Influence of diaphragm structure and function on the exercise ventilatory response in childhood cancer survivors and non-cancer controls.
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Although survival has greatly improved, most childhood cancer survivors (CCS) will experience cancer treatment-related side effects. Exertional dyspnea is one such side effect that can have a negative impact on exercise tolerance. CCS are at risk because of potential cancer treatment-related muscle dysfunction affecting diaphragm structure and function, thus altering the control of breathing during exercise. This study explored the influence of diaphragm structure and function on the exercise ventilatory response in 7 CCS and 10 healthy, typically developing, non-cancer controls (HTD), aged between 6-12 years. Diaphragm thickening fraction to total lung capacity was significantly lower in CCS (median in CCS = 0.66 [interquartile range = 0.36] vs. HTD = 1.17 [0.21], P = 0.019). However, no significant differences in the exercise ventilatory response were detected. Nonetheless, diaphragm thickness was inversely related to respiratory frequency (fr) and ventilatory equivalents for CO2 production (e/ co2) in HTD, but not in CCS. Whereas diaphragm excursion was inversely related to fr, e/ co2, and perceived exertion in CCS, but not in HTD. Chest wall excursion was inversely related to perceived exertion in both groups. As such, our findings suggest that the influence of diaphragm structure and function on the control of breathing during exercise has been altered in CCS while the influence of chest wall excursion was likely preserved. Thus, future work should explore how changing diaphragm and chest wall mechanics can influence the control of breathing in order to enhance therapies for exertional dyspnea and exercise intolerance in CCS.