Asthma

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File:Inhaler girl.png
A young girl with asthma using an inhaler.

Asthma is a disease of the respiratory system in which the airways unexpectedly and suddenly narrow, often in response to a "trigger" such as exposure to an allergen, cold air, exercise, or emotional stress. This narrowing causes symptoms such as wheezing, shortness of breath, chest tightness, and coughing, which are the hallmarks of asthma. Between episodes, patients normally feel fine.

The disorder is a chronic inflammatory condition in which the airways develop increased responsiveness to various stimuli, characterized by bronchial hyperresponsiveness, inflammation, increased mucus production and intermittent airway obstruction. The symptoms of asthma, which can range from mild to life threatening, can usually be controlled with a combination of drugs and lifestyle changes.

Public attention in the developed world has recently focused on asthma because of its rapidly increasing prevalence, affecting up to one in four urban children.information Administrator note Susceptibility to asthma can be explained in part by genetic factors, but no clear pattern of inheritance has been found. Asthma is a complex disease that is influenced by multiple genetic, developmental, and environmental factors, which interact to produce the overall condition.

History

The word asthma is derived from the Greek aazein ("sharp breath"), which first appears in the Iliad (although it is used here in its literal Greek sense, not in reference to the disease).information Administrator note Hippocrates was the first to use it to refer to a medical condition. He noticed that its associated "spasms" were more likely to occur in tailors, fisherman, and metal workers. Six centuries later, Galen wrote much about asthma and found that it was caused by bronchial obstruction. Moses Maimonides, an influential medieval rabbi, philosopher, and physician, wrote a treatise on asthma, describing its prevention, diagnosis, and treatment.information Administrator note In the 17th century, Bernardino Ramazzini noted a connection between asthma and organic dust. The use of bronchodilators started in 1901, but it was not until the 1960s that the inflammatory component of asthma was recognized, and anti-inflammatory medications were added to the regimen.

Signs and symptoms

An acute exacerbation of asthma is referred to colloquially as an asthma attack. The clinical hallmarks of an attack are shortness of breath (dyspnea) and wheezing, the latter "often being regarded as the sine qua non".information Administrator note A cough—sometimes producing clear sputum—may also be present. The onset is often sudden; there is a "sense of constriction" in the chest, breathing becomes difficult, and wheezing occurs (typically in both respiratory phases).

Signs of an asthmatic episode are wheezing, rapid breathing (tachypnea), prolonged expiration, a rapid heart rate (tachycardia), rhonchous lung sounds (audible through a stethoscope), and overinflation of the chest. During a serious asthma attack, the accessory muscles of respiration may be used, shown as in-drawing of tissues between the ribs and above the sternum and clavicles, and the presence of a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation).Template:An num During very severe attacks, an asthma sufferer can turn blue from lack of oxygen and can experience chest pain or even loss of consciousness. Severe asthma attacks may lead to respiratory arrest and even to death. Despite the severity of symptoms during an asthmatic episode, between attacks an asthmatic may show few signs of the disease.

Diagnosis

Diagnosing asthma

In most cases, a physician can diagnose asthma on the basis of typical findings in a patient's clinical history and examination. Asthma is strongly suspected if a patient suffers from eczema or other allergic conditions—suggesting a general atopic constitution—or has a family history of asthma. While measurement of airway function is possible for adults, most new cases are diagnosed in children who are unable to perform such tests. Diagnosis in children is based on a careful compilation and analysis of the patient's medical history and subsequent improvement with an inhaled bronchodilator medication. In adults, diagnosis can be made with a peak flow meter (which tests airway restriction), looking at both the diurnal variation and any reversibility following inhaled bronchodilator medication.

Testing peak flow at rest (or baseline) and after exercise can be helpful, especially in young asthmatics who may experience only exercise-induced asthma. If the diagnosis is in doubt, or if chronic obstructive pulmonary disease is suspected, a more formal lung function testing may be conducted. Once a diagnosis of asthma is made, a patient can use peak flow meter testing to monitor the severity of the disease.

Differential diagnosis

Before diagnosing someone as asthmatic, alternative possibilities should be considered. A physician taking a history should check whether the patient is using any known bronchoconstrictors (substances that cause narrowing of the airways, e.g., certain anti-inflammatory agents or beta-blockers).

Only a minority of asthma sufferers have any identifiable allergy trigger. The majority of these triggers can often be identified from the history; for instance, asthmatics with hay fever or pollen allergy will have seasonal symptoms, those with allergies to pets may experience an abatement of symptoms when away from home, and those with occupational asthma may improve during leave from work. Occasionally, allergy tests are warranted and, if positive, may help in identifying avoidable symptom triggers.

After pulmonary function has been measured, radiological tests, such as a chest X-ray or CT scan, may be required to exclude the possibility of other lung diseases. In some people, asthma may by triggered by gastroesophageal reflux disease, which can be treated with suitable antacids. Very occasionally, specialized tests after inhalation of methacholine—or even less commonly histamine—may be performed.

Pathophysiology

Bronchoconstriction

During an asthma episode, inflamed airways react to environmental triggers such as smoke, dust, or pollen. The airways narrow and produce excess mucus, making it difficult to breathe.

In essence, asthma is the result of an abnormal immune response in the bronchial airways.information Administrator note The airways of asthmatics are "hypersensitive" to certain triggers, also known as stimuli (see below). In response to exposure to these triggers, the bronchi (large airways) contract into spasm (an "asthma attack"). Inflammation soon follows, leading to a further narrowing of the airways and excessive mucus production, which leads to a coughing and other breathing difficulties.

There are seven categories of stimuli:

Bronchial inflammation

The mechanisms behind allergic asthma—i.e., asthma resulting from an immune response to inhaled allergens—are the best understood of the causal factors. When allergens are inhaled by any person (asthmatic or not), they travel to the inner airways, where they are ingested by certain cells there. These cells digest the allergen and present pieces of the allergen to other cells of the immune system. In most people, those other immune cells (TH0 cells) will check and ignore the allergen molecules. However, in people who will develop asthma, those immune cells will transform into a different type of cell (TH2) instead of passing by the pieces of allergen, for complex reasons that are not well understood. These TH2 cells activate mainly the antibody-related part of the immune system, thus producing antibodies against the original allergen. Later, when an asthmatic inhales the same allergen, those antibodies recognize the allergen and the immune system is activated. Inflammation results, producing chemicals that cause the airways to constrict and produce more mucus. In addition, other immune cells are summoned, which are responsible for the subsequent effects of the asthma attack.

The immune response

More technically, primary exposure to a foreign antigen—such as pollen or cigarette smoke—can trigger the development of asthmatic symptoms. Once an inhaled antigen becomes trapped in the airways, it is enzymatically degraded into shorter peptides by antigen presenting cells (APCs) such as dendritic cells. APCs take the peptides derived from the antigen and express them on the cell surface in the binding groove of the class II major histocompatiblity complex (MHC) molecule. Now located on the cell surface, the antigen-MHC complex is presented to T cells, which express a [[receptor {biochemistry)|receptor]] that is specific to the MHC II peptide.Template:An num

Presented with the antigen-MHC II complex, T helper 0 (TH0) cells become activated and start to differentiate into either T helper type 1 (TH1) or type 2 (TH2) cells. The selective differentiation of TH0 cells has profound consequences for the immune system: TH1 cell production leads to cell-mediated immunity, while the production of predominantly TH2 cells provides humoral immunity. The resulting balance of TH1 or TH2 cells is a crucial variable in the development of asthma. The dominance of the TH2 cell type appears to be necessary for the development of asthma. In one study, mice that lack the ability to create TH1 cells displayed an asthma-like phenotype.information Administrator note The variables that decide the fate of TH1 vs. TH2 cells are not well understood, but depend on many factors, including childhood exposure to infectious agents and the cytokines elicited by those agents.

One cytokine secreted by TH2 cells—IL-4—combined with the action of other cytokines induces synthesis by antigen-stimulated B cells of IgE, an allergen-specific antibody. IgE binds allergens and then receptors on mast cells, basophils, and eosinophils in the airway epithelium. Subsequent exposure of the same antigen to these cells in the airway epithelium initiates the acute-phase reaction of asthma. Stimulated mast cells in the airway release preformed granules of mediators such as histamine, eicosanoids, and cytokines. These molecules are responsible for the symptoms of asthma. They affect the mucosa of the airways, increasing mucosal edema, and mucus production, smooth muscle constriction, and recruit other immune cells, thereby exacerbating the reaction.

The late phase of an asthmatic reaction is characterized by an influx of inflammatory and immune cells during the first several hours after antigen exposure. These cells—particularly eosinophils—secrete a series of cytokines, leukotrienes, and polypeptides, which contribute to hyperresponsiveness, mucus secretion, bronchoconstriction, and sustained inflammation.

Pathogenesis

The fundamental problem in asthma appears to be immunological: young children in the early stages of asthma show signs of excessive inflammation in their airways. Epidemiological findings give clues as to the pathogenesis: the incidence of asthma seems to be increasing worldwide; asthma is more common in more affluent countries, and more common in wealthier socioeconomic groups.

One theory of pathogenesis is that asthma is a disease of hygiene. In nature, babies are exposed to bacteria and other antigens soon after birth, "switching on" the TH1 lymphocyte cells of the immune system that deal with bacterial infection. If this stimulus is insufficient—as it may be in modern, clean environments—then TH2 cells predominate, and asthma and other allergic diseases may develop. This "hygiene hypothesis" may explain the increase in asthma in affluent populations. The TH2 lymphocytes and eosinophil cells that protect us against parasites and other infectious agents are the same cells responsible for the allergic reaction. In the developed world, these parasites are now rarely encountered, but the immune response remains and is wrongly triggered in some individuals by certain allergens.

Another theory is based on the correlation of air pollution and the incidence of asthma. Although it is well known that substantial exposures to certain industrial chemicals can cause acute asthmatic episodes, it has not been proved that air pollution is responsible for the development of asthma. In Western Europe, most atmospheric pollutants have fallen significantly over the last 40 years, while the prevalence of asthma has risen.

Treatment

The most effective treatment for asthma is identifying triggers, such as pets or aspirin, and limiting or eliminating exposure to them. Desensitization is commonly attempted, but has not been shown to be effective. As is common with respiratory disease, smoking adversely affects asthmatics in several ways, including an increased severity of symptoms, a more rapid decline of lung function, and decreased response to preventitive medications.information Administrator note Asthmatics who smoke typically require additional medications to help control their disease. Furthermore, exposure by both nonsmokers and smokers to secondhand smoke is detrimental, resulting in more severe asthma, more emergency room visits, and more asthma-related hospital admissions.information Administrator note Smoking cessation and avoidance of those who smoke is strongly encouraged in asthmatics.information Administrator note

The specific medical treatment recommended to patients with asthma depends on the severity of their illness and the frequency of their symptoms. The Expert panel report 2: Guidelines for the diagnosis and management of asthma (EPR-2)Template:An num of the US National Asthma Education and Prevention Program, and the British guideline on the management of asthma information Administrator note are broadly used and supported by many doctors. Bronchodilators are recommended for short-term relief in all patients. For those who experience occasional attacks, no other medication is needed. For those with mild persistent disease (more than two attacks a week), low-dose inhaled glucocorticoids—or alternatively, a oral leukotriene modifier, a mast-cell stabilizer, or theophylline—may be administered. For those who suffer daily attacks, a higher dose of glucocorticoid in conjunction with a long-acting inhaled β-2 agonist may be prescribed; alternatively, a leukotriene modifier or theophylline may substitute for the β-2 agonist. In severe asthmatics, oral glucocorticoids may be added to these treatments during severe attacks.

For those in whom exercise can trigger an asthma attack (exercise-induced asthma), higher levels of ventilation and cold, dry air tend to exacerbate attacks. For this reason, activities in which a patient breathes large amounts of cold air, such as cross-country skiing, tend to be worse for asthmatics, whereas swimming in an indoor, heated pool, with warm, humid air, is less likely to provoke a response.Template:An num

Relief medication

A typical inhaler.

Symptomatic control of episodes of wheezing and shortness of breath is generally achieved with fast-acting bronchodilators. These are typically provided in pocket-sized, metered-dose inhalers (MDIs—see the image to the right). In young sufferers, who may have difficulty with the coordination necessary to use inhalers, or those with a poor ability to hold their breath for 10 seconds after inhaler use (generally the elderly), a device called an asthma spacer is used. An asthma spacer is an enclosed plastic cylinder that mixes the medication with air in a simple tube, making it easier for patients to receive a full dose of the drug (see top image). For a minority of patients with severe asthma, a nebulizer—which provides a larger, continuous dose—is sometimes required.

Relievers include:

  • Short-acting, selective beta2-adrenoceptor agonists (salbutamol [albuterol], levalbuterol, terbutaline, bitolterol, pirbuterol, procaterol, fenoterol, bitolterol, reproterol). The major side effect is tremors; however, this has been greatly reduced by the use of inhaled drugs, which are capable of targeting the lungs, rather than oral medications, which tend to be distributed throughout the body. There may also be cardiac side effects at higher doses; these have become rare with the advent of selective agents.
  • Older, less selective adrenergic agonists, such as inhaled epinephrine and ephedrine tablets—both of which, unlike other medications, are available over the counter in the US under the Primatene brand. Cardiac side effects, although uncommon, occurred more often with the less selective drugs. Nowadays, they are usually avoided in patients with heart disease.
  • Anticholinergic medications, such as ipratropium bromide may be used instead. They have no cardiac side effects and thus can be used in patients with heart disease; however, they take up to an hour to achieve their full effect and are not as powerful as the β2-adrenoreceptor agonists.

Prevention medication

Current treatment protocols recommend an inhaled corticosteroid, which helps to suppress inflammation and reduces the swelling of the lining of the airways in anyone who has frequent (greater than twice a week) need of relievers or who has severe symptoms. If symptoms persist, additional preventive drugs are added until the asthma is controlled.

Preventive agents include the following.

Long-acting β2-agonists

Long-acting bronchodilators (LABD) give a 12-hour effect and are used to give a smoothed symptomatic effect (used morning and night). While patients report improved symptom control, these drugs do not replace the need for routine preventers, and their slow onset means the short-acting dilators may still be required.

Currently available long-acting beta2-adrenoceptor agonists include salmeterol, formoterol, bambuterol, and sustained-release oral albuterol. Combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread; the most common combination currently in use is fluticasone/salmeterol (Advair in the United States, and Seretide in the UK.

Emergency treatment

When an asthma attack is unresponsive to a patient's usual medication, other treatments are available to the physician or hospital:information Administrator note

Alternative medicine

Many asthmatics, like those who suffer from other chronic disorders, use alternative treatments; surveys show that roughly 50% of asthma patients use some form of unconventional therapy.information Administrator note information Administrator note There are little data to support the effectiveness of most of these therapies. A Cochrane systematic review of acupuncture for asthma found that there was no evidence of efficacy.information Administrator note A similar review of air ionizers found no evidence that they improve asthma symptoms or benefit lung function; this applied equally to positive and negative ion generators.information Administrator note A study of "manual therapies" for asthma, including osteopathic, chiropractic, physiotherapeutic and respiratory therapeutic maneuvers, found no evidence to support their use in treating asthma;information Administrator note these maneuvers include various osteopathic and chiropractic techniques to "increase movement in the rib cage and the spine to try and improve the working of the lungs and circulation"; chest tapping, shaking, vibration, and the use of "postures to help shift and cough up phlegm". On the other hand, one meta-analysis found that homeopathy has a potentially mild benefit in reducing symptom intensity;information Administrator note however, the number of patients involved in the analysis was small, and subsequent studies have not supported this finding.information Administrator note Several small trials have suggested some benefit from various yoga practices, ranging from integrated yoga programsinformation Administrator note—"yogasanas, Pranayama, meditation, and kriyas"—to sahaja yogainformation Administrator note, a form of meditation. A randomized, controlled trial of just 39 patients suggested that the Buteyko breathing technique may moderately reduce the need for beta-agonists among asthmatics, but found no objective improvement in lung function.information Administrator note See also complementary and alternative medicine.

Prognosis

The prognosis for asthmatics is good, especially for children with mild disease. For asthmatics diagnosed during childhood, 54% will no longer carry the diagnosis after a decade. The extent of permanent lung damage in asthmatics is unclear. Airway remodelling is observed, but it is unknown whether these represent harmful or beneficial changes.Template:An num Although there are mixed reports, most studies show that early treatment with glucocorticoids prevents or ameliorates decline in lung function as measured by several parameters.information Administrator note However, there does not appear to be any progression from mild to moderate or moderate to severe asthma, regardless of treatment. For those who continue to suffer from mild symptoms, corticosteroids can help most to live their lives with few disabilities. The mortality rate for asthma is low, with around 6000 deaths per year in a population of some 10 million patients in the United States.Template:An num

Epidemiology

The prevalence of childhood asthma has increased since 1980, especially in younger children.

Asthma is usually diagnosed in childhood. The risk factors for asthma include:

  • a personal or family history of asthma or atopy;
  • triggers (see Pathophysiology above);
  • premature birth or low birth weight;
  • viral respiratory infection in early childhood;
  • maternal smoking;
  • being male, for asthma in prepubertal children; and
  • being female, for persistence of asthma into adulthood.

There is a reduced occurrence of asthma in people who were breast-fed as babies. Current research suggests that the prevalence of childhood asthma has been increasing. According to the Centers for Disease Control and Prevention's National Health Interview Surveys, some 9% of US children below 18 years of age had asthma in 2001, compared with just 3.6% in 1980 (see figure). The World Health Organization (WHO) reportsinformation Administrator note that some 8% of the Swiss population suffers from asthma today, compared with just 2% some 25–30 years ago. Although asthma is more common in affluent countries, and more common in higher socioeconomic groups within countries, it is by no means a problem restricted to the affluent; the WHO estimate that there are between 15 and 20 million asthmatics in India. In the US, urban residents and Hispanics and African Americans are affected more than the population as a whole. Globally, asthma is responsible for around 180,000 deaths annually.Template:An num

Asthma and athletics

Asthma appears to be more prevalent in athletes than in the general population. One survey of participants in the 1996 Summer Olympic Games showed that 15% had been diagnosed with asthma, and that 10% were on asthma medication.information Administrator note There appears to be a relatively high incidence of asthma in sports such as cycling, mountain biking, and long-distance running, and a relatively low incidence in weight lifting and divers. It is unclear how much of these disparities are because of the effects of training in the sport, and self-selection of sports that may appear to minimize the triggering of asthma.Template:An num information Administrator note


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