Sex Differences in Muscle-Respiratory Function Relationship in Lung Transplant Patients: A Longitudinal Study

Lung transplant recipients are at increased risk of sarcopenia and osteoporosis, which may negatively influence respiratory outcomes. Although muscle health is known to affect lung function, little is known about the long-term interplay between muscle parameters and pulmonary volumes, especially across sexes. The objective of this study is to evaluate the longitudinal relationship between muscle mass and strength and respiratory function in lung transplant patients, with sex-specific analysis.

This prospective cohort included three assessments (baseline ≥ 3 months after transplant, ~1 year and 2-3 years). The primary outcome was the longitudinal change in pulmonary function (VC, FVC, FEV1 and TLC) in relation to appendicular skeletal muscle mass index (ASMMI) and handgrip strength (HGS). Associations at baseline were tested with multivariable linear regression. Analyses were performed with linear mixed-effects models (LMM) including random intercepts for subject, time as a fixed effect and interactions between time and muscle parameters, adjusted for age, ADL, corticosteroid dose, vertebral fractures, osteoporosis, comorbidities and time since transplant.

We studied 155 recipients (43.2% women, age 48.7 ± 13.3 years). Primary indications were cystic fibrosis (30.1%), restrictive (22.2%), obstructive (15.7%), miscellaneous (26.8%) and vascular diseases (5.2%). At baseline, HGS was independently associated with higher VC (R²: 0.63, β = 0.35, p = 0.001 in women; R²: 0.58, β = 0.16, p < 0.001 in men) and FEV1 (R²: 0.51, β = 0.08, p = 0.020 in women; R²: 0.57, β = 0.19, p = 0.009 in men). ASMMI was independently associated with VC in both sexes (women: R²: 0.58, β = 0.31, p = 0.003; men: R²: 0.40, β = 0.16, p = 0.023). Longitudinally, LMMs showed that higher HGS was associated with more favourable trajectories of pulmonary function over follow-up. Specifically, among women with restrictive disease, lower ASMMI predicted higher FEV1 (β = -4.95, 95% CI -6.93 to -2.97, p = 0.007) and higher TLC (β = -2.22, 95% CI -4.56 to -1.12, p = 0.04) over time. In women with cystic fibrosis, stronger HGS was associated with improved TLC (β = 0.38, p = 0.04). All associations persisted after full adjustment.

Muscle mass and strength are associated with lung function after lung transplantation. These findings underscore the clinical importance of muscle health and support its integration into post-transplant management.