Effects of flow rate on transnasal pulmonary aerosol delivery of bronchodilators via high-flow nasal cannula for patients with COPD and asthma: protocol for a randomised controlled trial

INTRODUCTION: Both in vitro and in vivo radiolabelled studies on nebulisation via high-flow nasal cannula showed that inhaled dose decreases as the administered gas flow increases. In our previous in vitro study, we investigated the effects of the ratio of gas flow to subject’s peak inspiratory flow (GF:IF) on the aerosol deposition, which increased as the GF:IF decreased, with an optimal GF:IF between 0.1 and 0.5 producing a stable ‘lung’ deposition in both quiet and distressed breathing. Thus, we aim to validate our in vitro findings in subjects with reversible airflow limitations by assessing their response to inhaled bronchodilator. METHODS AND ANALYSIS: This is a single-centre, randomised controlled trial. Subjects with chronic obstructive pulmonary disease or asthma with positive response to 400μg albuterol via metered dose inhaler and valved holding chamber will be enrolled and consented. After a washout period (1–3 days), subjects will be randomly assigned to inhale albuterol with one of three gas flows: 50 L/min, GF:IF=1.0 and GF:IF=0.5. In each arm, subjects will inhale 2 mL saline, followed by escalating doubling doses (0.5, 1, 2 and 4 mg) of albuterol in a fill volume of 2 mL, delivered by a vibrating mesh nebuliser via heated nasal cannula set up at 37°C. An interval of 30 min between each dose of albuterol, with spirometry measured at baseline and after each inhalation. Titration will be terminated if forced expiratory volume in 1 s improvement is <5%, or adverse event is observed. ETHICS AND DISSEMINATION: This trial has been approved by the Ethic Committee of People’s Liberation Army General Hospital, Beijing, China (no. S2018-200-01). The results will be disseminated through peer-reviewed journals, national and international conferences. TRIAL REGISTRATION NUMBER: NCT03739359; Pre-results.