Severe pulmonary hypertension in idiopathic nonspecific interstitial pneumonia

Abstract

Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD), particularly in idiopathic pulmonary fibrosis (IPF) and ILD associated with connective tissue disease, where the underlying pathology is often a nonspecific interstitial pneumonia (NSIP) pattern. The degree of PH in ILD is typically mild to moderate and radiographic changes of ILD are usually prominent. We describe four patients with idiopathic NSIP and severe PH (mPAP > 40 mmHg). The average mean pulmonary artery pressure was 51±7 mmHg and pulmonary vascular resistance was 13±4 Wood's units. Pulmonary function was characterized by mild restriction (total lung capacity 63-94% predicted) and profound reductions in DLCO (19-53% predicted). Computed tomographic imaging revealed minimal to moderate interstitial thickening without honeycombing. In two of the cases, an initial clinical diagnosis of idiopathic pulmonary arterial hypertension was made. Both were treated with intravenous epoprostenol, which was associated with worsening of hypoxemia. All four patients died or underwent lung transplant within 4 years of PH diagnonsis. Lung pathology in all four demonstrated fibrotic NSIP with medial thickening of the small and medium pulmonary arteries, and proliferative intimal lesions that stained negative for endothelial markers (CD31 and CD34) and positive for smooth muscle actin. There were no plexiform lesions. Severe pulmonary hypertension can therefore occur in idiopathic NSIP, even in the absence of advanced radiographic changes. Clinicians should suspect underlying ILD as the basis for PH when DLCO is severely reduced or gas exchange deteriorates with pulmonary vasodilator therapy.

Keywords: interstitial lung disease; pulmonary artery pressure; vasculopathy.

Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1

Representative CT cuts from patients 1-4 demonstrating interstitial changes with reticular ground-glass opacities predominantly in the lower lobes.

Figure 2

Representative pathology. (A) Uniform interstitial fibrosis and mild chronic inflammation characteristic of fibrotic NSIP (H and E, ×4). (B) CD34 (×20) and (C) CD31 stains demonstrate subintimal proliferation by non-endothelial cells (×20). (D) H and E staining (×10) and (E) Movat staining (×20) demonstrate arterial medial hypertrophy with eccentric intimal proliferation. (F) Medial thickening and subintimal proliferation consisting of smooth muscle cells (smooth muscle actin stain, ×20). (G) Concentric intimal proliferation (H and E, ×20). (H) Venous muscularization (Movat statin, ×20).