William Kelly, MD, Consulting Staff, Officer-in-Charge, Pulmonary Disease Clinic, Madigan Army Medical Center; Assistant Professor of Medicine, Department of Pulmonary and Critical Care Medicine, Uniformed Services University of the Health Sciences
Gregory Argyros, MD, Assistant Chief, Program Director, Department of Medicine, Department of Medicine, Walter Reed Army Medical Center; Associate Professor, Uniformed Services University of the Health Sciences; Rohit K Katial, MD, Program Director Allergy and Immunology, Associate Professor of Medicine, National Jewish Medical and Research Center, Division of Allergy and Clinical Immunology, University of Colorado Health Sciences Center
Contributor Information and DisclosuresUpdated: May 30, 2006
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Overview
Differential Diagnoses & Workup
Treatment & Medication
Follow-up
References
Keywords
Introduction
Background
Asthma is a clinical syndrome characterized by episodic reversible airway obstruction, increased bronchial reactivity, and airway inflammation. Asthma results from complex interactions among inflammatory cells, their mediators, airway epithelium and smooth muscle, and the nervous system. In genetically susceptible individuals, these interactions can lead to symptoms of breathlessness, wheezing, cough, and chest tightness.
Risk factors for asthma include a family history of allergic disease, the presence of allergen-specific immunoglobulin E (IgE), viral respiratory illnesses, exposure to aeroallergens, obesity, and lower socioeconomic status.
Environmental exposure in sensitized individuals is a major inducer of airway inflammation, which is a hallmark finding in the asthmatic lung. Although triggers induce inflammation through different pathways, the resulting effects all lead to increased bronchial reactivity.
Exposure to dust mites within the first year of life is associated with later development of asthma and, possibly, atopy. Mite and cockroach antigens are common, and exposure and sensitization has been shown to increase asthma morbidity. Allergies trigger asthma attacks in 60-90% of children and in 50% of adults. Approximately 75-85% of patients with asthma have positive (immediate) skin test results. In children, this sensitization is associated with disease activity. The level of IgE is associated with the prevalence and severity of airway hyperresponsiveness (AHR) and asthma.
Although most people with asthma have aeroallergen-induced symptoms, some individuals manifest symptoms with nonallergic triggers. As many as 3-10% of people with asthma are sensitive to nonsteroidal anti-inflammatory drugs (NSAIDs). Approximately 5-10% of people with asthma have occupation- or industry-induced airway disease. Many individuals develop symptoms after viral respiratory tract infections.
Allergen avoidance and other environmental control efforts are feasible and effective. Symptoms, pulmonary function test findings, and AHR improve with avoidance of environmental allergens. Removing even one of many allergens can result in clinical improvement. However, patients frequently are not compliant with such measures.
Pathophysiology
The allergic response in the airway is the result of a complex interaction of mast cells, eosinophils, T lymphocytes, macrophages, dendritic cells, and neutrophils. Inhalation-challenge studies with allergens reveal an early allergic response (EAR), which occurs within minutes and peaks at 20 minutes following inhalation of the allergen. Clinically, the manifestations of the EAR in the airway include bronchial constriction, airway edema, and mucus plugging. These effects are the result of mast cell-derived mediators. Four to 10 hours later, one sees the late allergic response, which is characterized by infiltration of inflammatory cells into the airway and is most likely caused by cytokine-mediated recruitment and activation of lymphocytes and eosinophils.
Antigen-presenting cells (ie, macrophages, dendritic cells) in the airway capture, process, and present antigen to helper T cells, which, in turn, become activated and secrete cytokines. Helper T cells can be induced to develop into TH 1 (ie, interferon-gamma, interleukin [IL]-2) or TH 2 (ie, IL-4, IL-5, IL-9, IL-13). Allergens drive the cytokine pattern towards TH 2, which promotes B-cell IgE production and eosinophil recruitment. Subsequently, IgE binds to the high-affinity receptor for IgE, Fc-epsilon-RI, on the surface of mast cells and, with subsequent exposure to the allergen, the IgE is cross-linked. This leads to degranulation of the mast cell. Preformed mast cell mediators, such as histamine and proteases, are released, leading to the EAR.
Newly formed mediators such as leukotriene C4 and prostaglandin D2 also contribute to the EAR. Proinflammatory cytokines (IL-3, IL-4, IL-5, tumor necrosis factor-alpha) are released from mast cells and are generated de novo after mast cell activation. These cytokines contribute to the late allergic response by attracting neutrophils and eosinophils. The eosinophils release major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase into the airway, causing epithelial denudation and exposure of nerve endings. The lymphocytes that are attracted to the airway continue to promote the inflammatory response by secreting cytokines and chemokines, which further potentiate the cellular infiltration into the airway. The ongoing inflammatory process eventually results in hypertrophy of smooth muscles, hyperplasia of mucous glands, thickening of basement membranes, and continuing cellular infiltration. These long-term changes of the airway, referred toas airway remodeling, can ultimately lead to fibrosis and irreversible airway obstruction in some, but not most, patients.
Frequency
United States
Prevalence is difficult to determine because definitions and survey methods vary, but it is likely increasing as a result of greater sensitization to common allergens and the redefinition of some nonatopic wheezing as asthma. From 1982-1992, the average age-adjusted prevalence rate increased 42% (from 34.7/1000 to 49.4/1000). Asthma may affect 31 million people, including 9.2 million children (7.2% of adults by self-report). (more…)
