Asthma

Definition

Asthma is a chronic inflammatory disease of the respiratory system that causes breathing difficulty. Asthma comes from the Greek word for panting. The disease is an over-responsiveness of the respiratory system to stimulating factors. It is characterized by repeated, temporary episodes of constriction and inflammation of the airways and lungs, along with excess mucous production. Asthma causes wheezing, coughing, and shortness of breath. Asthma attacks are characterized by severe difficulty breathing, especially when exhaling. Severe attacks that are left untreated may become fatal. An individual with asthma may be completely without symptoms between attacks.

Description

Asthma is a chronic, lifelong disease that affects the complex network of air passageways of the respiratory system. People with asthma may experience from mild discomfort to life-threatening attacks that require immediate emergency treatment. The respiratory system is made up of bronchial tubes (airways) and the lungs. Asthma involves the inflammation of the bronchial tubes and lining of the lungs. The inflammation causes the airways to be overly sensitive to irritating factors, which cause constriction and obstruction to the passage of air into the lungs. Asthmatics also produce excess amounts of mucous in the respiratory tract. Mucous is a normal component of respiratory function that aids in carrying irritating particles up and out of the respiratory system to be expectorated (coughed up) from the body. Asthmatics produce excessive, abnormally thick mucous that interferes with breathing and contributes to the problem. Severe asthma attacks can be fatal. Persistent or chronic inflammation of the airways can cause permanent damage, or airway "remodeling," and reduce lung function so that breathing becomes less efficient even outside of asthma attacks. Asthmatics may experience chronic wheezing, coughing, shortness of breath, and a feeling of a tightening of the chest. Medication and careful management of the disease is often necessary for maintaining normal function.

Chronic asthma has both a genetic and an environmental component. Research has demonstrated that some individuals inherit a strong genetic predisposition for asthma that can be triggered by a variety of environmental factors. Stimuli for triggering asthmatic symptoms include repeated exposure to irritants, such as dust mites, pet hairs, and tobacco smoke. These types of stimuli are considered allergens, or particles that trigger an allergic response. Asthma may also be induced by exercise, especially in cold climates where the respiratory system has to work harder to warm and moisten inhaled air. Some asthmatics only experience symptoms during viral infections. Asthma may also be stimulated by emotional stress. Both physical and psychological factors may precipitate an asthma attack.

Genetic profile

Asthma is a complex heritable disease in which a number of different genes contribute to asthmatic predisposition. While genes may cause a predisposition to asthma, actual asthma attacks are triggered by stimulating environmental factors. It has been clearly established that asthma tends to run in families. Research demonstrates increased risk of developing asthma for children of asthmatics. Studies also show that identical twins are more likely to share a genetic predisposition for asthma than are fraternal (non-identical) twins.

According to the National Institutes of Health (NIH) in 2005, chromosomes 5, 6, 11, 14, and 12 have all been implicated in asthmatic predisposition. However the relative role each of these genes has in asthma predisposition is not clear. One of the most likely candidates for further investigation is chromosome 5. Chromosome 5 is full of genes-encoding molecules involved in the inflammatory response that characterizes asthma.

Research studies show that specific symptoms experienced by asthma patients, such as the inflammation of the airways and lungs, are initiated by the action of genes that regulate the activity of the immune system. In other words, these genes control how the immune system responds to the presence of substances that can potentially trigger asthma symptoms. Like a microscopic army, the immune system consists of a wide array of specialized cells that work together to neutralize threats to the system. Antigens are any foreign agent invading the body that triggers such an immune response. Antigens include disease-producing organisms such as viruses, toxic chemicals in the environment, or allergens such as animal dander and dust mites. In response to the identification of foreign antigen particles, some immune cells produce antibodies to attack specific types of antigens. This immune response occurs after an initial encounter with an antigen and is known as a primary immune response. The immune system recognizes past contact with specific antigens by maintaining specific levels of the antibodies customized to attack specific antigens. When the same antigen is encountered again, the specific antibodies that have been maintained in the body multiply and mount a stronger immune response than the primary response. This process is known as the secondary immune response.

One of the specific antibodies produced in response to allergens is a protein known as immunoglobulin E (IgE), encoded by chromosome 5. In a normal inflammatory response, IgE recognizes foreign antigens and initiates immune reactions against the antigen by binding to other immune cells such as mast cells. Mast cells release chemical mediators that contribute to inflammation directly, but also recruit more immune cells to the site of inflammation. The recruited immune cells also release mediators of inflammation, such as histamine, that amplify the response and cause inflammation. Chromosome 5 encodes for multiple components of this immune response. In asthmatics, the IgE mast cells are highly excitable, making them hypersensitive to stimulation. When foreign antigens are breathed into the respiratory system, the entire inflammatory process, including the recruitment of other immune cells that release histamine, becomes exaggerated, resulting in asthma.

Research indicates that asthmatics produce higher levels of IgE antibodies, more hyperactive mast cells, and higher levels of consequent histamine than non-asthmatics. Histamine is a type of chemical signal that initiates the inflammatory response. Histamine stimulates the dilation of blood vessels walls and makes them more porous. As a result, blood fluid and proteins leak out of the blood vessels and into surrounding tissue, causing the swelling and reddening typical of inflammation. Inflammation involves increased blood flow to affected tissues to allow the passage of the recruited immune cells from the blood into the affected tissues. The immune cells may then dispose of the foreign particles. While this response is designed to defend the tissue from foreign invasion of harmful particles, an exaggerated response can be dangerous. In asthma, the resultant inflammation, along with the reactive constriction of the muscles in walls of the bronchial airways, narrows the air passages and causes an asthma attack.

Another component of the immune defense is the production of nitric oxide gas (NO) by an enzyme called inducible nitric oxide synthase (iNOS). Cells lining the bronchial tubes contain this enzyme that produces NO in response to chemical signals released from immune cells. Asthmatics produce an abnormally high level of iNOS in their respiratory cells than do non-asthmatics. Asthmatics have higher levels of NO in their lungs and bronchial tubes that contribute to the disease.

While chromosome 5 is implicated in asthma, there is conflicting evidence as to whether the genes responsible for the hyperactivity of the immune response in bronchial passages are distinct from the genes that regulate the action of the immune system. However, a region of chromosome 5 involved in the regulation of the immune system has been named bronchial hyperresponsiveness-1 (BHR1). Research on the BHR1 region is currently being performed by the NIH, in addition to other genetic regions. Another possible contributing factor for the overproduction of IgE antibodies could be a lack of exposure to common childhood illnesses. For example, cold viruses and other respiratory illnesses stimulate the human immune system to produce a certain type of immune cell, called a helper T cell, which specifically targets these disease agents. However, in the absence of stimuli, the immune system instead produces another type of helper T cell that initiates the production of the IgE antibody.

Demographics

In the United States, about 15 million people had asthma in 2004; approximately five million were children. Asthma affects individuals of all ages, but often starts in childhood. More than 50% of asthma cases occur in children between two and 17 years of age. Asthma is the most prevalent childhood chronic disease, and is more common in children than adults. In children, more males have asthma than females. Male children have a 30% higher prevalence of asthma compared to females. In adults, the trend is reversed, with more females having asthma than males. Adult females have a 30% higher prevalence of asthma than adult males. Within ethnic groups, non-Hispanic blacks have more asthma attacks and are more likely to be hospitalized and die from asthma than non-Hispanic whites. Asthma is distinct from, but closely linked to, allergies. Most, but not all, people with asthma have allergies.

The Centers for Disease Control (CDC) conducted a National Health Interview Survey in 2002 regarding asthma. At the time of the survey, 30.8 million individuals in the United States had been diagnosed with asthma during their lifetime: 21.9 million were adults and 8.9 million were children. Among all racial and ethnic groups, Puerto Ricans had the highest rate of lifetime asthma. Puerto Ricans were approximately 80% more likely than non-Hispanic whites to have been diagnosed with asthma.

Asthma attack prevalence is a crude indicator of how many individuals have uncontrolled asthma and are at risk for hospitalization. In 2002, 12 million people had experienced an asthma attack within the past year. Asthma attack prevalence decreased with age, being most prevalent in children. Puerto Ricans had the highest asthma attack prevalence, a full 100% higher than non-Hispanic whites. The prevalence of an asthma attack was about 30% higher in non-Hispanic blacks than in non-Hispanic whites. In this survey, Non-Hispanic blacks were the most likely to die from asthma, with an asthma death rate more than 200% higher than non-Hispanic whites. Females had an asthma death rate approximately 40% higher than males. Differences in male and female hormones may cause this disparity.

Asthma has been described as the fastest-growing chronic disease and a worldwide epidemic. According to Global Initiative for Asthma (GINA), an asthma research and education program, asthma accounts for about one in every 250 deaths worldwide. Many of the deaths are believed to be preventable and are caused by poor medical care. GINA estimates there are over three million asthmatic individuals worldwide. In most countries, asthmatic cases are increasing 20–50% every decade. The United States is one of the top countries for prevalence of asthma, along with England, Australia, parts of South America, and Canada. In Australia, the incidence of asthma is very high in Caucasian children, but much lower in aboriginal children.

It is speculated that lifestyle factors, such as a lack of physical activity, increased obesity, and more time spent indoors, may contribute to higher rates of asthma in highly developed countries. It is also possible that environmental irritants, such as poor indoor and outdoor air quality, along with the presence of potent irritants such as cockroach allergens, may contribute to higher rates of childhood asthma in poorer communities. Other factors that may prompt the onset of asthma are viral respiratory infections, low birth weight, and smaller-than-average air passageways in asthmatic patients.

Another area of research concerns the connection between common childhood infections and asthma. Many studies have shown that children who are exposed to viruses that cause the common cold and other respiratory infections at a very young age are less likely to develop asthma than peers living in a more hygienic environment. Children living at home with older siblings and those who spend time in daycare centers may be less likely to develop asthma than children who do not interact with others of their own age group. A related factor could be the overuse of antibiotics. Frequent use of antibiotic medications to treat relatively minor infections may produce changes in a person's immune system that increase the chance of developing asthma later in life.

Signs and symptoms

Asthmatics may experience coughing that is often worse at night or early in the morning, making sleep difficult. Wheezing is a common symptom, creating a whistling or squeaky sound when breathing. Asthmatics experience tightness in the chest region, as if it is being compressed. Shortness of breath and the feeling of breathlessness are common symptoms. There is difficulty getting enough air in or out of the lungs, especially during exhalation. If airflow to the lungs is inadequate, a lack of sufficient oxygen to the tissues causes the body to breathe faster, in an attempt to get more oxygen. Asthmatics often breathe faster as a result.

Asthmatics often have wheezing during a cold, flu, or other illness. Emotional stress may also result in asthmatic symptoms, such as coughing or wheezing from prolonged crying or laughing. Many indoor and outdoor factors can trigger or initiate typical symptoms of asthma, including allergies, viral respiratory infections, weather changes, and exercise. Medications containing aspirin also act as an asthma trigger in about 10–20% of adult asthmatics.

When allergies stimulate an asthma attack, it is known as allergic asthma. Allergic asthma is stimulated when an affected individual is physically near an allergen or irritant. Research has confirmed that allergies cause the majority of childhood asthma cases. Allergic asthma is the most common form of asthma and tends to run in families. Common allergens that may contribute to allergies and asthmatic reactions include dust mites, dust particles, animal dander, animal hair or bird feathers, mold, plant pollen, and substances found in food. Food products containing peanuts, eggs, dairy products, or seafood can cause asthma attacks in some children with allergies to these foods. Food additives, such as sulfites, can also act as asthma triggers. Synthetic (manmade) products like the latex material used in surgical gloves can also trigger asthma episodes in susceptible individuals. Non-allergic factors that can stimulate or aggravate asthma symptoms include tobacco smoke, chalk dust, talcum powder, car exhaust, and fumes from chemicals such as household cleaners. Auto pollution is a major factor in asthma prevalence.

Exercise is a common trigger for asthma in about 80% of asthmatic individuals. Some asthmatics have exercise-induced symptoms precipitated by brisk activity such as running, especially during cold weather. Pretreatment medications, such as short-acting bronchodilators, quickly widen air passages and thus help prevent the onset of asthma while an asthmatic participates in physical activities. Activities that allow for frequent breaks rather than prolonged endurance are most suitable. Asthma does not have to be a barrier to participating in athletic activities. Many Olympic athletes have exercise-induced asthma that is controlled by medication.

Changes in the weather, such as temperature and humidity variations, can also negatively affect asthma patients. Cold climates may exacerbate asthma because the lungs have to work harder to warm and moisten inhaled air. Asthmatics exercising in such conditions could wear a surgical mask that can trap the warm, moist air exhaled with each breath. Viral infections of the respiratory system that tend to increase in number during winter months may trigger severe asthma attacks. Additionally, unclean and poorly maintained forced-air heating systems release many pollutants that further aggravate asthmatic symptoms.

Every asthma patient is unique. Because there are so many environmental conditions that affect individuals with a genetic predisposition for asthma, it is often difficult to pinpoint the primary cause of the disease in individual cases.

An asthmatic may have any combination of symptoms, with symptoms varying from one asthma attack to another. Symptoms may exhibit a range of severity, from mildly irritating to life-threatening. Symptoms occur with varying frequency from once every few months to every day. Asthma classifications are based on symptom levels in the absence of medication. Mild intermittent asthma is defined as symptoms of wheezing, coughing, or breathing difficulty less than twice a week or less, with night symptoms twice a month or less. Mild persistent asthma is defined as symptoms of wheezing, coughing, or breathing difficulty once a day or less, but more than twice a week. Symptoms occur at night more than twice a month. Moderate persistent asthma is defined as daily symptoms that require daily medication. Symptoms at night occur more than once a week. Symptoms may be severe enough to interfere with normal physical activity. Severe asthma is described as ongoing, persistent symptoms with more serious asthma attacks. Symptoms may occur throughout the day, with night symptoms occurring often. In severe asthma, physical activity is likely to be limited.

All types of asthmatics may have severe asthma attacks. However, with appropriate treatment and avoidance of asthma stimulators, most asthmatics can achieve a general condition of minimal or no symptoms. Asthmatics are encouraged to learn to recognize their own specific asthma stimulators and avoid them, and to recognize their specific pattern of early warning signs that signal the start of an attack. The first signs of a mild or moderate attack may be a slight tightening of the chest, coughing or wheezing, and spitting up mucous. Severe attacks can bring on a feeling of extreme tightening of the neck and chest, making breathing increasingly difficult. Asthmatics may struggle to speak or breathe. In advanced stages of severe attacks, lips and fingernails may take on a grayish or bluish tinge, indicating declining oxygen levels in the blood. Such attacks can be fatal in the absence of prompt medical attention. Fortunately, asthma symptoms are usually reversible with medication.

Diagnosis

The first stage of asthma diagnosis is from a history of asthmatic symptoms. These symptoms include periods of coughing, wheezing, shortness of breath, or chest tightness that come on suddenly in response to specific stimulants or time periods. A history of head colds that evolve into chest congestion or take more than 10 days to recover from is pertinent. Family history of asthma or allergies may also be part of the diagnosis.

A physical exam may reveal wheezing in the chest that can be heard with a stethoscope. A device called a spirometer may be used to check the function of the airways in children over five years of age and in adults. The test measures the volume of air and the speed with which air can be blown out of the lungs after a deep breath. If the airways are narrowed from inflammation and the muscles around the airways tightening up from asthma, the results will be lower than normal. If spirometry results are normal but asthma symptoms are present, other tests are performed. A bronchial challenge test involves inhalation of a substance such as methacholine, which causes narrowing of the airways in asthma. The effect is measured by spirometry to determine is asthma is present. Children under five years of age usually cannot use a spirometer successfully. In such cases, asthma medications are often attempted as part of the diagnosis to determine if they are able to alleviate the symptoms.

Allergy testing may be performed to determine if there are specific allergens that the individual is reactive to. A device called a peak flow meter may be used every day for several weeks to measure breathing efficiency. Tests may be performed to determine the reaction of the airways to exercise. In some cases, a chest x ray or an electrocardiogram may be used to determine if a foreign object, other lung disease, or heart disease could be causing asthma-like symptoms. The results of the medical history, physical exam, and lung function tests are used to diagnose the severity of asthma and determine treatment.

Treatment and management

Asthma is treated by avoiding stimulating factors and by medication. There are two main types of asthma medication. Acute medications give rapid, short-term treatment, and are only used when asthma symptoms require immediate relief. Acute medications are bronchodilators that may be inhaled and take effect within minutes to dilate the airways and allow normal breathing. Bronchodilators may be used at the beginning of an asthma attack to provide relief. Bronchodilators may also be used before exercise to prevent exercise-induced asthma symptoms. Long-term control medications are taken daily over long periods of time to control chronic symptoms and prevent asthma attacks. The full effect of these medications requires several weeks of use. Individuals with persistent asthma require long-term control medications.

The most effective, long-term control medication for asthma is an inhaled corticosteroid. Corticosteroids reduce the swelling of airways and help to prevent asthma attacks from occurring. Inhaled corticosteroids are preferred for treatment of all levels of persistent asthma. In some cases, steroid tablets or liquid medications are used temporarily to control asthma. Other types of asthma medications inhibit the inflammatory mediators released in the asthma response. Some of these long-term control medications may be used in combination with inhaled corticosteroids to treat moderate persistent and severe persistent asthma. Long-term control medications are used in a preventative manner and will not stop a currently occurring asthma attack. Many asthmatics require both a short-acting bronchodilator to use when symptoms worsen and a long-term daily asthma control medication to treat ongoing inflammation.

Uncontrolled asthma during pregnancy can be very dangerous. Lowered oxygen levels to the fetus may cause damage. Many asthma treatments are considered safe to use during pregnancy. Older adults may need adjustments in asthma treatment because of other present diseases or conditions. Some medications, such as beta-blockers used for hypertension, aspirin, and nonsteroidal anti-inflammatory drugs such as ibuprofen, can interfere with some asthma medications or cause asthma attacks. The use of corticosteroids may also adversely affect bone density in adults.

Asthmatics can monitor the function of their respiratory system with the aid of peak flow meters and spiro-meters. These devices measure the amount of air exhaled with each breath. They are used to regularly monitor the severity of asthma symptoms and to evaluate and manage treatment procedures for individual patients. Maintaining control over asthma symptoms, combined with a healthy lifestyle, are key components of asthma treatment.

Emergency care may become necessary during a severe asthma attack. Emergency care takes place in a hospital setting and may include treatment with high levels of bronchodilators and corticosteroids, additional medications, and oxygen administration in an attempt to restore normal respiratory activity. Delayed access to emergency treatment can lead to complete respiratory failure where the patient simply stops breathing and cannot be revived.

In cases of allergic asthma, allergy shots may also assist in reducing symptoms. Allergy shots, also known as allergen immunotherapy, are recommended for individuals who suffer from allergic asthma when it is not possible to avoid contact with the allergens that stimulate asthma. A series of shots with controlled and gradually increasing amounts of allergen may be given over a number of months or years. The shots are vaccines containing various allergens, such as pollen or dust mites. The increased exposure to the allergen desensitizes the immune system to allergen triggers. Allergy shots can diminish the severity of asthma symptoms and lower the dosage of required asthma medications.

Prognosis

There is currently no cure for asthma. Proper treatment and management has dramatically improved the quality of life for individuals with asthma. When medication is utilized properly, the prognosis for most asthmatics is excellent. An improvement in environmental conditions can reduce the number and severity of asthma attacks and improve the prognosis for asthmatics. Such improvement is also believed to affect the overall prognosis for a society, simply by decreasing the number of individuals sensitized to environmental triggers.

Resources

BOOKS

Katzung, B. G. Basic and Clinical Pharmacology, Seventh Edition. Stamford, CT: Appleton and Lange, 1998.

Roitt, I., J. Brostoff, and D. Male. Immunology, Fifth Edition. London, England: Mosby International, 1998.

PERIODICALS

"Clearing the Air: Asthma and Indoor Air Exposures." The New England Journal of Medicine 343 (December 14, 2000): 24.

"Day Care, Siblings, and Asthma—Please, Sneeze on My Child." The New England Journal of Medicine 343 (August 24, 2000): 8.

Folkerts, Gert, Gerhard Walzl, and Peter J. M. Openshaw. "Do Common Childhood Infections 'Teach' the Immune System Not to Be Allergic?" Immunology Today 21, no. 3 (2000): 118–120.

Herz, Udo, Paige Lacy, Harald Renz, and Klaus Erb. "The Influence of Infections on the Development and Severity of Allergic Disorders." Current Opinion in Immunology 12, no. 6 (2000): 632–640.

Illi, S., E. von Mutius, S. Lau, R. Bergmann, B. Niggemann, C. Sommerfeld, and U. Wahn. "Early Childhood Infectious Diseases and the Development of Asthma Up to School Age: A Birth Cohort Study." British Medical Journal 322 (February 17, 2001): 390–395.

Johnston, Sebastian L., and Peter J. M. Openshaw. "The Protective Effect of Childhood Infections—The Next Challenge Is to Mimic Safely This Protection Against Allergy and Asthma." British Medical Journal 322 (February 17, 2001): 376–377.

"Siblings, Day-Care Attendance, and the Risk of Asthma and Wheezing." The New England Journal of Medicine 343, no. 26 (December 28, 2000).

ORGANIZATIONS

Allergy and Asthma Network. Mothers of Asthmatics, Inc. 2751 Prosperity Ave., Suite 150, Fairfax, VA 22031. (800) 878-4403. Fax: (703) 573-7794.

American Academy of Allergy, Asthma & Immunology. 611 E. Wells St., Milwaukee, WI 53202. (414) 272-6071. Fax: (414) 272-6070. (April 18, 2005.) <http://www.aaaai.org/default.stm>.

American Lung Association. 1740 Broadway, New York, NY 10019. (212) 315-8700 or (800) 586-4872. (April 18, 2005.) <http://www.lungusa.org>.

Asthma and Allergy Foundation of America (AAFA). 1233 20th St. NW, Suite 402, Washington, DC 20036. (800) 7-ASTHMA. Fax: (202) 466-8940. (April 18, 2005.) <http://www.aafa.org>.

Division of Lung Diseases, National Heart, Lung and Blood Institute. Suite 10122, 6701 Rockledge Dr. MSC 7952, Bethesda, MD 20892-7952. (301) 435-0233. (April 18, 2005.) <http://www.nhlbi.nih.gov/index.htm>.

Global Initiative for Asthma (GINA). (207) 594-5008. Fax: (207) 594-8802. [email protected]. (April 18, 2005.) <http://www.ginasthma.com>.

KidsHealth. Nemours Center for Children's Health Media. PO Box 269, Wilmington, DE 19899. (April 18, 2005.) <http://www.kidshealth.org>.

National Asthma Education and Prevention Program (NAEPP). School Asthma Education Subcommittee. (April 18, 2005.) <http://www.nhlbi.nih.gov/health/dci/Diseases/Asthma/Asthma_WhatIs.html>.

National Center for Environmental Health. Centers for Disease Control and Prevention, Mail Stop F-29, 4770 Buford Highway NE, Atlanta, GA 30341-3724. (April 18, 2005.) <http://www.cdc.gov/asthma/>.

National Institutes of Health (NIH). PO Box 5801, Bethesda, MD 20824. (800) 352-9424. (April 18, 2005.) <http://www.ninds.nih.gov>.

OTHER

Asthma. National Heart, Lung, and Blood Institute. (April 18, 2005.) <http://www.nhlbi.nih.gov/health/public/lung/index.htm>.

Asthma and Allergies. Centers for Disease Control and Prevention. (April 18, 2005.) <http://www.cdc.gov/niosh/topics/asthma>.

Asthma Basics. National Institutes of Health. (April 18, 2005.) <http://www2.niaid.nih.gov/newsroom/focuson/asthma01/basics.htm>.

Asthma Prevalence, Health Care Use and Mortality, 2002. National Center for Health Statistics. (April 18, 2005.) <http://www.cdc.gov/nchs/products/pubs/pubd/hestats/asthma/asthma.htm>.

Breath of Life Exhibition. National Library of Medicine. (April 18, 2005.) <http://www.nlm.nih.gov/hmd/breath/breath_exhibit/mainframe.html>.

"What Makes Asthma Worse?" medfacts 2000. Lung Line, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. (303) 388-4461 (7700). (April 18, 2005.) <http://www.nationaljewish.org/medfacts/worse.html>.

Maria Basile, PhD