Lung functionIn the Tucson study (Bloom et al. 1987), regular marijuana use (approximately 1 joint/day on the average) by young persons was associated with significant impairment in measurements that reflect the function of the small airways—the major site of COPD. These changes were even greater than those noted in young regular tobacco smokers, and the effects of both marijuana and tobacco appeared to be additive. The authors concluded that regular marijuana smoking was a risk factor for the development of COPD, which, in its advanced stages, is characterized by disabling shortness of breath. In contrast, the Los Angeles study (Tashkin et al. 1987) failed to find any impairment in small airways function in association with even heavier regular use of marijuana (3 - joints per day), although mild, statistically significant narrowing of large, central airways was noted in the marijuana users. Recently, a longitudinal analysis of the lung function results obtained in Los Angeles (Tashkin et al. 1997) revealed an accelerated rate of decline in lung function with age (as is characteristic of tobacco smokers who are destined to develop symptomatic COPD) in the tobacco-smoking participants but failed to find such an effect in the marijuana smokers. The mixed findings from these two studies leave open the question as to whether habitual smoking of marijuana, in the absence of tobacco, can lead to COPD.
Bronchoscopic findings: visual appearance and microscopic alterations in bronchial wall biopsies
Bronchoscopy was performed in 53 NS, 40 MS, 31 IS, and 44 MTS who participated in the LosAngeles study (Fligiel et al. in press; Gong et al. 1987) to ascertain whether regular smoking of marijuana with or without tobacco might cause damage to the airways and lung that might not be reflected by abnormalities in lung function. Visual inspection of the appearance of the large, central airways showed that a large proportion of smokers of marijuana or tobacco alone (but rarely nonsmokers) showed evidence of increased redness (erythema) and swelling (edema) of the airway tissues and increased mucous secretions, and the findings in the combined smokers of both marijuana and tobacco appeared additive (Roth et al. 1996). These visual findings were correlated with microscopic evidence of increased numbers and size of small blood vessels in the bronchial wall, tissue edema, and replacement of the normal ciliated surface lining cells (ciliated columnar epithelial cells) by mucus-secreting goblet cells. These observations may explain the relatively high proportion of marijuana smokers who complain of chronic cough and phlegm. Overproduction of mucus by the increased numbers of mucus-secreting cells in the face of diminished numbers of ciliated cells (cells with hair-like projections) that normally function to transport the mucus toward the mouth by rapid ciliary motion might leave cough as the only mechanism to remove mucus from the airways.
Microscopic findings in biopsies of the bronchial mucosa (superficial layer of cells) revealed that a much higher proportion of MS than NS (and a proportion comparable to, if not greater than, that of IS) exhibited a variety of cellular abnormalities. The latter included abnormal proliferation of cells (reserve cells, goblet cells), transformation of normal ciliated cells into abnormal cells resembling skin (squamous metaplasia), accumulation of inflammatory cells, and abnormalities in the cell nuclei (Fligiel et al. in press; Gong et al. 1987). Some of these changes (e.g., nuclear alterations and squamous metaplasia) have been described as precursors to the subsequent development of lung cancer in tobacco smokers (Auerbach et al. 1961) and thus may be considered to be premalignant. Smokers of both marijuana and tobacco exhibited these microscopic cellular abnormalities to the greatest extent, suggesting an additive injurious effect of marijuana and tobacco on airway tissue. These findings in healthy, largely nonsymptomatic, young marijuana smokers confirm and extend previous bronchoscopic observations of Tennant (1980) in symptomatic U.S. servicemen who smoked cannabis (in the form of hashish) heavily.
Genetic markers of precancer progression
A specific combination of genes (oncogenes, tumor suppressor genes) that are responsible for regulating cell growth must be activated and/ or mutated for lung cells to transform into cancerous cells. Bronchoscopic biopsies from 63 participants in the Los Angeles study (12 MS, 9 MTS, 14 TS, and 28 NS), none of whom used crack cocaine, were examined for alterations in some of the genes known to be involved in the development of lung cancer. Immunohistology was used to detect the overexpression of the protein products of these genes by epithelial cells in the bronchial biopsies (Roth et al. 1996). Protein products for two of the three genes examined were markedly overexpressed in the biopsies from MS compared to NS (and even to a greater extent than in the biopsies from TS), and the effects of marijuana and tobacco were additive. Expression of the third gene, the p53 oncogene, which may play a role in as many as 75 percent of all lung cancers, was found only in a smoker of marijuana plus tobacco, as well as in one of 12 combined smokers of marijuana, cocaine, and tobacco who were also examined. These results indicate genetic evidence of extensive growth dysregulation in these relatively young smokers of marijuana alone and, particularly, in the combined smokers of marijuana and tobacco, implying an important role of marijuana use in progression to lung cancer.
Bronchoscopic findings: visual appearance and microscopic alterations in bronchial wall biopsies
Bronchoscopy was performed in 53 NS, 40 MS, 31 IS, and 44 MTS who participated in the LosAngeles study (Fligiel et al. in press; Gong et al. 1987) to ascertain whether regular smoking of marijuana with or without tobacco might cause damage to the airways and lung that might not be reflected by abnormalities in lung function. Visual inspection of the appearance of the large, central airways showed that a large proportion of smokers of marijuana or tobacco alone (but rarely nonsmokers) showed evidence of increased redness (erythema) and swelling (edema) of the airway tissues and increased mucous secretions, and the findings in the combined smokers of both marijuana and tobacco appeared additive (Roth et al. 1996). These visual findings were correlated with microscopic evidence of increased numbers and size of small blood vessels in the bronchial wall, tissue edema, and replacement of the normal ciliated surface lining cells (ciliated columnar epithelial cells) by mucus-secreting goblet cells. These observations may explain the relatively high proportion of marijuana smokers who complain of chronic cough and phlegm. Overproduction of mucus by the increased numbers of mucus-secreting cells in the face of diminished numbers of ciliated cells (cells with hair-like projections) that normally function to transport the mucus toward the mouth by rapid ciliary motion might leave cough as the only mechanism to remove mucus from the airways.
Microscopic findings in biopsies of the bronchial mucosa (superficial layer of cells) revealed that a much higher proportion of MS than NS (and a proportion comparable to, if not greater than, that of IS) exhibited a variety of cellular abnormalities. The latter included abnormal proliferation of cells (reserve cells, goblet cells), transformation of normal ciliated cells into abnormal cells resembling skin (squamous metaplasia), accumulation of inflammatory cells, and abnormalities in the cell nuclei (Fligiel et al. in press; Gong et al. 1987). Some of these changes (e.g., nuclear alterations and squamous metaplasia) have been described as precursors to the subsequent development of lung cancer in tobacco smokers (Auerbach et al. 1961) and thus may be considered to be premalignant. Smokers of both marijuana and tobacco exhibited these microscopic cellular abnormalities to the greatest extent, suggesting an additive injurious effect of marijuana and tobacco on airway tissue. These findings in healthy, largely nonsymptomatic, young marijuana smokers confirm and extend previous bronchoscopic observations of Tennant (1980) in symptomatic U.S. servicemen who smoked cannabis (in the form of hashish) heavily.
Genetic markers of precancer progression
A specific combination of genes (oncogenes, tumor suppressor genes) that are responsible for regulating cell growth must be activated and/ or mutated for lung cells to transform into cancerous cells. Bronchoscopic biopsies from 63 participants in the Los Angeles study (12 MS, 9 MTS, 14 TS, and 28 NS), none of whom used crack cocaine, were examined for alterations in some of the genes known to be involved in the development of lung cancer. Immunohistology was used to detect the overexpression of the protein products of these genes by epithelial cells in the bronchial biopsies (Roth et al. 1996). Protein products for two of the three genes examined were markedly overexpressed in the biopsies from MS compared to NS (and even to a greater extent than in the biopsies from TS), and the effects of marijuana and tobacco were additive. Expression of the third gene, the p53 oncogene, which may play a role in as many as 75 percent of all lung cancers, was found only in a smoker of marijuana plus tobacco, as well as in one of 12 combined smokers of marijuana, cocaine, and tobacco who were also examined. These results indicate genetic evidence of extensive growth dysregulation in these relatively young smokers of marijuana alone and, particularly, in the combined smokers of marijuana and tobacco, implying an important role of marijuana use in progression to lung cancer.
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