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Study of Humidified Air to Improve Mucociliary Clearance (MCC) in COPD

Study of Humidified Air to Improve Mucociliary Clearance (MCC) in COPD

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03935932
Enrollment
12
Registered
2019-05-02
Start date
2019-07-15
Completion date
2021-02-15
Last updated
2023-06-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COPD

Keywords

COPD, Chronic bronchitis

Brief summary

This purpose of this study is to determine whether nasal delivery of heated and humidified air for a period of 4 hours will improve the clearance of mucus from the lungs of patients with chronic obstructive pulmonary disease (COPD). Mucus clearance will be measured using a nuclear medicine imaging procedure called a mucociliary clearance scan. Humidified air (with added oxygen if needed) will be delivered from the Fisher and Paykel myAirvo2 heater/humidifier through an Optiflow nasal cannula.

Detailed description

Chronic bronchitis is a component of Chronic Obstructive Pulmonary Disease (COPD), along with emphysema. COPD is associated with smoking, exposure to environmental pollutants, or occupational exposures. In the airways mucus acts to trap inhaled toxins or pathogens. In a healthy lung mucus is cleared by mucociliary and cough clearance. Mucociliary clearance involves the synchronous motion of cilia underneath the mucus sheet that lines the airways. This drives the mucus sheet out of the airways (like a conveyer belt) continually clearing particulate and pathogens. In chronic bronchitis, mucus is overproduced due to toxic stimuli. Mucus clearance may also be defective due to airway obstruction and insufficient cough. This results in the accumulation of mucus that contributes to airway obstruction. Therapies for improving mucus clearance may decrease the degree of airway obstruction experienced by COPD patients. Heated, high-flow, humidified air or oxygen may improve mucus clearance by hydrating the mucus in the airways and may also help to increase airway patency. A similar intervention was shown to improve mucus clearance in subjects with bronchiectasis. The investigators have developed nuclear imaging-based methods for measuring mucus clearance from the lungs. These techniques have been applied to evaluate novel therapies for the treatment of cystic fibrosis lung disease. Here the investigators will apply these techniques to determine whether treatment with heated-humidified air will improve mucus clearance in subjects with COPD. Study participation involves 3 visits. Study day 1 includes: 1. A conversation with a physician and completion of informed consent 2. Pulmonary function testing (including albuterol administration) 3. The completion of a series of questionnaires Study days 2 and 3 include: 1. A urine pregnancy test (if applicable) 2. Performance of a Co57 transmission scan 3. The inhalation of a radiopharmaceutical (Technetium-99m sulfur colloid) from a nebulizer 4. Lying flat in a nuclear medicine camera for 90 minutes while scans are collected. 5. Remaining at the test center for a follow up scan approximately 2.5 hours later. This scan will take 10 minutes. 6. Nasal delivery of heated humidified air (with supplemental oxygen if needed) at a rate of 30 liters per minute through a nasal cannula, on one study day. This will be started during the first 10 minutes of the 90 minute scanning period and continued for 4 hours. One the other study day there will be no treatment so that a baseline measurement of mucociliary clearance can be made. The order of the study days will be randomized. Participants will be asked to refrain from using short-acting beta agonist (SABA) medications for 6 hours prior to study days 2 and 3, and long-acting beta agonists (LABA) or long-acting muscarinic antagonists (LAMA) for 24 hours prior to study days 2 and 3.

Interventions

DEVICEnasal delivery of heated and humidified air

Subjects will receive nasal delivery of heated and humidified air (plus oxygen if needed) at 30 liters/minute from the Fisher and Paykel myAirvo2 heater/humidifier using an Optiflow nasal cannula.

Sponsors

Fisher and Paykel Healthcare
CollaboratorINDUSTRY
Frank C Sciurba
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Masking description

Open label

Intervention model description

Open label, single treatment administration, crossover

Eligibility

Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No

Inclusion criteria

1. Male or Female 40 to 85 years old 2. Diagnosis of chronic bronchitis 3. Able to regularly produce sputum 4. Clinically stable 5. Current smoker or ex-smoker with a tobacco history of ≥10 pack-years (1 pack year = 20 cigarettes smoked per day for 1 year) 6. History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC\<0.70 and a post-bronchodilator FEV1\>20% and ≤70% of predicted normal value at enrollment. 7. CAT score ≥ 10, with questions 1 and 2 responses ≥ 5

Exclusion criteria

1. Pregnant or nursing or unwilling to perform pregnancy testing 2. Unwilling or unable to refrain for SABA/LABA use ahead of the study 3. Unable to lie recumbent for 90 min, 4. Clinically important pulmonary disease other than COPD (e.g. active lung infection, clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency and primary ciliary dyskinesia) or another diagnosed pulmonary or systemic disease that is associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hyper-eosinophilic syndrome) and/ or radiological findings suggestive of a respiratory disease other than COPD that is contributing to the subject's respiratory symptoms. 5. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and/or could: * Affect the safety of the subject throughout the study * Influence the findings of the study or their interpretation * Impede the subject's ability to complete the entire duration of study 6. Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 2 weeks prior to enrollment, based on last dose of steroids or last date of hospitalization whatever occurred later 7. Acute upper or lower respiratory infection within 2 weeks prior to enrollment 8. Supplemental oxygen use at greater than 3 liters/min

Design outcomes

Primary

MeasureTime frameDescription
Mucociliary Clearance Rate - 4 Hours0-4 hoursPercentage of radioactivity cleared from the right lung

Secondary

MeasureTime frameDescription
Mucociliary Clearance Rate - 90 Min0-90 minutesPercentage of radioactivity cleared from the right lung
Area Above Retention Curve - 90 Min0-90 minutesArea above the curve of normalized retention of radioactivity vs time from the right lung

Countries

United States

Participant flow

Participants by arm

ArmCount
Baseline Followed by Intervention
Subjects randomized to perform baseline measurement of clearance on study day 2 and measurement of clearance with nasal delivery of heated and humidified air on day 3 nasal delivery of heated and humidified air: Subjects will receive nasal delivery of heated and humidified air (plus oxygen if needed) at 30 liters/minute from the Fisher and Paykel myAirvo2 heater/humidifier using an Optiflow nasal cannula.
6
Intervention Followed by Baseline
Subjects randomized to perform measurement of clearance with nasal delivery of heated and humidified air on day 2 and baseline measurement of clearance on study day 3 nasal delivery of heated and humidified air: Subjects will receive nasal delivery of heated and humidified air (plus oxygen if needed) at 30 liters/minute from the Fisher and Paykel myAirvo2 heater/humidifier using an Optiflow nasal cannula.
6
Total12

Baseline characteristics

CharacteristicBaseline Followed by InterventionTotalIntervention Followed by Baseline
Age, Continuous68 years70 years70 years
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants12 Participants6 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
1 Participants2 Participants1 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
5 Participants10 Participants5 Participants
Region of Enrollment
United States
6 participants12 participants6 participants
Sex: Female, Male
Female
1 Participants3 Participants2 Participants
Sex: Female, Male
Male
5 Participants9 Participants4 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 120 / 12
other
Total, other adverse events
2 / 120 / 12
serious
Total, serious adverse events
0 / 120 / 12

Outcome results

Primary

Mucociliary Clearance Rate - 4 Hours

Percentage of radioactivity cleared from the right lung

Time frame: 0-4 hours

ArmMeasureValue (MEDIAN)
AIRVO DayMucociliary Clearance Rate - 4 Hours47 percent clearance
Baseline DayMucociliary Clearance Rate - 4 Hours56 percent clearance
p-value: 0.11Wilcoxon signed-rank
Secondary

Area Above Retention Curve - 90 Min

Area above the curve of normalized retention of radioactivity vs time from the right lung

Time frame: 0-90 minutes

ArmMeasureValue (MEDIAN)
AIRVO DayArea Above Retention Curve - 90 Min6.2 percent clearance x time (minutes)
Baseline DayArea Above Retention Curve - 90 Min8.0 percent clearance x time (minutes)
p-value: 0.35Wilcoxon signed-rank
Secondary

Mucociliary Clearance Rate - 90 Min

Percentage of radioactivity cleared from the right lung

Time frame: 0-90 minutes

ArmMeasureValue (MEDIAN)
AIRVO DayMucociliary Clearance Rate - 90 Min22 percent clearance
Baseline DayMucociliary Clearance Rate - 90 Min34 percent clearance
p-value: 0.11Wilcoxon (Mann-Whitney)

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026