Asthma in Adults

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 passes into the lungs through progressively smaller airways called bronchioles. The lungs contain millions of bronchioles, all leading to alveoli--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 that cause patients to cough, wheeze, and experience shortness of breath (dyspnea).

Asthma appears to have two primary stages. First, the airways of people with asthma have an exaggerated, or hyperreactive , response to inhaled allergens or other irritants that causes them to become excited. Smooth muscles in the airways then constrict, narrowing excessively. It should be noted that the airways in everyone's lungs respond by constricting when exposed to allergens or irritants, but people without asthma are able to breathe deeply to relax the airways and rid the lungs of the irritant. When asthmatics try to take those same deep breaths, their airways do not relax and the patients pant for breath. Smooth muscles in the airways of people with asthma may have a defect, perhaps the lack of a critical chemical that prevents the muscles from relaxing. This first stage is followed by a second inflammatory response in which the immune systems responds to allergens or other environmental triggers by delivering white blood cells and other immune factors to the airways, which causes the airways to swell, to fill with fluid, and to produce a thick sticky mucus. This combination of events results in coughing, 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?

The mechanisms that cause asthma are complex and vary among population groups and even individuals. Genetic susceptibility, which probably involves several genes, coupled with various environmental components are the major causes of asthma. Many asthma sufferers also have allergies and researchers are investigating factors in the allergic response that might cause asthma in some people. Not all people with allergies have asthma, however, and not all cases of asthma can be explained by allergic response. Some experts are seeking a link between viral infections and the development of asthma in genetically susceptible people. Researchers also are detecting in some asthma patients overproduction of a very powerful enzyme called endothelin, which is responsible for narrowing blood vessels and airways, airway hyperreactivity, mucus secretion, and may even trigger inflammatory agents. In addition to problems in the airways, researchers are also finding that abnormalities in the lung tissue itself may contribute to asthma. The disorder gastroesophageal reflux disease also contributes to some cases of asthma.

The Allergic Response.
In people who have asthma caused by an allergic response, a cascade of events not yet fully understood, leads to inflammation and hyperreactivity in the airways. The conductor in this orchestra of immune system factors appears to be white blood cells called TH2-cells, a subgroup of so-called helper T-cells. These cells overproduce interleukins (IL), a subgroup of the immune factors known as cytokines. Of special interest are IL 9 and IL 5. Interleukin 5, for example, appears to attract eosinophil cells that are important for airway hyperreactivity. Interleukin 9 stimulates the release of antibodies known as immunoglobulin E (IgE). During an allergic attack, these antibodies can bind to various cells in the immune system, including eosinophils, basophils, and mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. Once IgE binds to mast cells, these cells are programmed to release a number of chemicals, particularly those known as leukotrienes, that cause inflammatory changes in the airways of the lungs, including narrowing of the airways, mucus production, and stimulation of nerve endings in the airway lining.

Genetic Factors.
Genetic factors play a role in the disease; about one third of all persons with asthma share the problem with another member of their immediate family. In a recent major study, researchers found that specific genetic regions increase risk for asthma in different ethnic populations, i.e., African Americans, Hispanics, and Caucasians. Interestingly, the genetic regions associated with allergies and hyperresponsiveness--factors widely associated with asthma--were not as significant as others.

Environmental Factors that Precipitate Asthma Attacks.
Allergens and Other Common Triggers. The primary allergens that trigger asthma in the home are dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. Cockroaches are now known also to be major triggers. An asthma attack can also be induced by cold air, thunderstorms, exercise, extreme emotion, and direct irritants to the lung such as animal dander, tobacco smoke, pollen, molds, and fungi.

Occupational Triggers. An estimated 2% to 15% of all cases of asthma in men are caused by occupational exposure to asthma-causing agents. There are so many chemicals and substances used in the workplace that can cause an allergic response and subsequent asthma attack that it is impossible to list them all in this report. Occupational asthma may occur after a prolonged period of exposure or it may develop suddenly following intense exposure to chemicals, often chlorine and ammonia. A few of the chemicals that are particularly problematic are the following: isocyanates used in products made from polyurethane, paints, and in the manufacture of 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); vegetable dusts (soybeans, grains, flour, cotton, and gums); biologic agents (Bacillus subtilis , pancreatic enzymes); and pharmaceutical agents (penicillin, phenylglycine acid chloride).

Medications. Certain drugs can trigger asthma attacks, such as aspirin and beta blockers (taken for a number of disorders, including high blood pressure, angina, and arrhythmias) An excess number of deaths from asthma have been reported in people taking anti-psychotic medications, although these complication appear to be due to patient problems, not the drugs.

Air Pollutants. Air pollution has also been associated with the development of asthma. Specific pollutants targeted for their role in triggering asthma include ozone, diesel fumes, sulfur dioxide from power and paper industries, and nitrogen dioxide from exhaust and gas ovens.

Exercise. In 40% to 90% of people with asthma, exercise will trigger coughing, wheezing, or shortness of breath. Exercise-induced asthma (EIA) is distinct from ordinary allergic asthma; some people have just one type of asthma, but others have both. EIA occurs most often during intense exercise in cold dry air.

Infections. Studies indicate that respiratory infections, including those caused by the organisms Chlamydia pneumoniae , mycoplasma, adenovirus, and respiratory syncytial virus, may trigger many cases of severe adult-onset asthma. Chlamydia is under particular scrutiny. Some experts have found evidence of this microbe in 85% to 100% of people who developed asthma as adults. They believe that such people might have developed an allergy to the microbes. In one study, patients whose asthma was initiated after an infection had a more severe condition than those whose asthma had other causes, but asthma caused by infection did not last as long (5.6 years compared to 13.3 years).

Hormones. Hormones or changes in hormone levels appear to play a role in the severity of asthma in women. About one third of women experience fluctuations in asthma severity dependent on their menstrual cycle, with the most severe attacks usually occurring three days before and four days into the menstrual period. Some research indicates that in women with premenstrual asthma, the rise in progesterone and sharp decline in estrogen shortly before menstruation increase the risk for asthma attacks. One study found that taking oral contraceptives may help such asthma sufferers by leveling out hormonal changes. The relationship between female hormones and asthma is not clear cut, however. postmenopausal women who take hormone-replacement therapy, both with and without progesterone, have up to twice the risk for late-onset asthma. During pregnancy, one-third of asthmatic women suffer more from the condition, one-third suffer less, and the other third experience no difference in severity.

Food Allergies. Food allergies are rarely a cause of asthma attacks. Monosodium glutamate (MSG), which is sometimes used in restaurants and in processed foods (canned soups, cheese, and certain vegetables) has been identified as a trigger. Sulfites, used as preservatives or fresheners in wine and foods that include processed frozen potatoes and tuna are often blamed for asthma, although only 5% of asthmatics are sulfite-sensitive.

Low Birth Weight.
People who began life with low birth-weights appear to be at risk for asthma, bronchitis, and other lung disease throughout their life. Experts suggest that the airways develop abnormally in undernourished fetuses.

Contributing Medical Disorders.
As many as 89% of asthma patients also have gastroesophageal reflux disease (GERD), the cause of heartburn. GERD may trigger asthma in many adult-onset cases by spilling acid into the airways that triggers a hyperreactive response. GERD may be suspected in patients who do not respond to asthma treatments, whose asthma attacks follow episodes of heartburn, or whose attacks are worse after eating or exercise. In such cases, treating the heartburn may also resolve asthma [see, Heartburn and Gastroesophageal Reflux Disease ]. Sinusitis and rhinitis (inflammation in the sinuses and nasal passages) and polyps in the nose can contribute to asthma symptoms.

Who Gets Asthma?

An estimated 14.6 million Americans have asthma and the number of cases has increased by 61% between 1982 and 1994. Asthma occurs before the age of 15 more often in males, but after age 20, nearly three times as many women as men develop severe asthma. Asthma affects 5% to 10% of the world's population, and most evidence indicates that occurrence is on the rise. Some European studies attribute this phenomenon not to an increase in actual asthma cases but to other factors. One British study suggested that physicians in asthma clinics tended to over diagnose the condition, and experts who analyzed 16 studies that reported increased asthma rates found flaws in interpretation. They believe much of the increase is due to more parental awareness of the disease and differences in diagnostic criteria. Nonetheless, other respiratory diseases, sinusitis, and ear infections are clearly on the rise, suggesting that airborne or environmental factors may be at work.

About 6.1% of African-Americans have asthma compared to 5% of whites. Among Hispanics the risk is ranges from 2.7% for Mexican-Americans in the Southwest to 11.2% for Puerto Ricans in New York City. African-Americans are three times as likely as whites to die of the disease. The higher rates are probably boosted more by socioeconomic differences than by genetic factors; inner-city asthmatics are less likely to have access to adequate medical care and to be more exposed to allergens and pollutants. In some cities, more than half of all children with asthma get all their medical care only in emergency rooms.

Any worker exposed to occupational triggers may be at risk for asthma, including nonsmokers and people with no previous allergies. Some people at higher than normal risk include farmers, hair dressers, long-distant runners, and those who work in the garment, transportation equipment, and food industries. It is not clear whether professional drivers are at increased risk; studies have been conflicting, but a recent animal study showing that asthma increases with exposure to diesel fumes adds weight to the hypothesis.

Although allergens are common triggers of asthma attacks, it is not clear whether people with allergies and no symptoms of asthma are at risk for asthma. Some experts believe that allergic rhinitis (commonly called hay or rose fever) may predispose some people to the development of asthma. Recent research indicates that eosinophils and other factors in the immune system that cause inflammation also contribute to allergic rhinitis and asthma. Studies have reported, however, that only about 1% to 10% of children with allergic rhinitis developed asthma later on. Another study reported that cat allergies in adults (but not allergies to other common triggers such as ragweed or house dust) increase the risk for late-onset asthma.

What Are the Symptoms of Asthma?

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 before the patient even calls the doctor. Asthma is usually worse at night and attacks often occur between 2 and 4 AM for a number of reasons: chemical and temperature changes in the body during the night increase inflammation and narrowing of the airways; delayed allergic responses can occur from exposure to allergens during the day; and toward the early morning, the effect of inhaled medications may wear off and trigger an attack.

The classic symptoms of an asthma attack are coughing, wheezing, and shortness of breath (dyspnea). Some people first experience chest tightness or nonproductive cough that is not associated with wheezing. Wheezing when breathing out, however, is virtually always present during an attack. Symptoms vary in severity from occasional mild bouts of breathlessness to daily wheezing that persists despite taking large doses of medication. Usually the attack begins with wheezing and rapid breathing and as it becomes more severe, all breathing muscles become visibly active. The neck muscles may tighten and talking may become difficult or impossible. The end of an attack is often marked by a cough that produces a thick, stringy mucus.

Without effective treatment during an attack, exhaustion may contribute to worsening respiratory distress. As the chest labors to bring enough air into the lungs, breathing often becomes shallow. In a life-threatening situation, the skin becomes bluish, the skin around the ribs of the chest appears to be sucked in, and the patient begins to lose consciousness.

After an initial acute attack, inflammation persists for days to weeks. This second stage may cause no symptoms and yet inflammation must still be treated because it usually causes relapse, with renewed constriction of the airways and subsequent attacks.

What Other Diseases Show the Same Symptoms as Asthma?

A number of disorders may cause some or all of the symptoms of asthma. Asthma, chronic bronchitis, and emphysema all affect the lungs in similar ways and, in fact, may all be present in the same person. Unlike these other conditions, however, asthma usually first appears in patients less than 30 years old and is not revealed by abnormal chest x-rays. Other diseases that must be considered during diagnosis are respiratory tract infections, pulmonary embolism, cancer, heart failure, tumors, psychosomatic illnesses, and certain rare disorders. Panic disorder can coincide with asthma or be confused with it.

How Serious Is Asthma?

Asthma is usually chronic, although it occasionally goes into long periods of remission. Half of those with childhood asthma experience remission after age 16; in half of these, however, asthma flares up again in middle age. Asthma is now categorized by severity as mild intermittent, mild persistent, moderate persistent, and severe persistent. 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 lung and the timeliness and effectiveness of treatment. In severe persistent cases (about 10%), however, the structure of the walls of the airways changes, which leads to progressive and irreversible problems in lung function, even in aggressively treated patients.

The increase in asthma in general over the past 20 years has been world wide. About 90% of U.S. deaths from asthma occur among the elderly, the majority of whom are women. In addition to the elderly, the people at highest risk for severe asthma and death are the urban poor. This higher rate is most likely due to poorer health care; one study, for instance found that people in low-income areas were more likely to be treated just for symptoms and not given instructions for preventive treatments. The U.S. death rate from asthma increased between 1977 and 1994 from 1.5 to 3.7 per 100,000 African Americans and 0.5 to 1.2 per 100,000 whites. White women are at much greater risk of death than white men and the disparity is increasing. Some encouraging news includes reports of a general leveling off of asthma deaths in America since 1989 and a decline in British asthma deaths over the past decade. Hospitalizations for severe bouts have tripled since 1970, and annual health care costs related to asthma now total at least $6.2 billion.

Most deaths that occur from asthma are preventable. It is very rare for a person who is receiving proper treatment to die of asthma. Many individuals with asthma and even some physicians, however, underestimate the severity of this disease. One study reported that people at high risk for fatal or near-fatal asthma attacks had low awareness of their own reduced ability to breathe and therefore were slower in seeking help.

Other conditions are associated with asthma, some of which may be serious. Almost half of adults with allergic asthma have sinus abnormalities, and, according to various studies, between 17% and 30% of asthmatic patients develop true sinusitis. People with asthma that is associated with severe gastroesophageal reflux disorder may be at risk for long-term erosion of the esophagus.

Even when it is not life-threatening, asthma is debilitating and frightening. Sleeplessness is a common problem. 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 last year because of sleep disturbance.

What Tests May Be Required to Diagnose Asthma?

Medical History.
A diagnosis of asthma is suspected when a patient has a history of periodic attacks of shortness of breath, coughing, and wheezing, perhaps accompanied by tightness in the chest. The patient should describe any pattern of symptoms and possible precipitating factors, including whether symptoms are more frequent during the spring or fall (allergy seasons), and whether exercise, a respiratory infection, or exposure to cold air has ever triggered an attack. The patient should report any family history of allergic disorders, such as eczema, hives, or rhinitis (inflammation of the nasal passages). Positive responses to one or more of these questions provide additional support for a diagnosis of asthma. In adults, occupational exposure is often the trigger for an asthma attack and the physician should always ask about current and past work conditions. 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. It should be noted, however, that some studies indicate that asthma may be over diagnosed, particularly in smokers, who are likely to have temporary wheezing.

Pulmonary Function Tests.
If asthma is suspected, the physician will usually perform 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) the vital capacity (VC), which is the maximum volume of air that can be inhaled or exhaled; (2) the peak expiratory flow rate (PEFR), which is the maximum flow rate that can be generated during a forced exhalation; (3) and the forced expiratory volume (FEV1), which is the maximum volume of air expired in one second. During an attack, narrowing of the airways will decrease the PEFR and FEV1. If these measurements indicate that some degree of airway obstruction is present, the doctor may administer a bronchodilator (a drug that opens the air passages) and then measure the lung function again--reversal of the obstruction confirms a diagnosis of asthma. If there are no signs of airflow obstruction at the time the patient is examined, the doctor may perform a challenge test by administering a drug (histamine or methacholine) to induce an increase in airway resistance. A positive response to this test usually indicates the patient has asthma, although it may not be very accurate for people whose only symptom is persistent coughing. Another study showed that a negative response to a methacholine challenge test may be accurate enough to rule out work-related causes for asthma in people in high risk occupations. Another method for inducing airway resistance is to administer cold air. Although this so-called cold air hyperventilation test is very accurate for ruling out asthma, it is not sensitive enough to accurately identify adults who are actually asthmatic.

Laboratory 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 are not generally recommended for people with year-round asthma. The physician may also perform additional tests either to rule out other diseases or to obtain more information about the causes of asthma in the patient. Such tests may include a complete blood count, chest and sinus x-rays, and examination of the patient's sputum for eosinophils, white blood cells that are highly characteristic of the inflammatory aspect of asthma; sputum examination may be more accurate than blood tests for this purpose.

What Are the Drug Treatments for Asthma?

General Guidelines.
Asthma appears to be dangerously undertreated in most patients. Avoiding allergens, appropriate drug treatments, and home monitoring are key elements in preventing dangerous asthma attacks and hospitalization. Drug treatments are now categorized by their ability to (1) control long-term persistent inflammation or (2) relieve acute asthma symptoms. The primary drugs used to control inflammation are corticosteroids, leukotriene-antagonists, and cromolyn. Generally, the drugs that relieve symptoms are bronchodilators, which open the airways during an asthma attack; they include beta-adrenergic agonists (beta2 agonists), theophylline, and certain anticholinergic agents.

General Treatment Approaches. An acute attack may require hospitalization, during which beta-agonists are usually administered with a nebulizer (a device that administers the drug in a fine spray), although a recent study reports that most patients do well with hourly administration of inhaled beta-agonists. Oxygen is usually given, though a recent study found that giving 100% oxygen to very ill asthmatic patients may be harmful. A steroid may be administered if the patient does not respond to other treatments.

For maintenance therapy, experts debate whether a so-called step-up or step-down approach is best. With a step-up approach, the patient is started at low doses of medication and given increasing doses until symptoms improve. With the step-down approach, the patient is treated very aggressively at first, and then medication is reduced to the lowest effective dose. Usually, beta2 agonists are used treat symptoms of mild asthma and corticosteroid anti-inflammatory drugs are used for moderate to severe asthma. Before administering high-dose or long-term steroids for severe asthma, physicians are now being advised to add a long-term bronchodilator to the regimen. Combinations using long-acting beta2 agonists or theophylline with low or moderate doses of steroids are proving to be very effective in reducing severe and mild symptoms and improving lung function. In addition, the theophylline regimen is less expensive than high-dose steroids alone. Such combination regimens can be complicated, however, and compliance may therefore be low. Treating symptoms at night with a steroid or long-term bronchodilator or combinations so that the daily variation in peak expiratory flow is less than 10% appears to have a very positive impact on improving mental function during the day.

Drug Administration Methods. Some asthma drugs may be taken orally but most are inhaled, often using a metered-dose inhaler (MDI), which allows precise doses to be delivered directly to the lungs. These drugs must be used regularly as prescribed in order to be effective and safe. Some patients hold the inhaler too close to their mouths, or even inside them; others may exhale too forcefully before inhalation. Patients should receive detailed instructions for proper use of an inhaler from the physician. 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. Aerosol sprays release chlorofluorocarbons, which contribute to ozone depletion, a serious environmental concern. The FDA will phase out inhalers with chlorofluorocarbons when effective substitutes become widely available.

Anti-inflammatory Drugs.
Aerosol Corticosteroids. Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs currently recommended as the primary therapy for any asthmatic condition more serious than occasional episodes of mild asthma or if treatment with bronchodilators is not effective. Low-doses of inhaled steroids appear to be safe and effective for some people with mild asthma, particularly those who find themselves using beta2 agonists daily. Inhalation of corticosteroids using a metered-dose inhaler (MDI) makes it possible to provide effective local anti-inflammatory activity in the lungs with minimal systemic effects; oral steroids have considerable side effects. Corticosteroids are not bronchodilators (that is, they do not relax the airways) and have little effect if used only for acute asthma attacks. They work over time by reducing inflammation and allowing the lungs to function properly and may even prevent long-term complications. They must be taken regularly; it may take a month to perceive their effects and up to a year to achieve full benefits. A recent study showed that they reduced the rate of hospitalization from asthma by 50%; beta2 agonists had no such effect.

The older corticosteroids inhalants are beclomethasone (Beclovent, Vanceril), and dexamethasone (Decadron Phosphate Respihaler and others). Newer more powerful inhaled steroids or intranasal steroids include triamcinolone (Azmacort and others), flunisolide (AeroBid), budesonide (Pulmicort), and fluticasone (Flovent). Comparative studies indicate that fluticasone is the most potent, followed by budesonide, then flunisolide, triamcinolone, and beclomethasone. Fluticasone also costs less than budesonide. Of some concern are results of a study that suggested that fluticasone was significantly more powerful than budesonide in suppressing adrenal function, the cause of major side effects that occur when withdrawing from oral steroids [see oral corticosteroids, below ]. Studies are also showing that a single dose of one of the newer steroids, such as flunisolide or triamcinolone, may be as effective as taking two or even four doses a day in the standard regimens. Optimal timing of the dose is important and may vary depending on the medication.

Common side effects of inhaled steroids are throat irritation, hoarseness, and dry mouth. Rashes, wheezing, facial swelling (edema), fungal infections (thrush) in the mouth and throat, and bruising are also possible. Prolonged use at high doses may increase the risk of cataracts, glaucoma, osteoporosis, diabetes, and susceptibility to infections--side effects usually associated only with oral corticosteroids. Supplements of vitamin C and E may help reduce the risk of cataracts, and calcium supplements should be taken to prevent bone loss. No one should stop taking these medications, even inhaled steroids, without consulting a physician first, and if steroids are withdrawn, regular follow-up monitoring is necessary.

Oral Corticosteroids. Oral, also called systemic, corticosteroids are usually the last therapy to be added to an asthma treatment program and the first to be removed. Common oral corticosteroids that are used include prednisone, prednisolone, methylprednisolone, and hydrocortisone. They very effectively decrease inflammation but are generally used only for severe attack. A brief course of systemic corticosteroids can prevent hospitalization. In some severe cases, they may be used as maintenance. In such cases, they have numerous side effects, including but not limited to fluid retention, high blood pressure, high blood sugar, increased susceptibility to infection, osteoporosis, memory impairment, glaucoma, and cataracts. Long-term use of 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 awhile (sometimes up to a year) to regain its ability to produce natural steroids again. Uncommonly, switching from oral to inhaled steroids has caused severe adrenal insufficiency and, in rare cases, has resulted in death. The risk increases during times of stress. Patients should discuss with their physician measures for preventing adrenal insufficiency, particularly during stressful times. Investigators are studying the use of injections of some of the newer steroids, such as triamcinolone, that may allow lower doses of oral steroids. Results of one study showed promise, but some experts believe the study may have been limited, particularly since other studies have reported toxic effects with long-term triamcinolone injections that did not appear in this study.

Cromolyn and Similar Drugs. Cromolyn sodium (Intal) serves as both an anti-inflammatory drug and a specific blocking agent for triggers such as allergens or exercise. It is usually used in children with allergic asthma, but cromolyn is also the treatment of choice for preventing exercise-induced asthma (EIA) in all age groups, for pregnant women, and possibly for preventing allergic asthma in adults as well. Side effects include nasal congestion, cough, sneezing, wheezing, nausea, nosebleeds, and dry throat. Cromolyn is now administered for asthma by aerosol inhalations either before exercise for EIA or four times a day for allergic asthma. Although cromolyn can help prevent asthma attacks, particularly those precipitated by exercise, cold, and known allergens, it does not effectively treat asthma once an attack is underway. A cromolyn nasal spray called Nasalcrom has recently been approved for over-the-counter purchase, but at this time 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. Both drugs appear to be useful for aspirin-induced asthma. Nedocromil has an unpleasant taste and some people have complained of nausea, headache, and bronchospasm, but no serious side effects have been reported. Ketotifen, another similar drug that has antihistamine qualities, may be useful in preventing allergic asthma.

Leukotriene-Antagonists. Leukotriene-antagonists block leukotrienes, powerful immune system factors that are important in causing airway constriction and mucus production in allergy-related asthma. They are used for long-term prevention, not for treatment of acute asthma attacks. Zafirlukast (Accolate), montelukast (Singulaire), and zileuton (Ziflo) are now available. Other leukotriene-antagonists, including cinalukast and drugs known as 5-lipoxygenase activating protein (FLAP) inhibitors are showing promise. Leukotrienes-antagonists may be particularly effective for asthma induced by aspirin, sulfites, and exercise. They are also proving to be an effective companion in combination treating beta2 agonists for mild to moderate asthma and may make it possible for patients to avoid or reduce their use of steroids. Studies comparing these drug to steroids are still needed. One study reported that a combination of the antihistamine loratadine (Claritin) and zafirlukast was more effective than either drug alone for patients with allergic asthma. Very few side effects, except gastrointestinal distress, have been associated with the use of leukotriene-antagonists. Of some concern, however, are reports of Churg-Strauss syndrome in a few people as they were tapering off steroids and beginning to take zafirlukast; this condition is very rare, but it causes blood vessel inflammation in the lungs, flu-like symptoms, and can be life-threatening.

Bronchodilators.
Short-Acting Beta2 Agonists. Beta2 agonists do not decrease inflammation or airway responsiveness but serve as bronchodilators , relaxing and opening constricted airways during an acute asthma attack. Although they relieve symptoms of acute attacks, these drugs do not control the underlying inflammation always present in asthma--even in its mildest forms and when there are no active symptoms. Controversy has existed over whether beta2 agonists are responsible for increased the rate of asthma deaths by becoming less effective when taken regularly over time, causing over-use and increasing the risk for overdose. A number of studies, however, have not borne out an association between higher mortality rates and beta-2 agonists. Fairly conclusive research has indicated that most patients with mild asthma can use these drugs on a daily basis for months and still have a good response. One study has suggested, however, that some people with asthma may be genetically predisposed to develop an insensitivity to beta2 agonists. Another recent study reported that regular use of albuterol actually increased the presence in the airways of eosinophils, immune cells released during an allergy attack that contribute to the inflammatory response. Some experts believe this action may cause a later response to allergens, and others think that it may interfere with the actions of any corticosteroids being taken at the same time. Taking beta2 agonists on a regular schedule provides no additional benefit over taking them only when symptoms occur. The best current advice is for patients with mild asthma to use these drugs only to relieve symptoms during asthma attacks or as premedication for exercise-induced asthma. If symptoms are severe or frequent, however, the patient should consult a physician before increasing the use of the inhaler.

Bronchodilators are generally administered through inhalation. Albuterol (Proventil, Ventolin)--called salbutamol outside the U.S.--is the standard short-acting beta2 agonist in America. Other short-acting beta2 agonists are isoproterenol (Isuprel, Norisodrine, Medihaler-Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair), terbutaline (Brethine, Brethaire, Bricanyl), bitolterol (Tornalate), and isoetharine (Bronkometer, Bronkosol), which is available only in nebulizers in America. These drugs are effective for three to six hours.

Side effects of beta2 agonists include anxiety, tremor, restlessness, and 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 individuals with diabetes, high blood pressure, hyperthyroidism, an enlarged prostate, or a history of seizures. People with heart conditions who take beta2 agonists orally or with a nebulizer (but not from an inhalers) face an increased risk for sudden death from cardiac-related causes. 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.

Long-Acting Beta2 Agonists. Long-acting beta2 agonists are now available for preventing--but not for treating--an asthma attack. The first drug approved was salmeterol (Serevent). A similar drug formoterol (Foradil) may be released in the future. Adding salmeterol to a long-term steroid maintenance program could allow reduced dosages of the anti-inflammatory corticosteroids. It should be pointed out that even though salmeterol effectively reduces asthma symptoms when used alone, it has no effect on inflammation and studies are mixed about its benefit on lung function. The effects of one dose of salmeterol last for about 12 hours, so it is particularly effective during the night and for prevention of exercise-induced asthma in people who work out or labor for long hours. A study reported that after taking salmeterol for exercise-induced asthma for more than a month, it lost effectiveness after a few hours. Using slightly higher doses of inhaled steroids and not taking salmeterol daily may be helpful. Salmeterol is about four times more potent than albuterol but takes up to 20 minutes to become effective. Patients should be warned that deaths have been reported when people did not experience relief soon enough from an initial dose and subsequently overdosed from taking additional doses of salmeterol. The risk appears to be highest in elderly patients with severe asthma. The medication should not be stored in locations that are easily accessible during acute attacks, such as by the bed or in a pocketbook. They should never be used for treatment of acute episodes; for this purpose, albuterol or other short-acting bronchodilators should be used. Formoterol appears to have a faster action (less than 15 minutes) than salmeterol. [For side effects, see Short-Acting Beta2 Agonists, above.]

Theophylline. Theophylline 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. If theophylline is not taken exactly as prescribed, however, an overdose can easily occur. Toxicity causes nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in hearth rhythm and convulsions. A physician should be contacted immediately if any of these side effects occur. The risk for these adverse effects are small if the drug is taken exactly as prescribed. It should be noted that chronic smokers metabolize theophylline much more quickly and require higher doses of the drug than nonsmokers; prolonged-release versions are helpful for such people. People taking theophylline should keep their daily caffeine intake to the equivalent of six cups of coffee or below; 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. 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. People with heart conditions who take theophylline orally face an increased risk for sudden death from heart-related causes.

Anticholinergic Agents. Inhaled ipratropium bromide (Atrovent) acts as a bronchodilator over time. It is not approved specifically for asthma, but it may be useful for certain older patients who also have chronic obstructive lung disease. Ipratropium bromide alone is not useful for acute asthma attacks, nor does it add any benefit to a beta2 agonist in the first 90 minutes of an attack. The combination might be helpful, however, for patients who do not initially respond to treatment with beta2 agonists alone.

Antihistamines.
For years, people with asthma and allergies have been told to avoid antihistamines because they dry sinuses and cause constriction of the airways and sedation. Newer antihistamines, including fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec) may be beneficial for mild allergic asthma, but antihistamines are still problematic and are usually not beneficial for moderate to severe asthma. People should not use antihistamines if a sinus or respiratory infection is present. Used routinely, antihistamines thicken mucous secretions and can worsen respiratory infections. It is particularly important to treat any co-existing sinus infection in people with asthma because they might not respond to asthma treatments unless the infection is first cleared up.

Treatment of Other Disorders that Might Cause Asthma.
Treating gastroesophageal reflux disease may actually cure asthma in some patients who have both conditions. In one small study, asthmatic patients who had blood tests showing current or previous infection by Chlamydia pneumonia were aggressively treated with antibiotics and afterward showed significant or complete improvement in their asthma symptoms. Better controlled studies are needed, and antibiotics, in any case, would not be effective in patients whose asthma was triggered by allergens or unknown causes. Allergy shots may provide some relief for people whose asthma is worse during ragweed season, but some researchers view this therapy as impractical.

Experimental Treatments.
The common anesthetic lidocaine, which is also an anti-inflammatory agent, is showing promise as an alternative to steroids. Drugs that suppress the immune system, including cyclosporine, may prove to be effective and safe when used in spray form; they can have very serious side effects, however, and additional research is needed. Other drugs that are being designed to block agents in the inflammatory process include rhuMAb-E25 and CTLA4-IgG, which act against the antibody IgE, and rPAF-AH, which regulates another inflammatory factor. Heparin, a drug commonly used to prevent blood clots, may be as effective as cromolyn and even longer-acting in preventing exercise-induced asthma attacks when inhaled an hour before exercising.

How Can Asthma Attacks Be Prevented?

Lifestyle Changes.
Avoidance or control of the triggers that lead to asthma attacks is as much a priority as treatment of the disease. Everything possible should be done to identify the irritants that are causing the inflammatory response in the lungs. About 50% of adults with asthma exhibit allergic responses. Because there are so many substances that can trigger allergic responses, identifying and avoiding the allergens can be very difficult, even with the use of allergy skin tests. Patients can, however, take some relatively simple actions to avoid the most obvious and common problems.

Indoor Prevention. Air cleaners, filters for air conditioners, and vacuum cleaners with HEPA filters can help remove particles and small allergens found indoors. The American Lung Association recommends that air cleaners have filters that are efficient for at least several months and that they do not produce ozone levels over 0.05 ppm. They should contain a charged or uncharged fibrous media. Air cleaners help with some airborne particles but have little effect against cat allergies or dust mite feces which lodge in carpets and bedding. Another study found, however, that HEPA vacuum cleaners are effective in preventing cat allergens from being released into the air. Vacuuming does not remove mites and may, in fact, stir them up into the air. New air cleaners that convert harmful pollutants to harmless substances are showing promise. On-going humidifiers can be counterproductive because dust mites thrive in humidity, and because they can develop mold if not cleaned daily with a vinegar solution; humidity levels should not exceed 40%. It is best to avoid carpets or to consider treating them with a chemical that kills the mites, such as Acarosan. The chemical should also be applied to carpeted areas under furniture. Curtains should be replaced with shades or blinds and bedding washed using the highest temperature setting. Semipermeable mattress pads and pillows significantly reduce dust mite levels. Studies have found that synthetic pillows pose a risk for severe asthma attacks in children that is three times the risk from feather pillows or no pillows. Vinyl mattress covers limit airflow and may also exacerbate, or even cause, asthma in children. Electric stoves should replace gas ovens, which release nitrogen dioxide.

Outdoor Prevention. Patients should do everything possible to avoid unnecessary exposure to irritants, such as cigarette smoke and auto exhaust fumes. 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). It should be noted that ozone can affect the lungs of hikers even during low pollen months. Patients who are allergic to mold should avoid barns, hay, raking leaves, and mowing grass. (A recent study, however, found that mold was not associated with increased risk for severe asthma in adolescents.) Exposure to automobile fumes may worsen asthma. Fungi in car air conditioners can also be a problem...

Pets. Pets pose particular problems; they can trigger asthma but are often emotionally important to the household, particularly to children. Cats harbor significant allergens; dogs usually present fewer problems. Washing cats and dogs 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. Baths should be given by a non-allergic person, preferably outdoors.

Drugs. Aspirin and products containing aspirin can cause life-threatening asthma attacks in susceptible individuals. Acetaminophen (e.g., Tylenol) is an alternative for relief of minor pain. A pharmacist should be consulted if the ingredients of any over-the-counter preparations are not known. A number of drugs interact with asthma medications, so all drugs being taken should be discussed with the physician. Taking hormone replacement therapy may increase the risk for asthma, although women with asthma who take oral contraceptives may experience fewer symptoms around the time of menstruation.

Foods. People with asthma should avoid foods seasoned with MSG and those preserved with sulfites if they experience exacerbation of their asthma after eating such foods. Lowering salt intake and eating more fish may be protective, although canned tuna can contain sulfites and should be avoided.

Avoiding Respiratory Infections. People with asthma should try to minimize their risk for respiratory tract infections. Unless they are allergic to eggs, asthmatics should receive vaccinations against influenza each fall. Some people with asthma may also benefit from a single vaccination against pneumococcal pneumonia.

Exercise-Induced Asthma. Treatment for exercised-induced asthma (EIA) is very effective, allowing people with asthma to exercise at the same intensity as those without asthma, although the cardiorespiratory fitness of a person with asthma may be a bit lower. Being sure to warm-up before and cool-down after exercising may reduce the risk of an attack. People who enjoy running should probably choose an indoor track to avoid pollutants. While no study has shown conclusively that exercise and good cardiorespiratory fitness will improve the symptoms or condition of asthma, it goes without saying that all the usual benefits of exercise (lowering of blood pressure, increased physical fitness, lowered chances of cardiovascular problems, and a sense of well-being) are available to the person with asthma. People with asthma should consult their physicians for an exercise program suited to their specific condition.

Quitting Smoking. Cigarette smoke is a potent irritant that can initiate and aggravate asthma, and asthmatics who smoke are taking major risks with their health. [For help in quitting, see Smoking ].

Improving Psychologic Outlook. People with asthma have no higher rate of anxiety or depression than the general population, but those who have both asthma and emotional disorders report more severe symptoms. Negative emotions can discourage proper treatment and the ability to cope. Motivated self-education and a positive attitude can be of considerable help in the long-term management of asthma. One study showed that hypnosis helped reduce symptoms.

Controlling Occupational Factors. In people whose asthma is caused by workplace conditions, improved ventilation or face masks may help, but often even low levels of chemical agent can trigger a response. In such cases, leaving the job is the only way to prevent the condition from getting worse, especially because increased exposure to asthma triggers in the workplace worsens the condition. Although the effects may be life-long, in one study, 70% of people with asthma experienced significant improvement in symptoms after leaving the job. This can often be a severe emotional and financial hardship, and workers should be sure occupational substances are the cause 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.

Monitoring.
Studies show that people who self-manage their asthma using daily monitoring of peak air flow and adjusting their medications as needed have fewer hospitalizations and unplanned doctor's 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 by using a peak flow meter. The physician will demonstrate the proper way to use the flow meter. Some recommend taking readings two or three times a day, although for mild to moderate asthma, a single determination each morning usually suffices. 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 recognizing problems before they become serious. The overall treatment and management goal should be to achieve a less than 20% and ideally 10% difference between evening and morning rates. A device called AirWatch can help asthmatics monitor their breathing. To use it, the patient breathes into a hand-held monitor that measures and displays the rate of airflow, comparing it to the rates from previous days. Once monthly, 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.