Analysis of dose-response curves to methacholine. An approach suitable for population studies.
Dose-response curves to methacholine were examined in 9 normal and 10 asthmatic volunteers to determine whether the relationship between dose and response can be adequately summarized by means of a single, continuous measure that is not censored at lower levels of bronchial responsiveness. Subjects underwent a standard methacholine challenge test. There was a strong linear relationship between percent decline FEV1 and cumulative dose methacholine. We summarized each dose-response curve by the slope of a line extending from the origin to the last data point obtained. This summary dose-response slope effectively separated asthmatic from normal subjects, and there was a greater than 3,000-fold difference between the least and most responsive subjects. There was a high degree of correlation between the dose-response slope determined by the standard methacholine challenge protocol and that determined by an abbreviated protocol currently being used to examine nonspecific airway responsiveness in a large, longitudinal study of aging. Among the participants of the latter study, there is a unimodal, skewed distribution of dose-response slope. Dose-response slope is proposed as a quantitative measure of nonspecific airway responsiveness that avoids censoring and that may be particularly useful in epidemiologic studies.
O'Connor
G
G
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Sparrow
D
D
Taylor
D
D
Segal
M
M
Weiss
S
S
D000375:Aging / Q000187:drug effects / Q000502:physiology; D001249:Asthma / Q000175:diagnosis / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005541:Forced Expiratory Volume; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000008:administration & dosage*; D012016:Reference Values
D008688:Methacholine Compounds; D016210:Methacholine Chloride