Severity-Stratified Pulmonary Rehabilitation Modulates Diaphragm Function and Oxidative Stress in Hospitalized AECOPD Patients: A Randomized Controlled Trial

Hui Zeng,1,2,* Hongmin Ran,2,* Yan Wang,1 Yue Chen,2 Lijuan Zhang,1 Dehua Zhao,1 Dandan Fu,1 Nana Yang,3 Changxiu Li,3 Lina Ma,2 Jimei Luo,1,2 Qiuhang Hu,1,2 Lulu Huang1,2 1The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 2School of Nursing, Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 3Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Zeng, Email [email protected]: Diaphragmatic dysfunction and oxidative stress are central pathophysiological alterations in patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Evidence is lacking regarding early pulmonary rehabilitation protocols stratified by objective disease severity and their physiological effects. This study aimed to evaluate the impact of an individualized, severity-graded exercise rehabilitation program on diaphragmatic function and oxidative stress biomarkers in these patients.Methods: In this single-center randomized controlled trial, 132 AECOPD patients were first stratified into three severity grades (I, II, III) based on predefined clinical and physiological criteria, then randomly assigned to either a study group (n=66, receiving severity-graded rehabilitation) or a control group (n=66, receiving conventional rehabilitation).Diaphragmatic function was assessed by bedside ultrasonography measuring excursion (DE), end-inspiratory thickness (DTei), and end-expiratory thickness (DTee). Serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (TAOC) were determined. All measurements were taken before and after the intervention. The trial was registered with the Chinese Clinical Trial Registry (ChiCTR2500106687).Results: Compared to the control group, the study group showed significant improvements in all diaphragmatic function parameters (all p< 0.001). Furthermore, increases in SOD and TAOC levels were significantly greater in the study group (p=0.005 and p=0.025, respectively). Subgroup analysis revealed that patients with mild disease exhibited the most pronounced improvement in DE (p=0.044), and oxidative stress responses were heterogeneous across severity grades. Partial correlation analysis indicated that improvements in DE were significantly negatively correlated with improvements in all oxidative stress biomarkers only in the study group (r range: − 0.314 to − 0.331, all p< 0.05).Conclusion: Severity-graded exercise rehabilitation effectively improves diaphragmatic function and enhances endogenous antioxidant capacity in hospitalized AECOPD patients. The improvement in diaphragmatic excursion was significantly correlated with favorable changes in oxidative stress biomarkers, suggesting a potential physiological association. These findings support the efficacy of severity-graded rehabilitation but warrant further mechanistic studies.Keywords: acute exacerbation of chronic obstructive pulmonary disease, graded exercise rehabilitation, diaphragmatic function, oxidative stress