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

Not Applicable
Completed
Conditions
COPD Asthma
Interventions
Other: nasal cannula gas flow
Registration Number
NCT03739359
Lead Sponsor
Rush University Medical Center
Brief Summary

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

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%.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
75
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Gas flow 50 L/minnasal cannula gas flowIn this group, nasal cannula gas flow will be set at 50 L/min.
GF:IF=1nasal cannula gas flowIn this group, nasal cannula gas flow will be set at each individual patient's own inspiratory flow (GF:IF=1)
GF:IF=0.5nasal cannula gas flowIn this group, nasal cannula gas flow will be set at 50% of each individual patient's own inspiratory flow (GF:IF=0.5)
Primary Outcome Measures
NameTimeMethod
The number of patients who meet the positive criteria of responding to albuterol at the dose of 1.5 mg60 minutes

The number of patients in HFNC nebulization who respond to albuterol at the dose of 1.5mg

The number of patients who meet the positive criteria of responding to albuterol at the dose of 0.5mg30 minutes

The number of patients in HFNC nebulization who respond to albuterol at the dose of 0.5mg

The number of patients who meet the positive criteria of responding to albuterol at the dose of 3.5 mg90 minutes

The number of patients in HFNC nebulization who respond to albuterol at the dose of 3.5mg

The number of patients who meet the positive criteria of responding to albuterol at the dose of 7.5mg120 minutes

The number of patients in HFNC nebulization who respond to albuterol at the dose of 7.5mg

Secondary Outcome Measures
NameTimeMethod
the incidence of side effect (tremor) in each group120 minutes

the incidence of side effect (tachycardia) will be recorded in each group

the accumulative dose of albuterol required across groups to produce positive bronchodilation effects120 minutes

the accumulative dose of albuterol required to produce positive bronchodilation effects in each group

the incidence of side effect (tachycardia) in each group120 minutes

the incidence of side effect (tachycardia) will be recorded in each group

Trial Locations

Locations (1)

People's Liberation Army General Hospital

🇨🇳

Beijing, Beijing, China

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