This prospective, randomized crossover trial will enroll adult healthy volunteers. Initially, the subject's peak inspiratory flow will be measured using a mask connected with a respiratory monitor. Subsequently, the volunteers will undergo HFNC treatment at different flow settings while their peak inspiratory flow will be continuously monitored. The primary outcome of this study is the lung aeration with different flow settings. Secondary outcomes include the lung aeration with different devices, subject's comfort at different flow settings, and the correlation between the subject's peak inspiratory flow measured by HFNC and by a mask connected with a respiratory monitor.

Background: High-flow nasal cannula (HFNC) is a device that can reduce the work of breathing (WOB) and improve oxygenation by providing a flow that matches or exceeds patient's peak inspiratory flow during tidal breathing. Despite its widespread use, there remains a lack of consensus regarding the optimal flow settings. Two new HFNC devices that can provide information regarding patient's peak tidal inspiratory flow breath by breath are recently available, which might help guide set and titrate the flow settings. This study aims to investigate the effects of different flow settings on lung impedance in a cohort of healthy volunteers by using the two new HFNC devices.

Methods: This prospective, randomized crossover trial will enroll adult healthy volunteers. Initially, the subject's peak inspiratory flow will be measured using a mask connected with a respiratory monitor. Subsequently, the volunteers will undergo HFNC treatment at different flow settings while their peak inspiratory flow will be continuously monitored. The primary outcome of this study is the lung aeration with different flow settings. Secondary outcomes include the lung aeration with different devices, subject's comfort at different flow settings, and the correlation between the subject's peak inspiratory flow measured by HFNC and by a mask connected with a respiratory monitor.

Inclusion Criteria:

• Healthy volunteers between 21-65 years old

Exclusion Criteria:

• Chronic pulmonary diseases, including COPD, interstitial lung disease, cystic fibrosis, etc.
• Uncontrolled asthma;
• Pregnancy
• Subjects who have cold/flu symptoms (sore throat, runny nose, fever, chills, coughing)
• Nose abnormalities that can affect the functionality of the nasal prongs

Individual participant data will not be shared.

From the start of the experimental session until completion of all flow conditions (up to 4 hours)

Adverse events were monitored throughout the experimental session by direct observation. The study involved healthy volunteers undergoing brief respiratory interventions, with no clinical treatments or follow-up. No differences exist between the study's definitions of adverse events and ClinicalTrials.gov definitions.

This study was conducted in healthy adult volunteers in a controlled laboratory environment, which may limit generalizability to clinical populations. The short intervention duration and immediate outcome assessments do not allow evaluation of longer-term effects.