HHHFA in COPD Patients, With Chronic Bronchitis

Study Overview
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Brief Summary
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Heated, humidified high-flow air (HHHFA) devices improve airway clearance. HHHFA use for an average of 1.6 hours a day in COPD patients with chronic bronchitis improves health-related quality of life, lung function, and delays the first respiratory exacerbation. However, HHHFA for an average of 1.6 hours a day had no effect on COPD exacerbation frequency or hospitalization, dyspnea, or exercise capacity, likely due to short duration of the treatment. Conversely, the effect of HHHFA for longer time periods on chronic bronchitis patients has not been studied. Moreover, the effect of HHHFA on sleep quality has not been studied. A prior study in COPD patients showed that use of HHHFA for more than 7 hours during sleep can be achieved. The overall objective of this research is to examine the effect of HHHFA during sleep on COPD patients with chronic bronchitis. In this pilot study, the study team will examine the effect of HHHFA during sleep on clinically relevant short-term outcomes including: respiratory symptoms, quality of life and sleep, lung function and exercise capacity. Subjects will be recruited and consented. Once a subject agrees to be in the study the baseline visit will occur. The first test will be the Pulmonary Function testing. If the subject qualifies based on the PFT's they will complete the remainder of the baseline visit. During this visit subjects will complete questionnaires, have a physical, 6 minute walk test and CT scan. Subjects will receive device training on the heated, humidified high-flow air device. Subjects will have a followup call between 3-7 days to check in on how the subject is doing with the device. After 6 weeks the subject will return for another round of testing as was done at baseline. This will be the final study visit.

Detailed Description
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Chronic obstructive pulmonary disease (COPD) is characterized by respiratory exacerbations which increase in frequency as the severity of the disease progresses. COPD exacerbations may lead to hospitalizations, which make up the largest proportion of the total direct health-care cost of the disease and are a significant burden for patients and family. Chronic bronchitis, defined as chronic cough with sputum production for at least 3 months a year for 2 consecutive years, is one of the clinical manifestations of COPD. Chronic bronchitis doubles the risk of COPD exacerbations and hospitalizations, and is associated with increased dyspnea, worse health-related quality of life, and poorer quality of sleep. Chronic bronchitis also results in increased air trapping and hyperinflation, which decreases exercise capacity. Unfortunately, other than traditional inhaled pharmacological agents, there are no treatment options for COPD patients with chronic bronchitis. Heated, humidified high-flow air (HHHFA) devices improve airway clearance. HHHFA use for an average of 1.6 hours a day in COPD patients with chronic bronchitis improves health-related quality of life, lung function, and delays the first respiratory exacerbation. However, HHHFA for an average of 1.6 hours a day had no effect on COPD exacerbation frequency or hospitalization, dyspnea, or exercise capacity, likely due to short duration of the treatment. Conversely, the effect of HHHFA for longer time periods on chronic bronchitis patients has not been studied. Moreover, the effect of HHHFA on sleep quality has not been studied. A prior study in COPD patients showed that use of HHHFA for more than 7 hours during sleep can be achieved. The overall objective of this research is to examine the effect of HHHFA during sleep on COPD patients with chronic bronchitis. In this pilot study, the study team will examine the effect of HHHFA during sleep on clinically relevant short-term outcomes including: respiratory symptoms, quality of life and sleep, lung function and exercise capacity. Hypothesis 1: HHHFA during sleep in COPD patients with chronic bronchitis improves respiratory symptoms, sleep quality, lung function, and exercise capacity. Aim 1: To examine the effect of HHHFA during sleep on respiratory symptoms, sleep quality, lung function, and exercise capacity in COPD patients with chronic bronchitis. The effect of HHHFA on air trapping and hyperinflation has not been studied. Air trapping and hyperinflation as well as other radiographic measurements associated with chronic bronchitis (e.g. airway wall thickness) can be measured using chest CT. Hypothesis 2: HHHFA during sleep in COPD patients with chronic bronchitis improves air trapping and hyperinflation. Aim 2: To examine the effect of HHHFA in COPD patients with chronic bronchitis during sleep on air trapping and hyperinflation through chest CT imaging. Design: The study team will include COPD subjects with a post-bronchodilator FEV1%predicted below 70% and chronic bronchitis. The study team will include subjects with at least 2 exacerbations in the last year to identify patients with significant burden due to chronic bronchitis. The study team will exclude subjects with recent respiratory events or procedures as the study team want to capture the benefit of HHHFA on chronic, stable COPD participants. Subjects who meet eligibility criteria will be randomized to HHHFA or usual care (Controls). At baseline the study team will perform measurements in all subjects that include dyspnea, cough, health-related quality of life, sleep quality, spirometry, a 6-minute walk test, and chest CT. All subjects, from both groups will also use the SPIREHEALTH Tag Device to measure their daily heart rate, respiratory rate, patient activity and calories. The group that is randomized to use the HHHFA device will be provided the HHHFA device at the baseline visit. Subjects will use the device during sleep for 6 weeks and both the HHHFA arm and the control arm will return for a 6 week follow up visit. At the 6 week follow up visit, participants will repeat all baseline evaluations. The study team will compare variables (e.g. FEV1) between baseline and 6-week visit in each treatment group. The study team will also compare changes in those variables over time between groups. To evaluate the effect of treatment between baseline and 6 weeks, the study team will use linear mixed effect models controlling for demographics and lung function. Subjects who have been using the HHHFA device will be asked to stop using the device for the next 6 weeks. Both arms will then have a follow up phone call at the end of the 6 weeks (12 week follow up phone call visit). Subjects from both arms will continue to use the SPIREHEALTH and that data will be collected for both arms during that 6 week period. Subjects who were previously randomized to the HHHFA arm will be asked, at the 6 week follow up visit, if they would be interested in participating in an optional sub-study that would allow them to start using the HHHFA device again, after their 12 week follow up phone call for an additional 36 weeks (for a total study involvement of 48 weeks) The subjects will have follow up phone call visits at 24 weeks, 36 weeks, and 48 weeks. Subjects who were randomized to the HHHFA device but do not want to keep using the device will be given the option of continuing to participate but only will the follow up phone call visits. Respiratory exacerbations information will be collected at these phone call visits.

Official Title
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The Effect of Heated, Humidified High-flow Air in COPD Patients With Chronic Bronchitis

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Device: HHHFA Device
* Diagnostic Test: Spirometry
* Diagnostic Test: 6-minute walk
* Diagnostic Test: CT scan
* Other: Medical Research Council dyspnea scale (MRC)
* Other: St. George's Respiratory Questionnaire (SGRQ)
* Other: COPD Assessment Test (CAT)
* Other: Pittsburgh Sleep Quality Index (PSQI)
* Other: CASA-Q
* Other: Spirehealth Tag Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD diagnosis by health care provider Post-bronchodilator FEV1/FVC <0.7 Post-bronchodilator FEV1%predicted <70% Chronic bronchitis, defined as chronic cough with daily sputum production ≥2 COPD exacerbations within the last year Smart phone Exclusion Criteria: Obstructive sleep apnea and using positive airway pressure treatment Patients that use oxygen supplementation continuously (patients that use oxygen supplementation only at exertion will NOT be excluded) Any planned procedure that the PI believes would cause the subject to be ineligible. Unable to perform a spirometry, 6-minute walk test or chest CT Recent diagnosis (<4 weeks prior to study entry) of pneumonia, respiratory infection, COPD exacerbation, or acute bronchitis requiring antibiotics and new/increased dose of systemic corticosteroids Thoracic surgery or another procedure in the last six months that may result in instability of pulmonary status Recent medical or surgical history of upper airway disease that may interfere with intervention (e.g., sinus surgery, significant nasal polyps) Recent chest illness (trauma, pneumothorax etc). Basal skull surgery in the last 6 months Open skin ulcer or rash where the nasal cannula will be worn Tracheostomy or laryngectomy Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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
Interventional Model Description: Subjects will be randomized into two groups: One will receive the device and one will not. Study procedures will be the same for both groups.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HHHFA Randomized Group<br>Subjects will be randomized to use the HHHFA device during bedtime for at least 4 hours. Subjects will complete MRC, SGRQ, CAT, CASA-Q and PSQI questionnaires. They will do spirometry, 6-minute walk, and CT scan. These interventions will be done at baseline and at the completion of their study (6 weeks). Spirehealth Device will be worn by subject daily for 12 weeks. | Device: HHHFA Device<br>* Participants will be instructed to use the HHHFA for at least 4 hours during their sleep but will be allowed to use it as long as they want during sleep.<br>Diagnostic Test: Spirometry<br>* Pre and post spirometry using albuterol.<br>Diagnostic Test: 6-minute walk<br>* 6-minute walk<br>Diagnostic Test: CT scan<br>* CT scan<br>Other: Medical Research Council dyspnea scale (MRC)<br>* MRC questionnaire<br>Other: St. George's Respiratory Questionnaire (SGRQ)<br>* SGRQ questionnaire<br>Other: COPD Assessment Test (CAT)<br>* CAT questionnaire<br>Other: Pittsburgh Sleep Quality Index (PSQI)<br>* PSQI questionnaire<br>Other: CASA-Q<br>* CASA-Q questionnaire<br>Other: Spirehealth Tag Device<br>* Subjects will wear the Spirehealth Tag Device to measure heart rate, respiratory rate, sleep time, physical activity (movement), and calories burned with activity.<br>|
| Active Comparator: Control Group<br>Subjects will complete MRC, SGRQ, CAT, and PSQI questionnaires. They will do spirometry, 6-minute walk, and CT scan. These interventions will be done at baseline and at the completion of their study (6 weeks). Spirehealth Device will be worn by subject daily for 12 weeks. | Diagnostic Test: Spirometry<br>* Pre and post spirometry using albuterol.<br>Diagnostic Test: 6-minute walk<br>* 6-minute walk<br>Diagnostic Test: CT scan<br>* CT scan<br>Other: Medical Research Council dyspnea scale (MRC)<br>* MRC questionnaire<br>Other: St. George's Respiratory Questionnaire (SGRQ)<br>* SGRQ questionnaire<br>Other: COPD Assessment Test (CAT)<br>* CAT questionnaire<br>Other: Pittsburgh Sleep Quality Index (PSQI)<br>* PSQI questionnaire<br>Other: CASA-Q<br>* CASA-Q questionnaire<br>Other: Spirehealth Tag Device<br>* Subjects will wear the Spirehealth Tag Device to measure heart rate, respiratory rate, sleep time, physical activity (movement), and calories burned with activity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dyspnea Change | Medical Research Council Dyspnoea Questionnaire (MRC)will be done at baseline and completion of study. The questionnaire asks subjects to rate between 0-4 how breathless they get during activity, with examples of each score. 0 being breathless only with strenuous exercise and 4 being too breathless to leave the house or when dressing. | 6 weeks | 
| Health Related Quality of Life Change using the CAT Questionnaire | COPD Assessment Test (CAT) Questionnaires will be done at baseline and completion of study. This questionnaire will collect information regarding the subject's belief on the impact COPD is having on the wellbeing and daily life. | 6 weeks | 
| Health Related Quality of Life Change using the SGRQ Questionnaire | St. George's Respiratory Questionnaire (SGRQ) will be done at baseline and completion of study. The SGRQ collects information about which aspects of the subject's illness cause them the most problems and how often the subject reports experiencing the symptoms. | 6 weeks | 
| Sleep Quality using the PSQI Questionnaire | Pittsburgh Sleep Quality Index (PSQI) Questionnaires will be done at baseline and completion of study. This questionnaire will be used to collect information regarding the subject's usual sleep habits during the past month. | 6 Weeks | 
| Spirometry | Change in spirometry measurements | 6 weeks | 
| 6 minute walk | Change in 6 minute walk distance | 6 weeks |