A Home-based Intervention to Promote Mindful Breathing Awareness Through Pursed-lip Breathing Training for COPD Patients
Phase: PHASE3
Conditions: COPD
Sponsor: Mayo Clinic

 
 
A home-based intervention to promote mindful 
breathing awareness through pursed-lip 
breathing 
training for COPD patients 
 
NCT04517500 
 
June 8, 2021 

 
 
 
 
 
 
 
 
 
 
 
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General Study Information 
 
Principal Investigator:  Roberto Benzo, MD  
 
 
 
 
 
 
 
 
Study Title:    A home-based intervention to promote mindful breathing awareness through pursed-lip breathing 
training for COPD patients, IRB19-012772 
 
Protocol version number and date:   June 8, 2021, Version 3 
 
Research Question and Aims 
 
Hypothesis:   
We hypothesize that providing COPD patients with a mindful breathing module that is easy-to-use, prompts 
them to complete daily mindful breathing practice, and provides feedback will improve their breathing 
mechanics, emotional awareness, increase the time that they spend in heart rate coherence, and improve their 
quality of life. 
 
Aims, purpose, or objectives:    
The primary outcomes of the study are changes in breathlessness and emotions. Changes from baseline 
to three months on the two primary outcomes will be compared between the study arms using two-sample, two-
sided t-tests with 5% type I error rates. Means, SDs, medians, ranges, and frequency distributions will be 
reported and plotted over time by study arm. Linear models will be used to assess the impact of treatment arm 
on three-month outcomes after adjusting for the corresponding baseline measure and other variables related to 
the outcome (age, degree of breathlessness at baseline using the mMRC dyspnea, and FEV1). 
 
Background:   
COPD:   
COPD is a progressive lung disease that makes breathing difficult. Breathlessness usually worsens over time 
and eventually may make it difficult for people to carry out regular, simple daily activities, and cause anxiety 
and depressive symptoms. (8,35)  In the United States COPD is the fourth leading cause of death and continues 
to increase.(2-6)  It is also the third leading cause of hospital readmission in the US. There are currently an 
estimated 16 million Americans diagnosed with COPD(36)  and many millions more who are believed to have 
the disease and not know it.37,38 It is estimated that the direct costs of COPD in the United States are $29.5 
billion and the indirect costs $20.4 billion.(39) 
COPD is demanding for the individual patient due to breathlessness (dyspnea) that increases during the more 
severe stages of the disease and impairs quality of life.(7,40) Breathlessness is the most common symptom and 
the use of pharmacological treatments alone is not effective; thus, additional non-pharmacological approaches 
such as breath retraining exercises are suggested.(7) Anxiety and emotional symptoms are frequently associated 
with symptoms of breathlessness/dyspnea and the cause of higher health care utilization.(40,41) 
 
Pulmonary Rehabilitation (PR): 
 PR is an intervention that combines the promotion of physical activity and self-management. (42) It is regarded 
as an essential component of care for people with COPD and is supported by strong scientific evidence. (43-46) 

 
 
 
 
 
 
 
 
 
 
 
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PR reduces dyspnea, shortness of breath (13, 14), increases functional exercise capacity (13, 14), improves 
patients’ health status and sense of control over their condition (13, 14), improves health-related quality of life 
(14), and reduces anxiety and depression associated with COPD (14). It also reduces acute exacerbations as well 
as decreases hospital bed days, the number of hospital admissions (47), and the overall burden on the health 
system. (14, 47-59) 
 
Breathing Practice:  
Breathing practice is an important component of PR. A commonly taught technique, pursed-lipped breathing 
(PLB) consists of instructions to breathe through the nose like smelling a flower without forcing and exhale 
slowly through the mouth while pursing the lips, as if they are blowing out a candle. Patients are taught to 
concentrate on the breath and nothing else, like meditation. PLB can ease dyspnea (20-23,51,60) which is the 
most disabling symptom of COPD(7), a common reason for seeking medical attention(7), and may cause people 
to limit their activity.(1)  PLB can prevent the large airways from collapsing and can cause the release of more 
air from the lungs on exhale reducing dynamic hyperinflation. (24)  Current guidelines for COPD suggest that 
using PLB also has positive effects in treating stress and anxiety related disorders(25)  and it has an acute 
benefit to  exercise capacity and parasympathetic outflow (stress).(26) Spontaneous pursed lips breathing can be 
a useful technique to increase walking endurance and reduce oxygen desaturation during walking in patients 
with moderate to severe COPD.(27)  In a study of PLB with 16 COPD patients, researchers found that while 
practicing PLB patients had a significant decrease in respiratory rate and a significant increase in pulse oxygen 
saturation.(28) These effects have been demonstrated in previous studies.(29-32)  However, there has been 
some variability found in the effects PLB, which may be due to difficulty in tracking compliance at home and 
the need for ongoing guidance by a respiratory health care professional. (22)  Physicians and physical, 
occupational, and rehabilitation therapists teach PLB to their patients to ease shortness of breath; however, the 
benefits are short lived and up to 50% of patients lose them due to the lack of practice.61 Research suggests that 
regular practice of PLB may result in long-term benefit. Patients who participated in weekly PLB training (at a 
lab) demonstrate  improvement after 12 weeks in exertional dyspnea and physical function.(62)  Mindful PLB is 
a critical teaching   ring PR as it’s a practice that improves breathing mechanics, oxygenation and emotional 
buoyancy during breathlessness episodes. There is no remote system to foster the home practice of mindful 
PLB. (40) 
 
Cardiovascular Benefits of mindful PLB:   
 A guided breathing practice can have significant benefit in the cardiovascular system, the source of the most 
prevalent comorbidities in COPD. Briefly, the heart has a natural variation, from minute to minute, beat to beat 
– even sitting at rest. This phenomenon, known as Heart Rate Variability (HRV) is a sign of health, the greater 
the variability, the better the health. Heart rate is intimately tied to the bodily expression of emotions: in states 
of anxiety, fear, and sadness, extremely prevalent in patients with COPD (33, 63-66), the variation tends to be 
disordered and chaotic. On the contrary in positive emotional states such as gratitude, the variation tends to be 
rhythmic. This state of rhythmic variation is known as Heart Coherence (HRC). (67) 
 
When the heart is in a state of coherence, HRV synchronizes with the breath – a phenomenon known as 
Respiratory Sinus Arrhythmia. HRC is much more than a state of relaxation. It represents a dynamic balance 
within the Autonomic Nervous System and its two branches, the sympathetic and the parasympathetic, which 
work on the heart like an accelerator and brake respectively. On the in-breath, the sympathetic branch 
(accelerator) is active, and heart rate increases, while on the out-breath, the parasympathetic branch (brake) is 

 
 
 
 
 
 
 
 
 
 
 
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active, and the heart slows. Healthy heart rhythms have a beneficial effect on the emotional brain. Thus, HRC 
facilitates positive emotion and weakens negative emotion and improves thinking: cognitive performance can 
be faster and more accurate. HRC is not present all the time, but a few quiet periods of coherent heart breathing 
at various "breaks" in the day will be restorative and balancing. 
Dysfunctional breathing patterns, such as in patients with COPD, are not only biomechanically inefficient but 
also reflect decreased physiological resilience. (68)  Slow breathing with biofeedback assists patients in 
spending 
more time in an optimal heart rate variability pattern for health.(68-70) HRV biofeedback has been used in the 
treatment of multiple chronic diseases, including COPD.(68,69,71,72)  The use of biofeedback, to guide the 
user to breathe more deeply, has reported positive effects on dyspnea in patients with COPD,(22) as well as 
symptoms and quality of life in heart failure and hypertension.(73)  The use of biofeedback assists patients in 
achieving a state of mindfulness as it helps them to stay focused on the present, provides a concrete goal and 
motivation. 
The proposed HRV biofeedback training will provide patients with information on an on-going basis allowing 
the patient to see the effects of effort on HRC. Using HRV biofeedback training, most individuals with COPD 
may learn to engage in slow, effortless PLB (24) that will put them in a state of HRC and reduce dyspnea. The 
proposed system is critical to creating the “habit” of mindful breathing. Once the technique is learned, and the 
specific practice of breathing awareness is a habit, the individual no longer needs the support of biofeedback. 
 
Health Coaching:  
A key component of the researchers’ PR program is health coaching. Health coaching has demonstrated 
effectiveness in facilitating patient improvement in various aspects of health (74-79) by affecting patients’ 
knowledge, skill, self-efficacy, and behavior change (74). Health coaching utilizes motivational interviewing 
and goal-setting to facilitate behavior change. (80,81) Health coaching is a critical component of the current 
Chronic Care Model that involves patient-clinician collaboration and empowers patients to take on an active 
role in managing their health conditions and make important health behavior changes. The conceptual 
foundation of health coaching is Social Cognitive (Learning) Theory.(82)  Health coaching has demonstrated 
effectiveness in improving patient health outcomes, including health behaviors.(83) In our previous awards we 
demonstrated the “boosting effect” of health coaching in PR and care of COPD.(84-87) 
Regular feedback on a patient’s health status and progress is central to the self-awareness that leads to behavior 
change and is also needed for proper coaching. (52)  Since it is not practical or reliable (53) to collect this 
information daily from each patient, systems that transmit the necessary data to the health care professionals are 
needed. Multiple studies have found that providing regular feedback to the participant is effective in supporting 
behavior change. (54) Personalized feedback is more effective and preferred by patients.(54,55)   In one study 
of  COPD patients, there were clinically and statistically significant improvements in walking, QOL, self-
efficacy, disability, dyspnea, and heart rate variability after using biofeedback on heart rate variability and 
feedback from pulse oximetry for 10 weeks.(56) 
 
Existing PR system: 
The existing PR system consists of an Android Computer tablet with Verizon service, a Nonin Pulse Oximeter 
and a Garmin Vivofit activity tracker.   The home-based PR program is pinned on the Android tablet so that it is 
the home screen when the participant turns on the computer tablet and is the only accessible program on the 
computer tablet.  The computer tablet is preloaded with a daily to-do list, daily exercises and daily questions.   
 

 
 
 
 
 
 
 
 
 
 
 
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The Nonin Pulse Oximeter and the Garmin Vivofit are connected to the Android tablet via blue tooth.  A health 
coach at Mayo Clinic has access to the data through a health coach application.   
 
 
Pursed Lipped Breathing Module: 
Minnesota Health Solutions and Spire Health will design and integrate a PLB module and integrate it with the 
existing home-base PR system (currently in use in 18-002453 and 17-009449, previously used in 14-00906).  
The Mindful Breathing Lab (Dr. Benzo) will complete a randomized control trial to evaluate the mindful 
breathing module.   The study will evaluate the home-based PR system compared to the home-based PR system 
plus the mindful breathing module for its effects on breathlessness and emotions.  
 
A mindful breathing module was created and tested for feasibility in IRB 17-004445. In this study, while 
wearing the Nonin Pulse Oximeter, participants inhale and exhale while following an animated ball.  During an 
inhale, the ball climbs up a short hill, during the exhale the ball moves down a longer hill promoting pursed 
lipped breathing.  The inhale duration is 2 seconds while the exhale duration increases from 2 to 8 seconds.  The 
participant can tap the TOO DIFFICULT button the exhale duration will stop increasing.   Please see figure 1 
for an image of the mindful breathing module.   In the new mindful breathing module, the breathing rate will be 
collected by the Spire Health Tag.  
 
 
 
Spire Health Tags: 
The Intervention system will incorporate the Spire Health Tag 
.  Each health tag contains a battery, tri-axis accelerometer, blue tooth radio, vibro-tactile feedback 
mechanism, photo plethysmography sensor, and force sensor to sense relative changes in abdominal and/or 
thoracic excursion.  The health Tags can pick up respiration, pulse rate, activity and sleep duration and quality.  
The Health Tags adhere to existing clothing, can withstand the washer/dryer and last for about a year without 
charging.  The tags are attached to clothes that are worn most like bras, underwear or athletic wear.  The Health 
tags are attached with a fabric adhesive and can be removed by peeling the unit off.  The Spire Health Tags will 
be integrated with the existing home-based PR system.  Please see Figure 2 for images of the Health Tag. 
 
Figure 1 

 
 
 
 
 
 
 
 
 
 
 
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Study Design and Methods 
 
Methods: 
This project will involve two Phases: phase one in which mindful breathing by itself without any other 
device will be tested to make sure that is acceptable to patients and make a difference comparing to the 
usual protocol in use right now. Phase two will include a particular device that will guide the mindful 
breathing practice that we think will be more intuitive to practice and guide the mindful breathing and 
that device will be tested once we know that the acceptance to the mindful breathing practice, from phase 
one,  is appropriate. 
 
Phase 1:  A total of 70 adults diagnosed with COPD will be enrolled in the study.  Half of the participants will 
be randomized to receive the home-based PR with the Pursed Lipped Breathing Application (intervention) and 
half will receive the home-based PR (control).  Randomization will take place in a REDCap database and will 
be in equal proportion. 
 
Figure 2 

 
 
 
 
 
 
 
 
 
 
 
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Phase 2: A total of 70 adults diagnosed with COPD will be enrolled in the study.  Half of the participants will 
be randomized to receive the home-based PR with the mindful breathing module which consists of the Pursed 
Lipped Breathing Application and the Spire Health Tags (intervention) and half will receive the home-based PR 
(control).     Randomization will be take place in a REDCap database and will be in equal proportion.   
 
Both groups entail one week of baseline where the participants wear an ActiGraph activity tracker and answer 
questionnaires.  Baseline is followed by 12 weeks of home-based PR plus health coaching.   The Intervention 
group also has the mindful breathing module loaded on the Android tablet.  Both groups will also complete 
questionnaires and wear an ActiGraph activity monitor at 3 and 6 months. 
 
Please see Figure 3 for a diagram of the intervention and Figure 4 for a diagram of the control scheme. 
 
 
 
 
 
 
 
 
Figure 3 
Intervention  

 
 
 
 
 
 
 
 
 
 
 
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Questionnaires:   
Quality of Life will be assessed three times (baseline, 3 and 6 months) by the Medical Research Council 
(mMCR) questionnaire, the Chronic Respiratory Disease Questionnaire (CRQ), the Self-Management Ability 
Scale (SMAS30)  and the Mindful Attention and Awareness Scale (MAAS).  The questionnaires take about 20 
minutes to complete. 
At baseline additional health data will be collected from the medical record (chart review)  to complete the 
Charlson comorbidity index, including lung function, demographics, living condition (living alone or not), 
GOLD stage, and comorbidities. 
 
ActiGraph:  
Physical activity will be measured three times (baseline, 3 and 6 months) by the ActiGraph activity monitor.  
The ActiGraph activity monitor has tri-axial accelerometers and will be wrist worn for seven days.  See Figure 
5.  Important measures to be analyzed are daily number of steps,  activity counts, minutes per day spent in daily 
physical activities of at least moderate intensity, and sedentary time (<2 metabolic equivalents).
 
Figure 4 
Control 
Figure 5 

 
 
 
 
 
 
 
 
 
 
 
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The questionnaires and Act Graphs will be mailed to the participant with pre-paid shipping materials to send 
back.   
 
Health Coaching: 
All participants will receive a weekly coaching call to discuss their rehabilitation and health process.  The calls 
are structured using motivational interviewing.   The coach will review with the patient the data from the health 
coach system.  Collaboratively, goals for rehabilitation for the following week will be set, based on information 
gathered and the patients’ personal preferences.  Each call lasts about 20 minutes.  All calls will be taped to 
ensure compliance with the protocol.   
 
 
Subject Information 
 
 
Target accrual: 140 
 
Subject population (children, adults, groups):  Adults 40 years of age or older 
 
Inclusion Criteria:  
• Clinical diagnosis of COPD 
• At least 10 pack years of smoking 
 
 
Exclusion Criteria:   
• Unable to do mild exercise (orthopedic-neurologic problems or confined to a bed) 
• Unable to follow commands (cognitive impairment) 
• Have a high likelihood of being lost to follow-up (active alcohol or drug abuse)   
• Live in an area that does not have cellular service (Verizon) 
 
Potential participants will have the option of meeting a study coordinator in person (if they are on campus for a 
clinical appointment), meeting via Video Anywhere through Epic, or meeting over the phone.  If the patient 
desires, their consent can be digitally obtained and documented through PTRAX.  The patient also has the 
option of receiving the consent via mail and mailing back the consent in a provided postage paid envelope.  
Documentation of informed consent/HIPAA authorization will involve the use of the 
Research Participant Tracking (PTrax) Digital Signature Capture technology for research 
informed consent/HIPAA authorization forms. This is an institutionally approved process 
for documenting consent/HIPAA authorization only while the subject, and/or the subject’s 
representative, is in the physical presence of the person authorized to obtain 
consent/HIPAA authorization. The study team may print a copy of the signed consent 
form/HIPAA authorization form for the subject or their representative. The consent 
form/HIPAA authorization form will also be available to the subject via the patient 
portal. Note: If the subject or their representative prefers not to use the Digital 
Signature Capture technology, the study team will provide a paper consent form/HIPAA 
authorization form for signature. 
 

 
 
 
 
 
 
 
 
 
 
 
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Review of medical records, images, specimens  
 
 
  The study involves data that exist at the time of IRB submission and data that will be generated after IRB 
submission. Include this activity in the Methods section.  
The study plans to conduct a retrospective chart review and ask subjects to complete a questionnaire.  
 
 
 
 
 
 
Data Analysis 
 
 
Sample Size 
 
We calculated that sixty two participants will provide 80% power to detect 1 point of change in the two co 
primary outcomes (breathlessness and emotion as measured by the CRQ) with an alpha of 0.025. A 1 point 
change represents a clinically meaningful change.95  We expect about a 20 percent attrition rate (withdraw, not 
able to complete the 12 weeks of home-based rehab) and will therefore enroll 70 participants in each phase.  
 
Analysis Plan 
The primary outcomes of the study are changes in breathlessness and emotions. Changes from baseline to three 
months on the two primary outcomes will be compared between the study arms using two-sample, two-sided t-
tests with 5% type I error rates. Means, SDs, medians, ranges, and frequency distributions will be reported and 
plotted over time by study arm. Linear models will be used to assess the impact of treatment arm on three-
month outcomes after adjusting for the corresponding baseline measure and other variables related to the 
outcome (age, degree of breathlessness at baseline using the mMRC dyspnea, and FEV1). 
 
The Chronic Respiratory Disease Questionnaire (CRQ) is a 20-question inventory assessing the areas of 
dyspnea, fatigue, emotion, and feelings of mastery. The fatigue, emotion, and mastery subscales ask patients to 
rate how often in the last two weeks they have been afflicted with a particular feeling or experience on a scale 
of 1 to 7, with higher ratings indicating less symptom impairment. The CRQ has shown to be valid and has high 
internal consistency reliability. Test-retest reliability is adequate in all subscales, but is particularly high in the 
subscales of fatigue (r=0.90), emotion (r=0.93), and mastery (r=0.91). The minimal clinically important 
difference for this instrument of 0.5 points is universally recognized. The Domains Dyspnea (breathlessness) 
and Emotions are the two co primary outcomes. 
Physical activity will be measured at baseline, 3, and 6 months by the ActiGraph GX6 activity monitor, which 
has been used to assess physical activity in COPD populations. (92)  The number of daily steps at baseline, 3, 

 
 
 
 
 
 
 
 
 
 
 
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and 6 months and across the two groups will be compared. Emotional Intelligence will be measured by the Trait 
Emotional Intelligence questionnaire at baseline, 3, and 6 months .(84) Mindfulness will be measured by the 
Mindful Attention and Awareness Scale at baseline, 3, and 6 months.(93)   The participants HRC and 
respiratory rate will be tracked for the entire intervention period using the Spire Health Tags. At baseline 
additional health data will be collected from each participant’s medical record to complete the Charlson 
comorbidity index, including lung function, demographics, living condition (living alone or not), GOLD stage, 
and comorbidities.  
 
 
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