Asthma in Adults

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ASTHMA IN ADULTS

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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 ARE THE SYMPTOMS OF ASTHMA?

Asthma symptoms vary in severity from occasional mild bouts of breathlessness to daily wheezing that persists despite taking large doses of medication. After exposure to asthma triggers, symptoms rarely develop abruptly but progress over a period of hours or days. In some cases, the airways have become seriously obstructed by the time the patient even calls the doctor.

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 the elderly--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 CAUSES ASTHMA?

Asthma has dramatically risen worldwide over the past decades, particularly in developed countries, and experts are puzzling over the cause of this increase. The mechanisms that cause asthma are complex and vary among population groups and even from individual to individual. Many asthma sufferers have allergies, and so some researchers are targeting are common factors in both these conditions. Not all people with allergies have asthma, however, and not all cases of asthma can be explained by allergic response. Other contributing causes need to be studied. Asthma is most likely a convergence of factors that can include genes (probably several) and various environmental and biologic triggers (e.g., infections, dietary patterns, hormonal changes in women, and allergens).

The Allergic Response

In general the allergic response is heavily associated with childhood asthma but has not played as strong a causal role in adult asthma to date. Recent evidence suggests, however, that allergic asthma may be increasing in adult-onset cases. Certainly, in any event, many asthmatic adults first developed asthma as an allergy-related condition during their childhood.

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.

Female Hormones

Hormones or changes in hormone levels appear to play a role in the severity of asthma in women.

Menstrual-Related Asthma. Between 30% and 40% of women with asthma experience fluctuations in severity that are associated with their menstrual cycle. One study indicated that women with menstrually associated asthma tended to have the following characteristics:

Were older.
Had asthma for a long time.
Had severe asthma attacks that were likely to occur three days before and four days into the menstrual period.

Oral contraceptives (OCs) theoretically should help asthma sufferers by leveling out hormonal changes, but they do not appear to have much effect. (There have been a few reports of asthma exacerbation with OCs, but these are uncommon events.)

Asthma during Pregnancy. During pregnancy, one-third of asthmatic women suffers more from the condition, one-third suffers less, and the other third experience no difference in severity. One interesting but unsubstantiated study suggests that expectant asthmatic mothers carrying a female baby tend to have more severe symptoms than do those who are bearing a male.

Menopause and Asthma. Around the time of menopause (called perimenopause) when estrogen declines, the risk for hospitalization in women with asthma increases fourfold compared to previous years. Although it should then follow that hormone replacement therapy (HRT), which contains estrogen, should benefit postmenopausal women studies are inconsistent. As with OCs, if there is an effect one way or the other, it is likely to be weak.

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 children or adults who are aspirin sensitive is unknown, however.

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 but more research is needed to confirm their safety in people with this condition.

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)]

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).

Contributing Medical Conditions

Infections. The role of infections in asthma is complicated. Respiratory infections may play a role in some cases of adult-onset asthma, but may be protective against asthma in small children.

Researchers are particularly interested in the organisms Chlamydia pneumoniae, Mycoplasma pneumoniae, adenovirus, and the respiratory syncytial virus. They are major causes of both mild and serious respiratory infections and are becoming important suspects in many cases of severe adult asthma. (If such respiratory infections occur in young children, they are unlikely to have any affect on adult-onset asthma.)

In one study, patients whose asthma was initiated after infections had more severe conditions than those whose asthma was due to other causes. The infection-initiated asthma, however, lasted only 5.6 years compared to 13.3 years in the non-infection group.

In any age group, respiratory infections worsen existing asthma in people who have it already. Rhinovirus (the common cold virus) 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 and 44% in adults. Some research suggests that colds promote allergic inflammation and increase the intensity of airway responsiveness for weeks.

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.

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?

Hospitalization and Mortality Rates

The number of deaths from asthma increased from about 2,900 in 1908 to a high of 5,667 in 1996. The numbers appear to be declining slightly, and in 1999 about 4,600 people died because of asthma. Death from asthma is still a very uncommon event, considering that about 14 million people in the US have this condition. Most deaths from asthma, even when they occur in elderly adults are preventable. It is very rare for a person who is receiving proper treatment to die of asthma. And studies suggest that the use of inhaled corticosteroids can reduce the risk for death by 90%. In spite of this and similar research, these important drugs are greatly underused.

Risk Factors for Very Severe or Fatal Asthma

About 55% of US deaths from asthma occur among the elderly (over 65) and an estimated 25% occur in adults aged 45 to 64. Women have a higher risk for fatal asthma than men do. Being poor is also a significant risk factor for severe asthma. Hispanics and African Americans are at higher risk for death from asthma than Caucasians. Other specific risk factors for fatal asthma have been identified:

Previous history of respiratory failure.
Frequent visits to the emergency room.
Lack of continuous care and poor compliance with medications.
Having stopped treatment, particularly withdrawal from corticosteroids.
Having an emotional or psychiatric disorder. (Some evidence suggests that depression, anxiety, and stressful life situations can worsen asthma.)
Being a drug abuser.
Being in a lower socioeconomic and educational group.

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.

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.

Long-Term Outlook

Asthma is usually chronic, although it occasionally goes into long periods of remission. Long term outlook generally depends on severity:

In mild to moderate cases, asthma can improve over time, and many adults even become symptom free.

Even in some severe cases, adults may experience improvement depending on the degree of obstruction in the lungs and the timeliness and effectiveness of treatment.

In about 10% of severe persistent cases, changes in the structure of the walls of the airways lead to progressive and irreversible problems in lung function, even in aggressively treated patients.

Lung function in any case declines faster than average in asthmatics, particularly in those who smoke and in those with excessive mucus production (an indicator of poor treatment control). Overall, one study reported that 72% of men and 86% of women with asthma had symptoms fifteen years after an initial diagnosis. Only 19% of these people, however, were still seeing a doctor and only 32% used any maintenance medication.

Of note are patients who develop occupational asthma. They often experience asthmatic symptoms for years, even after avoiding the harmful agents, although improvement occurs over time in most people who leave such jobs.

Miscellaneous Complications or Associations

Emotional Problems. Even when it is not life threatening, asthma is debilitating and frightening. It significantly lowers the quality of life.

Sleep Disorders. Sleeplessness and daytime sleepiness are common problems. Studies indicate that between 80% and 93% of asthmatics have sleeping problems about three times a week. In one poll, 40% missed work an average of 11 days a year because of sleep disturbance. Asthma has been associated with snoring and obstructive sleep apnea, a condition in which blockage of the upper airway causes the sleeper to temporarily stop breathing, then resume with a gasp, often many times during each hour of sleep.

Asthma and Pregnancy. Uncontrolled asthma in pregnant women puts them at higher risk for complications that can include early labor, hypertension, gestational diabetes, and hemorrhage. Asthma also places the babies at risk for lower birth weight and breathing disorders. Teenage mothers with asthma face higher risks than older women. Fortunately, studies indicate that most asthma drugs are safe to take during pregnancy, and good control of asthma reduces these risks to normal levels. Fortunately, a number of asthma medications are safe during pregnancy.

Heart Disease. There have been some reports of an association between asthma and a heightened risk for heart disease. Some experts believe that the inflammatory process may be the common factor linking the two conditions, although there is no evidence to date confirming any causal association.

WHICH ADULTS ARE AT RISK FOR ASTHMA?

General Risk Factors

According to a major national 2001 survey, American adults have a 10% lifetime risk for developing asthma. As of 2000, an estimated 14.6 million adults had the disorder. Between 1980 and 1996 the prevalence of asthma increased by nearly 74%, but it may be stabilizing. Other respiratory diseases, sinusitis, and ear infections are also on the rise, suggesting that airborne or environmental factors may be at work that affect all of these conditions, including asthma.

Gender

Before puberty, asthma occurs more often in males, but after adolescence, it appears to be more common in females. In adults with similar cases of actual air way obstruction, women are likely to report more severe symptoms than men are. In addition, women may be at much greater risk of death from asthma than men.

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 .]

Smoking

In one study of elderly people with severe adult-onset asthma, smoking was the most significant risk factor for developing this condition. Smoking, in any case, contributes to decline in lung function in everyone.

Population Differences

Urban Life and Poverty. African Americans have higher rates of asthma than Caucasian Americans or other ethnic groups. They are also more likely to die of the disease. Ethnicity and genetics, however, are less likely to play a role in these differences than socioeconomic differences, such as having less access to optimal health care. Poverty is a consistent risk factor in most studies. Both the elderly and the urban poor have the highest risk for severe asthma and death. Urban life, in fact, has been associated with a higher risk for asthma in all income groups and among both children and adults. Twin studies also suggest that people who have lower educational levels (as well as those who exercise less) are at higher risk for adult-onset asthma, further suggesting a link to lower economic status.

Geographical Differences. To confound matters, however, asthma rates vary widely among different populations regardless of socioeconomic factors. For example, asthma and hospitalization rates are dramatically higher in New York Puerto Ricans than in Hispanic-Americans who live in Los Angeles or the Southwest. Among the US states, rates are lowest in Louisiana and highest in Maine.

And, there are significant differences even among nations. In a major study of 22 nations published in 2001, the countries with the highest asthma rates were Britain, Ireland, Australia, New Zealand, and the US. (According to another study, asthma rates are also significantly higher in Canadian adults than they are in comparable European groups. ) Low rates were reported in Iceland, Norway, Spain, Germany, Italy, Algeria, India, and Eastern European nations. The reasons for these variations are still unknown. .

WHAT TESTS MAY BE REQUIRED TO DIAGNOSE ASTHMA?

Medical and Personal History

When asthma is suspected, the patient should describe for the physician any pattern related to the 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.
Any occupational or long-term exposure to chemicals. Early detection of occupational asthma is very important. If symptoms improve on weekends and vacation and are worse at work, the job is likely to be the source of the asthma, although this is not always the case. Asthma is common, and exacerbation at work may be coincidental.

Ruling Out Other Diseases

A number of disorders may cause some or all of the symptoms of asthma:

Asthma and chronic obstructive lung diseases (chronic bronchitis and emphysema) affect the lungs in similar ways and, in fact, may all be present in the same person. Unlike the other chronic lung conditions, asthma usually first appears in patients less than 30 years old and with chest x-rays that are normal. Still, it may be difficult to distinguish these disorders in some adults with late onset asthma.

Panic disorder can coincide with asthma or be confused with it.
Gastroesophageal reflux disorder (GERD) is a common companion in asthma and may affect treatment.
Other diseases that must be considered during diagnosis are pneumonia, bronchitis, severe allergic reactions, pulmonary embolism, cancer, heart failure, tumors, psychosomatic illnesses, and certain rare disorders (such as tapeworm and trichomoniasis).

Pulmonary Function Tests

If symptoms and a patient's history are indicative of asthma, the physician 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 physician will determine several values:

1. Vital capacity (VC), which is the maximum volume of air that can be inhaled or exhaled.

2. 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.

3. Forced expiratory volume (FEV1), which is the maximum volume of air expired in one second.

Ιf the airways are obstructed, then these measurements will fall. Depending on the results, the physician will take the following steps:

If measurements fall, then the physical typically asks the patient to inhale a bronchodilator. This is a drug that is used in asthma to open the air passages. The measurements are taken again. If the measurements are more normal, than 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 the doctor still suspects asthma, he or she may perform a challenge test. In this case a specific drug (histamine or methacholine) is administered that usually increases airway resistance only when asthma is present. The challenge test may be quite useful in ruling out occupational asthma. It is not always accurate, particularly in asthmatic patients whose only symptom is persistent coughing.
method for inducing airway resistance is to administer cold air. This test is very accurate for ruling out asthma, but it is not sensitive enough to accurately identify adults who actually are asthmatic.

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.)
If aspirin-induced asthma (AIA) is suspected, an investigative non-invasive test called acoustic rhinometry may be useful. A solution of lysine acetylsalicylic acid (L-ASA) is instilled into the patient's nostril. Patients who experience symptoms such as sneezing, itching, congestion, and secretion are likely to have AIA.

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.
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

Patients can greatly reduce the frequency and severity of asthma attacks by understanding the difference between coping with asthma attacks and controlling the disease over time. According to a few studies, most patients 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. Such patients, then, are not controlling the basic disease process that can lead to lung damage. They also tend to over-use their bronchodilators, which can have serious consequences. Furthermore, the patients who underuse steroids tend to be elderly, the group at highest risk for severe asthma.

Administering Inhaled Drugs

Most asthma drugs are inhaled using special devices or nebulizers. The standard inhalers have used ozone-depleting chlorofluorocarbons as propellants, but alternative delivery methods and propellants are increasingly available that do not threaten the environment and may even be better in delivering the drugs.

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 the new dry-powder inhalers [ see below ].

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).

Nebulizers. A nebulizer is a device that administers the drug in a fine spray that the patient breathes in. They are mostly used in hospital settings or when the patient cannot use an inhaler. Nebulizers may be important for delivering newer agents used in asthma treatment.

Monitoring

People who self-manage their asthma using daily monitoring of peak air flow and adjusting their medications as needed have fewer hospitalizations, fewer unplanned doctors visits, and, generally, a better quality of life than those who rely only on the occasional physician or emergency room visit to control symptoms. Physicians recommend that patients with even mild asthma monitor their own conditions.

In general, monitoring involves the following steps:

A peak flow meter is the standard monitoring device for measuring peak expiratory flow rate (PEFR).
Patients 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.
Patients should keep an ongoing record of their peak flow readings to help them detect worsening of their condition.
They should also record attacks, exposure to any allergens or triggers, and medications taken.
After about two months, patients and physicians can use the data recorded for administering medications effectively and to recognize problems before they become serious.

In general, many people fail to monitor their asthma. Experts believe that, ideally, portable monitors should be available to measure forced expiratory volume (FEV1), which is more accurate gauge of lung function, and the results should be electronically transmitted to the physician.

New monitoring devices are showing promise in accomplishing one or more of these goals, although they are not covered by most insurers. For example, the AirWatch is a hand-held digital monitor that measures and displays the rate of airflow and compares it to the rates from previous days. Once a month, or whenever there is a problem, the person plugs the device into a standard telephone jack and the daily readings are sent to an automated data center which creates tables and charts for the patient and the doctor.

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. They are used alone only for patients with mild and intermittent asthma. Patients with more severe cases should use them in combination with other agents.

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 agents, then patients should discuss corticosteroids or other drugs to treat underlying inflammation.

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, particularly in people with existing heart conditions. Such patients face an increased risk for sudden death from cardiac related causes. This risk is higher with oral or nebulized agents, but there have also been reports of heart attacks and angina in some patients using inhaled beta2 agonists.

Beta2-agonists have serious interactions with certain other drugs, such as beta-blockers, and patients should tell the physician about any other medications they are taking. Individuals with diabetes, existing heart disease, high blood pressure, hyperthyroidism, an enlarged prostate, or a history of seizures should take these drugs with caution.

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 reduce the effect of short-acting forms.

It's a major concern that patients who perceive beta2 agonists as being less effective may over-use them. Overdose can be serious and in rare cases even life-threatening, particularly in patients with heart disease.

Theophylline and Similar Agents

Theophylline. Theophylline (Theo-Dur, Theolair, Slo-Phyllin, Slo-bid, Constant-T, Respbid) relaxes the muscles around the bronchioles and also stimulates breathing. One study reported that it 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; 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:

Chronic smokers metabolize theophylline much more quickly and require higher doses of the drug than nonsmokers; prolonged-release versions are helpful for such people.
Too much caffeine can increase the concentration of this drug and the amount of time it stays in the body.
Theophylline also interacts with many other drugs that are taken for other common medical conditions, including asthma. Caution should be exercised if beta2-agonists and theophylline are used together.
Theophylline should not be taken by anyone who has a peptic ulcer and should be taken with caution by the elderly and by individuals with heart disease, liver disease, hypertension, seizure disorders, or congestive heart failure. Of special note, people with heart conditions who take theophylline orally face an increased risk for sudden death from heart-related causes.

Xanthines. Drugs similar to theophylline called xanthines, such as doxofylline, may prove to be effective bronchodilators without the adverse effects on the heart that theophylline and beta2 agonists have. More research is needed.

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. It may, however, have benefits in certain cases:

It may be useful for certain older asthma patients who also have emphysema or chronic bronchitis.
A combination with a beta2-agonist might be helpful for patients who do not initially respond to treatment with a beta2-agonist alone.

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

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:

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 doses, 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.
Inhalers that combine both long-acting beta2-agonists and corticosteroids are now available. [ See Combinations of Corticosteroids and Long-Acting Beta2 Agonists.]

Inhaled corticosteroids must be taken regularly. It may take a month to perceive their effects and up to a year to achieve full benefits. Some of these agents may have some immediate benefits; in one study, inhaled budesonide reduced inflammation in the airways within six hours.

Optimal timing of the dose is important and may vary depending on the medication. Most of the newer inhaled steroids and even some older ones are now available as a single daily dose, which some patients may respond to.

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.

Inhaled steroids are generally considered safe and effective and only rarely cause any of the more serious side effects reported with prolonged use of oral steroids. A 2001 study, however, reported a higher risk for cataracts in patients over age 40. (No higher risk was observed in younger people.) Others are reporting a higher risk for bone loss in patients who take inhaled steroids regularly. (A number of bone-preserving medications are now available that might safely offset this effect.) 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.)

Of note, during pregnancy, inhaled budesonide and beclomethasone are considered to be generally safe.

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, methylprednisolone, and hydrocortisone. They very effectively reduce inflammation but are generally used only after hospitalization for an acute attack. In some severe cases, they may be used as maintenance.

effects of prolonged use of oral steroids include cataracts, glaucoma, osteoporosis, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and psychosis. Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, bisphosophonates, or hormone replacement therapy in post-menopausal women. Vitamin C and E may help reduce the risk of cataracts.

Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. It should be noted that there have been a few cases of severe adrenal insufficiency that occurred when switching from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a physician first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their physician measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

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. Single devices that contain both agents are now available in the US (Advair) and parts of Europe (Seretide, Symbicort). These inhalers appear to be safe and possibly more effective than either agent used alone for patients who do not respond well to other agents.

Warning on Salmeterol. Both salmeterol and formoterol are beneficial and improve the quality of life. Formoterol has a much faster action than salmeterol 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. Salmeterol, however, requires up to 20 minutes to achieve effectiveness and should never be used for stopping an attack. There is a danger then of overdose if a patient is not aware of this delay and takes additional doses to achieve faster relief. (Overdose has been fatal in rare cases.) The risk appears to be highest in elderly patients with severe asthma. People using long-acting beta2 agonists should take the following precautions:

The medication should not be stored in locations that are easily accessible during acute attacks, such as by the bed or in a pocketbook.
Salmeterol should never be used for treatment of acute episodes; for this purpose, short-acting bronchodilators should be used. (Formoterol has a faster action and may, in some cases, be used for treating symptoms, but patients should check with their physician.)

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?]

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. Nedocromil (Tilade) is similar to cromolyn. 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.

Candidates. Cromolyn is often used in children with allergic asthma, but it has also been an important treatment for exercise-induced asthma (EIA) in all age groups, for pregnant women, and possibly for preventing allergic asthma in adults as well as children. Both cromolyn and nedocromil appear to be useful for patients with aspirin-induced asthma. These agents do not effectively treat asthma once an attack is underway. They also have very little long-term benefits on lung function compared to inhaled corticosteroids.

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

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 used for prevention and not 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, and possibly for exercise-induced asthma or aspirin-induced asthma. They may also reduce the severity of allergy symptoms, regardless of whether or not asthma is also present.

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.

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 INVESTIGATIVE AND OTHER TREATMENTS 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 process. Interleukins serve many functions in the asthma process, some protective and some destructive.

Of particular promise is an agent called soluble IL-4 receptor that blocks interleukin 4 (IL-4), which regulates many of the events in the allergic response.
On other hand, researchers are investigating ways of employing other interleukins (as IL-10 and IL-12) that may actually be helpful, because they have anti-allergenic effects.

Treatment of Disorders that Might Cause Asthma

Treatments for GERD. Treating gastroesophageal reflux disease (GERD) with drugs that reduce acid may reduce symptoms of both conditions in some patients who also have asthma. Not all such patients report improved asthma symptoms with GERD treatments, and they do not appear to have much effect, in any case, on actual lung function. But studies suggest this approach works in only certain patients, with one study suggesting that such asthmatic individuals tended to be overweight and to have severe GERD in the lower part of the esophagus. [ See Report #85, Heartburn and Gastroesophageal Reflux Disease. ]

Managing Hormonal-Related Asthma. Women who suspect that menstrual-related changes may influence asthma severity should keep a diary recording their menstrual dates and times of asthma attacks. In some cases, adjusting medications in anticipation of menstruation may help prevent attacks. Some small studies have suggested that hormonal agents called gonadotropin-releasing hormone (GnRH) analogues may help women with severe premenstrual asthma. Such drugs reduce or suppress estrogen levels, however, and can have severe side effects. More research is needed to determine if the disadvantages outweigh the benefits.

Antibiotics

Certain antibiotics, such as Clarithromycin (Biaxin), are being studied for the ability to increase the anti-inflammatory effects of corticosteroids.

Alternative Treatments

According to some studies, alternative therapies such as acupuncture, hypnosis, and breathing relaxation techniques are being widely used by both children and adults with asthma with some good results. Research also suggests that meditation practices are very effective companion therapies for asthma patients.

The Buteyko Breathing Method. The Buteyko breathing method is 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 are reporting that patients use 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 US.

Herbal Remedies. Herbal remedies have been used with apparent success in Eastern nations, but few have been studied rigorously in the United States. It should be noted that even when natural remedies appear to be effective in trials, there are no standards or regulations in the US to guarantee their quality, effectiveness, or safety. Of great concern are their growing use and the possibilities of serious drug interactions. Patients who try alternative treatments must be sure to inform their physician.

WHAT ARE WAYS TO MANAGE ASTHMA AND REDUCE THE ALLERGIC RESPONSE?

About 50% of adults with asthma exhibit allergic responses. Avoidance or control of the triggers that lead to asthma attacks is as much a priority as treatment of the disease. An asthma attack can be induced or aggravated by direct irritants to the lungs. 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. (In one study, allergies to dust mites did not appear to have any affect on hospitalization, although they are capable of triggering asthma attacks.)
Animal dander.
Pollen.
Molds.
Fungi.
Cockroaches. Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.

Of some concern are studies reporting no change in asthmatic symptoms after controlling cat or dust mite allergens. More research is needed to identify the reasons for this.

Controlling Pets

Patients who already have pets and are not allergic to them probably have a low risk for developing allergies. If pets trigger asthma, however, they should be 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 that remove allergens from skin and fur and are easier to administer than wet shampoos.

Indoor Protection

Removing Allergens from the Air and Carpets. Air cleaners, filters for air conditioners, and vacuum cleaners with HEPA filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo is effective in removing mites. In fact, vacuuming stirs up both mites and cat allergens.

Carpets and rugs are major sources of allergens in any case and should be avoided if possible. HEPA vacuum cleaners appear to be effective in reducing levels of second-hand smoke and preventing cat allergens from being released into the air. Neither vacuuming nor the use of anti-mite carpet shampoo is effective in removing mites. In fact, vacuuming, even with a HEPA filter, stirs up both mites and cat allergens.

House dust itself, however, can be a reservoir for pollen, so keeping a house dust-free is still helpful. A 2002 study reported that spray furniture polishing is very effective for reducing both dust and allergens.

Bedding and Curtains. Using semipermeable coverings to fully encase mattresses and pillows is the most proven effective step in reducing dust mite levels. (Vinyl mattress covers limit airflow and may also exacerbate, 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.) Curtains should be replaced with shades or blinds and bedding washed using the highest temperature setting.

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

Gas Stoves and Kerosene. People with asthma who cook should choose electric ovens rather than gas, which release nitrogen dioxide, a substance that can aggravate asthma symptoms. (Children do not appear to be affected by gas cooking.) Kerosene (used in space heaters and lamps) may also produce allergic reactions.

Exterminating Cockroaches and House Mice. Cockroaches should be eliminated by professional exterminators, although a study reported that ridding a home of cockroaches and cleaning the house using standard housecleaning techniques failed to eliminate the cockroach allergens themselves. Mice should be eliminated, and attempts should be made to remove all dust, which might contain mouse urine and dander.

Avoiding Smoking and Cigarette Smoke. Cigarette smoke can accelerate the decline in lung function related to asthma. Even exposure to secondhand smoke can double the risk of asthma-related emergency room visits. In one study, it was the most frequently cited trigger of asthma symptoms. Everyone should quit smoking and encourage others around them to quit. [For help in quitting, see , Report # 41, Smoking.]

Outdoor Protection

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

Camping and hiking trips should not be scheduled during times of high pollen count (in the Northern states, 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. It is not clear why. Some evidence points to a build-up of ozone that accompanies such storms. One study suggested that 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.
Exposure to Air Pollution. A number of studies have linked air pollution to asthma. An important 2000 study found a strong association between higher mortality rates from heart and lung diseases and high levels of specific pollutants (ozone, carbon monoxide, sulfur dioxide, and nitrogen dioxide). 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. Nevertheless, evidence strongly suggests that air pollution can worsen existing asthma and patients should take precautions if they are exposed to polluted air.

Allergy Shots

Allergy shots (immunotherapy) are proving to be highly effective in reducing allergic asthma symptoms in both adults and children. Immunotherapy can also prevent the development of new allergies, the worsening of allergic symptoms, and the onset of asthma in susceptible people.

Preventing and Treating Respiratory Infections

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

There has been some question concerning influenza vaccinations because of some reports that vaccines may worsen asthma. Recent and major studies have been reporting, however, that the vaccination is safe for adults and children. It is also very important for patients to reduce their risk for respiratory diseases. Still, 90% of asthma patients remain unvaccinated.

Asthma patients should ask their physicians about the flu vaccine and also whether they should receive the vaccination against pneumococcal pneumonia.

Zanamivir, a new drug used for treating influenza, is now considered safe for asthma patients 12 years of age or older. And, in one study, asthma patients treated with zanamivir experienced fewer flu symptoms and their lung function improved. [ See Report #94, Colds, Flus, Sore Throats, and Acute Bronchitis .]

Occupational Asthma and Reducing Risk

A number of studies have estimated that between 2% and 26% of adult-asthma cases are related to work history. Some experts encourage physicians to suspect occupational factors in all cases of adult-onset asthma. Although workers who have allergies, who smoke, or both are at higher risk than others, any worker exposed to occupational triggers may be at risk for asthma.

Work-related asthma is one of two types:

Work-aggravated asthma, in which existing asthma symptoms are triggered by irritants at the workplace.
Occupational asthma, which is new-onset asthma strongly associated with conditions at work.

Occupational asthma is further categorized as the following:

Nonlatent (symptoms occur right after exposure to an irritant, usually high concentrations of gas, fumes, dust, or chemicals).
Latent (symptoms develop after prolonged exposure to substances in the workplace).

Occupational Triggers. Over 250 agents have been identified as potential occupational triggers of asthma and the list is growing. A few of the chemicals and substances that are particularly problematic include:

Isocyanates used in the manufacture of polyurethane, paints, steel, and electronics.
Trimellitic anhydrides (TMA) used in many plastics and epoxies.
Western red cedar, oak, redwood, and mahogany.
Metal salts (platinum, nickel, and chrome) and metal working fluids.
Vegetable dusts (soybeans, grains, flour, cotton, and gums).
Biologic agents ( Bacillus subtilis , pancreatic enzymes).
Xylanase used in the baking industry.
Pharmaceutical agents (penicillin, phenylglycine acid chloride).
Glutaraldehyde used to sterilize medical equipment.
Red dye made from the cochineal insect.

Workers in these industries and others, including farmers, hairdressers, and those who work in the garment industries, are at risk for asthma.

Preventing Occupational Asthma. In people whose asthma is caused by workplace conditions, improved ventilation or face masks may help.

Sometimes, however, even low levels of chemical agents can trigger an asthma attack. In such cases, leaving the job is the only way to prevent the condition from getting worse. Because such a step can be emotionally and financially threatening, workers should be sure that occupational substances are the cause of the asthma by having a complete check-up by a lung specialist.

If the diagnosis of occupational asthma is certain, patients should obtain advice on available compensation plans for disability. The effects of workplace asthma can be permanent. However, in one study, 70% of people with asthma experienced significant improvement in symptoms after leaving the job.

Dietary Factors

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

Antioxidant Foods and Supplements. Some evidence indicates that having low dietary intake of antioxidant nutrients (vitamins A, C, and E, selenium and other food chemicals) could increase the risk for lung damage. Taking supplements does not appear to have any effective. Such nutrients are best obtained from fresh, deep green and yellow-orange fruits and vegetables, which contain other chemicals that might be lung protective. In one study, people who consumed selenium-rich foods (fish, red meat, grains, eggs, chicken, liver, and garlic) had a lower risk for asthma. In the same study, eating apples was also associated with protection. (Apples contain important food chemicals called flavonoids.)

Fish Oil. Omega-3 fatty acids, found in cold water oily fish and in supplements (usually DHA-EPA) have anti-inflammatory effects and may be helpful for asthma.

Role of Food Allergies. Although 67% of asthmatics believe their symptoms are aggravated by food allergies, studies indicate that this belief may be true in only 5% of cases. The primary suspects are monosodium glutamate, or MSG (found in some canned soups, cheese, and certain vegetables), and sulfites (preservatives in wine and foods that include processed frozen potatoes and tuna). Contrary to what many believe, dairy products do not appear to exacerbate asthma symptoms in people who are not already allergic to them.

Exercise

It should be noted that asthma is no reason to avoid exercise. Historically, about 10% of US athletes who participated in the Olympics have been asthmatic. Some studies are indicating that long-term exercise may even help control asthma and reduce hospitalization. Patients should consult their physicians before embarking on any exercise program, however. It should be strongly noted that uncontrolled asthma can be dangerous and, in rare cases, fatal for athletes, even some with mild asthma. Use of the inhaler is extremely important.

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.

Exercise-induced asthma is a limited condition that has specific recommendations. [ See Box Exercise-Induced Asthma (EIA)]

Reducing Stress and Mood Disorders

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.

On the other hand, a positive attitude and relaxation techniques may be very helpful in the long-term management of asthma. [See the Report # 31 Stress.]

WHERE ELSE CAN PEOPLE WITH ASTHMA GET HELP?

The American Lung Association, 1740 Broadway, New York, New York 10019-4374.
Call (800-LUNG-USA) or (212-315-8700) (www.lungusa.org/)
The association is very responsive and offers a wide range of information and services.

American College of Allergy, Asthma & Immunology, 85 West Algonquin Road, Suite 550, Arlington Heights, IL 60005.
Call (847-427-1200) or fax (847-427-1294) or (http://www.allergy.mcg.edu/) or their journal Annals of Allergy, Asthma & Immunology (http://www.annallergy.org/)
This organization publishes information sheets on specific allergies and offers a number for referrals to allergists in local areas.

American Academy of Allergy, Asthma, and Immunology, 611 East Wells St., Milwaukee, WI 53202.
Call (800-822-2762) or (414-272-6071) for printed information, or (http://www.aaaai.org/)

National Heart, Lung, and Blood Institute, P.O. Box 30105, Bethesda, MD 20824-0105.
Call (301- 496-4000) or (www.nhlbi.nih.gov/index.htm)
This government institute publishes booklets and other information. Information on the National Asthma Education and Prevention Program (NAEPP) is available online at www.nhlbi.nih.gov/about.naepp.index.htm.

National Jewish Center for Immunology and Respiratory Medicine, 1400 Jackson Street, Denver, CO 80206.
Call (800-222-LUNG or 303-388-4461) or (303-388-7700 outside US) for the recorded service Lung Facts call (800-552-LUNG) or (www.njc.org).

National Allergy Supply, Inc., 1620 Satellite Blvd, Suite D, Duluth, GA 30097.
(Call 800-522-1448) or (770-623-3237 outside US) or (http://www.natlallergy.com/)

Allergy Control Products, Inc., 96 Danbury Road, Ridgefield, CT 06877.
Call (800-422-DUST or 3878) or (www.allergycontrol.com)