Thermophysiological and perceptual responses to exercise heat-stress in people with cystic fibrosis on Elexacaftor/Tezacaftor/Ivacaftor

The objective of this study was to investigate thermophysiological and perceptual responses to exercise heat stress in people with cystic fibrosis (pwCF) on Elexacaftor/Tezacaftor/Ivacaftor (ETI) versus healthy controls, and to explore their lived experiences of heat stress. This mixed-methods, multi-study project comprised: (i) a laboratory study where pwCF (n = 6) and matched controls (n = 6) completed two 30 minutes cycling bouts in the heat (35°C, 30% relative humidity), at 150 and 250 W·m−2 metabolic heat production. Measures included sweat sodium chloride ([Na+Cl−]), local and whole body sweat rate, deep body and skin temperatures, heart rate (HR), forearm and finger skin blood flow (SkBF), and perceptual responses (exertion, thermal sensation and comfort, thirst, heat-illness symptom index (HISI)); and (ii) a pilot e-survey (n = 30) exploring free-living sweating, heat experiences, hydration and salt-supplementation practices. Laboratory data showed no significant differences in sweat [Na+Cl−] (CON: 45 (36–106) mmol·L−1; pwCF: 75 (59–92) mmol·L−1, P = 0.45), sweating rate, deep body and skin temperature, HR, SkBF, perceived exertion, thermal comfort, thermal sensation, or HISI (P > 0.05). However, pwCF reported greater thirst at baseline (P = 0.045) and after 30 minutes cycling (P = 0.01), despite comparable hydration status. Survey responses indicated some pwCF perceive reduced sweating since starting ETI, yet their salt supplementation is unchanged. PwCF treated with ETI show thermophysiological/perceptual responses equivalent to healthy individuals during exercise heat stress. Together with survey insights, this suggests ETI may reduce previous heat-related vulnerabilities and better prepare pwCF for exercise in hot conditions. Updated evidence is needed to refine salt-replacement and hydration strategies, modernise clinical guidance, and support safe physical activity in a warming climate.