Chronic Hypersensitivity Pneumonitis, an Interstitial Lung Disease with Distinct Molecular Signatures

Overview

Journal Am J Respir Crit Care Med

Specialty Critical Care

Date 2020 Jul 1

PMID 32602730

Citations 45

Authors

Haruhiko Furusawa

Jonathan H Cardwell

Tsukasa Okamoto

Avram D Walts

Iain R Konigsberg

Jonathan S Kurche

Tami J Bang

Marvin I Schwarz

Kevin K Brown

Jonathan A Kropski

Mauricio Rojas

Carlyne D Cool

Joyce S Lee

Paul J Wolters

Ivana V Yang

David A Schwartz

Affiliations

Soon will be listed here.

Abstract

Chronic hypersensitivity pneumonitis (CHP) is caused by an immune response to antigen inhalation and is characterized by variable histopathological and clinical features. A subset of subjects with CHP have usual interstitial pneumonia and appear to be clinically similar to subjects with idiopathic pulmonary fibrosis (IPF). To determine the common and unique molecular features of CHP and IPF. Transcriptome analysis of lung samples from CHP ( = 82), IPF ( = 103), and unaffected controls ( = 103) was conducted. Differential gene expression was determined adjusting for sex, race, age, and smoking history and using false discovery rate to control for multiple comparisons. When compared with controls, we identified 413 upregulated and 317 downregulated genes in CHP and 861 upregulated and 322 downregulated genes in IPF. Concordantly upregulated or downregulated genes in CHP and IPF were related to collagen catabolic processes and epithelial development, whereas genes specific to CHP (differentially expressed in CHP when compared with control and not differentially expressed in IPF) were related to chemokine-mediated signaling and immune responsiveness. Using weighted gene coexpression network analysis, we found that among subjects with CHP, genes involved in adaptive immunity or epithelial cell development were associated with improved or reduced lung function, respectively, and that MUC5B expression was associated with epithelial cell development. MUC5B expression was also associated with lung fibrosis and honeycombing. Gene expression analysis of CHP and IPF identified signatures common to CHP and IPF, as well as genes uniquely expressed in CHP. Select modules of gene expression are characterized by distinct clinical and pathological features of CHP.

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