Consensus network analysis reveals pathways associated with lung function decline in both COPD and IPF

Introduction: COPD and IPF are both diseases associated with smoking and aging but with contrasting pathologies: COPD by tissue destruction and IPF with increased fibrotic tissue. However, IPF patients also commonly present with Combined Pulmonary Fibrosis and Emphysema (CPFE) suggesting that despite very different phenotypes, common pathways may occur in both COPD and IPF. In this study, we analyzed gene expression using a weighted gene connectivity consensus network to identify groups of genes with correlated expression that are present in both COPD and IPF. Methods: GEO dataset 47460 consisting of 105 control, 211 COPD, and 159 IPF subjects collected by the Lung Tissue Research Consortium was analyzed. A consensus WGCNA was applied to the COPD and IPF samples to determine overlapping groups of correlated genes. These modules were then correlated to lung function (DLCO, FEV1, FVC) with adjustment for multiple comparisons. Genes in each module that were correlated to both module and lung function were used to determine GO pathways. Results: A total of 44 consensus modules were identified with 19 having significant correlation with lung function (p Conclusion: This study highlights pathways that are present in both COPD and IPF that are related to lung function decline using network analysis. We found overlapping immune response and cellular stress pathways and downregulation of pathways related to cellular adhesion present in both COPD and IPF. Further confirmation on CPFE lungs to determine clinical relevance is required.