Dose Response to Transnasal Pulmonary Administration of Bronchodilator Aerosols via Nasal High-Flow Therapy in Adults with Stable Chronic Obstructive Pulmonary Disease and Asthma.

There has been increasing interest in transnasal pulmonary aerosol administration, but the dose-response relationship has not been reported. To determine the accumulative bronchodilator dose at which patients with stable mild-to-moderate asthma and chronic obstructive pulmonary disease (COPD) achieve similar spirometry responses before and after bronchodilator tests using albuterol via a metered dose inhaler with a valved holding chamber (MDI + VHC). Adult patients who met ATS/ERS criteria for bronchodilator responses in pulmonary function laboratory were recruited and consented to participate. After a washout period, patients received escalating doubling dosages (0.5, 1, 2, and 4 mg) of albuterol in a total volume of 2 mL delivered by vibrating mesh nebulizer via a nasal cannula at 37°C with a flow rate of 15-20 L/min using a Venturi air entrainment device. Spirometry was measured at baseline and after each dose. Titration was stopped when an additional forced expiratory volume in 1 second (FEV1) improvement was <5%. 42 patients (16 males) with stable mild-to-moderate asthma (n = 29) and COPD (n = 13) were enrolled. FEV1 increment after a cumulative dose of 1.5 mg of albuterol via nasal cannula at 15-20 L/min was similar to 4 actuations of MDI + VHC (0.34 ± 0.18 vs. 0.34 ± 0.12 L, p = 0.878). Using ATS/ERS criteria of the bronchodilator test, 33.3% (14/42) and 69% (29/42) of patients responded to 0.5 and 1.5 mg of albuterol, respectively. With a nasal cannula at 15-20 L/min, transnasal pulmonary delivery of 1.5 mg albuterol resulted in similar bronchodilator response as 4 actuations of MDI + VHC.

Li J ，Zhao M ，Hadeer M ，Luo J ，Fink JB ... -  《-》

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.

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. 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. 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. NCT03739359; Pre-results.

Li J ，Luo J ，Chen Y ，Xie L ，Fink JB ... -  《-》

Automatic replacement of albuterol nebulizer therapy by metered-dose inhaler and valved holding chamber.

Hendeles L ，Hatton RC ，Coons TJ ，Carlson L ... -  《-》

Factors Determining In Vitro Lung Deposition of Albuterol Aerosol Delivered by Ventolin Metered-Dose Inhaler.

Biswas R ，Hanania NA ，Sabharwal A 《-》

Nebulization versus metered-dose inhaler and spacer in bronchodilator responsiveness testing: a retrospective study.

Lu R ，Li Y ，Hu C ，Pan P ，Zhao Q ，He R ... -  《-》