Adaptive and degenerative remodeling of the diaphragm in patients with interstitial lung disease: A cross-sectional...

Interstitial lung diseases may affect the diaphragm due to continuous muscle overload caused by increased lung elastance, and functional alterations have already been described in patients with interstitial lung disease. However, the histological remodeling of the diaphragm is unknown. Our objective was to compare the histological and ultrastructural findings of the diaphragm in patients with and without interstitial lung disease. In this cross-sectional study with internal and external controls, we evaluated diaphragmatic and peripheral muscle (internal controls) biopsies from patients with and without chronic interstitial lung disease (external controls). Patients without interstitial lung disease underwent open lung biopsy for pulmonary nodules. Muscle samples were analyzed using histology, histochemistry, stereology, and electron microscopy. We quantified fiber type distribution, cross-sectional area, tissue volumes, and markers of adaptive and degenerative remodeling. We showed that diaphragms from patients with interstitial lung disease exhibited greater muscle, connective tissue, and nuclear volumes. Adaptive features included sarcomere elongation, and mitochondrial proliferation. Degenerative alterations comprised sarcomere misalignment, abnormal mitochondrial cristae, and collagen deposition. No significant differences were observed in peripheral muscles between patients with or without chronic interstitial lung disease. In conclusion, interstitial lung disease is associated with adaptive and degenerative diaphragmatic remodeling. These changes, absent in peripheral muscles, suggest a selective disease-specific effect. Identifying such alterations may guide interventions to preserve diaphragmatic function, inform rehabilitation programs design, and improve patient-centered outcomes, such as dyspnea.