Microvascular changes and microvascular reactivity in stable patients with Chronic Obstructive Pulmonary Disease using non-invasive retinal imaging

Rationale: COPD is considered as a complex, heterogeneous, and multicomponent condition in which comorbidities are frequently present. Indeed, patients with COPD are more likely to be diagnosed with (risk factors for) cardiovascular disease. Smoking is the most important risk factor for the development of COPD and has negative effects on the airway epithelium, the endothelium and microvasculature in multiple organs. Retinal image analysis is an unobtrusive procedure for visualizing the microcirculation. Since similarities exist between retinal blood vessels and the microvasculature of the heart, lungs, and brain, retinal imaging can be used to identify diseases of the eye but also cardiovascular diseases and risk factors. To date, little is known about microvascular changes and the possible beneficial effect of physical activity in patients with COPD.


Objective: Part 1: to determine the presence of changes in the retinal microvasculature in patients with COPD; Part 2: to determine the effect of physical activity on the function of the retinal microvasculature.


Study design: Prospective observational study.


Study population: Clinically stable patients with COPD entering pulmonary rehabilitation at Ciro+ in Horn.


Intervention (if applicable): All COPD patients will participate in a regular comprehensive rehabilitation program at Ciro+. Retina photos will be taken during standard begin assessment and outcome assessment (part 1). In addition, 6 photos will be taken before and after a high-intensity exercise, which is part of the standard rehabilitation program (part 2).


Main study parameters/endpoints: The presence of changes in the retinal microvasculature in patients with COPD. The changes are quantified as changes in the diameter of the central retinal arteriolar equivalent and the central retinal venular equivalent.


Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All interventions take place at Ciro+ in Horn as part of regular pulmonary rehabilitation. In addition, retina photos will be taken in participating patients. When taking the photo, patient will experience a flash of the camera. The possible inconvenience of this flash will disappear completely after a few seconds. It takes less than 5 minutes to take the retinal photo. The EndoPAT is completely safe and harmless, however, the 5 minutes occlusion of the brachial artery may cause some minor discomfort and tingling in the fingers. The risks of participation in the study are almost zero.

Since cigarette smoke has effects on the airway epithelium, but also causes endothelial damage and loss of the microvasculature in multiple organs, it seems reasonable to assume that microvascular changes are more present in patients with COPD compared to healthy control subjects.
Since physical exercise has a positive effect on the structure and functionality of the blood vessels, it seems reasonable to assume that an 8-week pulmonary rehabilitation program has a beneficial effect on retinal microvascular status and endothelial function in patients with COPD.

Measurements will be performed before and after an 8-week pulmonary rehabilitation program.

Before and after rehabilitation, microvascular changes and reactivity will be measured using retinal imaging and endothelial function will be analyzed via reactive hyperemia, blood pressure and ankle brachial index.