EVALUATION OF METHACHOLINE DOSE-RESPONSE CURVES BY LINEAR AND EXPONENTIAL MATHEMATICAL-MODELS - GOODNESS-OF-FIT AND VALIDITY OF EXTRAPOLATION

Several models have been proposed to analyse dose-response curves reco rded in bronchoprovocation challenge tests, The aims of the present wo rk were: 1) to investigate which model (linear vs exponential) and whi ch minimization method (trials and errors vs Levenberg-Marquardt) give s better results in terms of data interpolation (goodness-of-fit); and 2) to verify the validity of extrapolation by comparing forced expira tory volume in one second (FEV(1)) observed after 4 mg methacholine wi th values extrapolated after truncation of the curves at 2 mg. For the se purposes, methacholine dose-response curves were obtained in 832 su bjects from a random population sample, as part of the European Commun ity Respiratory Health Survey (ECRHS) in Italy. Methacholine was inhal ed up to a maximum dose of 6 mg by dosimeter technique. The coefficien t of determination (r(2)) was significantly higher with the exponentia l model (0.81+/-0.22; mean+/-SD) than with the linear model (0.69+/-0. 27). With both models, extrapolated values were usually lower than obs erved values, As a consequence, a 20% fall in FEV(1) with respect to p ostsaline FEV(1) was observed in only 24% and 21% of the tests, where a 20% fall had been predicted, respectively, according to the linear a nd the exponential model. In conclusion, exponential models are better than linear models with respect to data interpolation of methacholine dose-response curves, However, they are worse with respect to extrapo lation to higher doses, With any model, extrapolation of dose-response curves by one doubling-dose should be avoided. (C)ERS Journals 1996.