MRC/ABPI COPD Consortium Work Package 1: COPD Phenotyping

COPD (which used to be called chronic bronchitis and emphysema) is a common disease which causes considerable difficulty to sufferers. The pharmaceutical industry has been relatively unsuccessful in bringing new treatments to the marketplace for COPD, with many products failing when they are first given to patients. This is largely because not all COPD sufferers are the same and it is likely that drugs will treat certain aspects of the disease and therefore are more likely to benefit some but not all patients. We propose to try to understand what makes people with COPD different from each other and to use these differences to further our understanding of which types of drugs will benefit which types of people. Using this approach we aim to identify markers in blood and sputum that will help us to predict the progression of COPD and response to therapy.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and healthcare expenditure in the UK (#1B/annum). Worldwide, over 27,000 people died from COPD in 2004 and the WHO forecasts COPD to be the 3rd leading cause of death in the world by 2030. Current therapies are ineffective in preventing the progressive airway remodelling and emphysema, or recurrent exacerbations which are COPD hallmarks. New therapeutic approaches targeting these processes would address a major unmet need. This application will provide the patient-specific data and samples that will underpin the phenotyping effort described here and all the mechanistic studies described in the other work packages of the consortium. This MRC/ABPI COPD consortium will build on existing COPD cohorts and bio-resources from early to established disease and relevant controls. These cohorts and bio-resources include MRC funded, Industry, EU-FP7, NIH, and NIHR-led cohorts. Importantly this application provides the framework for the consortium to evolve to support its changing needs and is sufficiently flexible to allow integration with future initiatives. The available data comprise extensive clinical characterisation, standard physiological measurements, CT-scans, and biological phenotyping from genome to proteome. Additional data are available from some cohorts at exacerbation events complemented with detailed molecular microbiology and virology. In others detailed measures of co-morbidities, activity monitoring, systemic inflammation and skeletal muscle biology has been assessed. We shall harmonise the data between the cohorts and will add follow-up data, and in pre-specified subgroups innovative small airway physiology, imaging and the sampling of tissue and blood to facilitate, target validation and ex vivo modelling and potentially high throughput ?omic? analyses. These data will be used to identify biologically relevant sub-phenotypes required to support the studies outlined in the other work packages, and will be interrogated using bio-statistical modelling to identify novel phenotypes to drive future hypothesis driven mechanistic studies. This connectivity with the other work packages will undergo an iterative process of ?test? and ?validation? groups each further refining the phenotyping effort; informing the mechanistic studies and the sample sizes required for adequate statistical power. Through this integrated joint academic and industry consortium we shall provide the framework necessary to achieve a step-change in our understanding of COPD which we anticipate will lead onto improvements in the treatment of this devastating disease.