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Introduction

Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska

Correspondence and requests for reprints should be addressed to Stephen I. Rennard, M.D., F.C.C.P., Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, 985125 Nebraska Medical Center, Omaha, NE 68198-5125. E-mail: srennard{at}unmc.edu

Advances in the understanding of biological processes are revealing complex networks of components interacting at multiple levels. At the molecular level, multiple classes of molecules act as aggregates in complex sequences in order to effect highly regulated processes. Similarly, multiple types of cells interact to determine tissue structure and function. For an organism, health depends on the interactions of multiple organs. From a medical perspective, the interactions of multiple individuals within social structures both influence health and affect attempts to improve it.

The multiplicity of components and their complex interactions create both opportunities and challenges for the development and implementation of novel treatments. It is increasingly likely that effective treatments will require multiple agents that separately target different steps in the complex biological network. The most appropriate methods for assessing combination therapy, however, are by no means clear. Clinical end points used to gauge pharmacologic effects result from complex interactions of the biological networks. The pharmacodynamic and dose–response relationship of such end points to potential therapeutics, particularly when used in combination, is likely to be difficult to ascertain.

The current symposium was designed to discuss the problems of combination therapy as related to the treatment of chronic obstructive pulmonary disease. In this context, combination pharmacotherapy is already used in the acute and chronic management of chronic obstructive pulmonary disease. Moreover, pharmacotherapy is often combined with other forms of treatment, notably rehabilitation. The development and implementation of these treatments, however, have raised issues relating to the outcomes used to assess treatments and the strategies by which they are used clinically. This symposium was designed to discuss these issues against the background of current understanding of chronic obstructive pulmonary disease pathogenesis.

This symposium was made possible by an unrestricted grant from GlaxoSmithKline. The scientific committee, consisting of Drs. Myron Toews, James Donohue, Robert Schleimer, Malcolm Johnson, and myself, was charged with organizing the scientific program for which we are responsible. We greatly appreciate the support of GlaxoSmithKline and of the attendees, both presenters and discussants, whose enthusiastic support was essential for the symposium. The communications and discussion summaries that follow reflect the content of the main scientific sessions, but capture only part of the lively interactions relating to this important and rapidly evolving topic that the symposium made possible.

	FOOTNOTES

 
Conflict of Interest Statement: S.I.R. has participated as a speaker in scientific meetings and courses under the sponsorship of GlaxoSmithKline (GSK). He has consulted with GSK with relevance to the topics noted in the present article. He serves on advisory boards for Roche and Altana. He has been sponsored by GSK for several clinical trials and has received laboratory support. Over 3 years, the total for this approximates $1,800,000. He has also conducted clinical trials for Roche ($60,000) and Altana ($80,000). He has conducted both clinical trials and basic studies under the sponsorship of Centocor ($140,000). He has conducted clinical trials for Pfizer ($80,000). A patent is pending on the use of PDE4 inhibitors in repair; S.I.R. is a coinventor of the patent owned by the University of Nebraska Medical Center.

(Received in original form April 19, 2005; accepted in final form April 27, 2005)

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rennard, S. I. Search for Related Content PubMed Articles by Rennard, S. I.