Time Course of Respiratory Oscillometry Parameters During Nasal High-Flow Therapy in Stable Chronic Obstructive Pulmonary Disease (NHFlOscillo)

NHFlOscillo is a prospective, open-label, single-center, single-arm physiological study involving adults with stable severe to very severe chronic obstructive pulmonary disease (COPD). The study is designed to characterize the time course of respiratory oscillometry parameters during a standardized 4-hour exposure to heated and humidified nasal high-flow therapy.

Participants will attend a single study visit and will be instructed to take their usual medications before the visit. After providing written informed consent, baseline characteristics will be recorded, and participants will complete the modified Medical Research Council Dyspnea Scale (mMRC), the St George's Respiratory Questionnaire (SGRQ), the COPD Assessment Test (CAT), and the Leicester Cough Questionnaire (LCQ). Baseline impulse oscillometry (IOS) will then be performed using a calibrated Vyntus IOS system, with the participant seated and breathing quietly, in accordance with current European Respiratory Society technical standards.

Nasal high-flow therapy will be initiated at a flow rate of 15 L/min and a temperature of 34 °C. After 3 minutes, the temperature will be increased to 37 °C if tolerated; otherwise, it will be maintained at 34 °C. The flow rate will then be increased every 3 minutes to an individualized level consistent with usual clinical practice, up to a maximum of 40 L/min. In participants receiving long-term oxygen therapy, supplemental oxygen will be titrated to maintain an oxygen saturation comparable to that observed under their usual conditions without nasal high-flow therapy.

The exposure will be continued for a total of 4 hours and will be briefly interrupted to perform oscillometry measurements immediately after titration and at 30, 60, 120, 180, and 240 minutes after the start of nasal high-flow therapy.

The target sample size is 20 participants. Changes in oscillometry parameters over time will be analyzed using linear mixed-effects models, with measurement time included as a fixed effect and participant included as a random effect. Each post-exposure time point will be compared with the pre-exposure baseline. Results will be reported as mean differences with 95% confidence intervals and interpreted according to the minimal clinically important difference for each outcome, when available.

Prespecified subgroup analyses will be conducted in participants receiving long-term oxygen therapy and in participants with cough and sputum production. Cough and sputum production will be identified using two alternative operational definitions:

CAT: a score ≥2 on both items 1 and 2; SGRQ: cough on most days or several days per week (response option 1 or 2 to the item "I cough") and sputum production on most days or several days per week (response option 1 or 2 to the item "I bring up sputum").