Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/33200
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dc.contributor.authorGhebre, M. A.-
dc.contributor.authorBafadhel, M.-
dc.contributor.authorDesai, D.-
dc.contributor.authorCohen, S. E.-
dc.contributor.authorNewbold, P.-
dc.contributor.authorRapley, L.-
dc.contributor.authorWoods, J.-
dc.contributor.authorRugman, P.-
dc.contributor.authorPavord, I. D.-
dc.contributor.authorNewby, C.-
dc.contributor.authorBurton, P. R.-
dc.contributor.authorMay, R. D.-
dc.contributor.authorBrightling, Christopher E.-
dc.date.accessioned2015-10-08T11:06:53Z-
dc.date.available2015-10-08T11:06:53Z-
dc.date.issued2014-08-13-
dc.identifier.citationJournal of Allergy and Clinical Immunology, 2015, 135 (1), pp. 63-72en
dc.identifier.urihttp://www.sciencedirect.com/science/article/pii/S0091674914009518en
dc.identifier.urihttp://hdl.handle.net/2381/33200-
dc.description.abstractBACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. OBJECTIVE: We sought to determine, in terms of their sputum cellular and mediator profiles, the extent to which they represent distinct or overlapping conditions supporting either the "British" or "Dutch" hypotheses of airway disease pathogenesis. METHODS: We compared the clinical and physiological characteristics and sputum mediators between 86 subjects with severe asthma and 75 with moderate-to-severe COPD. Biological subgroups were determined using factor and cluster analyses on 18 sputum cytokines. The subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58) cohorts. Two techniques were used to assign the validation subjects to subgroups: linear discriminant analysis, or the best identified discriminator (single cytokine) in combination with subject disease status (asthma or COPD). RESULTS: Discriminant analysis distinguished severe asthma from COPD completely using a combination of clinical and biological variables. Factor and cluster analyses of the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and neutrophilic. Validation subjects were classified into 3 subgroups using discriminant analysis, or disease status with a binary assessment of sputum IL-1β expression. Sputum cellular and cytokine profiles of the validation subgroups were similar to the subgroups from the test study. CONCLUSIONS: Sputum cytokine profiling can determine distinct and overlapping groups of subjects with asthma and COPD, supporting both the British and Dutch hypotheses. These findings may contribute to improved patient classification to enable stratified medicine.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/25129678-
dc.rightsCopyright © the authors, 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectAsthma and COPD overlapen
dc.subjectcytokinesen
dc.subjectfactor and cluster analysesen
dc.subjectAgeden
dc.subjectAsthmaen
dc.subjectCluster Analysisen
dc.subjectCytokinesen
dc.subjectFemaleen
dc.subjectForced Expiratory Volumeen
dc.subjectGreat Britainen
dc.subjectHumansen
dc.subjectLeukocyte Counten
dc.subjectMaleen
dc.subjectMiddle Ageden
dc.subjectPulmonary Disease, Chronic Obstructiveen
dc.subjectSputumen
dc.titleBiological clustering supports both "Dutch" and "British" hypotheses of asthma and chronic obstructive pulmonary diseaseen
dc.typeJournal Articleen
dc.identifier.doi10.1016/j.jaci.2014.06.035-
dc.identifier.eissn1097-6825-
dc.identifier.piiS0091-6749(14)00951-8-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article;Research Support, Non-U.S. Gov't-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGYen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themesen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Molecular & Cellular Bioscienceen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Respiratory Scienceen
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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