Becker EJ, Faiz A, van den Berge M, et al. - Leveraging previous work showing bronchial airway COPD-related gene expression changes, researchers herein investigated whether there exist alterations related to variations in the rate of FEV ₁ reduction. Participants were ever smokers with and without COPD who at baseline underwent bronchial brushings profiled by Affymetrix microarrays and underwent longitudinal lung function recordings (n = 134; mean follow-up = 6.38±2.48 years). Expression variations in 171 genes were found to be related to rate of FEV ₁ reduction (false discovery rate <0.05). In this study, an airway gene expression signature related to the rate of FEV ₁ reduction was found and replicated. This signature’s aspects were identified to be linked with elevated expression of XBP1-regulated genes, a transcription factor implicated in the unfolded protein response, and genes associated with mucin generation. Taken together, these findings indicate that molecular processes associated with the rate of FEV ₁ decrease can be identified in airway epithelium, detect a likely indicator of FEV ₁ reduction and allow identification of, in an early phase, ever smokers with and without COPD most at risk of rapid FEV ₁ decline.