FAA Office of Aerospace Medicine
Civil Aerospace Medical Institute

Report No: DOT/FAA/AM-21/25

Title and Subtitle: Transcriptional Responses to Altitude-Induced Hypoxia in Bronchial Epithelium, Broncho-alveolar Cells, and Blood Differ Between Smokers and Nonsmokers

Report Date: September 2018

Authors: Nicholson SJ, Munster SK, Uyhelji HA, Hutchings DC, White VL, Booth JL, Burian DM, Metcalf JP

Abstract: The hypoxic environment of an aircraft cabin may exacerbate underlying health conditions related to respiratory ailments, including those induced by smoking. In order to assay the differences between smokers and nonsmokers during flight, we analyzed the gene expression profiles of bronchial epithelium, alveolar cells, and blood in smokers and nonsmokers before, during, and after exposure in a hypobaric chamber to an 8,000-ft cabin pressurization. Unique transcriptional changes were observed between smokers and nonsmokers exposed to flight conditions. Smoker bronchial epithelial cells exhibited inhibition of the hypoxic response and activation of cellular death pathways compared to nonsmokers. Smoker alveolar cells displayed a mixed hypoxic regulatory profile and activation of cellular recruitment and inflammation pathways. Smoker blood displayed very little difference to that of nonsmokers, but presented a restricted hypoxic response.

In summary, smokers exhibit an inhibition of the hypoxic response compared with nonsmokers during exposure to flight conditions, resulting in alternate cellular responses that may mitigate the inhibition of the hypoxic response.

Key Words: Hypoxia, Gene Expression, RNA microarray, smoking, pathway analysis

No. of Pages: 36