This randomized pilot trial evaluated the feasibility and preliminary effects of using asymmetric high-flow nasal cannula (A-HFNC) during exercise-based pulmonary rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD). Thirty patients were randomly assigned to conventional PR or PR supplemented with A-HFNC during aerobic training, completing 12 supervised sessions. The study assessed whether A-HFNC could be safely and acceptably incorporated into PR, and whether it enabled higher training intensity and improved exercise performance. Results showed that the intervention was feasible and safe, with 83% adherence in both groups and no adverse events. Patients in the A-HFNC group trained at significantly higher treadmill inclination and showed a clinically meaningful trend toward greater improvement in maximal exercise tolerance. These findings support the design of a larger definitive trial.

Chronic obstructive pulmonary disease (COPD) is a major cause of disability worldwide. Pulmonary rehabilitation (PR) is the most effective non-pharmacological intervention for COPD, but adherence is limited by exercise intolerance and dyspnea. Strategies that reduce ventilatory demand during exercise may help patients tolerate higher training intensities, potentially improving outcomes.

Asymmetric high-flow nasal cannula (A-HFNC) delivers heated and humidified gas at high flow rates through an asymmetric nasal interface, promoting dead-space washout and reducing the work of breathing. These mechanisms may facilitate higher exercise intensity during PR.

This pilot trial randomized 30 patients with COPD to two groups. The control group received a conventional 12-session supervised PR program including treadmill aerobic exercise, resistance training, and patient education. The experimental group followed the same program with A-HFNC applied during all aerobic training sessions. Flow rate, temperature, and fraction of inspired oxygen were individualized according to oxygen saturation and patient tolerance.

Primary feasibility outcomes were recruitment rate, protocol adherence, and absence of serious adverse events. Exploratory clinical outcomes included six-minute walk distance, incremental load test performance (modified Bruce protocol), and COPD Assessment Test score, assessed at baseline and after the 12-session program. Secondary outcomes included heart rate, blood pressure, oxygen saturation, rate-pressure product, and perceived dyspnea.

The study was conducted at the cardiopulmonary rehabilitation center of Hospital Clínico San José, Santiago, Chile, between May and September 2025. Ethics approval was obtained from the institutional review board (No. 276/2025). The trial was registered retrospectively upon manuscript preparation.

Inclusion Criteria:

• Age 40 years or older
• Spirometry-confirmed COPD diagnosis (post-bronchodilator FEV1/FVC ratio less than 0.70)
• Modified Medical Research Council (mMRC) dyspnea grade 2 or higher
• Spirometry performed within the preceding 12 months

Exclusion Criteria:

• Acute respiratory exacerbation within the preceding three months
• Uncontrolled respiratory symptoms or any acute condition compromising clinical stability
• Current use of home non-invasive mechanical ventilation or artificial airway
• Hospitalization within the preceding three months
• Neuromuscular or osteoarticular conditions limiting physical activity
• Cognitive or communication difficulties precluding adherence to instructions
• Recent acute cardiovascular events
• Decompensated comorbidities

Individual participant data will not be shared publicly due to the small sample size, which could compromise participant confidentiality despite anonymization procedures.