Asthma is a chronic inflammatory disorder of the airways characterized by increased responsiveness of the tracheobronchial tree to a variety of stimuli. Many cells and cellular elements play a role, particularly mast cells, eosinophils, T lymphocytes, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment.
Various subtypes of asthma exist. The most important consideration is the identification of exacerbating factors whenever possible. A well-known system classifies asthmas as either extrinsic or intrinsic. Although this system is conceptually helpful, its two groups are not mutually exclusive. Whereas extrinsic asthma (or allergic asthma) most commonly affects children and young adults and involves infectious, environmental, psychological, or physical factors, intrinsic asthma (or idiosyncratic asthma) usually develops in middle age without specifically identifiable attack-provoking stimuli. The term atopy, which refers to a hereditary, immunoglobulin E (IgE)–mediated, clinical hypersensitive state, is often used when extrinsic asthma is described.
Up to 15 million persons in the United States have asthma. It is the most common chronic disease of childhood, affecting an estimated 4.8 million children. People with asthma collectively have more than 100 million days of restricted activity and 470,000 hospitalizations annually. More than 5000 people die of asthma each year.
Asthma is a heterogeneous clinical syndrome characterized by episodes in which airways are hyperresponsive, interspersed with symptom-free periods. Bronchoconstriction is a factor long associated with the asthmatic symptom complex, but asthma is much more than bronchoconstriction. Airway inflammation and a nonspecific hyperirritability of the tracheobronchial tree are now recognized as being central to the pathogenesis of even mild cases of asthma. Permanent changes in airway anatomy, referred to as airway remodeling, magnify the inflammatory response.
Allergic asthma (atopic or immunologic disease) is triggered by antigens that provoke a T-lymphocyte–generated, IgE-mediated immune response. It is often associated with a personal or familial history of allergic disease. Potent biochemical mediators released from proinflammatory and airway epithelial cells promote vasoconstriction, increased smooth muscle tone, enhanced mucous secretion, submucosal edema, increased vascular permeability, and inflammatory cell chemotaxis. Leukotrienes have been identified as especially potent spasmogenic and proinflammatory substances. Released molecules that are toxic to the airway epithelium cause patchy desquamation, which exposes cholinergic nerve endings and compounds the bronchoconstrictive and hyperresponsive response.
The asthmatic diathesis creates airways that are inflamed, edematous, and hypersensitive to irritant stimuli, and the degree of airway hyperresponsiveness and bronchoconstriction appears to parallel the extent of inflammation. When airway reactivity is high, asthmatic symptoms are generally more severe and unrelenting, and the amount of therapy required to control the episode is greater.
The mechanisms underlying idiosyncratic asthma (nonimmunologic disease) are less clearly defined. Nonimmunologic asthma occurs in patients with no history of allergy and normal serum IgE. These patients typically develop asthmatic symptoms in response to some provocative or noxious stimulus such as cold air, airway instrumentation or irritation, climate changes, or an upper respiratory illness. Recent upper respiratory infection may precipitate bronchospasm in any patient, but the risk is higher in patients with a history of asthma.
The mechanism of exercise-induced asthma is unknown. Regardless of the mechanism, most symptoms last less than 1 hour and are usually quickly reversed with administration of β2-adrenergic receptor agonists. Occupational asthma develops when irritants directly stimulate vagal nerve endings in the airway epithelium. Infection-induced asthma with acute inflammation of the bronchi may be caused by viral, bacterial, or mycoplasmal infections. Aspirin-induced asthma occurs when, in some predisposed persons, cyclooxygenase promotes an increase in leukotriene levels via the arachidonic acid pathway, thereby triggering the asthma attack. This peculiar response can occur with the use of other nonsteroidal anti-inflammatory agents. The aspirin-induced asthma variant is not IgE mediated or allergic in nature; furthermore, it is clinically associated with nasal polyps. Patients with aspirin-induced asthma may be at increased risk of bronchospasm after ketorolac (Toradol) administration.