COMPARISON OF PD20 WITH 2 ALTERNATIVE MEASURES OF RESPONSE TO HISTAMINE CHALLENGE IN EPIDEMIOLOGIC STUDIES

Bronchial responsiveness to histamine or methacholine provides a usefu l objective measure for epidemiological studies of airways disease, bu t most people in a community population do not have a 20% fall in forc ed expiratory volume in one second (FEV) with the highest dose adminis tered. Histamine challenge data were analysed to compare the repeatabi lity, Normality and separation of symptom groups of the early dose-res ponse slope with provocative dose producing a 20% fall in FEV1 (PD20). Tests were continued until a 20% fall in FEV, occurred, or 4 mumol ha d been given. Data were available for 510 randomly selected subjects, and for an additional 283 with wheeze. A repeat test was obtained in 1 04 individuals. PD20 was estimated by curve fitting, with extrapolatio n to 8 mumol. Least-squares slope of percentage decline in FEV1 on his tamine dose was calculated, using all the measured points and two-poin t slope as the fall from the post-saline measurement to the maximum cu mulative dose divided by the maximum dose. Log transformation of PD20 and shifted reciprocal transformations of slope produced constant vari ance. Over all subjects the three measures had similar repeatability; in subjects with PD20 >8 mumol the intraclass correlation for two-poin t slope was only 0.26, but was 0.66 for least-squares slope. Neither m easure of slope was normally distributed, but the distribution of log( PD20) was consistent with a censored normal distribution. In conclusio n, least-squares slope is preferable to two-point slope for epidemiolo gical studies. Either PD20 or least-squares slope can be analysed; the former requires methods for censored data, but the latter requires tr ansformation with an arbitrary constant, +10% mumol-1 being recommende d, and methods requiring normality should be used with caution.