Microvascular changes in COPD patients with severe pulmonary hypertension

Introduction: When pulmonary hypertension (PH) develops during the course of chronic obstructive pulmonary disease (COPD), mean pulmonary pressure (mPAP) levels at rest usually range between 25 and 35mmHg. However, a subset of COPD patients show higher levels of mPAP. For the group of patients with mPAP≥35mmHg, now called severe PH-COPD, little is known about a particular involvement of the pulmonary circulation and specific underlying histological changes. Our objective was to assess and to quantify these changes. Methods: We analysed lungs from transplanted patients and retrospectively compared histology in 3 groups of COPD patients according to the level of mPAP: ≥35mmHg (n=10), 25-34mmHg (n=10), <25mmHg (n=10). We evaluated wall thickness of muscular-type pulmonary arteries (100-350µm in diameter), degree of microvascular muscularization (arterioles and venules) and degree of pulmonary capillary density, using computer-assisted semi-automated morphometry on different histochemical and immunohistochemical stainings. Results: Patients with severe PH had lower PaO2 (p=0.016), higher FEV₁/FVC ratio (p=0.049) and lower TLC (p=0.0079) than patients without PH. As compared with the moderate PH group, muscular hyperplasia of microvessels was significantly increased (p=0.0045), and capillary density was decreased (p=0.0049) in the severe PH-COPD group. Alterations of muscular-type pulmonary arteries, which are important in idiopathic and heritable PH, were not discriminating. Conclusion: Patients with severe PH-COPD appear to have a specific histological pattern that is not present in COPD patients with moderate PH or without PH. Our results indicate a subgroup among COPD patients with specific involvement of microvessels.