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

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)

This article has been cited by other articles:

				A. Ek, L. Palmberg, B.-M. Sundblad, and K. Larsson Salmeterol Does Not Alter Increased Bronchial Responsiveness Caused by Organic Dust Exposure Chest, October 1, 2005; 128(4): 3038 - 3047. [Abstract] [Full Text] [PDF]

				S Chinn and J P Schouten Reproducibility of non-specific bronchial challenge in adults: implications for design, analysis and interpretation of clinical and epidemiological studies Thorax, May 1, 2005; 60(5): 395 - 400. [Abstract] [Full Text] [PDF]

				G. de Meer, G. B. Marks, J. C. de Jongste, and B. Brunekreef Airway responsiveness to hypertonic saline: dose-response slope or PD15? Eur. Respir. J., January 1, 2005; 25(1): 153 - 158. [Abstract] [Full Text] [PDF]

				J. Manfreda, M. R. Sears, M. R. Becklake, M. Chan-Yeung, H. Dimich-Ward, H. C. Siersted, P. Ernst, L. Sweet, L. Van Til, D. M. Bowie, et al. Geographic and Gender Variability in the Prevalence of Bronchial Responsiveness in Canada Chest, May 1, 2004; 125(5): 1657 - 1664. [Abstract] [Full Text] [PDF]

				I Sayers, S Barton, S Rorke, B Beghe, B Hayward, P Van Eerdewegh, T Keith, J B Clough, S Ye, J W Holloway, et al. Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma Thorax, May 1, 2003; 58(5): 417 - 424. [Abstract] [Full Text] [PDF]

				S Chinn Comparing and combining studies of bronchial responsiveness Thorax, May 1, 2002; 57(5): 393 - 395. [Abstract] [Full Text] [PDF]

				S.A. Lewis, S.T. Weiss, and J.R. Britton Airway responsiveness and peak flow variability in the diagnosis of asthma for epidemiological studies Eur. Respir. J., December 1, 2001; 18(6): 921 - 927. [Abstract] [Full Text] [PDF]

				S. Godfrey, L. Palmer, P. Burton, and W. Cookson INDEPENDENT INHERITANCE OF SERUM IMMUNOGLOBULIN E CONCENTRATIONS AND AIRWAY RESPONSIVENESS Am. J. Respir. Crit. Care Med., March 15, 2001; 163(4): 1030 - 1030. [Full Text]

				S. Chinn Methodology of bronchial responsiveness Thorax, November 1, 1998; 53(11): 984 - 988. [Full Text]