Kritikou S; Aristotle University of Thessaloniki, Thessaloniki, GREECE.
Zafeiridis A; Markopoulou A; Boutou A; Zacharias A; Rampiadou
C; Kounti G; Gkalgkouranas I; Kastritseas L; Chloros D; Stanopoulos I;
Pitsiou G; Dipla K

Medicine & Science in Sports & Exercise. 58(4):650-660, 2026 Apr 01.

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 yr), on antifibrotic
therapy, completed a 12-mo supervised PR intervention involving aerobic,
resistance, flexibility, and breathing exercises. Pre- and
post-intervention assessments included spirometry, cardiopulmonary
exercise testing, cerebral oxygenation via near-infrared-spectroscopy,
Mini-Mental State Examination, Hospital Anxiety/Depression Scale, and
International Physical Activity Questionnaire.

RESULTS: After the PR intervention, cerebral oxygenated hemoglobin (O 2
Hb mean-response ) during exercise was higher ( P = 0.04) compared with
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 VO 2 peak ( P = 0.01), cardiopulmonary
exercise testing duration, and peak workload ( P = 0.02). Hospital
Anxiety/Depression Scale anxiety/depression scores decreased ( P = 0.01; P
< 0.001); the Mini-Mental State Examination 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 (VO 2 peak
% predicted , r = 0.54, P = 0.03; Workload peakr = 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.