Source: International Congress 2014 – Novel approaches in transcriptomics and epigenomics in inflammatory lung diseases and lung cancer
Disease area: Airway diseases

Abstract

We have recently described COPD-associated gene-expression differences in bronchial airway epithelium that define a COPD field of injury. In this study, we sought to validate our COPD gene-expression signature and identify gene-expression changes associated with inhaled budesonide/formoterol (BUD/FORM; Symbicort^®; 160/4.5 mcg x 2 puffs bid) in COPD patients.Methods: Current and former smokers with (n=15) and without (n=13) COPD were enrolled and underwent baseline collection of bronchial epithelium via bronchoscopy. Re-sampling was performed on 10 COPD subjects after initiation of BUD/FORM therapy (median 97 days). RNA was hybridized to arrays. A linear model adjusting for age was used to identify gene expression changes associated with baseline COPD status, while changes associated with therapy were found using a paired t-test within COPD subjects. Relationships with previously published signatures were assessed using GSEA.Results: Expression levels of 496 genes were altered at baseline in COPD subjects (p<0.05). Importantly, our previous 98-gene airway field of injury signature was enriched in this independent cohort (p<0.001). Expression levels of 896 genes were altered following BUD/FORM therapy (p<0.05). The 50 genes most repressed in COPD subjects were enriched in the group of genes increased by BUD/FORM (p<0.001).Conclusions: Our study shows that components of the COPD-associated alterations in airway gene-expression are reversible following short-term budesonide/formoterol treatment. This suggests that the airway field of injury in COPD is dynamic with therapy, raising the possibility that molecular profiles in the relatively accessible airway epithelium may serve as markers of therapeutic efficacy.

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Citations should be made in the following way:
Y. Gesthalter, K. Steiling, M. Lenburg, A. Spira, F. Schembri (Boston, United States Of America). The impact of budesonide/formoterol on the airway transcriptome in COPD. Eur Respir J 2014; 44: Suppl. 58, 400

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