The Proceedings of the American Thoracic Society 3:459-460 (2006)
© 2006 The American Thoracic Society
doi: 10.1513/pats.200603-027MS
Introduction
Norbert F. Voelkel, M.D.
Chair, 48th Annual Aspen Lung Conference
The 48th Annual Aspen Lung Conference (which now bears the name of Thomas L. Petty) on the Pathobiology of COPD was blessed by great weather, great science, and a record number of attendees. Progress was made on many levels, above and beyond what the investigators stated in 1958 at the time of the first Aspen Lung Conference, which was a well-attended symposium on "Emphysema and the Chronic Bronchitis Syndrome" (Aspen, Colorado, June 13–15, 1958). This historical event was introduced by Dr. Ben Eiseman and Dr. John Zarit from Denver, Colorado, who said "My challenge to you is that we be granted the serenity of accepting what we cannot change, the courage to change the things we can change, and the wisdom to know the difference." We refer everyone interested in the history of this group of diseases to the proceedings, which were printed in the American Review of Respiratory Diseases, Volume 80, in July 1959.
In June 2005, the discussions revolved around inflammation and infections, the consequences of infections, the pathology of the small airways, the involvement of the immune system, and systemic manifestations of chronic obstructive pulmonary disease (COPD). Many of the topics explored during the 1958 conference were touched on again this year, indicating that there has been continual debate but no definitive solution. For example, Richard Ebert formulated, in 1958, "In considering the natural history of emphysema, we must admit that there are a number of patients who do not follow the classical clinical course ... one of the controversial aspects of emphysema is its relationship to bronchial asthma." Attempts surfaced this year to provide an integrated hypothesis for the cellular and molecular biology of COPD and asthma. Oxidative stress, alternatively activated macrophages, Th1/Th2 polarization, and an "inflammatory patient phenotype" were some of the hot-button topics for very animated discussions. One goal of this conference was to send the clear message that COPD is a very complex disorder, that complex biological systems are chaotic, and that COPD is scientifically a very complex spectrum of disease manifestations. Indeed, the complexity became somewhat more transparent and convincing to some in the audience, but greatly confusing to others. The task before us has not changed during the last 50 years, which is to answer the old questions and to ask the new and hard ones, which likely will be clinical questions.
We wish to thank all of the participants, the splendid State of the Art speakers, and the Summarizer. They all came together and formed a critical mass of individuals who examined, in great detail, the visible tip of the iceberg and speculated about the unseen, submerged part of it.
The hard new questions are as follows: How much of the information generated by the elegant genetic rodent models of emphysema can be translated to the human condition? Is COPD a serpinopathy? What exactly is the genetic condition (or genetic conditions) that allows the chronic and progressive destruction of the lungs of some, but by far not all, cigarette smokers? What can be learned about those individuals who successfully master the chronic onslaught of xenobiotics and develop neither COPD nor lung cancer? Is there perhaps a spectrum of chronic airway obstructive diseases, with asthma on one end and emphysema on the other? Figure 1 attempts to connect the major disease manifestations of bronchiolitis, alveolar septal cell destruction, and airway fibrosis with activated cells of the immune system. This figure is hopelessly oversimplified, but it may bring home the point that most, if not all, chronic and progressive lung diseases do not respect compartment borders. Instead, they affect, to a varying extent, airways, vessels, interstitium, and perhaps even the pleura. The years to come will show whether the prefix "auto" can be attached to "immune attack" and whether this new concept will lead to new forms of therapy. The work goes on.
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Figure 2. Left to right: William Vandivier, M.D., Thomas L. Petty, M.D., William MacNee, M.D., and Norbert Voelkel.
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FOOTNOTES
Conflict of Interest Statement: N.F.V. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
