{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:03:42Z","timestamp":1788401022264,"version":"build-2803163510"},"reference-count":156,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T00:00:00Z","timestamp":1607817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and\/or CRS, genome\u2013environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria\/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control.<\/jats:p>","DOI":"10.3390\/ijms21249477","type":"journal-article","created":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T23:39:36Z","timestamp":1607902776000},"page":"9477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Monoclonal Antibodies and Airway Diseases"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7221-1227","authenticated-orcid":false,"given":"Annina","family":"Lyly","sequence":"first","affiliation":[{"name":"Inflammation Centre, Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, P.O. Box 160, 00029 HUS Helsinki, Finland"},{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, 00029 HUS Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5109-6944","authenticated-orcid":false,"given":"Anu","family":"Laulajainen-Hongisto","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, 00029 HUS Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gevaert","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Upper Airway Research Laboratory, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1065-330X","authenticated-orcid":false,"given":"Paula","family":"Kauppi","sequence":"additional","affiliation":[{"name":"Heart and Lung Center, Pulmonary Department, University of Helsinki and Helsinki University Hospital, 00029 HUS Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-6686","authenticated-orcid":false,"given":"Sanna","family":"Toppila-Salmi","sequence":"additional","affiliation":[{"name":"Inflammation Centre, Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, P.O. Box 160, 00029 HUS Helsinki, Finland"},{"name":"Medicum, Haartman Institute, University of Helsinki, 00029 HUS Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dierick, B.J., Van Der Molen, T., Flokstra-de-Blok, B.M.J., Muraro, A., Postma, M.J., Kocks, J.W., and Van Boven, J.F. (2020). Burden and socioeconomics of asthma, allergic rhinitis, atopic dermatitis and food allergy. Expert Rev. Pharm. Outcomes Res., 1\u201317.","DOI":"10.1080\/14737167.2020.1819793"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1398-9995.2011.02646.x","article-title":"Chronic rhinosinusitis in Europe\u2014An Underestimated Disease. A GA2LEN study","volume":"66","author":"Hastan","year":"2011","journal-title":"Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.2500\/ajra.2013.27.3927","article-title":"Nonallergic Rhinitis","volume":"27","author":"Settipane","year":"2013","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1002\/alr.21557","article-title":"Asthma risk factors","volume":"5","author":"Toskala","year":"2015","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_6","unstructured":"(2020, April 20). Global Strategy for Asthma Management and Prevention. Available online: www.ginasthma.org."},{"key":"ref_7","first-page":"1","article-title":"Allergic rhinitis","volume":"6","author":"Bousquet","year":"2020","journal-title":"Nat. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/j.1365-2222.2009.03298.x","article-title":"Intrinsic asthma: Not so different from allergic asthma but driven by superantigens?","volume":"39","author":"Barnes","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4049\/jimmunol.1400844","article-title":"Natural Antibodies Bridge Innate and Adaptive Immunity","volume":"194","author":"Panda","year":"2014","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13223-018-0278-1","article-title":"An introduction to immunology and immunopathology","volume":"14","author":"Marshall","year":"2018","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/256495a0","article-title":"Continuous cultures of fused cells secreting antibody of predefined specificity","volume":"256","author":"Milstein","year":"1975","journal-title":"Nature"},{"key":"ref_12","first-page":"11","article-title":"The Molecular Mechanisms That Underlie the Immune Biology of Anti-drug Antibody Formation Following Treatment with Monoclonal Antibodies","volume":"11","author":"DeKosky","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jaad.2020.02.020","article-title":"Comparison of C3d immunohistochemical staining to enzyme-linked immunosorbent assay and immunofluorescence for diagnosis of bullous pemphigoid","volume":"83","author":"Wang","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/icb.1997.10","article-title":"A brief history of the discovery of the immunoglobulins and the origin of the modern immunoglobulin nomenclature","volume":"75","author":"Black","year":"1997","journal-title":"Immunol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.anai.2016.01.003","article-title":"The discovery of IgE 50 years later","volume":"116","author":"Heymann","year":"2016","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1001\/jama.2017.8372","article-title":"Diagnosis and management of asthma in adults a review","volume":"318","author":"McCracken","year":"2017","journal-title":"JAMA\u2014J. Am. Med. Assoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1440868","DOI":"10.1080\/20018525.2018.1440868","article-title":"Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults","volume":"5","author":"Porsbjerg","year":"2018","journal-title":"Eur. Clin. Respir. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1136\/thoraxjnl-2017-210531","article-title":"Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population","volume":"73","author":"Kerkhof","year":"2017","journal-title":"Thorax"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/00016480252814199","article-title":"The Estimated Incidence of Symptomatic Nasal Polyps","volume":"122","author":"Larsen","year":"2002","journal-title":"Acta Oto-Laryngol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1177\/000348940311200709","article-title":"Prevalence of Nasal Polyps in Adults: The Skovde Population-Based Study","volume":"112","author":"Johansson","year":"2003","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11882-020-00916-6","article-title":"Phenotypes in Chronic Rhinosinusitis","volume":"20","author":"McCormick","year":"2020","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jaci.2015.12.1324","article-title":"Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers","volume":"137","author":"Tomassen","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lyly, A., Laulajainen-Hongisto, A., Turpeinen, H., Vento, S.I., Myller, J., Numminen, J., Sillanp\u00e4\u00e4, S., Sahlman, J., Kauppi, P., and Toppila-Salmi, S. (2020). Factors affecting upper airway control of NSAID-exacerbated respiratory disease: A real-world study of 167 patients. Immun. Inflamm. Dis., in press.","DOI":"10.1002\/iid3.347"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1398-9995.2011.02709.x","article-title":"Asthma in adults and its association with chronic rhinosinusitis: The GA2LEN survey in Europe","volume":"67","author":"Jarvis","year":"2012","journal-title":"Allergy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"BBI.S34610\u201325","DOI":"10.4137\/BBI.S34610","article-title":"Use of Metatranscriptomics in Microbiome Research","volume":"10","author":"Bashiardes","year":"2016","journal-title":"Bioinform. Biol. Insights"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fcell.2020.00204","article-title":"Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases","volume":"8","author":"Luukkainen","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41577-020-0301-x","article-title":"Heterogeneity in the initiation, development and function of type 2 immunity","volume":"20","author":"Gause","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/pai.12410","article-title":"Allergic multimorbidity of asthma, rhinitis and eczema over 20 years in the German birth cohort MAS","volume":"26","author":"Gough","year":"2015","journal-title":"Pediatric Allergy Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1111\/all.13971","article-title":"Risk of adult-onset asthma increases with the number of allergic multimorbidities and decreases with age","volume":"74","author":"Chanoine","year":"2019","journal-title":"Allergy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-genom-083117-021651","article-title":"The Genetics and Genomics of Asthma","volume":"19","author":"Cookson","year":"2018","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.jaci.2006.07.024","article-title":"Clinical and pathologic perspectives on aspirin sensitivity and asthma","volume":"118","author":"Stevenson","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1056\/NEJMra1712125","article-title":"Aspirin-Exacerbated Respiratory Disease","volume":"379","author":"White","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/all.13599","article-title":"Diagnosis and Management of NSAID-Exacerbated Respiratory Disease (N-ERD)\u2014A EAACI Position Paper","volume":"74","author":"Kowalski","year":"2018","journal-title":"Allergy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.jaci.2005.08.035","article-title":"Aspirin sensitivity and severity of asthma: Evidence for irreversible airway obstruction in patients with severe or difficult-to-treat asthma","volume":"116","author":"Mascia","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1111\/resp.12076","article-title":"Low prostaglandin E2and cyclooxygenase expression in nasal mucosa fibroblasts of aspirin-intolerant asthmatics","volume":"18","author":"Pereda","year":"2013","journal-title":"Respirology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s12016-012-8340-0","article-title":"Aspirin-Intolerant Asthma: A Comprehensive Review of Biomarkers and Pathophysiology","volume":"45","author":"Velazquez","year":"2012","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhino12.000","article-title":"EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists","volume":"50","author":"Fokkens","year":"2012","journal-title":"Rhinol. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/0091-6749(80)90143-8","article-title":"Aspirin-sensitive asthma: Tolerance to aspirin after positive oral aspirin challenges","volume":"66","author":"Stevenson","year":"1980","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1016\/j.jaip.2020.06.063","article-title":"High Discontinuation Rates of Peroral ASA Treatment for CRSwNP: A Real-World Multicenter Study of 171 N-ERD Patients","volume":"8","author":"Turpeinen","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/alr.22473","article-title":"The role of biologics in chronic rhinosinusitis: A systematic review","volume":"10","author":"Iqbal","year":"2019","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kim, C., Han, J., Wu, T., Bachert, C., Fokkens, W., Hellings, P., Hopkins, C., Lee, S., Mullol, J., and Lee, J.T. (2020). Role of Biologics in Chronic Rhinosinusitis with Nasal Polyposis: State of the Art Review. Otolaryngol. Neck Surg.","DOI":"10.1177\/0194599820939964"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.anai.2019.12.001","article-title":"Biologics in chronic rhinosinusitis with nasal polyposis","volume":"124","author":"Laidlaw","year":"2020","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/all.14027","article-title":"New biological treatments for asthma and skin allergies","volume":"75","author":"Eyerich","year":"2020","journal-title":"Allergy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/ni.2617","article-title":"TH2, allergy and group 2 innate lymphoid cells","volume":"14","author":"Kim","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1007\/s11882-014-0435-7","article-title":"Cytokine profiles in allergic rhinitis topical collection on rhinitis","volume":"14","author":"Scadding","year":"2014","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s11882-014-0495-8","article-title":"Molecular mechanisms of nasal epithelium in rhinitis and rhinosinusitis","volume":"15","author":"Fokkens","year":"2015","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1164\/rccm.2105079","article-title":"Anti\u2013Interleukin-9 Antibody Treatment Inhibits Airway Inflammation and Hyperreactivity in Mouse Asthma Model","volume":"166","author":"Cheng","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ni.3045","article-title":"Respiratory epithelial cells orchestrate pulmonary innate immunity","volume":"16","author":"Whitsett","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_49","first-page":"1","article-title":"Targeting cell signaling in allergic asthma","volume":"4","author":"Athari","year":"2019","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev.genom.6.080604.162254","article-title":"Modifier Genetics: Cystic Fibrosis","volume":"6","author":"Cutting","year":"2005","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2500\/ajra.2012.26.3716","article-title":"Acquired Cilia Dysfunction in Chronic Rhinosinusitis","volume":"26","author":"Gudis","year":"2012","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/ACI.0000000000000588","article-title":"Th2 inflammatory responses in the development of nasal polyps and chronic rhinosinusitis","volume":"20","author":"Ryu","year":"2020","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.jaci.2016.03.045","article-title":"Staphylococcal serine protease\u2013like proteins are pacemakers of allergic airway reactions to Staphylococcus aureus","volume":"139","author":"Stentzel","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1164\/rccm.201207-1292OC","article-title":"Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression","volume":"187","author":"Takabayashi","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1111\/all.13410","article-title":"The asthma-rhinitis multimorbidity is associated with IgE polysensitization in adolescents and adults","volume":"73","author":"Siroux","year":"2018","journal-title":"Allergy"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1901592","DOI":"10.1183\/13993003.01592-2019","article-title":"Staphylococcus aureus and its IgE-inducing enterotoxins in asthma: Current knowledge","volume":"55","author":"Bachert","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.jaci.2010.07.007","article-title":"Presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in nasal polyps is associated with comorbid asthma","volume":"126","author":"Bachert","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1111\/all.12230","article-title":"Staphylococcus aureus enterotoxin-specific IgE is associated with asthma in the general population: A GA(2)LEN study","volume":"68","author":"Tomassen","year":"2013","journal-title":"Allergy"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.jaip.2020.03.007","article-title":"Endotypes of Chronic Rhinosinusitis with Nasal Polyps: Pathology and Possible Therapeutic Implications","volume":"8","author":"Bachert","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1164\/rccm.201710-2112OC","article-title":"Staphylococcus aureusInduces a Mucosal Type 2 Immune Response via Epithelial Cell\u2013derived Cytokines","volume":"198","author":"Lan","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jprot.2017.12.003","article-title":"Staphylococcus aureus controls interleukin-5 release in upper airway inflammation","volume":"180","author":"Bachert","year":"2018","journal-title":"J. Proteom."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.jaci.2018.07.006","article-title":"Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis","volume":"143","author":"Takeda","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3892\/etm.2016.3951","article-title":"Different roles of Staphylococcus aureus enterotoxin in different subtypes of nasal polyps","volume":"13","author":"Cheng","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1111\/j.1398-9995.2011.02637.x","article-title":"The association between bacterial colonization and inflammatory pattern in Chinese chronic rhinosinusitis patients with nasal polyps","volume":"66","author":"Ba","year":"2011","journal-title":"Allergy"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"34","DOI":"10.2500\/ajra.2013.27.3831","article-title":"Antibody Deficiency in Chronic Rhinosinusitis: Epidemiology and Burden of Illness","volume":"27","author":"Ocampo","year":"2013","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Yu, X., and Cragg, M.S. (2020). Engineered antibodies to combat viral threats. Nature.","DOI":"10.1038\/d41586-020-03196-2"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.tim.2015.07.005","article-title":"Antiviral Monoclonal Antibodies: Can They Be More Than Simple Neutralizing Agents?","volume":"23","author":"Pelegrin","year":"2015","journal-title":"Trends Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.jaip.2018.12.028","article-title":"Serum IgG Concentrations in Adult Patients Experiencing Virus-Induced Severe Asthma Exacerbations","volume":"7","author":"Verduyn","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13223-017-0219-4","article-title":"Asthma biomarkers in the age of biologics","volume":"13","author":"Kim","year":"2017","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_70","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_71","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/cea.12880","article-title":"Revisiting Type 2-high and Type 2-low airway inflammation in asthma: Current knowledge and therapeutic implications","volume":"47","author":"Robinson","year":"2017","journal-title":"Clin. Exp. Allergy"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.2147\/TCRM.S125964","article-title":"Dupilumab in the management of moderate-to-severe asthma: The data so far","volume":"13","author":"Barranco","year":"2017","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_73","first-page":"1","article-title":"The Role of Periostin in the Occurrence and Progression of Eosinophilic Chronic Sinusitis with Nasal Polyps","volume":"7","author":"Xu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.jaci.2015.09.005","article-title":"Association of periostin expression with eosinophilic inflammation in nasal polyps","volume":"136","author":"Wang","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"234","DOI":"10.4193\/Rhino16.215","article-title":"Periostin as a marker of mucosal remodelling in chronic rhinosinusitis","volume":"55","author":"Ebenezer","year":"2017","journal-title":"Rhinol. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.chest.2018.08.1032","article-title":"Looking for Airways Periostin in Severe Asthma: Could it Be Useful for Clustering Type 2 Endotype?","volume":"154","author":"Carpagnano","year":"2018","journal-title":"Chest"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jim.2009.08.012","article-title":"Analytical validation of a highly sensitive microparticle-based immunoassay for the quantitation of IL-13 in human serum using the Erenna\u00ae immunoassay system","volume":"350","author":"Ledger","year":"2009","journal-title":"J. Immunol. Methods"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.cca.2016.10.020","article-title":"Development of a new ARCHITECT automated periostin immunoassay","volume":"464","author":"Jeanblanc","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"152","DOI":"10.4193\/Rhin16.314","article-title":"The effect of systemic treatments on periostin expression reflects their interference with the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps","volume":"55","author":"Schryver","year":"2017","journal-title":"Rhinology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S0140-6736(15)00149-X","article-title":"Atopic dermatitis","volume":"387","author":"Weidinger","year":"2016","journal-title":"Lancet"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.drudis.2014.09.003","article-title":"An overview of FDA-approved biologics medicines","volume":"20","author":"Kinch","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_82","first-page":"1","article-title":"Endotype-driven treatment in chronic upper airway diseases","volume":"7","author":"Hellings","year":"2017","journal-title":"Clin. Transl. Allergy"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.jaci.2020.01.019","article-title":"Endotypes of chronic rhinosinusitis: Impact on management","volume":"145","author":"Cardell","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.anai.2018.07.033","article-title":"Selecting the right biologic for your patients with severe asthma","volume":"121","author":"Manka","year":"2018","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nri1181","article-title":"The regulation of immunoglobulin E class-switch recombination","volume":"3","author":"Geha","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1177\/1753466618810192","article-title":"Omalizumab, the first available antibody for biological treatment of severe asthma: More than a decade of real-life effectiveness","volume":"12","author":"Pelaia","year":"2018","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jaci.2004.06.032","article-title":"Omalizumab-induced reductions in mast cell Fc\u03b5RI expression and function","volume":"114","author":"Beck","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.4049\/jimmunol.158.3.1438","article-title":"Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody","volume":"158","author":"MacGlashan","year":"1997","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Novosad, J., and Kr\u010dmov\u00e1, I. (2020). Evolution of our view on the IgE molecule role in bronchial asthma and the clinical effect of its modulation by omalizumab: Where do we stand today?. Int. J. Immunopathol. Pharmacol., 34.","DOI":"10.1177\/2058738420942386"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1056\/NEJM199010113231505","article-title":"Eosinophilic Inflammation in Asthma","volume":"323","author":"Bousquet","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nrd3838","article-title":"Targeting eosinophils in allergy, inflammation and beyond","volume":"12","author":"Fulkerson","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.3389\/fphys.2019.01514","article-title":"Interleukin-5 in the Pathophysiology of Severe Asthma","volume":"10","author":"Pelaia","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_93","first-page":"321","article-title":"Technology evaluation: Mepolizumab, GlaxoSmithKline","volume":"5","author":"Gnanakumaran","year":"2003","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2217\/imt.15.102","article-title":"Mepolizumab in the treatment of severe eosinophilic asthma","volume":"8","author":"Fainardi","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1093\/intimm\/11.12.1935","article-title":"Mapping and characterization of the epitope(s) of Sch 55700, a humanized mAb, that inhibits human IL-5","volume":"11","author":"Zhang","year":"1999","journal-title":"Int. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.jaci.2010.04.004","article-title":"MEDI-563, a humanized anti\u2013IL-5 receptor \u03b1 mAb with enhanced antibody-dependent cell-mediated cytotoxicity function","volume":"125","author":"Kolbeck","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1517\/14712598.2012.642359","article-title":"Benralizumab\u2014A Humanized Mab to IL-5r\u03b1 with Enhanced Antibody-Dependent Cell-Mediated Cytotoxicity\u2014A Novel Approach for the Treatment of Asthma","volume":"12","author":"Ghazi","year":"2012","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1111\/cea.13720","article-title":"Benralizumab strongly reduces blood basophils in severe eosinophilic asthma","volume":"50","author":"Lommatzsch","year":"2020","journal-title":"Clin. Exp. Allergy"},{"key":"ref_99","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. Engl. J. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.cell.2007.12.030","article-title":"Molecular and Structural Basis of Cytokine Receptor Pleiotropy in the Interleukin-4\/13 System","volume":"132","author":"Laporte","year":"2008","journal-title":"Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrd4624","article-title":"Targeting key proximal drivers of type 2 inflammation in disease","volume":"15","author":"Gandhi","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1080\/07853890701449354","article-title":"Triggers of IgE class switching and allergy development","volume":"39","author":"Poulsen","year":"2007","journal-title":"Ann. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev.immunol.21.120601.141142","article-title":"IL-13 effector functions","volume":"21","author":"Wynn","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.jaci.2007.03.048","article-title":"Eosinophil trafficking in allergy and asthma","volume":"119","author":"Rosenberg","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/all.14151","article-title":"Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4R\u03b1 antibody, is required to broadly inhibit type 2 inflammation","volume":"75","author":"Allinne","year":"2020","journal-title":"Allergy"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.cyto.2015.05.018","article-title":"Strategies targeting the IL-4\/IL-13 axes in disease","volume":"75","author":"May","year":"2015","journal-title":"Cytokine"},{"key":"ref_107","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":"2013","journal-title":"Eur. Respir. J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1701782","DOI":"10.1183\/13993003.01782-2017","article-title":"Care pathways for the selection of a biologic in severe asthma","volume":"50","author":"Bousquet","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/all.12616","article-title":"EAACI IG Biologicals task force paper on the use of biologic agents in allergic disorders","volume":"70","author":"Boyman","year":"2015","journal-title":"Allergy"},{"key":"ref_110","first-page":"1","article-title":"A Comparison of Biologicals in the Treatment of Adults with Severe Asthma\u2014Real-Life Experiences","volume":"6","author":"Kotisalmi","year":"2020","journal-title":"Asthma Res. Pract."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Normansell, R., Walker, S., Milan, S.J., Walters, E.H., and Nair, P. (2014). Omalizumab for asthma in adults and children. Cochrane Database Syst. Rev., CD003559.","DOI":"10.1002\/14651858.CD003559.pub4"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1702523","DOI":"10.1183\/13993003.02523-2017","article-title":"Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: The STELLAIR study","volume":"51","author":"Humbert","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"00068","DOI":"10.1183\/23120541.00068-2020","article-title":"Response to mepolizumab treatment is sustained across 4-weekly dosing periods","volume":"6","author":"Pavord","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_114","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":"ref_115","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.chest.2016.03.032","article-title":"Reslizumab for Inadequately Controlled Asthma with Elevated Blood Eosinophil Levels: A Randomized Phase 3 Study","volume":"150","author":"Bjermer","year":"2016","journal-title":"Chest"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/S0140-6736(16)31324-1","article-title":"Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting \u03b22-agonists (SIROCCO): A randomised, multicentre, placebo-controlled phase 3 trial","volume":"388","author":"Bleecker","year":"2016","journal-title":"Lancet"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Kavanagh, J.E., Hearn, A.P., Dhariwal, J., D\u2019Ancona, G., Douiri, A., Roxas, C., Fernandes, M., Green, L., Thomson, L., and Nanzer, A.M. (2020). Real-World Effectiveness of Benralizumab in Severe Eosinophilic Asthma. Chest.","DOI":"10.1183\/13993003.congress-2020.2261"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1056\/NEJMoa1804093","article-title":"Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma","volume":"378","author":"Rabe","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jaci.2012.07.047","article-title":"Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma","volume":"131","author":"Gevaert","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"318","DOI":"10.4193\/Rhino09.144","article-title":"A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis","volume":"48","author":"Pinto","year":"2010","journal-title":"Rhinol. J."},{"key":"ref_121","first-page":"226","article-title":"Omalizumab in patients with NSAIDs-exacerbated respiratory disease","volume":"58","author":"Stergioudi","year":"2020","journal-title":"Rhinology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.jaci.2020.05.032","article-title":"Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials","volume":"146","author":"Gevaert","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.jaci.2006.05.031","article-title":"Nasal IL-5 levels determine the response to anti\u2013IL-5 treatment in patients with nasal polyps","volume":"118","author":"Gevaert","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.jaci.2017.05.044","article-title":"Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial","volume":"140","author":"Bachert","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jaci.2011.07.056","article-title":"Mepolizumab, a humanized anti\u2013IL-5 mAb, as a treatment option for severe nasal polyposis","volume":"128","author":"Gevaert","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Chong, L.Y., Piromchai, P., Sharp, S., Snidvongs, K., Philpott, C., Hopkins, C., and Burton, M.J. (2020). Biologics for chronic rhinosinusitis. Cochrane Database Syst. Rev., 2020.","DOI":"10.1002\/14651858.CD013513.pub2"},{"key":"ref_127","first-page":"4616","article-title":"Late Breaking Abstract\u2014Add-on mepolizumab for chronic rhinosinusitis with nasal polyps: SYNAPSE study","volume":"56","author":"Hopkins","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/S0140-6736(19)31881-1","article-title":"Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): Results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials","volume":"394","author":"Bachert","year":"2019","journal-title":"Lancet"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/bjd.17869","article-title":"Conjunctivitis in dupilumab clinical trials","volume":"181","author":"Akinlade","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Golebski, K., Van Tongeren, J., Van Egmond, D., De Groot, E.J., Fokkens, W.J., and Van Drunen, C.M. (2016). Specific Induction of TSLP by the Viral RNA Analogue Poly(I:C) in Primary Epithelial Cells Derived from Nasal Polyps. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152808"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1056\/NEJMoa1402895","article-title":"Effects of an Anti-TSLP Antibody on Allergen-Induced Asthmatic Responses","volume":"370","author":"Gauvreau","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.pharmthera.2011.09.005","article-title":"Monoclonal antibodies for the treatment of asthma","volume":"132","author":"Catley","year":"2011","journal-title":"Pharmacol. Ther."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1111\/all.12708","article-title":"Treatment with anti-OX40L or anti-TSLP does not alter the frequency of T regulatory cells in allergic asthmatics","volume":"70","author":"Baatjes","year":"2015","journal-title":"Allergy"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1056\/NEJMoa1704064","article-title":"Tezepelumab in Adults with Uncontrolled Asthma","volume":"377","author":"Corren","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Michel, O., Dinh, P.H.D., Doyen, V., and Corazza, F. (2014). Anti-TNF inhibits the Airways neutrophilic inflammation induced by inhaled endotoxin in human. BMC Pharmacol. Toxicol., 15.","DOI":"10.1186\/2050-6511-15-60"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1517\/13543784.17.8.1203","article-title":"Anti-TNF-\u03b1 therapies in chronic obstructive pulmonary diseases","volume":"17","author":"Antoniu","year":"2008","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/01.all.0000199798.10047.74","article-title":"Anti-TNF-\u03b1 and Th1 cytokine-directed therapies for the treatment of asthma","volume":"6","author":"Cazzola","year":"2006","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1517\/13543784.15.2.181","article-title":"Infliximab for chronic obstructive pulmonary disease: Towards a more specific inflammation targeting?","volume":"15","author":"Antoniu","year":"2006","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1164\/rccm.201212-2318OC","article-title":"Randomized, Double-Blind, Placebo-controlled Study of Brodalumab, a Human Anti\u2013IL-17 Receptor Monoclonal Antibody, in Moderate to Severe Asthma","volume":"188","author":"Busse","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/MCP.0000000000000120","article-title":"Therapeutic implications of \u201cneutrophilic asthma\u201d","volume":"21","author":"Nair","year":"2015","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_141","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":"ref_142","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S2213-2600(16)30227-2","article-title":"Efficacy and safety of a CXCR2 antagonist, AZD5069, in patients with uncontrolled persistent asthma: A randomised, double-blind, placebo-controlled trial","volume":"4","author":"Metev","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and Inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1042\/CS20160487","article-title":"Cellular and molecular mechanisms of asthma and COPD","volume":"131","author":"Barnes","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/ni.2104","article-title":"Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161","volume":"12","author":"Trifari","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/MCP.0000000000000544","article-title":"Targeting lipid mediators in asthma: Time for reappraisal","volume":"25","author":"Diamant","year":"2019","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/all.13642","article-title":"Comparing biologicals and small molecule drug therapies for chronic respiratory diseases: An EAACI Taskforce on Immunopharmacology position paper","volume":"74","author":"Adcock","year":"2019","journal-title":"Allergy"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13223-017-0183-z","article-title":"Efficacy and safety of setipiprant in seasonal allergic rhinitis: Results from Phase 2 and Phase 3 randomized, double-blind, placebo- and active-referenced studies","volume":"13","author":"Ratner","year":"2017","journal-title":"Allergy, Asthma Clin. Immunol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/cea.12357","article-title":"Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics","volume":"44","author":"Diamant","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1183\/09031936.00092111","article-title":"Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459","volume":"41","author":"Singh","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/j.1365-2222.2011.03813.x","article-title":"A randomized, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma","volume":"42","author":"Barnes","year":"2012","journal-title":"Clin. Exp. Allergy"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.pupt.2015.03.003","article-title":"Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment","volume":"32","author":"Hall","year":"2015","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.pupt.2016.06.005","article-title":"The oral CRTh2 antagonist QAW039 (fevipiprant): A phase II study in uncontrolled allergic asthma","volume":"39","author":"Erpenbeck","year":"2016","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1700670","DOI":"10.1183\/13993003.00670-2017","article-title":"Fevipiprant, an oral prostaglandin DP2receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids","volume":"50","author":"Bateman","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jaci.2012.10.013","article-title":"Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients","volume":"131","author":"Busse","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Brightling, C., Gaga, M., Inoue, H., Li, J., Maspero, J., Wenzel, S., Maitra, S., Lawrence, D., Brockhaus, F., and Lehmann, T. (2020). Effectiveness of fevipiprant in reducing exacerbations in patients with severe asthma (LUSTER-1 and LUSTER-2): Two phase 3 randomised controlled trials. Lancet Respir. Med.","DOI":"10.1016\/S2213-2600(20)30412-4"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9477\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:44:30Z","timestamp":1760179470000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,13]]},"references-count":156,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21249477"],"URL":"https:\/\/doi.org\/10.3390\/ijms21249477","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,13]]}}}