Comparison of PD20 with two alternative measures of response to histamine challenge in epidemiological studies

Abstract

Bronchial responsiveness to histamine or methacholine provides a useful objective measure for epidemiological studies of airways disease, but most people in a community population do not have a 20% fall in forced expiratory volume in one second (FEV1) with the highest dose administered. Histamine challenge data were analysed to compare the repeatability. Normality and separation of symptom groups of the early dose-response slope with provocative dose producing a 20% fall in FEV1 (PD20). Tests were continued until a 20% fall in FEV1 occurred, or 4 mumol had been given. Data were available for 510 randomly selected subjects, and for an additional 283 with wheeze. A repeat test was obtained in 104 individuals. PD20 was estimated by curve fitting, with extrapolation to 8 mumol. Least-squares slope of percentage decline in FEV1 on histamine dose was calculated, using all the measured points and two-point slope as the fall from the post-saline measurement to the maximum cumulative dose divided by the maximum dose. Log transformation of PD20 and shifted reciprocal transformations of slope produced constant variance. Over all subjects the three measures had similar repeatability; in subjects with PD20 > 8 mumol the intraclass correlation for two-point slope was only 0.26, but was 0.66 for least-squares slope. Neither measure of slope was normally distributed, but the distribution of log(PD20) was consistent with a censored normal distribution. In conclusion, least-squares slope is preferable to two-point slope for epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Measuring bronchial responsiveness in epidemiology

“…Dose-response slopes calculated by more sophisticated methods, as described by CHINN et al [11] in the current issue of the ERJ, essentially offer similar problems. Another way to overcome the problem of cens' ored data is the assessment of regression methods for censored data that allow analysis of PD 20 as a continuous variable.…”

“…Another way to overcome the problem of cens' ored data is the assessment of regression methods for censored data that allow analysis of PD 20 as a continuous variable. The paper by CHINN et al [11] provides an evaluation of dose• response slope, least-square slope and PD 20 using a regression method for censored data. Repeatability, normality, stability of variance, applicability, and inter• pretability of the various measures are discussed.…”