Holden A; Royal Hospital for Children, Glasgow, UK.
Burns P; Devenny A; Thomson L; et al

Journal of Cystic Fibrosis. 25(5):819-826, 2026 Sep.

BACKGROUND: Improved survival in cystic fibrosis (CF) has shifted clinical
focus toward late complications, including altered body composition, bone
health and cardiopulmonary fitness. The effects of
Elexacaftor/Tezacaftor/Ivacaftor (ETI) on these outcomes in paediatric
patients remain unclear.

METHODS: This retrospective cohort study included paediatric CF patients
undergoing dual-energy X-ray absorptiometry (DXA) at annual review before
and 2 years after ETI initiation. Lean mass index (LMI), fat mass index
(FMI), lumbar spine bone mineral apparent density (LS-BMAD) and total body
less head bone mineral content (TBLH-BMC) were converted to age and
sex-adjusted standard deviation scores (SDS). Spirometry and
cardiopulmonary exercise testing (CPET) assessed lung function and
cardiopulmonary fitness. A matched CF control group not receiving
modulators was included.

RESULTS: 47 children were included (ETI n = 23, controls n = 24). LMI
declined significantly following ETI (mean change -0.64, p = 0.02) but
remained stable in controls (p = 0.36). LS-BMAD declined in the ETI group
(mean change -0.45, p = 0.009) with no change in controls (p = 0.31).
VO2peak % predicted decreased in the ETI group (median change -12%, p =
0.0018) alongside reductions in anaerobic threshold (-14%, p < 0.01) and
increased breathing reserve (+15%, p < 0.01), controls showed no
significant changes. FEV1 % predicted remained stable in both groups.

CONCLUSIONS: Despite preserved lung function, ETI treated children
exhibited declines in lean mass, trabecular bone density and
cardiopulmonary fitness, consistent with deconditioning. DXA and CPET
provide important complementary information beyond BMI and spirometry,
supporting targeted physical activity and nutritional interventions in ETI
treated paediatric CF patients.