Trial Outcomes & Findings for Capnography-Assisted Learned Monitored (CALM) Breathing Therapy for COPD (NCT NCT04786184)

NCT ID: NCT04786184

Last Updated: 2024-07-03

Results Overview

Attendance rate will be measured from the total number of sessions completed out of the 8 total.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 42 participants
• Primary outcome timeframe: 4 weeks
• Results posted on: 2024-07-03

Participant Flow

Participant milestones

Measure	CALM Breathing CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Overall Study STARTED	20	22
Overall Study Randomized	20	22
Overall Study Started Pulmonary Rehab	11	18
Overall Study COMPLETED	9	19
Overall Study NOT COMPLETED	11	3

Reasons for withdrawal

Measure	CALM Breathing CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Overall Study Adverse Event	4	0
Overall Study Withdrawal by Subject	3	1
Overall Study Lost to Follow-up	4	2

Baseline Characteristics

Capnography-Assisted Learned Monitored (CALM) Breathing Therapy for COPD

Baseline characteristics by cohort

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.	Total n=42 Participants Total of all reporting groups
Age, Continuous	72 years STANDARD_DEVIATION 7 • n=5 Participants	70 years STANDARD_DEVIATION 12 • n=7 Participants	71 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	18 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Supplemental Oxygen (home use)	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: This outcome measure is only measuring attendance for individuals who received the CALM breathing intervention.

Attendance rate will be measured from the total number of sessions completed out of the 8 total.

Outcome measures

Measure	CALM Breathing n=19 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Mean Attendance Rate of CALM Breathing Treatment Sessions	84.2 percentage of completed sessions Interval 0.0 to 100.0	—

PRIMARY outcome

Timeframe: 3 months

Population: This outcome measure is only looking to measure the drop-out rate for the CALM Breathing arm.

The drop-out rate will be calculated from the total number of participants who drop-out from receiving the CALM Breathing therapy.

Outcome measures

Measure	CALM Breathing n=19 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Drop-Out Rate	1 Participants	—

PRIMARY outcome

Timeframe: 4 weeks

Population: Only data from the 17 participants who completed the satisfaction questionnaire from the CALM Breathing arm was collected and analyzed.

The acceptability of the CALM Breathing therapy will be evaluated based on mixed methods data collected from CALM Breathing satisfaction ratings.

Participants were asked item 8 of FACIT ("how do rate this treatment overall?"), which was rated from 0 to 4 (0 = "poor" and 4 = "excellent") in which higher scores indicate more satisfaction (better outcome).

Outcome measures

Measure	CALM Breathing n=17 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
CALM Breathing Satisfaction Rating	2 score on a scale Interval 0.0 to 4.0	—

SECONDARY outcome

Timeframe: Baseline, 4 weeks, 3 months

This questionnaire measures the impact of chronic obstructive pulmonary disease (COPD) on a person's life. It consists of 20 items across 4 domains (dyspnea, fatigue, emotional function, and master). Items are on a 7-point Likert scale (1 - 7) and are scored from 1 (most severe) to 7 (no impairment) (better outcome). For this trial, questions 4a- 4e are included which is the dyspnea domain. The 5 scores are summated and divided by the number of items. The range is 1-7. Higher scores indicate better outcomes.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Chronic Respiratory Disease Questionnaire (CRQ) Score Baseline	4.63 score on a scale Standard Deviation 1.5	4.06 score on a scale Standard Deviation 1.42
Chronic Respiratory Disease Questionnaire (CRQ) Score 4 weeks	5.24 score on a scale Standard Deviation 1.26	4.19 score on a scale Standard Deviation 1.25
Chronic Respiratory Disease Questionnaire (CRQ) Score 3 months	4.94 score on a scale Standard Deviation 1.45	4.31 score on a scale Standard Deviation 1.60

SECONDARY outcome

Timeframe: 4 weeks

The DMQ-CAT is a 71-item questionnaire that measures dyspnea anxiety. Raw scores range from 0 (low) to 6 (high). These raw scores are converted into T-scores with a mean score of 50 and a standard deviation of ±10. The full range of T-scores is 0 to 100 for DMQ-CAT Self-Efficacy, DMQ-CAT Intensity and DMQ-CAT Anxiety scales. The DMQ-CAT software automatically scores these scales. Higher scores indicate better outcomes.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Dyspnea Management Questionnaire Computer Adaptive Test (DMQ-CAT) Score DMQ-CAT Self-Efficacy	54.9 T-score Standard Deviation 6.1	53 T-score Standard Deviation 7
Dyspnea Management Questionnaire Computer Adaptive Test (DMQ-CAT) Score DMQ-CAT Intensity	57 T-score Standard Deviation 8	54 T-score Standard Deviation 10
Dyspnea Management Questionnaire Computer Adaptive Test (DMQ-CAT) Score DMQ-Anxiety	58 T-score Standard Deviation 7	52.1 T-score Standard Deviation 6

SECONDARY outcome

Timeframe: 3 months

The DMQ-CAT is a 71-item questionnaire that measures dyspnea anxiety. Raw scores range from 0 (low) to 6 (high). These raw scores are converted into T-scores with a mean score of 50 and a standard deviation of ±10. The full range of T-scores is 0 to 100 for DMQ-CAT Self-Efficacy, DMQ-CAT Intensity and DMQ-CAT Anxiety scales. The DQM-CAT software automatically scores these scales. Higher scores indicate better outcomes.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Dyspnea Management Questionnaire Computer Adaptive Test (DMQ-CAT) Score DMQ-CAT Self-Efficacy	54.9 T-score Standard Deviation 5.8	54.0 T-score Standard Deviation 8.0
Dyspnea Management Questionnaire Computer Adaptive Test (DMQ-CAT) Score DMQ-CAT Intensity	55.0 T-score Standard Deviation 10.0	53.0 T-score Standard Deviation 12.0
Dyspnea Management Questionnaire Computer Adaptive Test (DMQ-CAT) Score DMQ-Anxiety	57 T-score Standard Deviation 8	52.7 T-score Standard Deviation 6

SECONDARY outcome

Timeframe: 4 weeks

The Modified Borg Scale is most commonly used to assess symptoms of breathlessness. On the 11-item scale, a score of 0 indicates "No Exertion" and a score of 10 indicates "Maximal" exertion (10-point scale). The full range is 0-10 for Borg-Dyspnea and Borg-Fatigue. Higher scores indicate worse outcomes (i.e. more exertion).

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Modified Borg Scale Score Borg Dyspnea	4 score on a scale Standard Deviation 2	5 score on a scale Standard Deviation 4
Modified Borg Scale Score Borg Fatigue	3 score on a scale Standard Deviation 3	5 score on a scale Standard Deviation 4

SECONDARY outcome

Timeframe: 3 months

The Modified Borg Scale is most commonly used to assess symptoms of breathlessness. On the 11-item scale, a score of 0 indicates "No Exertion" and a score of 10 indicates "Maximal" exertion (10-point scale). The full range is 0-10 for Borg-Dyspnea and Borg-Fatigue. Higher scores indicate worse outcomes (i.e. more exertion).

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Modified Borg Scale Score Borg Dyspnea	3 score on a scale Standard Deviation 2	5 score on a scale Standard Deviation 2
Modified Borg Scale Score Borg Fatigue	2 score on a scale Standard Deviation 3	4 score on a scale Standard Deviation 3

SECONDARY outcome

Timeframe: 3 months

Population: Data was not collected.

The General Anxiety Disorder-7 is a 7-item screening tool and symptom severity measure for the four most common anxiety disorders. This is calculated by assigning scores of 0 ("not at all"), 1 ("several days'), 2 ("more than half the days"), or 3 ("nearly every day"). GAD-7 total score for the seven items ranges from 0 to 21. Higher scores indicate worse outcomes (i.e. greater anxiety).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 4 weeks, 3 months

The PSS is a 10-item classic stress assessment instrument. Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Perceived Stress Scale Score (PSS) Baseline	12 score on a scale Standard Deviation 9	18 score on a scale Standard Deviation 7
Perceived Stress Scale Score (PSS) 4 weeks	13 score on a scale Standard Deviation 9	21 score on a scale Standard Deviation 8
Perceived Stress Scale Score (PSS) 3 months	10 score on a scale Standard Deviation 8	19 score on a scale Standard Deviation 7

SECONDARY outcome

Timeframe: Baseline, 4 weeks, 3 months

This is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
6 Mile Walking Distance Score (6MWT) Baseline	304 meters Standard Deviation 86	341 meters Standard Deviation 109
6 Mile Walking Distance Score (6MWT) 4 weeks	283 meters Standard Deviation 106	319 meters Standard Deviation 121
6 Mile Walking Distance Score (6MWT) 3 months	295 meters Standard Deviation 109	369 meters Standard Deviation 94

SECONDARY outcome

Timeframe: 3 months

Population: Data was not collected for this analysis.

This 12-item questionnaire uses frequency, duration, and intensity level of activity over the previous week to assign a score, ranging from 0 to 793, with higher scores indicating greater physical activity.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 4 weeks, 3 months

The CAT quantifies the impact of COPD symptoms on patients' overall health. Participants assign a score ranging from 0 to 5 for each of the 8 areas. A score of 0 means there is no impairment in that area. A score of 5 means severe impairment. The overall score will range from 0 to 40. The score is a composite score.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Change in COPD Assessment Test (CAT) Score Change from Baseline to 4 weeks	1 score on a scale Standard Deviation 37	19 score on a scale Standard Deviation 5
Change in COPD Assessment Test (CAT) Score Change from Baseline to 3 months	-6 score on a scale Standard Deviation 47	7 score on a scale Standard Deviation 35

SECONDARY outcome

Timeframe: 4 weeks

This is a 10-item tool used to measure patient-reported outcomes (PROs) relevant across common medical conditions. The response options are presented as a 5-point rating scale, with higher scores indicating a healthier patient (better outcome). Scores are standardized to the general population using the "T-Score", with the average T-score for the US population is 50 points, with a SD of 10 points. This applies to PROMIS Social, PROMIS Fatigue, PROMIS Physical, and PROMIS Sleep Disturbance.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Patient-Reported Outcomes Measurement Information System (PROMIS-24). PROMIS Social	52 T-score Standard Deviation 10	45 T-score Standard Deviation 11
Patient-Reported Outcomes Measurement Information System (PROMIS-24). PROMIS Fatigue	48 T-score Standard Deviation 12	59 T-score Standard Deviation 12
Patient-Reported Outcomes Measurement Information System (PROMIS-24). PROMIS Physical	40.1 T-score Standard Deviation 6.6	36 T-score Standard Deviation 7
Patient-Reported Outcomes Measurement Information System (PROMIS-24). PROMIS Sleep Disturbance	50.9 T-score Standard Deviation 6.9	54.7 T-score Standard Deviation 6.4

SECONDARY outcome

Timeframe: 3 months

This is a 10-item tool used to measure patient-reported outcomes (PROs) relevant across common medical conditions. The response options are presented as a 5-point rating scale, with higher scores indicating a healthier patient (better outcome). Scores are standardized to the general population using the "T-Score", with the average T-score for the US population is 50 points, with a SD of 10 points. This applies to PROMIS Social, PROMIS Fatigue, PROMIS Physical, and PROMIS Sleep Disturbance.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Patient-Reported Outcomes Measurement Information System (PROMIS-24). PROMIS Social	52 T-score Standard Deviation 11	45 T-score Standard Deviation 9
Patient-Reported Outcomes Measurement Information System (PROMIS-24). PROMIS Fatigue	52 T-score Standard Deviation 12	59 T-score Standard Deviation 10
Patient-Reported Outcomes Measurement Information System (PROMIS-24). PROMIS Physical	39.4 T-score Standard Deviation 7.2	38 T-score Standard Deviation 7
Patient-Reported Outcomes Measurement Information System (PROMIS-24). PROMIS Sleep Disturbance	51.3 T-score Standard Deviation 6.6	54.4 T-score Standard Deviation 5.5

SECONDARY outcome

Timeframe: Baseline, 4 weeks, 3 months

This measures the partial pressure of CO2 at the end of an exhaled breath.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
End-tidal CO2 Baseline	30 mmHg Standard Deviation 7	32.5 mmHg Standard Deviation 5.4
End-tidal CO2 4 weeks	34 mmHg Standard Deviation 8	31.1 mmHg Standard Deviation 6.0
End-tidal CO2 3 months	31 mmHg Standard Deviation 6	29.8 mmHg Standard Deviation 3.7

SECONDARY outcome

Timeframe: Baseline, 4 weeks, 3 months

Pulmonary Rehabilitation Engagement will be measured using the Patient Activation Measure (PAM), which is a 10 or 13 item questionnaire that measures patients on a 0-100 scale and can segment patients into one of four activation levels along an empirically derived continuum. Each activation level reveals insight into an array of health-related characteristics, including attitudes, motivators, behaviors, and outcomes. A higher score indicates a better outcome.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Patient Activation Measure (PAM) Score Baseline	45 score on a scale Standard Deviation 5	43 score on a scale Standard Deviation 5
Patient Activation Measure (PAM) Score 4 weeks	45 score on a scale Standard Deviation 6	42 score on a scale Standard Deviation 6
Patient Activation Measure (PAM) Score 3 months	46 score on a scale Standard Deviation 5	44 score on a scale Standard Deviation 5

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 4 weeks, 3 months

The SEBQ contains 12 items and assesses the patient's perception of their breathing difficulties and gives an insight into the effort of breathing and the feeling of air hunger. Responses to these items are on a 4-point Likert scale: (0) never/not true at all; (1) occasionally/a bit true; (2) frequently-mostly true; and, (3) very frequently/very true. SEBQ scores for sum of the original items ranged from 0 to 36, with a lower total indicating a better outcome.

Outcome measures

Measure	CALM Breathing n=20 Participants CALM Breathing: CALM Breathing is a mind-body breathing therapy that links CO2 changes to dyspnea and anxiety symptoms and targets breathing efficiency and self-efficacy in COPD. CALM Breathing: Individual interoception- based breathing therapy with capnography (non- exercise training) Home Program: Monitored home- based breathing exercises; RR biofeedback; goal setting; exercise logging. Coaching: Motivational interviewing. Personnel: PT, EP, occupational therapist, or nurse. Frequency: 1-hour sessions, twice per week for 4 weeks. Exercises: • 10 core breathing exercises with ETCO2 biofeedback in recovery postures at rest and with body movement (gentle stretches and brief low-moderate intensity physical activity). • Breathing biofeedback (ETCO2, RR, airflow pattern). Education: Education on anxiety; COPD Patient Guide.	Wait-List Control n=22 Participants Traditional outpatient PR: After referral to Columbia's outpatient pulmonary rehabilitation (PR) program, participants randomized to the Wait-List control group will be put on a PR wait list (usual care). In Phase II, all participants will receive PR of 1-hour sessions, twice per week for 10 weeks. Traditional outpatient PR: Group exercise training (ET) combined with pursed lips breathing (PLB) training; 1:2 therapist to patient ratio. Home Program: Unmonitored walking exercise 1-2 days/week; no biofeedback monitoring. Coaching: Traditional monitoring and verbal cueing. Personnel: PT or EP. Frequency: 1-hour sessions, twice per week for 10 weeks. Exercises: • ET of muscles of ambulation with exercise equipment, such as on a treadmill or cycle ergometer (30-min), plus 15-min strengthening and posture exercises; O2 supplementation as needed. No breathing biofeedback. • PLB instruction only during exercise training. Education: Verbal and written information.
Self-Evaluation of Breathing Questionnaire (SEBQ) Score Baseline	12 score on a scale Standard Deviation 8	19 score on a scale Standard Deviation 7
Self-Evaluation of Breathing Questionnaire (SEBQ) Score 4 weeks	11 score on a scale Standard Deviation 9	17 score on a scale Standard Deviation 6
Self-Evaluation of Breathing Questionnaire (SEBQ) Score 3 months	11 score on a scale Standard Deviation 9	17 score on a scale Standard Deviation 8

Adverse Events

All Participants

Serious events: 5 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	All Participants n=42 participants at risk All AEs that occurred for any study participant was recorded but not stratified per arm. AEs were not collected per arm and therefore stratified data is not available.
Cardiac disorders Chest Tightness	2.4% 1/42 • Number of events 1 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.
Renal and urinary disorders Hospitalization due to Missed Hemodialysis	2.4% 1/42 • Number of events 1 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.
Respiratory, thoracic and mediastinal disorders Pulmonary Edema	2.4% 1/42 • Number of events 2 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.
Infections and infestations COVID-19 Infection	4.8% 2/42 • Number of events 2 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.

Other adverse events

Measure	All Participants n=42 participants at risk All AEs that occurred for any study participant was recorded but not stratified per arm. AEs were not collected per arm and therefore stratified data is not available.
Infections and infestations Stomach Flu	2.4% 1/42 • Number of events 1 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.
Social circumstances Anxiety	2.4% 1/42 • Number of events 1 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.
Respiratory, thoracic and mediastinal disorders COPD Requiring Modified Treatment	14.3% 6/42 • Number of events 6 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.
Infections and infestations UTI	2.4% 1/42 • Number of events 1 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.
General disorders Sleepiness	2.4% 1/42 • Number of events 1 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.
General disorders Fall (outdoors)	2.4% 1/42 • Number of events 1 • AE data was collected over 3 months from baseline or until the participants completed/withdrew from the study.

Additional Information

Annamaria Norweg, PhD

Columbia University

Phone: 212-305-1651

Email: amn2212@cumc.columbia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place