{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:24:35Z","timestamp":1793424275165,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute for Health Research","doi-asserted-by":"crossref","award":["#CIF-9768"],"award-info":[{"award-number":["#CIF-9768"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014446","name":"Tula Foundation","doi-asserted-by":"publisher","award":["R01HL114447"],"award-info":[{"award-number":["R01HL114447"]}],"id":[{"id":"10.13039\/100014446","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014446","name":"Tula Foundation","doi-asserted-by":"publisher","award":["5R01 HL095388"],"award-info":[{"award-number":["5R01 HL095388"]}],"id":[{"id":"10.13039\/100014446","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL114447"],"award-info":[{"award-number":["R01HL114447"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002g","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01 HL095388"],"award-info":[{"award-number":["5R01 HL095388"]}],"id":[{"id":"10.13039\/100000002g","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The relatively sparse but diverse microbiome in human lungs may become less diverse in chronic obstructive pulmonary disease (COPD). This article examines the relationship of this microbiome to emphysematous tissue destruction, number of terminal bronchioles, infiltrating inflammatory cells, and host gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Culture-independent pyrosequencing microbiome analysis was used to examine the V3\u2013V5 regions of bacterial 16S ribosomal DNA in 40 samples of lung from 5 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 4) and 28 samples from 4 donors (controls). A second protocol based on the V1\u2013V3 regions was used to verify the bacterial microbiome results. Within lung tissue samples the microbiome was compared with results of micro\u2013computed tomography, infiltrating inflammatory cells measured by quantitative histology, and host gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Ten operational taxonomic units (OTUs) was found sufficient to discriminate between control and GOLD stage 4 lung tissue, which included known pathogens such as Haemophilus influenzae. We also observed a decline in microbial diversity that was associated with emphysematous destruction, remodeling of the bronchiolar and alveolar tissue, and the infiltration of the tissue by CD4+ T cells. Specific OTUs were also associated with neutrophils, eosinophils, and B-cell infiltration (P\u2009&amp;lt;\u20090.05). The expression profiles of 859 genes and 235 genes were associated with either enrichment or reductions of Firmicutes and Proteobacteria, respectively, at a false discovery rate cutoff of less than 0.1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results support the hypothesis that there is a host immune response to microorganisms within the lung microbiome that appears to contribute to the pathogenesis of COPD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201502-0223oc","type":"journal-article","created":{"date-parts":[[2015,5,6]],"date-time":"2015-05-06T13:00:35Z","timestamp":1430917235000},"page":"438-445","source":"Crossref","is-referenced-by-count":219,"title":["Host Response to the Lung Microbiome in Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"192","author":[{"given":"Marc A.","family":"Sze","sequence":"first","affiliation":[{"name":"Centre for Heart Lung Innovation, Providence Heart\u2009+\u2009Lung Institute at St. Paul\u2019s Hospital, Vancouver, British Columbia, Canada"},{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A.","family":"Dimitriu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Life Sciences Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation, Providence Heart\u2009+\u2009Lung Institute at St. Paul\u2019s Hospital, Vancouver, British Columbia, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"McDonough","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation, Providence Heart\u2009+\u2009Lung Institute at St. Paul\u2019s Hospital, Vancouver, British Columbia, Canada"},{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh D.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Brothers","sequence":"additional","affiliation":[{"name":"Division of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Erb-Downward","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary B.","family":"Huffnagle","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizu","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation, Providence Heart\u2009+\u2009Lung Institute at St. Paul\u2019s Hospital, Vancouver, British Columbia, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Mark","family":"Elliott","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation, Providence Heart\u2009+\u2009Lung Institute at St. Paul\u2019s Hospital, Vancouver, British Columbia, Canada"},{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Thoracic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don D.","family":"Sin","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation, Providence Heart\u2009+\u2009Lung Institute at St. Paul\u2019s Hospital, Vancouver, British Columbia, Canada"},{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc E.","family":"Lenburg","sequence":"additional","affiliation":[{"name":"Division of Computational Biomedicine, Department of 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