ABSTRACTS were quantifiable in advanced COPD but not from other disease stages. Bronchoalveolar lavage neutrophil and macrophage counts were significantly higher in mice challenged intratracheally with N. panipatense compared with control mice (P , 0.01). Frequencies of neutrophils and macrophages in lung tissue were increased in mice challenged with N. panipatense in room air compared with control mice. The effect of cigarette smoke in conjunction with N. panipatense was unclear and necessitates further elucidation. Conclusions: Novosphingobium ssp. was associated with lung inflammation in mice and may play a role in more severe COPD disease. Author disclosures are available with the text of this abstract at www.atsjournals.org.
(Received in original form June 27, 2013; accepted in final form July 1, 2013) Correspondence and requests for reprints should be addressed to J. Kirk Harris, Ph.D., Department of Pediatrics, Pulmonary Medicine, University of Colorado Denver, 13123 E. 16th Avenue, Box B395, Aurora, CO 80045. E-mail:
[email protected] Ann Am Thorac Soc Vol 11, Supplement 1, pp S76–S77, Jan 2014 Copyright © 2014 by the American Thoracic Society Internet address: www.atsjournals.org
from lung apex to base (McDonough JE, et al., N Engl J Med 2011;365:1567–1576). From each slice one sample was examined by micro–computed tomography to measure emphysematous destruction, another to measure the inflammatory immune cell infiltration by quantitative histology, and a third was used to study bacteria by quantitative polymerase chain reaction and 454 pyrotag sequencing (Sze MA, et al., Am J Respir Crit Care Med 2012;185:1073–1080). Results: The average numbers of 16S/1000Rpp40 gene copies were 7.44 6 18.6 and 7.77 6 16.3 (COPD vs. controls; P . 0.05). In contrast, comparison of upper lung tissue samples (COPD vs. controls) showed an increase in detectable bacteria (P , 0.05) with no difference between lower lung tissue samples (P . 0.05). Sequencing identified a core population of bacteria that was significantly associated (P , 0.05) with the inflammatory and tissue-remodeling response as well as with surface area and numbers of terminal bronchioles (P , 0.05). Conclusion: The accumulations of specific bacteria within the human lung microbiome are associated with inflammatory cell infiltration and progressive emphysematous destruction. Author disclosures are available with the text of this abstract at www.atsjournals.org.
Received in original form June 24, 2013; accepted in final form June 24, 2013 Supported by Merck IIS 38970, NIH # 5P50HL084922, 5P50HL084948, 1R01HL95388, and CIHR # CIF-97687.
Host Response to the Lung Microbiome in Lung Tissue Undergoing Emphysematous Destruction Marc Sze1, Pedro A. Dimitriu2, Masaru Suzuki1, John E. McDonough1, John V. Gosselink1, Mark W. Elliott1, William W. Mohn2, Don D. Sin1, Shizu Hayashi1, and James C. Hogg1 1 UBC James Hogg Research Centre, St. Paul’s Hospital/ Providence Health Care-University of British Columbia, and 2Department of Immunology and Microbiology, University of British Columbia, Vancouver, British Columbia, Canada
Correspondence and requests for reprints should be addressed to Marc Sze, UBC James Hogg Research Centre, Room 166, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6. E-mail:
[email protected] Ann Am Thorac Soc Vol 11, Supplement 1, p S77, Jan 2014 Copyright © 2014 by the American Thoracic Society Internet address: www.atsjournals.org
The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease Alexa A. Pragman1, Hyeun Bum Kim2, Cavan S. Reilly3, Christine Wendt4, and Richard E. Isaacson2 1
Rationale: The progression of chronic obstructive pulmonary disease (COPD) has been associated with infiltration of peripheral lung tissue by inflammatory immune cells that form tertiary lymphoid organs. These observations have documented the presence of an adaptive immune response without indentifying the antigens that drive it (Hogg JC, et al., N Engl J Med 2004;350:2645– 2653).
Department of Medicine, Division of Infectious Diseases and International Medicine, University of Minnesota Medical Center, St. Paul, Minnesota; and Departments of 2Veterinary 4 3 Biosciences, Biostatistics, and Medicine, University of Minnesota, St. Paul, Minnesota
Hypothesis: Bacteria within the human lung microbiome drive the host inflammatory immune response associated with progression of COPD.
Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial lung infection contributes to roughly 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora.
Methods: Whole lungs donated by patients with severe COPD (n = 5) were compared with unused donor lungs (n = 4) that served as controls. These specimens were inflated with air, rapidly frozen in liquid nitrogen vapor, and cut into 2-cm-thick slices
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