Pulmonary hypertension in interstitial lung disease: a systematic review and meta-analysis

Abstract

Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances. What are the diagnostic evaluation, epidemiology, associated factors, prognostic significance, and outcome measures in interventional trials for PH in patients with ILD in current literature? Ovid MEDLINE, Embase, and CENTRAL databases were searched for original research evaluating PH in participants with ILD of any aetiology. The definition of PH was based on the investigators' criteria. 302 studies were included, with varying diagnostic evaluation used to define PH. Commonly used diagnostic tests were right heart catheterisation (RHC) (56%) and transthoracic echocardiogram (TTE) (50%). The pooled prevalence for PH in general ILD populations was 36% (95%CI 30-42%) using RHC, and 34% (95%CI 29-38%) using TTE. Lower diffusion capacity for carbon monoxide, worse oxygenation status, reduced exercise capacity, increased pulmonary artery to aorta ratio and pulmonary artery diameter, and elevated serum brain natriuretic peptide were consistently associated with the presence of PH in at least 60% of reported studies. The presence of PH was associated with increased symptom burden and worse prognosis. Outcome measures in interventional trials of PH in ILD focused on changes in pulmonary vascular haemodynamic and 6-minute walk distance. PH is a common complication in ILD with significant health impacts. A standardised definition with prospective evaluation of risk-stratified assessments for PH using identified associated risk factors is warranted. Our findings provide an evidence base for validation as surrogate endpoints in future PH interventional trials in ILD.