Porth's Essentials of Pathophysiology, 4e

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Disorders of Ventilation and Gas Exchange

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disorders, such as hay fever, urticaria, and eczema. Attacks are related to exposure to specific allergens. Among air-borne allergens implicated in perennial (year- round) asthma are house dust mite allergens, cockroach allergens, animal danders, and Alternaria (a fungus). The mechanisms of response to allergens in atopic asthma can be described in terms of the early-phase and the late-phase responses 15,16 (Fig. 23-4). The symp- toms of the early-phase response (also called the acute- phase response ), which usually develop within 10 to 20 minutes of exposure to the allergen, are caused by the release of chemical mediators from presensitized IgE-coated mast cells. In the case of air-borne antigens, the reaction occurs when antigen binds to previously sensitized mast cells on the mucosal surface of the air- ways (Fig. 23-5A). Mediator release results in the infil- tration of inflammatory cells, opening of the mucosal intercellular junctions, and increased access of antigen to the more prevalent submucosal mast cells. In addi- tion, there is bronchospasm caused by stimulation of parasympathetic receptors, mucosal edema caused by increased vascular permeability, and increased mucus secretions. The acute response usually can be inhibited or reversed by bronchodilators, such as β 2 -agonists, but not by the anti-inflammatory actions of corticosteroids. The late-phase response, which develops 4 to 8 hours after exposure to an asthmatic trigger, involves inflam- mation and increased airway responsiveness that

vascular permeability, and mucus production. 15,16 In some persons, persistent changes in airway structures occur, including injury to epithelial cells, smooth muscle hyper- trophy, and blood vessel proliferation. Recent research has focused on the role of T lym- phocytes in the pathogenesis of bronchial asthma. It is now known that there are two subsets of T-helper cells (T H 1 and T H 2) that develop from the same precursor CD4 + T lymphocyte (see Chapter 15). 15 T H 1 cells dif- ferentiate in response to microbes and stimulate the differentiation of B cells into immunoglobulin (Ig) M and IgG-producing plasma cells. T H 2 cells, on the other hand, respond to allergens by stimulating B cells to differentiate into IgE-producing plasma cells that bind to mucosal mast cells. Subsequent IgE-mediated reactions to inhaled allergens elicit an asthmatic attack (see Chapter 16, Fig. 16-1). In persons with allergic asthma, T-cell differentiation appears to be skewed toward T H 2 cells. Although the molecular basis for this preferential differentiation is unclear, it seems likely that both genetic and environmental factors play a role. Atopic Asthma. Atopic asthma is typically initiated by a type I hypersensitivity reaction induced by exposure to an extrinsic antigen or allergen. 15,16 It usually has its onset in childhood or adolescence and is seen in persons with a family history of atopic allergy (see Chapter 16). Persons with atopic asthma often have other allergic

Allergen

Early-phase response

Mast cells

Bronchospasm

Release histamine, leukotrienes, interleukins, and prostaglandins

Infiltration of inflammatory cells

Airflow limitation

Release cytokines, interleukins, and other inflammatory mediators

Late-phase response

Increased airway responsiveness

Airway inflammation

Epithelial injury

Edema

Impaired mucociliary function

FIGURE 23-4. Mechanisms of early- and late-phase IgE-mediated bronchospasm.