{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:04:01Z","timestamp":1791644641297,"version":"4.3.4"},"reference-count":171,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010609","name":"Medical University of Gda\u0144sk","doi-asserted-by":"crossref","award":["61-00206"],"award-info":[{"award-number":["61-00206"]}],"id":[{"id":"10.13039\/501100010609","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Neutrophilic asthma (NA) is an inflammatory phenotype of asthma, characterized by predominantly neutrophilic infiltrations in bronchial mucosa. It is usually diagnosed on the basis of high neutrophil count in induced sputum (from &gt;40% to &gt;76%) with low eosinophils (&lt;2%). The prevalence of NA ranges from 16% to 28% of the adult asthma population depending on the definitions and study methods applied. A clinical picture of NA is characterized by late onset of symptoms, higher exacerbation rate, lower level of symptoms control, and poorer response to steroids compared to eosinophilic phenotype. Comorbidities such as obesity and GERD as well as the influence of environmental factors (air pollution, smoking, bacterial infections) contribute to the development and severe course of the disease. NA is T2-low disease with predominantly Th1\/Th17-type inflammation. Neutrophils are key cells responsible for initiating and sustaining inflammation. In addition to their primary functions like phagocytosis, degranulation, and NETosis, neutrophils release several pro-inflammatory cytokines (IL-1\u03b1, IL-1\u03b2, IL-6, TNF) and chemokines (CXCL-1, -2, -8, -9, -10) responsible for the recruitment of other neutrophils or T cells. Increasing knowledge about the biology of neutrophiles and their role in asthma results in new potential therapies that could improve control of NA, particularly new biologicals targeting Th1\/Th17-related cytokines. In this review, we discuss the prevalence, mechanisms, and clinical features of neutrophilic asthma. Furthermore, current therapeutic options and some promising perspectives for the near future are presented.<\/jats:p>","DOI":"10.3390\/jcm14207137","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:47:08Z","timestamp":1760104028000},"page":"7137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Neutrophilic Asthma\u2014From Mechanisms to New Perspectives of Therapy"],"prefix":"10.3390","volume":"14","author":[{"given":"Ilona","family":"Iwaszko","sequence":"first","affiliation":[{"name":"Department of Allergology, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1821-1266","authenticated-orcid":false,"given":"Krzysztof","family":"Specjalski","sequence":"additional","affiliation":[{"name":"Department of Allergology, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Che\u0142mi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Allergology, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Niedoszytko","sequence":"additional","affiliation":[{"name":"Department of Allergology, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","unstructured":"Global Initiative for Asthma (2025). Global Strategy for Asthma Management and Prevention. GINA 2025 Report, Global Initiative for Asthma. Available online: https:\/\/ginasthma.org\/2025-gina-strategy-report\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.18176\/jiaci.0871","article-title":"Prevalence, T2 Biomarkers, and Cost of Severe Asthma in the Era of Biologics: The BRAVO-1 Study","volume":"34","author":"Domingo","year":"2024","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1248\/bpb.b19-00095","article-title":"Steroid-Resistant Asthma and Neutrophils","volume":"43","author":"Nabe","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1136\/thorax.57.10.875","article-title":"Analysis of induced sputum in adults with asthma: Identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids","volume":"57","author":"Green","year":"2002","journal-title":"Thorax"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1440-1843.2006.00784.x","article-title":"Inflammatory subtypes in asthma: Assessment and identification using induced sputum","volume":"11","author":"Simpson","year":"2006","journal-title":"Respirology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1016\/j.jaci.2013.10.011","article-title":"Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis","volume":"133","author":"Moore","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","first-page":"16","article-title":"Detailed analysis of sputum and systemic inflammation in asthma phenotypes: Are paucigranulocytic asthmatics really non-inflammatory?","volume":"5","author":"Demarche","year":"2016","journal-title":"BMC Pulm. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.jaip.2018.11.013","article-title":"What Are Those Neutrophils Doing in Severe Asthma Anyway?","volume":"7","author":"Busse","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jaip.2018.08.024","article-title":"Children with Neutrophil-Predominant Severe Asthma Have Proinflammatory Neutrophils with Enhanced Survival and Impaired Clearance","volume":"7","author":"Grunwell","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_10","first-page":"036","article-title":"Clinical Features and Management of Neutrophilic Asthma","volume":"6","author":"Syabbalo","year":"2020","journal-title":"J. Pulm. Med. Respir. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1900068","DOI":"10.1183\/13993003.00068-2019","article-title":"Elevated serum IgE, oral corticosteroid dependence and IL-17\/22 expression in highly neutrophilic asthma","volume":"54","author":"Bullone","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1164\/ajrccm.161.2.9903097","article-title":"Induced sputum cell counts in healthy adults","volume":"161","author":"Belda","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/resp.12079","article-title":"Relationship between airway neutrophilia and ageing in asthmatics and non-asthmatics","volume":"18","author":"Brooks","year":"2013","journal-title":"Respirology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1471-2466-13-11","article-title":"Distribution of sputum cellular phenotype in a large asthma cohort: Predicting factors for eosinophilic vs neutrophilic inflammation","volume":"13","author":"Schleich","year":"2013","journal-title":"BMC Pulm. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1378\/chest.119.5.1329","article-title":"Heterogeneity of airway inflammation in persistent asthma: Evidence of neutrophilic inflammation and increased sputum interleukin-8","volume":"119","author":"Gibson","year":"2001","journal-title":"Chest"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1186\/s12890-021-01722-0","article-title":"Distribution of inflammatory phenotypes among patients with asthma in Jilin Province, China: A cross-sectional study","volume":"21","author":"Shi","year":"2021","journal-title":"BMC Pulm. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1183\/09031936.00170110","article-title":"Different inflammatory phenotypes in adults and children with acute asthma","volume":"38","author":"Wang","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/MCP.0000000000000120","article-title":"Therapeutic implications of \u2018neutrophilic asthma\u2019","volume":"21","author":"Nair","year":"2015","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1111\/all.13184","article-title":"Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes","volume":"72","author":"Ntontsi","year":"2017","journal-title":"Allergy"},{"key":"ref_20","first-page":"267","article-title":"Inflammatory phenotypes of severe asthma in India","volume":"36","author":"Dasgupta","year":"2019","journal-title":"Lung India"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1164\/rccm.201109-1640OC","article-title":"A large subgroup of mild-to-moderate asthma is persistently noneosinophilic","volume":"185","author":"McGrath","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41390-018-0268-5","article-title":"Phenotypes of the inflammatory cells in the induced sputum from young children or infants with recurrent wheezing","volume":"85","author":"Guo","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1016\/j.jaip.2018.12.027","article-title":"Lung Lavage Granulocyte Patterns and Clinical Phenotypes in Children with Severe, Therapy-Resistant Asthma","volume":"7","author":"Teague","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1183\/09031936.06.00137704","article-title":"Determining asthma treatment by monitoring sputum cell counts: Effect on exacerbations","volume":"27","author":"Jayaram","year":"2006","journal-title":"Eur. Respir. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1136\/thx.2009.126722","article-title":"Effects of steroid therapy on inflammatory cell subtypes in asthma","volume":"65","author":"Cowan","year":"2010","journal-title":"Thorax"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100739","DOI":"10.1016\/j.blre.2020.100739","article-title":"CIN or not: An approach to the evaluation and management of chronic idiopathic neutrophilia","volume":"46","author":"Otieno","year":"2021","journal-title":"Blood Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1136\/thx.2003.012468","article-title":"Acute effects of cigarette smoke on inflammation and oxidative stress: A review","volume":"59","author":"Postma","year":"2004","journal-title":"Thorax"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1901846","DOI":"10.1183\/13993003.01846-2019","article-title":"Neutrophilic asthma: Welcome back!","volume":"54","author":"Gibson","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1164\/ajrccm\/148.3.713","article-title":"Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa?","volume":"148","author":"Sur","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12931-021-01619-w","article-title":"Asthma in elderly is characterized by increased sputum neutrophils, lower airway caliber variability and air trapping","volume":"22","author":"Schleich","year":"2021","journal-title":"Respir. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.2147\/JAA.S327659","article-title":"Severe Asthma in a General Population Study: Prevalence and Clinical Characteristics","volume":"14","author":"Axelsson","year":"2021","journal-title":"J. Asthma Allergy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107881","DOI":"10.1016\/j.rmed.2024.107881","article-title":"Factors associated with uncontrolled severe asthma in the biologic era","volume":"236","author":"Yasui","year":"2025","journal-title":"Respir. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.jaci.2016.10.034","article-title":"Identification of IL-17F\/frequent exacerbator endotype in asthma","volume":"140","author":"Ricciardolo","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1164\/ajrccm.160.5.9806170","article-title":"Neutrophilic inflammation in severe persistent asthma","volume":"160","author":"Jatakanon","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1373\/clinchem.2016.267450","article-title":"Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen General Population Study","volume":"63","author":"Lange","year":"2017","journal-title":"Clin. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1111\/cea.12762","article-title":"Exacerbation risk in severe asthma is stratified by inflammatory phenotype using longitudinal measures of sputum eosinophils","volume":"46","author":"Walsh","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.it.2017.07.003","article-title":"Neutrophilic Inflammation in Asthma and Association with Disease Severity","volume":"38","author":"Ray","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/j.1440-1843.2011.02097.x","article-title":"Role of neutrophils in persistent airway obstruction due to refractory asthma","volume":"17","author":"Choi","year":"2012","journal-title":"Respirology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1378\/chest.07-1047","article-title":"Association between neutrophilic airway inflammation and airflow limitation in adults with asthma","volume":"132","author":"Shaw","year":"2007","journal-title":"Chest"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/0091-6749(94)90333-6","article-title":"The effects of glucocorticoids on human eosinophils","volume":"94","author":"Schleimer","year":"1994","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tao, Z., Zhu, H., Zhang, J., Huang, Z., Xiang, Z., and Hong, T. (2022). Recent advances of eosinophils and its correlated diseases. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.954721"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4719","DOI":"10.4049\/jimmunol.154.9.4719","article-title":"Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes","volume":"154","author":"Cox","year":"1995","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.rmed.2004.06.007","article-title":"Increase in airway neutrophils after oral but not inhaled corticosteroid therapy in mild asthma","volume":"99","author":"Nguyen","year":"2005","journal-title":"Respir. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.4049\/jimmunol.2200288","article-title":"Mechanisms of Corticosteroid Resistance in Type 17 Asthma","volume":"209","author":"Hong","year":"2022","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/j.cell.2020.12.008","article-title":"Serum Amyloid A Proteins Induce Pathogenic Th17 Cells and Promote Inflammatory Disease","volume":"183","author":"Lee","year":"2020","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1378\/chest.11-1838","article-title":"The neutrophilic inflammatory phenotype is associated with systemic inflammation in asthma","volume":"142","author":"Wood","year":"2012","journal-title":"Chest"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1016\/j.jaip.2022.04.034","article-title":"Cigarette Smoking and Asthma","volume":"10","author":"Thomson","year":"2022","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_48","unstructured":"World Health Organization (2025). Obesity and Overweight. Fact Sheet, World Health Organization. Available online: http:\/\/www.who.int\/mediacentre\/factsheets\/fs311\/en\/."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1053\/rmed.2002.1317","article-title":"High prevalence of obesity in asthmatic patients on sick leave","volume":"96","author":"Nathell","year":"2002","journal-title":"Respir. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Uribe-Querol, E., and Rosales, C. (2022). Neutrophils Actively Contribute to Obesity-Associated Inflammation and Pathological Complications. Cells, 11.","DOI":"10.3390\/cells11121883"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1096\/fsb2fasebj.12.1.57","article-title":"Leptin regulates proinflammatory immune responses","volume":"12","author":"Loffreda","year":"1998","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1465-9921-8-32","article-title":"Body mass index is associated with reduced exhaled nitric oxide and higher exhaled 8-isoprostanes in asthmatics","volume":"8","author":"Komakula","year":"2007","journal-title":"Respir. Res."},{"key":"ref_53","first-page":"469","article-title":"Effects of obesity on asthma: Immunometabolic links","volume":"128","author":"Miethe","year":"2018","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"C375","DOI":"10.1152\/ajpcell.00379.2020","article-title":"Adipose tissue inflammation and metabolic dysfunction in obesity","volume":"320","author":"Kawai","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1096\/fasebj.13.10.1231","article-title":"Leptin induces oxidative stress in human endothelial cells","volume":"13","author":"Bouloumie","year":"1999","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1189\/jlb.69.3.414","article-title":"Leptin: A potential regulator of polymorphonuclear neutrophil bactericidal action?","volume":"69","author":"Poulin","year":"2001","journal-title":"J. Leukoc. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.metabol.2008.05.005","article-title":"White blood cell count and abdominal fat distribution in female obese adolescents","volume":"57","author":"Kim","year":"2008","journal-title":"Metabolism"},{"key":"ref_58","first-page":"1019","article-title":"Blood Neutrophil Count is Associated with Body Mass Index in Adolescents with Asthma","volume":"3","author":"Rhee","year":"2018","journal-title":"JSM Allergy Asthma"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1183\/09031936.00139810","article-title":"Airway inflammation is augmented by obesity and fatty acids in asthma","volume":"38","author":"Scott","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"107418","DOI":"10.1016\/j.rmed.2023.107418","article-title":"Severity of adult-onset asthma\u2014A matter of blood neutrophils and severe obesity","volume":"219","author":"Stridsman","year":"2023","journal-title":"Respir. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"107529","DOI":"10.1016\/j.rmed.2024.107529","article-title":"The interplay between obesity and blood neutrophils in adult-onset asthma","volume":"222","author":"Backman","year":"2024","journal-title":"Respir. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1111\/all.13370","article-title":"Comorbid \u201ctreatable traits\u201d in difficult asthma: Current evidence and clinical evaluation","volume":"73","author":"Tay","year":"2018","journal-title":"Allergy"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1378\/chest.116.5.1257","article-title":"Gastroesophageal reflux in asthmatics: A double-blind, placebo-controlled crossover study with omeprazole","volume":"116","author":"Kiljander","year":"1999","journal-title":"Chest"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/j.1440-1746.2009.06035.x","article-title":"Prevalence of gastroesophageal reflux disease in patients with asthma and chronic obstructive pulmonary disease","volume":"25","author":"Bor","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_65","first-page":"1227","article-title":"Prevalence of gastroesophageal reflux in difficult asthma: Relationship to asthma outcome","volume":"127","author":"Leggett","year":"2005","journal-title":"Chest"},{"key":"ref_66","first-page":"66","article-title":"Neutrophilic asthma is characterised by increased rhinosinusitis with sleep disturbance and GERD","volume":"32","author":"Simpson","year":"2014","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/ACI.0000000000000705","article-title":"Gastroesophageal reflux and asthma: When, how, and why","volume":"21","author":"Paoletti","year":"2021","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1080\/02770903.2019.1641204","article-title":"Effect of anti-reflux treatment on gastroesophageal reflux-associated chronic cough: Implications of neurogenic and neutrophilic inflammation","volume":"57","author":"Takeda","year":"2020","journal-title":"J. Asthma"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2300826","DOI":"10.1183\/13993003.00826-2023","article-title":"Advances in non-type 2 severe asthma: From molecular insights to novel treatment strategies","volume":"64","author":"Liu","year":"2024","journal-title":"Eur. Respir. J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2500\/aap.2016.37.3944","article-title":"Influence of cigarette smoking on airway inflammation and inhaled corticosteroid treatment in patients with asthma","volume":"37","author":"Shimoda","year":"2016","journal-title":"Allergy Asthma Proc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1111\/cea.12907","article-title":"Cigarette smoking increases bronchial mucosal IL-17A expression in asthmatics, which acts in concert with environmental aeroallergens to engender neutrophilic inflammation","volume":"47","author":"Siew","year":"2017","journal-title":"Clin. Exp. Allergy"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12931-018-0799-7","article-title":"Modelling the asthma phenotype: Impact of cigarette smoke exposure","volume":"19","author":"Belvisi","year":"2018","journal-title":"Respir. Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Turan, N., van der Veen, T.A., Draijer, C., Fattahi, F., Ten Hacken, N.H., Timens, W., van Oosterhout, A.J., van den Berge, M., and Melgert, B.N. (2021). Neutrophilic Asthma Is Associated With Smoking, High Numbers of IRF5+, and Low Numbers of IL10+ Macrophages. Front. Allergy, 2.","DOI":"10.3389\/falgy.2021.676930"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1016\/j.jaip.2021.01.004","article-title":"Heterogeneity of Paucigranulocytic Asthma: A Prospective Cohort Study with Hierarchical Cluster Analysis","volume":"9","author":"Deng","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","unstructured":"Papaioannou, A.I., Fouka, E., Ntontsi, P., Stratakos, G., and Papiris, S. (2022). Paucigranulocytic Asthma: Potential Pathogenetic Mechanisms, Clinical Features and Therapeutic Management. J. Pers. Med., 12.","DOI":"10.3390\/jpm12050850"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jaci.2022.12.004","article-title":"Neutrophils in host defense, healing, and hypersensitivity: Dynamic cells within a dynamic host","volume":"151","author":"Siwicki","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nri1785","article-title":"Neutrophils and immunity: Challenges and opportunities","volume":"6","author":"Nathan","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.immunol.23.021704.115653","article-title":"How neutrophils kill microbes","volume":"23","author":"Segal","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1111\/febs.15589","article-title":"NET formation\u2014Mechanisms and how they relate to other cell death pathways","volume":"288","author":"Rosazza","year":"2021","journal-title":"FEBS J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nature12175","article-title":"Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo","volume":"498","author":"Afonso","year":"2013","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.cell.2019.02.028","article-title":"Resident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage","volume":"177","author":"Uderhardt","year":"2019","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1182\/blood-2012-04-421040","article-title":"VEGF-A recruits a proangiogenic MMP-9-delivering neutrophil subset that induces angiogenesis in transplanted hypoxic tissue","volume":"120","author":"Christoffersson","year":"2012","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.cell.2020.10.003","article-title":"Co-option of neutrophil fates by tissue environments","volume":"183","author":"Ballesteros","year":"2020","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"14816","DOI":"10.1523\/JNEUROSCI.5511-12.2013","article-title":"Neutrophils express oncomodulin and promote optic nerve regeneration","volume":"33","author":"Kurimoto","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3109\/01902149109063278","article-title":"Interleukin-8 (IL-8): The major neutrophil chemotactic factor in the lung","volume":"17","author":"Kunkel","year":"1991","journal-title":"Exp. Lung Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.pharmthera.2008.10.005","article-title":"CXCR2 antagonists for the treatment of pulmonary disease","volume":"121","author":"Chapman","year":"2009","journal-title":"Pharmacol. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s10238-021-00750-8","article-title":"Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma","volume":"22","author":"Varricchi","year":"2022","journal-title":"Clin. Exp. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s12931-018-0883-z","article-title":"Proteinase 3; a potential target in chronic obstructive pulmonary disease and other chronic inflammatory diseases","volume":"19","author":"Crisford","year":"2018","journal-title":"Respir. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s12931-024-02923-x","article-title":"The role of extracellular traps released by neutrophils, eosinophils, and macrophages in asthma","volume":"25","author":"Gu","year":"2024","journal-title":"Respir. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1083\/jcb.201006052","article-title":"Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps","volume":"191","author":"Papayannopoulos","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Lewis, B.W., Ford, M.L., Rogers, L.K., and Britt, R.D. (2021). Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD. Antioxidants, 10.","DOI":"10.3390\/antiox10091335"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1182\/blood-2010-06-290171","article-title":"Myeloperoxidase is required for neutrophil extracellular trap formation: Implications for innate immunity","volume":"117","author":"Metzler","year":"2011","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1164\/ajrccm\/137.1.57","article-title":"Association between nonspecific bronchial hyperreactivity and superoxide anion production by polymorphonuclear leukocytes in chronic air-flow obstruction","volume":"137","author":"Postma","year":"1988","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1165\/ajrcmb.21.2.f158","article-title":"Nitric oxide in asthma. Pathogenic, therapeutic, or diagnostic?","volume":"21","author":"Sanders","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1096\/fj.00-0085com","article-title":"Extracellular glutathione peroxidase induction in asthmatic lungs: Evidence for redox regulation of expression in human airway epithelial cells","volume":"15","author":"Comhair","year":"2001","journal-title":"FASEB J."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Makena, P., Kikalova, T., Prasad, G.L., and Baxter, S.A. (2023). Oxidative Stress and Lung Fibrosis: Towards an Adverse Outcome Pathway. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512490"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3934\/genet.2017.2.103","article-title":"DNA damage by lipid peroxidation products: Implications in cancer, inflammation and autoimmunity","volume":"4","author":"Gentile","year":"2017","journal-title":"AIMS Genet."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"19683","DOI":"10.1074\/jbc.REV119.006217","article-title":"Detection, identification, and quantification of oxidative protein modifications","volume":"294","author":"Hawkins","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Juan, C.A., P\u00e9rez de la Lastra, J.M., Plou, F.J., and P\u00e9rez-Lebe\u00f1a, E. (2021). The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094642"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1074\/jbc.M309778200","article-title":"Integrins and cytokines activate nuclear transcription factor-kappaB in human neutrophils","volume":"279","author":"Kettritz","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"7851","DOI":"10.1007\/s11033-023-08688-8","article-title":"Exploring redox imbalance and inflammation for asthma therapy","volume":"50","author":"Barnabas","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/resp.12730","article-title":"Neutrophil extracellular traps are associated with inflammation in chronic airway disease","volume":"21","author":"Wright","year":"2016","journal-title":"Respirology"},{"key":"ref_105","first-page":"69","article-title":"Extracellular RNAs from lung cancer cells activate epithelial cells and induce neutrophil extracellular traps","volume":"55","author":"Li","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/cea.12859","article-title":"Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma","volume":"47","author":"Pham","year":"2017","journal-title":"Clin. Exp. Allergy"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11010-015-2396-0","article-title":"HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1\/2","volume":"405","author":"Liang","year":"2015","journal-title":"Mol. Cell Biochem."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Hosoki, K., Ying, S., Corrigan, C., Qi, H., Kurosky, A., Jennings, K., Sun, Q., Boldogh, I., and Sur, S. (2015). Analysis of a Panel of 48 Cytokines in BAL Fluids Specifically Identifies IL-8 Levels as the Only Cytokine that Distinguishes Controlled Asthma from Uncontrolled Asthma, and Correlates Inversely with FEV1. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126035"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.12659\/MSM.896458","article-title":"Plasma Inflammatory Cytokine IL-4, IL-8, IL-10, and TNF-\u03b1 Levels Correlate with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap Syndrome","volume":"22","author":"Huang","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2147\/JAA.S275039","article-title":"Targeting TSLP in Asthma","volume":"15","author":"Parnes","year":"2022","journal-title":"J. Asthma Allergy"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"8183","DOI":"10.4049\/jimmunol.174.12.8183","article-title":"Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity","volume":"174","author":"Ying","year":"2005","journal-title":"J. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.4049\/jimmunol.181.4.2790","article-title":"Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease","volume":"181","author":"Ying","year":"2008","journal-title":"J. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1084\/jem.20062211","article-title":"Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells","volume":"204","author":"Allakhverdi","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1084\/jem.20051135","article-title":"TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand","volume":"202","author":"Ito","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1084\/jem.20030240","article-title":"Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells","volume":"197","author":"Gilliet","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1365-2222.2008.03151.x","article-title":"Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2-polarizing conditions","volume":"39","author":"Tanaka","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1183\/09031936.00144307","article-title":"Enhancement of neutrophil function by the bronchial epithelium stimulated by epidermal growth factor","volume":"31","author":"Uddin","year":"2008","journal-title":"Eur. Respir. J."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Yamasaki, A., Okazaki, R., and Harada, T. (2022). Neutrophils and Asthma. Diagnostics, 12.","DOI":"10.3390\/diagnostics12051175"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.jaci.2009.02.024","article-title":"T(H)17-associated cytokines (IL-17A and IL-17F) in severe asthma","volume":"123","author":"Chouiali","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/1465-9921-7-135","article-title":"IL-17 mRNA in sputum of asthmatic patients: Linking T cell driven inflammation and granulocytic influx?","volume":"7","author":"Bullens","year":"2006","journal-title":"Respir. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1111\/j.1365-2222.2010.03544.x","article-title":"Induction of glucocorticoid receptor-beta expression in epithelial cells of asthmatic airways by T-helper type 17 cytokines","volume":"40","author":"Semlali","year":"2010","journal-title":"Clin. Exp. Allergy"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12950-022-00323-w","article-title":"Combination of IL-17A\/F and TNF-\u03b1 uniquely alters the bronchial epithelial cell proteome to enhance proteins that augment neutrophil migration","volume":"19","author":"Altieri","year":"2022","journal-title":"J. Inflamm."},{"key":"ref_123","first-page":"391","article-title":"Interleukin-8: An expanding universe beyond neutrophil chemotaxis and activation","volume":"72","author":"Mukaida","year":"2000","journal-title":"Int. J. Hematol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00408-017-0058-6","article-title":"IL-8 Gene Variants and Expression in Childhood Asthma","volume":"195","author":"Charrad","year":"2017","journal-title":"Lung"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.rmed.2019.06.024","article-title":"Serum levels of IL-5, IL-6, IL-8, IL-13 and IL-17A in pre-defined groups of adult patients with moderate and severe bronchial asthma","volume":"154","author":"Dimitrova","year":"2019","journal-title":"Respir. Med."},{"key":"ref_126","first-page":"260","article-title":"Elevated Serum Interleukin-8 Level as a Preferable Biomarker for Identifying Uncontrolled Asthma and Glucocorticosteroid Responsiveness","volume":"16","author":"Zhang","year":"2017","journal-title":"Tanaffos"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1159\/000237218","article-title":"Interleukin-8 in airway inflammation in patients with asthma and chronic obstructive pulmonary disease","volume":"109","author":"Nocker","year":"1996","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1164\/ajrccm.161.3.9809071","article-title":"Interleukin-8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma","volume":"161","author":"Norzila","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.cytogfr.2011.10.001","article-title":"Understanding the mechanism of IL-1\u03b2 secretion","volume":"22","author":"Brough","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/356768a0","article-title":"A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes","volume":"356","author":"Thornberry","year":"1992","journal-title":"Nature"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1164\/rccm.201609-1830OC","article-title":"Role for NLRP3 Inflammasome-mediated, IL-1\u03b2-Dependent Responses in Severe, Steroid-Resistant Asthma","volume":"196","author":"Kim","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jaci.2010.10.024","article-title":"Transcriptional phenotypes of asthma defined by gene expression profiling of induced sputum samples","volume":"127","author":"Baines","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"107847","DOI":"10.1016\/j.pharmthera.2021.107847","article-title":"The central role of IL-33\/IL-1RL1 pathway in asthma: From pathogenesis to intervention","volume":"225","author":"Hesse","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"220144","DOI":"10.1183\/16000617.0144-2022","article-title":"Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD","volume":"32","author":"Calderon","year":"2023","journal-title":"Eur. Respir. Rev."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Griesenauer, B., and Paczesny, S. (2017). The ST2\/IL-33 Axis in Immune Cells during Inflammatory Diseases. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00475"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"22","DOI":"10.4168\/aair.2024.16.1.22","article-title":"ST2-Mediated Neutrophilic Airway Inflammation: A Therapeutic Target for Patients with Uncontrolled Asthma","volume":"16","author":"Quoc","year":"2024","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1073\/pnas.1115884109","article-title":"IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G","volume":"109","author":"Roga","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Van Nevel, S., van Ovost, J., Holtappels, G., DeRuyck, N., Zhang, N., Braun, H., Maes, T., Bachert, C., and Krysko, O. (2021). Neutrophils affect IL-33 processing in response to the respiratory allergen Alternaria. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.677848"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.mucimm.2023.07.002","article-title":"IL-33-induced neutrophilic inflammation and NETosis underlie rhinovirus-triggered exacerbations of asthma","volume":"16","author":"Curren","year":"2023","journal-title":"Mucosal Immunol."},{"key":"ref_140","first-page":"049","article-title":"Role of IL-17 and IL-23 in the Pathogenesis of Neutrophilic Asthma","volume":"7","author":"Syabbalo","year":"2020","journal-title":"Int. J. Immunol. Immunother."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Xiong, D.J.P., Martin, J.G., and Lauzon, A.M. (2022). Airway smooth muscle function in asthma. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.993406"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.jaci.2003.08.013","article-title":"Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucocorticoids","volume":"112","author":"Cundall","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000195961","article-title":"Role of enzymes from inflammatory cells on airway submucosal gland secretion","volume":"58","author":"Nadel","year":"1991","journal-title":"Respiration"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1164\/ajrccm.157.2.9703070","article-title":"Increased levels of elastase and alpha1-antitrypsin in sputum of asthmatic patients","volume":"157","author":"Vignola","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.jaci.2010.12.1117","article-title":"TH17 cytokines induce human airway smooth muscle cell migration","volume":"127","author":"Chang","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nri3707","article-title":"The IL-23-IL-17 immune axis: From mechanisms to therapeutic testing","volume":"14","author":"Gaffen","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1165\/rcmb.2010-0027TR","article-title":"Role of transforming growth factor-\u03b2 in airway remodeling in asthma","volume":"44","author":"Halwani","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1067\/mai.2000.110556","article-title":"Peripheral blood and airway tissue expression of transforming growth factor beta by neutrophils in asthmatic subjects and normal control subjects","volume":"106","author":"Chu","year":"2000","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"485","DOI":"10.37349\/eaa.2024.00060","article-title":"Tezepelumab: A promising therapy for severe uncontrolled asthma","volume":"2","author":"Klironomou","year":"2024","journal-title":"Explor. Asthma Allergy"},{"key":"ref_150","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-IL-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_151","unstructured":"Amgen (2022, September 21). A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Brodalumab in Subjects with Inadequately Controlled Asthma and High Bronchodilator Reversibility, Available online: https:\/\/clinicaltrials.gov\/study\/NCT01902290."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1159\/000235117","article-title":"Interleukin-1 release by alveolar macrophages in asthmatic patients and healthy subjects","volume":"91","author":"Pujol","year":"1990","journal-title":"Int. Arch. Allergy Appl. Immunol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.jaci.2014.07.039","article-title":"IL-1 receptor antagonist reduces endotoxin-induced airway inflammation in healthy volunteers","volume":"135","author":"Hernandez","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_154","first-page":"521","article-title":"The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation","volume":"138","author":"Ulich","year":"1991","journal-title":"Am. J. Pathol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1183\/09031936.02.00253602","article-title":"Chemokines, innate and adaptive immunity, and respiratory disease","volume":"19","author":"Sabroe","year":"2002","journal-title":"Eur. Respir. J."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/1465-9921-14-137","article-title":"Inhibition of LPS-induced airway neutrophilic inflammation in healthy volunteers with an oral CXCR2 antagonist","volume":"14","author":"Leaker","year":"2013","journal-title":"Respir. Res."},{"key":"ref_157","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_158","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_159","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13223-015-0081-1","article-title":"Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma","volume":"11","author":"Chu","year":"2015","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e1044","DOI":"10.1002\/cti2.1044","article-title":"Effects of interleukin-6 receptor blockade on allergen-induced airway responses in mild asthmatics","volume":"8","author":"Revez","year":"2019","journal-title":"Clin. Transl. Immunol."},{"key":"ref_161","unstructured":"University of North Carolina (2025, June 19). PrecISE (Precision Interventions for Severe and\/or Exacerbation-Prone Asthma) Network Study, Available online: https:\/\/www.clinicaltrials.gov\/study\/NCT04129931."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.jaci.2021.03.044","article-title":"Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial","volume":"148","author":"Kelsen","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1056\/NEJMoa2024257","article-title":"Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma","volume":"385","author":"Wechsler","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"00718","DOI":"10.1183\/23120541.00718-2023","article-title":"AERIFY-1\/2: Two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD","volume":"10","author":"Rabe","year":"2024","journal-title":"ERJ Open Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e13874","DOI":"10.1111\/cts.13874","article-title":"Pharmacokinetics and pharmacodynamics of itepekimab in adults with moderate-to-severe atopic dermatitis: Results from two terminated phase II trials","volume":"17","author":"Kosloski","year":"2024","journal-title":"Clin. Transl. Sci."},{"key":"ref_166","first-page":"A65","article-title":"Frontier-3: A randomized, phase 2a study to evaluate the efficacy and safety of torozakimab (an interleukin-33 monoclonal antibody) in early-onset asthma","volume":"79","author":"Corren","year":"2024","journal-title":"Thorax"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/cea.14229","article-title":"Exploring proteomic plasma biomarkers in eosinophilic and neutrophilic asthma","volume":"53","author":"Kere","year":"2023","journal-title":"Clin. Exp. Allergy"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/s12276-021-00652-5","article-title":"S100A9 in adult asthmatic patients: A biomarker for neutrophilic asthma","volume":"53","author":"Quoc","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4168\/aair.2022.14.1.40","article-title":"Serum amyloid a1: A biomarker for neutrophilic airway inflammation in adult asthmatic patients","volume":"14","author":"Bich","year":"2022","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1080\/02770903.2022.2051544","article-title":"Identification of hub genes and potential biomarkers of neutrophilic asthma: Evidence from a bioinformatics analysis","volume":"60","author":"Lin","year":"2022","journal-title":"J. Asthma"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1115938","DOI":"10.3389\/fmed.2023.1115938","article-title":"YKL-40 as a possible marker of neutrophilic asthma","volume":"10","author":"Specjalski","year":"2023","journal-title":"Front. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/20\/7137\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:24:14Z","timestamp":1760243054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/20\/7137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":171,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["jcm14207137"],"URL":"https:\/\/doi.org\/10.3390\/jcm14207137","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]}}}