Comparison of bronchial responses to prostaglandin F2 alpha and methacholine

We examined bronchial responsiveness to prostaglandin (PG) F2 alpha to determine its applicability in clinical practice and to compare it with bronchial responsiveness to the pharmacologically dissimilar agent, methacholine. Inhalation tests with two fold 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 (PC20). The range of concentrations required to determine the PC20 was greater with PGF2 alpha (0.0001 to less than 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 PGF2 alpha. Repeat measurements in the same subjects showed that response to PGF2 alpha were as highly reproducible (r = 0.98, p less than 0.001) as previously reported with methacholine, and there was a cumulative dose effect (p less than 0.001). PC20PGF2 alpha correlated with PC20 methacholine (r = 0.5, p less than 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 PGF2 alpha 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 less than 0.001). The results suggests that (1) PGF2 alpha 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 PGF2 alpha and methacholine is usually well correlated and is thus unrelated to specific receptor activity, and (3) there is a relative reduction in responsiveness to PGF2 alpha in some asthmatics, particularly those with ASA intolerance.