High-intensity exercise triggers greater airway epithelial cell stress in young men
A randomized trial of 20 healthy young men found that 20 minutes of high-intensity treadmill exercise (85–90% max heart rate) produced larger increases in club cell protein 16 (CC16), a marker of airway epithelial cell damage, compared to moderate-intensity exercise (65–70% max heart rate), though systemic inflammation markers did not differ significantly between groups.
Researchers randomly assigned 20 healthy young men to perform 20 minutes of continuous treadmill exercise at either high intensity (85–90% of maximum heart rate, n=10) or moderate intensity (65–70% of maximum heart rate, n=10). Blood was drawn before exercise and at 1 hour and 24 hours afterward to measure three airway epithelial integrity markers—club cell protein 16 (CC16), surfactant protein D (SP-D), and the CC16/SP-D ratio—as well as high-sensitivity C-reactive protein (hs-CRP), a standard marker of systemic inflammation.
CC16 concentrations at 1 hour post-exercise were significantly higher in the high-intensity group than the moderate-intensity group (p=0.002), and this difference persisted in the CC16/SP-D ratio at 24 hours (p=0.005). By contrast, SP-D release and hs-CRP—which reflects whole-body inflammation—showed no significant difference between groups. The findings suggest that exercise intensity selectively stresses the airway epithelium, measured by CC16 release, without triggering a broader systemic inflammatory response.
The CC16/SP-D ratio is thought to reflect the balance between epithelial cell injury (CC16 release) and protective responses (SP-D); the study found this ratio was elevated 24 hours after high-intensity exercise but normalized after moderate exercise. Notably, hs-CRP—the inflammatory marker most commonly measured in clinical practice—did not increase significantly in either group, suggesting the airway-specific stress does not translate to measurable systemic inflammation in healthy individuals. The mechanism may involve mechanical shear stress and rapid airway fluid turnover during intense breathing; airway epithelial cells respond by shedding CC16 into the bloodstream as a sign of transient barrier disruption. These findings align with prior observational work showing exercise-induced changes in exhaled biomarkers, but this is one of the first controlled trials to quantify intensity-dependent differences in serum epithelial markers. A key limitation is the small sample size and restriction to healthy young men, so generalization to older adults, women, or people with asthma or chronic airway disease is uncertain.
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Open in Cadence →References
- The Effects of High- and Moderate-Intensity Exercise on Epithelial Integrity Markers and Inflammatory Responses in Healthy Young Men. — European journal of sport science (Read the original)