Sex-Related Differences in Pulmonary Function following 6 Months of Cigarette Exposure: Implications for Sexual Dimorphism in Mild COPD

• Published in: PloS one 2016-10, Vol.11 (10), p.e0164835-e0164835
• Main Authors: Tam, Anthony, Bates, Jason H T, Churg, Andrew, Wright, Joanne L, Man, S F Paul, Sin, Don D
• Format: Article
• Language: English
• Subjects: Airway Resistance - drug effects; Animals; Biology and Life Sciences; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarettes; Comparative analysis; Exposure; Female; Gender differences; Health risks; Hormones; House mouse; Inspiratory Capacity - drug effects; Lung - drug effects; Lung - physiopathology; Lung diseases; Male; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mouse devices; Obstructive lung disease; Ovariectomy; Pulmonary Disease, Chronic Obstructive - etiology; Pulmonary function tests; Pulmonary functions; Remodeling; Research and Analysis Methods; Respiration; Respiratory function; Respiratory system; Respiratory tract diseases; Rodents; Sex; Sex differences; Sex Factors; Sex hormones; Sexual dimorphism; Smoke; Smokers; Smoking; Tam, Jason; Tobacco smoke; Tobacco Smoke Pollution - adverse effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164835

Female smokers have increased risk of chronic obstructive pulmonary disease (COPD) compared with male smokers who have a similar history of cigarette smoke exposure. We have shown previously that chronic smoke exposure for 6 months leads to increased airway wall remodeling in female C57BL/6 mice compared with male C57BL/6 mice. These differences, however, were not evident in female ovariectomized mice exposed to cigarette smoke. Herein, we report on the pulmonary function test results from the flexiVent system, which was used to determine the potential functional consequences of the histologic changes observed in these mice. We found that tissue damping (G) was increased in female compared to male or ovariectomized female mice after smoke exposure. At low oscillating frequencies, complex input resistance (Zrs) and impedance (Xrs) of the respiratory system was increased and decreased, respectively, in female but not in male or ovariectomized female mice after smoke exposure. Quasistatic pressure-volume curves revealed a reduction in inspiratory capacity in female mice but not in male or ovariectomized female mice after smoke exposure. The remaining lung function measurements including quasistatic compliance were similar amongst all groups. This is the first study characterizing a sexual dimorphism in respiratory functional properties in a mouse model of COPD. These findings demonstrate that increased airway remodeling in female mice following chronic smoke exposure is associated with increased tissue resistance in the peripheral airways. These data may explain the importance of female sex hormones and the increased risk of airway disease in female smokers.