NHLBI Workshop, Bronchiectasis

Discussion

Bronchiectasis is associated with diseases such as cystic fibrosis, primary ciliary dyskinesia, chest wall abnormalities, a variety of obstructive lung diseases, immune defects, and also frequently seen in tall, thin, nonsmoking, middle-aged and elderly women. This disease process destroys lung tissue and is notoriously difficult to manage. Microbes associated with bronchiectasis such as nontuberculous mycobacteria (NTM), Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia and Aspergillus are frequently resistant to many antibiotics and repeated long courses of toxic multi-drug regimens are only partially successful in controlling the infection.  

Bronchiectasis linked to NTM is being reported with increased frequency. Chronic lung disease due to non-tuberculous mycobacteria in addition to being associated with the factors listed above has also been reported in otherwise healthy individuals who have indoor hot tubs ? (the bacteria probably live in the hot water and conditions are right for creating an aerosol).

Lung pathology and imaging were briefly outlined and the role of genetics and modifier genes as predisposing factors in the pathogenesis were discussed.  The migration and contribution of neutrophils and proteases to the destruction of the airway wall and the function of lung matrix were also examined. The characteristics of several microbial agents were reviewed along with antibiotics currently used for treatment. The use of hypertonic agents to liquefy and mobilize secretions was covered, with a focus on hypertonic manitol.

The group identified issues and made recommendations for future research as follows:

• More information is needed on phenotype ? among the factors to be considered are:
  • Age, sex, morphometrics, effects of menopause
  • Computed tomography (CT) to delineate both focal and diffuse disease
  • History ? including: respiratory distress in neonate, ear infections, sinus infections, virus infection (HIV), cigarettes, COPD, cystic fibrosis, primary ciliary dyskinesia
  • Pulmonary function tests
  • Polymorphonuclear leukocytes, With or without lipopolysaccharide
  • Serum - Alpha(1)-antytrypsin, immune  globulins
  • Sputum - microscopic appearance, per cent solids, proteases
  • Alveolar epithelial cells
• There was a consensus of the participants that bronchiectasis is an important component of lung disease of itself and as part of other lung diseases. The group concluded that bronchiectasis deserves further exploration and recognition, including better information regarding its prevalence.
• Future research resources and needs include the following:
  • Tissue ? could be obtained at time of transplant ? obtain properly inflated lung tissue (explanted lung)
  • Registry/Epidemiology
  • Cells/cell lines
  • Banked blood specimens
  • CT scans
  • Training program
  • Microbial sequences/annotation nontuberculous mycobacteria and other microbes
  • Therapeutic trial(s) - NTM and non NTM bronchiectasis
  • Animal models

Working Group Members

Chair

• Richard Boucher, M.D., University of North Carolina , Chapel Hill , NC

Members

• Charles Daley, M.D., National Jewish Medical and Research Center, Denver, CO
• Claire Doerschuk, M.D., Rainbow Babies & Children's Hospital, Cleveland, OH
• Paul A .Greenberger, M.D., Northwestern University, Chicago, IL
• Cedric Grigg, Ph.C., DBA Pharmaxis, Rochester, NY
• James Hogg, M.D., Ph.D., St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada
• Steven Holland, M.D., National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD
• Barbara Iglewski, Ph.D., University of Rochester, Rochester, NY*
• Michael Iseman, M.D., National Jewish Medical & Research Center, Denver, CO
• Michael R. Knowles, M.D., The University of North Carolina at Chapel Hill, CF/Pulmonary Research & Treatment Center, Chapel Hill, NC
• David Naidich, M.D., New York University School of Medicine, New York, NY
• Enid Neptune, M.D., Johns Hopkins School of Medicine, Baltimore, MD
• Carol Novak, Ph.D., Siemens Corporate Research, Princeton, NJ
• Anne O’Donnell, M.D., Georgetown University Hospital, Washington, DC
• Kenneth Olivier, M.D., National Institute of Allergy and Infectious Diseases, Bethesda, MD
• Williams C. Parks, Ph.D., University of Washington, Seattle, WA
• Richard A. Robbins, M.D., University of Arizona, Tucson, AZ
• Gerard Turino, M.D., St. Luke’s-Roosevelt Hospital Center, New York, NY
• Richard Wallace, M.D., University of Texas Health Center at Tyler, Tyler, TX

* Unable to attend – sent material presented by Dr. Boucher

Patient interest Organization Representatives

• Philip Leitman, NTM research Inc., Coral Gables, FL
• Michael Mayer, COPD Foundation, Miami, FL
• Colin W. Scarborough, COPD Foundation, Miami, FL
• John Walsh, COPD Foundation, Miami, FL

NHLBI Staff

• Sandra Colombini Hatch, M.D., Division of Lung Diseases, Bethesda, MD
• Dorothy B. Gail, Ph.D., Division of Lung Diseases, Bethesda, MD
• James P. Kiley, Ph.D., Division of Lung Diseases, Bethesda, MD
• Hannah H. Peavy, M.D., Division of Lung Diseases, Bethesda , MD
• Susan Banks Schlegel, Ph.D., Division of Lung Diseases, Bethesda, MD

NIAID Extramural Staff

• Gail Jacobs, M.S., M.A., Division of Microbiology and Infectious Diseases, Bethesda, MD
• Chris Lambros, Ph.D., Division of Acquired Immunodeficiency Syndrome, Bethesda, MD
• Barbara Laughon, Ph.D., Division of Acquired Immunodeficiency Syndrome, Bethesda, MD
• Mamodikoe Makhene, M.D., MP.H., Division of Microbiology and Infectious Diseases, Bethesda, MD