Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.
benralizumab
dupilumab
exacerbations
omalizumab
severe allergic asthma
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
04
02
2020
accepted:
11
02
2020
pubmed:
18
2
2020
medline:
15
5
2021
entrez:
18
2
2020
Statut:
ppublish
Résumé
Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50 - 0.81); dupilumab IRR 0.58 (95%CI 0.47 - 0.73); and omalizumab IRR 0.56 (95%CI 0.42 - 0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug-related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6-12 years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45-0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 -1.83)], reduced ICS [mean difference (MD) -0.45 (95% CI -0.58 to -0.32)] and rescue medication use [ MD -0.41 (95%CI -0.66 to -0.15)].
Substances chimiques
Anti-Asthmatic Agents
0
Antibodies, Monoclonal, Humanized
0
Biological Products
0
Omalizumab
2P471X1Z11
dupilumab
420K487FSG
benralizumab
71492GE1FX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1043-1057Informations de copyright
© 2020 John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Références
https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf. Accessed December 23, 2019.
Agache I, Lau S, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: house dust mite-driven allergic asthma al. Allergy. 2019;74(5):855-873.
Ring J, Jutel M, Papadopoulos N, Pfaar O, Akdis C. Provocative proposal for a revised nomenclature for allergy and other hypersensitivity diseases. Allergy. 2018;73(10):1939-1940.
Boonpiyathad T, Sözener ZC, Satitsuksanoa P, Akdis CA. Immunologic mechanisms in asthma. Semin Immunol. 2019;46:101333.
Matucci A, Vultaggio A, Maggi E, Kasujee I. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respir Res. 2018;19(1):113.
Agache I, Cojanu C, Laculiceanu A, Rogozea L. Critical points on the use of biologicals in allergic diseases and asthma. Allergy Asthma Immunol Res. 2020;12(1):24-41.
Palomares Ó, Sánchez-Ramón S, Dávila I, et al. dIvergEnt: how IgE axis contributes to the continuum of allergic asthma and anti-IgE therapies. Int J Mol Sci. 2017;18(6):E1328.
Huang YC, Weng CM, Lee MJ, Lin SM, Wang CH, Kuo HP. Endotypes of severe allergic asthma patients who clinically benefit from anti-IgE therapy. Clin Exp Allergy. 2019;49(1):44-53.
Khumalo J, Kirstein F, Scibiorek M, Hadebe S, Brombacher F. Therapeutic and prophylactic deletion of IL-4Rα-signaling ameliorates established ovalbumin induced allergic asthma. Allergy. 2019. [Epub ahead of print]. https://doi.org/10.1111/all.14137
Djukanović R, Wilson SJ, Kraft M, et al. Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med. 2004;170(6):583-593.
Mukherjee M, Kjarsgaard M, Radford K, et al. Omalizumab in patients with severe asthma and persistent sputum eosinophilia. Allergy Asthma Clin Immunol. 2019;15:21.
Haselkorn T, Szefler SJ, Simons FE, et al. Allergy, total serum immunoglobulin E, and airflow in children and adolescents in TENOR. Pediatr Allergy Immunol. 2010;21(8):1157-1165.
Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. Am J Respir Crit Care Med. 2010;181(4):315-323.
European Network for Understanding Mechanisms of Severe Asthma. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. European Network for Understanding Mechanisms of Severe Asthma. Eur Respir J. 2003;22:470-477.
Shaw D, Sousa AR, Fowler SJ, et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J. 2015;46(5):1308-1321.
Lafeuille MH, Gravel J, Figliomeni M, Zhang J, Lefebvre P. Burden of illness of patients with allergic asthma versus non-allergic asthma. J Asthma. 2013;50(8):900-907.
https://www.ema.europa.eu/en/medicines/human/EPAR/xolair. Accessed December 23, 2019.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/103976s5225lbl.pdf. Accessed December 23, 2019.
https://www.ema.europa.eu/en/medicines/human/EPAR/fasenra. Accessed December 23, 2019.
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761070Orig1s000Approv.pdf. Accessed December 23, 2019.
https://www.ema.europa.eu/en/medicines/human/summaries-opinion/dupixent-0. Accessed December 23, 2019.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761055s007lbl.pdf. Accessed December 23, 2019.
Higgins JP, Altman DG, Gøtzsche P, et al. The cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
Evers S, Goossens M, de Vet H, van Tulder M, Ament A. Criteria list for assessment of methodological quality of economic evaluations: consensus on health economic criteria. Int J Technol Assess Health Care. 2005;21(2):240-245.
Hutter F, Antoñanzas F. Economic evaluations in the EURONHEED: a comparative analysis. Pharmacoeconomics. 2009;27(7):561-570.
Nixon J, Rice S, Drummond M, Boulenger S, Ulmann P, de Pouvourville G. Guidelines for completing the EURONHEED transferability information checklists. Eur J Health Econ. 2009;10(2):157-165.
Rücker G, Cates CJ, Schwarzer G. Methods for including information from multi-arm trials in pairwise meta-analysis. Res Synth Methods. 2017;8(4):392-403.
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926.
Guyatt GH, Oxman AD, Sultan S, et al. GRADE guidelines. rating up the quality of evidence. J Clin Epidemiol. 2011;64(12):1311-1316.
Santanello NC, Zhang J, Seidenberg B, Reiss TF, Barber BL. What are minimal important changes for asthma measures in a clinical trial? Eur Respir J. 1999;14(1):23-27.
Jones PW. Interpreting thresholds for a clinically significant change in health status in asthma and COPD. Eur Respir J. 2002;19(3):398-404.
Juniper EF, Svensson K, Mörk AC, Ståhl E. Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir Med. 2005;99(5):553-558.
Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602-615.
Chipps BE, Newbold P, Hirsch I, Trudo F, Goldman M. Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2018;120(5):504-511.
FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128-2141.
Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25):2448-2458.
Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378(26):2486-2496.
Corren J, Castro M, O'Riordan T, et al. Dupilumab efficacy in patients with uncontrolled, moderate-to-severe allergic asthma. J Allergy Clin Immunol Pract. 2019;8(2):516-526.
Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184-190.
Finn A, Gross G, van Bavel J, et al. Omalizumab improves asthma-related quality of life in patients with severe allergic asthma. J Allergy Clin Immunol. 2003;111(2):278-284.
Lanier BQ, Corren J, Lumry W, Liu J, Fowler-Taylor A, Gupta N. Omalizumab is effective in the long-term control of severe allergic asthma. Ann Allergy Asthma Immunol. 2003;91(2):154-159.
Ayres J, Higgins B, Chilvers ER, Ayre G, Blogg M, Fox H. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergic asthma. Allergy. 2004;59(7):701-708.
Bardelas J, Figliomeni M, Kianifard F, Meng X. A 26-week, randomized, double-blind, placebo-controlled, multicenter study to evaluate the effect of omalizumab on asthma control in patients with persistent allergic asthma. J Asthma 2012;49(2):144-152.
Bousquet J, Siergiejko Z, Swiebocka E, et al. Persistency of response to omalizumab therapy in severe allergic (IgE-mediated) asthma. Allergy. 2011;66(5):671-678.
Siergiejko Z, Świebocka E, Smith N, et al. Oral corticosteroid sparing with omalizumab in severe allergic (IgE-mediated) asthma patients. Curr Med Res Opin. 2011;27(11):2223-2228.
Solèr M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18(2):254-261.
Buhl R, Hanf G, Soler M, et al. The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma. Eur Respir J. 2002;20(5):1088-1094.
Chanez P, Contin-Bordes C, Garcia G, et al. Omalizumab-induced decrease of FcξRI expression in patients with severe allergic asthma. Respir Med. 2010;104(11):1608-1617.
Corren J, Wood RA, Patel D, et al. Effects of omalizumab on changes in pulmonary function induced by controlled cat room challenge. J Allergy Clin Immunol. 2011;127(2):398-405.
Cruz AA, Lima F, Sarinho E, et al. Safety of anti-immunoglobulin E therapy with omalizumab in allergic patients at risk of geohelminth infection. Clin Exp Allergy. 2007;37(2):197-207.
Hanania NA, Alpan O, Hamilos DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med. 2011;154(9):573-582.
Holgate ST, Chuchalin A, Hebert J, et al. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy. 2004;34(4):632-638.
Hoshino M, Ohtawa J. Effects of adding omalizumab, an anti-immunoglobulin E antibody, on airway wall thickening in asthma. Respiration. 2012;83(6):520-528.
Humbert M, Beasley R, Ayres J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60(3):309-316.
Niven R, Chung KF, Panahloo Z, Blogg M, Ayre G. Effectiveness of omalizumab in patients with inadequately controlled severe persistent allergic asthma: an open-label study. Respir Med. 2008;102(10):1371-1378.
Ledford D, Busse W, Trzaskoma B, et al. A randomized multicenter study evaluating Xolair persistence of response after long-term therapy. J Allergy Clin Immunol. 2017;140(1):162-169.
van Rensen EL, Evertse CE, van Schadewijk WA, et al. Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment. Allergy. 2009;64(1):72-80.
Pasha MA, Jourd'heuil D, Jourd'heuil F, et al. The effect of omalizumab on small airway inflammation as measured by exhaled nitric oxide in moderate-to-severe asthmatic patients. Allergy Asthma Proc. 2014;35(3):241-249.
Li J, Kang J, Wang C, Yang J, et al. Omalizumab improves quality of life and asthma control in Chinese patients with moderate to severe asthma: a randomized phase III study. Allergy Asthma Immunol Res. 2016;8(4):319-328.
Ohta K, Miyamoto T, Amagasaki T, Yamamoto M, 1304 Study Group. Efficacy and safety of omalizumab in an Asian population with moderate-to-severe persistent asthma. Respirology. 2009;14(8):1156-1165.
Prieto L, Gutiérrez V, Colás C, et al. Effect of omalizumab on adenosine 5'-monophosphate responsiveness in subjects with allergic asthma. Int Arch Allergy Immunol. 2006;139(2):122-131.
Rubin AS, Souza-Machado A, Andradre-Lima M, Ferreira F, Honda A. Effect of omalizumab as add-on therapy on asthma-related quality of life in severe allergic asthma: a Brazilian study (QUALITX). J Asthma. 2012;49(3):288-293.
Vignola AM, Humbert M, Bousquet J, et al. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR. Allergy. 2004;59(7):709-717.
Zielen S, Lieb A, De La Motte S, et al. Omalizumab protects against allergen- induced bronchoconstriction in allergic (immunoglobulin E-mediated) asthma. Int Arch Allergy Immunol. 2013;160(1):102-110.
Busse WW, Morgan WJ, Gergen PJ, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364(11):1005-1015.
Milgrom H, Berger W, Nayak A, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001;108(2):E36.
Lemanske RF Jr, Nayak A, McAlary M, Everhard F, Fowler-Taylor A, Gupta N. Omalizumab improves asthma-related quality of life in children with allergic asthma. Pediatrics. 2002;110(5):e55.
Lanier B, Bridges T, Kulus M, Taylor AF, Berhane I, Vidaurre CF. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009;124(6):1210-1216.
Kulus M, Hébert J, Garcia E, Fowler Taylor A, Fernandez Vidaurre C, Blogg M. Omalizumab in children with inadequately controlled severe allergic (IgE-mediated) asthma. Curr Med Res Opin. 2010;26(6):1285-1293.
ICER. Institute for Clinical and Economic Review. Biologic Therapies for Treatment of Asthma Associated with Type 2 Inflammation: Effectiveness, Value, and Value-Based Price Benchmarks. https://icer-review.org/material/asthma-final-evidence-report/.Accessed September 2019.
Tikhonova I, Long L, Ocean N. Benralizumab for treating severe asthma: A Single Technology Appraisal. Peninsula Technology Assessment Group (PenTAG).2018.
Brown R, Turk F, Dale P, Bousquet J. Cost-effectiveness of omalizumab in patients with severe persistent allergic asthma. Allergy. 2007;62(2):149-153.
Campbell JD, Spackman DE, Sullivan SD. The costs and consequences of omalizumab in uncontrolled asthma from a USA payer perspective. Allergy. 2010;65(9):1141-1148.
Negro D, Pradelli L, Tognella S, Micheletto C, Iannazzo S. Cost-utility of add-on omalizumab in difficult-to-treat allergic asthma in Italy. Eur Ann Allergy Clin Immunol. 2011;43(2):45-53.
Negro D, Tognella S, Pradelli L. A 36-month study on the cost/utility of add-on omalizumab in persistent difficult-to-treat atopic asthma in Italy. J Asthma. 2012;49(8):843-848.
Dewilde S, Turk F, Tambour M, Sandström T. The economic value of anti-IgE in severe persistent, IgE-mediated (allergic) asthma patients: adaptation of INNOVATE to Sweden. Curr Med Res Opin. 2006;22(9):1765-1776.
Entrenas Costa MF, Soto Campos JG, Padilla-Galo A, et al. Economic impact and clinical outcomes of omalizumab add-on therapy for patients with severe persistent asthma: a real-world study. Pharmacoecon Open. 2019;3(3):333-342.
Faria R, McKenna C, Palmer S. Optimizing the position and use of omalizumab for severe persistent allergic asthma using cost-effectiveness analysis. Value Health. 2014;17(8):772-782.
Jahnz-Rozyk K, Lis J, Warchoł M, Kucharczyk A. Clinical and economic impact of a one-year treatment with omalizumab in patients with severe allergic asthma within a drug programme in Poland. BMC Pulm Med. 2018;18(1):48.
Levy AN, García a Ruiz AJ, García-Agua Soler N, Sanjuan MV. Cost-effectiveness of omalizumab in severe persistent asthma in Spain: a real-life perspective. J Asthma. 2015;52(2):205-210.
Menzella F, Facciolongo N, Piro R, et al. Clinical and pharmacoeconomic aspects of omalizumab: a 4-year follow-up. Ther Adv Respir Dis. 2012;6(2):87-95.
Morishima T, Kai H, Imanaka Y. Cost-effectiveness analysis of omalizumab for the treatment of severe asthma in japan and the value of responder prediction methods based on a multinational trial. Value Health Reg Issues. 2013;2(1):29-36.
Norman G, Faria R, Paton F, et al. Omalizumab for the treatment of severe persistent allergic asthma: a systematic review and economic evaluation. Health Technol Assess. 2013;17(52):1-342.
Oba Y, Salzman GA. Cost-effectiveness analysis of omalizumab in adults and adolescents with moderate-to-severe allergic asthma. J Allergy Clin Immunol. 2004;114(2):265-269.
Suzuki C, Lopes da Silva N, Kumar P, Pathak P, Ong SH. Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting. J Med Econ. 2017;20(8):832-839.
van Nooten F, Stern S, Braunstahl GJ, Thompson C, Groot M, Brown RE. Cost-effectiveness of omalizumab for uncontrolled allergic asthma in the Netherlands. J Med Econ. 2013;16(3):342-348.
Vennera M, Valero A, Uría E, Forné C, Picado C. Cost-effectiveness analysis of omalizumab for the treatment of severe persistent asthma in real clinical practice in Spain. Clin Drug Investig. 2016;36(7):567-578.
Wu AC, Paltiel AD, Kuntz KM, Weiss ST, Fuhlbrigge AL. Cost-effectiveness of omalizumab in adults with severe asthma: results from the asthma policy model. J Allergy Clin Immunol. 2007;120(5):1146-1152.
Zafari Z, Sadatsafavi M, Mark FitzGerald J, Canadian Respiratory Research Network. Cost-effectiveness of tiotropium versus omalizumab for uncontrolled allergic asthma in US. Cost Eff Resour Alloc. 2018;16:3.
Zafari Z, Sadatsafavi M, Marra CA, Chen W, FitzGerald JM. Cost-effectiveness of bronchial thermoplasty, omalizumab, and standard therapy for moderate-to-severe allergic asthma. PLoS ONE. 2016;11(1):e0146003.
Zhou H, Lu Y, Wu B, Che D. Cost-effectiveness of omalizumab for the treatment of inadequately controlled severe allergic asthma in Chinese children. J Asthma. 2020;57(1):87-94.
Lloyd A, Turk F, Leighton T, Canonica GW. Psychometric evaluation of global evaluation of treatment effectiveness: a tool to assess patients with moderate-to-severe allergic asthma. J Med Econ. 2007;10(3):285-296.
Tian BP, Zhang GS, Lou J, Zhou HB, Cui W. Efficacy and safety of benralizumab for eosinophilic asthma: a systematic review and meta-analysis of randomized controlled trials. J Asthma. 2018;55(9):956-965.
Liu W, Ma X, Zhou W. Adverse events of benralizumab in moderate to severe eosinophilic asthma: a meta-analysis. Medicine (Baltimore). 2019;98(22):e15868.
Zayed Y, Kheiri B, Banifadel M, et al. Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials. J Asthma. 2018;1-10. Epub ahead of print. https://doi.org/10.1080/02770903.2018.1520865
Normansell R, Walker S, Milan SJ, Walters EH, Nair P. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;1:CD003559.
Rodrigo GJ, Neffen H. Systematic review on the use of omalizumab for the treatment of asthmatic children and adolescents. Pediatr Allergy Immunol. 2015;26(6):551-556.
Corren J, Kavati A, Ortiz B, et al. Efficacy and safety of omalizumab in children and adolescents with moderate-to-severe asthma: a systematic literature review. Allergy Asthma Proc. 2017;38(4):250-263.
McQueen RB, Sheehan DN, Whittington MD, van Boven JFM, Campbell JD. Cost-effectiveness of biological asthma treatments: a systematic review and recommendations for future economic evaluations. Pharmacoeconomics. 2018;36(8):957-971.
Rodriguez-Martinez CE, Sossa-Briceño MP, Castro-Rodriguez JA. Cost effectiveness of pharmacological treatments for asthma: a systematic review. Pharmacoeconomics. 2018;36(10):1165-1200.
Einarson TR, Bereza BG, Nielsen TA, Van Laer J, Hemels ME. Systematic review of models used in economic analyses in moderate-to-severe asthma and COPD. J Med Econ. 2016;19(4):319-355.
Lundh A, Lexchin J, Mintzes B, Schroll JB, Bero L. Industry sponsorship and research outcome. Cochrane Database Syst Rev. 2017;2:MR000033.
Aburuz S, McElnay J, Gamble J, Millership J, Heaney L. Relationship between lung function and asthma symptoms in patients with difficult to control asthma. J Asthma. 2005;42(10):859-864.
MacDonald KM, Kavati A, Ortiz B, Alhossan A, Lee CS, Abraham I. Short- and long-term real-world effectiveness of omalizumab in severe allergic asthma: systematic review of 42 studies published 2008-2018. Expert Rev Clin Immunol. 2019;15(5):553-569.
Hastie AT, Moore WC, Li H, et al. Biomarker surrogates do not accurately predict sputum eosinophil and neutrophil percentages in asthmatic subjects. J Allergy Clin Immunol. 2013;132(1):72-80.
Wagener AH, de Nijs SB, Lutter R, et al. External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015;70(2):115-120.