{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:29:34Z","timestamp":1790386174160,"version":"4.1.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["annallergy.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Annals of Allergy, Asthma & Immunology"],"published-print":{"date-parts":[[2016,8]]},"DOI":"10.1016\/j.anai.2016.05.016","type":"journal-article","created":{"date-parts":[[2016,8,5]],"date-time":"2016-08-05T01:15:43Z","timestamp":1470359743000},"page":"121-125","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":108,"title":["Characterization of asthma endotypes: implications for therapy"],"prefix":"10.1016","volume":"117","author":[{"given":"Jeffrey R.","family":"Stokes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas B.","family":"Casale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.anai.2016.05.016_bib1","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.jaip.2014.09.008","article-title":"Asthma phenotypes: an approach to the diagnosis and treatment of asthma","volume":"2","author":"Lockey","year":"2014","journal-title":"J\u00a0Allergy Clin Immunol Pract"},{"key":"10.1016\/j.anai.2016.05.016_bib2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jaci.2015.05.052","article-title":"Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap syndromes","volume":"136","author":"Barnes","year":"2015","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.anai.2016.05.016_bib3","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1111\/j.1365-2222.2012.04014.x","article-title":"Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial","volume":"42","author":"Nair","year":"2012","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.anai.2016.05.016_bib4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ajem.2014.09.036","article-title":"A\u00a0randomized trial of benralizumab, an anti interleukin 5 receptor \u03b1 monoclonal antibody, after acute asthma","volume":"33","author":"Nowak","year":"2015","journal-title":"Am J Emerg Med"},{"key":"10.1016\/j.anai.2016.05.016_bib5","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1164\/rccm.200701-085OC","article-title":"A\u00a0study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma","volume":"176","author":"Flood-Page","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.anai.2016.05.016_bib6","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1056\/NEJMoa0808991","article-title":"Mepolizumab and exacerbations of refractory eosinophilic asthma","volume":"360","author":"Haldar","year":"2009","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.anai.2016.05.016_bib7","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0140-6736(12)60988-X","article-title":"Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo controlled trial","volume":"380","author":"Pavord","year":"2012","journal-title":"Lancet"},{"key":"10.1016\/j.anai.2016.05.016_bib8","doi-asserted-by":"crossref","first-page":"e59872","DOI":"10.1371\/journal.pone.0059872","article-title":"Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo controlled trials","volume":"8","author":"Liu","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.anai.2016.05.016_bib9","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1056\/NEJMoa1403290","article-title":"Mepolizumab treatment in patients with severe eosinophilic asthma","volume":"371","author":"Ortega","year":"2014","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.anai.2016.05.016_bib10","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1056\/NEJMoa0805435","article-title":"Mepolizumab for prednisone-dependent asthma with sputum eosinophilia","volume":"360","author":"Nair","year":"2009","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.anai.2016.05.016_bib11","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1056\/NEJMoa1403291","article-title":"Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma","volume":"371","author":"Bel","year":"2014","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.anai.2016.05.016_bib12","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1513\/AnnalsATS.201312-454OC","article-title":"Cluster analysis and characterization of response to mepolizumab. A step closer to personalized medicine for patients with severe asthma","volume":"11","author":"Ortega","year":"2014","journal-title":"Ann Am Thorac Soc"},{"key":"10.1016\/j.anai.2016.05.016_bib13","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.jaci.2013.11.026","article-title":"Outcomes after cessation of mepolizumab therapy in severe eosinophilic asthma: a 12-month follow-up analysis","volume":"133","author":"Haldar","year":"2014","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.anai.2016.05.016_bib14","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1164\/rccm.201103-0396OC","article-title":"Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study","volume":"184","author":"Castro","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.anai.2016.05.016_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.chest.2016.03.018","article-title":"Phase 3 study of reslizumab in patients with poorly controlled asthma: effects across a broad range of eosinophil counts","author":"Corren","year":"2016","journal-title":"Chest"},{"key":"10.1016\/j.anai.2016.05.016_bib16","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S2213-2600(15)00042-9","article-title":"Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials","volume":"3","author":"Castro","year":"2015","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.anai.2016.05.016_bib17","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1586\/17476348.2015.1000867","article-title":"Efficacy and safety of reslizumab in patients with moderate to severe eosinophilic asthma","volume":"9","author":"Lim","year":"2015","journal-title":"Expert Rev Respir Med"},{"key":"10.1016\/j.anai.2016.05.016_bib18","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.jaci.2013.05.020","article-title":"Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia","volume":"132","author":"Laviolette","year":"2013","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.anai.2016.05.016_bib19","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S2213-2600(14)70201-2","article-title":"Benralizumab, an anti-interleukin 5 receptor \u03b1 monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study","volume":"2","author":"Castro","year":"2014","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.anai.2016.05.016_bib20","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1164\/rccm.201510-2032PP","article-title":"Roles of periostin in respiratory disorders","volume":"193","author":"Izuhara","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.anai.2016.05.016_bib21","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1056\/NEJMoa1106469","article-title":"Lebrikizumab treatment in adults with asthma","volume":"365","author":"Corren","year":"2011","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.anai.2016.05.016_bib22","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.jaci.2013.03.051","article-title":"Dose ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids","volume":"132","author":"Noonan","year":"2013","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.anai.2016.05.016_bib23","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1136\/thoraxjnl-2014-206719","article-title":"Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies","volume":"70","author":"Hanania","year":"2015","journal-title":"Thorax"},{"key":"10.1016\/j.anai.2016.05.016_bib24","doi-asserted-by":"crossref","unstructured":"Investor update. http:\/\/www.roche.com\/investors\/updates\/inv-update-2016-02-29.htm. Published February 29, 2016. Accessed March 28,\u00a02016.","DOI":"10.12968\/htup.2016.5.28"},{"key":"10.1016\/j.anai.2016.05.016_bib25","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1183\/09031936.00223411","article-title":"A\u00a0phase II placebo controlled study of tralokinumab in moderate-to-severe asthma","volume":"41","author":"Piper","year":"2013","journal-title":"Eur Respir J"},{"key":"10.1016\/j.anai.2016.05.016_bib26","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S2213-2600(15)00197-6","article-title":"Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial","volume":"3","author":"Brightling","year":"2015","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.anai.2016.05.016_bib27","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1056\/NEJMoa1304048","article-title":"Dupilumab in persistent asthma with elevated eosinophil levels","volume":"368","author":"Wenzel","year":"2013","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.anai.2016.05.016_bib28","unstructured":"Positive phase 2b data for treatment of asthma with dupilumab. http:\/\/www.rtmagazine.com\/2015\/05\/positive-phase-2b-data-asthma-dupilumab\/. Published May 21, 2015. Accessed March 28,\u00a02016."},{"key":"10.1016\/j.anai.2016.05.016_bib29","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/S0140-6736(07)61600-6","article-title":"Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies","volume":"370","author":"Wenzel","year":"2007","journal-title":"Lancet"},{"key":"10.1016\/j.anai.2016.05.016_bib30","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jaci.2012.03.030","article-title":"IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti\u2013IL-4 receptor \u03b1 antagonist","volume":"130","author":"Slager","year":"2012","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.anai.2016.05.016_bib31","doi-asserted-by":"crossref","first-page":"243ra85","DOI":"10.1126\/scitranslmed.3008961","article-title":"Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime epitope reduces IgE production","volume":"6","author":"Gauvreau","year":"2014","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.anai.2016.05.016_bib32","first-page":"A5168","article-title":"Efficacy and safety of quilizumab in adults with allergic asthma inadequately controlled on inhaled corticosteroids and a second controller (COSTA Study) C101. Allergic airway inflammation and hyperresponsiveness: novel mechanism and therapy","volume":"191","author":"Harris","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.anai.2016.05.016_bib33","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1111\/cea.12400","article-title":"Pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-affinity anti-IgE antibody, in atopic subjects","volume":"44","author":"Arm","year":"2014","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.anai.2016.05.016_bib34","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jaip.2014.03.010","article-title":"Omalizumab in asthma: an update on recent developments","volume":"2","author":"Humbert","year":"2014","journal-title":"J\u00a0Allergy Clin Immunol Pract"},{"key":"10.1016\/j.anai.2016.05.016_bib35","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1164\/rccm.201208-1414OC","article-title":"Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study","volume":"187","author":"Hanania","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.anai.2016.05.016_bib36","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.jaci.2013.02.032","article-title":"High eosinophil count: a potential biomarker for assessing successful omalizumab treatment effects","volume":"132","author":"Busse","year":"2013","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.anai.2016.05.016_bib37","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1111\/all.12451","article-title":"Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459","volume":"69","author":"Pettipher","year":"2014","journal-title":"Allergy"}],"container-title":["Annals of Allergy, Asthma & Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1081120616302666?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1081120616302666?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:15:18Z","timestamp":1761052518000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1081120616302666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["S1081120616302666"],"URL":"https:\/\/doi.org\/10.1016\/j.anai.2016.05.016","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726620128.793543756","asserted-by":"object"}]},"ISSN":["1081-1206"],"issn-type":[{"value":"1081-1206","type":"print"}],"subject":[],"published":{"date-parts":[[2016,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Characterization of asthma endotypes: implications for therapy","name":"articletitle","label":"Article Title"},{"value":"Annals of Allergy, Asthma & Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.anai.2016.05.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}