Background: Marijuana and alkaloidal cocaine (''crack'') are the two m
ost commonly smoked substances in the United States after tobacco. Whi
le regular tobacco smoking has been found to be associated with extens
ive microscopic alterations in bronchial mucosa, little information is
available concerning the effect of crack cocaine and marijuana on tra
cheobronchial histopathology. Study objective: To determine the relati
ve impact of smoked substances (cocaine, marijuana, and tobacco) alone
and in combination on the histopathology of the tracheobronchial muco
sa and to assess whether the effects of habitual smoking of two or mor
e 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 smok
ers of tobacco only (TS), 16 current smokers of both cocaine and marij
uana (CMS), 12 current smokers of both cocaine and tobacco (CTS), 44 c
urrent smokers of both marijuana and tobacco (MTS), and 31 current smo
kers of cocaine, marijuana, and tobacco (CMTS). Methods: After prelimi
nary screening evaluation, including a detailed respiratory and genera
l health questionnaire and routine pulmonary function studies, subject
s underwent fiberoptic bronchoscopy with endobronchial biopsies of the
mucosa of the primary carina and randomly selected secondary or terti
ary carinae. Biopsy specimens were processed for light microscopy, sta
ined with hematoxylineosin or periodic acid-Schiff, and examined to as
sess epithelial, basement membrane, and submucosal alterations by one
or two pathologists who were masked to the smoking status of the subje
ct. Results: Smokers of cocaine, marijuana, or tobacco alone all exhib
ited more frequent abnormalities than NS in 10 (CS) or all 11 (MS and
TS) of the histopathologic features assessed. For most features, MS an
d TS showed significantly more frequent alterations than NS (p less th
an or equal to 0.02), while CS showed significantly more frequent abno
rmalities than NS in only three features (p < 0.05) and nearly signifi
cant differences from NS in two additional, features (p less than or e
qual to 0.09). Alterations were noted most frequently in CTS (six feat
ures) and MTS (three features), while abnormalities were relatively in
frequent in CMS. For 10 features, MTS had more frequent alterations th
an MS and TS. With a single exception, CMTS did not show more frequent
alterations than CTS or MTS. Conclusion: Marijuana and tobacco smokin
g each produces significant bronchial mucosal histopathology and the e
ffects of marijuana and tobacco appear additive. Cocaine appears to le
ad to fewer significant bronchial mucosal alterations than marijuana o
r tobacco when smoked alone and does not add to the changes associated
with marijuana, When smoked together with tobacco, however, cocaine a
ppears to augment the bronchial injury caused by tobacco smoking.