Lung cancer and passive smoking: Association an artefact due to misclassification of smoking habits?☆
Abstract
1775 subjects were asked about their current use of tobacco products or nicotine chewing gum. 1537 provided a sample of saliva for cotinine analysis. Of 808 who claimed not to be users of such products, 20 (2.5%) had cotinine values above 30 , suggesting their self-reports were false. In another study, 540 subjects were interviewed on two occasions. 10% of subjects claiming on one occasion never to have smoked made inconsistent statements on the other occasion. A third study showed a strong tendency for smokers to marry smokers.
Bias caused by misclassification of smoking habits coupled with between-spouse smoking habit concordance can completely explain reported apparent excesses in lung cancer risk in non-smokers married to smokers.
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Cited by (46)
Seasonal assessment of environmental tobacco smoke and respirable suspended particle exposures for nonsmokers in Bremen using personal monitoring
2001, Environment InternationalThe study was designed to determine seasonal differences in personal exposures to respirable suspended particles (RSP) and environmental tobacco smoke (ETS) for nonsmokers in Bremen, Germany. The subjects were office workers, either living and working in smoking locations or living and working in nonsmoking locations. One hundred and twenty four randomly selected nonsmoking subjects collected air samples close to their breathing zone by wearing personal monitors for 24 h or, in some cases, for 7-day periods during the winter of 1999. The investigation was repeated in the summer with 126 subjects, comprised of as many of the studied winter population (89 subjects) as possible. Saliva cotinine analyses were undertaken to verify the nonsmoking status of the subjects. Subjects wore one personal monitor while at work and one while away from the workplace on weekdays, and a third monitor at the weekend. Collected air samples were analysed for RSP, nicotine, 3-ethenylpyridine (3-EP) and ETS particles. The latter were estimated using ultraviolet absorbance (UVPM), fluorescence (FPM) and solanesol (SolPM) measurements. ETS exposure was consistently higher in the winter than in the summer, this pattern being particularly evident for subjects both living and working with smokers. The highest median 24-h time weighted average (TWA) concentrations of ETS particles (SolPM, 25 μg m−3) and nicotine (1.3 μg m−3) were recorded for subjects performing weekday monitoring during the winter. These were significantly higher than equivalent levels of ETS particles (SolPM, 2.4 μg m−3) and nicotine (0.26 μg m−3) determined during the summer. There were no appreciable differences between winter and summer percent workplace contributions to median TWA ETS particle and nicotine weekday concentrations, the workplace in Bremen, in general, contributing between 35% and 61% of reported median concentrations. Workers, on average, spent one-third of their time at work during a weekday, indicating that concentrations were either comparable or higher in the workplace than in the home and other locations outside the workplace. Median 24-h weekend ETS particle and nicotine concentrations for smoking locations were not significantly different from equivalent weekday levels during the winter, but were significantly lower during the summer. Based upon median 24-h TWA SolPM and nicotine concentrations for the winter, extrapolated to 1 year's ETS exposure, those subjects both living and working in smoking locations (the most highly exposed group) would potentially inhale 13 cigarette equivalents/year (CEs/y). However, based on a similar extrapolation of summer measurements, the same group of subjects would potentially inhale between 1.3 and 1.9 CEs/y. The most highly exposed subjects in this study, based upon 90th percentile concentrations for those both living and working in smoking locations during the winter, would potentially inhale up to 67 CEs/y in the winter and up to 22 CEs/y in the summer. This clearly demonstrates that seasonal effects should be taken into account in the design and interpretation of ETS exposure studies. Air sampling over a 7-day period was shown to be technically feasible, and subsequent RSP, ETS particle and nicotine levels determined by 7-day monitoring were not found to be significantly different from equivalent levels determined by 24-h monitoring. However, the longer sampling period resulted in the collection of an increased quantity of analytes, which improved the limits of quantitation (LOQ) and allowed a more accurate determination of low level ETS exposure. This was reflected by a reduced percentage of data falling below the LOQ for 7-day monitoring compared with 24-h monitoring. The use of a liquid chromatographic method with tandem mass spectrometric detection for saliva cotinine measurement afforded a greatly improved LOQ and greater accuracy at low concentrations compared with the radioimmunoassay (RIA) method used in previous studies by these authors. In this study, 17 subjects out of 180 tested (9.4%) were found to have saliva cotinine levels exceeding the selected threshold of 25 ng ml−1 used to discriminate between smokers and nonsmokers.
Exposure to environmental tobacco smoke and the risk of lung cancer: A meta-analysis
2000, Lung CancerA meta-analysis was carried out to calculate a pooled estimate of relative risk of lung cancer following exposure to environmental tobacco smoke (ETS) and to determine whether there was any heterogeneity in the pooled estimates according to selected characteristics of the studies. A total of 35 case-control and five cohort studies providing quantitative estimates of the association between lung cancer and exposure to ETS published between January 1981 and March 1999 were identified. Using fixed- and random-effects models, we calculated pooled estimates of relative risk for exposure to ETS from subjects’ parents (during childhood), spouses, and coworkers. As well, we investigated whether the pooled estimates of relative risk varied by study location, degree of control of potential confounding variables, proportion of cases confirmed histologically, proportion of surrogate respondents, nonresponse rates, and year of publication. The relative risk of lung cancer among non smoking women ever exposed to ETS from their husbands’ smoking was 1.20 (95% confidence interval (CI): 1.12-1.29). The pooled relative risk was 1.19 (95% CI: 1.10–1.29) for case-control studies and 1.29 (95% CI: 1.04–1.62) for cohort studies. In various subgroup and meta-regression analyses, we found no statistically significant differences by selected characteristics of the studies. In addition, we found that the risk of lung cancer increased consistently with increasing levels of exposure. The 11 studies reporting relative risks among male non smokers yielded a pooled relative risk of 1.48 (95% CI: 1.13–1.92) for ever exposed to ETS, and the relative risk of lung cancer for ever being exposed to ETS at work was a 1.16 (95% CI: 1.05–1.28). These results are consistent with the hypothesis that exposure to ETS increases the risk of lung cancer. While there may be alternative explanations to the data, it is more likely that the observed association is not an artifact and that ETS causes lung cancer in non smokers.
Assessment of environmental tobacco smoke and respirable suspended particle exposures for nonsmokers in Basel by personal monitoring
1999, Atmospheric EnvironmentOne hundred and ninety-six randomly selected nonsmoking subjects collected air samples close to their breathing zone by wearing personal monitors for 24 h. The study was centred in Basel, Switzerland, and comprised housewives in one group, primarily for assessing exposures in the home, and office workers in a second group to assess the contribution of the workplace to overall exposure. Samples collected were analysed for respirable suspended particles (RSP), nicotine, 3-ethenylpyridine and environmental tobacco smoke (ETS) particles by using ultraviolet absorbance, fluorescence and solanesol measurements. Saliva cotinine analyses were also undertaken to confirm the nonsmoking status of the subjects. Based upon median 24 h time weighted average concentrations, office workers who live and work with smokers were exposed to 39 μg m-3 RSP, 6.6 μg m-3 ETS particles and 0.90 μg m-3 nicotine. Housewives living with smokers were exposed to median concentrations of 34 μg m-3 RSP, 1.4 μg m-3 ETS particles and 0.60 μg m-3 nicotine. Workplaces where smoking occurred were estimated, on average, to contribute between 34 and 46% to annual exposure of ETS particles and nicotine. Based upon 90th percentile values the most highly exposed housewives, those living with smokers, would potentially inhale 18 cigarette equivalents per year whilst the most highly exposed office workers, both living and working with smokers, might inhale 61 cigarette equivalents. The rate at which subjects misreported their nonsmoking status varied between 9.7 and 12.2%.
Assessment of environmental tobacco smoke and respirable suspended particle exposures for nonsmokers in Hong Kong using personal monitoring
1998, Environment InternationalOne hundred and ninety-four randomly selected nonsmoking subjects collected air samples in their breathing zone by wearing personal monitors for 24 h. The study was centered in Hong Kong, and comprised housewives in one group, primarily for assessing exposures in the home, and office workers in a second group to assess the contribution of the workplace to overall exposure. Samples collected were analysed for respirable suspended particles (RSP), nicotine, 3-ethenylpyridine, and environmental tobacco smoke (ETS) particles using ultraviolet absorbance (UVPM), fluorescence (FPM), and solanesol measurements (SolPM). Saliva cotinine analyses were also undertaken to confirm the nonsmoking status of the subjects and to investigate their correlation with ETS exposure measurements. Approximately 6% of the subjects in Hong Kong misclassified their nonsmoking status. Median time-weighted average (TWA) RSP concentrations varied from 43 to 54 μg m−3 with no significant differences detected between any of the groups investigated. Office workers who lived and worked with smokers were exposed to 2.6 μg m−3 ETS particles (SolPM) and 0.44 μg m−3 nicotine, based on median TWA concentrations. Median concentrations of ETS particles and nicotine were below the limits of quantification for housewives living with smokers and were not significantly different from those for housewives living with nonsmokers. It would therefore be unreliable in Hong Kong to use a smoking spouse as a marker for assessing health risks related to ETS exposure. The office workers in this study were significantly more exposed to ETS than housewives from either smoking or nonsmoking homes, and the workplace was estimated to contribute over 33% of the annual exposure to ETS particles and nicotine. Exposure estimates suggest that the most highly exposed office workers in this study receive between 11 and 50 cigarette equivalents per year, based upon upper decile levels for ETS particles and nicotine, respectively.
Assessment of air quality in Paris by personal monitoring of nonsmokers for respirable suspended particles and environmental tobacco smokes
1998, Environment InternationalExposure to respirable suspended particles (RSP), environmental tobacco smoke (ETS) particles, nicotine, and 3-ethenylpyridine (3-EP) was assessed in Paris for 222 subjects during March and April 1995. Personal monitors were worn over a 24-h period, each subject providing a saliva sample for cotinine analysis both prior to and following the monitoring period. Comprehensive lifestyle questionnaires were also completed before and after the monitoring period. The study comprised housewives in one group, primarily for assessing exposures in the home, and office workers in a second group to assess exposures in the workplace. A single personal monitor was worn by each housewife, while employed subjects wore one monitor at work and a separate monitor at home and elsewhere. Based on median 24-h time-weighted average exposures, the most highly exposed subjects to RSP, ETS particles, nicotine, and 3-EP were office workers living with smokers. Additionally, based upon nicotine exposures, subjects who were also employed in locations where smoking was allowed were the most exposed. Based upon median levels, housewives living in nonsmoking households would be exposed to 1 cigarette equivalent per y or less, compared with between 1.2 and 3 cigarette equivalents per y for housewives living in smoking households. Subjects living and working with smokers had the highest median saliva cotinine level of 1.6 ng mL−1. Using a cut off level of 25 ng mL−1 to indicate active smoking, up to 4.7% of the subjects were found to have misreported themselves as nonsmokers.
Assessment of environmental tobacco smoke and respirable suspended particle exposures for nonsmokers in Lisbon by personal monitoring
1998, Environment InternationalOne hundred and ninety seven randomly selected nonsmoking subjects collected air samples near their breathing zone by wearing personal monitors for 24-h. The study was centred in Lisbon, Portugal and comprised housewives in one group, primarily for assessing exposures in the home, and office workers in a second group to assess the contribution of the workplace to overall exposure. Samples collected were analysed for respirable suspended particles (RSP), nicotine, 3-ethenylpyridine and environmental tobacco smoke (ETS) particles using ultraviolet absorbance, fluorescence and solanesol measurements. Saliva cotinine analyses were also undertaken to confirm the nonsmoking status of the subjects. A large proportion of the data was below the limit of quantification and, apart from housewives from nonsmoking homes, there were few significant differences noticeable in 24-h time weighted average (TWA) concentrations between subject groups. Based on median TWA concentrations the highest exposed office workers encountered 43 μg m−3 RSP, 9.3 μg m−3 ETS particles and 0.58 μg m−3 nicotine. Overall the workplace contributed the most to nicotine and ETS particle exposure, whereas RSP exposure was higher away from the workplace. Annualised exposure estimates suggest that the most highly exposed subjects would receive approximately 20 cigarette equivalents per annum based upon upper decile levels.
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Presented at the International Experimental Toxicology Symposium on Passive Smoking, October 23–25, 1986, Essen (F.R.G.).
Any views expressed in this paper are those of the author and not of the organisation board of the symposium.