subject: Asthma Pathology and pathophsiology [print this page] PathologyThe pathologic features of asthma have been studied chiefly in fatalcases; some bronchoscopic data are available for mild and moderate asthma.
The histologic hallmarks of asthma include mucous gland hypertrophy,mucus hypersecretion, epithelial desquamation, wideningof the basement membrane, and infiltration by eosinophils.PathophysiologyBronchial hyperresponsiveness is common to all forms of asthma.It is measured by assessing pulmonary function before and afterexposure to methacholine, histamine, cold air, or exercise. Prolongedaerosol corticosteroid therapy reduces bronchial hyperresponsiveness.Prolonged therapy with certain other anti-inflammatory drugs (eg,cromolyn sodium, nedocromil) also reduces bronchial hyperresponsiveness.Note that although both cromolyn and nedocromilwere originally touted as "antiallergic" (they inhibit mast cell activation),they affect most cells involved in inflammation; also, the effectson these cells occur at lower doses than those that inhibit mast cellactivation
. Bronchial hyperresponsiveness generally is present in all forms ofasthma
mediators that have important roles in the development of endobronchialinflammation and smooth muscle changes that occur afteracute exposure to allergen. Mast cells and basophils are prominentduring the immediate-phase reaction.
In the immediate-phase reaction, mast cells and basophils areimportant.In the so-called late-phase reaction to allergen exposure, the bronchidisplay histologic features of chronic inflammation and eosinophilsbecome prominent in the reaction
. In the late-phase reaction, eosinophils become prominent.Patients who have chronic asthma and negative results on allergyskin tests seem to have an inflammatory infiltrate in the bronchi andhistologic findings dominated by eosinophils when asthma is active.Patients with sudden asphyxic asthma may have a neutrophilic ratherthan an eosinophilic infiltration of the airway.Various hypotheses explain the development of nonallergicasthma.One proposal is that the initial inflammation represents anautoimmune reaction arising from a viral or other microbial infectionin the lung and, for reasons unknown, inflammation becomeschronic and characterized by a lymphocyte cytokine profile in whichinterleukin (IL)-5 is prominent. The intense eosinophilic inflammationis thought to come from the IL-5 influence of T cells in thechronic inflammatory infiltrate.
IL-5 stimulates eosinophils.The 2 types of helper T cells are TH1 and TH2. In general, TH1cells produce interferon- and IL-2, and TH2 cells produce IL-4 andIL-5. IL-4 stimulates IgE synthesis. Hence, many clinical scientistsbelieve that atopic asthma is caused by a preferential activation ofTH2 lymphocytes.
IL-4 stimulates IgE synthesis.
TH2 lymphocytes produce IL-4 and IL-5.Important characteristics of cytokines are summarized in Table 2-2.IL-1, IL-6, and tumor necrosis factor are produced by antigen-presentingcells and start the acute inflammatory reaction against aninvader; IL-4 and IL-13 stimulate IgE synthesis; IL-2 and interferon- stimulate a cell-mediated response; and IL-10 is the primaryanti-inflammatory cytokine.Genetics of AsthmaThe genetics of asthma is complex and confounded by environmentalfactors. No "asthma gene" has been discovered.The gene encoding the subunit of the high-affinity IgEreceptor is located on chromosome 11q13 and is linked to totalIgE, atopy, and bronchial hyperreactivity. Polymorphic variantsof the 2-adrenergic receptor are linked to bronchial hyperreactivity.The gene for IL-4 is located on chromosome 5q31 and is linkedto total IgE.
