Introduction

ANN J. WOOLCOCK and PETER J. BARNES

Institute of Respiratory Medicine, Sydney, Australia; and National Heart and Lung Institute, Imperial College, London, United Kingdom

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TOP ARTICLE REFERENCES

In spite of more and more research in different disciplines, abnormalities present in the airways of individuals with asthma remain to be defined. Furthermore, the special skills needed to work in molecular biology, airway physiology, and pathology make it difficult for anyone to have a good overview of developments in the understanding of this disease. We have tried over the last 12 years to do this by holding a series of meetings with publications in this journal entitled "AsthmaThe Important Questions" (1). The fourth meeting was held in Port Douglas, Australia in June 1999 and this is a summary of the deliberations of that meeting.

The aims of the meeting were to discuss the questions about asthma that remain unanswered in 1999, with emphasis on the smooth muscle and its relationship to airway inflammation. Each contributor was asked to produce a manuscript that summarized the present state of knowledge, with a few figures and a large number of up-to-date references. They were asked to list the important questions that now need to be addressed. It is hoped that the references will help those who might want to pursue some of these questions, which are outlined below. Progress depends to some extent on asking relevant questions that will lead us forward.

At the beginning of the meeting the present knowledge of the relationship between allergic inflammation, as measured by allergic status, and abnormal airway behavior, as measured by airway hyperresponsiveness, was briefly addressed by Ann Woolcock as an introduction to the first important question, which was "What makes the airways contract abnormally in asthma?" This area was addressed in terms of perturbed equilibrium of myosin binding by Jeffrey Fredberg, in terms of behavior as a complex system by Peter Macklem, in terms of inflammation by Julian Solway, and in terms of airway remodeling by Jack Elias.

The second important question was "Why does inflammation persist?" This was addressed in terms of atopy in infancy by Patrick Holt, in terms of lack of inhibitory mechanisms by Peter Barnes, in terms of failure to treat early by Søren Pedersen, and in terms of leukotrienes by Paul O'Bryne.

The third question was "What determines asthma phenotypes?" This was addressed in terms of the interaction between -agonists and steroid receptors by Gary Anderson, in terms of polymorphism of ₂-receptors by Stephen Liggett, in terms of genetic predisposition by Peter Paré, in terms of interaction between allergens and airway smooth muscle by Judith Black, and in terms of interactions between infections and allergens by Robyn O'Hehir.

The questions developed by each contributor were then reviewed and are presented at the end of each article.

We are very grateful to AstraZeneca for sponsoring this meeting and are particularly grateful to Mark Milton-Edwards and Jorgen Book (Lund, Sweden) and Therese Jones (AstraZeneca, Australia) for help with running the meeting.

	Footnotes

	References

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1. Woolcock, A. J.. 1988. State of the art: asthmawhat are the important experiments? Am. J. Respir. Crit. Care Med. 138: 730-744 .

2. Woolcock, A. J., and P. J. Barnes. 1992. Asthma: the important questions. Part 2.  Am. Rev. Respir. Dis. 146: 1349-1366 [Medline].

3. Woolcock, A. J., and P. J. Barnes. 1996. Asthma: the important questions. Part 3.  Am. J. Respir. Crit. Care Med. 153(Suppl.): S1-S31 .