The Role of Gas Flow in Transnasal Pulmonary Aerosol Delivery: A Double-blinded, Randomized Controlled Trial

Study Overview
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Brief Summary
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Aerosol delivery via nasal cannula has gained increasing popularity, due to its combined benefits from aerosolized medication and heated warm oxygen therapy. In our previous in vitro study, we investigated the effects of the ratio of nasal cannula gas flow to subject's peak inspiratory flow (GF: IF) on the aerosol lung deposition, and we found that aerosol deposition in lung increased as the GF: IF decreased with an optimal GF: IF between 0.1 to 0.5 producing a stable lung deposition in both quiet and distress breathing. Thus we aimed to further validate such an optimal GF: IF in patients with reversible airflow limitations by the delivery of bronchodilators. Adult COPD or asthma patients who met ATS/ERS criteria for bronchodilator response in pulmonary function lab will be recruited and consented. After a washout period (1-3 days), patients will receive an escalating doubling dosage (0.5, 1, 2, and 4mg) of albuterol in total volume of 2mL, delivered by mesh nebulizer via nasal cannula. Patients will be randomly assigned to inhale bronchodilator into 3 group using different flows: 50 L/min,GF: IF = 1.0, and GF: IF = 0.5.

Detailed Description
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Introduction Both in vitro and in vivo radiolabeled studies on nebulization via high flow nasal cannula (HFNC) showed that aerosol lung deposition decreased with the increasing nasal cannula gas flow, which, however, was not observed in patients with distressed breathing. In our previous in vitro study, we investigated the effects of the ratio of nasal cannula gas flow to subject's peak inspiratory flow (GF: IF) on the aerosol lung deposition, and we found that aerosol deposition in lung increased as the GF: IF decreased with an optimal GF: IF between 0.1 to 0.5 producing a stable lung deposition in both quiet and distress breathing. Thus we aimed to further validate such an optimal GF: IF in patients with reversible airflow limitations by the delivery of bronchodilators. Methods and analysis COPD and asthma patients with positive response to four actuations of albuterol via metered dose inhaler (MDI) and valved holding chamber (VHC) will be enrolled and consented in the study. After a washout period (1-3 days), patients will be randomly assigned to three groups with different nasal cannula gas flow: 50L/min, GF: IF = 1.0, and GF: IF = 0.5. In each treatment arm, patients will firstly receive saline, then followed by an escalating doubling dosages (0.5, 1, 2, and 4mg) of albuterol in a total volume of 2mL, delivered by mesh nebulizer (VMN, Aerogen, Ireland) via heated nasal cannula at 37℃. An interval of 30 min will be maintained between two doses of albuterol, and pulmonary spirometry will be measured at baseline and after each dose. Titration will be terminated when an additional FEV1 improvement was < 5%.

Official Title
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Investigating the Role of Gas Flow in Transnasal Pulmonary Aerosol Delivery Via Nasal Cannula: A Double-blinded, Randomized Controlled Trial

Conditions
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COPD Asthma

Intervention / Treatment
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* Other: nasal cannula gas flow


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with positive bronchodilator responses to four actuations of albuterol (Ventolin, GSK, UK) via MDI with VHC (OptiChamber Diamond, Philips, USA) will be eligible for enrollment. A positive bronchodilator response is defined in accordance with ATS/ERS guidelines as follows: an increase in FEV1 of ≥ 12% and absolute change ≥ 200 mL from baseline. Exclusion Criteria: age ≥ 90 years old; pregnancy; pulmonary exacerbation within two weeks before enrollment; reluctant to participate; inability to complete the follow-up spirometry after each bronchodilator inhalation; resting heart rate > 100bpm; resting systolic blood pressure > 160mmHg or diastolic blood pressure > 110mmHg.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gas flow 50 L/min<br>In this group, nasal cannula gas flow will be set at 50 L/min. | Other: nasal cannula gas flow<br>* High flow nasal cannula (HFNC) is a relatively new oxygen device, which provides warmed and humidified oxygen for patients. When patients need to inhale aerosolized medication during HFNC, the nebulizer will be placed in-line in order to provide both treatments. This study will investigate the influence of three flow settings (50 L/min, GF:IF=1, GF:IF=0.5) on the clinical effects of nebulization.<br>|
| Experimental: GF:IF=1<br>In this group, nasal cannula gas flow will be set at each individual patient's own inspiratory flow (GF:IF=1) | Other: nasal cannula gas flow<br>* High flow nasal cannula (HFNC) is a relatively new oxygen device, which provides warmed and humidified oxygen for patients. When patients need to inhale aerosolized medication during HFNC, the nebulizer will be placed in-line in order to provide both treatments. This study will investigate the influence of three flow settings (50 L/min, GF:IF=1, GF:IF=0.5) on the clinical effects of nebulization.<br>|
| Experimental: GF:IF=0.5<br>In this group, nasal cannula gas flow will be set at 50% of each individual patient's own inspiratory flow (GF:IF=0.5) | Other: nasal cannula gas flow<br>* High flow nasal cannula (HFNC) is a relatively new oxygen device, which provides warmed and humidified oxygen for patients. When patients need to inhale aerosolized medication during HFNC, the nebulizer will be placed in-line in order to provide both treatments. This study will investigate the influence of three flow settings (50 L/min, GF:IF=1, GF:IF=0.5) on the clinical effects of nebulization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients who meet the positive criteria of responding to albuterol at the dose of 0.5mg | The number of patients in HFNC nebulization who respond to albuterol at the dose of 0.5mg | 30 minutes | 
| The number of patients who meet the positive criteria of responding to albuterol at the dose of 1.5 mg | The number of patients in HFNC nebulization who respond to albuterol at the dose of 1.5mg | 60 minutes | 
| The number of patients who meet the positive criteria of responding to albuterol at the dose of 3.5 mg | The number of patients in HFNC nebulization who respond to albuterol at the dose of 3.5mg | 90 minutes | 
| The number of patients who meet the positive criteria of responding to albuterol at the dose of 7.5mg | The number of patients in HFNC nebulization who respond to albuterol at the dose of 7.5mg | 120 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the accumulative dose of albuterol required across groups to produce positive bronchodilation effects | the accumulative dose of albuterol required to produce positive bronchodilation effects in each group | 120 minutes | 
| the incidence of side effect (tachycardia) in each group | the incidence of side effect (tachycardia) will be recorded in each group | 120 minutes | 
| the incidence of side effect (tremor) in each group | the incidence of side effect (tachycardia) will be recorded in each group | 120 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasal cannula, Aerosol therapy, Gas flow