RT Journal Article SR Electronic T1 Lung tissue gene-expression signature for the ageing lung in COPD JF Thorax JO Thorax FD BMJ Publishing Group Ltd and British Thoracic Society SP thoraxjnl-2017-210074 DO 10.1136/thoraxjnl-2017-210074 A1 Maaike de Vries A1 Alen Faiz A1 Roy R Woldhuis A1 Dirkje S Postma A1 Tristan V de Jong A1 Don D Sin A1 Yohan Bossé A1 David C Nickle A1 Victor Guryev A1 Wim Timens A1 Maarten van den Berge A1 Corry-Anke Brandsma YR 2017 UL http://thorax.bmj.com/content/early/2017/12/06/thoraxjnl-2017-210074.abstract AB Introduction COPD is a chronic, progressive, inflammatory disease of the lungs and the third leading cause of death worldwide. The current knowledge of the pathophysiology of COPD is limited and novel insights in underlying disease mechanisms are urgently needed. Since there are clear parallels between ageing and COPD, we investigated genes underlying lung ageing in general and abnormal lung ageing in COPD.Methods Whole genome mRNA profiling was performed on lung tissue samples (n=1197) and differential gene expression with increasing age was analysed using an adjusted linear regression model. Subsequent pathway analysis was performed using GeneNetwork and the gene-expression signature was compared with lung ageing in the Genotype-Tissue Expression (GTEx) project. In a subset of patients with COPD (n=311) and non-COPD controls (n=270), we performed an interaction analysis between age and COPD to identify genes differentially expressed with age in COPD compared with controls, followed by gene set enrichment pathway analysis.Results We identified a strong gene-expression signature for lung ageing with 3509 differentially expressed genes, of which 33.5% were found nominal significant in the GTEx project. Interestingly, we found EDA2R as a strong candidate gene for lung ageing. The age*COPD interaction analysis revealed 69 genes significantly differentially expressed with age between COPD and controls.Conclusions Our study indicates that processes related to lung development, cell-cell contacts, calcium signalling and immune responses are involved in lung ageing in general. Pathways related to extracellular matrix, mammalian target of rapamycin signalling, splicing of introns and exons and the ribosome complex are proposed to be involved in abnormal lung ageing in COPD.