood and lymph vessels enter), or both. The tumor has extended directly into lymph nodes within the lung. In N2, the cancer has spread to lymph nodes in the middle of the chest that are still next to the affected lung, to the nodes below the carina, or to both regions.

In N3 the cancer has spread to lymph nodes in the middle of the chest that are next to the opposite lung, to the hilum in the opposite lung, to lymph nodes in nearby or opposite muscle tissue, or to lymph nodes above the collar bone.

M Stages refer to metastasis. In M0, metastasis has not occurred.

In M1 distant metastasis has occurred. This includes the presence of a separate tumor in a different lobe.

Staging factors are used to help determine treatment and outlook. The following suggest a more aggressive disease:

The presence of respiratory symptoms
A tumor larger than 3 cm
High numbers of blood vessels in the tumor

Researchers are always looking for more accurate ways to determine a treatment and outlook for lung cancer. For example, some research involves specific biomarkers and related blood vessel development within tumors. These markers might eventually help determine how aggressive a cancer is likely to be, and what the best treatment approach is.

If the cancer is still localized, surgery can produce 5-year survival rates of up to 75% in stage I patients and up to 50% in stage II patients. Unfortunately, very few patients are diagnosed at such early stages. In locally advanced stages, the standard treatment is concurrent radiation and chemotherapy. However, even with this approach average survival times are less than 2 years. Even if an initial tumor has been surgically removed or irradiated, cancer recurrence rates are very high. The risk for recurrence is lower in smokers who quit after treatment.

On an encouraging note, advances in therapies for later stage lung cancer are now offering some hope for improving survival. Still at this time, the mortality rate for lung cancer is still extremely high, and reports of improved response or survival rates using drugs or combinations of therapies do not mean cures. Ultimately, the patient must weigh a diminished quality of life using aggressive treatments against a chance for a modestly prolonged life.

Surgical Procedures

Surgery is performed in the following circumstances:

The surgical removal of an entire lobe or parts of a lung is the primary treatment for eligible patients in early stages of cancer. Recurrence is high after surgery, although the new tumor is often operable.
Some patients with stage IIIA cancer may also benefit from surgery. The intent at this stage is to extend survival time, rather than cure the disease.
Surgery is not out of the question in rare cases of metastasis when the cancer appears in a single operable location, such as the brain.

Unfortunately, lung surgery may be too risky for patients with other lung diseases or serious medical conditions, and because lung cancers tend to occur in smokers over 50, such health problems are likely to be present. Long-term survival rates appear to be better in patients treated at hospitals that perform large numbers of lung cancer surgeries, and when surgeries are performed by thoracic surgeons, who specialize in chest procedures.

The type of surgery depends on the amount of lung or other tissue that needs to be removed.

Wedge Resection or Segmentectomy. Wedge resection and segmentectomy remove only a small part of the lung; consequently, they preserve almost normal breathing function after the operation.

Lobectomy. Removal of one of the lobes of the lung is called lobectomy. The patient's lung function must be adequate before undergoing this procedure. The operation carries an overall mortality rate of 3 - 5%, with older patients having the highest risk.

Click the icon to see an illustrated series detailing surgery to remove diseased lobes of the lung.

Pneumonectomy. Pneumonectomy removes the entire lung. The procedure itself carries a mortality rate of 5 - 8%, with the oldest patients having the greatest risk. In such patients, recurrence almost always occurs.

Surgical advances are allowing a wider range of options, including minimal surgeries for early cancers and surgeries that relieve cancer symptoms in late stages of the disease.

Thoracoscopy. Thoracoscopy, also known as video-assisted thoracic surgery (VATS), is a less-invasive technique that employs a thin tube containing a miniature camera and surgical instruments. It requires much smaller incisions than open surgery and speeds recovery to the point that patients are up within hours. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients. The death and complication rates following VATS are lower than those following conventional surgeries. Pain is reduced, and patients are released from the hospital quicker. Several studies found that the 5-year survival and recurrence rates in patients with stage I NSCLC treated with VATS were comparable to those in patients treated with traditional open chest surgeries.

Laser Surgery. Laser surgeries allow removal of minimal amounts of lung tissue and are proving useful for improving symptoms in stage II and IIIA patients. They may also be beneficial in treating cancers that have spread to the throat, obstructing it.

Photodynamic Therapy. Photodynamic therapy uses bronchoscopy and special laser light beams combined with a light-sensitive drug, called porfimer sodium (Photofrin), to kill cancer cells. The most common side effect is sun sensitivity. Serious side effects include bleeding in the lungs. Photodynamic therapy may be considered for patients in early-stage disease who are not candidates for other surgical procedures. It may also be used to reduce symptoms in late-stage disease.

Cryosurgery. Cryosurgery uses a probe chilled to below freezing to destroy the tumor cells on contact and is being investigated in combination with radiation therapy. It may also be an alternative in early stage cancer for patients who cannot have surgery.

Electric Cauterization. Electric cauterization, the use of electricity to produce heat that destroys tissue, is also under investigation as a treatment for early-stage disease.

Back Surgery. Spinal cord compression is a common cause of pain in patients with advanced lung cancer. Because such patients can live for a year or longer, some research indicates that back surgery followed by radiation therapy can significantly improve the quality of life for many of these patients.

Radiation Treatments

In addition to surgery, radiation is the other primary treatment for early-stage lung cancer. Doctors are also studying the benefits of radiation treatment in advanced lung cancer.

Radical Radiation in Early-Stage Cancer. Radical radiation is used as the sole procedure in stage I and some stage II patients who have adequate lung function but, for medical or other reasons, cannot be treated with surgery. In these cases, the 5-year survival rate is about 20%, and the cancer is likely to recur. Survival rates may be higher or lower, depending on the tumor size. In general, treatment with radiation therapy alone shows less benefit with larger tumors. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. Nevertheless, a recent study confirmed earlier results that show that radiation therapy by itself is as effective as surgery in patients who are unable or unwilling to have surgery for early stage non-small cell lung cancer.

Combined Treatments for Improving Survival in Advanced Cancer. Radiation is also being investigated in various combinations with chemotherapy, surgery, or both. At this time, concurrent radiation treatment plus platinum-based chemotherapy may extend survival times in advanced lung cancer. Other combinations are showing promise.

Palliative Radiation. Doctors use palliative radiation to shrink tumors and reduce pain and symptoms. Palliative radiation is appropriate for patients with advanced disease and poor lung functions, or in those with metastasized cancer. In up to 85% of patients with advanced disease, palliative radiation therapy helps relieve pain, shortness of breath, the superior vena cava syndrome, coughing up blood, and symptoms caused by brain metastases. Radiation, in these cases, is not generally used with the intention of reducing mortality rates, although it may increase survival in some patients, such as those with excellent lung function whose tumors are small.

Delaying radiation therapy until symptoms develop does not appear to reduce survival times or impair quality of life compared to starting it right away, in patients with minimal or no symptoms.

Radiation Therapy in Metastasis to the Brain. Radiation is the primary treatment when cancer has spread to the brain unless the cancer is small enough to be treated surgically. When radiation is used, a technique called stereotactic radiosurgery may be used to deliver powerful, highly targeted radiation to specific areas in the brain. Some trials are investigating using radiation to the head to prevent metastasis to the brain.

The goal of radiation treatment is to administer doses as high as possible to kill as many cancer cells as possible, without destroying surrounding healthy tissues or causing a dangerous reaction. Doctors may try different procedures for the same patient. The exact radiation procedure depends on the site of the cancer or how far it has spread:

External-Beam Radiation. External-beam radiation therapy focuses a beam of radiation directly on the tumor. It is generally used for metastasized cancer.
Brachytherapy. Brachytherapy involved the implantation of radioactive seeds through thin tubes directly into the cancer sites. Brachytherapy may be used for lung cancers that have spread to the throat and caused obstruction. High-dose-rate brachytherapy may also have some value for patients with inoperable tumors in the central region of the lung.

Hyperfractionated radiotherapy gives smaller than standard doses a number of times a day (usually two or three). This allows doctors to use a higher cumulative dose over the whole course of treatment. It is not as useful as therapy by itself, but should be combined with chemotherapy to have any survival benefits.

Hyperfractionated Accelerated Radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART) administers multiple doses per day but uses standard doses. This allows the total dose of radiation to be administered over a shorter time period than the standard 6 weeks. CHART is proving to extend survival rates of patients with localized cancer over that of standard radiotherapy or non-accelerated hyperfractionated radiation. It can cause severe swallowing problems. A modification in which treatment is suspended for 2 days out of 7 may help reduce this effect.

Three-dimensional (3-D) conformal radiotherapy delivers external-beam radiation designed to closely match the specific targeted organs or tissues. This allows significantly higher doses to attack the cancer while reducing the risk to healthy cells. In a 2003 report, 3-year survival rates in stage IIIA patients were nearly 60%, and nearly half the patients experienced no side effects.

Stereotactic body radiotherapy, an advance on conformal radiation, uses a body frame and an abdominal press to immobilize the patient's body and limit breath movement. This allows a more accurate delivery of high-energy radiation. The technique is still investigational.

Radiation can have significant side effects when used as part of intensive treatments, such as hyperfractionated radiotherapy or radiotherapy in combination with chemotherapy. Among the most serious problems is severe inflammation in the esophagus (esophagitis) or the lungs (pneumonitis). Infection is also a danger.

The use of targeted approaches, such as conformal radiotherapy, may help reduce these complications. Investigators are also studying drugs, notably amifostine, which appear to help reduce throat and lung inflammation caused by radiation, without reducing its cancer-fighting effects.

Treatment Options by Stages

In the occult stage (TX, N0, M0), cancer cells are found in a sample of a patient's coughed-up sputum, but no cancer cells have yet been detected in the lung.

Treatment Options. Surgical removal of the tumor, if one can be located, allows identification of its stage and often results in cure.

Stage 0 or carcinoma in situ (Tis, N0, M0) are noninvasive cancers and only a few layers of cancer cells are detected within one local area. The cancer has not grown through to the top lining in the lung and can be surgically removed. There is a high risk for development of a second tumor, however.

Treatment Options:

Surgery, often a limited procedure, where only part of a lobe is removed from the lung.
In patients who cannot be treated surgically, consider photodynamic therapy, cryotherapy, or brachytherapy.

In stage I, the cancer has reached higher layers of the lung but has not spread into the lymph nodes or beyond the lung.

General Treatment Options. The primary treatment is surgery, such as lobectomy (removal of a whole lobe), if possible. Patients with poor lung function should undergo partial lobectomy, if possible. Radiation treatments may be appropriate and beneficial for patients who cannot have surgery. It is not clear if early-stage lung cancer patients, who have radiation or chemotherapy in addition to surgery, have higher survival rates. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. An analysis of studies using chemotherapy in addition to surgery or radiotherapy, however, indicated benefits in survival. The overall 5-year survival rates for early stage-cancer are in the range of 30 - 50%. Patients should consider clinical trials for prevention of recurring (returning) cancer after the initial treatment. The risk for recurrence is highest in patients who continue to smoke.

Stage IA (T1, N0, M0). The 5-year survival rates for stage IA patients after successful treatment can be as high as 80%. Treatment options are:
- Lobectomy or sometimes pneumonectomy (removal of one lung)
- Wedge or segment removal, particularly in patients with poor lung function who cannot withstand lobectomy
- Radiation in selected patients whose condition is inoperable (for example, frail patients with T1 tumors); 5-year survival rates can be equal to those with surgery, between 32 - 60%
- Clinical trials of adjuvant chemotherapy following surgery

Stage 1B (T2, N0, M0). Stage IB survival rates after treatment can be better than 60%. Treatment options are:
- Lobectomy or sometimes pneumonectomy; wedge or segment removal, particularly patients with poor lung function
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy; studies are promising)
- Clinical trials for radiation treatments in selected patients whose condition is inoperable
- Clinical trials of chemotherapy before, after, or during radiation treatments

In stage II the cancer cells have spread to nearby lymph nodes.

General Treatment Options. Surgery, usually removal of a lobe (lobectomy) or one lung (pneumonectomy), is the treatment of choice. Five-year survival rates associated with stage II surgery can vary. A 2000 review of existing research places the numbers as high as 40 - 50%, but notes that they can drop to 25% and below if the cancer has spread beyond the immediate lymph nodes.

Patients whose cancer is inoperable may consider radiation treatments. In patients who can complete treatment, 5-year survival rates average 20 - 30%, with higher rates for stage IIA. Patients should consider clinical trials for prevention of recurring cancer after primary treatment. To date, however, supplementing surgical treatment with radiation or chemotherapy does not appear to prolong survival rates.

Stage IIA (T1, N1, M0). Survival rates can be as high as 60%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before, after, or during radiation treatments
- Clinical trials of chemotherapy to reduce tumor size before surgery (induction therapy)
Stage IIB (T2, N1, M0) or (T3, N0, M0). Survival rates can be over 40%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy)
- Clinical trials of chemotherapy before, after, or given at the same time as radiation treatments

In stage III, the cancer cells have spread beyond the lung to the chest wall, diaphragm, or further lymph nodes, such as those in the neck.

General Treatment Options. Generally, the treatment of choice for stage III tumors is radiation and sometimes surgery, chemotherapy, or combinations of all three.

Combination approaches may be significantly more effective than single treatments. For example, of particular interest is a treatment approach that starts with chemotherapy and radiation, given at the same time, followed by surgery. In one study, 5-year survival in stage III patients treated this way was nearly 50%.

Stage IIIA (T1, N2, M0) or (T2, N2, M0) or (T3, N1, M0) or (T3, N2, M0).
- Surgery, if the tumor and affected lymph nodes can be completely removed. Consider platinum-based chemotherapy or radiation therapy after surgery.
- Radiation treatment plus platinum-based chemotherapy, given at the same time, is an option for those in otherwise good health. This regimen should be followed by surgery, if possible.
- Consider clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation.
- Consider other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs.
Stage IIIB (Any T, N3, M0) or (T4, Any N, M0). Some patients may consider surgery if there is no lymph node involvement (T4, N0), and tumor can be removed. Surgery is not an option for other patients with stage IIIB cancer. Treatment options are:
- Radiation alone, usually for symptom control; it may improve survival in certain patients, such as those with lymph node involvement above the collar bone
- Chemotherapy alone
- Concurrent (given at the same time) cisplatin-based chemotherapy plus radiation, sometimes followed by surgery if possible
- Clinical trials using induction chemotherapy alone to shrink tumors, which may then be treated with surgery or radiation
- Clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation
- Other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs

In stage IV (any T, any N, M1), the cancer has spread (metastasized) to other parts of the body.

Treatment Options are:

Combination of two- or three-drug chemotherapies that include platinum-based drugs and newer agents; the best patient candidates are those in otherwise good health, who have a limited number of distant metastasized sites. Chemotherapy is not recommended for patients who are too ill
External-beam radiation for symptom relief
Paclitaxel or gemcitabine as a single medication
Other clinical trials
If metastasized cancer involves only one or two areas in the brain, it may respond to surgery followed by radiation to the brain

Recurring or additional new tumors occur, usually in the lung again, in half of treated patients. Research shows that a single tumor in the lung is more often a new tumor that, in many cases, may be operable.

Treatment Options are:

Radiation for symptom control
Chemotherapy with or without bevacisumab (Avastin)
If the cancer spread to only one site in the brain, it may respond to surgery, followed by whole-brain radiation. Extended disease-free survival is possible. If the brain tumor is not operable, it is treated with radiation. Even if cancer returns in the brain (in 50% of cases), treating it again is possible in many patients, if the disease has not spread elsewhere
Laser therapy or interstitial radiation for tumors inside the airways
Stereotactic radiosurgery (in a few selected patients)

Chemotherapy Treatments

Chemotherapy is the use of drugs given by mouth or by injection to destroy cancer cells that may have spread beyond the tumor. Until recently, there has been some doubt about the effectiveness of chemotherapy for lung cancer. A major 2002 analysis of 52 trials supported its use, particularly with platinum-based regimens, and with the use of supportive care.

Chemotherapy in early stages: Chemotherapy is proving to be beneficial in many patients as an additional (adjuvant) treatment with surgery or radiation.
Chemotherapy in advanced disease: Chemotherapy may be used as first-line treatment in patients with inoperable or metastasized lung cancer. It is typically used in late stages to reduce symptoms and, in some cases, extend survival. Since 2006, the combination of bevacizumab (Avastin, a monoclonal antibody) and platinum-based chemotherapy is also a first line treatment choice for such patients, if the cancer is the non-squamous type

Powerful platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), are the basis for most chemotherapy regimens. Two-drug combinations, with one drug being a platinum-based agent, are currently the preferred regimens. Reasonable combinations include paclitaxel (Taxol) and carboplatin or cisplatin. This regimen can also include gemcitabine, docetaxel, or vinblastine or its derivative (vindesine or vinorelbine). There does not seem to be any significant differences in effectiveness among them. Gemcitabine and vinorelbine combination might be a good option for patients who cannot tolerate platinum compounds. Chemotherapy for lung cancer may have reached its peak. Still, investigative chemotherapeutic drugs may yet improve response. Many experts are pinning their hope on agents called biologic response modifiers, such as gefitinib (Iressa) or LY900003 (Affinitak). To date, however, they have not achieved better results than standard platinum-based chemotherapies. Gefitinib (Iressa), a second-line therapy for non-small cell lung cancer (NSCLC), is now available only for a limited group of patients. These patients have benefited from gefitinib in the past, or they are enrolled in a clinical study with the drug. While this medicine initially showed great promise in clinical trials, results from a newer study failed to show that it prolonged survival in advanced lung cancer patients who failed other treatments.

If you are currently taking gefitinib, do not stop taking it without talking to your doctor.

Erlotinib (Tarceva) is in the same medication class as gefitinib. It is approved for patients with locally advanced or metastatic NSCLC, who have failed one type of chemotherapy treatment in the past (it is a second-line treatment). Unlike gefitinib, erlotinib shows survival and progression-free benefits compared to placebo. However, it should not be combined with platinum-based chemotherapy.

Chemotherapy treatments are usually performed in an outpatient setting and in regular cycles for several months. How many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs are still matters of investigation. For instance, research suggests that a three- or four-course cycle may achieve the same survival times and better quality of life than the standard of six or more course cycles. Changing even one day in a drug sequence can sometimes significantly affect outcome. Such fine-tuning of chemotherapy regimens is likely to have the most effect on patients with advanced-stage disease, which requires more tailored treatment than early-stage disease.

Treatment for lung cancer depends on the type of cancer and the stage of the disease. Chemotherapy is a form of treatment for lung cancer that may cure, shrink, or keep the cancer from spreading.

Side effects of chemotherapy treatments are common, and they are more severe with higher doses. Side effects increase over the course of treatment. Some trials suggest that they can be reduced by giving the drugs for shorter durations, without loss of cancer-killing effects. Common side effects include the following:

Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression
Nausea and vomiting: Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these two side effects. Serotonin antagonists work well in nearly all patients given moderate drugs, and in most patients who take drugs that are more powerful. In one study, a combination of dexamethasone (a steroid) with ondansetron, taken within 24 hours of chemotherapy, achieved either a major or complete reduction in nausea and vomiting.
Anemia: Anemia, an abnormally low number of red blood cells, is common in lung cancer. Treatments include transfusions or injections of erythropoietin, an agent that causes more red blood cell production. Erythropoietin is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp), which requires fewer injections. These agents improve well-being and quality of life. Trials are in progress to determine if they may have survival benefits as well.

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days per month.

Serious complications of chemotherapy can also occur and may vary depending on the specific drugs. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia): Certain chemotherapy drugs, such as taxanes, pose a higher risk for this complication than other drugs. White blood cell count can improve with the addition of a type of drug called granulocyte colony-stimulating factor (filgrastim and lenograstim).
Liver and kidney damage: Amifostine (Ethyol) reduces the risk for kidney damage in patients taking repeated regimens of cisplatin-based therapy. It is also a radioprotector; that is, it helps prevent severe effects in the esophagus from radiotherapy, with or without chemotherapy.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based agents: A simple skin test is under investigation that may identify people with a potential allergic response.

Second-line chemotherapy is used for patients whose cancers have recurred after first-line chemotherapy. Some experts believe that the longer survival rates for advanced lung cancer seen for the past 5 years may be due to these drugs. Because platinum-based agents are most often used first, they are not beneficial for second-line therapy. The following are commonly used second-line agents.

Docetaxel (Taxotere). Docetaxel is the drug of choice at this time for cancers that do not respond to initial chemotherapy. Studies have reported that it achieves longer survival times than supportive care alone. It is usually given every 21 days. This regimen causes more side effects than pemetrexed, the newer major second-line drug. Weekly doses of docetaxel are effective and less toxic than the 3-week schedule. It is not clear if survival rates are comparable to those of pemetrexed with that schedule, however.

Pemetrexed (Alimta). Pemetrexed, known as an anti-folate, is another promising new agent for second-line therapy and possibly for first-line treatment as well. The drug targets a number of enzymes that play a role in how cancer cells increase. Some research suggests that it is as effective as docetaxel. Pemetrexed does have some serious toxic effects, but they can be significantly reduced with folic acid and vitamin B12 supplements. It is then less toxic than docetaxel, when docetaxel is given every 21 days, but not when it is given weekly.

Gefitinib (Iressa) and Other Tyrosine Kinase Inhibitors. Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Compounds called growth factors, which may be important in cancer cell production, control the growth of these new blood vessels. Researchers, then, are interested in medications that literally turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In so doing, the agents may be able to cut off cancer's lifeblood. Gefitinib and erlotinib are angiogenesis inhibitors that target receptors of an epidermal growth factor called tyrosine kinase. Interestingly, studies are finding that NSCLC tumors in people who have never smoked have a much higher rate of EGFR mutations. This helps to explain why gefitinib and erlotinib are more effective in treating NSCLC in people who have never smoked.

Gefitinib (Iressa) was approved in 2003 as a second-line therapy for non-small cell lung cancer. Many patients report significant improvement in symptoms and quality of life, and the drug initially showed great promise. In one study, gefitinib reduced tumor size by 50% in about 10% of the patients. However, recent large-scale clinical trial results have failed to confirm any survival advantage for most patients. At this time, gefitinib is available only for patients who have benefited from it in the past.
Erlotinib (Tarceva) was approved as a single agent second-line therapy in November 2004. Study results show that the drug prolonged survival by several more months than placebo (6.7 versus 4.7 months). Erlotinib is administered orally and has very low toxicity (rash and diarrhea are common).

Chemotherapy Following Surgery (Adjuvant Chemotherapy). Chemotherapy is being evaluated in combination with surgery, radiation therapy, or both. Fairly strong evidence is now supporting the use of platinum-based chemotherapy as adjuvant treatment after surgery in patients with lung cancers in stages Ib-IIIa, with some research indicating a 5% improvement in five-year survival rates. Not all studies confirm survival benefits, however, and trials are ongoing.

Chemotherapy before Surgery (Induction Chemotherapy). Some researchers are testing induction chemotherapy, which is used to shrink potentially operable tumors before surgery. Studies have been mixed in reporting any survival benefits in patients with advanced lung cancer.

Combined and Multi-Modal Therapy. In stage III cancers, investigators are researching very intensive treatments that use two or more combinations of chemotherapy, radiation, and surgery.

For example, radiation plus chemotherapy may be helpful in patients whose tumors are surgically removable.

In inoperable lung cancer, combining radiation with chemotherapy is proving to extend the time to recurrence, the overall duration of survival, or both, compared to radiation alone. Evidence also suggests that giving radiation treatments at the same time as chemotherapy (instead of in separate cycles) improves 5-year survival rates, compared to a sequential approach (separate cycles following each other). Chemotherapy and radiation treatments given at the same time are more toxic, however.

Other approaches use even more intensive multi-modal therapy. For example, some trials use radiation therapy with chemotherapy, followed by surgery. Patients are then sometimes given additional chemotherapy or radiation. In other promising regimens, patents are given concurrent radiation and chemotherapy followed by chemotherapy alone. Such approaches are very toxic but appear to improve survival in selected patients.

Severe inflammation in the esophagus is the most common severe side effect of the radiation and chemotherapy combination. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus. Long-term antibiotic therapy may be needed.

Although patients over 70 may suffer more from toxic effects than younger patients, studies now suggest that they can achieve survival rates with combined treatments that are equal to those in younger patients.

There are many painkilling medications available. Research shows that aggressive pain relief can help patients manage cancer treatment symptoms (in addition to pain) better. For example, a 2001 study suggested that reducing pain in elderly cancer patients markedly lowered their fatigue levels, and improved other symptoms as well.

Opioids are the most potent painkillers. The correct use of these strong medications is very important for reaching acceptable pain relief, and preventing a toxic response. For example, the long-lasting version of oxycodone (OxyContin) must be swallowed whole; chewing, inhaling, or injecting it can create a deadly overdose.

Investigative Agents

According to a 2001 article, of the nearly 500 cancer drugs currently in development, 58 of them (about 13%) are aimed at fighting lung cancer. Only the number of breast cancer drugs exceeded that percentage. Unfortunately, none to date have shown any real benefit in terms of patient survival. However, some drugs are showing promise, and at this time, these agents are the best hope for improving lung cancer survival rates.

Monoclonal antibodies (MAbs) are genetically designed immune factors. MAbs mark foreign compounds called antigens for attack by the immune system. Trastuzumab (Herceptin) and cetuximab (Erbitux) are MAbs under investigation for lung cancer. Bevacizumab (Avastin) was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.

All three of these MAbs block epidermal growth factor. These agents are of particular interest for patients who have cancers that produce too much of the protein called HER2. These agents show great promise in combination with chemotherapies and newer drugs, such as the tyrosine kinase inhibitors. For example, the disease-free survival time in patients with advanced NSCLC is longer when adding bevacizumab to platinum-based chemotherapy.

Antisense oligonucleotides are drugs being used to block molecules that result in too many cells that cause cancers. LY900003 (Affinitak), for example, targets an enzyme called PKC-alpha, which promotes tumor growth. Early studies with Affinitak showed some promising results. However, a 2003 study found no difference in survival when patients received Affinitak in combination with platinum-based chemotherapy, compared to patients receiving chemotherapy alone.

Genasense (G3139, oblimersen) blocks Bcl-2. Bcl-2 is a protein that is expressed in abnormally high amounts in some cancers. This antisense drug is also under investigation.

Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. In one early study, 60% of patients experienced partial or total tumor shrinkage when the agent was used in combination with radiation therapy. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Three of the stabilized patients remained stable for over 9 months. One patient had a partial response to Advexin. The only side effect of the multiple doses given was a passing fever that disappeared within 24 hours. Advexin is in Phase II clinical trials for NSCLC.

Vaccines use inactivated genetic materials from cancer cells, such as defective p53 or ras genes, to cause a highly targeted immune response to attack the cancer.

Retinoids are vitamin A-like antioxidant chemicals that help repair cell damage and appear to support growth of lung cells. A number of retinoid-like agents (retinal palmitate, TAC-101, 23-cis-retinoic acid, N-acetyl-cysteine) are being studied for the treatment or prevention of lung cancer.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.cancercare.org -- Cancer Care
www.lungusa.org -- The American Lung Association
www.asco.org -- American Society of Clinical Oncology
www.alcase.org -- Alliance for Lung Cancer
www.lungcancer.org -- Joint project of Cancer Care and the Oncology Nursing Society
www.nccn.org -- National Comprehensive Cancer Network
www.lungcanceronline.org -- Lung cancer information
www.epa.gov/iaq/radon -- National radon information
www.clinicaltrials.gov -- Find clinical trials
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKena WG. Clinical Oncology. 3rd ed. Orlando, Fl: Churchill Livingstone; 2004:1690-1701.

American Cancer Society. Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society; 2006.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, Ga.: American Cancer Society; 2007:34.

Janne PA. Non-small Cell Lung Cancer in Never-smokers: A Biologically and Clinically Distinct Type of Lung Cancer. In: ASCO 2007 Educational Book. Meeting of the American Society of Clinical Oncology, Chicago, Ill.: June 1-5, 2007.

Kagawa S, Fujiwara T, Saijo Y, et al. A multicenter phase I study of adenoviral p53 (ADVEXIN) in Japanese patients with advanced non-small cell lung cancer. Journal of Clinical Oncology. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 2564.

Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med. 2006 Jul 10;166(13):1359-67.

National Cancer Institute. Lung Cancer Home Page. Bethesda, Md.: U.S. National Institutes of Health. Available online.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 1.2007. Available online.

Tarceva [Package Insert]. Melville, NY: OSI Pharmaceuticals; 2005.

U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. List of Approved Oncology Drugs with Approved Indications. In: Oncology Tools. Available online.

U.S. Preventive Services Task Force. Lung cancer screening. Ann Int Med. 2004;140:738-739.

Xin M, Deng X. Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation. J Biol Chem. 2005 Mar 18;280(11):10781-9.

Review Date:
8/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Hodgkin's disease

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Risk Factors
Symptoms
Diagnosis
Outlook
Staging and Treatment Guide...
Treatment Options by Stage...
Radiation Treatments
Chemotherapy
Transplantation
Immunotherapy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

Chemotherapy can cause anemia, a drop in red blood cell (hemoglobin) levels. Erythropoiesis-stimulating drugs, which boost the production of red blood cells, are administered to counteract this complication. However, these drugs, including epoietin alfa (Epogen, Procrit) and darbepoietin alfa (Aranesp), can also cause serious side effects and adversely affect survival when hemoglobin levels are raised too high.

In 2007, the U.S. Food and Drug Administration (FDA) made several changes to the prescribing labels for erythropoiesis-stimulating drugs. The new labels contain stronger warnings and updated dosing-related safety information.

The FDA advises that for treating anemia associated with chemotherapy, dosing should increase hemoglobin levels to no more than 12 g/dL. Treatment with these drugs should stop as soon as the chemotherapy course is completed. Erythropoiesis-stimulating drugs are not safe or appropriate for all patients undergoing chemotherapy. Patients should discuss the risks and benefits with their oncologists. The FDA is currently reviewing additional data concerning the safety of these drugs.

Preventing Infection after Cancer Treatment

Both chemotherapy and stem cell transplants increase the risk for serious infections. Patients must take precautions to avoid exposure to germs. Ways to prevent infection include:

Practice good hygiene, including regular handwashing and dental care (brushing, flossing)
Avoid crowds, especially during cold and flu season
Eat only well-cooked foods (no raw fruits or vegetables)
Boil tap water before drinking it
Do not keep fresh flowers or plants in your house as they may carry mold

Introduction

Hodgkin's disease is a type of lymphoma. Lymphomas are cancers of the lymphatic system. They are generally subdivided into two groups: Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). NHL is discussed in another report. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas.]

The lymphatic system filters fluid from around cells. It is an important part of the immune system. When people talk about swollen glands in the neck, they are usually referring to swollen lymph nodes. Common areas where lymph nodes can be easily felt, especially if enlarged, are: the groin, armpits (axilla), above the clavicle (supraclavicular), in the neck (cervical), and the back of the head just above hairline (occipital).

HD is the major tumor in a group known as malignant lymphomas. Most often HD starts in B cell lymphocytes located in lymph nodes in the neck area, although any lymph node may be the site of initial disease.

Click the icon to see an image of the lymph nodes in the head and neck.

The following is a possible description of the process leading to HD:

In early development, B cells normally undergo a series of genetic rearrangements until they create immunoglobulins, proteins that act as antibodies.
Antibodies are produced by the immune system. They contain receptors that match and bind to a wide array of foreign substances (such as viral proteins) called antigens. Antibodies help launch an immune attack against antigens.
B cells normally undergo limited cycles of genetic rearrangement that result in immunoglobulin production. In rare cases, however, the genetic arrangements create a mutation that does produce immunoglobulins. The results are large, abnormal cells referred to as Reed-Sternberg cells.
Without immunoglobulin, Reed-Sternberg cells can be infected by certain viruses (notably the Epstein-Barr virus -- the cause of infectious mononucleosis). Genetic byproducts of these viruses appear to inhibit a natural process of self-destruction (called apoptosis) that would normally kill off these natural cells. Instead, the abnormal B cells grow non-stop, causing most forms of HD.

Click the icon to see an image of an antibody.

Only a very small percentage (about 1%) of cells found in the affected lymph tissues of HD are actually Reed-Sternberg cells. Researchers are unable to completely explain why so few cells can cause such severe symptoms. One explanation is that these cells trigger production of very powerful immune system proteins called cytokines (including those known as interleukin-1, interleukin-6, and tumor necrosis factor). These cytokines produce an inflammatory response that can cause local pain, fever, and other symptoms typical of HD. The dominance of different kinds of cytokines may also explain why HD takes different forms.

Classical Hodgkin's Lymphoma. Based on the variations and numbers of Reed-Sternberg cells, as well as other features, four major subtypes of classical HD have been identified:

Nodular Sclerosis. Nodular sclerosis is the most common subtype, representing almost 60% of HD cases. Younger patients are more likely to have this type. The nodes first affected are often those located in the center of the chest (the mediastinum).
Mixed Cellularity. Mixed cellularity is the next most common HD form, occurring in about 25% of patients, mostly in older patients, children, and those with immune disorders, such as AIDS. It usually indicates a more severe condition.
Lymphocyte Depleted. Lymphocyte-depleted HD occurs in about 4% of patients, nearly always in elderly people. It indicates extensive disease and a poor outlook. It can easily be confused with non-Hodgkin's lymphoma.
Lymphocyte-Rich Classical Hodgkin's Lymphoma. This form is similar to nodular lymphocyte predominant HD, but has more cell characteristics that conform to classical HD.

Nodular Lymphocyte-Predominant Hodgkin's Disease. Nodular lymphocyte-predominant Hodgkin's disease (LPHD) occurs in about 5% of patients. The cells in LPHD known as lymphocytic and histolytic cells are proving to be distinctly different from classic Reed-Sternberg B cells. Patients with lymphocyte predominance are usually young men, who often have no symptoms. LPDH is very slow growing and may be associated with long survival. There is a 3% risk, however, that LPDH will transform to non-Hodgkin's lymphoma. In fact, lymphocyte-predominant HD may eventually be defined as a non-Hodgkin's lymphoma.

Lymphomas represent tumors of the lymphatic system. This system is a network of organs, ducts, and nodes. The system interacts with the blood's circulatory system to transport a watery clear fluid called lymph throughout the body. The lymphatic system contains lymphocytes, which are important cells involved in defending the body against infections. This system also restores 60% of the fluid that leaks out from blood capillaries back into circulation. Its ducts provide transportation for fats, proteins, and other substances collected from the body's tissues.

Lymphocytes. The lymphatic system helps produce and transport lymphocytes, white blood cells that are a primary component of the immune system. Some lymphocytes produce antibodies that can target and attack specific foreign substances (antigens).

Lymphocytes develop in the bone marrow or thymus gland. They are categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells).
B cells complete their structural growth and definition (known as differentiation) and mature in the bone marrow.
T cells also start out in the bone marrow, but differentiate and mature in the thymus gland, located beneath the breastbone (sternum). This small gland is active mostly in the fetal stage through the first 10 years of life, after which it shrinks.
B-cell and T-cell lymphocytes leave these organs through the bloodstream, which eventually branches out into the tiny blood vessels called capillaries.
Some lymphocytes, along with fluid, proteins, and other substances, move out of the capillaries into the surrounding tissues. Some enter the lymphatic vessels.
Lymphatic vessels begin as tiny, blind-ended tubes. They lead to larger lymphatic ducts and branches, and drain into two ducts in the neck, where the fluid re-enters the bloodstream.
Along the way, the fluid passes through lymph nodes, which are oval structures composed of lymph vessels, connective tissue, and white blood cells. Here, the lymphocytes are either filtered out or added to the contents of the node.

Lymph Nodes. In a lymph node, lymphocytes typically receive their initial exposure to foreign substances, such as bacteria. This exposure prompts the lymphocytes to perform their immune functions. The size of a lymph node varies generally from that of a pinhead to a bean. Most nodes are clustered throughout the body. Important node clusters are found in the neck, lower arm, armpit, and groin.

Other Structures in the Lymphatic System. The tonsils and adenoids are secondary lymphatic organs. They are composed of masses of lymph tissue that also play a role in the lymphatic system. The spleen is another important organ that processes lymphocytes from incoming blood.

Click the icon to see an animation about lymph nodes.

Click the icon to see an image of an antibody.

Click the icon to see an image of the immune system structures.

Risk Factors

Hodgkin’s disease accounts for about 11.5% of all types of lymphomas. According to the American Cancer Society, about 8,200 new cases of Hodgkin's disease (HD) were diagnosed in the United States in 2007 and about 1,000 people died of the disease. Experts believe that the malignant process leading to Hodgkin's disease is triggered by a combination of environmental and genetic factors along with a susceptible immune system. The exact triggers, however, are unknown.

Hodgkin's disease occurs most often in people between the ages of 15 - 40, (especially in the 20s), and in people over age 55. About 10 - 15% of Hodgkin’s disease cases are diagnosed in children and teenagers.

Hodgkin's disease is slightly more common among males than females. Women who get Hodgkin's disease appear to have a slightly lower risk for relapse after treatment than men.

Infectious mononucleosis (“mono”), which is caused by the Epstein-Barr virus (EBV), appears to increase the risk for Hodgkin’s disease. Research suggests that the virus activates some pathway within the lymphocyte cell that leads to cell proliferation. However, only 1 in 1,000 patients with mononucleosis develops Hodgkin's disease. The Epstein-Barr virus itself is present in 90% of the population and, in the great majority of these cases, causes a mild infection or none at all. Very few people who have had mononucleosis go on to develop HD. Other factors must be present to trigger the malignancy.

Hodgkin's disease runs in families in about 5% of cases. Siblings have three times more risk than the general population.

Symptoms

The onset of Hodgkin's disease symptoms is highest during late winter months, with lymph node enlargement usually being the first sign. Lymph nodes may be enlarged in the following regions:

The most common first sign of Hodgkin's disease is painless enlargement of one or more lymph nodes above the diaphragm, most often those in the neck, chest, or armpits.
Enlarged lymph nodes are often detected in the chest cavity between the lungs (the mediastinum), particularly in younger patients.
Only about 15% of cases occur exclusively below the diaphragm.

Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site.

If it spreads below the diaphragm, it usually reaches the spleen first; the disease may then spread to the liver and bone marrow.
If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs.

Symptoms in or around the Lymph Nodes. Occasionally, patients may have a cough or chest pain if the disease is located in the middle of the chest, but usually the enlarged nodes produce no symptoms. Sometimes patients experience pain in the diseased lymph nodes after drinking alcohol.

Systemic (B) Symptoms. Between 20 - 40% of patients have systemic symptoms that affect the whole body rather than just the specific location of the disease. Some of systemic symptoms are referred to as B symptoms. Patients who have B symptoms have a more severe condition than asymptomatic patients with the same cancer stage or tumor location or size.

Systemic symptoms include:

Drenching night sweats and weight loss (B symptoms)
Fever -- may occur only at night in episodes that come and go (B symptoms)
Itching all over the body -- caused by the release of histamines, substances ordinarily triggered by an allergic response. In the case of Hodgkin's disease, histamine release is due to abnormalities in the immune system. Although itching is a systemic symptom, it is not usually considered a B symptom if other systemic symptoms are not also present.
Rash (late stages)

Many patients seek medical help for abnormally swollen lymph nodes (commonly referred to as “swollen glands”). Swollen glands can be caused by many conditions, most often infections, and are rarely serious.

Infections. In the great majority of cases, swollen glands are caused by an infection:

For example, although Hodgkin's often first appears in the neck, enlarged lymph nodes in that location are much more likely to be a sign of strep throat, or other throat infections.
Infectious mononucleosis (caused by the Epstein Barr virus) is a common cause of swollen lymph nodes in young people.
Recent travel, particularly to countries with a high incidence of tropical diseases, can trigger similar symptoms.
Other infections that cause similar symptoms include cat scratch fever, Lyme or other tick-borne disease, HIV, tularemia, tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, and hepatitis.

Lymph nodes play an important part in the body's defense against infection. Swelling might occur even if an infection is small or not apparent.

Non-Hodgkin's Lymphomas. Although both Hodgkin's disease and non-Hodgkin's lymphomas are malignancies of the lymph nodes, they can usually be distinguished by certain characteristics. It is extremely important to differentiate between Hodgkin's lymphomas and non-Hodgkin's lymphomas, since the treatments for these two conditions differ. In particular, a subtype of lymphoma called anaplastic large-cell lymphoma (ALCL) might be confused with Hodgkin’s disease under some circumstances. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas.]


Characteristics	Hodgkin's Disease	Non-Hodgkin's Lymphomas
Age and Prevalence	Average age is 27.7 with two age peaks, the major one between 15 - 24 with a lesser peak after age 55. It is less common than NHL.	Average age is about 67. It is more common than HD.
Location	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. However, in HD it is also more likely to appear in the chest cavity between the lungs (the mediastinum), particularly in younger patients. Only about 15 - 20% of cases are found in areas below the diaphragm. Disease occurs outside the nodes in about 4% of cases.	In both malignancies, the disease occurs most often in lymph nodes above the collarbone. In NHL, however, it is also more likely to appear in the nodes in the abdomen (called the mesenteric nodes). The disease occurs in the chest cavity in less than 40% of patients. (An exception, lymphoblastic lymphoma, which is seen most often in young people, is likely to first appear in the chest.) Disease occurs outside the nodes in about 23% of patients. Slow-growing lymphomas are common in the liver and bone marrow.
Symptoms	More likely than NHL (40%) to have systemic symptoms (such as fever and night sweats) at the time of diagnosis.	Less likely to have systemic symptoms (27%) at the time of diagnosis.
Progression	Less likely than NHL to be diagnosed in stage IV (10%). Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site. If it spreads below the diaphragm, it usually reaches the spleen first; the disease then may spread to the liver and bone marrow. If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs.	More likely than HD to be diagnosed in stage IV (36%). The lymphomas are less predictable in their course than Hodgkin's disease and they are more apt to spread.

Other Cancers or Serious Conditions in the Lymphatic System. Other cancers that can travel to lymph nodes include breast cancer and leukemia.

Very serious causes of enlarged lymph nodes include disorders of the lymph system that include Castleman's disease, lymphomatoid granulomatosis, and angioimmunoblastic lymphadenopathy. These lymph system disorders, although noncancerous, involve abnormal lymph cells. They are often fatal and can be very difficult to distinguish from lymphomas. Many of the other serious illnesses involving diseased lymph nodes develop simultaneously at multiple sites, while Hodgkin's nearly always starts at one location before spreading to nearby nodes. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas or Report #86: Acute lymphocytic leukemia.]

Exposure to Chemicals. Exposure to industrial chemicals or certain medications, such as phenytoin (Dilantin), may cause enlarged nodes. In addition, other drugs, such as cephalosporins, penicillins, or sulfonamides, can cause enlarged nodes and other symptoms, including fever and rash that may resemble Hodgkin's disease.

Diagnosis

The doctor will take a medical history and perform a physical examination. If these simple procedures point to Hodgkin's disease, a number of additional tests may be needed to either rule out other diseases or confirm HD and determine the extent of the cancer.

The doctor will examine not only the affected lymph nodes but also the surrounding tissues and other lymph node areas for signs of infection, skin injuries, or tumors. The consistency of the node is sometimes indicative of certain conditions. For example, a stony, hard node is often a sign of cancer, usually one that has metastasized (spread to another part of the body). A firm, rubbery node may indicate lymphoma (including Hodgkin's). Soft nodes suggest infection or inflammatory conditions.

Blood tests are performed to measure white and red blood cells, blood protein levels, the uric acid level, blood proteins, and the liver's function. Another blood test is the erythrocyte sedimentation rate (ESR), which is sometimes elevated in Hodgkin's disease (although it is not specific for this condition).

Click the icon to see an image of the formed elements of blood.

Chest X-Ray. A chest x-ray shows the lymph nodes in the chest and neck area, where Hodgkin's disease usually starts. It a useful step for detection of enlarged lymph nodes.

Click the icon to see an image of an x-ray machine.

Computer Tomography. Computed tomography (CT) scans are more accurate than x-rays. They can detect abnormalities in the chest and neck area, as well as revealing the extent of the cancer and whether it has spread. CT scans are used to evaluate symptoms and help diagnose lymphomas, help with staging of the disease, monitor response to treatment, and evaluate when the symptoms occur. A CT scan is also often used in detecting lymphomas in the abdominal and pelvic areas, the brain, and chest area.

Click the icon to see an image of a CT machine.

Positron Emission Tomography (PET). PET scans combined with CT scans can help doctors clarify the location of the cancer. PET scans can also provide information on whether or not an enlarged lymph node is benign or cancerous and are more accurate than CT scans or other imaging tests for staging lymphomas. PET scans may also help doctors determine how well a patient has responded to treatment, if any residual cancer exists, and if a patient has achieved remission.

A biopsy of the suspicious lymph node is the most definitive way to diagnose Hodgkin's disease. A biopsy has risks, and should be performed only by a qualified and experienced doctor. Sometimes a doctor may choose to wait and observe the involved lymph nodes, which will usually regress on their own if a temporary infection is causing the enlargement. However, some lymphomas may regress and appear to be benign, only to reappear at a later time.

The Procedure. During a biopsy, the doctor usually removes the node and checks the surrounding areas. The tissue in the node is then examined for signs of infection and blood cell or other abnormalities. Biopsies of bone marrow may also be performed in patients with existing Hodgkin's disease if the doctor suspects that it may have spread to the marrow.

Biologic markers, called biomarkers for short, are high levels of substances that are released by tumors and indicate the level of cancer activity. Biomarkers can be found in sputum, blood, and tissue samples. Biomarkers can be enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some under investigation include:

CD44 is a molecule that binds to the surface of cells and may be involved in metastasis. High levels of this molecule may suggest a more aggressive disease.
Interleukin (IL) 10 is another immune factor that may indicate a poor outlook when it occurs in high levels.

Outlook

Hodgkin’s disease is considered one of the most curable forms of cancer, especially if it is diagnosed and treated early. Unlike other cancers, Hodgkin's disease is even potentially curable in late stages. About 85% of patients with Hodgkin’s disease survive at least 5 years after cancer treatment. Five-year survival rates for patients diagnosed with stage I or II Hodgkin’s disease are 90 - 95%. Patients who survive 15 years after treatment are more likely to later die from other causes than Hodgkin’s disease.

Survival rates are poorest for:

Those who relapse within a year of treatment
Patients who do not respond to the first-line therapy and have signs of disease progression

The good news about Hodgkin's disease is that treatment can cure the disease. The bad news is that survivors face a higher than average risk for long-term complications of these treatments, some very serious.

Many patients may experience chronic fatigue that could persist for years. One study indicated that aerobic exercise may significantly improve fatigue; in doing so it could have a positive effect on mood as well.

The most serious complications are secondary cancers and heart disease, which occur over the 2 - 3 decades following treatments. Secondary cancers include non-Hodgkin's lymphoma, leukemia, melanoma, stomach and lung cancers, and breast and uterine cancers. Heart disease complications include coronary artery disease, stroke, heart valve problems, and cardiomyopathy (weakening of the heart muscle). Thyroid disorders are also a potential complication. Combinations of radiation and chemotherapies are especially associated with these problems.

A 2006 study in the New England Journal of Medicine evaluated the long-term health status of adult survivors of various childhood cancers. The study found that, 30 years after treatment, patients with Hodgkin’s disease had among the highest risk of developing serious health problems. Female survivors had a significantly greater risk than male survivors. In particular, women who received chest radiation are at very high risk for developing breast cancer. Still, in a 2000 study, 20 years after treatment, 90% of patients who had survived treatments were still living.

Patients with Hodgkin’s disease should get a written record of the treatments they received as children, and the potential risks of these treatments. These records can help the doctors who later oversee their care monitor for potential health problems. Survivors of Hodgkin’s disease should receive regular screening tests for cancer and heart disease. They may need to get these tests at a younger age than most patients. In particular, patients who were treated with chest radiation should get blood tests every 5 years to measure their cholesterol levels. Female patients who received chest radiation should get early and frequent mammograms.

Although HD is highly curable, it can have many psychologic consequences. Depression and anxiety are common in survivors, particularly those who suffer additional medical conditions. Fatigue persists in the majority of patients for years. Still, many survivors have an excellent quality of life.

Staging and Treatment Guidelines

Multiple treatment approaches are available for patients with Hodgkin's disease at nearly every stage, often resulting in similar rates of cure. Ultimately, the choice of treatment is based on a consideration of various prognostic factors as well as treatment side effects, both short and long term. Treatment decisions are individualized, and patients should discuss the pros and cons of various approaches with their doctors.

Staging the disease according to how far the cancer has spread (I through IV) is a primary method for determining both treatment options and prognosis. There are two levels of staging: Clinical staging and pathological staging.

Clinical stages are determined by conducting a thorough examination, which may include blood tests and different kinds of x-rays.
Pathologic staging is conducted after a laparotomy and biopsy of the tissue to help determine treatment options. It involves a much more detailed examination, but is not required as often as in the past for making treatment decisions.

In general, the prognosis according to stage is as follows:

If the disease is treated in stages I or II, the cure rates are as high as 90%. (Slightly more than half of all patients are diagnosed in these stages.)
Patients in stages III or IV are usually diagnosed with advanced Hodgkin's disease. (Even in such stages, survival at 5 years can be as high as 85%.)

The staging system can be further refined according to other features or factors that indicate a more or less severe condition and can help determine whether treatments should be more or less aggressive.

Presence or Absence of B Symptoms. For example, stages I through III are further categorized as either A or B according to whether certain widespread symptoms are absent (A) or present (B). The presence of B symptoms increases the risk of relapse.

The patient is classified as B if they have unexplained weight loss of more than 10% within 6 months, unexplained fever, and drenching night sweats. Fever and weight loss are the most important indications of B symptoms; night sweats alone do not always mean that such symptoms are present. Itching by itself is not considered a reliable B symptom.
If the patient has none of these symptoms, the disease is considered at A, which is less severe than the B form at any stage.
Another letter used to further refine a stage is E, which indicates that the malignancy is still local but has gone beyond the lymph node into surrounding tissue.

Indicators for Aggressive Treatments. Certain factors are indicators of a more serious case at any stage and the need for aggressive treatment:

The malignancy is "bulky" (a large mass)
Blood tests show high levels of erythrocyte sedimentation rates
Multiple tumors in the spleen
Greater involvement in the abdomen

Even if a patient has stage II disease, the presence of a bulky tumor or multiple tumors in the spleen indicates the patient may be treated as if they had advanced Hodgkin's disease.

Cell Types. The cell type of Hodgkin's disease may also influence treatment. For example, those with mixed cellularity type might require more aggressive therapy in certain cases than those with a slower-growing form, such as lymphocyte-predominant Hodgkin's disease (LPHD). In fact, some studies suggest that LPHD is the mildest form of Hodgkin's disease and that patients with LPHD are more likely to die of treatment-related disease than from Hodgkin's itself. Some experts are investigating the role of limiting radiation doses in such patients, although the most optimal approach is not yet known.

Other Prognostic Risk Factors. The International Prognostic Factors Project on Advanced Hodgkin’s Disease has developed seven factors that help determine which patients with advanced Hodgkin's disease would benefit from more or less aggressive chemotherapy. They are also useful to help determine success in patients with relapsed or persistent HD who are undergoing stem cell transplantation. The score is determined by the number of yes answers to the following questions. The more yes answers, the more likely the patient needs to be treated aggressively:

Is the patient male?
Is the patient older than 45?
Does the patient have stage IV disease?
Does the patient have blood tests showing lower than normal albumin levels? (Albumin is a protein found throughout the body.)
Does the patient have abnormally low hemoglobin levels? (Hemoglobin is the oxygen-carrying compound in red blood cells, so low levels suggest anemia.)
Does the patient have an abnormally high white blood cell count (15,000 or more)?
Does the patient have abnormally low levels of lymphocytes?

To avoid putting patients through unnecessary treatments that may actually be as or even more lethal than the disease itself over time, doctors are attempting to identify more specifically those patients who would or would not benefit from aggressive therapy.

Preventing Infection. Both the disease and some of the treatments suppress the immune system, increasing the risk for infections. Widespread, life-threatening infection is a particular danger if the spleen has been removed and both radiation and chemotherapy are administered. A week before any treatment, patients are often vaccinated against three bacteria: pneumococcus, meningococci, and Haemophilus influenza.

Measures for Infertility. People who wish to have children should discuss the possibility for receiving treatments that may lessen the risk for infertility. Examples include the following:

Men with Hodgkin's disease may want to consider sperm freezing and assisted reproductive techniques. One encouraging study on male survivors of childhood Hodgkin's disease, reported that although treatments had reduced their sperm count and quality, the actual genetic material was healthy. Such men, then, would still be good candidates for assisted reproductive techniques.
Women should ask their doctors about the possibility for preserving fertility by taking hormonal drugs called GnRH analogs before and during chemotherapy.

[For more information on fertility preservation treatments, see In-Depth Report #67: Male infertility and In-Depth Report #22: Female infertility.]

Considerations During Pregnancy. Women who are pregnant need special preparation and treatments.

Periodic examination for recurrent Hodgkin's disease is necessary for years after treatment, since relapse is not uncommon, even after treatment for early stages, and can occur a decade or more after treatment. Chest x-rays and CT scans of the abdomen are useful for detecting relapsed disease. Relapse is more likely to occur in early-stage disease, probably because limited radiation normally used in such cases did not destroy all malignancies. Patients who had large tumors in the chest are also at higher risk for recurrence. Patients also need to be monitored for long-term effects of the treatments themselves. Conditions to watch for include inflammation in the lungs and thyroid disease from radiation in the chest and heart disease and cancers from combined treatments, chemotherapy (particularly the use of MOPP), and blood stem cell transplantation.

Because Hodgkin's disease often occurs in young adults, treatment for pregnant women is of particular concern. Therapy must be effective enough to protect the mother without hurting the fetus. Treatment choice must be individualized, taking into consideration the mother's wishes, the severity and pace of the disease, and the length of the remaining pregnancy. The treatment plan may need to be changed as the pregnancy progresses.

Early in the Term. Unfortunately, an abortion may sometimes be the most prudent approach if the disease occurs in the first trimester. Chemotherapy is rarely used during that period, because it poses a risk for birth defects. Deciding on a course of action when Hodgkin's disease occurs in the first trimester is very difficult and emotionally wrenching. Prospective parents should not be shy about consulting with more than one doctor if they are uncertain about how to proceed.

Later in the Term. If the disease develops in the second half of the pregnancy, it may be possible to postpone therapy until after an early induced delivery. Alternatively, some evidence suggests that chemotherapy in pregnant women after the first trimester may be beneficial without harming the fetus. If full-dose standard chemotherapy is not deemed possible, vinblastine alone may be beneficial; this drug is not usually associated with fetal abnormalities in the second half of pregnancy.

Steroids may also be used late in the pregnancy both because of their antitumor effect and their effect in hastening fetal lung maturity. As an alternative, a short course of radiation (with extensive shielding of the fetus) can sometimes be considered prior to delivery if the mother is experiencing lung problems because of a rapidly enlarging mass in the chest. Combination chemotherapy may also be safe in the second half of pregnancy.

In one study, the 20-year survival rate of pregnant women with Hodgkin's disease was no different from that of nonpregnant women matched for similar stage of disease and age at diagnosis.

Treatment Options by Stage

Treatment is guided by the stage of the disease and usually relies on the location and extent of the disease. Treatment may vary within a stage, depending on whether it is categorized as either A or B. (Systemic symptoms are absent in "A" and present in "B.”) The presence of B symptoms increases the risk of relapse, and so may require more aggressive treatments for that stage.

Early Stages (I or II). For disease in stages I or II, the following treatments may be used:

Treatment in Adults. Doctors usually recommend radiation first for adults with HD. It provides excellent remission rates, although studies have reported a number of serious long-term complications in some patients. Selected patients in early stages may also be candidates for radiation limited only to areas above the diaphragm (called the mantle field), which can also have excellent results although still pose a considerable risk for late serious complications.
Treatment in Children. Chemotherapy and low-dose radiation is the standard treatment for most children and adolescents who have not reached full growth. Specific chemotherapy combinations have been developed to reduce the risks for infertility, leukemia, and toxic effects on the heart and lungs. Researchers are studying the use of chemotherapy alone in this group.

Later Stages. For stage III disease, chemotherapy, often with radiation, is a standard treatment. For stage IV disease, chemotherapy alone is generally recommended. The latest chemotherapy regimens are achieving survival rates that reach 90%.

Relapse. Relapse after treatment occurs in 20 - 35% of patients. Treatments for relapse include chemotherapy, radiation, and bone marrow or blood stem cell transplantation. Many patients respond favorably to such treatments, although another relapse is still possible.

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

Disease is limited to a single node region (I) or has involved one neighboring area or a single nearby organ (IE). The standard treatment for stage I disease is usually radiation for adult patients who have determined the stage using pathologic staging with laparotomy. Chemotherapy with low-dose radiation is now the standard approach for children and adolescents. Cure rates can be greater than 90%.

Stage IA. Treatments depend on location. For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:

Radiation therapy to the mantle field (chest, neck, and arm pits) and to the lymph nodes in the upper abdomen and spleen
Radiation therapy to a mantle field in certain patients -- best candidates are females with nodular sclerosis or lymphocyte predominant cell types, who are no older than 40 years, have no "B" symptoms, and have erythrocyte sedimentation rate (ESR) levels less than 50
Radiation therapy to a mantle field, the lymph nodes in the upper abdomen, and the spleen (subtotal node irradiation)
Chemotherapy alone is under investigation

If the malignancy is bulky, above the diaphragm, and involves a large part of the chest, chemotherapy plus radiation therapy is commonly used.

If the malignancy is below the diaphragm, treatment includes chemotherapy with or without radiation. Radiation therapy may be directed to the lymph nodes in the upper abdomen and pelvis, and sometimes the spleen or groin. Total nodal irradiation is an option which includes these regions plus the mantle field.

Stage IB. Treatments depend on location. For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:

Chemotherapy plus radiation therapy to a mantle field (in patients who have severe symptoms and did not undergo laparotomy to determine the extent of the disease below the diaphragm)
Radiation therapy to the mantle field and to the lymph nodes in the upper abdomen is sometimes considered, but relapse rate can be high if significant B symptoms are present
Chemotherapy alone under investigation for children

If the malignancy is bulky, above the diaphragm, and involves a large part of the chest, chemotherapy plus radiation therapy is commonly used.

If the malignancy is below the diaphragm, treatment includes chemotherapy with or without radiation to the upper abdomen and pelvis, to the areas that contain cancer, or to the spleen. Total nodal irradiation or radiation to lymph nodes in the upper abdomen and pelvis is another option.

Disease is limited to two or more lymph nodes on the same side of the diaphragm (II) or involvement of a single neighboring organ or area and one or more nearby lymph nodes; other lymph nodes on the same side of the diaphragm may be involved (IIE).

There are few differences between treatments for stage IIA and IIB, and the approach for both depends on the extent and location of the disease:

Non-bulky disease:

Radiation alone for adult and possibly adolescent (especially male) patients
Chemotherapy with low-dose radiation is used for children

For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:

Radiation therapy to a mantle field and to the lymph nodes in the upper abdomen
Radiation therapy to a mantle field only (See Stage I Hodgkin's Disease section above)

Chemotherapy alone or with radiation therapy (combined modality) is being evaluated for those with non-bulky stage IIA. Also under investigation is radiation therapy to a mantle field only in patients with lymphocyte predominant cell types, who are no older than 40 years.

If the malignancy is above the diaphragm and does involve a large part of the chest, chemotherapy plus radiation therapy to a mantle field is the common approach.

If the malignancy is below the diaphragm, treatment includes chemotherapy with or without radiation to the upper abdomen and pelvis, and possibly the spleen. Total nodal irradiation is another option.

Disease is in lymph nodes on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an associated organ or site outside the lymph node (IIIE), by involvement of the spleen (IIIS), or by both (IIIE+S). In addition, stage III may be further categorized by the extent of its spread into the spleen or where it has spread in the abdominal area. Survival rates in some cases can be as high as 90%.

Stage IIIA. Chemotherapy is the most common treatment approach for most adults and children. Radiation may be added under certain circumstances, especially to provide localized treatment of bulky areas. (Radiation does not appear to offer any survival advantage for patients whose disease is in complete remission after chemotherapy.)

For a malignancy above the diaphragm, which does not involve a large part of the chest, the following may be used:

Chemotherapy alone
Chemotherapy with radiation therapy (combined modality)
Total or subtotal nodal radiation therapy alone -- for adults if disease is only in the upper abdomen and fewer than five nodes in the spleen are affected

If the malignancy involves a large part of the chest, the following may be used:

Standard chemotherapy alone
Chemotherapy plus radiation therapy (combined modality)
Investigative treatments

Stage IIIB. Chemotherapy alone is the standard treatment for most adults and children. Radiation is often added to treat areas of bulky tumor.

Disease has spread to organs outside the lymph system, such as liver, lung, or bone marrow. Even in this population, high long-term survival rates of over 85% are possible, including in children.

Treatment may include:

Chemotherapy alone
Chemotherapy with limited radiation to places of bulky disease
A clinical trial of investigational chemotherapy regimens or of stem-cell transplantation

Click the icon to see an image of liver involvement in Hodgkin's disease.

When disease recurs or persists after initial treatment either in the same area or in another part of the body, the next round of therapy depends on where the disease returns and the previous treatment used.

If the previous treatment was radiation therapy without chemotherapy, salvage chemotherapy is the usual choice.
If the patient was previously treated with chemotherapy, the choice may be radiation therapy to the lymph nodes with or without salvage chemotherapy.
In some patients, if the disease has persisted or if relapse has occurred after chemotherapy with or without radiation, high-dose chemotherapy and stem cell transplantation may be given.

Radiation Treatments

High-dose radiation therapy, which shrinks the tumors, has been used for more than 50 years for treating Hodgkin's disease. High-dose radiation is generally reserved for adults. Radiation treatments are highly toxic for children and appear to add little benefit. In such young age groups radiation is mostly used if there are large areas of disease in the chest; otherwise, chemotherapy with possibly low-dose radiation is the best option with excellent survival rates.

Radiation is directed to specific areas depending on the location of the disease:

If HD is above the diaphragm, “extended field radiation” is delivered to the neck, chest, and under arms (called the mantle field). Extended-field radiation is sometimes expanded to include lymph nodes in the upper abdomen.
If cancer is below the diaphragm, an "inverted Y" field is sometimes used, in which radiation is directed at lymph nodes in the upper abdomen, spleen, and pelvis.
Inverted Y-field radiation therapy combined with mantle-field radiation is called “total nodal radiation.”
"Involved field radiation" targets only lymph node regions that are known to have cancer. By contrast, extended-field radiation targets lymph node regions with cancer as well as adjacent, uninvolved lymph node regions. Involved-field radiation is usually given after several rounds of chemotherapy.

A 2006 study indicated that radiation therapy alone, without chemotherapy, may help older patients with early-stage Hodgkin’s disease. If chemotherapy is given, another 2006 study suggested that involved-field is a better option than extended-field radiation for elderly adults with early-stage unfavorable Hodgkin’s lymphoma.

In general, recent research suggests that extended-field radiation adds little survival advantage and carries a greater risk of serious side effects. Involved-field radiation is now becoming the preferred method. Some researchers recommend that involved-field radiation therapy plus chemotherapy should become the standard treatment for patients with early-stage Hodgkin’s disease who have a good prognosis. More research is needed before standard practice guidelines can be implemented.

It is very important that radiation treatments cover the entire diseased area and that the radiation therapy be powerful enough to destroy the malignant cells' capacity to grow and divide. Unfortunately, this means that normal cells are also affected, which can cause serious side effects. Different approaches may be used to prevent complications.

Devices called planning simulators allow doctors to plan x-ray treatments that accurately conform to the patient's anatomy so that protective shields can be created to precisely protect the regions outside the treatment areas.
Long-term complications generally occur at higher radiation doses (over 35 Gy). Investigators are studying the doses as low as 20 Gy (in children). Studies indicate that radiation alone in doses under 35 Gy can control the disease as well as higher doses in most stage I and II patients, although some patients may require more aggressive treatment.
To protect ovaries, a technique called ovarian transposition may sometimes be performed. The procedure uses a laparoscope (a thin tube containing tiny instruments and cameras) that is introduced through a small incision. The doctor uses the laparoscope to move the ovaries out of the range of areas being treated with radiation.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Infections. Infections may be a particular problem with radiation combined with chemotherapy. All patients should be vaccinated against pneumonia and influenza.

Inflammation in the Lungs. With carefully conducted therapy, the risks for lung complications are small. Lung impairment may not even be evident, and the lungs usually recover after 2 - 3 years.

Click the icon to see an image of the lungs.

Infertility. Radiation therapy to the pelvic area can adversely affect later fertility in women and men. Such negative effects may be worse in women; sperm usually recover within 5 years.

Heart Disease and Stroke. Radiation is associated with a future risk of heart disease, which includes atherosclerosis (hardening of the arteries) and diseases of the heart valves. Lower doses pose less risk. Recent research suggests that adults who survived childhood Hodgkin’s disease have a four times higher risk of having a stroke than healthy patients.

Fatigue. Fatigue is significant and chronic in many survivors. It is more highly associated with intensive chemotherapy, but it also may be a late response to radiation treatment.

Secondary Cancers. Second cancers (such as breast, stomach, lung, melanoma) may develop later in areas within or at the edge of the radiation area. Thyroid, respiratory tract, and digestive tract secondary cancers may affect patients who were treated as children. The risks are twice as high with treatments that are combined with chemotherapy.

Lung cancer in survivors is highly associated with smoking after treatment, and no survivor should smoke. The risk for breast cancer increases significantly in young women after treatment, particularly with high radiation doses and combined chemotherapy and radiation. The risk can persist for 25 years or more after radiotherapy, and lifetime monitoring (including frequent mammograms) is essential.

Thyroid Disorders. Hypothyroidism (underactive thyroid) occurs in a number of patients treated with radiation treatments. There is also a 5% chance for hyperthyroidism (overactive thyroid).

Click the icon to see an image of hypothyroidism.

Click the icon to see an image of hyperthyroidism.

Impaired Growth in Children. Children and adolescents are at special risk for impaired bone growth.

Chemotherapy

Chemotherapy uses drugs to kill cancer cells. The drugs are called cytotoxic medications. Chemotherapy is referred to as body-wide, or systemic, therapy because the drugs travel throughout the entire body.

Cytotoxic drugs may be taken by mouth or given by injection. Treatment may be administered at a medical center, doctor's office, or even a patient's home. Some patients receiving chemotherapy may need to remain in the hospital for several days so the effects of the drug can be monitored.

Patients may receive 4 - 8 cycles of chemotherapy, depending on the stage. A cycle is usually 28 days and consists of several doses of drug administration followed by a period of rest.

The standard chemotherapy regimens for Hodgkin’s disease are ABVD and Stanford V.

ABVD consists of a 4-drug combination:

Doxorubicin (Adriamycin)
Bleomycin
Vinblastine
Dacarbazine

Stanford V consists of a 7-drug combination:

Doxorubicin (Adriamycin)
Mechlorethamine (nitrogen mustard)
Vincristine
Vinblastine
Bleomycin
Etoposide
Prednisone

BEACOPP (bleomycin, etoposide, Adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) is a chemotherapy regimen reserved for high-risk patients. This regimen is proving to be extremely effective, particularly in advanced stages, with studies reporting remission rates of over 95% in patients with advanced Hodgkin's. However, this regimen also increases the risk for developing secondary cancers such as leukemia. Patients who are treated with BEACOPP should receive long-term follow-up care to monitor for side effects from this therapy.

Side effects and complications of any chemotherapeutic regimen are common, are more severe with higher doses, and increase over the course of treatment, though some trials suggest that toxicities can be reduced by administering the drugs for shorter duration without loss of cancer-killing effects.

Common Side Effects. Common side effects include the following:

Nausea and vomiting -- drugs known as serotonin antagonists, including ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs.
Diarrhea
Hair loss
Weight loss
Depression

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days a month.

Serious Side Effects. Serious side effects can also occur and may vary depending on the specific drugs used. They include:

Neutropenia is a severe drop in white blood cells. Neutropenia increases the chance for infection from suppression of the immune system and is a potentially life-threatening condition. Drugs known as granulocyte colony stimulating factor (G-CSF) are used to help boost white blood cell count. These drugs, which include filgrastim (Neupogen) and pegfilgrastim (Neulasta) can help lessen the risk for neutropenia occurrence and, if neutropenia does occur, to reduce its length and severity.
Anemia is a lack of red blood cells. Erythropoietin stimulates red blood cell (hemoglobin) production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). In 2007, the FDA released strict dosing guidelines for these drugs. In patients with cancer, they should be used to only treat anemia associated with chemotherapy and to increase hemoglobin levels to no more than 12 g/dL. Treatment should stop as soon as chemotherapy is complete. These drugs may not be safe or appropriate for all patients.
Infection. Patients must take precautions against infections (see "Infection Prevention" in Transplant section).
Liver and kidney damage
Abnormal blood clotting (thrombocytopenia)
Allergic reaction

Long-Term Complications.

Fatigue and general aches and pains are called somatic symptoms. Fatigue is especially common after chemotherapy and can even last for years.
Many women stop menstruating after chemotherapy. The risk for infertility is highest for women with advanced stage Hodgkin’s disease who are treated after age 30. Studies indicate that the risk for infertility is higher with BEACOPP than with ABVD. Researchers are studying whether taking oral contraceptives during chemotherapy can reduce the risk.
Bone thinning (osteoporosis) may be related to steroid treatments such as prednisone.
Heart failure may occur with the use of anthracyclines (such as doxorubicin).
Bleomycin (Blenoxane), an antibiotic, is particularly toxic to the lungs. Vinblastine may also pose a risk when used in combination with radiation therapy.

In general, these serious late side effects are dependent on the cumulative drug dose and rate of administration.

Regimens. Chemotherapy (usually ABVD) plus radiation, referred to as combined modality, is a common treatment approach for patients with more advanced-stage disease and for those who have early-stage bulky (large mass) disease.

Chemotherapy with low-dose radiation is being used in children with excellent results, even for late stage cancer. In one study, 82% of the children were still disease free at 5 years. Some chemotherapy drugs or high doses of radiation may be more deleterious to a boy's future fertility than to a girl's. A gender-specific combined regimen for pediatric Hodgkin's reduces the amount of radiation given to boys and also substitutes etoposide for procarbazine in the chemotherapy mixture (procarbazine, vincristine, prednisone, and doxorubicin).

Side Effects and Long-Term Complications. Side effects of combination treatments can be very serious. Examples include:

Combined modality poses a higher risk for secondary cancers than the use or radiation or chemotherapy alone. They include breast, lung, thyroid, melanoma, and gastrointestinal cancers, which usually develop in near or in the areas treated with radiation. Of note, the risk for breast cancer is lower when chemotherapies using alkylated drugs or radiation treatments damage the ovaries, suggesting that hormone stimulation plays a role in this higher risk. Newer drugs used in combined modalities may reduce the risk, at least for breast cancer.
ABVD and other regimens containing bleomycin increase the risk for severe effects on the lungs when used before or after mantle-field radiation. EVA (etoposide, vinblastine, and doxorubicin) is considered to be an effective substitute in patients with lung disease for whom bleomycin and radiation present an unacceptable risk.

Transplantation

Patients with relapsed or progressive HD are often treated with high-dose chemotherapy followed by stem cell transplantation procedures. (Transplantation does not appear to offer an advantage compared to standard chemotherapy as initial treatment for patients with high-risk advanced HD.)

This treatment involves removal and replacement of stem cells, which are produced in the bone marrow. This allows the patient to receive high-dose chemotherapy without destroying these important cells. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments harm growing cells as well as cancer cells, and so the healthy stem cells must be replaced by transplanting them.

For Hodgkin’s disease, the most common type of transplant is an autologous procedure, using the patient’s own cells. An allogeneic transplant, using cells from a donor, is more risky for patients with Hodgkin’s disease and is generally used only when an autologous transplant has failed. (This section provides information pertinent to autologous procedures. Detailed information on allogeneic transplants, including such complications as graft-versus-host-disease, can be found in In-Depth Report #84: Non-Hodgkin’s Lymphoma.)

Stem cells must first be collected in one of the following ways:

Directly from blood (peripheral blood stem cell transplantation)
From bone marrow (bone marrow transplantation)

Click the icon to see an illustrated series detailing bone marrow transplant surgery.

Stem cells are collected several weeks before the procedure. They are frozen and stored while the patient undergoes high-dose chemotherapy. Some patients receive high-dose whole body radiation therapy along with chemotherapy.

After the patient completes the pre-transplant therapy, the frozen cells are thawed and then infused into the patient. Within a few weeks, these cells start to generate new white blood cells and then new red blood cells.

The risk for infection greatest during the first 6 weeks following the transplant. During this period, a patient usually remains in isolation and receives antibiotics and intravenous nutrition. It takes 6 - 12 months post-transplant for a patient’s immune system to fully recover.

Many patients develop severe herpes zoster virus infections (shingles) or have a recurrence of herpes simplex virus infections (cold sores and genital herpes). Pneumonia, cytomegalovirus, aspergillus (a type of fungus), and Pneumocystis carinii (a protozoan) are among the most important life-threatening infections.

It is very important that patients take precautions to avoid infections. Guidelines for infection prevention include:

Discuss with your doctor what vaccinations you need and when you should get them.
Avoid crowds, especially during cold and flu season.
Be diligent about handwashing, and make sure that visitors wash their hands.
Avoid eating raw fruits and vegetables -- food should be well cooked. Do not eat foods purchased at salad bars or buffets. In the first few months after the transplant, be sure to eat protein-rich foods to help restore muscle mass and repair cell damage caused by chemotherapy and radiation.
Boil tap water before drinking it.
Dental hygiene is very important, including daily brushing and flossing. Schedule regular visits with your dentist.
Do not sleep with pets. Avoid contact with pets’ excrement.
Avoid fresh flowers and plants as they may carry mold. Do not garden.
Swimming may increase exposure to infection. If you swim, do not submerge your face in water. Do not use hot tubs.
Report to your doctor any symptoms of fever, chills, cough, difficulty breathing, rash or changes in skin, and severe diarrhea or vomiting. Fever is one of the first signs of infection.
Report to your ophthalmologist any signs of eye discharge or changes in vision. Patients who undergo radiation or who are on long-term steroid therapy have an increased risk for cataracts.

Common side effects of stem cell transplants include nausea, vomiting, fatigue, mouth sores, and loss of appetite.

The procedures themselves are fairly dangerous and carry a small risk for death. When it was first used, transplantation procedures had 10 - 25% morality rates. Now mortality rates are below 5%.

There is a small long-term risk for leukemia after transplantation in young people. Chemotherapy itself increases the risk of secondary cancers. Recent studies suggest that transplantation after chemotherapy does not add any additional risks. In addition, use of newer chemotherapeutic drugs may not pose as high a danger as older treatments.

Other serious potential complications include:

Bleeding because of reduced platelets (highest risk within the first 4 weeks); blood transfusions may be required
Infertility
Organ complications to the liver, heart, kidney, or lungs
Failure of the transplant
Muscle problems including stiffness, cramps, and joint pain
Frequent urination and bladder control problems
Older patients should be screened for osteoporosis (bone thinning) and hypothyroidism (underactive thyroid)

Immunotherapy

Investigational approaches to Hodgkin's disease include immunotherapies, which are drugs that take advantage of the patients' own immune factors to attack the disease.

One important approach uses genetically designed immune factors called monoclonal antibodies (MAb) that recognize and attack specific molecules found on the surface of cells associated with HD.

Rituximab (Rituxan) was the first monoclonal antibody to be approved for any cancer. It is an unconjugated MAb that targets the CD-20 antigen, which is found on most B-cell lymphomas and normal mature B cells (although not stem cells). It is used in non-Hodgkin's lymphomas, but it may have benefits for some patients with Hodgkin's disease as well.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.lymphoma.org -- Lymphoma Research Foundation
www.leukemia.org -- Leukemia and Lymphoma Society
www.canceradvocacy.org -- National Coalition for Cancer Survivorship
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.marrow.org -- National Marrow Donor Program
www.oncolink.org -- Cancer information
www.lymphomainfo.net -- Lymphoma Information Network
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Fermé C, Eghbali H, Meerwaldt JH, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27.

Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10;25(5):571-8. Epub 2007 Jan 22.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hodgkin Disease / Lymphoma. V.1.2007.

Review Date:
1/21/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

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