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Immuno-genetics and immuno-phenotypes of chronic lung disease: Revealing the immunological dys-regulations that characterize Asthma, COPD and IPF

September 25-26, 2008

Purpose

The National Heart, Lung, and Blood Institute convened a meeting of investigators on September 25-26 2008, in Bethesda, Maryland. The purpose was to identify opportunities for joint research in basic and clinical immunological aspects of Asthma, COPD (Chronic Obstructive Pulmonary Disease), and IPF (Interstitial Pulmonary Fibrosis). The group focused on individual immuno-genetic and -phenotypic characteristics that could reveal immune dysfunctions important for disease definition, patient sub-type classification and therapy in these chronic lung diseases.

Several experts in basic and clinical research from both the immunology and lung communities reported on how the enormous progress achieved in recent years in understanding and manipulating immune responses represents an invaluable asset that may be leveraged, not only to better understand the basic pathogenetic mechanisms of chronic lung disease, but also to explore new, targeted, therapeutic approaches. Asthma, has long been known to have an immunological basis, and other chronic lung conditions, including COPD and IPF, have recently been shown to have an immune determinant in their pathophysiology. Additionally, all three diseases manifest signs of systemic involvement during their progression. The group assessed how the relationship between the immunological phenotypic and genotypic characteristics of individual patients may determine the natural history of disease and the response to therapies. The participants reviewed available studies and recommended future research to clarify known immune pathogenetic mechanisms and identify immuno-genetic and -phenotypic characteristics that will establish common grounds for disease definition, patient sub-type classification and to explore new specific therapeutic opportunities. The workshop started with a series of presentations that address how new immunological and technological discoveries are influencing our understanding of human pathology. The following questions were discussed: Which research directions should the research community take? What are the implications for the study of chronic lung diseases? Are there steps that can be taken to increase the translational potential of the new findings? What is the role of –omics and systems biology? Are there useful parallels with the intestinal mucosal or other systems?

A General Discussion on "Moving the field from basic knowledge to practical application of phenotyping to diagnostic and therapeutic purposes" followed.

At the conclusion of the workshop, the participants urged the research community to identify the pathophysiologic processes that lead to the establishment of immunopathologic phenotypes of Asthma, COPD or IPF in humans. They also encouraged the use of multidisciplinary and systems biology approaches to analyze the role of adaptive immunity, autoimmunity and abnormalities in lymphocyte homing in the initiation and progression of these lung diseases, while examining the influences of environmental exposure, treatments, and disease progression.

Recommendations

  1. Explore the mechanisms of maintenance of barrier integrity and immune tolerance in the airways and its role in the pathogenesis of Asthma, COPD or IPF, posing particular attention to the role played by lymphocytes, dendritic cells and epithelial cells.
  2. Examine the role of the microbiome in Asthma, COPD or IPF, analyzing the changes that occur in the lung microbiome during disease and exploring the role of microorganism colonizations, and acute or chronic infections in the initiation and progression of the diseases. Analyze the influence of the gut microbiome on immune function of the normal lung and the effects of manipulating the microbiome in the gut and the lung on Asthma, COPD or IPF initiation and progression.
  3. Investigate what is the influence of smoking on the immune phenotype in Asthma, COPD or IPF in regard to the effects on inflammatory and parenchymal cells in the lungs, on the microbiome, on the susceptibility/altered response to infections, and on the cooption or avoidance of protective pathways of inflammation.
  4. Explore the influence of age and immune senescence on initiation and progression of Asthma, COPD or IPF in humans.
  5. Investigate the molecular and cellular control points that modulate Asthma, COPD or IPF initiation and progression with focus on epigenetic mechanisms, hormonal and cytokine mechanisms, cellular signaling mechanisms, lymphoneogenesis, and local expansion of T cells.
  6. Encourage the assembly of investigative teams with multiple PIs that will support collaborative research in Asthma, COPD or IPF between basic and clinical investigators promoting multi- and inter-disciplinary studies oriented toward the understanding of disease pathogenesis, the validation and improvement of disease models, proof of principle pilot clinical trials, and the validation of preclinical findings in patients.

Workshop Co-Chairs

  • Patricia Finn M.D., University of California, San Diego
  • Robert Schleimer Ph.D., Northwestern Feinberg School of Medicine, Chicago

Workshop Participants

  • Jacques Banchereau, Ph.D., Baylor Institute for Immunology Research, Dallas
  • Homer A. Boushey, M.D., University of California, San Francisco
  • Damien Chaussabel, Ph.D., Baylor Institute for Immunology Research, Dallas
  • Jeffrey Curtis, M.D., University of Michigan Health System, Ann Arbor
  • Tony Eissa, M.D., Ph.D., Baylor College of Medicine, Houston
  • John V. Fahy, M.D., M.Sc., University of California, San Francisco
  • Gary Hunninghake, M.D., University of Iowa, Iowa City
  • Naftali Kaminski, M.D., University of Pittsburgh Medical Center, Pittsburgh
  • Farrah Kheradmand, M.D., Baylor College of Medicine, Houston
  • Joel N. Kline, M.D., M.Sc., University of Iowa, Iowa City
  • Jay K. Kolls, M.D., Children's Hospital of Pittsburgh, Pittsburgh
  • Monica Kraft, M.D., Duke Asthma Allergy and Airway Center, Durham
  • Dan Littman, M.D., Ph.D., Skirball Institute of Biomolecular Medicine, New York
  • Patricia J. Sime, M.D., FRCP, University of Rochester School of Medicine, Rochester
  • Rubin M. Tuder, M.D., Division of Pulmonary and Critical Care Medicine, Denver

NHLBI Staff

  • Antonello Punturieri, M.D., Ph.D., Division of Lung Diseases
  • Patricia Noel, Ph.D., Division of Lung Diseases
  • Herbert Y. Reynolds, M.D., Division of Lung Diseases

Last Updated: November 2013

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