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Irish asthma research

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Dr Conor Burke was recently awarded a significant grant from the Gabriel Project to fund his research into asthma at Connolly Hospital, Dublin. Here he explains the need for basic research into asthma epidemiology and how this can be applied in the clinical setting

Essentially, the Gabriel Project (the word Gabriel doesn’t stand for anything in particular, but is merely a descriptive term) was inaugurated by the EU with funding of €20 million three years ago, in 2006.

The project consists of research teams from 19 different universities in 37 different countries throughout Europe. It is the largest consortium ever funded anywhere to develop new therapy for asthma and related airway disease.

The constituent members of the Gabriel Project include a wide variety of basic scientists including those working in genetics, genomics, proteomics, immunology, molecular biology, epidemiology and bio-statistics.

The purpose of the project is to elucidate the genetic causes of asthma and how the environment interacts with these genes to produce the relevant findings phenotype, i.e., clinical asthma.

The consortium has made very significant progress in three years.
Prof Bill Cookson, co-chair of the project (with Prof Erica Von Mutius of the Department of Epidemiology in Munich University) has recently described the gene responsible for childhood asthma.

This is by any standards a breakthrough research finding. Prof Von Mutius has contributed much of the epidemiology work which underlines the so-called hygiene hypothesis and delineates the various risk factors and protective factors for asthma in various occupations in various countries, and urban versus rural districts.

While elucidation of the gene that causes asthma in children is a major step forward, it does not itself provide a cure, a prevention or even a new treatment for the clinical disease. Similar considerations apply to the environmental risk factors and environmental protective factors identified by the work of Prof Von Mutius and her colleagues in Munich.

Consequently, at the last meeting of the Gabriel Consortium nine months ago, it was decided to run a European competition to recruit a clinical department of respiratory medicine to join the research departments currently constituting the Gabriel Consortium.

The competition was advertised throughout Europe and in March, Prof Bill Cookson announced that our department at Connolly Hospital had won the invitation to join the Gabriel Project after a peer review process of all the applicants.

The purpose of recruiting a clinical department is, of course, to facilitate the process of so-called translational research, whereby clues and novel mechanisms proposed by research laboratories can be validated or otherwise in the clinical arena.

The process works in the reverse direction also, whereby hypotheses on mechanisms of disease and causation of disease derived from clinical evaluation can be verified in the genetic and proteomic research laboratories.

This process of so-called translational medicine is a much more efficient methodology for development of new treatments than the older model, whereby basic research was carried out on the university campus and patients were treated in the hospital which process militated against any significant interaction between clinical and basic scientists.

The specific purpose of the Gabriel Project is to develop new treatments for asthma by elucidating how environmental triggers and genetic predispositions combine to trigger the disease phenotype; in this case, asthma.

Prevalence
The reason why such a large project targets asthma relates, of course, to the prevalence of the condition. Current EU figures show that approximately 32 million residents of the EU have asthma.

The economic cost to the EU of asthma is approximately 17.5 billion euro per annum. One person dies from asthma in Europe every hour. Ireland has the highest prevalence of asthma in the world and more than one person dies from asthma in Ireland every week, so asthma represents an enormous humanitarian, clinical and financial challenge to the EU.

The new clinical department of respiratory medicine was opened in Connolly Hospital in early March. It comprises fully clinical facilities and will see over 250 patients per week with a capacity for further expansion.

In addition to clinical facilities the department comprises a series of lung function laboratories to document not only basic lung function, but also body plethysmography, cardio-pulmonary stress exercise protocols, occupational challenge, bronchial provocation protocols and sleep laboratories.

The department also houses a state of the art tissue specimen laboratory that can store biological specimens (blood, sputum, bronchioscopic samples) so a library of various asthma phenotypes can be generated.

The department therefore includes all the facilities necessary for the clinical management of asthma and related respiratory diseases together, with a functional and research capacity to look at mechanisms of disease, with a view to identifying new targets for treatment. Integration of these facilities into the wider Gabriel Project will greatly enhance our capacity for new and better treatments and prevention of these common diseases.

Dr Conor Burke, Department of Respiratory Medicine, Connolly Hospital, Blanchardstown, Dublin

 

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