Grant: Travel Awards - Institute Community Support

Introduction: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death. Despite a 50% decline in cigarette smoking over the past 5 decades, the burden of COPD has not decreased. These observations suggest that identification of risk factors, beyond smoking, that contribute to COPD are needed. We recently demonstrated- by standard computed tomography (CT Scan)- that two variations in the airways tree that occur in one quarter of a large population. These airway branch variants were associated with up to two-fold higher odds of prevalent COPD, and there was a genetic association between one of these variations with mutations in a gene encoding for a protein named fibroblast growth factor 10 (Fgf10). Fgf10 is required for the development of many branched organs, including the lungs, but the role of FGF10 in COPD is not completely known. Hypothesis: Fgf10 reduction or mutations is associated with smaller airway lumens, a feature that increase susceptibility to the development of COPD. Methods: Mice that express less Fgf10 (named Fgf10+/-) were obtained from UCSF (Dr. Ophir klein). Airway structure was assessed using micro-CT (for animals). Lung functions (resistance of airways, resistance and elastance of lung) were measured using machine named Flexivent (SCIREQ, Montréal). Results: Fgf10+/- mice have narrowed airways comparing with the control mice. Moreover, we showed that Fgf10+/- mice has more airway resistance. Conclusion: We demonstrated that reduction in the amount of Fgf10 exhibit the similar COPD structure-function phenotype that we previously observed in 2 cohorts (ie. narrowed airways). Variations in airway anatomy, due to genetic factors, could be thus a COPD risk factor and easily identifiable by CT scan.