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

**Authors:** Chiara Ceolin, Agnese Alessi, Anna Citron, Monica Loy, Mario Virgilio Papa, Carlotta Andaloro, Bruno Micael Zanforlini, Maria Devita, Sara Bertolino, Sara Gonnelli, Daniele Michele Seccia, Anna Bertocco, Federico Rea, Giuseppe Sergi, Marina De Rui

PMC · DOI: 10.1002/jcsm.70244 · 2026-03-05

## TL;DR

This study finds that muscle health is linked to better lung function in lung transplant patients, with differences observed between men and women.

## Contribution

The study provides new insights into the longitudinal relationship between muscle parameters and respiratory function in lung transplant patients, with a focus on sex-specific differences.

## Key findings

- Higher handgrip strength is independently associated with better pulmonary function in both male and female lung transplant recipients.
- In women with restrictive disease, lower muscle mass predicts higher FEV1 and TLC over time.
- Muscle health is shown to have a significant and persistent impact on respiratory outcomes after lung transplantation.

## Abstract

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 (R
2: 0.63, β = 0.35, p = 0.001 in women; R
2: 0.58, β = 0.16, p < 0.001 in men) and FEV1 (R
2: 0.51, β = 0.08, p = 0.020 in women; R
2: 0.57, β = 0.19, p = 0.009 in men). ASMMI was independently associated with VC in both sexes (women: R
2: 0.58, β = 0.31, p = 0.003; men: R
2: 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.

## Linked entities

- **Diseases:** cystic fibrosis (MONDO:0009061)

## Full-text entities

- **Genes:** PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, HGS (hepatocyte growth factor-regulated tyrosine kinase substrate) [NCBI Gene 9146] {aka HRS}, CYP27A1 (cytochrome P450 family 27 subfamily A member 1) [NCBI Gene 1593] {aka CP27, CTX, CYP27}
- **Diseases:** Low muscle mass (MESH:C536030), loss of skeletal muscle (MESH:D005207), fragility fractures (MESH:D005600), fever (MESH:D005334), COPD (MESH:D029424), thoracic kyphosis (MESH:D007738), LMMs (MESH:D004195), vitamin D deficiency (MESH:D014808), chronic respiratory failure (MESH:D012131), osteopenia (MESH:D001851), CF (MESH:D003550), atrophy (MESH:D001284), vascular diseases (MESH:D014652), lung disease (MESH:D008171), neoplasms (MESH:D009369), Fracture (MESH:D050723), muscle (MESH:D019042), Comorbidity (MESH:D004194), Sarcopenia (MESH:D055948), inflammation (MESH:D007249), lung fibrosis (MESH:D005355), chronic disease (MESH:D002908), restrictive disease (MESH:D002313), interstitial lung disease (MESH:D017563), reduced muscle mass (MESH:D009135), low muscle strength (MESH:D009800), loss of lean mass (MESH:D013851), bone disease (MESH:D001847), weight loss (MESH:D015431), Osteoporosis (MESH:D010024), obstructive lung disease (MESH:D008173), infection (MESH:D007239), Vertebral fractures (MESH:C535781), obstructive diseases (MESH:D001157), ASMMI (MESH:D001259), decrease in muscle strength (MESH:D009123)
- **Chemicals:** azathioprine (MESH:D001379), phosphate (MESH:D010710), phosphorus (MESH:D010758), mycophenolate (MESH:D009173), vitamin D (MESH:D014807), calcium (MESH:D002118), steroid (MESH:D013256), tacrolimus (MESH:D016559), 25-hydroxy-vitamin D (MESH:C104450), everolimus (MESH:D000068338), cyclosporine (MESH:D016572), phospho (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12961349/full.md

---
Source: https://tomesphere.com/paper/PMC12961349