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Trachea epithelium as a "canary" for cigarette smoking-induced biologic phenotype of the small airway epithelium.

ABSTRACT: The initial site of smoking-induced lung disease is the small airway epithelium, which is difficult and time consuming to sample by fiberoptic bronchoscopy. We developed a rapid, office-based procedure to obtain trachea epithelium without conscious sedation from healthy nonsmokers (n= 26) and healthy smokers (n= 19, 27 +/- 15 pack-year). Gene expression differences (fold change >1.5, p < 0.01, Benjamini-Hochberg correction) were assessed with Affymetrix microarrays. A total of 1,057 probe sets were differentially expressed in healthy smokers versus nonsmokers, representing >500 genes. Trachea gene expression was compared to an independent group of small airway epithelial samples (n= 23 healthy nonsmokers, n= 19 healthy smokers, 25 +/- 12 pack-year). The trachea epithelium is more sensitive to smoking, responding with threefold more differentially expressed genes than small airway epithelium. The trachea transcriptome paralleled the small airway epithelium, with 156 of 167 (93%) genes that are significantly up- and downregulated by smoking in the small airway epithelium showing similar direction and magnitude of response to smoking in the trachea. Trachea epithelium can be obtained without conscious sedation, representing a less invasive surrogate "canary" for smoking-induced changes in the small airway epithelium. This should prove useful in epidemiologic studies correlating gene expression with clinical outcome in assessing smoking-induced lung disease.

SUBMITTER: Turetz ML

PROVIDER: S-EPMC3875387 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Although smoking-induced lung disease tends to be more common in the upper lobe, it is not known if this results from the skewed distribution of inhaled cigarette smoke or increased susceptibility of the upper lobes to these disorders. The distribution of inhaled cigarette smoke within the lung is complex, depending on lung pressure-volume relationships, gravity, individual smoking habits and the properties of the individual components of cigarette smoke. With the knowledge that the small airway epithelium is the earliest site of smoking-induced lung disease, and that the small airway epithelium is acutely sensitive to inhaled cigarette smoke with significant changes in the up- and down-regulation of hundreds of genes, we compared upper vs lower lobe gene expression in the small airway epithelium of the same cigarette smokers to determine if the gene expression patterns were similar or different. Active smokers (n=11) with early evidence of smoking-induced lung disease (normal spirometry but low diffusing capacity) underwent bronchoscopy and brushing of the small airway epithelium to compare upper vs lower lobe genome-wide gene expression assessed by microarray. Interestingly, cluster and principal component analysis demonstrated that, for each individual, the expression of the known small airway epithelium smoking-responsive genes were remarkably similar as upper vs lower lobe pairs, although, as expected, there were differences in the smoking-induced changes in gene expression from individual to individual. Thus, while there may be topographic differences in the distribution of cigarette smoke, sufficient smoke reaches the upper vs lower lobe small airway epithelium so that, within each smoker, the upper vs lower lobe gene expression are similar. These observations support the concept that the topographic differences in the occurrence of the smoking-induced lung diseases are likely secondary to topographic differences in the susceptibility of the upper vs lower lobes to cigarette smoke, not the topographic differences in distribution of inhaled cigarette smoke.

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Trachea epithelium as a "canary" for cigarette smoking-induced biologic phenotype of the small airway epithelium.

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