Continuation of an ongoing cohort study is proposed to determine whether heavy, habitual smokers of marijuana (M) alone (MS) (greater than or equal to 10 joints/wk, greater than or equal to 5 years) or with tobacco (T) (MTS) exhibit a greater longitudinal rate of decline in lung function and a greater frequency of developing lung function abnormality and symptoms (sx) of acute and chronic bronchitis compared with nonsmokers of M who do or do not smoke T (TS and NS, respectively). The study groups will consist of 75 MTS, 72 MS, 45 TS and 62 NS initially examined in 1983-84, already retested in 1985-86 and currently undergoing a third examination in 1986-87. These subjects will be invited to participate in an extended follow-up study involving annual reexaminations of lung function and respiratory sx in 1988 through 1991. To determine the relative dose to the lung of M versus T smoke constituents (tar, CO) during customary smoking, we will also quantitate smoking dynamics, pre- and post-smoking end- expired CO and the amount of insoluble participates deposited in the lung during the smoking of M or T cigarettes of low and high THC content (less than 1% and greater than 3% delta 9-THC) or low-and high nicotine/tar content. Detailed self-reports of current and recent M smoking will be validated by analysis of hair samples for 11-nor-9 carboxy delta 9-THC. Smoking of another illicit substance (""""""""freebase"""""""" cocaine) has become increasing prevalent in our society. To evaluate the long-term effects of smoking alkaloidal cocaine (C) on the lung, an additional cohort of 200 frequent smokers of freebase C (greater than 0.5 gm/day greater than 1 yr) who do or do not smoke M and/or T regularly will be invited to undergo the same detailed examination of lung function and respiratory sx annually for 3-4 consecutive years. Validity of self-reports of recent C use will be assessed using the hair analysis for C and benzoylecgonine. Sixty of the 200 subjects who smoke C with or without M and/or T, in addition to 20 non-C smokers (5 NS, 5 TS, 5 MS and 5 MTS) will be invited to undergo fiberoptic bronchoscopy with bronchial mucosal biopsies and bronchoalveolar lavage to evaluate the impact of smoking C with and without other inhaled substances on tracheobronchial histopathology and alveolar macrophage ultrastructure and function (oxidative metabolism, microbial killing, proliferative activity and immune function). Results in concurrently as well as previously studied NS, TS, MS and MTS (total of 20 in each smoking category) will serve as reference groups for comparison of bronchial histopathologic and BAL results with those obtained in the C smokers in the same M and T smoking categories.
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