LAUSR

We examined the relationship between the work of breathing (Wb) during exercise and in vivo measures of airway size in healthy females and males. We hypothesized that sex-differences in airway luminal area (Ai) would explain the larger resistive Wb during exercise in females. Healthy participants (n=11 females and n=11 males; 19-30 y) completed a cycle exercise test to exhaustion where Wb was assessed using an esophageal balloon catheter. On a separate day, participants underwent a bronchoscopy procedure for optical coherence tomography measures of airways in the left (n=3) and right (n=4) lung. In vivo measures of Ai were made for the 4th-8th airway generations. A composite index of airway size was calculated as the sum of the Ai for each generation and the total area was calculated based on Weibel's model. We found that index of airway size (males: 37.4±6.3 mm2 vs. females: 27.5±7.4 mm2) and airway area calculated based on Weibel's model (males: 2274±557 mm2 vs. females: 1594±389 mm2) were significantly larger in males (both p=0.003). When minute ventilation was greater than ~60 l·min-1, the resistive Wb was higher in females. At the highest equivalent flow achieved by all subjects, resistance to inspired flow was larger in females and significantly associated with two measures of airway size: index of airway size (r=0.559, p=0.007) and Weibel area (r=0.541, p=0.009). Our findings suggest that innate sex-differences in Ai result in a greater resistive Wb during exercise in females compared to males.