HHHFA in COPD Patients, With Chronic Bronchitis
HHHFA in 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.

 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.
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.
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