Inflammation and Oxidative Stress in COPD

N/AEnrolling By InvitationNCT07376161

Deniz Bilici27 enrolled

Overview

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, characterized by persistent airflow limitation, chronic inflammation, and increased oxidative stress. Despite optimal pharmacological treatment, many patients continue to experience symptoms, reduced exercise capacity, and frequent exacerbations. Pulmonary rehabilitation (PR) is an evidence-based, non-pharmacological intervention that improves symptoms, functional capacity, quality of life, and survival in patients with COPD; however, its biological effects on inflammatory and oxidative stress pathways remain insufficiently defined. This study aims to evaluate the effects of pulmonary rehabilitation on systemic inflammation and oxidative stress in patients with stable COPD. Serum levels of pro-inflammatory cytokines (IL-6, TNF-α) and the epithelial alarmin IL-33, which is released in response to airway epithelial injury, as well as NRF-2 gene and/or protein expression as a key regulator of antioxidant defense, will be measured before and after a standardized pulmonary rehabilitation program. By assessing changes in these biomarkers, this study seeks to determine whether pulmonary rehabilitation exerts disease-modifying effects beyond symptomatic improvement and functional outcomes. The findings are expected to provide novel insights into the biological mechanisms of pulmonary rehabilitation and to support its role as a targeted, cost-effective intervention in the comprehensive management of COPD.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Inflamation COPD Oxidative Stress Pulmonary Rehabilitation

Interventions

Pulmonary RehabilitationBEHAVIORAL

Participants will undergo a standardized, supervised pulmonary rehabilitation program consisting of exercise training, breathing exercises, and patient education. The program will include aerobic exercise training (treadmill or cycle ergometer), strength training of upper and lower limb muscles, and respiratory muscle training, conducted under the supervision of a multidisciplinary rehabilitation team. Sessions will be performed multiple times per week over a predefined program duration. The intervention will be applied in addition to standard pharmacological treatment, with no changes to maintenance medications during the study period.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adults aged 40-80 years with a diagnosis of stable chronic obstructive pulmonary disease (COPD) * Airflow limitation defined according to GOLD criteria (FEV₁/FVC \< 70% and FEV₁ \< 70% predicted) * Former smokers with a smoking history of at least 10 pack-years * Clinically stable disease at the time of enrollment * Ability and willingness to participate in the pulmonary rehabilitation program * Provision of written informed consent Exclusion Criteria: * Current smokers * History of acute COPD exacerbation or respiratory infection within the past 6 weeks * Presence of other chronic lung diseases (e.g., bronchiectasis, interstitial lung disease, asthma) * Active malignancy * Severe or uncontrolled cardiovascular disease, including recent acute myocardial infarction or malignant arrhythmias * Neurological, orthopedic, or psychiatric conditions that preclude objective functional assessment or participation in exercise training * Use of antioxidant or vitamin supplementation within the past 4 weeks * Determination by a cardiologist that participation in an exercise-based rehabilitation program is not medically appropriate

Outcomes

Primary Outcomes

Change in Inflammatory and Oxidative Stress Biomarkers After Pulmonary Rehabilitation in COPD Patients

Primary outcome is the change in serum levels of inflammatory and oxidative stress biomarkers following the pulmonary rehabilitation program in patients with stable COPD. Serum concentrations of IL-6, TNF-α, and IL-33, as well as NRF-2 gene and/or protein expression, will be measured before and after the intervention to evaluate the biological effects of pulmonary rehabilitation on systemic inflammation and oxidative stress.

Time frame: Baseline (before pulmonary rehabilitation) and after 8 weeks of pulmonary rehabilitation

Secondary Outcomes

Association Between Changes in Inflammatory and Oxidative Stress Biomarkers and Clinical and Functional Outcomes After Pulmonary Rehabilitation

Secondary outcome is the relationship between levels and changes in inflammatory and oxidative stress biomarkers and changes in clinical and functional parameters following pulmonary rehabilitation in patients with stable COPD. Changes in serum IL-6, TNF-α, IL-33, and NRF-2-related parameters will be correlated with post-rehabilitation changes in dyspnea severity, exercise capacity, and health-related quality of life measures.