"Interstitial lung disease with associated severe pulmonary hypertension is rarely idiopathic by clinical or...

Interstitial lung disease (ILD) patients who develop severe pulmonary hypertension (PH) have rapidly progressive disease and increased mortality, but their clinical and pathologic phenotypes are poorly defined. Improved understanding and identification of these patients will expedite beneficial PH-targeted therapeutics and referral for lung transplantation.

We conducted a comprehensive retrospective study of a large cohort of ILD patients who underwent lung transplant at UCLA. Multidisciplinary Discussion (MDD) was used to establish ILD etiologies incorporating all available clinical, radiographic, and pathologic data. Severe pre-capillary PH was defined as pulmonary vascular resistance >5 Wood units on cardiac catheterization. Quantitative histopathologic analysis of explanted idiopathic pulmonary fibrosis (IPF) lungs was performed using blinded whole-slide annotation by two pulmonary pathologists, comparing the pathologic features of IPF with severe PH to IPF without PH.

Among 347 ILD patients, 13% had severe PH. In the large majority of cases (86%), the correct ILD diagnosis/etiology was established clinically with MDD alone. Only 20% of severe PH cases were classified as IPF, with the most common subtype identified as autoimmune-associated ILD. On histopathology, IPF patients with severe PH demonstrated a similar extent of usual interstitial pneumonia but markedly less normal lung and a greater burden of atypical pathology, particularly nonspecific interstitial pneumonia, compared to IPF patients without PH.

Our study illustrates the low prevalence of IPF in severe PH-ILD, describes a novel finding of distinct histopathologic features of IPF patients with severe PH versus no PH, and demonstrates the diagnostic utility of MDD without explant pathology.