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

Pulmonary Division, Department of Medicine, Atlanta Department of Veterans Affairs Medical Center, Emory University School of Medicine, Atlanta, Georgia [S. M. A.]; Pulmonary Sciences Division, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, University of Colorado Health Sciences Center, Denver, Colorado [T. E. K.]; Medical Oncology Division, Department of Medicine, Denver Veterans Affairs Medical Center, University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado [M. A. K.]; Denver Veterans Affairs Medical Center, University of Colorado Health Sciences Center, Denver, Colorado [K. M. S.]; Pulmonary Sciences Division, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado [W. S., L. M. N., T. L. P.]; and Pulmonary Sciences and Medical Oncology Divisions, Department of Medicine, Denver Veterans Affairs Medical Center, Eleanor Roosevelt Institute for Cancer Research, University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado [Y. E. M.]

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 determine 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 cigarette 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 (P = 0.04), asymptomatic cigarette smokers also have increased BLP levels in their urine compared with normal nonsmokers (P = 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 detectable urinary BLP levels, and there was a positive correlation between BLP levels in urine and BAL fluid (r = 0.625, P < 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.