Rationale: Chronic obstructive pulmonary disease (COPD) is characterised by a high prevalence of peripheral muscle dysfunction, which can have significant clinical consequences, including decreased exercise capacity, reduced quality of life, and even a higher mortality rate. Reduction of lung hyperinflation using bronchoscopic lung volume reduction treatment with one-way endobronchial valves (EBV) is a minimally invasive intervention which improves exercise capacity and physical activity in patients with severe emphysema. This positive effect is also related to weight gain and alterations in body composition. The physiologic and structural adaptations of skeletal muscle function after EBV treatment has never been investigated before.
Objective: To investigate the physiological and structural adaptations of peripheral muscle function at a cellular level in response to EBV treatment.
Study design: A single center, prospective clinical trial with a single-arm pretest-posttest design. Patients with severe emphysema who will receive a bronchoscopic lung volume reduction treatment are asked to undergo additional in-magnet exercise testing and muscle biopsies before and after placement of EBVs.
Study population: Patients with severe emphysema who are scheduled to undergo EBV treatment.
Main study parameters/endpoints: The difference in quadriceps phosphocreatine concentration (PCr), quadriceps inorganic phosphorus concentration (Pi), and quadriceps pH at rest, during progressive exercise, and recovery rate will be measured by 31P-MRS to assess the physiological effect of EBV treatment on skeletal muscle function and its bioenergetics. Furthermore, we will perform a detailed histological and biochemical analysis of muscle fiber type composition, mitochondrial density, master regulators of muscle oxidative programming, and mitochondrial respiration before and after EBV treatment.
Patient is scheduled for a bronchoscopic lung volume treatment using one-way endobronchial valves;
Patient read, understood and signed the Informed Consent Form.
Inability to perform a cycle ergometry test;
Contraindications for undergoing a magnetic resonance imaging scan (e.g. claustrophobia, implanted cardiac devices);
Body length >190cm;
Any anticoagulant therapy;
The study population exists of patients with severe emphysema who undergo a bronchoscopic lung volume reduction treatment with one-way endobronchial valves.
Cohort
Prospective
31P-Magnetic Resonance Spectroscopy (31P-MRS)
Diagnostic test31P-Magnetic Resonance Spectroscopy will be performed during exercise testing.
Change in quadriceps phosphocreatine concentration measured by 31P-MRS.
To assess the physiological adaptations, in terms of cellular bioenergetics, of the quadriceps muscle in patients with severe COPD in response to EBV treatment. This will be done by performing 31P-MRS during exercise testing in a MR-compatible ergometer at baseline and at 6 months follow-up, for which the quadriceps phosphocreatine concentration (PCr) at rest and during progressive exercise will be assessed.
Change in muscle fiber type composition measured in muscle biopsies.
Change in muscle fiber type composition 6 months after EBV treatment measured in muscle biopsies.
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