{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:18:58Z","timestamp":1791242338737,"version":"4.1.0"},"reference-count":142,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"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>Allergic asthma is the most common asthma phenotype and is characterized by IgE sensitization to airborne allergens and subsequent typical asthmatic symptoms after exposure. A form of type 2 (T2) airway inflammation underlies allergic asthma. It usually arises in childhood and is accompanied by multimorbidity presenting with the occurrence of other atopic diseases, such as atopic dermatitis and allergic rhinitis. Diagnosis of the allergic endotype is based on in vivo (skin prick tests) and\/or in vitro (allergen-specific IgE levels, component-resolved diagnosis (CRD)) documentation of allergic sensitization. Biomarkers identifying patients with allergic asthma include total immunoglobulin E (IgE) levels, fractional exhaled nitric oxide (FeNO) and serum eosinophil counts. The treatment of allergic asthma is a complex procedure and requires a patient-tailored approach. Besides environmental control involving allergen avoidance measurements and cornerstone pharmacological interventions based on inhaled drugs, allergen-specific immunotherapy (AIT) and biologics are now at the forefront when it comes to personalized management of asthma. The current review aims to shed light on the distinct phenotype of allergic asthma, ranging over its current definition, clinical characteristics, pathophysiology and biomarkers, as well as its treatment options in the era of precision medicine.<\/jats:p>","DOI":"10.3390\/jpm12071162","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T03:41:33Z","timestamp":1658115693000},"page":"1162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Allergic Asthma in the Era of Personalized Medicine"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-3089","authenticated-orcid":false,"given":"Niki","family":"Papapostolou","sequence":"first","affiliation":[{"name":"Allergy Unit, 2nd Department of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, \u201cAttikon\u201d University Hospital, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Makris","sequence":"additional","affiliation":[{"name":"Allergy Unit, 2nd Department of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, \u201cAttikon\u201d University Hospital, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1016\/S0140-6736(12)61729-2","article-title":"Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990\u20132010: A systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Vos","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ccm.2018.10.010","article-title":"Asthma and Corticosteroid Responses in Childhood and Adult Asthma","volume":"40","author":"Ramadan","year":"2019","journal-title":"Clin. Chest Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.anai.2019.08.462","article-title":"Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4\/5 therapy in the United States","volume":"123","author":"Settipane","year":"2019","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1164\/rccm.201901-0016OC","article-title":"The Projected Economic and Health Burden of Uncontrolled Asthma in the United States","volume":"200","author":"Yaghoubi","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","unstructured":"Global Initiative for Asthma (2022, June 04). 2021 GINA Report, Global Management for Asthma Management and Prevention (2021 Update). Available online: https:\/\/ginasthma.org\/gina-reports."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1164\/rccm.202009-3631CI","article-title":"Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes","volume":"203","author":"Wenzel","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/nm.2678","article-title":"Asthma phenotypes: The evolution from clinical to molecular approaches","volume":"18","author":"Wenzel","year":"2012","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1034\/j.1398-9995.2001.t01-1-00001.x","article-title":"A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force","volume":"56","author":"Johansson","year":"2001","journal-title":"Allergy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jaip.2014.09.004","article-title":"The allergic asthma phenotype","volume":"2","author":"Schatz","year":"2014","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1034\/j.1398-9995.2002.23504.x","article-title":"Allergic vs. nonallergic asthma: What makes the difference?","volume":"57","author":"Charpin","year":"2002","journal-title":"Allergy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/all.13123","article-title":"Overview of systematic reviews in allergy epidemiology","volume":"72","author":"Genuneit","year":"2017","journal-title":"Allergy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1111\/all.13561","article-title":"Provocative proposal for a revised nomenclature for allergy and other hypersensitivity diseases","volume":"73","author":"Ring","year":"2018","journal-title":"Allergy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/all.14425","article-title":"EAACI Biologicals Guidelines-Recommendations for severe asthma","volume":"76","author":"Agache","year":"2021","journal-title":"Allergy"},{"key":"ref_14","unstructured":"Global Initiative for Asthma (2022, June 01). Difficult-to-Treat and Severe Asthma in Adolescent and Adult Patients: Diagnosis and Management. A GINA Pocket Guide for Health Professionals. Available online: https:\/\/ginasthma.org\/wpcontent\/uploads\/2019\/04\/GINA-Severe-asthma-Pocket-Guide-v2.0-wms-1.pdf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jaci.2003.10.041","article-title":"Distinguishing severe asthma phenotypes: Role of age at onset and eosinophilic inflammation","volume":"113","author":"Miranda","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1164\/rccm.200906-0896OC","article-title":"Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program","volume":"181","author":"Moore","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1046\/j.1365-2222.2003.01674.x","article-title":"Relationships of allergic sensitization, total immunoglobulin E and blood eosinophils to asthma severity in children of the EGEA Study","volume":"33","author":"Siroux","year":"2003","journal-title":"Clin. Exp. Allergy"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.jaci.2006.08.019","article-title":"Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide","volume":"118","author":"Fitzpatrick","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jaci.2005.04.017","article-title":"Contemporaneous maturation of immunologic and respiratory functions during early childhood: Implications for development of asthma prevention strategies","volume":"116","author":"Holt","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S2213-2600(20)30413-6","article-title":"Trajectories of asthma and allergies from 7 years to 53 years and associations with lung function and extrapulmonary comorbidity profiles: A prospective cohort study","volume":"9","author":"Bui","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1016\/j.jaip.2020.01.011","article-title":"Persistent Asthma from Childhood to Adulthood Presents a Distinct Phenotype of Adult Asthma","volume":"8","author":"To","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1056\/NEJMoa022363","article-title":"A longitudinal, population-based, cohort study of childhood asthma followed to adulthood","volume":"349","author":"Sears","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_23","first-page":"621","article-title":"Long-term follow-up studies of bronchial asthma in children. I. Prognosis and risk factors","volume":"39","author":"Maruo","year":"1990","journal-title":"Arerugi=[Allergy]"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e435","DOI":"10.1542\/peds.2013-0741","article-title":"Remission and persistence of asthma followed from 7 to 19 years of age","volume":"132","author":"Andersson","year":"2013","journal-title":"Pediatrics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.pupt.2013.07.003","article-title":"Complex phenotypes in asthma: Current definitions","volume":"26","author":"Wenzel","year":"2013","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/j.1398-9995.2012.02832.x","article-title":"Untangling asthma phenotypes and endotypes","volume":"67","author":"Agache","year":"2012","journal-title":"Allergy"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jaci.2010.11.037","article-title":"Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome","volume":"127","author":"Akdis","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1111\/all.12637","article-title":"Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis","volume":"70","author":"Bousquet","year":"2015","journal-title":"Allergy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.jaci.2016.06.059","article-title":"Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents","volume":"138","author":"Pongracic","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.jaci.2016.06.060","article-title":"Pathways through which asthma risk factors contribute to asthma severity in inner-city children","volume":"138","author":"Liu","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2147\/JAA.S348369","article-title":"Maintenance of Asthma Control in Adolescents with Severe Asthma After Transitioning to a Specialist Adult Centre: A French Cohort Experience","volume":"15","author":"Dufrois","year":"2022","journal-title":"J. Asthma Allergy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.chest.2019.10.053","article-title":"Characterization of Severe Asthma Worldwide: Data from the International Severe Asthma Registry","volume":"157","author":"Wang","year":"2020","journal-title":"Chest"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Louhaichi, S., Hamdi, B., Khalfallah, I., Akkad, A., Ammar, J., Berraies, A., and Hamzaoui, A. (2019). Analysis of phenotypes in a group of severe asthma. Eur. Respir. J., 54.","DOI":"10.1183\/13993003.congress-2019.PA4098"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0140-6736(06)69286-6","article-title":"Perennial allergen sensitisation early in life and chronic asthma in children: A birth cohort study","volume":"368","author":"Illi","year":"2006","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.jaci.2017.08.003","article-title":"Role of viral infections in the development and exacerbation of asthma in children","volume":"140","author":"Jartti","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/j.1398-9995.2010.02505.x","article-title":"Viruses and bacteria in acute asthma exacerbations\u2014A GA2 LEN-DARE systematic review","volume":"66","author":"Papadopoulos","year":"2011","journal-title":"Allergy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/cea.12450","article-title":"To what extent is allergen exposure a risk factor for the development of allergic disease?","volume":"45","author":"Custovic","year":"2015","journal-title":"Clin. Exp. Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1111\/pai.12881","article-title":"Contribution of repeated infections in asthma persistence from preschool to school age: Design and characteristics of the PreDicta cohort","volume":"29","author":"Xepapadaki","year":"2018","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.jaci.2016.08.048","article-title":"U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics","volume":"139","author":"Lefaudeux","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1164\/rccm.200711-1754OC","article-title":"Cluster analysis and clinical asthma phenotypes","volume":"178","author":"Haldar","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nri3786","article-title":"Type 2 inflammation in asthma--present in most, absent in many","volume":"15","author":"Fahy","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12016-018-8712-1","article-title":"Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease","volume":"56","author":"Kuruvilla","year":"2019","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41577-021-00538-7","article-title":"Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions?","volume":"21","author":"Akdis","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1016\/j.chest.2016.10.042","article-title":"Epithelial-Derived Cytokines in Asthma","volume":"151","author":"Mitchell","year":"2017","journal-title":"Chest"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nri3476","article-title":"Type 2 immunity and wound healing: Evolutionary refinement of adaptive immunity by helminths","volume":"13","author":"Gause","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nm.2731","article-title":"Innate and adaptive immune responses in asthma","volume":"18","author":"Holgate","year":"2012","journal-title":"Nat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s41467-020-20499-0","article-title":"Disulfide disruption reverses mucus dysfunction in allergic airway disease","volume":"12","author":"Morgan","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1056\/NEJMra0910061","article-title":"Airway mucus function and dysfunction","volume":"363","author":"Fahy","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nm.2755","article-title":"IgE and mast cells in allergic disease","volume":"18","author":"Galli","year":"2012","journal-title":"Nat. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0140-6736(17)30879-6","article-title":"After asthma: Redefining airways diseases","volume":"391","author":"Pavord","year":"2018","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.jaci.2016.06.033","article-title":"Interleukins (from IL-1 to IL-38), interferons, transforming growth factor \u03b2, and TNF-\u03b1: Receptors, functions, and roles in diseases","volume":"138","author":"Akdis","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_54","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_55","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_56","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.cell.2018.07.017","article-title":"Innate Lymphoid Cells: 10 Years On","volume":"174","author":"Vivier","year":"2018","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ccm.2018.10.014","article-title":"Proinflammatory Pathways in the Pathogenesis of Asthma","volume":"40","author":"Peebles","year":"2019","journal-title":"Clin. Chest Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/nm.3300","article-title":"Eosinophils in the spotlight: Eosinophilic airway inflammation in nonallergic asthma","volume":"19","author":"Brusselle","year":"2013","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa0906312","article-title":"A large-scale, consortium-based genomewide association study of asthma","volume":"363","author":"Moffatt","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"174ra26","DOI":"10.1126\/scitranslmed.3004812","article-title":"Lipoxin A4 regulates natural killer cell and type 2 innate lymphoid cell activation in asthma","volume":"5","author":"Barnig","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Oppenheimer, J., Hoyte, F.C., Phipatanakul, W., Silver, J., Howarth, P., and Lugogo, N.L. (Ann. Allergy Asthma Immunol., 2022). Allergic and eosinophilic asthma in the era of biomarkers and biologics: Similarities, differences and misconceptions, Ann. Allergy Asthma Immunol., in press.","DOI":"10.1016\/j.anai.2022.02.021"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jaci.2005.11.005","article-title":"Vascular endothelial growth factor-mediated induction of angiogenesis by human rhinoviruses","volume":"117","author":"Psarras","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2045-7022-2-14","article-title":"Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features","volume":"2","author":"Skevaki","year":"2012","journal-title":"Clin. Transl. Allergy"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.jaci.2005.04.007","article-title":"Duration of postviral airway hyperresponsiveness in children with asthma: Effect of atopy","volume":"116","author":"Xepapadaki","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1183\/09031936.02.00103602","article-title":"The effects of respiratory infections, atopy, and breastfeeding on childhood asthma","volume":"19","author":"Oddy","year":"2002","journal-title":"Eur. Respir. J."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Biomarkers Definitions Working Group (2001). Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin. Pharmacol. Ther., 69, 89\u201395.","DOI":"10.1067\/mcp.2001.113989"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1111\/all.13806","article-title":"Toward clinically applicable biomarkers for asthma: An EAACI position paper","volume":"74","author":"Diamant","year":"2019","journal-title":"Allergy"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1056\/NEJMra2032506","article-title":"Biologic Therapies for Severe Asthma","volume":"386","author":"Brusselle","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/all.12798","article-title":"IgE antibodies in relation to prevalence and multimorbidity of eczema, asthma, and rhinitis from birth to adolescence","volume":"71","author":"Ballardini","year":"2016","journal-title":"Allergy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1111\/all.12939","article-title":"A new framework for the interpretation of IgE sensitization tests","volume":"71","author":"Roberts","year":"2016","journal-title":"Allergy"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Fontanella, S., Frainay, C., Murray, C.S., Simpson, A., and Custovic, A. (2018). Machine learning to identify pairwise interactions between specific IgE antibodies and their association with asthma: A cross-sectional analysis within a population-based birth cohort. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002691"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.jaci.2015.08.044","article-title":"Distinguishing benign from pathologic TH2 immunity in atopic children","volume":"137","author":"Holt","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1164\/rccm.200905-0695OC","article-title":"Use of exhaled nitric oxide measurement to identify a reactive, at-risk phenotype among patients with asthma","volume":"181","author":"Dweik","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"(2005). ATS\/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am. J. Respir. Crit. Care Med., 171, 912\u2013930.","DOI":"10.1164\/rccm.200406-710ST"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Xepapadaki, P., Korovessi, P., Bachert, C., Finotto, S., Jartti, T., Lakoumentas, J., Kowalski, M.L., Lewandowska-Polak, A., Lukkarinen, H., and Zhang, N. (2020). Evolution of Airway Inflammation in Preschoolers with Asthma-Results of a Two-Year Longitudinal Study. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010187"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/S2213-2600(15)00050-8","article-title":"Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: A systematic review and meta-analysis","volume":"3","author":"Korevaar","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1164\/rccm.9120-11ST","article-title":"An official ATS clinical practice guideline: Interpretation of exhaled nitric oxide levels (FENO) for clinical applications","volume":"184","author":"Dweik","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1136\/thoraxjnl-2016-208704","article-title":"Accuracy of FENO for diagnosing asthma: A systematic review","volume":"72","author":"Karrasch","year":"2017","journal-title":"Thorax"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1164\/rccm.200903-0392OC","article-title":"T-helper type 2-driven inflammation defines major subphenotypes of asthma","volume":"180","author":"Woodruff","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1752-699X.2009.00162.x","article-title":"Inflammatory phenotypes in adult asthma: Clinical applications","volume":"3","author":"Gibson","year":"2009","journal-title":"Clin. Respir. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1136\/thoraxjnl-2018-211540","article-title":"Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): A systematic review and meta-analysis","volume":"73","author":"Petsky","year":"2018","journal-title":"Thorax"},{"key":"ref_82","unstructured":"Global Initiative for Asthma (2022, June 04). 2022 GINA Report, Global Management for Asthma Management and Prevention (2022 Update). Available online: https:\/\/ginasthma.org\/gina-reports."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1900588","DOI":"10.1183\/13993003.00588-2019","article-title":"Management of severe asthma: A European Respiratory Society\/American Thoracic Society guideline","volume":"55","author":"Holguin","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/all.12101","article-title":"Blood eosinophil counts rarely reflect airway eosinophilia in children with severe asthma","volume":"68","author":"Ullmann","year":"2013","journal-title":"Allergy"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"256","DOI":"10.4103\/lungindia.lungindia_73_16","article-title":"Correlation of total serum immunoglobulin E level, sputum, and peripheral eosinophil count in assessing the clinical severity in bronchial asthma","volume":"34","author":"Kumar","year":"2017","journal-title":"Lung India"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.anai.2014.04.013","article-title":"Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles","volume":"113","author":"Zoratti","year":"2014","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_87","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_88","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jaip.2018.04.043","article-title":"Omalizumab Effectiveness by Biomarker Status in Patients with Asthma: Evidence from PROSPERO, A Prospective Real-World Study","volume":"7","author":"Casale","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_89","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":"ref_90","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":"ref_91","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1080\/02770903.2018.1455855","article-title":"Serum periostin levels serve as a biomarker for both eosinophilic airway inflammation and fixed airflow limitation in well-controlled asthmatics","volume":"56","author":"Takahashi","year":"2019","journal-title":"J. Asthma"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.resinv.2020.02.003","article-title":"Role of serum periostin in the management of asthma and its comorbidities","volume":"58","author":"Matsumoto","year":"2020","journal-title":"Respir. Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jaci.2016.05.020","article-title":"Periostin upregulates the effector functions of eosinophils","volume":"138","author":"Noguchi","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2332\/allergolint.13-RAI-0678","article-title":"Serum periostin: A novel biomarker for asthma management","volume":"63","author":"Matsumoto","year":"2014","journal-title":"Allergol. Int."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12948-015-0027-7","article-title":"Biomarkers and severe asthma: A critical appraisal","volume":"13","author":"Chiappori","year":"2015","journal-title":"Clin. Mol. Allergy"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s40521-016-0106-0","article-title":"Biomarkers for the Phenotyping and Monitoring of Asthma in Children","volume":"3","author":"James","year":"2016","journal-title":"Curr. Treat. Options Allergy"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jaci.2016.10.019","article-title":"A single intervention for cockroach control reduces cockroach exposure and asthma morbidity in children","volume":"140","author":"Rabito","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.amepre.2011.05.012","article-title":"Effectiveness of home-based, multi-trigger, multicomponent interventions with an environmental focus for reducing asthma morbidity: A community guide systematic review","volume":"41","author":"Crocker","year":"2011","journal-title":"Am. J. Prev. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1056\/NEJMoa032097","article-title":"Results of a home-based environmental intervention among urban children with asthma","volume":"351","author":"Morgan","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1164\/rccm.201609-1966OC","article-title":"Preventing Severe Asthma Exacerbations in Children. A Randomized Trial of Mite-Impermeable Bedcovers","volume":"196","author":"Murray","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3390\/ph3030514","article-title":"Inhaled corticosteroids","volume":"3","author":"Barnes","year":"2010","journal-title":"Pharmaceuticals"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jaci.2004.12.1129","article-title":"Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids","volume":"115","author":"Deykin","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jaci.2004.11.014","article-title":"Characterization of within-subject responses to fluticasone and montelukast in childhood asthma","volume":"115","author":"Szefler","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.jaci.2008.12.1120","article-title":"Patient characteristics associated with improved outcomes with use of an inhaled corticosteroid in preschool children at risk for asthma","volume":"123","author":"Bacharier","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1016\/j.jaci.2016.09.028","article-title":"Individualized therapy for persistent asthma in young children","volume":"138","author":"Fitzpatrick","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1513\/AnnalsATS.202105-613OC","article-title":"Biomarkers to Predict Response to Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists in Adolescents and Adults with Mild Persistent Asthma","volume":"19","author":"Krishnan","year":"2022","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jaci.2008.11.016","article-title":"Phenotypic predictors of long-term response to inhaled corticosteroid and leukotriene modifier therapies in pediatric asthma","volume":"123","author":"Knuffman","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.jaip.2019.10.023","article-title":"Atopy Modifies the Association Between Inhaled Corticosteroid Use and Lung Function Decline in Patients with Asthma","volume":"8","author":"Marcon","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2020.02.005","article-title":"Immunotherapy in allergic diseases\u2014Improved understanding and innovation for enhanced effectiveness","volume":"66","author":"Mitsias","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1111\/pai.12807","article-title":"EAACI guidelines on allergen immunotherapy: Prevention of allergy","volume":"28","author":"Halken","year":"2017","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/all.12638","article-title":"Clinical contraindications to allergen immunotherapy: An EAACI position paper","volume":"70","author":"Pitsios","year":"2015","journal-title":"Allergy"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1046\/j.1365-2222.2001.01161.x","article-title":"Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study","volume":"31","author":"Pajno","year":"2001","journal-title":"Clin. Exp. Allergy"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3389\/fped.2018.00231","article-title":"Immunotherapy and Asthma in Children","volume":"6","author":"Tosca","year":"2018","journal-title":"Front. Pediatr."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1111\/all.13749","article-title":"EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven allergic asthma","volume":"74","author":"Agache","year":"2019","journal-title":"Allergy"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.jaci.2017.03.050","article-title":"Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision","volume":"140","author":"Bousquet","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.jaci.2015.04.047","article-title":"International consensus on allergy immunotherapy","volume":"136","author":"Jutel","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1111\/all.13208","article-title":"Allergen immunotherapy for allergic asthma: A systematic review and meta-analysis","volume":"72","author":"Dhami","year":"2017","journal-title":"Allergy"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1111\/j.1398-9995.2012.02865.x","article-title":"International consensus on (ICON) pediatric asthma","volume":"67","author":"Papadopoulos","year":"2012","journal-title":"Allergy"},{"key":"ref_119","first-page":"CD001186","article-title":"Allergen immunotherapy for asthma","volume":"4","author":"Abramson","year":"2003","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.anai.2016.09.438","article-title":"Effect of asthma therapies on the natural course of asthma","volume":"117","author":"Abrams","year":"2016","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jaci.2010.09.034","article-title":"Allergen immunotherapy: A practice parameter third update","volume":"127","author":"Cox","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2500\/aap.2019.40.4173","article-title":"Systemic reaction rates with omalizumab, subcutaneous immunotherapy, and combination therapy in children with allergic asthma","volume":"40","author":"Har","year":"2019","journal-title":"Allergy Asthma Proc."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.jaci.2004.11.053","article-title":"The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation","volume":"115","author":"Holgate","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1016\/j.rmed.2009.06.014","article-title":"\u201cReal-life\u201d effectiveness of omalizumab in patients with severe persistent allergic asthma: The PERSIST study","volume":"103","author":"Brusselle","year":"2009","journal-title":"Respir. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1067\/mai.2001.117880","article-title":"Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma","volume":"108","author":"Busse","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1056\/NEJMoa1009705","article-title":"Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children","volume":"364","author":"Busse","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_127","first-page":"CD003559","article-title":"Omalizumab for asthma in adults and children","volume":"1","author":"Normansell","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1056\/NEJMoa1804092","article-title":"Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma","volume":"378","author":"Castro","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"00204-2019","DOI":"10.1183\/23120541.00204-2019","article-title":"Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma","volume":"6","author":"Castro","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_130","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_131","doi-asserted-by":"crossref","first-page":"1901633","DOI":"10.1183\/13993003.01633-2019","article-title":"Clinical utility of fractional exhaled nitric oxide in severe asthma management","volume":"55","author":"Mansur","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_132","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_133","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S0140-6736(15)00388-8","article-title":"Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: A randomised, placebo-controlled, dose-ranging phase 2b trial","volume":"387","author":"Simpson","year":"2016","journal-title":"Lancet"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/cea.13614","article-title":"Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort","volume":"50","author":"Dupin","year":"2020","journal-title":"Clin. Exp. Allergy"},{"key":"ref_135","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_136","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. Engl. J. Med."},{"key":"ref_137","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. Engl. J. Med."},{"key":"ref_138","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_139","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_140","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 \u03b2(2)-agonists (SIROCCO): A randomised, multicentre, placebo-controlled phase 3 trial","volume":"388","author":"Bleecker","year":"2016","journal-title":"Lancet"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1016\/S0140-6736(16)31322-8","article-title":"Benralizumab, an anti-interleukin-5 receptor \u03b1 monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"388","author":"FitzGerald","year":"2016","journal-title":"Lancet"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1056\/NEJMoa1703501","article-title":"Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma","volume":"376","author":"Nair","year":"2017","journal-title":"N. 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