Asthma and Chronic Obstructive Pulmonary Disease (COPD)
R
esearch background
Estimates suggest that 100-150 million people worldwide have asthma. In the UK the prevalence of asthma is particularly high, a recent report showed that in Scotland more than 18% of people experienced asthma symptoms and in England and Wales similar figures were reported, 17% and 15.3% respectively (Global Initiative for Asthma 2004).
COPD is a composite term encompassing several diseases including chronic bronchitis and emphysema. COPD is the fourth most common cause of death worldwide (WHO 2004).
Asthma and COPD are complex disease involving both genetic and environmental factors resulting in disease expression.
What we are doing about asthma and COPD
On-going research in the Division of Respiratory Medicine aims to further understand the mechanisms underlying asthma and COPD using a combination of molecular genetics and cell biology approaches.
Molecular genetics
Professor Ian Hall and Dr Ian Sayers have a key interest in the identification of genetic factors underlying susceptibility to develop asthma and COPD. Using positional cloning and candidate gene approaches several potential asthma susceptibility genes have been identified e.g. PLAUR, ALOX5AP (lead Sayers). More recently using the current method of choice i.e. Genome Wide Association (GWA) and large populations involving 1000s of individuals multiple loci associated with lung function and severe asthma have been identified with confidence (lead Hall/Sayers). Current approaches include GWAS meta-analyses, focussed re-sequencing, exome SNP analyses and exome sequencing. The Sayers/Hall group have a long standing collaboration with the Genetic Epidemiology Group based at the University of Leicester (lead Professor Martin Tobin). Parallel projects aim to translate these genetic findings to altered biology in the airways of patients using cell and tissue approaches particularly for genes identified as determinants of lung function (lead Hall) and genes identified as contributing to asthma (lead Sayers).
Cell biology
In addition to genetics several studies are investigating altered biology of airway structural cells in the lungs of asthma patients where intrinsic differences in e.g. airway epithelium barrier formation are thought to at least in part contribute to asthma disease mechanisms.
Drs Dominick Shaw and Sayers lead investigations into these epithelial mechanisms by studying cells isolated from asthma patients and healthy controls including evaluating novel and existing medicines on these cell functions. Similarly, the investigation of altered airway smooth muscle function in asthma is a focus including studies of altered calcium homeostasis (Professor Ian Hall), mechanisms of transcriptional regulation particularly epigenetic control (Professor Alan Knox, Professor Linhua Pang) and alterations in a family of proteases called matrix metalloproteinases (MMPs) (Professor Simon Johnson).
We are also studying the role of integrin mediated TGFbeta activation in driving airway remodelling in response to influenza infection (Gisli Jenkins) and are developing 3D scaffolding airway models in conjunction with colleagues in tissue engineering (Dr Felicity Rose) and clinical immunology (Dr Amir Ghaemmaghami). We are also part of an MRC/ABPI consortium (MRCMAP) in COPD looking at mechanisms involved in airway and alveolar remodelling in collaboration with academic partners at Imperial, Newcastle and Southampton and several industrial partners.
Links with clinical trials
There is a strong translational focus to these laboratory based approaches with links with on-going clinical trials to use patient resources to investigate mechanisms underlying e.g. extrapulmonary associations of chronic respiratory disease (Dr Charlotte Bolton) and the cellular basis for clinical efficacy of existing drugs used in the treatment of asthma (Dr Dominick Shaw).
Funding
Asthma and COPD research is funded by significant grants from Asthma UK, MRC, BBSRC, NC3Rs, Wellcome Trust, British Medical Association and Pfizer.