Activation of regenerative pathways by exercise training in patients with chronic obstructive pulmonary disease

Background: COPD is an increasing worldwide health problem characterized by progressive tissue destruction. Exercise training has been a cornerstone in COPD treatment for many years and studies have shown improved life quality and prolonged survival. However, so far, little is known about what actually occurs on a cell- and molecular level when these patients increase their physical activity.

Objectives: Our hypothesis is that adjusted exercise training improves disease outcome. We aim to identify factors stimulating lung regeneration in patients with COPD and find biomarkers mirroring systemic processes involved in repair. By evaluating how exercise training may induce amelioration in disease outcome on a cellular- and molecular level, we anticipate to identify regenerative pathways as potential targets for future interventions.

Work plan:

1. Basic explorative examination - baseline measurements such as general health conditions, relevant questionnaires, lung function tests, physical capacity, imaging and blood- and urine samples. 2. Physiotherapy intervention - supervised exercise-training program and follow-up examination post-exercise training.

3. Analysis of biological samples - parameters concerning inflammatory and regenerative processes (stem cell activity, matrix turnover, inflammatory patterns) will be correlated to vital lung parameters and physical capacity etc.

4. In vitro evaluation - studies of cell behaviour and remodelling/regenerative processes altered in COPD patients upon exercise training.

Significance: With deeper mechanistic insight in molecular- and cellular activities induced by exercise training, we hope to be able to repair what was previously perceived as irreversible. This will have a great impact on how we manage COPD in the future. Positive signals obtained from exercise training may also be further enhanced by pharmacological intervention strategies.

A training protocol that improves disease would benefit society socioeconomically due to reduced hospitalizations and increased work capacity. We foresee that this project may create a foundation for other patient group, especially in light of the current COVID-19 pandemic, where an early intervention with adjusted exercise training may have a huge impact on recovery time and quality of life.