Mechanisms of Vascular Damage in Patients With Chronic Obstructive Pulmonary Disease

Randomized Controlled Trial on the Cardiovascular Effects of Lung Volume Reduction Surgery in Patients With Chronic Obstructive Pulmonary Disease

A randomised controlled trial will be performed to evaluate the effects of lung volume reduction surgery (LVRS) in patients with COPD on systemic inflammation, oxidative stress, endothelial function, arterial stiffness and blood pressure. We hypothesize that LVRS will lead to a reduction of systemic inflammation, oxidative stress, arterial stiffness and blood pressure and to improved endothelial function.

For this purpose 30 patients with severe/very severe COPD (GOLD III-IV) and pulmonary emphysema who are to undergo LVRS will be randomised to one of two groups: group 1 receiving immediate LVRS and group 2 receiving LVRS after a delay of 3 months.

Measures of systemic inflammation, oxidative stress, endothelial function, arterial stiffness and blood pressure will be measured at baseline and 3 months after surgery and no surgery, respectively (group 2 receiving surgery only after a delay of 3 months will serve as control group) to investigate the effects of LVRS on the described outcomes.

Not desired

Inclusion criteria:

• Dyspnea at rest or at minimal physical activity, severe limitation of exercise capacity (6-min walk distance < 350 m).
• Acceptance of an increased perioperative mortality (approximately 2 %) and/or morbidity (long lasting hospitalization due to prolonged air leaks)
• COPD (GOLD guidelines) with severe obstructive ventilatory defect (FEV1 <35% predicted)
• Functional aspects of lung emphysema, i.e. irreversible hyperinflation with a residual volume to total lung capacity ratio (RV/TLC) of >0.65 and an impaired total lung diffusion capacity (DLCO), usually < 40% predicted.
• Pulmonary emphysema confirmed by high resolution computer tomography

Exclusion criteria: - Current smokers

• Age > 75years
• "Vanishing" lung or diffuse lung emphysema on CT, FEV1 <20% predicted and DLCO <20% predicted, and hypercapnia (PaCO2 >7.3kPa)
• Overt active coronary artery disease, severe left ventricular function impairment
• Pulmonary hypertension with a mean pulmonary artery pressure >35 mmHg at rest
• Acute bronchopulmonary infection, bronchiectasis on high resolution tomography
• Pulmonary cachexia (body mass index <18kg/m2)
• Neoplastic disease with a life expectancy of less than 2 years
• Addiction to alcohol/drugs
• Relevant renal (creatinine >150ug/ml), active gastroenterological (GI-bleeding in the previous year, abnormal liver function, active inflammatory bowel disease) or active neurological disease.