A 3-Week Inpatient Rehabilitation Programme Improves Body Composition in People with Cystic Fibrosis with and Without Elexacaftor/Tezacaftor/Ivacaftor Therapy

Abstract

Background: The introduction of cystic fibrosis transmembrane conductance regulator modulators, especially the triple therapy elexacaftor, tezacaftor, ivacaftor (ETI), has improved outcomes in people with cystic fibrosis (pwCF), reducing underweight but increasing overweight rates.

Objectives: This study investigates the effect of ETI on appetite control, body composition, and energy balance during a 3-week inpatient rehabilitation programme with regular exercise.

Methods: In 54 pwCF (38 on ETI, 16 without ETI), changes in body composition (fat mass index, FMI; fat-free mass index, FFMI) and energy balance (calculated from body composition changes) were assessed. Appetite control was evaluated via plasma peptide YY (PYY) levels and post-exercise meal energy intake.

Results: The programme significantly increased BMI (+0.3 ± 0.1 kg/m²; CI 0.1-0.4) and energy balance (+4317 ± 1976 kcal/3 weeks), primarily through FFMI gains (+0.3 ± 0.1 kg/m²; CI 0.1-0.4). Despite higher post-exercise meal energy intake and a tendency towards lower PYY levels in the ETI group, changes in body composition and energy balance did not differ between groups. This is explained by a higher prevalence of exocrine pancreatic insufficiency in the ETI group (92% vs. 50%, p < 0.001). Small sample sizes limit the interpretation of data on appetite control and energy intake.

Conclusions: A 3-week inpatient rehabilitation programme improved body composition in pwCF, without resulting in a more positive energy balance with ETI therapy. This is due to a higher prevalence of pancreatic insufficiency in this group.

Keywords: CF rehabilitation; Elexacaftor/Tezacaftor/Ivacaftor; appetite control; body composition; energy balance; triple CFTR modulators.

Figure 1

Study protocol at baseline (T0) and at the end (T1) of the 3-week rehabilitation programme. Participants had breakfast, followed by a training session (High-Intensity Interval Training or Moderate-Intensity Continuous Training) on a cycle ergometer for 30 min. Meal energy intake post-exercise was assessed with an ad libitum test meal (pasta dish) 90 min after the end of the training session. Subjective appetite ratings were obtained using visual analogue scales (VASs) at six time points: before and after exercise, 60 min post-exercise, before and after the test meal, and 60 min post-meal. Appetite-regulating hormones were measured in blood samples taken before training (plasma peptide YY, PYY, and plasma leptin) and 60 min after training (plasma PYY). Participants documented 24 h energy intake with smartphone photos and written entries using a web application (Meal-Tracking Web App, Institute of Human Nutrition, Kiel University, Kiel, Germany).

Figure 2

Comparison of appetite scores, satiety quotients, plasma PYY concentrations, and post-exercise meal energy intake between the ETI group (Elexacaftor/Tezacaftor/Ivacaftor therapy) and the non-ETI group (no CFTR modulator therapy) at baseline (T0) and at the end (T1) of the rehabilitation programme. Appetite scores (a,b) (mean of subjective appetite ratings of hunger, fullness, desire to eat, and prospective food consumption) were assessed using visual analogue scales at six time points: before and after exercise (30 min on cycle ergometer), 60 min post-exercise, before and after the ad libitum test meal, and 60 min post-meal. Satiety quotients (c,d) show the change in hunger ratings before vs. immediately after or 60 min after the test meal in relation to the energy content of the meal (kcal). Plasma PYY concentrations (e,f) were analysed from blood samples taken 60 min post-exercise. Post-exercise meal energy intake (g,h) 90 min after the exercise, expressed as a percentage of calculated resting energy expenditure according to Harris and Benedict (1918) [39]. (a–d): ETI, n = 22; non-ETI, n = 11. (e,f): ETI, n = 24; non-ETI, n = 12. (g,h): ETI, n = 25; non-ETI, n = 12. REE, resting energy expenditure; PYY, peptide YY. Results are adjusted for training type and sex. Dots indicate data points identified as outliers. p-values indicate differences between the ETI and non-ETI groups assessed by contrast tests (based on linear mixed model), ** p  <  0.01.