CLINICAL TRIAL article
Front. Med.
Sec. Pulmonary Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1538832
Physiological effects of bi-level high-flow nasal cannula in healthy individuals: a proof of concept trial
Provisionally accepted
Jin Won Huh1
Woo Jung Seo2
Jee Hwan Ahn1Su Yeon Lee1Hee Jung Suh3Ga Jin Seo3Eun Young Kim3Min Kyung Jang3Chae-Man Lim1*- 1Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Seoul, Republic of Korea
- 2Inje University Ilsan Paik Hospital, Goyang-si, Republic of Korea
- 3Respiratory Care Services, Asan Medical Center, Seoul, Republic of Korea
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background High-flow nasal cannula (HFNC) delivers a continuous, unidirectional high flow of oxygen (Uniflow) throughout the respiratory cycle. Despite its positive pressure effects in the nasopharynx, the persistent high flow during expiration imposes additional work of breathing and disrupts the patient's neural respiratory cycle. We devised a bi-level high-flow system (Biflow) allowing separate flow rate adjustments for inspiration and expiration.We conducted a randomized crossover pilot study which we included healthy volunteer at ASAN Medical Center (April 2021 to June 2021). The data of twelve healthy volunteers (7 male, 5 female, average age 46.3 years) were analysed. For Uniflow, flow settings of 30 (U30), 40 (U40), and 50 (U50) L/min were tested. In the Biflow, inspiratory flow rates were matched to the Uniflow settings, while expiratory flow rates varied from 10 L/min to 30 L/min. The sequence of each flow (Uniflow vs. Biflow) was randomized and each flow setting was maintained for 3 minutes. Physiologic parameters, nasopharyngeal pressure-time product (N-PTP) as an energy cost proxy, end-expiratory lung impedance (EELI), and participant comfort were assessed.Uniflow decreased respiratory rate and elongated expiratory time compared to natural breathing. However, these effects were less pronounced during Biflow. Compared with the Uniflow, both expiratory and inspiratory N-PTP were lower during the Biflow. Transcutaneous CO2 was lower during the Biflow compared with natural breathing or Uniflow. EELI did not differ between modes. All participants completed the study protocol without side effects.In healthy participants, compared with the conventional HFNC (Uniflow), Biflow showed less interference with the natural respiratory cycle of the participants. Compared with Uniflow, energy cost occurring in the nasopharynx was lower during Biflow (Trial registration:
Keywords: High flow nasal cannula, Biflow, Respiratory cycle, Pressure-time product, Concept trial
Received: 03 Dec 2024; Accepted: 26 Mar 2025.
Copyright: © 2025 Huh, Seo, Ahn, Lee, Suh, Seo, Kim, Jang and Lim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chae-Man Lim, Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Seoul, Republic of Korea
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.