Parenchymal and Vascular Interactions in the Pathogenesis of Nonspecific Interstitial Pneumonia in Systemic Sclerosis and Idiopathic Interstitial Pneumonia

Abstract

Background: Interstitial lung disease is a well-recognized prognostic factor in systemic sclerosis (SSc). As the prognosis in nonspecific interstitial pneumonia (NSIP) has been described to be better in collagen vascular disorders compared to the idiopathic forms, we hypothesize that the mechanisms of repair and remodeling are different between these 2 forms of the disease. Objectives: To compare the mechanisms of repair and remodeling between SSc-associated NSIP and the idiopathic form, its impact on pulmonary function tests and survival rates. Methods: We analyzed 18 biopsies from patients with NSIP associated with SSc and 22 with idiopathic NSIP and compared the epithelial and vascular densities as well as vascular activity. Results: Epithelial cell density was lower in SSc-NSIP when compared with idiopathic NSIP (p < 0.0001). Type II pneumocytes and Clara cells were reduced in idiopathic NSIP (p = 0.02). A decrease in microvessel density was found in SSc-NSIP compared to idiopathic NSIP (p < 0.0001). The vascular activity measured by VCAM expression was higher in NSIP-SSc when compared to the idiopathic group (p < 0.0001). The DLCO/VA in SSc-NSIP was more compromised. A direct association between vascular density and DLCO/VA was found (p = 0.02). There was no difference in the survival rate between the 2 groups after a follow-up of 36 months. Conclusions: Alterations in the epithelium and vasculature seem to differ in the pathogenesis of SSc-NSIP when compared to the idiopathic form of the disease. Further studies may be required to assess the significance of these findings and explore if they can provide prognostic and/or treatment information.

CD4+ and CD8+ T lymphocytes in lung tissue of NSIP: Correlation with T lymphocytes in BALF

“…It can be associated with many conditions such as connective tissue disease, drug exposure and hypersensitivity pneumonia. 1 This histologic pattern is characterized by infiltration of inflammatory cells in the interstitium, consisting of lymphocytes and plasma cells. Infiltrating lymphocytes, predominantly CD4þ T lymphocytes, with an elevated CD4þ/CD8þ T cell ratio were found in NSIP patients.…”

The role of lung biopsy for diagnosis and prognosis of interstitial lung disease in systemic sclerosis: a systematic literature review

“…Lung biopsies were obtained by surgery in 13 studies: VATS in 6) [ 18 , 23 , 25 , 26 , 28 , 31 , 32 ] and open surgical biopsy in 7) [ 22 , 24 , 28 – 30 , 33 , 34 ]. In one study, endobronchial biopsy was performed to study the bronchial mucosa [ 27 ].…”

Biomarkers of connective tissue disease‐associated interstitial lung disease in bronchoalveolar lavage fluid: A label‐free mass spectrometry‐based relative quantification study

“… 32 , 33 Lung specimens from patients with SSc and mainly cellular nonspecific interstitial pneumonia show increased VCAM‐1 expression. 34 Compared with that in SSc, the expression of VCAM‐1 is more pronounced in granulomatosis with polyangiitis. High VCAM‐1 protein levels in the peripheral blood of patients with idiopathic pulmonary fibrosis can predict mortality.…”

“…Because VCAM‐1 is expressed in large and small blood vessels after being stimulated by cytokines and it mediates the adhesion of lymphocytes, monocytes, eosinophils, and basophils to vascular endothelium, playing a role in signal transduction 32,33 . Lung specimens from patients with SSc and mainly cellular nonspecific interstitial pneumonia show increased VCAM‐1 expression 34 . Compared with that in SSc, the expression of VCAM‐1 is more pronounced in granulomatosis with polyangiitis.…”