{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:51:52Z","timestamp":1782287512189,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Many questions concerning responders (R) and nonresponders (NR) in severe eosinophilic asthma (SEA) after blocking the IL-5 (interleukin 5) pathway are still not clear, especially regarding the early parameters of response to biologics in personalized treatment strategies. We evaluated 17 SEA patients treated with anti-IL-5 biologics (16 patients mepolizumab, one patient benralizumab) before the introduction of biologics, and at a week 16 follow-up. Clinical, cellular and immunological parameters in peripheral blood were measured in R and NR. Sputum induction with the measurement of cellular and immunological parameters was performed at 16 weeks only. There were 12 R and 5 NR to biologics. After 16 weeks, there was a significant improvement in percentages of FEV1 (p = 0.001), and asthma control test (ACT) (p = 0.001) in the R group, but not in NR. After 16 weeks, the eosinophils in induced sputum were 27.0% in NR and 4.5% in R (p = 0.05), with no difference in IL-5 concentrations (p = 0.743). Peripheral eosinophilia decreased significantly in NR (p = 0.032) and R (p = 0.002). In patients with SEA on anti-IL-5 therapy, there was a marked difference in airway eosinophilic inflammation between R and NR already at 16 weeks, after anti-IL-5 introduction.<\/jats:p>","DOI":"10.3390\/jpm12010070","type":"journal-article","created":{"date-parts":[[2022,1,9]],"date-time":"2022-01-09T23:06:15Z","timestamp":1641769575000},"page":"70","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heterogeneous Response of Airway Eosinophilia to Anti-IL-5 Biologics in Severe Asthma Patients"],"prefix":"10.3390","volume":"12","author":[{"given":"Maru\u0161a Kopa\u010d","family":"\u0160oki\u0107","sequence":"first","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-4952","authenticated-orcid":false,"given":"Matija","family":"Rijavec","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"},{"name":"Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Koro\u0161ec","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"},{"name":"Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ur\u0161ka","family":"Bidovec-Stojkovi\u010d","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2418-5025","authenticated-orcid":false,"given":"Izidor","family":"Kern","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"Vantur","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"\u0160krgat","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia"},{"name":"Department of Pulmonology, Division of Internal Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1056\/NEJMra1608969","article-title":"Severe and difficult-to-treat asthma in adults","volume":"377","author":"Israel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1800703","DOI":"10.1183\/13993003.00703-2018","article-title":"Consequences of long-term oral corticosteroid therapy and its side-effects in severe asthma in adults: A focused review of the impact data in the literature","volume":"52","author":"Volmer","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s11136-014-0801-x","article-title":"A qualitative study of the impact of severe asthma and its treatment showing that treatment burden is neglected in existing asthma assessment scales","volume":"24","author":"Hyland","year":"2015","journal-title":"Qual. Life Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1164\/rccm.201810-1944CI","article-title":"Role of Biologics in Asthma","volume":"199","author":"McGregor","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1056\/NEJMoa1403290","article-title":"MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma","volume":"371","author":"Ortega","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/S0140-6736(06)69290-8","article-title":"Asthma: Defining of the persistent adult phenotypes","volume":"368","author":"Wenzel","year":"2006","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1016\/S0140-6736(02)11679-5","article-title":"Asthma exacerbations and sputum eosinophil counts: A randomised controlled trial","volume":"360","author":"Green","year":"2002","journal-title":"Lancet"},{"key":"ref_8","unstructured":"Asthma GIf (2020, October 10). Global Strategy for Asthma Management and Prevention. Available online: https:\/\/ginasthma.org\/wp-content\/uploads\/2020\/06\/GINA-2020-report_20_06_04-1-wms.pdf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/cea.13841","article-title":"Clinical evaluation of type 2 disease status in a real-world population of difficult to manage asthma using historic electronic healthcare records of blood eosinophil counts","volume":"51","author":"Azim","year":"2021","journal-title":"Clin. Exp. Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.2217\/imt.13.118","article-title":"An update on biologic-based therapy in asthma","volume":"5","author":"Walsh","year":"2013","journal-title":"Immunotherapy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1902420","DOI":"10.1183\/13993003.02420-2019","article-title":"Mepolizumab Effectiveness and Identification of Super-Responders in Severe Asthma","volume":"55","author":"Harvey","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.chest.2020.03.042","article-title":"Real-World Effectiveness and the Characteristics of a \u2018Super-Responder\u2019 to Mepolizumab in Severe Eosinophilic Asthma","volume":"158","author":"Kavanagh","year":"2020","journal-title":"Chest"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S2213-2600(17)30344-2","article-title":"Predictors of enhanced response with benralizumab for patients with severe asthma: Pooled analysis of the SIROCCO and CALIMA studies","volume":"6","author":"FitzGerald","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S2213-2600(16)30031-5","article-title":"Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: A secondary analysis of the DREAM and MENSA studies","volume":"4","author":"Ortega","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"113978","DOI":"10.1016\/j.bcp.2020.113978","article-title":"Prediction of response to biological treatment with monoclonal antibodies in severe asthma","volume":"179","author":"Kroes","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1164\/rccm.201504-0763PP","article-title":"Evolving concepts of asthma","volume":"192","author":"Gauthier","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.jaci.2014.09.034","article-title":"High blood eosinophil counts predict sputum eosinophilia in patients with severe asthma","volume":"135","author":"Fowler","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/S2213-2600(15)00419-1","article-title":"Blood or sputum eosinophils to guide asthma therapy?","volume":"3","author":"Mukherjee","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1111\/cea.12695","article-title":"Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone-dependent severe asthma","volume":"46","author":"Sehmi","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"ref_20","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. Allergy Clin. Immunol."},{"key":"ref_21","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":"ref_22","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.jaip.2020.10.010","article-title":"Long-term therapy response to anti-interleukin-5 biologics in severe asthma\u2014A real life evaluation","volume":"9","author":"Eger","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1183\/09031936.00202013","article-title":"International ERS\/ATS guidelines on definition evaluation and treatment of severe asthma","volume":"43","author":"Chung","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_24","first-page":"309","article-title":"Guidelines for methacholine and exercise challenge testing 1999","volume":"161","author":"Crapo","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1164\/ajrccm.160.6.ats8-99","article-title":"Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide in Adults and Children\u20141999","volume":"160","author":"Slutsky","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1183\/09031936.96.09061174","article-title":"Measurement of inflammatory indices in induced sputum: Effects of selection of sputum to minimize salivary contamination","volume":"9","author":"Pizzichini","year":"1996","journal-title":"Eur. Respir. J."},{"key":"ref_27","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. Engl. J. Med."},{"key":"ref_28","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. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.iac.2018.06.003","article-title":"Airway eosinophilopoietic and autoimmune mechanisms of eosinophilia in severe asthma","volume":"38","author":"Bhalla","year":"2018","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.jaci.2015.03.013","article-title":"Monoclonal antibodies in excess: A simple way to avoi immunogenicity in patients?","volume":"136","author":"Chaigne","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jaip.2019.08.005","article-title":"Secondary loss of response to mepolizumab in severe eosinophilic asthma","volume":"8","author":"Cormier","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2000117","DOI":"10.1183\/13993003.00117-2020","article-title":"Suboptimal treatment response to anti-IL-5monoclonal antibodies in severe eosinophilic asthmatics with airway autoimmune phenomena","volume":"56","author":"Mukherjee","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1801127","DOI":"10.1183\/13993003.01127-2018","article-title":"Exacerbations of severe asthma in patients treated with mepolizumab","volume":"52","author":"Shrimanker","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaci.2019.05.031","article-title":"Phenotypes and endotypes of adult asthma: Moving toward precision medicine","volume":"144","author":"Kaur","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nri3786","article-title":"Type 2 inflammation in asthma\u2014present in most, absent in many","volume":"15","author":"Fahy","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1440-1843.2006.00784.x","article-title":"Inflammatory subtypes in asthma: Assessment and identification using induced sputum","volume":"11","author":"Simpson","year":"2006","journal-title":"Respirology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/j.jaci.2013.10.011","article-title":"Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis","volume":"133","author":"Moore","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_38","first-page":"81","article-title":"Patient profiles and clinical utility of mepolizumab in severe eosinophilic asthma","volume":"11","author":"Haldar","year":"2017","journal-title":"Biologics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/14737167.2017.1298444","article-title":"Economic analysis of the phase III MENSA study evaluating mepolizumab for severe asthma with eosinophilic phenotype","volume":"17","author":"Basu","year":"2017","journal-title":"Expert. Rev. Pharmacoecon. Outcomes Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/j.jaci.2008.02.033","article-title":"Anti-IL-5 [mepolizumab] therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels","volume":"121","author":"Stein","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","first-page":"PA1132","article-title":"Increase in systemic IL-5 is associated with mepolizumab treatment failure in patients with severe asthma","volume":"52","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1111\/all.14643","article-title":"Basophil activation and serum IL-5 levels as possible monitor biomarkers in severe eosinophilic asthma patients treated with anti-IL-5 drugs","volume":"76","author":"Caruso","year":"2021","journal-title":"Allergy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13223-016-0174-5","article-title":"Airway autoimmune responses in severe eosinophilic asthma following low-dose Mepolizumab therapy","volume":"13","author":"Mukherjee","year":"2017","journal-title":"Allergy Asthma Clin. Immunol."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/1\/70\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:13:05Z","timestamp":1760364785000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/1\/70"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,7]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["jpm12010070"],"URL":"https:\/\/doi.org\/10.3390\/jpm12010070","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,7]]}}}