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(partial) translation : | Français/French |  :-) Previous edito Décembre 96 Planning for asthma research by the Millennium: Looking for the cause(s) of asthma? EDITORIAL FOR ASMANET - 16th Jan 1997 K. F. Chung (f.chung (at) ic.ac.uk) National Heart & Lung Institute Imperial College School of Medicine Royal Brompton Hospital London SW3 There is little doubt that together with the increasing prevalence of asthma there is now greater awareness of the problem of asthma world-wide. Data that are now becoming available indicate that asthma does pose an important socio-economic problem in many Western countries and also likely in developing countries. The chronicity of the disease in an important proportion of asthmatics appears to be a greater burden while the deaths rates from asthma, although unacceptable at whatever levels, have levelled off in countries such as New Zealand where there was an unexpected rise in the late 80’s. The setting-up of proposals for guidelines that could be applied worldwide under the aegis of the World Health Organisation has also served to focus the problem of asthma and of the delivery of asthma care and prevention in third world countries. Increasingly, therefore, asthma is being recognised as a world-wide problem. Together with this recognition, there has been an unprecedented interest in research in asthma at all levels, from the assessment of disease activity, to looking for genetic markers, to discovering new antiasthma drugs and to pinpointing the cells and cytokines involved in the chronic inflammatory process. The diversity of the research can be illustrated by looking through the pages of recent journals. For example, in the October 1996 issue of the American Journal of Respiratory and Critical Care Medicine, one can see 12 original articles under the section of asthma which deals with risk factors for asthma, peak flows and symptom scores, induced sputum to assess airway inflammation, leukotrienes, lidocaine/mexilitine in treating asthma, interleukin-1ß etc. Therefore, there are increasing number of investigations into an ever-widening range of areas relating to asthma, which does illustrate the breadth and depth of asthma research undertaken also by a large number of talented investigators, both in the clinical and scientific arenas, around the world.

Like researchers in the basic sciences, investigators in asthma (outside the pharmaceutical industry) do not have any constraints in choosing the fields that they wish to investigate. At present, funding bodies are not, at least overtly, biased towards one area vis-a-vis another, although there are areas that would be more favourably looked upon at one time than another. The pharmaceutical industry on the other hand has a more focused objective, but there is the growing realisation that the development of drug targets depends on a greater understanding of the basic process of asthma (more ‘blue skies’ research). With limited research funding, it is necessary that research in asthma be more cost-effectively organised and carried out. This would necessarily entail prioritizing asthma research by deciding the crucial areas for investigation in order to answer the most important questions of asthma pathogenesis and ultimately treatment.

What then are the major questions that need to be tackled in asthma? It may be considered too premature to consider finding the cause of asthma or a cure for asthma, but there are several immediate areas that needs addressing. These have been recently considered in two recent supplements of the American Journal of Respiratory and Critical Care Medicine, one dealing with childhood asthma (Feb 95) and the other mainly adult asthma (June 96). The priority questions raisedare:

1. Knowledge of childhood asthma is scanty compared to adult asthma, given that much of asthma starts in early chilhood. Studies of populations at risk would be more appropriate (but more difficult) in the very young. The influence of environmental exposure usually starts at an early age and the role of IgE (the mechanisms of its development) is likely to be more important at that time.
2. The possibility of discovering asthma susceptibility genes: since asthma appears to have multifactorial components, it is likely that this condition may occur through the interaction of various genes or that these may determine the severity, phenotypic expression and response to treatments.
3. Continuing to examine the airways of the asthmatic for clues to the important pathophysiological mechanisms, the role of certain inflammatory cells (macrophages, T-cells, eosinophils) and cytokines, which may determine chronicity and severity, and look for genetic polymorphisms. What is probably more important is to select the susceptible ‘pre-asthmatic’ for doing such studies, perhaps using validated non-invasive procedures to obtain airway samples
4. The importance of trigger factors such as viruses and allergens, and environmental factors such as pollutants and cigarette smoking.
5. For those with established on-going asthma, sometimes the treatment afforded by corticosteroids is not entirely adequate and in these difficult asthmatics, a significant advance in pharmacological control of the condition is clearly needed. Clearly, asthma research will continue to be an interdisciplinary cooperation between geneticists, epidemiologists, immunologists, pharmacologists, cell biologists and clinicians including paediatricians.

If these are the priority questions, can asthma research be organised in a better way? Increased cooperation between research groups will certainly allow better selection of bigger study populations, pool scant resources, and discussion allows for better protocols and ideas to address hypotheses. Already, in the United States, ATS/ALA is funding a limited number of large centres for coordinated research in asthma, while in Europe, funds have been available for improving links between European centres (but not centrally determined). In my opinion, the answer to a lot of asthma will be found by studying actual populations of asthma and information gathered on such populations should remain the core of an asthma research centre through which the various scientists (epidemiologists, pharmacologists, cell biologists, geneticists etc.) will interact. Of particular importance is the pivotal role of the clinical scientist in defining the clinical phenotype, which is not an easy task and on which a lot of asthma research depends. The asthma centre would be a large comprehensive centre and need ‘hard core’ funding.

With asthma being a global problem, increasing dialogue between research groups is a necessity, and is provided usually under the auspices of regional/international respiratory/allergy meetings. In the European Respiratory Society and the American Thoracic Society, workshops have been set-up to discuss priorities, and to encourage research in certain priority areas. More could probably be achieved at meetings devoted entirely to asthma, such as Interasma organised in Montpellier in 1995 and the World Asthma Congress that was first organised by ATS in Chicago in 1995. Another World Asthma Congress is planned in Europe in 1998.

As we look towards the Millennium and with the great strides in cell and molecular biology, one cannot but hope to see some light at the end of the tunnel. Will it be a new wonder drug, or an encompassing mechanism that explains the onset of asthma? Who knows, but once priorities are set, and large asthma centres are set-up through regional funding, we should be optimistic.

16th Jan 1997

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