Long-Term Pulmonary Rehabilitation Enhances Cerebral Oxygenation, Functional Capacity, and Psychological Health in Idiopathic Pulmonary Fibrosis

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by exertional dyspnea, desaturation, and exercise intolerance. Desaturation may contribute to cerebral hypoxia during exercise, and in turn, to exercise intolerance. Although pulmonary rehabilitation (PR) has been shown to improve functional capacity and symptom management, it remains unclear whether these benefits are partially mediated by improved brain oxygenation. Purpose: To evaluate whether a 12-month PR program enhances cerebral oxygenation during exercise in patients with IPF. Secondary outcomes included exercise capacity, cognitive function, depression/anxiety, and physical activity levels. Methods: Sixteen patients with IPF (68.7± 6.4 years), on antifibrotic therapy, completed a 12-month supervised PR intervention involving aerobic, resistance, flexibility, and breathing exercises. Pre- and post-intervention assessments included spirometry, cardiopulmonary exercise testing (CPET), cerebral oxygenation via near-infrared-spectroscopy (NIRS), Mini-Mental State Examination (MMSE), Hospital Anxiety/Depression Scale (HADS), and International Physical Activity Questionnaire (IPAQ). Results: Following the PR intervention, cerebral oxygenated-hemoglobin (O₂Hb mean-response ) during exercise was higher (p=0.04) compared to pre-PR exercise testing. Isowork O 2 Hb responses (at 50% and 75% of pre-PR peak workload) were significantly elevated (p=0.006). The PR-intervention resulted in improved VO₂peak (p=0.01), CPET duration and peak workload (p=0.02). HADS anxiety/depression scores decreased (p=0.01; p<0.001); the MMSE was not significantly changed (p=0.054). Physical activity levels increased from “low” to “moderate” (p<0.001). Training-induced cerebral oxygenation improvements were significantly correlated with improvements in exercise capacity (VO₂peak % predicted , r=0.54, p=0.03; Workload peak r=0.54, p=0.03) and mMRC. (r=0.63, p=0.01). Conclusions: A 12-month PR program enhanced cerebral oxygenation during exercise, improved exercise capacity, physical activity levels, and psychological well-being of IPF patients. Importantly, our findings suggest a potential association between improved cerebral oxygenation and enhanced exercise capacity in IPF.