Urinary Levels of Bombesin-Iike Peptides in Asymptomatic Cigarette Smokers: A Potential Risk Marker for Smoking-related Diseases1

Bombesin-like peptides (BLP) produced by pulmonary neuroendocrine cells have many physiological actions which are relevant to the pathobiology of cigarette smoking. The objectives of this study were to deter mine whether cigarette smokers excrete increased levels of BLP in their urine compared with nonsmokers, to determine the relationship between BLP levels in urine and bronchoalveolar lavage (BAL) fluid, and whether urinary BLP levels are merely a reflection of exposure to cigarette smoke. Simultaneous BAL fluid and urine samples were obtained from ten clinically normal smokers and 22 normal nonsmoker volunteers. Urine samples were also obtained from 39 normal smokers and 30 normal nonsmokers who did not have BAL performed. BLP levels were measured in urine and BAL fluid using an enzyme-linked immunoassay. Expired air content of carbon monoxide, which reflects recent exposure to ciga rette smoke, was determined in 34 of the clinically normal smokers and correlated with urinary BLP levels. We found that, in addition to having increased BLP levels in BAL fluid (/' = 0.04), asymptomatic cigarette smokers also have increased BLP levels in their urine compared with normal nonsmokers (/' = 0.007). Of note, a subgroup of smokers have markedly increased BLP levels which do not overlap with the nonsmokers. Urinary BLP levels correlated with expired air content of carbon monoxide (r = 0.49, P < 0.01). However, not all smokers with increased expired air content of carbon monoxide exhibited increased BLP levels. Finally, all smokers with detectable BLP levels in BAL fluid had detect able urinary BLP levels, and there was a positive correlation between BLP levels in urine and BAL fluid (r = 0.625, /' < 0.001). We conclude that a subgroup of asymptomatic cigarette smokers exhibit increased BLP levels, measurable in both urine and BAL fluid, which precede the onset of clinically detectable disease and which are not strictly dependent on smoking intensity. We speculate that smokers with increased BLP levels may have a greater risk for smoking-related diseases. biology of cigarette smoking (1-11). We have reported that some asymptomatic cigarette smokers without clinically detect able disease have increased BLP levels in their BAL fluid (12). This suggests that increased BLP levels precede the onset of clinical problems associated with smoking and, because of the aforementioned BLP effects, evokes the possibility of NE cells and BLP having a pathogenetic role in these disorders. In addition, although there is no evidence that smokers with increased BLP levels have an increased risk for developing smoking-related diseases, recent investigations suggest that pul monary NE cells with BLP immunoreactivity are increased in patients with tobacco-associated lung diseases (13-15), com pared with normal smokers without lung disease. In order to test the hypothesis that persistently high levels of BLP are associated with development of smoking-related dis orders, a prospective evaluation of a large cohort of cigarette smokers seems a reasonable project. Unfortunately, BAL is an invasive and expensive procedure, not optimal for screening large populations during cross-sectional and prospective stud ies, or to assess the effect of interventions such as smoking cessation on BLP levels. Therefore, we sought to determine whether, in addition to having increased BAL fluid BLP levels, asymptomatic cigarette smokers also excrete increased levels of BLP in their urine and whether there is a correlation between BAL fluid and urinary levels of BLP. Finally, because there is some correlation between greater cigarette consumption and risk for developing lung disease, we investigated the possibility that urinary BLP levels reflect intensity of exposure to cigarette smoke.