Body mass index-related heterogeneity in diaphragm thickening fraction response to exercise training in stable...

Diaphragmatic dysfunction contributes to exercise intolerance in COPD, but whether BMI shapes baseline function and response to exercise remains unclear. This secondary analysis characterized BMI-related diaphragmatic phenotypes and whether diaphragm thickening fraction (TFdi) links exercise training to functional improvement.

Data were analyzed from 103 patients with stable COPD in a completed 2×2 factorial randomized trial. Because no exercise-by-acupuncture interaction was detected for 4-week TFdi, participants were regrouped as exercise-exposed or non-exercise. Associations between BMI and baseline TFdi were assessed using restricted cubic splines and threshold models. Regression models estimated exercise effects on 4-week TFdi and 6-minute walk distance (6MWD), with BMI-stratified interaction and exploratory mediation analyses.

BMI showed a nonlinear association with baseline TFdi, with an adjusted turning point at 23.7 kg/m². Below this threshold, BMI was positively associated with TFdi (β=0.05, 95% CI 0.03-0.08); above it, the association was negative (β=-0.05, 95% CI -0.07 to -0.03). Exercise was associated with higher 4-week TFdi (β=0.15, 95% CI 0.01-0.29) and longer 6MWD (β=59.61 m, 95% CI 10.65-108.57). The TFdi response was most pronounced at BMI ≥25.0 kg/m², with borderline interaction evidence. Exploratory mediation suggested TFdi partially mediated exercise-related 6MWD gains, particularly in this BMI group.

This study integrates BMI phenotyping, diaphragm ultrasound, and mediation analysis to show that diaphragmatic function and exercise-induced diaphragmatic adaptation in COPD are BMI dependent. BMI may help identify patients most likely to derive diaphragmatic benefit from rehabilitation.