Rationale: Development of dynamic hyperinflation is a primary limiting factor of exercise tolerance in chronic obstructive pulmonary disease (COPD). To lessen the development of dynamic hyperinflation, and to improve exercise tolerance in COPD patients, we have developed a breathing- retraining technique to be used during pulmonary rehabilitation. This breathing-retraining technique is designed to decrease respiratory rate and prolong exhalation. We demonstrated that, in the short- term, hyperinflation and exercise duration improved more with breathing-retraining plus exercise- training than with exercise-training alone. Because a crucial aspect of pulmonary rehabilitation is the maintenance its short-term benefits over the long-term, we now propose to test whether short- term benefits of breathing-retraining plus exercise followed by an adherence-intervention program are sustainable over the long-term Primary Hypothesis: (H1) In COPD patients, improvements in exercise duration on a constant- load treadmill test will be greater after 12 weeks of breathing- retraining plus exercise-training followed by a 42-week adherence-intervention program (1 yr. total) than after 12 weeks of exercise-training alone followed by a 42-week adherence-intervention program (1 yr. total). Secondary Hypotheses: One year after randomization, exercise-induced dynamic hyperinflation will be less during a constant-load treadmill test (H2), 6-minute walking distance will be longer (H3), and mastery over breathing will be greater (H4) in the breathing- retraining plus exercise-training group than in the exercise-alone group. Lastly (exploratory objective), we will assess the effect of the patient's physiologic, psychologic and clinical phenotype on short-term and long-term responsiveness to pulmonary rehabilitation. Methods: The proposed study is a randomized, controlled clinical trial in which 250 patients with moderate-to-severe COPD will be enrolled. One hundred forty of these patients are expected to qualify for randomization into the breathing-retraining plus exercise-training group or the exercise-training alone group. Patients will receive 12-weeks of supervised training according to group assignment (three times weekly) followed by an adherence-intervention program (weekly phone motivational interviews, home-exercise program, and monthly laboratory booster sessions). Follow-up testing will be completed at 12 weeks, and at 6 and 12 months. Testing will include pulmonary function test, incremental-load and constant-load treadmill tests, 6-minute walk test, measurements of dyspnea, assessment of respiratory and quadriceps muscle strength and endurance and quadriceps ultrasonography. Analysis: In the principal analysis of the primary outcome measure (exercise duration; H1) we will compare changes in exercise duration (constant work-rate treadmill test) from baseline to end of study using 2-sample t-test (two-tailed ?=.05). The primary analysis will be based on intention-to-treat principles. Multiple imputation will be used for study subjects missing the 12-month measurement. This imputation model will be based on baseline characteristics of study participants. Several secondary analyses of the primary outcome measure will be performed (H2-H4). Linear regression will be used to determine whether the observed treatment benefits persist after adjustment for baseline covariates and measures of adherence to treatment. Since several measurements will be taken on each patient, mixed-models analysis will be used to compare the changes on the constant- load treadmill test over time between the two groups.

Public Health Relevance

to the VA. COPD is the 3rd leading cause of death in the United States and the 6th most common chronic condition cited among veterans enrolled in the Veterans Health Administration (VHA). In 2010, nearly 300,000 VA patients were diagnosed with COPD. Moreover, COPD is the 5th leading cause of VHA hospitalization. Compared with the general population, COPD patients are more likely to rate their health as poor, to report more limitations in daily activities and more disability days, to visit a physician, and to be hospitalized. In the short- term, pulmonary rehabilitation can improve several chronic hindrances of COPD. Unfortunately, is unclear how to maintain rehabilitation benefits over the long-term. We reason that developing a successful strategy to ensure long-term maintenance of physical activity and breathing-retraining in COPD, as planned in this proposal, has the potential to modify the spiraling pattern of increasing respiratory impairment leading to mounting physical limitations and, possibly, reduce health-care cost and mortality in COPD.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01RX001325-03
Application #
9136713
Study Section
Musculoskeletal/Orthopedic Rehabilitation (RRD2)
Project Start
2014-10-01
Project End
2018-09-30
Budget Start
2016-10-01
Budget End
2017-09-30
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Edward Hines Jr VA Hospital
Department
Type
DUNS #
067445429
City
Hines
State
IL
Country
United States
Zip Code
60141
Laghi, Franco; Khan, Najeeb; Schnell, Thimothy et al. (2018) New device for nonvolitional evaluation of quadriceps force in ventilated patients. Muscle Nerve 57:784-791