Effects of Pulmonary Rehabilitation on Skeletal Muscle in COPD Patients

Study Overview
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Brief Summary
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In a former study, the investigator observed significant differences in the response to pulmonary rehabilitation between COPD patients with the normal genetic variant of alpha-1 antitrypsin (PiMM) and those with a homozygous deficient variant (PiZZ) (Jarosch et al., 2016, DOI: 10.1159/000449509). PiZZ COPD patients showed less improvement in exercise capacity compared to PiMM patients. This latter finding was mirrored by an increase of oxidative myofiber type I proportion - that is important for aerobic exercises in daily life - in PiMM but not PiZZ patients. Based on this finding of impaired skeletal muscle adaptation, the aim of this study is to compare the effects of pulmonary rehabilitation including exercise training on a) specific enzymes of energy metabolism reflecting the oxidative capacity of the skeletal muscle and b) the analogue gene expression of these oxidative enzymes in a cohort of PiMM and PiZZ COPD patients.

Official Title
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Effects of Pulmonary Rehabilitation on Skeletal Muscle Morphology and Metabolism in PiMM vs. PiZZ COPD Patients

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Procedure: Pulmonary rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic obstructive pulmonary disease phenotype PiMM or PiZZ written informed consent Exclusion Criteria: any comorbidities that prevent patients from participating in an exercise Training program necessity of anticoagulant therapy other genetic variants of alpha-1 antitrypsin than PiMM or PiZZ

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PiMM patients<br>COPD patients with the Alpha-1 antitrypsin genetic variant PiMM (Smoking-related COPD) | Procedure: Pulmonary rehabilitation<br>* 3-weeks of inpatient pulmonary Rehabilitation including exercise Training (daily endurance and strength Training)<br>|
| Experimental: PiZZ patients<br>COPD patients with alpha-1 antitrypsin deficiency (genotype PiZZ) | Procedure: Pulmonary rehabilitation<br>* 3-weeks of inpatient pulmonary Rehabilitation including exercise Training (daily endurance and strength Training)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endurance time | Will be measured during a constant work rate cycling test | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myofibre type I Distribution | Skeletal muscle sample will be taken from the M.vastus lateralis via Bergström muscle biopsy needle | 3 weeks | 
| Capillary to fibre ratio | Skeletal muscle sample will be taken from the M.vastus lateralis via Bergström muscle biopsy needle | 3 weeks | 
| muscle strength | strength test in the right knee Extensor and flexor | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alpha-1 antitrypsin deficiency, pulmonary rehabilitation, exercise training, skeletal muscle biopsy