A cohort study is proposed to determine whether heavy, habitual smokers (S) of marijuana (M) (Greater than or equal to 10 joints/wk, Greater than or equal to 5 yrs) with or without tobacco (T) exhibit a greater longitudinal rate of decline in lung function and a greater frequency of development of lung function abnormality and symptoms of chronic bronchitis than a comparison group of lifelong never (or former infrequent) MS with or without T. The study groups will consist of 293 heavy, habitual MS and 149 non-MS examined in 1983-84 as part of a cross-sectional study of the pulmonary effects of heavy, habitual M use. Both the M-smoking and control subjects in the cross-sectional study will be invited to participate in a 3-yr follow-up study, consisting of the annual administration over 3 yrs (1985-88) of an interval respiratory and drug use questionnaire and the same lung function tests that were performed at baseline. Methacholine inhalation challenges will also be performed to evaluate airways reactivity as a possible risk factor for development of M-induced airways abnormality. To estimate the relative dose to the lung of M vs T smoke during customary smoking, we will also quantitate smoking topography and respiratory deposition of inhaled particulates in 20 MTS, 10 MS and 20 TS during smoking of M of low (1%) and high (2.8%) THC content and/or T of low and high nicotine/tar content. In addition, a subset of 40 M smokers (1/2 with and 1/2 without T), including 20 subjects already bronchoscoped in 1983-84, and 20 control non-smokers of M (10 with and 10 without T) will be invited to undergo fiberoptic bronchscopy with bronchial mucosal biopsy and bronchial alveolar lavage (BAL). In view of the frequent histopathologic abnormalities noted in bronchial mucosal biopsies from the M smokers (with and without T) who underwent bronchoscopy in 1983-84, the proposed study should permit assessment of a) the specificity of these abnormalities for M, b) possible additive or synergistic effects of M+T, and c) possible progression or regression of previously noted histologic abnormalities and alveolar macrophage (AM) dysfunction with continued heavy M smoking or cessation or reduction in M use. To evaluate further the effect of M (with or without T) on the lung's defenses, additional studies are proposed using the BAL fluid obtained at bronchoscopy to determine the effect of M and/or T on chemotaxis for BAL-derived AM and peripheral neutrophils, AM activity in fungal and bacterial phagocytosis and killing, AM effects on lymphocyte blastogenesis, AM oxidative metabolism, bronchoalveolar and peripheral blood T-cell subsets, and anti-protease activity in BAL fluid.
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