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Patients with chronic obstructive lung disease (COPD) suffer from a progressive loss of lung function that leads to poor quality of life, and often invalidity and early death. Regular exercise can improve quality of life in these patients, but the health care system lack the underlying mechanism of exercise-induced improvement in COPD and it is widely thought not to have any effect on lung function. The aim of the present study is to investigate to which extent lung tissue mass and rest-to-exercise diffusion capacity changes differ in COPD patients compared to the healthy state. In order to design prospective clinical trials on the putative impact of high-intensity interval training (HIIT) investigating these parameters, and a secondary aim is to assess the feasibility of such a study in terms of patient inclusion, adherence and methodology.
Patients with Chronic obstructive pulmonary disease (COPD) suffer from a progressive loss of lung function that leads to poor quality of life, and often invalidity and early death. Regular exercise is considered the most effective non-pharmacological intervention for improving quality of life in these patients. However, its use is halted by the lack of understanding of the mechanism of exercise-induced improvement in COPD, and is widely thought not to have any effect on lung function in the clinical setting. Exercise is thus mainly considered a way to alleviate symptoms, primarily by improving skeletal muscle function, but without the potential to reverse the disease. Therefore, relatively short and low-intensity exercise interventions are typically prescribed and are often not pursued in patients with the greatest symptom burden.
The reasoning for not prescribing exercise more widely in COPD is based on two assumptions: 1) new tissue cannot be formed in the adult lung, and 2) no consistent exercise training-induced changes in lung function have previously been documented.
However, de novo tissue formation has repeatedly been demonstrated in the adult lung, both in animals and humans, primarily in response to prolonged hypoxia and pneumonectomy. It has recently been reported that interval-based training counteracts the progressive loss of lung tissue in animal models of experimental COPD. The most likely stimulus is the mechanical strain, and if any measurable changes are to be induced by training, a high-intensity interval training (HIIT) scheme is preferable to be initiated in pulmonary rehabilitation.
On this basis, this study aim to conduct a prospective randomised trial, in which the impact of HIIT on lung weight (assessed by CT), rest-to-exercise diffusion capacity, 3-dimensional distribution of pulmonary perfusion measured by single photon emission computed tomography (SPECT)-low dose CT are addressed. Indeed, the latter is an especially useful clinical tool for the pathophysiological classification of COPD patients, and rest-to-exercise SPECT has the potential as a diagnostic tool that 'pinpoints' the exact cause of dyspnoea in the individual COPD patient, but has not yet been validated for this purpose. While all the methods are established, there is a need for more information regarding COPD-associated changes in lung tissue mass ('lung weight') and rest-to-exercise pulmonary diffusion changes compared to the healthy state. An assessment of the feasibility of an extended HIIT-trial using these methods in COPD patients as well as estimates of the in-study changes in the resultant physiological estimates (for the purpose of sample size estimations) is warranted.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| COPD patients | Experimental | This arm will consist of only COPD patients. |
|
| Healthy controls | Experimental | This arm will consist of age and BMI matched healthy controls. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High intensity interval training | Other | Participants will undergo 12 weeks of supervised HIIT training (3 times per week). The HIIT protocol will consist of 4x4 min. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Lung tissue mass | Change in lung weight in COPD patients compared to matched controls using CT-scans. | CT-scans at baseline and at 12 week follow up. |
| Rest-to-exercise diffusion capacity | Change in rest-to-exercise pulmonary diffusion capacity between COPD patients and matched healthy controls measured by DLNO/CO. | DLNO/CO measured at baseline and at 12 week follow up. |
| Measure | Description | Time Frame |
|---|---|---|
| Rest-to-exercise pulmonary perfusion ratio change | Rest-to-exercise pulmonary perfusion ratio change in COPD patients compared to matched controls measured by single photon emission computed tomography (SPECT). | At baseline and at 12 week follow up |
| Rest-to-exercise leg blood flow change in COPD |
| Measure | Description | Time Frame |
|---|---|---|
| Rest-to-exercise cardiac output change | Cardiac output measured by oxygen pulse. | At baseline and at 12 week follow up |
| VO2peak (and estimated VO2max) | Incremental exercise test on bike ergometer with COSMED system using breath by breath analysis. |
Inclusion criteria -patients
Inclusion criteria - controls
Exclusion criteria - patients
Exclusion criteria - controls
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ronan Martin Griffin Berg, MD | Contact | (+45) 3545 7641 | ronan.martin.griffin.berg@regionh.dk | |
| Jacob Peter Hartmann, MD | Contact | 40924285 | jacob.peter.okholm.hartmann.01@regionh.dk |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Physical Activity Research (CFAS) | Recruiting | Copenhagen | 2100 | Denmark |
Can be retrieved upon request from primary investigator.
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| D000072696 | High-Intensity Interval Training |
| ID | Term |
|---|---|
| D064797 | Physical Conditioning, Human |
| D015444 | Exercise |
| D009043 | Motor Activity |
| D009068 | Movement |
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12 COPD will undergo the intervention in one arm and 12 healthy, age and BMI matched individuals will undergo the same intervention.
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Rest-to-exercise leg blood flow change in COPD patients compared to matched controls measured by ultrasound doppler in a single leg knee extensor model. |
| At baseline and at 12 week follow up |
| At baseline and at 12 week follow up |
| VO2 verification bout | Confirmation of maximum oxygen consumption measured 20 minutes after intitial VO2 peak test at a 110 % of maximum workload. | At baseline and at 12 week follow up |
| The maximal workload (knee extension) | Incremental exercise test on one leg knee extensor chair. | At baseline and at 12 week follow up. |
| Hand-grip strength | Measured with a dynamometer. | At baseline and at 12 week follow up. |
| Body composition | total fat mass, lean body mass measured with dual energy x-ray absorption. | At baseline and at 12 week follow up. |
| Lung function: FEV1 | Change in Forced expiratory volume in 1 second (FEV1) (ml) | At baseline and at 12 week follow up. |
| Lung function: TLC | Change in total lung capacity (TLC)(ml) | Measured during the 12 week intervention. |
| Lung function: FVC | Change in forced vital capacity (FVC)(ml) | Measured during the 12 week intervention. |
| Lung function: RV | Change in residual volume (RV) (ml) | Measured during the 12 week intervention. |
| Lung function: VA | Change in alveolar volume (VA) (ml) | Measured during the 12 week intervention. |
| Lung function: DLCOc | Single-breath diffusion capacity to carbon monoxide corrected for hemoglobin (ml/min/mmHg) | Measured during the 12 week intervention. |
| 6-minute walking test | Distance transversed during 6 minutes of maximum effort walking. | At baseline and at 12 week follow up. |
| Chronic obstructive pulmonary disease Assessment Test (CAT-score) | Health-related quality of life - COPD Assessment Test, (CAT) score. Higher values meaning a smaller burden of symptoms. | At baseline and at 12 week follow up. |
| Oxygen extraction in lower limb musculature during small mass exercise | Calculated from paired arterial and venous blood gases obtained from intraarterial and venous catheters. | At baseline and at 12 week follow up. |
| Intima media thickness in the carotid artery | Measured with ultrasound. | At baseline and at 12 week follow up. |
| Exercise feasibility: exercise sessions attendance rate. | Exercise attendance rate (%) defined as number of attended exercise sessions / by number of prescribed sessions x 100. | Measured during the 12 week intervention. |
| Exercise feasibility: Relative dose intensity (RDI) | RDI (%) of exercise, defined as prescribed exercise dose / performed exercise dose x 100 | Measured during the 12 week intervention. |
| Exercise feasibility: early exercise termination | Incidence of early termination of attended exercise sessions, defined as termination of an exercise session before the prescribed exercises have been performed | Measured during the 12 week intervention. |
| Withdrawal rate | Incidence of permanent discontinuations of the exercise intervention, defined as participants that withdraw entirely from the exercise intervention. | Measured during the 12 week intervention. |
| Exercise feasibility: Patient-reported symptomatic adverse events (paint, dizziness, nausea, fatigue, other) | Changes in patient-reported symptomatic adverse events (pain, dyspnea, fatigue, cough, sore muscles) | Measured during the 12 week intervention. |
| Glucose | Exercise induced changes in plasma levels of glucose | At baseline and at 12 week follow up. |
| IL-1 | Exercise induced changes in plasma levels of interleukin 1 | At baseline and at 12 week follow up. |
| IL-1RA | Exercise induced changes in plasma levels of interleukin-1 receptor antagonist | At baseline and at 12 week follow up. |
| TNF-alfa | Exercise induced changes in plasma levels of tumor necrosis factor alfa | At baseline and at 12 week follow up. |
| IL-6 | Exercise induced changes in plasma levels of interleukin-6 | At baseline and at 12 week follow up. |
| IL-10 | Exercise induced changes in plasma levels of interleukin 10 | At baseline and at 12 week follow up. |
| Adiponectin | Exercise induced changes in plasma levels of adiponectin | At baseline and at 12 week follow up. |
| IL-15 | Exercise induced changes in plasma levels of interleukin 15 | At baseline and at 12 week follow up. |
| HS-CRP | Exercise induced changes in plasma levels of high sensitive c-reactive protein | At baseline and at 12 week follow up. |
| HDL | Exercise induced changes in plasma levels of High density lipoprotein | At baseline and at 12 week follow up. |
| LDL | Exercise induced changes in plasma levels of low density lipoprotein | At baseline and at 12 week follow up. |
| Insulin | Exercise induced changes in plasma levels of insulin | At baseline and at 12 week follow up. |
| Creatinine | Exercise induced changes in plasma levels of creatinine | At baseline and at 12 week follow up. |
| Leptin | Exercise induced changes in plasma levels of leptin | At baseline and at 12 week follow up. |
| Carbamide | Exercise induced changes in plasma levels of carbamide | At baseline and at 12 week follow up. |
| ALAT | Exercise induced changes in plasma levels of alanine-aminotransferase | At baseline and at 12 week follow up. |
| Leucocytes | Exercise induced changes in plasma levels of leucocytes | At baseline and at 12 week follow up. |
| Rigshospitalet | Recruiting | Copenhagen | 2100 | Denmark |
|
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009142 |
| Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |