Human Interindividual Variability in Susceptibility to FEV1 Decline from Smoking

摘要

The report is part of an extended series of studies seeking new methods forquantitative risk assessment for noncancer health effects from smoking. The data sets from two studies of the effects of smoking on forced expiratory volume in 1 second (FEV1) are reviewed. In each case the data could be adequately described with a mixture of two normal distributions in which 31 to 34% of the population was contained in a subgroup with lower average FEV1's and greater variability in observed FEV1's in comparison to standard regression model predictions. Some interindividual variability in the response to cigarette smoke appeared in both populations studied here. For the Six Cities data set, the initial estimate of interindividual variability was described by a geometric standard deviation of 1.9, expressed as the antilog. Interindividual variability in the other data set, the Tucson data set, was best described by a geometric standard deviation of 4.2. As more is learned about the human interindividual variability at various mechanistic steps on the causal pathway from cigarette smoke and/or other lung damaging agents to decline in FEV1, the extent of human interindividual variability in each individual pharmacokinetic or pharmacodynamic parameter should be less than the overall variability tentatively assessed in the study.