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

Abstract

RationaleIn end-stage COPD patients, 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. ObjectiveTo quantify remodeling of pulmonary arteries, airways and parenchyma in random samples of explanted end-stage COPD lungs. MethodsWe quantified thickening of small pulmonary arteries, remodeling of 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. ResultsWe included n=17 SevPH-COPD (mPAP=43 [39–45]mmHg), n=17 MildPH-COPD (mPAP=28 [24–31]mmHg), n=5 NoPH-COPD (mPAP=18 [16–19]mmHg), n=10 IPAH (mPAP=72 [65–91]mmHg) and n=10 healthy donor lungs. SevPH-COPD vs. MildPH-COPD was characterized by better preserved forced vital capacity (51%vs.40%predicted,p<0.05), less emphysema (MID 169µmvs.279µm,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. Over the full range of COPD, 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 281µm), suggesting that emphysema per se is not associated with PH. ConclusionEnd-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.