Pulmonary hypertension associated with COPD: a phenotype analysis

Abstract

Background: Pulmonary hypertension (PH) associated with COPD (PH-COPD) exhibits diverse phenotypes, challenging therapeutic management. This study aimed to describe the characteristics of COPD patients with distinct phenotypes, namely end-stage COPD with or without PH (group 1), other COPD patients with mild-to-moderate pre-capillary PH-COPD (group 2) and COPD patients with a pulmonary vascular phenotype (PVP) (group 3).

Methods: We performed a retrospective analysis of COPD patients who underwent right heart catheterisation from 2015 to 2022.

Results: 81 patients were included in group 1, 37 in group 2 and 35 in group 3. The groups differed in terms of clinical, functional, haemodynamic and imaging characteristics. Group 1 had significantly marked lung hyperinflation with increased total lung capacity and residual volume, a feature not observed in group 3. These results were confirmed by analysis of chest CT scans, which confirmed varying degrees of emphysema, as follows: severe in group 1, moderate in group 2 and mild in group 3, with median total emphysema indices of 55% (48-62), 32% (16-49) and 16% (3.4-31), respectively, p<0.0001.

Conclusions: Our results highlight the broad spectrum of PH in COPD, from PH associated with end-stage COPD (phenotype/group 1), characterised by predominant alveolar wall damage with severe emphysema, to PVP (phenotype/group 3), mainly due to pulmonary vascular changes. Phenotype/group 2 represents an intermediate state combining features of both. In the current debate on how to distinguish PH-COPD phenotypes, it might be of interest to include quantitative thresholds for emphysema in future diagnostic and management algorithms.

FIGURE 1

Flowchart of the study. All patients had a ventilation/perfusion lung scan to exclude chronic thromboembolic pulmonary hypertension (PH). Fluid challenge was performed during right heart catheterisation (RHC) when pulmonary arterial wedge pressure was between 12 and 15 mmHg to exclude post-capillary PH. ^#: Associated cardiac hyperflow: n=1; combined with associated post-capillary PH: n=11; chronic renal failure on dialysis+taking anorectic drugs: n=1; taking anorexigens: n=2; associated with post-capillary PH and chronic pulmonary artery obstruction: n=4; associated cirrhosis or liver transplantation: n=3; restrictive respiratory failure associated with scoliosis: n=2; combined with post-capillary PH and restrictive syndrome on obesity: n=1; associated with chronic pulmonary artery obstruction: n=4; pulmonary veno-occlusive disease: n=2; associated sarcoidosis: n=3; associated blood disease: n=1; patent foramen ovale requiring closure+poor tolerance of treatment and refusal of care: n=1; associated with interstitial lung disease (one indeterminate; the others related to scleroderma, to hypersensitivity pneumonitis and to rheumatoid arthritis): n=4. FEV₁: forced expiratory volume in 1 s; PVR: pulmonary vascular resistance; WU: Wood units.

FIGURE 2

Comparison of total emphysema index (%) between the three phenotypes. Cluster 1 was divided into three groups according to the severity of pulmonary hypertension (PH). ^#: Note that only n=2 for the subgroup of phenotype 1+severe PH. Results are expressed as median+95% confidence interval.

FIGURE 3

Correlation test between a) mean pulmonary artery pressure (mPAP) and ratio of main pulmonary artery diameter to ascending aorta diameter (PA:A), b) mPAP and emphysema, c) residual volume (RV) and emphysema, d) total lung capacity (TLC) and emphysema, e) forced expiratory volume in 1 s (FEV₁) and emphysema, and f) arterial oxygen partial pressure (P_aO2) and emphysema, and g) pulmonary vascular resistance (PVR) and P_aO2. Patients in groups 1, 2 and 3 are represented in blue, green and red, respectively.

FIGURE 4

Kaplan–Meier overall survival curve between a) groups/phenotypes 2 and 3 and b) post-transplant survival curve in group/phenotype 1. PH: pulmonary hypertension.

FIGURE 5

Phenotyping of pulmonary hypertension associated with COPD (PH-COPD) based on the three groups/phenotypes of the study. ^#: Lung transplantation or, in some cases, volume reduction surgery. BNP: brain natriuretic peptide; D_LCO: lung diffusing capacity for carbon monoxide; FEV₁: forced expiratory volume in 1 s; iPAH: idiopathic pulmonary arterial hypertension; PA:A: ratio of pulmonary artery diameter to ascending aorta diameter; PAH: pulmonary arterial hypertension; PH: pulmonary hypertension; PVR: pulmonary vascular resistance, RHC: right heart catheterisation; WU: Wood units.