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ASTHMA IN CHILDREN AND ADOLESCENTS

* Please note that most treatment modalities listed below are based on conventional medicine. PreventDisease.com does advocate the use of any pharmaceutical drug treatments. Long-term drug therapy is detrimental to human health. All drug information is for your reference only and readers are strongly encouraged to research healthier alternatives to any drug therapies listed.

WHAT IS ASTHMA?

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.

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.

Hyperreactive Response

In the hyperreactive response, smooth muscles in the airways constrict and narrow excessively in response to inhaled allergens or other irritants. It should be noted that the airways in everyone's lungs respond by constricting when exposed to allergens or irritants. There are major differences, however, in the hyperreactive response the 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 and the patients 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.

Inflammatory Response

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, to fill with fluid, and to produce a thick sticky mucus.
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.

WHAT CAUSES ASTHMA IN CHILDREN?

Factors Contributing to the Worldwide Increase of Asthma

Asthma is the most common chronic childhood illness. About half of all cases of asthma develop before the age of 10 and about 80% develop symptoms before age five. It has dramatically risen worldwide over the past decades, and experts are puzzling over the cause of this phenomenon.

The mechanisms that cause asthma are complex and vary among population groups and even individuals. Among the causes and factors that are suspects in asthma in children are the following:

Asthma in children is highly associated with allergies. Not all children with allergies have asthma, however, and not all cases of asthma can be explained by allergic response.
A family history of asthma also plays a major role in childhood asthma, although probably several genes are involved that make a child susceptible to environmental triggers, such as infections, dietary patterns, air pollution, and allergens.
Early lung development, particularly having smaller lungs, affects the chances for later asthma.
One 2000 study suggested that 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.
Some experts observe that 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.
Immunizations that prevent many childhood diseases may actually cause changes in immune factors that make people more susceptible to the allergic response.
Survival rates are now higher in low-birth-weight babies, who may be more susceptible to asthma.
Declining rates in nursing may be contributor. Breast milk contains important anti-inflammatory agents, such as omega-3 fatty acids, which might protect against asthma.
Some experts suggest that part of the dramatic rise in childhood asthma is not due to an increase in actual cases but to higher parental awareness of the disease and differences in diagnostic criteria. Nonetheless, related disorders (e.g., allergies, sinusitis, and ear infections) are also on the rise. This suggests that airborne or other environmental factors are at work, and, in fact, many experts believe asthma is actually underdiagnosed.

The Allergic Response

The allergic response plays a strong role in childhood asthma. (Its significance in adult-onset asthma is less clear.) About 75% to 80% of children with asthma have allergies, and studies indicate that the more indoor allergens a child is allergic to, the higher the risk for severe asthma. Asthma and nonseasonal or seasonal allergic rhinitis (hay fever or rose fever caused by pollen allergies) often coexist. However, although most people with asthma have a history of allergic rhinitis, only 1% to 20% of children with allergic rhinitis actually develop asthma. About 8% to 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 major predictor of asthma.

The allergic process, called atopy, and its connection to asthma is 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, powerful agents of 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, over-produce 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.

Remodeling and Causes of Persistent Asthma

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 these 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, overgrowth of cells in the smooth muscles that line the airways and scarring in the airways.

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

Genetic Factors

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 and they share certain genetic markers, but they are not always inherited together. Research, then, on the genetics of these conditions is confusing and difficult.

The Complex Role of Early Respiratory Infections

Early respiratory infections, particularly those caused by the respiratory syncytial virus (RSV), the adenovirus, and the organisms Chlamydia pneumoniae and Mycoplasma pneumoniae have been investigated for their role in asthma. Theories exist that suggest respiratory infections may play causal, worsening, or protective roles, depending on specific conditions.

Protective Role of Early Respiratory Infections. An important theory blames the dramatic increase in asthma on the elimination of childhood infections since immunization has become widespread. The basic theory is as follows:

In the past, when unvaccinated children developed these infections, the immune system released helper T-1 (TH1) white blood cells that stimulate the body's infection-fighters.
At the same time, it also suppresses production of the helper T-2 (TH2) cells, which are believed to be major contributors to the allergic response. [ See The Allergic Response above.]
In genetically susceptible children who are vaccinated, the TH2 cells become active (instead of the TH1 cells) and trigger the inflammatory events leading to asthma.
Of some support for this theory are studies reporting that being part of a large family or attending day care increases the risk for early infections but reduces the risk of childhood asthma.

It should strongly be pointed out that 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. Having a cold every now and then, however, may be protective.

Evidence now weighs against a significant causal role in asthma in children, except in certain cases. (Respiratory infections, however, may play an important role in adult-onset asthma). It should be noted, too, that even if respiratory viruses do not cause asthma in children, they can worsen asthma in children who have it. Rhinovirus, or the common cold virus, for example, has been reported to be the most common infectious agent associated with asthma attacks. In one study, it was associated with 61% of asthma exacerbations in children. Some research suggests that colds promote allergic inflammation and increase the intensity of airway responsiveness for weeks.

Other Contributing Medical Conditions

GERD. At least half of asthmatic patients 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.

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

Acid leaking from the lower esophagus in GERD stimulates the vagus nerves , which run through the gastrointestinal tract. These stimulated nerves in turn trigger the nearby airways in the lung to constrict, which causes 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 asthmatic 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 asthmatic patients.)

Treating GERD symptoms with anti-acid agents resolves asthma in some (but not all) patients who share both conditions. [ See , 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% and 30% of asthmatic patients develop true sinusitis. The presence of sinusitis, however, does not appear to increase the severity of asthma.

Parental Migraines and Childhood Asthma. Some studies have reported a link between childhood asthma and parental migraines, with one small 2000 study suggesting that children are about five times more likely to develop asthma if their parents have a history of migraines.

Exercise-Induced Asthma

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath. [ See Box Exercise-Induced Asthma (EIA)]

NSAIDs and Acetaminophen.

Aspirin-Induced Asthma. About 10% of asthmatic adults and some fewer children have aspirin-induced asthma (AIA). With this condition, asthma gets worse when patients take aspirin. 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.

Alternative Agents. Patients with aspirin-induced asthma (AIA) should avoid aspirin and most likely other non-steroidal anti-inflammatory agents (NSAIDs), including ibuprofen (Advil) and naproxen (Aleve). Acetaminophen (e.g., Tylenol) has been the traditional alternative for relief of minor pain. Unfortunately, recent evidence has muddied these recommendations. Some evidence has linked asthmatic responses to high consumption of acetaminophen-called paracetamol in Europe 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. Whether these results apply to people, including adults, who are aspirin sensitive is unknown, however. This is of particular concern, since acetaminophen is the pain reliever of choice in small children.

Experts hope that the new NSAIDs COX-2 inhibitors, which include celecoxib (Celebrex) and rofecoxib (Vioxx), may be safe for AIA. To date, studies are promising, although more research is needed to confirm their safety in people with this condition.

Nocturnal Asthma

Asthma occurs primarily at night (called nocturnal asthma) in as many as 75% of asthma patients. Attacks often occur between 2 and 4 AM. 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)

Description of EIA

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. (It should be noted that some people have both forms of asthma.) People who only have 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 agent, 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.
Some interesting evidence suggests that restricting dietary salt might help reduce EIA.

HOW SERIOUS IS ASTHMA IN CHILDREN?

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 five, because their airways are very narrow.

Degree of Severity

The severity of asthma is graded using the following categories: mild intermittent and mild, moderate, and severe persistent. [See Table National Asthma Education and Prevention Program: Classification of Asthma Severity.] It should be noted that a patient in any of these categories, even mild intermittent, can still experience a severe and even life-threatening attack. In fact, according to one report, 30% of asthma deaths occur in patients with mild asthma.

National Asthma Education and Prevention Program Classification of Asthma Severity

Classification	Symptoms	Nighttime Symptoms	Lung Function
Mild intermittent	Symptoms occur twice a week or less. No symptoms and normal lung function between attacks. Attacks are brief (from a few hours to a few days) and may vary in intensity.	Symptoms occur twice a month or less.	FEV 1 or PEF is 80% or more than predicted. PEF variability is less than 20%.
Mild Persistent	Symptoms occur more than twice a week but less than once a day. Asthma attacks may be severe enough to affect activity.	More than twice a month.	FEV 1 or PEF is 80% or more than predicted, PEF variability is between 20% and 30%.
Moderate Persistent	Daily symptoms and use of inhaled short-acting beta2-agonists. Symptoms twice a week or more and may last for days. Asthma attacks twice a week or more and may be severe enough to affect activity.	More than once a week.	FEV 1 or PEF is between 60% and 80% of predicted, PEF variability is more than 30%.
Severe Persistent	Continual symptoms. Limited physical activity. Frequent asthma attacks.	Frequent.	FEV 1 or PEF is 60% or less than predicted, PEF variability is more than 30%.
NOTE: The presence of one of the features of severity is sufficient to place a patient in that category. An individual should be assigned to the most severe grade in which any feature occurs. The characteristics noted in this figure are general and may overlap because asthma is highly variable. It should be noted that many life-threatening situations have started in patients categorized with mild asthma. An individual's classification may also change over time. Patients at any level of severity can have mild, moderate, or severe asthma attacks. Some patients with intermittent asthma experience severe and life-threatening exacerbations separated by long periods of normal lung function and no symptoms.
Adapted from National Asthma Education and Prevention Program (National Heart, Lung, and Blood Institute) Second Expert Panel on the Management of Asthma. Expert panel reports 2: guidelines for the diagnosis and management of asthma. Bethesda, Md.: National Institutes of Health, 1997; publication no. 97-4051.

Risk Factors for Life-Threatening Asthma

Asthma is rarely fatal in children, with only 176 asthma deaths reported in 1999 in children under age 15. (About 444 fatalities occurred in people between ages 15 and 34.) But even these low numbers are unacceptable, since asthma deaths are largely preventable.

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

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 Caucasian-Americans in the age groups of four and under and 15 to 24 years. Hispanic children also have a higher risk. A 2002 study suggested that these children tend to be given inferior treatments compared to Caucasian children.

Symptoms of a Life-Threatening Attack

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. It should be noted that early symptoms or lack of them do not always reflect the ultimate severity of an attack. In fact, some studies 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 therefore 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.

Long-Term Outlook

Half of asthmatic children achieve remission after age 16. In half of these, however, asthma flares up again in middle age and remains a problem. Children whose condition is serious enough to require steroids are less likely to outgrow their asthma than others.

There is now some evidence that severe asthma can cause long-lasting damage and possibly permanent scarring. Many experts urge introduction of anti-inflammatory medications early on in children with severe conditions. Children adapt well to living with asthma, however, and even with severe asthma they can function as well as healthy children in virtually all areas of life.

Psychologic Factors

Studies are mixed over the effects of emotional disorders on the severity of asthma. In fact, one indicated that parents of asthmatic children may suffer greater psychological stress than their children do. A 2000 study, in fact, reported that having mild to moderate asthma does not significantly affect the psychological well being of most children aged 5 to 12. Teenagers and preteens have particular difficulty coping with what they perceive as the social stigma of asthma. Often they will deny their condition and refuse to comply with their drug regimen. Parents and older children should not hesitate to seek help from support groups, physicians, friends, or family members. Supporting programs in camp and school may help children to better manage their asthma and may even reduce hospitalization.

Effect on School and Work

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.

WHAT CHILDREN GET ASTHMA?

At this time, asthma affects about 5.3 million American children between the ages of five and 14, and some experts believe that about half of American children may be undiagnosed. Asthma has dramatically increased worldwide over the last few decades, in both developed and developing countries. The prevalence of asthma increased by 60% in America, since the early 80s, and in Europe it has doubled. The incidence increased most rapidly in children under age four. There is a wide variation in asthma incidence, however, ranging from over 50% among children in the Caroline Islands to virtually 0% in Papua New Guinea. The reasons for this wide variation are not yet known.

Gender

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

Socioeconomic Factors

Urban Life. Urban life is strongly associated with a higher risk. Although poverty plays a significant role, urban life, in fact, 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 Chicago study reported 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 may 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. For example, a 2000 study found that African American children may have significantly higher levels of IgE than Caucasian children, suggesting a genetic susceptibility. (IgE are immune factors that play a critical role in asthma.)

Issues Surrounding Birth

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

Winter Birth. One study suggests that children born in the winter are at greater risk for asthmatic allergies to cockroaches than children born at other times of the year.

Breast Feeding. Reports on breast feeding are mixed. Although a 2001 study suggested breast feeding may increaseslightly the risk for asthma, other studies, including a major 2001 analysis, report protection. More research is warranted. It should be noted that breast feeding has many benefits for the child and this study should not discourage any mother from nursing her infant.

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 2000 study also reported that delivery procedures such as Cesarean section, the use of vacuum extraction or forceps also raised the risk of childhood asthma.

Obesity

In both adults and children, the incidence of obesity and asthma has been increasing in parallel 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 studies in 2000 and 2001 found no difference in activity levels between people with or without asthma. One 2000 study suggested that many obese people may be misdiagnosed as having asthma when in fact they are simply short of breath, possibly because of the increased effort required for breathing.

In any case, there is some evidence that losing weight can relieve asthma symptoms. Weight loss in anyone who is obese and has asthma or shortness of breath reduces airway obstruction and improves lung function. [See the Report on Weight Control and Diet.]

Other Risk Factors

Damp Homes. Studies from different parts of the world reported that children who live in damp homes have a much higher risk for asthma.

Parental Migraines and Childhood Asthma. Some studies have reported a link between childhood asthma and parental migraines, with one small 2000 study suggesting that children are about five times more likely to develop asthma if their parents have a history of migraines.

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, in fact, suggested that high stress levels can predict the onset and severity of asthma in children genetically at risk for asthma.

WHAT ARE THE SYMPTOMS OF ASTHMA IN CHILDREN?

In children with asthmatic symptoms, it is particularly 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.

Typical Asthma Symptoms

The classic symptoms of an asthma attack are the following:

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 asthma patients, although severe dyspnea does not always reflect a serious attack or reduced lung function. In fact, some patients, particularly elderly patients, may not experience significant dyspnea but still have very poor lung function.
Coughing. In some people the first symptom of asthma is a nonproductive cough. In fact, in a 2001 survey, 12% of asthma patients reported coughing as a significant problem. Patients surveyed tended to feel that daytime cough was even more distressing than wheezing or sleep disturbances.
Chest tightness or pain. Initial chest tightness without any other symptoms may be an early indicator of a serious attack.
The neck muscles may tighten, and talking may become difficult or impossible.
Rapid heart rate.
Sweating.
Chest pain occurs in about three-quarters 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 a 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.)

WHAT TESTS MAY BE REQUIRED TO DIAGNOSE ASTHMA?

Medical History

The doctor will seriously consider a diagnosis of asthma if the 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 the following:

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.

Ruling Out Other Diseases

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).

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.

Allergy Tests

The patient may be given skin or blood allergy tests, particularly if a specific allergen or occupational agent 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.

Other Tests

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.
Examination of the patients sputum for eosinophils (white blood cells that in high levels are associated with severe allergic asthma).
Investigative measurements of markers of airway inflammation, either in sputum or in exhaled air. Markers include nitric oxide and hydrogen peroxide. (It is not clear yet whether they will be useful in assessing.)

WHAT ARE THE GENERAL GUIDELINES FOR TREATING ASTHMA?

Emergency Treatment for an Acute Attack

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 may be administered with a nebulizer (a device that administers the drug in a fine spray) or inhaled hourly.
A corticosteroid (commonly called a steroid) is usually given if the patient does not respond to beta2-agonist treatments. They may be given intravenously or orally. Unfortunately, according to one study, almost one in four adolescents who are hospitalized due to uncontrollable asthma do not respond to steroid treatment. Of some promise are reports intravenous immunoglobulin may be effective in such patients.
Antibiotics may be given if sinusitis, pneumonia, or bronchitis is suspected or present.
Oxygen is usually administered, and can be life saving in severe cases. Some studies report that a mixture of helium and oxygen (heliox) may be beneficial. A major 2001 analysis of current data, however, found no strong evidence to support its role in initial treatment. In a 2002 study, for example, it was no better than air in improving lung function tests. Nevertheless, patients reported significantly less breathlessness with the heliox.
Infusions of magnesium sulfate may be effective in treating severe attacks in children and although some studies report no clear advantage.
In life-threatening situations, the patient may require mechanical ventilation.

Discharge and Relapse After Hospitalization. It typically takes about three to four hours to determine if a patient can be safely sent home or if they need to stay. Patients are generally discharged under the following circumstances:

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

Discharged patients generally take oral corticosteroids for five to seven days. Despite reasonable precautions, about 20% of patients relapse within two weeks, although the risk is very low if they keep taking their medication after they leave.

Guidelines for Treating Asthma at Home

Avoiding allergens, following appropriate drug treatments, and home monitoring are key elements in preventing dangerous asthma attacks and hospitalization. A combination of medications is important and effective for both treating and preventing asthma attacks. In addition, good communication between the physician and patients is a key factor in a successful management program.

Understanding the Difference between Treating Symptoms and Controlling the Disease

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. According to a few studies, most parents do not discriminate between medications that provide rapid short term relief and long term symptom control.

Medications for asthma are categorized by their ability to achieve either of the following:

Drugs used to relieve acute asthma symptoms. Anyone experiencing a moderate or severe asthma attack should promptly be given medications that open the airways. Generally, these are bronchodilator called short-acting beta-adrenergic agonists (beta2-agonists). Others sometimes used in special cases include theophylline, and certain anticholinergic agents. None of these agents have any effect on the disease process itself. They are only useful for treating symptoms.
Drugs used to control long-term persistent inflammation and prevent lung injury. For long-term control of the disease, patients with moderate to severe asthma require medications to control inflammation. Typically, these are patients who are taking the short-acting beta2 agonists more than twice a week. The standard agents for maintenance treatments are inhaled corticosteroids (commonly called steroids). Others include leukotriene-antagonists, and cromolyn. Combinations of steroids and other medications (such as long-acting beta2 agonists or leukotriene-antagonists) are proving to be effective for both treating and preventing asthma attacks in patients with moderate to severe asthma.

Simply coping with asthma symptoms without also controlling the inflammation is a common and serious error. Unfortunately, studies are finding that a significant number of moderate or severely asthmatic patients overuse their inhaled beta-agonists and underuse their corticosteroid medications. Asthma flare-ups are much more common in children who do not comply with the prescribed treatment. Unfortunately, on average, less than half of children adhere to their drug regimens, and the situation is far worse in inner city children with asthma, a group at high risk for severe complication.

Administering Inhaled Drugs

Most asthma drugs are inhaled using various forms of inhalers or nebulizers. Inhaled agents 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 some are easier to use than others. In one study, only 29% of children used the dry-powder inhalers (DPIs) correctly, while 67% of children used the metered-dose inhaler (MDI) appropriately. Newer easier-to-use inhalers, both DPIs and MDIs, can improve these rates considerably.

Metered-Dose Inhaler. The standard device for administering asthma medication has been the metered-dose inhaler (MDI). This device allows precise doses to be delivered directly to the lungs. Until recently, MDIs have used chlorofluorocarbons (CFCs) as their propellants, which are damaging to the environment.

Many devices now use propellants (e.g., hydrofluoroalkane) that are equally effective to CFCs and are environmentally safe. They also do not chill the device as CFCs do. Some of the non-CFC inhalers (such as Respimat, which uses a soft-mist spray) may be more effective at delivering medications than even the new dry-powder inhalers [ see below ].

In other comparison studies, patients have been very successful with the breath-actuated inhalers (Easi-Breathe and Autohaler).

The holding chambers for the MDIs also vary in their ability to deliver medication. For example, in one study the AiroChamber-Plus was more effective than the EasiVent in delivering an inhaled steroid.

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. Often, the devices continue to deliver propellant after the drug has been used up. Patients should track their medicine and throw the device away when the last dose has been administered.

Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of medications directly into the lungs and do not threaten the environment. 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. The Discus is another effective DPI; it has a dose counter and protects against exhalation effects. More research is needed.

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

Dry-powder may cause tooth erosion and children are advised to rinse their mouths out right after taking the drug and to brush twice a day with a fluoride toothpaste.

Nebulizers. Nebulizers are often used for children younger than three years and sometimes for older children who have difficulty using the MDI. A nebulizer is a machine that delivers a fine spray of medication-containing liquid. It takes five to 10 minutes to administer any medication using a nebulizer. And, 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. Of note: if children must use an albuterol nebulizer, parents should be sure that it does not contain the preservative benzalkonium, which actually narrows the airways.

Monitoring

Children with asthma who are monitored daily for peak air flow and whose medications are adjusted accordingly tend to have fewer hospitalizations and a better quality of life than those who rely on the occasional physician or emergency room visit to control symptoms. For children who are too young for peak flow meters, parents should keep a diary of all their children's respiratory complaints and any incident or allergen that might have triggered them.

Monitoring typically involves the following steps:

A peak flow meter is the standard monitoring device for measuring peak expiratory flow rate (PEFR).
Parents of children with severe asthma should take PEFR readings two or three times a day. The overall goal should be to achieve less than a 20% (and ideally only 10%) variation in readings between evening and morning rates. For mild to moderate asthma, a single determination each morning usually suffices, but patients should check with their physicians.
It is important to use the meter at the same times each day and to stand or sit in the same position in order to keep an accurate record.
Parents should keep an ongoing record of their child's peak flow readings to help detect worsening of their condition.
Parents should also record attacks, the child's exposure to any allergens or triggers, and medications taken.
After about two months, parents and physicians can use the data recorded for administering medications effectively and to recognize problems before they become serious.

Non-Medical Management Strategies

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 the following:

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.
Giving the child warm liquids, such as soup or hot cider, is 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.

WHAT ARE THE SPECIFIC DRUGS USED TO TREAT SYMPTOMS OF ACUTE ASTHMA ATTACKS?

Short-Acting Beta2-Agonists

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.

Specific short-acting beta2-agonists include the following:

Albuterol (Proventil, Ventolin), called salbutamol outside the US, 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 agents. Studies have indicated that levalbuterol is as effective as albuterol with fewer side effects. Xopenex is administered with a nebulizer and is available without preservatives. (It is very expensive, however.)

Short-acting bronchodilators are generally administered through inhalation and are effective for three to six 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

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

Anxiety.
Tremor.
Restlessness.
Headache.
Patients may experience fast and irregular heartbeats. A physician should be notified immediately if such side effects occur.
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 physician about any other medications their child is taking.

Loss of Effectiveness and Overdose. There has been some concern that both 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 beta 2 agonists may increase the chances of a reduced effect from the short-acting forms.

Other Bronchodilators

Theophylline. 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.

It does have some problems, however. Side effects include changes in behavior, mood, and memory. If theophylline is not taken exactly as prescribed, an overdose can easily occur. Toxicity causes the following symptoms: nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in heart rhythm and convulsions. A physician should be contacted 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 asthmatic children reach one year old, 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 on-going basis, the doctor should monitor the drug level at the start of therapy and at regular intervals thereafter.

Anticholinergic Agents. 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, although it does not appear to offer any advantage over the use of intravenous beta2 agonists. (This agent has no benefits in any case if it is used alone in this situation.)

WHAT ARE THE SPECIFIC DRUGS USED TO PREVENT ASTHMA ATTACKS AND REDUCE AIRWAY INFLAMMATION?

Cromolyn and Similar Drugs

Cromolyn sodium (Intal) serves as both an anti-inflammatory drug and has antihistamine properties that block asthma triggers such as allergens, cold, or exercise. Because of its proven safety record, cromolyn has been the anti-inflammatory agent of choice for prevention of asthma attacks in children over four with chronic moderate asthma. It is not a corticosteroid, so does not inhibit growth in children. Studies indicate that it also may reduce hospitalization rates almost as well as corticosteroids do, and that up to 70% of children who need asthma maintenance therapy would do well on cromolyn. (It may not provide any real benefit for children under four.)

A cromolyn nasal spray called Nasalcrom has been approved for over-the-counter purchase, but only to relieve nasal congestion caused by allergies. Asthmatic patients should not use it for self-medication without the advice of a physician. Nedocromil (Tilade) is similar to cromolyn and also prevents asthmatic reactions to cold and exercise. Ketotifen, a similar drug, may be useful in preventing allergic asthma, but may not be as effective as cromolyn.

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.

Corticosteroids

Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs. Steroids are not bronchodilators (that is, 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. Many studies have now shown that the use of inhaled corticosteroids in patients with moderate to severe asthma significantly reduce the rate of rehospitalizations and deaths from asthma. Nevertheless, they are still significantly underprescribed in the patients who need them most.

Inhaled Corticosteroids. Inhalation of corticosteroids makes it possible to provide effective local anti-inflammatory activity in the lungs with minimal systemic effects. (Oral steroids have considerable side effects.) They are currently 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 are the following (not all are available to children):

The most recent generation of inhaled steroids include (in order of potency) fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, the newer agents, are more powerful than the older generation of inhaled agents. Experts have some concern, then, that these potent agents, particularly fluticasone, may produce major side effects similar to oral agents. Studies are now suggesting, however, that the same benefits can be achieved with low doses of fluticasone as with high ones, thus reducing risks for serious side effects. (Of note, budesonide appears to be safe during pregnancy.)
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 inhaler systems for, however, such as QVAR, which uses extra fine formulations of beclomethasone to allow deep delivery into the lungs may prove to be as effective as the newer, more potent steroids.
Budesonide (Pulmicort Respules) is available in a jet nebulizer for children from 12 months to 8 years. It is, in fact, the first such medication to be approved for children in this age group.
Inhalers that combine both long-acting beta2-agonists and corticosteroids are now available. [ See Combinations of Corticosteroids and Long-Acting Beta2 Agonists.]

Evidence strongly suggests that early treatment is important for children with severe asthma to prevent deterioration in lung function. In addition, a major 2000 study reported that inhaled steroids may be beneficial and safe even for children with mild to moderate asthma. In the study, inhaled budesonide was more effective than nedocromil in controlling asthma and any effect on growth was slight and temporary.

Unfortunately an estimated 10% of children do not respond to inhaled steroids, and one 1998 study has reported that as many as 25% of adolescents may be insensitive to the drug. Of some promise is a report that the added use of intravenous immunoglobulin may be effective in such patients and reduce the need for steroids.

Side effects of inhaled steroids are the following:

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 are not common with inhalators.
Some children experience changes in mood, memory, and behavior, but they are not permanent.
Some studies have suggested a higher risk for gum inflammation.
It is well known that oral steroids reduce bone density and much research has focused on the effects of inhaled steroids on growth in children. Of some comfort are two major 2000 studies confirming previous ones that reported only a slight (about half an inch) and temporary effect on children's growth. It is not yet known, however, whether inhaled steroids effect lung growth in very young children. Steroids administered using nebulizers are of particular concern. At this time, then, experts caution against them for infants and toddlers with mild asthma and urge close monitoring especially for children under five with severe asthma who are receiving high doses. Calcium supplements appear to help prevent bone loss due to inhaled steroids.
There is also some concern that the more potent agents, particularly fluticasone, suppress the adrenal system (which secretes natural steroids) to a greater degree than other steroid inhalants. (This is a serious side effect of oral steroids.)

Oral Corticosteroid s. Oral agents are usually the last drugs to be added to an asthma treatment program and the first to be removed. Common oral corticosteroids include prednisone/prednisolone, dexamethasone, methylprednisolone, and hydrocortisone. They reduce inflammation very effectively, but children generally take them only for five days after hospitalization for an acute attack. Compliance among children can be low, however, since these agents have a bitter taste and can cause vomiting. Taking oral dexamethasone for two days may be as effective and more tolerable than the standard a five-day regimen of prednisone/prednisolone. Prolonged use of oral steroids has widespread effects, and so they are not generally give to children for longer than a few days.

Long-Acting Beta2-Agonists and Corticosteroid Combinations

Long-acting beta2-agonists, including salmeterol (Serevent) and formoterol (Foradil), are used for preventing an asthma attack (not for treating 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 agents also may be used for prevention of exercise-induced asthma in people and to protect against aspirin-induced asthma.

As with short-acting beta2-agonists, the long-acting forms have no effect on inflammation, and they should not be used alone on any regular on basis. Evidence suggests that such use may reduce the effectiveness of the short-acting beta2 agonists, which are the mainstays for treating acute attacks. In patients with moderate to severe asthma, the long-acting beta2 agonists are best used in combination with anti-inflammatory drugs. Adding these agents to a steroid regimen, in fact, may help prevent the need for higher doses of steroids.

The long-acting drugs used most are salmeterol (Serevent) and formoterol (Foradil). In comparison studies, they appear to be equally beneficial, although Formoterol has a much faster action and may achieve better control of nighttime asthma. Formoterol, in fact, works almost as fast as the short-acting albuterol and is sometimes used to treat asthma symptoms. Studies indicate that these are safe for children and may, in fact, be particularly effective for them. In one year-long study of children with mild to moderate asthma, salmeterol was not as effective as the corticosteroid beclomethasone, but it did reduce asthma symptoms without retarding growth.

A single inhaler (Advair Diskus) that combines both long-acting beta2-agonists and corticosteroids is now available for children over age 12. This inhaler appears to be safe and possibly more effective that either agent used alone for patients who do not respond well to other treatments.

Side Effects. Side effects of long-acting beta2 agonists are similar to the short-acting agents. [S ee Short-Acting Beta2 Agonists under What Are the Specific Drugs Used to Treat Symptoms of Acute Asthma Attacks?]

Leukotriene-Antagonists

Leukotriene-antagonists are oral medications that block leukotrienes, 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 agents, leukotrienes are not used for treating acute asthma attacks.

The leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These agents are proving to be effective for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID)-induced asthma. Many studies to date, however, are not finding any advantages compared to the more potent inhaled corticosteroids. Their anti-inflammatory actions are different from those of steroids, and a combination of the two agents is proving to be particularly effective, although it is not yet clear when such combinations would be useful.

Nevertheless, studies suggest that montelukast, which comes in a chewable tablet, may be particularly useful for managing asthma in small children (ages two to five) with asthma, since they have trouble with inhaled steroids. As suggested by another 2000 study on the effects of zafirlukast, they may also reduce the severity of cat allergies, regardless of whether or not asthma is also present.

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 agents 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 leukotrienes-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.

WHAT ARE THE EXPERIMENTAL AND OTHER TREATMENTS USED FOR ASTHMA?

Monoclonal Antibodies

Monoclonal antibodies (MAb) are genetically-developed agents that are designed to target and attack very specific factors. The following are under investigation.

A Mab known as omalizumab (Xolair) prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to asthmatic attacks. Studies are very promising for all age groups. Because IgE may play a greater role in causing childhood asthma, however, omalizumab be even more helpful for children than adults.
Keliximab is another monoclonal antibody under investigation that attacks white blood cells called CD4 lymphocytes, which may be critical in the asthmatic inflammatory process.

Interleukins

Other immune agents under investigation are interleukins, a subgroup of immune factors called cytokines, which are important in the inflammatory