{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:53:16Z","timestamp":1793829196590,"version":"4.6.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Bacterial colonization of neonatal airways with the pathogenic bacterial species, Moraxella catarrhalis, Streptococcus pneumoniae, and Haemophilus influenzae, is associated with later development of childhood asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To study a possible association between colonization with pathogenic bacterial strains and the immune signature of the upper airways in healthy neonates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 20 cytokines and chemokines were quantified in vivo in the airway mucosal lining fluid of 662 neonates from the Copenhagen Prospective Study of Asthma in Childhood 2010 birth cohort. Colonization of the hypopharynx with M. catarrhalis, S. pneumoniae, H. influenzae, and Staphylococcus aureus was assessed simultaneously. The association between immune signatures and bacterial colonization or noncolonized controls was analyzed using conventional statistical methods supplemented by a multivariate approach for pattern identification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Colonization with M. catarrhalis and H. influenzae induced a mixed T helper cell (Th) type 1\/Th2\/Th17 response with high levels of IL-1\u03b2 (M. catarrhalis, P = 2.2 \u00d7 10\u221212; H. influenzae, P = 7.1 \u00d7 10\u221210), TNF-\u03b1 (M. catarrhalis, P = 1.5 \u00d7 10\u22129; H. influenzae, P = 5.9 \u00d7 10\u22127), and macrophage inflammatory protein-1\u03b2 (M. catarrhalis, P = 1.6 \u00d7 10\u221211; H. influenzae, P = 2.7 \u00d7 10\u22127). S. aureus colonization demonstrated a Th17-promoting profile with elevated IL-17 levels (P = 1.6 \u00d7 10\u221224). S. pneumoniae colonization was not significantly associated with any of the mediators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>M. catarrhalis and H. influenzae colonization of the airways of asymptomatic neonates is associated with an inflammatory immune response of the airway mucosa, which may result in chronic inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201207-1297oc","type":"journal-article","created":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T08:39:15Z","timestamp":1359707955000},"page":"589-595","source":"Crossref","is-referenced-by-count":143,"title":["Pathogenic Bacteria Colonizing the Airways in Asymptomatic Neonates Stimulates Topical Inflammatory Mediator Release"],"prefix":"10.1093","volume":"187","author":[{"given":"Nilofar V.","family":"F\u00f8lsgaard","sequence":"first","affiliation":[{"name":"Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Schj\u00f8rring","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo L.","family":"Chawes","sequence":"additional","affiliation":[{"name":"Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten A.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Food Science, University of Copenhagen, Frederiksberg C, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Krogfelt","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Brix","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Bisgaard","sequence":"additional","affiliation":[{"name":"Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,3,15]]},"reference":[{"key":"2026032100581454200_bib1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1159\/000335596","article-title":"High indoor microbial levels are associated with reduced Th1 cytokine secretion capacity in infancy","volume":"159","author":"Lappalainen","year":"2012","journal-title":"Int Arch Allergy Immunol"},{"key":"2026032100581454200_bib2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1471-2180-12-79","article-title":"Cluster analysis of host cytokine responses to biodefense pathogens in a whole blood ex vivo exposure model (WEEM)","volume":"12","author":"Chromy","year":"2012","journal-title":"BMC Microbiol"},{"key":"2026032100581454200_bib3","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1378\/chest.10-1800","article-title":"Epigenetics and prenatal influences on asthma and allergic airways disease","volume":"139","author":"Martino","year":"2011","journal-title":"Chest"},{"key":"2026032100581454200_bib4","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/00130832-200304000-00006","article-title":"Early origins of allergic disease: a review of processes and influences during early immune development","volume":"3","author":"Prescott","year":"2003","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"2026032100581454200_bib5","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1067\/mai.2003.172","article-title":"Hygiene hypothesis: fact or fiction?","volume":"111","author":"Liu","year":"2003","journal-title":"J Allergy Clin Immunol"},{"key":"2026032100581454200_bib6","doi-asserted-by":"crossref","first-page":"SII12","DOI":"10.1016\/S0140-6736(99)90437-3","article-title":"Role of microbial burden in aetiology of allergy and asthma","volume":"354","author":"Martinez","year":"1999","journal-title":"Lancet"},{"key":"2026032100581454200_bib7","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1056\/NEJMoa052632","article-title":"Childhood asthma after bacterial colonization of the airway in neonates","volume":"357","author":"Bisgaard","year":"2007","journal-title":"N Engl J Med"},{"key":"2026032100581454200_bib8","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1164\/rccm.201108-1471OC","article-title":"Neonatal cytokine profile in the airway mucosal lining fluid is skewed by maternal atopy","volume":"185","author":"F\u00f8lsgaard","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100581454200_bib9","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.jaci.2010.01.039","article-title":"A novel method for assessing unchallenged levels of mediators in nasal epithelial lining fluid","volume":"125","author":"Chawes","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"2026032100581454200_bib10","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1046\/j.1440-1754.2003.00237.x","article-title":"New concepts of cytokines in asthma: is the Th2\/Th1 paradigm out the window?","volume":"39","author":"Prescott","year":"2003","journal-title":"J Paediatr Child Health"},{"key":"2026032100581454200_bib11","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/01.all.0000162309.97480.45","article-title":"Cytokines, allergy, and asthma","volume":"5","author":"Ngoc","year":"2005","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"2026032100581454200_bib12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s00228-011-1123-3","article-title":"Multivariate analysis of the relation between diet and warfarin dose","volume":"68","author":"Rasmussen","year":"2012","journal-title":"Eur J Clin Pharmacol"},{"key":"2026032100581454200_bib13","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/cs0730217","article-title":"Measurement of secretion in nasal lavage","volume":"73","author":"Bisgaard","year":"1987","journal-title":"Clin Sci"},{"key":"2026032100581454200_bib14","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1056\/NEJM198706113162403","article-title":"Inhibition of mediator release in allergic rhinitis by pretreatment with topical glucocorticosteroids","volume":"316","author":"Pipkorn","year":"1987","journal-title":"N Engl J Med"},{"key":"2026032100581454200_bib15","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1111\/j.1365-2133.2009.09051.x","article-title":"Neonatal colonization with Staphylococcus aureus is not associated with development of atopic dermatitis","volume":"160","author":"Skov","year":"2009","journal-title":"Br J Dermatol"},{"key":"2026032100581454200_bib16","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/j.jaci.2012.05.003","article-title":"TH17 and TH22 cells: a confusion of antimicrobial response with tissue inflammation versus protection","volume":"129","author":"Akdis","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"2026032100581454200_bib17","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1056\/NEJMra0707449","article-title":"Interleukin-17 and type 17 helper T cells","volume":"361","author":"Miossec","year":"2009","journal-title":"N Engl J Med"},{"key":"2026032100581454200_bib18","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1146\/annurev.immunol.021908.132710","article-title":"IL-17 and Th17 Cells","volume":"27","author":"Korn","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"2026032100581454200_bib19","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-immunol-030409-101212","article-title":"Differentiation of effector CD4 T cell populations","volume":"28","author":"Zhu","year":"2010","journal-title":"Annu Rev Immunol"},{"key":"2026032100581454200_bib20","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1203\/01.PDR.0000139408.89119.F2","article-title":"Endotracheal colonization at birth is associated with a pathogen-dependent pro- and antiinflammatory cytokine response in ventilated preterm infants: a prospective cohort study","volume":"56","author":"De Dooy","year":"2004","journal-title":"Pediatr Res"},{"key":"2026032100581454200_bib21","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1164\/rccm.200207-728OC","article-title":"Adaptive immunity to nontypeable Haemophilus influenzae","volume":"167","author":"King","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032100581454200_bib22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.coi.2012.01.014","article-title":"Helper T cell diversity and plasticity","volume":"24","author":"Nakayamada","year":"2012","journal-title":"Curr Opin Immunol"},{"key":"2026032100581454200_bib23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2174\/138945012799424697","article-title":"Combat pneumococcal infections: adhesins as candidates for protein-based vaccine development","volume":"13","author":"Gamez","year":"2012","journal-title":"Curr Drug Targets"},{"key":"2026032100581454200_bib24","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.str.2009.10.019","article-title":"Structural basis of host cell recognition by the pilus adhesin from Streptococcus pneumoniae","volume":"18","author":"Izor\u00e9","year":"2010","journal-title":"Structure"},{"key":"2026032100581454200_bib25","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nature06764","article-title":"Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome","volume":"452","author":"Milner","year":"2008","journal-title":"Nature"},{"key":"2026032100581454200_bib26","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/ni.1882","article-title":"The dual nature of T(H)17 cells: shifting the focus to function","volume":"11","author":"O\u2019Connor","year":"2010","journal-title":"Nat Immunol"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/187\/6\/589\/67266822\/ajrccm_187_6_589.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/187\/6\/589\/67266822\/ajrccm_187_6_589.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:58:23Z","timestamp":1774069103000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/187\/6\/589\/8510065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3]]},"references-count":26,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2013,3,15]]},"published-print":{"date-parts":[[2013,3,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201207-1297oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,3]]},"published":{"date-parts":[[2013,3]]}}}