Asthma
Asthma is a condition in which the airways narrow--usually reversibly--in response to certain stimuli.
Asthma affects about 17 to 18 million people in the United States and is becoming more common. Between 1982 and 1992, the number of people with asthma increased by 42%. Asthma is particularly common in blacks living in urban environments (affecting about 7%) and even more so in Hispanic populations living in urban environments (affecting about 11%). The condition also seems to be becoming more serious, requiring more people to be hospitalized. Between 1982 and 1992, the death rate from asthma in the United States increased by 35%. The condition usually begins in childhood, although some adults develop asthma, even at an old age. Asthma in children can interfere with normal growth and development (see Section 23, Chapter 274).
The reason for the increase in the prevalence of asthma among children is not known, but it may relate to one or both of the following theories. One theory is that the widespread use of vaccines and antibiotics in children has shifted the activity of a special subgroup of white blood cells (called lymphocytes) in the body from fighting infection to releasing chemical substances that inadvertently promote the development of allergies. Another theory is that, because children are spending more time indoors and living in better-insulated homes than they were in the past, the exposure to potentially allergic substances is increased. There are few data to support either theory.
The most important characteristic of asthma is airway obstruction. The airways of the lungs (the bronchi) are basically tubes with muscular walls (see Section 4, Chapter 38). Cells lining the bronchi have microscopic structures, called receptors. There are three main types of receptors: beta-adrenergic, cholinergic, and peptidergic. These receptors sense the presence of specific substances and stimulate the underlying muscles to contract and relax, thus altering the flow of air. Beta-adrenergic receptors respond to chemicals such as epinephrine and make the muscles relax, thereby widening (dilating) the airways and increasing airflow. Cholinergic receptors respond to a chemical called acetylcholine, making the muscles contract and decreasing airflow. Peptidergic receptors respond to substances called neurokinins, also making the underlying muscles of the airways contract.
Causes
Airway obstruction is often caused by abnormal sensitivity of cholinergic and peptidergic receptors, which cause the muscles of the airways to contract when they should not. Certain cells in the airways, particularly mast cells, are thought to be responsible for initiating the airway narrowing. Mast cells throughout the bronchi release substances such as histamine and leukotrienes, which cause smooth muscle to contract, mucus secretion to increase, and certain white blood cells to migrate to the area. Eosinophils, a type of white blood cell found in the airways of people with asthma, release additional substances, contributing to airway narrowing.
 See the figure How Airways Narrow.
In an asthma attack, the smooth muscles of the bronchi narrow (called bronchoconstriction), and the tissues lining the airways swell from inflammation and secrete mucus into the airways. The top layer of the lining of the airways can become damaged and shed cells. These actions further narrow the diameter of the airways; the narrowing requires the person to exert more effort to move air in and out of the lungs. In asthma, airway obstruction is reversible, meaning that with appropriate treatment or on their own, the muscular contractions of the airways stop, the airway obstruction ends, and the airflow into and out of the lungs returns to normal.
 See the animation How Airways Narrow.
In a person who has asthma, the airways narrow in response to stimuli that usually do not affect the airways in normal lungs. The narrowing can be triggered by many inhaled allergens, such as pollens, particles from dust mites, body secretions from cockroaches, particles from feathers, and animal dander. These allergens combine with immunoglobulin E (a type of antibody) on the surface of mast cells to trigger the release of asthma-causing chemicals from these cells. (This type of asthma is called allergic asthma.) Although food allergies induce asthma only rarely, certain foods (such as shellfish and peanuts) can induce severe attacks in people who are sensitive to these foods.
Cigarette smoke, cold air, and viral infections can also provoke asthma attacks. Additionally, a person who has asthma can develop bronchoconstriction when exercising. Stress and anxiety can trigger mast cells to release histamine and leukotrienes and stimulate the vagus nerve (which connects to the airway smooth muscle), which then contracts and narrows the bronchi.
Symptoms and Complications
Asthma attacks vary in frequency and severity. Some people who have asthma are symptom-free most of the time, with only an occasional, brief, mild episode of shortness of breath. Other people cough and wheeze most of the time and have severe attacks after viral infections, exercise, or exposure to allergens or irritants, including cigarette smoke. Crying or hearty laughing may bring on symptoms in some people. Some people with asthma produce a clear and at times sticky (mucoid) phlegm (sputum). Asthma attacks occur most often in the early morning hours when the effects of protective medications wear off and the body is least able to prevent bronchoconstriction.
An asthma attack may begin suddenly with wheezing, coughing, and shortness of breath. Wheezing is particularly noticeable when the person breathes out. At other times, an asthma attack may come on slowly with gradually worsening symptoms. In either case, people with asthma usually first notice shortness of breath, coughing, or chest tightness. The attack may be over in minutes, or it may last for hours or days. Itching on the chest or neck may be an early symptom, especially in children. A dry cough at night or while exercising may be the only symptom.
During an asthma attack, shortness of breath may become severe, creating a feeling of severe anxiety. The person instinctively sits upright and leans forward, using the neck and chest muscles to help in breathing, but still struggles for air. Sweating is a common reaction to the effort and anxiety. The pulse usually quickens, and the person may feel a pounding in the chest.
In a very severe asthma attack, a person is able to say only a few words without stopping to take a breath. However, wheezing may diminish, because hardly any air is moving in and out of the lungs. Confusion, lethargy, and a blue skin color (cyanosis) are signs that the person's oxygen supply is severely limited, and emergency treatment is needed. Usually, a person recovers completely with appropriate treatment, even from a severe asthma attack. Rarely, some people develop attacks so quickly that they may lose consciousness before they can give themselves effective therapy. Such people should wear a medical alert bracelet and perhaps carry a cellular phone to call 911.
Rarely, the small air sacs of the lung (alveoli) may rupture, allowing air to accumulate in the space between the membrane layers covering the lungs and inner chest wall (the pleural space). This complication (pneumothorax) greatly worsens the shortness of breath; often a chest tube needs to be inserted into the affected pleural space to drain the air and re-expand the collapsed lung (see Section 4, Chapter 52).
 See the sidebar Status Asthmaticus.
Diagnosis
A doctor suspects asthma based largely on a person's report of characteristic symptoms. A diagnosis of asthma can be confirmed using spirometry tests. During an asthma attack, the test reveals decreased air flow, but over hours or days, narrowing improves and is therefore reversible. More commonly, the doctor performs spirometry or pulmonary function tests (see Section 4, Chapter 39) before and after giving the person an inhaled beta-adrenergic agonist. If results are significantly better after the person receives the beta-adrenergic agonist, asthma is thought to be present. If the airways are not narrowed at the time of the first test, a diagnosis can be confirmed by a test in which the person inhales a chemical (usually methacholine but histamine may be used also) in doses too low to affect a normal person but which causes airway narrowing in a person who has asthma.
Spirometry is also used to assess the severity of the airway obstruction and to monitor treatment. Peak expiratory flow (the fastest rate at which air can be exhaled) can be measured using a small handheld peak flow meter. Often, this test is used at home to monitor the severity of asthma. Usually, peak flow rates are lowest between 4:00 and 6:00 a.m. and highest at 4:00 p.m. However, more than a 30% difference in rates at these times is considered evidence of moderate to severe asthma.
Determining what triggers a person's asthma is often difficult. Allergy testing is appropriate when there is a suspicion that some avoidable substance is stimulating attacks. Skin testing can help identify allergens that may trigger asthma symptoms. However, an allergic response to a skin test does not necessarily mean that the allergen being tested is causing the asthma. The person still has to note whether attacks occur after exposure to this allergen. If a doctor suspects a particular allergen, a blood test that measures the level of antibody produced in response to the allergen (the radioallergosorbent test [RAST]) can be performed to determine the degree of sensitivity.
To test for exercise-induced asthma, an examiner uses spirometry before and after exercise on a treadmill or stationary bicycle to measure forced expiratory volume in 1 second. If the forced expiratory volume in 1 second decreases more than 15%, the person's asthma can be induced by exercise.
A chest x-ray is not generally helpful in diagnosing asthma. Doctors use chest x-rays when considering another diagnosis. However, a chest x-ray is often obtained when a person with asthma needs to be hospitalized or is treated in the emergency department with severe asthma.
Prevention and Treatment
There is an array of drugs that can be used to prevent and treat asthma attacks. Most of the drugs used to prevent asthma are also used to treat an asthma attack but in higher doses or in different forms. Some people need to use more than one drug to prevent and treat their symptoms.
Therapy is based on two classes of antiasthmatic drugs. The first are anti-inflammatory drugs, which suppress the inflammation that triggers the airways to narrow. The second are bronchodilators, which help to relax and widen (dilate) the airways. Within each of these two classes, several drugs are available. Anti-inflammatory drugs include corticosteroids (which are inhaled, taken by mouth, or given intravenously), leukotriene modifiers, and cromolyn. Bronchodilators include beta-adrenergic agonists and theophylline.
 See the figure How to Use a Metered-Dose Inhaler.
Education about how to prevent and treat asthma attacks is beneficial for all people who have asthma and often for their family members. Proper use of inhalers is essential for effective treatment. People should know what can stimulate an attack, what helps to prevent an attack, how to use drugs properly, and when to seek medical care. Many people use a handheld peak flow meter to evaluate their breathing and determine when they need intervention, before their symptoms get extreme. A person who experiences frequent, severe asthma attacks should know how to reach help quickly.
Many people have a written treatment plan that was devised in collaboration with their doctor. Such a plan allows them to take control of their own treatment and has been shown to decrease the number of times people need to seek care for asthma in the emergency department.
Preventing Attacks
Asthma is a chronic condition that cannot be prevented or cured; however, individual attacks can often be prevented. Asthma attacks may commonly be prevented if the factors that trigger them are identified and treated or avoided. People who have asthma should avoid cigarette smoke. Often, attacks triggered by exercise can be blocked by taking medication beforehand. When dust and allergens are the problem, air filters, air conditioners, and other types of barriers (such as mattress covers, which reduce the amount of particles from dust mites that are in the air) can help considerably. For people whose asthma is stimulated by allergies, desensitization through the use of allergy shots may prevent attacks.
Some people who have asthma may have a sensitivity to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs); if this is the case, these drugs must be avoided. Drugs that block the beneficial effects of beta-adrenergic agonists (called beta-blockers) usually worsen asthma.
Most people with asthma take drugs, such as inhaled or oral corticosteroids, leukotriene modifiers, long-acting beta-adrenergic agonists, theophylline, antihistamines, or cromolyn to prevent attacks. Prevention efforts are individualized according to the frequency of attacks and the stimuli that trigger the attacks.
A new treatment for asthma is being studied and developed based on use of a special antibody (given intravenously or injected just under the skin) that binds immunoglobulin E, blocking its attachment to mast cells. By preventing immunoglobulin E from attaching to mast cells, these cells can no longer release the substances that cause allergic asthma.
See the sidebar Avoiding Common Causes of Asthma Attacks.
Treating Attacks
An asthma attack can be frightening, both to the person experiencing it and to others around. Even when relatively mild, the symptoms provoke anxiety and alarm. A severe asthma attack is a life-threatening emergency that requires immediate, skilled, professional care. If not treated adequately and quickly, a severe asthma attack can cause death.
People who have asthma are generally able to treat most attacks without assistance from a health care professional. Typically, they use an inhaler to deliver a dose of a short-acting beta-adrenergic agonist, move into fresh air (away from cigarette smoke or other irritants), and sit down and rest. Some people may inhale a corticosteroid in addition to a beta-adrenergic agonist. An attack usually subsides in 5 to 10 minutes. An attack that does not subside in 15 minutes or that gets worse is likely to require additional treatment supervised by a doctor.
Because people with severe asthma commonly have low blood oxygen levels, a doctor may check the level of oxygen either by using a sensing monitor on a finger or ear or by taking a sample of blood from an artery (see Section 4, Chapter 39). Supplemental oxygen may be given during attacks. However, in severe attacks, a doctor also needs to monitor carbon dioxide levels, and this test requires a sample of blood from an artery. A doctor may also check pulmonary function, usually with a spirometer or a peak flow meter. Usually, a chest x-ray is needed only in severe asthma attacks. People experiencing very severe asthma attacks may need to have an artificial airway passed through their mouth and throat (intubation) and be placed on a mechanical ventilator (see Section 4, Chapter 55).
Generally, people who have severe asthma are admitted to the hospital if their lung function does not improve after receiving a beta-adrenergic agonist and corticosteroids or if they have a seriously low blood oxygen level or a high blood carbon dioxide level.
Intravenous fluids may be needed if the person is dehydrated. Antibiotics also may be needed if a doctor suspects a lung infection; however, most such infections are due to viruses for which (with a few exceptions) no treatment exists.
Drugs for Preventing or Treating Attacks
Drugs allow most people with asthma to lead relatively normal lives. Most of the drugs used to treat an asthma attack can be used (often in lower doses) to prevent attacks.
Short-acting Beta-adrenergic Agonists: Short-acting beta-adrenergic agonists are usually the best drugs for relieving asthma attacks. They can prevent certain attacks, such as exercise-induced asthma. These drugs are also referred to as bronchodilators because they stimulate beta-adrenergic receptors to widen (dilate) the airways. Bronchodilators that act on all beta-adrenergic receptors throughout the body, such as epinephrine, cause side effects such as rapid heartbeat, restlessness, headache, and muscle tremors. Bronchodilators (such as albuterol) that act mainly on beta2-adrenergic receptors, which are found primarily on cells in the lungs, have little effect on other organs and thus cause fewer side effects. Most beta-receptor agonists, especially the inhaled ones, act within minutes, but the effects last only 2 to 6 hours. New, longer-acting bronchodilators are available, but because they do not begin to act as quickly, they are used for prevention rather than for attacks of asthma. When the long-acting beta-adrenergic agonists are used together with inhaled corticosteroids, better results are obtained. A combination of salmeterol (a long-acting beta-adrenergic agonist) with a corticosteroid in an inhaler is also available.
Most often, beta-adrenergic agonists are inhaled using metered-dose inhalers (handheld cartridges containing gas under pressure). The pressure turns the drug into a fine spray containing a measured dose of drug. Inhalation deposits the drug directly in the airways, so that it acts quickly, but the drug may not reach the airways that are severely obstructed. For people who have difficulty using a metered-dose inhaler, spacers or holding chambers can be used. With any type of inhaler, proper technique is vital; if the device is not used properly, the drug will not reach the airways. A dry powder drug formulation is also available. The powder formulation is easier for some people to use, in part because it requires less coordination with breathing.
Beta-adrenergic agonists can also be delivered directly to the lungs using a metered-dose inhalers. A nebulizer creates a mist of drug, and its use does not have to be coordinated with breathing. Nebulizers are more portable than they were in the past; some units can even be plugged into a cigarette lighter in a car.
Beta-adrenergic agonists can also be taken in liquid or tablet form or injected. However, the oral drugs tend to work slower than the inhaled or injected ones and are more likely to cause side effects. Side effects include abnormal heart rhythms, which may suggest excessive use.
Other bronchodilators may be combined with beta-adrenergic agonists for acute attacks, including intravenous infusions of aminophylline (a type of theophylline) and nebulized ipratropium. A combination of ipratropium with albuterol in a metered-dose inhaler is also available.
Quick medical attention should be sought when a person who has asthma feels the need to use more of a beta-adrenergic agonist than is recommended. Overusing these drugs can be very dangerous. The need for continuous use indicates severe bronchoconstriction, which can lead to respiratory failure and death.
Theophylline: Theophylline is another drug that produces bronchodilation. It is usually taken by mouth but can be given intravenously in the hospital. Oral theophylline comes in many forms, from short-acting tablets and syrups to longer-acting sustained release capsules and tablets. Theophylline is used for both prevention and treatment of asthma.
The amount of theophylline in the blood can be measured in a laboratory and must be closely monitored by a doctor. Too little drug in the blood may provide little benefit, and too much drug may cause life-threatening abnormal heart rhythms or seizures. When first taking theophylline, a person who has asthma may feel slightly jittery and may develop headaches. These side effects usually disappear as the body adjusts to the drug. Larger doses may cause a rapid heartbeat, nausea, or palpitations. A person may also experience insomnia, agitation, vomiting, and seizures.
Anticholinergic Drugs: Anticholinergic drugs, such as ipratropium, block acetylcholine from causing smooth muscle contraction and from producing excess mucus in the bronchi. These drugs are usually inhaled but can be given intravenously in the hospital. These drugs further widen (dilate) the airways in people who have already been given beta-adrenergic agonists. However, doctors use anticholinergic drugs mainly in the emergency department in combination with a beta-adrenergic agonist. When used alone, anticholinergics are only marginally effective.
Leukotriene Modifiers: Leukotriene modifiers, such as montelukast, zafirlukast, and zileuton, are the newest drugs available to help control asthma. They are anti-inflammatory drugs, preventing the action or synthesis of leukotrienes, chemicals made by the body that cause bronchoconstriction. These drugs, which are taken by mouth, are used more to prevent asthma attacks than to treat them, although because leukotrienes are increased in acute asthma, these drugs potentially can be used during an attack as well.
Cromolyn and Nedocromil: These drugs, which are inhaled, are thought to inhibit the release of inflammatory chemicals from mast cells and make the airways less likely to narrow. Thus, they are also anti-inflammatory drugs. They are useful for preventing but not treating an attack. These drugs may be helpful for children who have asthma and for people who develop asthma from exercise. Cromolyn and nedocromil are very safe and must be taken regularly even when a person is free of symptoms.
Corticosteroids: These drugs block the body's inflammatory response and are exceptionally effective at reducing asthma symptoms. They are the most potent form of anti-inflammatory drugs and have been an important part of asthma treatment for decades. They are given in the inhaled form to prevent attacks and improve lung function. They are given by mouth in higher doses for people experiencing severe attacks. Corticosteroids given by mouth are generally continued for at least several days after a severe attack. Corticosteroids can be taken in several different forms. Often, inhaled versions are best because they deliver the drug directly to the airways and minimize the amount sent throughout the body. They come in several strengths and are generally used twice a day. The person should rinse the mouth after use to decrease the likelihood that an infection of the mouth (thrush) develops (see Section 17, Chapter 197). Oral or injected corticosteroids may be used in high doses to relieve a severe asthma attack and are generally continued for 1 to 2 weeks. Oral corticosteroids are prescribed on a long-term basis only when no other treatments can control the symptoms.
If taken for long periods, corticosteroids gradually reduce the likelihood of an asthma attack by making the airways less sensitive to a number of provocative stimuli. Long-term use of corticosteroids, especially larger doses taken by mouth, can produce side effects.
 See the drug table Drugs Used to Treat Asthma.
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