Increase of club cell (Clara) protein (CC16) in plasma and urine after exercise challenge in asthmatics and healthy controls, and correlations to exhaled breath temperature and exhaled nitric oxide

Abstract

Exercise is known to affect the airway epithelium through dehydration, followed by a release of mediators, such as club cell (Clara) protein (CC16). The aim of this study was to follow the CC16 levels at repeated time points in plasma and urine after exercise in asthmatic subjects and controls, and to relate the findings to exhaled breath temperature (EBT) and exhaled nitric oxide (NO). Twenty-two asthmatics and 18 healthy subjects performed an exercise challenge test on a treadmill. Lung function, CC16 in plasma and urine, EBT and fractional exhaled NO were investigated before and repeatedly for 60min after the exercise. The increase in CC16 concentration in plasma was seen already one minute after exercise (p<0.001) and increased further after 20 (p=0.009) until 60min (p=0.001). An increase in urinary levels of CC16 peaked after 30min (p<0.001), and declined after 60min but were still higher than baseline (p=0.002). There were no differences in plasma or urine CC16 levels between asthmatics and controls, but males had higher plasma levels compared to females (p<0.001) at all time points. EBT peaked at 15min (p<0.001) and thereafter declined, and FENO50 (p<0.0001), alveolar NO concentration (p=0.049) and bronchial flux of NO (p=0.0055) decreased after exercise. In conclusion, this study shows that CC16 in plasma increased during 60min after exercise, not synchronized with CC16 levels in urine. CC16 levels in plasma correlated to EBT and exhaled NO, reflecting an overall epithelial involvement. There was no difference between asthmatics and healthy controls, showing a physiological rather than pathophysiological response.