Porth's Essentials of Pathophysiology, 4e

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Respiratory Function

U N I T 6

prolong the asthma attack and set into motion a vicious cycle of exacerbations. 18 Typically, the response reaches a maximum within a few hours and may persist for 12 to 24 hours or longer. An initial trigger in the late- phase response causes the release of inflammatory medi- ators from mast cells, macrophages, and epithelial cells. These substances induce the migration and activation of other inflammatory cells (e.g., basophils, eosinophils, neutrophils), which then produce epithelial injury and edema, changes in mucociliary function, reduced clear- ance of respiratory tract secretions, and increased airway responsiveness (see Fig. 23-5B). Chronic inflammation can lead to airway remodeling, in which case airflow limitations may be only partially reversible. 19 NonatopicAsthma. Intrinsic or nonatopic asthma trig- gers include respiratory tract infections, exercise, hyper- ventilation, cold air, drugs and chemicals, hormonal changes and emotional upsets, air-borne pollutants, and gastroesophageal reflux. Respiratory tract infec- tions, especially those caused by viruses, may produce their effects by causing epithelial damage and stimulat- ing the production of IgE antibodies directed toward the viral antigens. In addition to precipitating an asth- matic attack, viral respiratory infections increase airway responsiveness to other asthma triggers. This hyperre- sponsiveness may persist for weeks beyond the original infection. Exercise-induced asthma occurs in a number of per- sons with bronchial asthma. 23 Although the cause of exercise-induced asthma is unclear, hyperventilation and corresponding changes in airway physiology may play a role. It has been suggested that the increased ven- tilatory rate required to meet higher oxygen demands during exercise challenges the ability of the airways to condition the inhaled air to the correct moist and heat levels before the air reaches the alveoli. Vigorous exer- cise results in the inhalation of increased volumes of relatively cold and dry air and loss of body heat from the respiratory mucosa, which in turn induces mast cells and epithelial cells to release proinflammatory media- tors such as histamine and leukotrienes. The response commonly is exaggerated when the person exercises in a cold environment. Wearing a mask over the nose and mouth often minimizes the attack or prevents it. In addition to inflammatory cytokines, airway cooling stimulates cholinergic receptors in the airways, with a resultant increase in airway resistance. A warm-up period alleviates the symptoms for some persons. Inhaled irritants, such as tobacco smoke and strong odors, are thought to induce bronchospasm by way of irritant receptors and a vagal reflex. Exposure to parental smoking has been reported to increase asthma severity in children. 24 Occupational asthma is caused by sensitizing agents or irritants encountered in the work- place. 25,26 Occupational asthma from sensitizers usually presents with a latent period of exposure, followed by the onset of disease. Irritant or nonimmunologic asthma results from high levels of exposure to irritant gases such as sulfur dioxide, nitrogen dioxide, and ozone, which may induce inflammatory exacerbations of airway

Antigen

Increased mucus production

IgE

Mast cell

Mucus- producing goblet cell

Cytokines

Bronchial smooth muscle

A

Bronchospasm

Mucus

Epithelial cell injury

Basophil

Neutrophil

Increased vascular

Eosinophil

permeability and edema

Afferent and efferent vagal fibers

B

Bronchospasm and heightened airway responsiveness

FIGURE 23-5. Pathogenesis of bronchial asthma. (A) The early-phase response triggered by an IgE-mediated release of mediators from sensitized mast cells.The release of chemical mediators results in increased mucus production, opening of mucosal intercellular junctions with exposure of submucosal mast cells to antigen, and bronchospasm. (B) The late-phase response involves epithelial cell injury with decreased mucociliary function and accumulation of mucus; release of inflammatory mediators with recruitment of neutrophils, eosinophils, and basophils; increased vascular permeability and edema; and increased airway responsiveness and bronchospasm.