Study of Humidified Air to Improve Mucociliary Clearance (MCC) in COPD
Phase: NA
Conditions: COPD
Sponsor: Frank C Sciurba

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Study of Humidified Air to Improve Mucociliary Clearance (MCC) in COPD:  
NCT03935932 
Tim Corcoran, Ph.D., Frank Sciurba, M.D.   
Pulmonary, Allergy and Critical Care Medicine 
University of Pittsburgh 
 
Hypothesis:  The delivery of humidified air by nasal cannula will result in real-time improvement in 
mucociliary clearance. 
Intervention:   Delivery of humidified air using Fisher and Paykel myAirvo 2 and Optiflow nasal cannula 
for  4 hours at 30 L/min, reduced to 25 L/min if required for tolerance and 37 degrees C.   
Population:  n=12, female or male subjects 40 – 85 years of age with chronic bronchitis 
Inclusion criteria:  
(1) Male or Females 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. (5) 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  

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(8) Supplemental oxygen use at greater than 3L/min 
Study procedures: 
MCC assessment 
1) Subjects will perform 2 MCC assessment study days.  One to measure baseline MCC and the other to 
measure MCC during treatment with the cannula.  Study days will be separated by 4-7 days.   The order 
of the days will be randomized.   Subjects will refrain from SABA use for 6 hours and LABA/LAMA use for 
24 hours prior to Visits 2 and 3. 
2) Subjects will arrive in nuclear medicine.  They will lie recumbent in the nuclear medicine camera while 
background images are collected.  They will then perform a Cobalt-57 transmission scan which allows for 
visualization of the lung outlines.  Both scans are utilized during image analysis. 
3) Subjects will be seated for the inhalation of the radiolabeled particles.  4 mCi of Technetium 99m sulfur 
colloid (Tc-SC) in 2ml of saline will be added to a DeVilbiss 646 Nebulizer driven by a DeVilbiss 8650D 
compressor and attached to a Spira Dosimeter.  Using standardized procedures developed the Cystic 
Fibrosis Foundation (1), we will deliver the aerosol for 5 approximately minutes using a specified breathing 
pattern (30 breaths/minute) using inhalation flowrates of ~0.5 L/s.    
4) Subjects will then return to the camera and lie recumbent while serial two-minute gamma camera 
images are collected for 90 minutes.   On the intervention day, the nasal cannula will be applied after 5 
images are collected.   On the baseline day there will be no intervention.   Coughs will be manually logged 
by study personnel.  
5) After 90 minutes the subjects will exit the camera and remain in the waiting areas around radiology.  
They will continue inhaling from the cannula on the intervention day.   Subjects will perform a 10 minute 
follow up image at t=4 hours and 10 minutes after the start of the imaging sequence.  The 10 minute 
image may be delayed for several minutes if the gamma camera is in use at the specified time Subjects 
would resume their normal medications.  
6) We will plot normalized retention vs. time and compare the percentage of deposited material cleared 
at t=90 min and up to 6 hours on the intervention days.   Areas above the curve 90 min clearance curve 
will also be compared.  We will calculate the central deposition percentage of the Tc-SC aerosol to ensure 
that Tc-SC aerosol delivery was similar on both testing days.  
7) Previous measurements from our group demonstrated a standard deviation of the intrasubject 
differences in MCC measurements (σ) = 7.7% (2).  Assuming α=0.05, β=0.2, and n=12 matched pairs, we 
could detect a 6.8% (absolute) change in MCC rates via paired t-test.   Average MCC rates in control 
subjects over 90 minutes have been reported to be 28.2% (1).    MCC rate differences reported by Hasani 
et al were approximately 8% after 7 days of daily therapy (3).   
8) We will replace subjects who do not complete both testing days until we have a total of 12 subjects 
with completed studies.   
Spirometry Testing 

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Each subject will undergo baseline spirometry assessment to determine eligibility. All subjects will 
perform baseline pre and post bronchodilator spirometry at Visit1 . Subjects will be asked to hold their 
bronchodilator (albuterol) for 2 hours prior to the PFT test. 
Subjects who meet the PFT criteria at Visit 1 will be required to be tested for COVID-19 prior to undergo 
the MCC measurements at Visits 2 and 3. The COVID testing will be done at the CTRC Montefiore 
Hospital by a trained nurse.  The COVID testing is a safety measure requested by the PI to make sure 
staff present during the MCC measurements will not be placed at risk of contracting the virus during 
the study procedures. Subjects found ineligible per the PFT results, will be considered a screen fail and 
will not be tested.  
Only patients with COVID testing negative will be invited to complete study visits 2 and 3. 
Study Questionnaires 
All subjects will complete the following self-administered questionnaires at Visit 1: 
1) St. George’s Respiratory Questionnaire (SGRQ) 
2) COPD Assessment Test (CAT) 
3) Modified Medical Research Council Dyspnea Scale (mMRC) 
4) Exacerbation history  
Schedule of Assessments 
Visit schedule 
 
Visit 1 
Visit 2 
Visit 3 
Baseline MCC* 
 
X 
 
Treatment MCC* 
 
 
X 
Questionnaires 
X 
 
 
Pre and Post Bronchodilator Spirometry 
X 
 
 
 
 
 
 
* Baseline and Treatment MCC are randomized. 
 
The Fisher and Paykel myAirvo2 heater/humidifier and Optiflow nasal cannula are commercially 
available devices that are used together to deliver heated humidified air or oxygen for breathing.  The 
purpose of this study is to determine whether 4 hours of use of this device will improve mucus clearance 
in patients with chronic bronchitis.  This may occur through hydration of airway secretions and possibly 
through splinting of the airways.  Twelve subjects will be enrolled and perform two imaging days and a 
possible screening day.   The primary outcome measure is mucociliary clearance as measured using a 
nuclear medicine imaging technique.   
References 
 
1. Bennett WD, Laube BL, Corcoran T, Zeman K, Sharpless G, Thomas K, Wu J, Mogayzel PJ, Jr., Pilewski J, 
Donaldson S. Multisite comparison of mucociliary and cough clearance measures using 
standardized methods. Journal of aerosol medicine and pulmonary drug delivery 2013; 26: 157-
164. 

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2. Locke LW, Myerburg MM, Weiner DJ, Markovetz MR, Parker RS, Muthukrishnan A, Weber L, Czachowski 
MR, Lacy RT, Pilewski JM, Corcoran TE. Pseudomonas infection and mucociliary and absorptive 
clearance in the cystic fibrosis lung. Eur Respir J 2016; 47: 1392-1401. 
3. Hasani A, Chapman TH, McCool D, Smith RE, Dilworth JP, Agnew JE. Domiciliary humidification improves 
lung mucociliary clearance in patients with bronchiectasis. Chron Respir Dis 2008; 5: 81-86.