New concepts in the pathogenesis of asthma. 1989

G L Larsen
Department of Pediatrics, University of Colorado School of Medicine, Denver 80206.

Heightened airways reactivity is a major characteristic of asthma. Several stimuli capable of producing an inflammatory reaction within the respiratory tract can increase airways reactivity in both normal and asthmatic subjects. The association between lower airways inflammation and alterations in airways function has been studied most extensively after antigen exposure leading to an immediate and/or late asthmatic response in atopic subjects. The late asthmatic response (LAR) is of special interest because it lasts for hours, is prevented by corticosteroids and not adrenergic agents, and is associated with more severe asthma as well as increases in airways responsiveness. While late phase reactions in the lung and skin were initially thought to be Arthus reactions, more recent observations in man and animal models suggest they may be initiated when antigen-specific IgE is present, and may be blunted by antigen-specific IgG. In terms of pathology, immediate reactions are characterized primarily by edema while late phase reactions are associated with infiltration of the involved tissues with inflammatory cells. The potential importance of granulocytes to the reactions in the skin of rats and the lungs of rabbits was suggested when cytotoxic drugs that produced granulocytopenia prevented late phase responses. Several other factors also appear to be important in determining if an LAR will occur. These include the antigen load, level of airways reactivity, histamine releasing factors, lymphocyte populations within the lung, and endogenous corticosteroid levels. While various mediators of inflammation and hypersensitivity such as platelet activating factor and cyclooxygenase and lipoxygenase products of arachidonic acid metabolism produce some of the clinical features seen in asthma, one mediator is unlikely to be responsible for all the manifestations of this disorder. Rather, a series of cell-to-cell interactions mediated through the products they release are likely to produce the pathologic and physiologic features of the disease.

UI MeSH Term Description Entries
D006967 Hypersensitivity Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. Allergy,Allergic Reaction,Allergic Reactions,Allergies,Hypersensitivities,Reaction, Allergic,Reactions, Allergic
D007073 Immunoglobulin E An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). IgE
D012137 Respiratory System The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. Respiratory Tract,Respiratory Systems,Respiratory Tracts,System, Respiratory,Tract, Respiratory
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001249 Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). Asthma, Bronchial,Bronchial Asthma,Asthmas
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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