Background: Marijuana and alkaloidal cocaine (''crack'') are the two most commonly smoked substances in the United States after tobacco. While regular tobacco smoking has been found to be associated with extensive microscopic alterations in bronchial mucosa, little information is available concerning the effect of crack cocaine and marijuana on tracheobronchial histopathology. Study objective: To determine the relative impact of smoked substances (cocaine, marijuana, and tobacco) alone and in combination on the histopathology of the tracheobronchial mucosa and to assess whether the effects of habitual smoking of two or more substances (cocaine, marijuana, and/or tobacco) are additive. Design: Observational cohort study. Subjects: Fifty-three nonsmoking control subjects (NS), 14 current, habitual smokers of crack cocaine only (CS), 40 current, regular smokers of marijuana only (MS), 31 regular smokers of tobacco only (TS), 16 current smokers of both cocaine and marijuana (CMS), 12 current smokers of both cocaine and tobacco (CTS), 44 current smokers of both marijuana and tobacco (MTS), and 31 current smokers of cocaine, marijuana, and tobacco (CMTS). Methods: After preliminary screening evaluation, including a detailed respiratory and general health questionnaire and routine pulmonary function studies, subjects underwent fiberoptic bronchoscopy with endobronchial biopsies of the mucosa of the primary carina and randomly selected secondary or tertiary carinae. Biopsy specimens were processed for light microscopy, stained with hematoxylineosin or periodic acid-Schiff, and examined to assess epithelial, basement membrane, and submucosal alterations by one or two pathologists who were masked to the smoking status of the subject. Results: Smokers of cocaine, marijuana, or tobacco alone all exhibited more frequent abnormalities than NS in 10 (CS) or all 11 (MS and TS) of the histopathologic features assessed. For most features, MS and TS showed significantly more frequent alterations than NS (p less than or equal to 0.02), while CS showed significantly more frequent abnormalities than NS in only three features (p < 0.05) and nearly significant differences from NS in two additional, features (p less than or equal to 0.09). Alterations were noted most frequently in CTS (six features) and MTS (three features), while abnormalities were relatively infrequent in CMS. For 10 features, MTS had more frequent alterations than MS and TS. With a single exception, CMTS did not show more frequent alterations than CTS or MTS. Conclusion: Marijuana and tobacco smoking each produces significant bronchial mucosal histopathology and the effects of marijuana and tobacco appear additive. Cocaine appears to lead to fewer significant bronchial mucosal alterations than marijuana or tobacco when smoked alone and does not add to the changes associated with marijuana, When smoked together with tobacco, however, cocaine appears to augment the bronchial injury caused by tobacco smoking.
