Dataset Information

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension.

ABSTRACT: Objective:We sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH). Methods:Two pulmonary pathologists blindly evaluated 360 histologic slides from lungs of 31 SSc-PF explants or autopsies with (n = 22) and without (n = 9) PH. The presence of abnormal small arteries, veins, and capillaries (pulmonary microcirculation) was semiquantitatively assessed in areas of preserved lung architecture. Capillary proliferation (CP) within the alveolar walls was measured by its distribution, extent (CP % involvement), and maximum number of layers (maximum CP). These measures were then evaluated to determine the strength of their association with right heart catheterization-proven PH. Results:Using consensus measures, all measures of CP were significantly associated with PH. Maximum CP had the strongest association with PH (P = 0.013; C statistic 0.869). Maximum CP 2 or more layers and CP % involvement 10% or greater were the optimal thresholds that predicted PH, both with a sensitivity of 56% and specificity of 91%. The CP was typically multifocal rather than focal or diffuse and was associated with a background pattern of usual interstitial pneumonia. There was a significant but weaker relationship between the presence of abnormal small arteries and veins and PH. Conclusion:In the setting of advanced SSc-PF, the histopathologic feature of the pulmonary microcirculation best associated with PH was capillary proliferation in architecturally preserved lung areas.

SUBMITTER: Seki A

PROVIDER: S-EPMC6858021 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension.

Seki Atsuko A Anklesaria Zafia Z Saggar Rajeev R Dodson Mark W MW Schwab Kristin K Liu Ming-Chang MC Charan Ashana Deepshikha D Miller William D WD Vangala Sitaram S DerHovanessian Ariss A Channick Richard R Shaikh Faisal F Belperio John A JA Weigt Stephen S SS Lynch Joseph P JP Ross David J DJ Sullivan Lauren L Khanna Dinesh D Shapiro Shelley S SS Sager Jeffrey J Gargani Luna L Stanziola Anna A Bossone Eduardo E Schraufnagel Dean E DE Fishbein Gregory G Xu Haodong H Fishbein Michael C MC Wallace William D WD Saggar Rajan R

ACR open rheumatology 20190315 1

<h4>Objective</h4>We sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH).<h4>Methods</h4>Two pulmonary pathologists blindly evaluated 360 histologic slides from lungs of 31 SSc-PF explants or autopsies with (n = 22) and without (n = 9) PH. The presence of abnormal small arteries, veins, and capillaries (pulmonary microcirculation) was semiquanti ...[more]

PMID: 31777777

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Project description:ObjectiveTo compare time to clinical worsening (TTCW) based on initial oral therapy for pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc)-related PAH.MethodsUsing data from the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) registry (a multicenter prospective observational study enrolling SSc patients with incident pulmonary hypertension), we selected patients with group 1 PAH (World Health Organization Clinical Classification system) who received initial therapy (for 6 months) with an endothelin receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, or a combination of these 2 agents (ERA/PDE5 inhibitor). The main outcome was TTCW, defined as the first occurrence of death, PAH-related hospitalization, lung transplantation, initiation of parenteral prostacyclin treatment, or worsening symptoms.ResultsNinety-eight patients (24 in the ERA group, 59 in the PDE5 inhibitor group, and 15 in the ERA/PDE5 inhibitor group) were included. No significant differences in the baseline characteristics of the patients were observed. TTCW was significantly worse in patients in the ERA group compared with those in the PDE5 inhibitor group or the ERA/PDE5 inhibitor group. Ten patients (41.6%) in the ERA group died during the 3-year observation period, compared with 4 patients (6.8%) in the PDE5 inhibitor group and 1 patient (6.7%) in the ERA/PDE5 inhibitor group. Baseline factors that were independently associated with a shorter TTCW were initial treatment with an ERA (hazard ratio [HR] 2.63 [P = 0.009]), lower diffusing capacity for carbon monoxide (HR 0.69 per 10% of predicted change [P = 0.04]), and higher pulmonary vascular resistance (HR 1.10 per Wood unit change [P = 0.007]).ConclusionCompared with initial treatment with a PDE5 inhibitor or combination therapy with an ERA and a PDE5 inhibitor, initial therapy with an ERA in patients with SSc-related PAH was associated with significantly worse TTCW, even after adjustment for commonly accepted prognostic factors. Further study into the optimal initial oral therapy for patients with SSc-related PAH is needed.

Project description:Objective: Pulmonary complications in systemic sclerosis (SSc), including pulmonary fibrosis (PF) and pulmonary arterial hypertension (PAH), are the leading cause of mortality. We compared the molecular fingerprint of SSc lung tissues and matching primary lung fibroblasts to those of normal donors, and patients with idiopathic pulmonary fibrosis (IPF) and idiopathic pulmonary arterial hypertension (IPAH). Methods: Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively. Results: We identified a consensus of 242 and 335 genes that were differentially expressed in lungs and primary fibroblasts, respectively. Enriched function groups in SSc-PF and IPF lungs included fibrosis, insulin-like growth factor signaling and caveolin-mediated endocytosis. Functional groups shared by SSc-PAH and IPAH lungs included antigen presentation, chemokine activity, and IL-17 signaling. Conclusion: Using microarray analysis on carefully phenotyped SSc and comparator lung tissues, we demonstrated distinct molecular profiles in tissues and fibroblasts of patients with SSc-associated lung disease compared to idiopathic forms of lung disease. Unique molecular signatures were generated that are disease- (SSc) and phenotype- (PF vs PAH) specific. These signatures provide new insights into pathogenesis and potential therapeutic targets for SSc lung disease. Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively.

Dataset Information

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension.

Publications

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension.

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