Severity-adapted graded exercise rehabilitation reduces systemic inflammation and improves functional capacity in hospitalized AECOPD: an assessor-blinded randomized controlled trial

Background: Hospitalized acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is characterized by heightened systemic inflammation and rapid decline in functional capacity. Although exercise rehabilitation is recommended, the physiological appropriateness of exercise intensity during acute hospitalization remains uncertain, particularly across different levels of disease severity. Methods: This prospective, assessor-blinded, randomized controlled trial enrolled 141 hospitalized patients with AECOPD. Participants were stratified by disease severity (Grade I-III) and randomized to either a severity-adapted graded exercise rehabilitation program (Study group, n=70) or conventional exercise rehabilitation (Control group, n=71) for 2 weeks from admission, in addition to standard medical treatment. The severity-adapted program applied an inverse matching strategy to optimize relative physiological load, whereby patients with more severe disease received lower-intensity exercise and those with milder disease received higher-intensity exercise. Primary outcomes were changes in systemic inflammatory biomarkers (interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor-α [TNF-α], high-sensitivity C-reactive protein [hs-CRP], and white blood cell count [WBC]). Secondary outcomes included functional capacity and symptom-related measures, assessed using the 6-minute walk test (6MWT), modified Medical Research Council dyspnea scale (mMRC), COPD Assessment Test (CAT), and Hospital Anxiety and Depression Scale (HADS). Results: Compared with conventional rehabilitation, severity-adapted graded exercise resulted in a more favorable inflammatory marker profile and greater improvements in functional capacity and symptom burden. Among the inflammatory outcomes, the most statistically robust between-group differences were observed for IL-8, TNF-α, and WBC, whereas IL-6 and hs-CRP showed directionally consistent but more modest evidence. Within the severity-adapted group, patients with milder disease tended to show larger anti-inflammatory and functional gains under higher, well-tolerated relative exercise intensity, whereas patients with moderate-to-severe disease achieved stable improvements under low-to-moderate intensity training. No consistent severity-dependent response pattern was observed in the control group. Conclusion: Severity-adapted graded exercise rehabilitation initiated during hospitalization for AECOPD was associated with a more favorable inflammatory profile and greater improvements in functional capacity and symptom-related outcomes than conventional exercise rehabilitation. These findings support a severity- and function-informed strategy for individualized exercise prescription in hospitalized patients with AECOPD. Clinical trial registration: https://www.chictr.org.cn, ChiCTR; ChiCTR2300072409.