A 15-year-old boy is subjected to recurrent attacks of asthma. A careful clinical history reveals that the asthma attacks occur most frequently after aspirin administration. Which of the following is the pathogenetic mechanism in this form of asthma?

Correct Answer: Inhibition of cyclooxygenase pathway
Description: Aspirin-induced asthma is an infrequent form of asthma. It is related to the direct pharmacologic action of aspirin on the metabolism of arachidonic acid. Aspirin inhibits the cyclooxygenase pathway without affecting the lipoxygenase pathway, leading to a decreased ratio of prostaglandins (bronchodilators) to leukotrienes (bronchoconstrictors). The disrupted balance between these two groups of arachidonic acid metabolites leads to bronchoconstriction in predisposed patients. Direct release of bronchoconstrictor substances is one of several pathogenetic mechanisms that may mediate occupational asthma, triggered by inhalation of a number of chemicals, including epoxy resins, plastics, cotton fibers, toluene, formaldehyde, and penicillin products. Enhanced vagal stimulation plays an essential role in non-atopic asthma. This variety of asthma, AKA non reaginic asthma, is initiated by viral infections of the upper respiratory tract (e.g., common cold and flu), which appear to lower the threshold of respiratory mucosa to parasympathetic (vagal) stimulation. Recall that vagal stimulation exes a bronchoconstrictor influence on the lungs. Type I hypersensitivity reactions are crucial in the pathogenesis of atopic asthma following prior exposure to a number of allergens. T-cell activation instructs B cells to produce IgE directed against a given allergen. On re-exposure, IgE on the surface of mast cells binds the allergen and induces mast cell degranulation. The mediators released from mast cells cause bronchospasm and recruit more inflammatory cells, including eosinophils, lymphocytes, and basophils. Ref: Barnes P.J. (2012). Chapter 254. Asthma. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison's Principles of Internal Medicine, 18e.
Category: Pharmacology
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