Abstract
PURPOSE: Pulmonary rehabilitation (PR) is a well-established non-pharmacological intervention for patients with asthma. While PR improves asthma control and exercise capacity, its impact on airway inflammation remains unclear. Fractional exhaled nitric oxide (Fe(NO)) is a biomarker of type 2 airway inflammation, yet its response to PR has not been extensively studied. Therefore, aim of this study was to investigate diurnal variations in Fe(NO) and how Fe(NO) develops during PR in asthmatic patients with different levels of Fe(NO). PATIENTS AND METHODS: This prospective, single-center study investigated Fe(NO) changes in asthma patients undergoing a comprehensive three-week inpatient PR program. The study observation period covered 15 consecutive days of FeNO measurements. Patients were divided into three subgroups according to their initial Fe(NO) measurement: low (<25 ppb), intermediate (25-50 ppb) and high (>50 ppb). Fe(NO) was measured three times a day, along with assessments of asthma control, lung function, blood eosinophils and exercise capacity before and after PR. RESULTS: Sixty-two patients were included. Only patients in the high Fe(NO) group (n=22) showed a significant 40% decrease in Fe(NO) from pre to post PR (93±29 ppb to 56±27 ppb, p<0.001), independent of medication changes. Fe(NO) levels of patients with low (17±8 ppb to 16±10 ppb) and intermediate levels (39±12 ppb to 30±10 ppb) remained unchanged. Asthma control and exercise capacity improved across all three subgroups, with the greatest gains observed in patients with initially high Fe(NO). No significant Fe(NO) changes occurred in the low and intermediate Fe(NO) groups. CONCLUSION: PR significantly reduced Fe(NO) levels in asthma patients with high baseline Fe(NO), suggesting an anti-inflammatory effect beyond pharmacological treatment. These findings highlight the role of PR as a complementary strategy in asthma management, particularly for patients with persistent airway inflammation despite optimized medication. Further randomized trials are needed to confirm these results and explore long-term effects.