biologic phenotyping of the human small airway epithelial response to cigarette smoking生物表现型的人类小气道上皮反应吸烟.pdf

Biologic Phenotyping of the Human Small Airway Epithelial Response to Cigarette Smoking 1,2 1 1 1 1 Ann E. Tilley , Timothy P. O’Connor , Neil R. Hackett , Yael Strulovici-Barel , Jacqueline Salit , Nancy 2 3 1 5 4 5 Amoroso , Xi Kathy Zhou , Tina Raman , Larsson Omberg , Andrew Clark , Jason Mezey , Ronald G. Crystal1,2* 1 Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America, 2 Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, New York, United States of America, 3 Department of Public Health, Weill Cornell Medical College, New York, New York, United States of America, 4 Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America, 5 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America Abstract Background: The first changes associated with smoking are in the small airway epithelium (SAE). Given that smoking alters SAE gene expression, but only a fraction of smokers develop chronic obstructive pulmonary disease (COPD), we hypothesized that assessment of SAE genome-wide gene expression would permit biologic phenotyping of the smoking response, and that a subset of healthy smokers would have a ‘‘COPD-like’’ SAE transcriptome. Methodology/Principal Findings: SAE (10th–12th generation) was obtained via bronchoscopy of healthy nonsmokers, healthy smokers and COPD smokers and microarray analysis was used to identify differentially expressed genes. Indivi