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

RATIONALE 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 CHP patients have usual interstitial pneumonia and appear to be clinically similar to patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVES To determine the common and unique molecular features of CHP and IPF. METHODS Transcriptome analysis of lung samples from CHP (N=82), IPF (N=103), and unaffected controls (N=103) was conducted. Gene expression was determined adjusting for sex, race, age and smoking history, and using false discovery rate (FDR) to control for multiple comparisons. MEASUREMENTS AND MAIN RESULTS When compared to controls, we identified 413 upregulated and 317 downregulated genes in CHP, and 861 upregulated and 322 downregulated genes in IPF. Concordantly up/down-regulated genes in CHP and IPF were related to collagen catabolic processes and epithelial development, whereas genes specific to CHP were related to chemokine-mediated signaling and immune responsiveness. Using weighted gene co-expression network analysis (WGCNA), 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. CONCLUSIONS 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.