Kruimelpad

ERS 2017

  • Aanvrager: Dr I.M. Boudewijn

European Respiratory Society International Congress 2017, Milan, 9-13 September 2017

A nasal gene expression profile differentiates individuals with and without COPD and overlaps bronchial gene expression

Ilse M Boudewijn1,2, Alen Faiz1,2, Katrina Steiling3,4, Erica van der Wiel1,2, Eef D Telenga1,2, Susan JM Hoonhorst1,2, Nick H T ten Hacken1,2, Corry-Anke Brandsma2,5, Huib AM Kerstjens1,2, Wim Timens2,5, Irene H Heijink1,2,5, Marnix R Jonker5, Harold G de Bruin5, J Sebastiaan Vroegop6, Henk R Pasma7, Wim G Boersma8, Pascal Wielders9, Frank van den Elshout10, Khaled Mansour11, Avrum Spira3,4, Marc E Lenburg3,4, Dirkje S Postma1,2, Maarten van den Berge1,2

1University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands
2University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
3Division of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts
4Bioinformatics Program, Boston University, Boston, Massachusetts
5University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands
6Martini Hospital Groningen, Department of Pulmonary Diseases, Groningen, the Netherlands
7Medical Centre Leeuwarden, Department of Pulmonary Diseases, Leeuwarden, the Netherlands
8Noordwest Ziekenhuisgroep, Department of Pulmonary Diseases, Alkmaar, the Netherlands
9Catharina Hospital Eindhoven, Department of Pulmonary Diseases, Eindhoven, the Netherlands
10Rijnstate Hospital, Department of Pulmonary Diseases, Arnhem, the Netherlands
11Orbis Concern, Department of Pulmonary Diseases, Sittard, the Netherlands

Introduction
Nasal gene expression profiling is a promising method to characterize COPD non-invasively. First, we aimed to identify a nasal gene expression profile that distinguishes COPD patients from healthy controls. Next, we investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile in the lower airways, i.e. the bronchial epithelium.

Methods
Genome wide gene expression analysis was performed on nasal epithelial brushes of 76 COPD patients and 39 healthy controls, using Affymetrix Human Gene 1.0 ST Arrays. To compare findings in nasal and bronchial epithelium, we repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of COPD patients and controls.

Results
We found 2673 genes to be significantly differentially expressed in nasal epithelium between COPD patients and controls, 1158 being up- and 1515 downregulated in COPD (false discovery rate <0.05). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of nasal and bronchial COPD-associated changes in gene expression in both independent cohorts (FDRGSEA < 0.001). We found 591 genes significantly associated with COPD in the same direction in nasal and bronchial epithelium, 350 genes being up- and 241 downregulated.

Conclusion
We identified a nasal gene expression profile that differentiates individuals with and without COPD. Of interest, part of the nasal gene expression changes in COPD is comparable to differentially expressed genes in the bronchus. These findings indicate that nasal gene expression has the potential to be developed as a non-invasive biomarker in COPD.