Compartment-specific remodeling patterns in end-stage chronic obstructive pulmonary disease with and without severe pulmonary hypertension

Katarina Zeder; Leigh M Marsh; Alexander Avian; Luka Brcic; Anna Birnhuber; Philipp Douschan; Vasile Foris; Teresa Sassmann; Konrad Hoetzenecker; Panja M Boehm; Grazyna Kwapiszewska; Andrea Olschewski; Horst Olschewski; Gabor Kovacs

doi:10.1016/j.healun.2024.02.1044

Compartment-specific remodeling patterns in end-stage chronic obstructive pulmonary disease with and without severe pulmonary hypertension

J Heart Lung Transplant. 2024 Feb 19:S1053-2498(24)01087-8. doi: 10.1016/j.healun.2024.02.1044. Online ahead of print.

Authors

Affiliations

¹ Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
² Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
³ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
⁴ Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.
⁵ Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Division of Physiology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria.
⁶ Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
⁷ Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
⁸ Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Division of Physiology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria; Institute for Lung Health, Giessen, Germany.
⁹ Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Experimental Anaesthesiology, Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.
¹⁰ Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. Electronic address: horst.olschewski@medunigraz.at.

PMID: 38382583
DOI: 10.1016/j.healun.2024.02.1044

Abstract

Background: In patients with end-stage chronic obstructive pulmonary disease (COPD), severe pulmonary hypertension (PH) is frequently associated with less severe airway obstruction as compared to mild or no PH. However, the histologic correlate of this finding is not clear. We aimed to quantify remodeling of pulmonary arteries, airways, and parenchyma in random samples of explanted end-stage COPD lungs.

Methods: We quantified remodeling of small pulmonary arteries, small airways, and the degree of emphysema (mean interseptal distance [MID]) with dedicated software. As primary objective, we compared COPD patients with severe PH (SevPH-COPD) with age- and sex-matched MildPH-COPD. For comparison, we also investigated COPD lungs with no PH (NoPH-COPD), idiopathic PAH (IPAH), and healthy donors.

Results: We included n = 17 SevPH-COPD (mPAP = 43 [39-45]mm Hg), n = 17 MildPH-COPD (mPAP = 28 [24-31]mm Hg), n = 5 NoPH-COPD (mPAP = 18 [16-19]mm Hg), n = 10 IPAH (mPAP = 72 [65-91]mm Hg), and n = 10 healthy donor lungs. SevPH-COPD versus MildPH-COPD was characterized by better preserved forced vital capacity (51% vs 40% predicted, p < 0.05), less emphysema (MID 169 µm vs 279 µm, p < 0.001), and less PAS-positive and CD45-positive mucosa cells (15% vs 22%, p = 0.063% and 5% vs 7%, p = 0.058) suggesting less airway inflammation. In COPD patients, intimal and medial thickening were strongly correlated with mPAP (r = 0.676, p < 0.001 and r = 0.595, p < 0.001). MID was negatively correlated with mPAP (r = -0.556, p < 0.001) and was highest in NoPH-COPD (mean 281 µm), suggesting that emphysema per se is not associated with PH.

Conclusions: End-stage COPD with severe PH is characterized by pronounced pulmonary vascular remodeling, less inflammation of small airways, and less emphysema as compared to COPD with mild PH or no PH, suggesting that COPD with severe PH may represent a unique phenotype of COPD.

Keywords: chronic obstructive pulmonary disease; emphysema; histology; pulmonary hypertension; remodeling.