title: Provocative dose and dose-response curve to inhaled propranolol in asthmatic patients with bronchial hyperresponsiveness to methacholine.
abstract: This study was carried out to compare bronchial responses to inhaled propranolol (P) and methacholine (M) in a group of asthmatic subjects with mild to moderate bronchial hyperresponsiveness to M; to determine the short term reproducibility of bronchial response to propranolol; and to examine the shape of dose-response curve to P relative to that of M. Doses of M and P were given in mumoles and bronchial responses to both agents were expressed as the provocative dose that induced a 20 percent fall in FEV1 (PD20 FEV1). In 16 asthmatic patients, there was no correlation between the PD20 of the two agents. Mean PD20 M (+/- SD in log scale) was approximately nine times lower than mean PD20 P (0.64 +/- 0.96 and 5.80 +/- 1.65, respectively). This difference was statistically significant (t = 4.58, p less than 0.001). In six asthmatic patients, the reproducibility of PD20 P was similar to that of M (intraclass correlation coefficient 0.969 and 0.957, respectively). The shape of the dose-response curves to P was different from that of M in five of nine asthmatic patients when all experimental points were analyzed by double-reciprocal plot. We noticed that even small doses of inhaled P may cause a severe bronchoconstriction. Therefore, special caution should be taken to increase P doses very gradually, when studying the dose-response curve. We demonstrated that P inhalation induced a measurable bronchoconstriction in subjects with mild to moderate hyperresponsiveness and it was reproducible. However, the bronchial sensitivity to P was lower than to M. Our findings suggest that P and M have different mechanisms of action.
authors.forename: A
authors.initials: A
authors.lastname: Foresi
authors.forename: A
authors.initials: A
authors.lastname: Chetta
authors.forename: G M
authors.initials: GM
authors.lastname: Corbo
authors.forename: A
authors.initials: A
authors.lastname: Cuomo
authors.forename: D
authors.initials: D
authors.lastname: Olivieri
mesh_terms: D001249:Asthma / Q000175:diagnosis*; D001985:Bronchial Provocation Tests; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D011433:Propranolol
chemical_list: D008688:Methacholine Compounds; D016210:Methacholine Chloride; D011433:Propranolol