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Furthermore, established asthma is associated with systemic low\u2010grade inflammation. We here report on the association between neonatal colonization with pathogenic bacteria in hypopharynx and the development of systemic low\u2010grade inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bacterial colonization of the hypopharynx with <jats:italic>Moraxella catharralis, Haemophilus influenzae,<\/jats:italic> and\/or <jats:italic>Streptococcus pneumoniae<\/jats:italic> was assessed in asymptomatic children from the Copenhagen Prospective Studies on Asthma in Childhood<jats:sub>2000<\/jats:sub> (<jats:styled-content style=\"fixed-case\">COPSAC<\/jats:styled-content><jats:sub>2000<\/jats:sub>) cohort at age 1 month by culturing technique (N = 238) and by quantitative polymerase chain reaction (<jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>) technique (N = 249) and in the <jats:styled-content style=\"fixed-case\">COPSAC<\/jats:styled-content><jats:sub>2010<\/jats:sub> cohort by culturing at age 1 month (N = 622) and again at age 3 months (N = 613). Systemic low\u2010grade inflammation was determined in both cohorts at age 6 months by measuring plasma levels of high\u2010sensitivity C\u2010reactive protein (hs\u2010<jats:styled-content style=\"fixed-case\">CRP<\/jats:styled-content>), tumor necrosis factor\u2010\u03b1 (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1), and interleukin\u20106 (<jats:styled-content style=\"fixed-case\">lL<\/jats:styled-content>\u20106).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In both cohorts, bacterial colonization was associated with increased levels of hs\u2010<jats:styled-content style=\"fixed-case\">CRP<\/jats:styled-content>:<jats:styled-content style=\"fixed-case\"> COPSAC<\/jats:styled-content><jats:sub>2000<\/jats:sub>, 1 month culturing (geometric mean ratio of colonized\/noncolonized [95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>]), 1.39 [0.97\u20102.01], <jats:italic>P<\/jats:italic> = .08; 1 month <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>, 1.55 [1.14\u20102.10], <jats:italic>P<\/jats:italic> &lt; .01; <jats:styled-content style=\"fixed-case\">COPSAC<\/jats:styled-content><jats:sub>2010<\/jats:sub>, 1 month, 1.52 [1.23\u20101.87], <jats:italic>P<\/jats:italic> &lt; .01; and 3 month, 1.57 [1.30\u20101.90], <jats:italic>P<\/jats:italic> &lt; .01. A multiparametric principal component analysis incorporating hs\u2010<jats:styled-content style=\"fixed-case\">CRP<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> TNF<\/jats:styled-content>\u2010\u03b1, and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 confirmed a systemic inflammatory profile in children colonized with <jats:italic>M. catharralis, H. influenzae<\/jats:italic>. and\/or <jats:italic>S. pneumoniae<\/jats:italic> in the hypopharynx compared to noncolonized children (<jats:italic>P<\/jats:italic>\u2010values &lt; .05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The composition of the upper airway microbiome in early life may cause systemic low\u2010grade inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13461","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T19:59:57Z","timestamp":1524167997000},"page":"2150-2159","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Neonates colonized with pathogenic bacteria in the airways have a low\u2010grade systemic inflammation"],"prefix":"10.1111","volume":"73","author":[{"given":"N.","family":"Rahman Fink","sequence":"first","affiliation":[{"name":"COPSAC Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. L.","family":"Chawes","sequence":"additional","affiliation":[{"name":"COPSAC Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Thorsen","sequence":"additional","affiliation":[{"name":"COPSAC Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Stokholm","sequence":"additional","affiliation":[{"name":"COPSAC Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. A.","family":"Krogfelt","sequence":"additional","affiliation":[{"name":"Bacterial Infections Department of Bacteria Parasites and Fungi Statens Serum Institut Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Schj\u00f8rring","sequence":"additional","affiliation":[{"name":"Bacterial Infections Department of Bacteria Parasites and Fungi Statens Serum Institut Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kragh","sequence":"additional","affiliation":[{"name":"Disease Systems Immunology Department of Biotechnology and Biomedicine Technical University of Denmark Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"B\u00f8nnelykke","sequence":"additional","affiliation":[{"name":"COPSAC Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Copenhagen 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