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Periodic Report Summary 2 - EVA (Markers for emphysema versus airway disease in COPD)
Quality validation date:2013-02-01
Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lung. It is a global problem in that in 2004 it was the 4th leading cause of death worldwide http://www.who.int/respiratory/copd/burden. The disease is related to smoking and in the developing world to the exposure to indoor smoke from cooking fire. When patients with COPD avoid further exposure, e.g. when they stop smoking the disease process continues. The mechanisms driving this are unknown. There is, however, evidence to suggest a contribution of genetics to the COPD phenotype since only 15% of smokers develop COPD and since COPD runs in families (Silverman Proc Am Thorac Soc.3:405, 2006). Current therapies can improve lung function and reduce frequency of exacerbations but this has little impact on mortality (Calverly, N Engl J Med. 2007;356:775). Therefore new therapies based on an understanding of the mechanisms of disease are required.
The ambitious targets required dedicated efforts by all partners of the project and it required extension of the recruitment period to 3 years and 3 months such that with recruitment complete only 3 months remained until the end of the funding period. Still the genetic assays with DNA and RNA sequencing and the protein assays have been executed, but the analysis and exploitation of the data is still ongoing.
The original strategy for the EVA project was to recruit patients, who are subjected to CT of the lung. Based on image analysis patients with emphysema-predominant and airway disease predominant disease were to be selected. These patients were to be offered bronchoscopy with the aim of obtaining material from 300 patients. Alongside 300 controls were to be recruited for bronchoscopy but no CT. Also, DNA was proposed to be used for genome wide association studies (GWAS). In order to identify disease specific mutations it was planned to sequence 1 MB of DNA for 60 samples.
The new strategy was implemented by the consortium because of difficulties in patient compliance with a long waiting period between CT and bronchoscopy. The new steps were to recruit 500 patients, perform CT and offer bronchoscopy to all of the patients irrespective of the result of the CT image analysis. A recruitment-above-target was necessary because of a 20% drop-out rate, originally calculated to be only 10%. All of these changes required some reallocation of budget in order to cover the associated costs. In the genetic studies priority was given to transcriptome analysis using the powerful RNA sequencing approach on the epithelial cells and alveolar macrophages from the lung. In addition, with novel technology available, the consortium decided to perform whole genome sequencing on 21 samples from blood and lung. Taken together the EVA study has been able to recruit a tremendous number of patients and controls to this invasive study and this will allow for informative analysis in a disease, which comes in different stages and consists of sub-phenotypes.
Collaboration sought:N/A
Related Programme(s)/Projects
| Programme | Project reference | Project title |
| FP7-HEALTH | 200605 | Markers for emphysema versus airway disease in COPD |
Contact person
Organization:HELMHOLTZ ZENTRUM MUNCHEN DEUTSCHESFORSCHUNGSZENTRUM FUR GESUNDHEIT UND UMWELT GMBH
Name:
Position:Head Project Management
Address:
WT
MUENCHEN
DEUTSCHLAND
Region: BAYERN OBERBAYERN München, Kreisfreie Stadt
Tel:+49-8931873022
Fax:+49-8931872212
Email:Contact
URL:http://www.eva-copd.eu/
Organization type:
Additional information
Subject index:Biotechnology, Medicine, Health
Subject descriptors:Pharmacy, pharmacology, Microbiology, Biotechnology, Cell biology
Subject class:Biology, Medicine
Remarks:Source: SESAM
Record control number:54427
