Comparison of bronchial responses to prostaglandin F 2α and methacholine

Abstract

We examined bronchial responsiveness to prostaglandin (PG) F 2α to determine its applicability in clinical practice and to compare it with bronchial responsiveness to the pharmacologically dissimilar agent, methacholine. Inhalation tests with twofold increasing concentrations of the two agents were carried out in 19 asthmatic and four normal subjects. The results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 sec (PC 20). The range of concentrations required to determine the PC 20 was greater with PGF 2α (0.0001 to <5 mg/ml) than that with methacholine (0.07 to 30.96 mg/ml). Side effects of cough, retrosternal irritation, and expectoration of sputum were more frequent after PGF 2α. Repeat measurements in the same subjects showed that responses to PGF 2α were as highly reproducible (r = 0.98, p < 0.001) as previously reported with methacholine, and there was a cumulative dose effect (p < 0.001). PC 20PGF 2α correlated with PC 20 methacholine (r = 0.5, p < 0.01), but to a lesser degree than was previously demonstrated between histamine and methacholine. The poorer correlation was explained by the results of four subjects tolerant to PGF 2α relative to methacholine, three of whom were aspirin (ASA) intolerant; the correlation was much stronger when these subjects were excluded from analysis (r = 0.91, p < 0.001). The results suggest that (1) PGF 2α is not a suitable agent to use in clinical practice to measure nonspecific bronchial responsiveness because of the wide dose range and unpleasant side effects, (2) the bronchial responsiveness of different individuals to PGF 2α and methacholine is usually well correlated and is thus unrelated to specific receptor activity, and (3) there is a relative reduction in responsiveness to PGF 2α in some asthmatics, particularly those with ASA intolerance.