Pulmonary Hypertension in Interstitial Lung Disease: A Systematic Review and Meta-Analysis

Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances.

What are the diagnostic evaluation, epidemiologic features, associated factors, prognostic significance, and outcome measures in interventional trials for PH in patients with ILD in the current literature?

The Ovid MEDLINE, Embase, and CENTRAL databases were searched for original research evaluating PH in participants with ILD of any cause. The definition of PH was based on the investigators' criteria.

Three hundred two studies were included, with varying diagnostic evaluations used to define PH. Commonly used diagnostic tests were right heart catheterization (56%) and transthoracic echocardiography (50%). The pooled prevalence for PH in general populations with ILD was 36% (95% CI, 30%-42%) using right heart catheterization and 34% (95% CI, 29%-38%) using transthoracic echocardiography. Lower diffusion capacity of the lungs 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 consistently were 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 hemodynamics and 6-min walk distance.

PH is a common complication in ILD with significant health impacts. A standardized 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 end points in future PH interventional trials in ILD.

International Prospective Register of Systematic Reviews; No.: CRD42021255394; URL: https://www.crd.york.ac.uk/prospero/.