Tissue Regeneration in Patients With Chronic Obstructive Pulmonary Disease After an Exercise Intervention.

Official title

Activation of Regenerative Pathways by Exercise Training in Patients With Chronic Obstructive Pulmonary Disease

Overview

The main objective of this project is to identify mechanisms for lung regeneration in patients with COPD induced by exercise training. The hypothesis is that adjusted exercise training improves disease outcome in these patients by decrease remodelling processes linked to oxidative stress, inflammatory and/or immunological pathways in the lung. Along the way, the investigator also expect to identify (or validate) biomarkers mirroring systemic processes such as reduced inflammation and ameliorating the epithelial barrier in these patients. These events may additionally act as potential targets for interventions. Objectives (i) Evaluate biomarkers for regenerative processes, matrix turnover, stem cell activity and inflammatory patterns in lung tissue biopsies, blood- and urine samples correlated to vital lung parameters and physical capacity, before and after attending an exercise-training program. (ii) Study the effects of exercise training on the pulmonary ventilation/perfusion ratio and quality of life. (iii) Evaluate the relation between pathophysiology in the lung evaluated by CT scan, and systemic response measured by muscle biopsies and biomarkers in blood/urine. (iv) Investigate in vitro cell behaviour and remodelling/regenerative processes altered in COPD patients upon exercise training (aim 1).

Detailed description

Chronic obstructive pulmonary disease (COPD) is an increasing worldwide health problem characterized by progressive destruction of lung tissue. In the shadow of the pandemic, COPD patients may suffer more severely from COVID-19 with worse prognosis and higher mortality rate. This may be due to common underlying risk factors such as smoking, cardiovascular disease and a sedative life style. To cope with the soaring burden on the health care system posed by the aftermath of the pandemic in the context of chronic diseases such as COPD, the importance of self-responsibility to increase quality of life is emerging. New guidelines from the 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease support exercise in the management of COPD and after COVID-19 infection, even during mild COVID-19 symptoms. However, little is known about the molecular alterations induced by exercise training and how to boost the body´s ability to halt disease progression in COPD.

The hypothesize is that adjusted exercise training increases the ability to cope with biological stress, which is increased in COPD due to i.e. chronic inflammation and a history of smoking, and may facilitate restoration of damaged tissue. In this proposal the anticipation is to link the effects of physical exercise to amelioration of vital lung parameters, physical strength including 6 min walk test, and quality of life, by evaluating biomarkers for stem cell activity, regeneration and inflammation in lung tissue biopsies and blood samples. This will also result in the recognition of pathways that are targetable for novel pharmaceuticals that could synergize with the training effect.

Interventions

• Other Exercise regime
  Exercise

Primary outcome measures

• Pulmonary Function [Time frame: Baseline, post intervention at 12 wks]

Secondary outcome measures (5)

• Physical capacity [Time frame: Baseline, post intervention at 12 wks]
• Inflammation markers [Time frame: Baseline, post intervention at 12 wks]
• Level of emphysema [Time frame: Baseline, post intervention at 12 wks]
• Maximal physical capacity ( Wmax) [Time frame: Baseline, post intervention at 12 wks]
• COPD Assessment Test (CAT) [Time frame: Baseline, post intervention at 12 wks]

Eligibility criteria

Inclusion criteria

• Forced expiratory volume in one second (FEV1) 85-30 % of predicted post bronchodilator
• Optimal medical treatment according to GOLD and the Swedish National Guidelines
• Absence of other significant diseases that could contribute to physical exercise limitation
• Non-smoking since at least one year
• Free from exacerbations (last 4 weeks)
• BMI = 18- 35

Exclusion criteria

• Regular participation in adjusted/specially designed exercise sessions
• Unstable cardiovascular or pulmonary disease
• Smoking
• Any other criteria that at the discretion of the investigator prevent the study subject from participating in an exercise-training program

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 2 centers

• Lund University — Lund
• Uppsala University — Uppsala

Publications

• Larsson C, Elowsson L, Tufvesson E, Cederberg A, Ohrneman H, Falcones B, Karlsson L, Akbarshahi H, Ankerst J, Bjermer L, Palm A, Londahl J, Malinovschi A, Janson C, Emtner M, Westergen-Thorsson G. Activation of regenerative pathways by exercise intervention in subjects with chronic obstructive pulmonary disease - a study protocol. Respir Res. 2025 Dec 12;27(1):16. doi: 10.1186/s12931-025-03443-y. PMID 41388411

Identifiers

NCT: NCT06335992 · Dnr 2022-00831-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗