A Retrospective Controlled Study on the Effects of Four-Limb Linkage Training on Clinical Efficacy and Antioxidative Mechanisms in Patients with Chronic Obstructive Pulmonary Disease

Xijiao Liu,1 Li Chen,2 Zonghui Wei,2 Jinshan Jiang,2 Yunyan Yu,2 Zhishan Wang2 1Department of Respiratory Medicine, Bishan Hospital Affiliated to Chongqing Medical University (Bishan District People’s Hospital), Chongqing, People’s Republic of China; 2Department of Respiratory Medicine, Nanchuan District People’s Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Zhishan Wang, Email [email protected]: To investigate the effects of systematic four-limb linkage training on pulmonary function, exercise capacity, dyspnea, and quality of life in patients with chronic obstructive pulmonary disease (COPD), and to explore its potential antioxidative mechanisms.Methods: This retrospective controlled study included 114 patients with COPD admitted between August 2023 and April 2025. Patients were divided into a control group (n=57), receiving lower-limb cycling training, and an observation group (n=57), receiving four-limb linkage training. Both groups underwent continuous rehabilitation intervention for 8 weeks. Pulmonary function indices (FEV1, FVC, FEV1/FVC, FEV1%pred), dyspnea scores (modified Medical Research Council and Borg scales), exercise capacity (6-minute walking distance, 6MWD), disease severity (BODE index), quality of life (St. George’s Respiratory Questionnaire, SGRQ), and oxidative stress markers [thioredoxin (TRX) and thioredoxin-interacting protein (TXNIP) at mRNA and protein levels] were assessed at Pre-intervention and Post 8-week intervention.Results: At Post 8-week intervention, pulmonary function indices, exercise capacity, and quality-of-life scores were significantly improved, while dyspnea scores and BODE index were significantly reduced in both groups compared with Pre-intervention (P< 0.05). The magnitude of improvement was significantly greater in the four-limb linkage training group than in the control group (P< 0.05). In addition, TRX mRNA and protein expression levels were significantly increased, whereas TXNIP mRNA and protein expression levels were significantly decreased at Post 8-week intervention compared with Pre-intervention, with more pronounced changes observed in the observation group (P< 0.05).Conclusion: Four-limb linkage training significantly improves pulmonary function, exercise capacity, dyspnea, and quality of life in patients with COPD. These benefits may be mediated, at least in part, by enhanced antioxidative activity through upregulation of TRX and suppression of TXNIP. Compared with lower-limb training alone, four-limb linkage training provides a more comprehensive rehabilitation strategy for COPD management.Keywords: chronic obstructive pulmonary disease, four-limb linkage training, pulmonary rehabilitation, oxidative stress, thioredoxin, quality of life