Respiratory Muscles in End-stage Lung Disease: Pathophysiological Processes & Clinical Consequences

Rationale: In patients with chronic lung diseases, the role of respiratory muscle dysfunction has been underestimated. Also, current treatment options, like chronic NIV and lung transplantation (LTx), might also have deleterious effects on the respiratory muscles, and the mechanisms are poorly understood. Therefore in this exploratory study the objectives are to: 1. Determine in vivo respiratory muscle function and progression of respiratory muscle dys-function in end-stage COPD patients 2. Establish the correlation between changes in the structure and contractility of respiratory myofibers and in vivo respiratory muscle function. 3. Establish the effect of chronic NIV on structure and contractility of respiratory muscle fi-bers 4. Determine whether the structure and contractility of respiratory muscles cells at the time of LTx predicts clinical recovery post-LTx. Study design: The study will be an exploratory observational cohort study following patients on the LTx waiting list during the waiting period and afterwards until they showed functional recovery of respiratory muscle function. Study population: Adult COPD patients on the LTx waiting list will be included. Intervention (if applicable): None Main study parameters/endpoints: To assess clinical functioning of the respiratory muscles we will assess respiratory electrical activity as a measure of respiratory effort by surface EMG, and thickening fraction of the diaphragm and intercostal muscles and diaphragm excursions by ultrasound and maximal in- and expiratory pressure to assess muscle output; all before and after LTx. We will relate and correct these data for hyperinflation and degree of lung damage by using data from standard care lung function tests and CT scans, and will relate these measurements to prior treatment (NIV settings) and outcome after LTx, by retrieving these data from the EPD. To assess contractility of respiratory myofibers and in vivo respiratory muscle function, biopsies will be t