NHLBI Working Group

Lung Cancer and COPD, Different Outcomes of a Common Etiopathogenetic Pathway?

Executive Summary

The National Heart, Lung, and Blood Institute in collaboration with the Division of Cancer Prevention/National Cancer Institute convened a meeting of investigators on June 26-27, 2007, in Bethesda, Maryland. The scope was to evaluate evidence for a pathogenetic link between COPD (Chronic Obstructive Pulmonary Disease) and lung cancer, to recommend future research that may be needed to further clarify this relationship and to translate this understanding into better approaches for the prevention and treatment of both diseases. This workshop and the possible initiatives that will develop are intended to foster inter-IC collaborations on topics of prominent public health issues.

Experts from both the cancer and lung communities were encouraged to identify common pathogenetic aspects and opportunities for joint research. Topics discussed included basic and clinical research of pathogenetic mechanisms, genetic similarities in disease susceptibility, and the efficacy of chemoprevention in COPD and lung cancer. The general consensus was that the mechanisms behind the association of lung cancer and COPD need to be further investigated at the epidemiological, patho-biological, and clinical levels. Therapeutic approaches, beneficial or detrimental to either disease, need to be addressed. It was general consensus that a stronger collaboration between the researchers studying these two diseases should not only be facilitated, but also constitute a requirement when studying subjects at risk.

Several recommendations on priorities for future research directions were generated.

The general recommendations of the Working Group were:

1. Clarify co-epidemiology of lung cancer and COPD -- including clinical characteristics and molecular phenotypes with attention to early molecular events, timing, subsequent course of each, discrete sub-phenotypes of each disease and relationships of ethnicity, race, gender, and well established and emerging environmental exposures.
2. Identify shared genetic and epigenetic risk factors for COPD and lung cancer. Delineate gene-environment interactions.
3. Identify and validate biomarkers, molecular signatures, and imaging measures of risk, presence, severity, and progression of COPD and lung cancer and of responses to therapy.
4. Identify, publicize, and enable the evaluation and analyses of existing data sets and repositories of biospecimens. Consider expansion of ongoing studies to provide data that would address mechanisms of comorbidity.
5. Obtain phenotypic and outcome data and biospecimens from large, well designed cohorts of subjects with and/or at risk for COPD and lung cancer.
6. Determine common and disparate mechanisms involved in the pathogenesis of COPD and lung cancer. Consider innate and adaptive immunity, redox balance, proteinases, repair, stem cell proliferation, epigenetics, somatic mutations, microenvironment, and epithelial-mesenchymal transition.
7. Develop and utilize animal and other preclinical models to investigate pathogenetic links between COPD and lung cancer.
8. Conduct early phase clinical trials of potential chemopreventive agents expected to modify pathways involved in both disease processes, with comprehensive characterization of biological effects.
9. In future clinical studies of lung cancer or COPD, incorporate baseline phenotyping and outcome measures for both diseases.
10. Expand collaborative efforts between NCI and NHLBI addressing the interface of pulmonary disease and lung cancer. Consider additional meetings and mechanisms for fostering synergism between the research communities.

Working Group Members

Chair

• Steven M. Dubinett, M.D., David Geffen School of Medicine at UCLA, Los Angeles, CA
• Steven D. Shapiro, M.D., University of Pittsburgh , Pittsburgh, PA

Members

• David Au, M.D., VA Puget Sound Health Care System, Seattle, WA
• Shyam Biswal, M.D., Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
• Peter Bitterman, M.D., University of Minnesota, Minneapolis, MN
• James S. Brody, M. D., Boston University, Boston, MA
• James D. Crapo, M.D., National Jewish Medical & Research Center, Denver, CO
• A. McGarry Houghton, M.D., University of Pittsburgh, Pittsburgh, PA
• Stephen C. Lam, M.D., British Columbia Cancer Agency, CANADA
• David M. Mannino, M.D., University of Kentucky, Lexington, KY
• Pierre Massion, M.D., Vanderbilt University Medical Center, Nashville, TN
• York Miller, M.D., University of Colorado, Denver, CO
• Ann G. Schwartz, M.D., Karmanos Cancer Center, Detroit, MI
• Jill M. Siegfried, M.D. University of Pittsburgh, Pittsburgh, PA
• Edwin K. Silverman, M.D., Harvard Medical School, Boston, MA
• Ping Yang, Ph.D., Mayo Clinic, Rochester, MN

NHLBI Staff

• Antonello Punturieri, M.D., Ph.D. Division of Lung Diseases, Bethesda, MD
• Thomas Croxton, Ph.D., M.D., Division of Lung Diseases, Bethesda, MD
• Gail Weinmann, M.D., Division of Lung Diseases, Bethesda, MD

NCI Staff

• Eva Szabo, M.D., Division of Cancer Prevention, Bethesda, MD

August 2007