The role of eosinophils in the management of acute paediatric wheeze: a scoping review

Abstract

Acute wheeze is one of the most common paediatric presentations to emergency care. Although blood eosinophils (BEO) are an established biomarker of type 2 inflammation in stable asthma, their role in guiding acute management-particularly systemic corticosteroid use-remains unclear. The aim of this review was to map and synthesise the existing evidence on the measurement and clinical utility of BEO sampled during acute wheeze exacerbations in children. A scoping review was conducted in accordance with Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) guidelines. Medline, Embase, Cochrane Library and Web of Science were searched for studies published in the last 20 years involving children under 16 years presenting acutely with wheeze and undergoing eosinophil testing. Prospective and retrospective studies were included. Data were summarised descriptively according to eosinophil measurement methods, reported values, cut-offs and associations with characteristics and treatment response. Eight heterogeneous studies (n = 855) met inclusion criteria, comprising five observational or retrospective studies and three randomised controlled trials. BEO reporting varied widely, with inconsistent units, cut-offs and poorly described sampling timing. No study utilised point-of-care testing. Across studies, eosinophil dynamics differed by age, wheeze phenotype, disease severity and viral aetiology, preventing meaningful comparison. Evidence supporting eosinophil-guided corticosteroid use was limited. Two studies demonstrated improved outcomes with systemic corticosteroids in children with rhinovirus-associated wheeze and higher BEO, while lower BEO were observed in respiratory syncytial virus (RSV)-associated wheeze. There is a paucity of high-quality data describing BEO during acute wheeze exacerbations in children. Current evidence underpinning eosinophil-guided care is largely derived from stable outpatient cohorts and may not be directly applicable to acute settings. Prospective studies with standardised sampling of BEO during acute presentations are needed to inform precision-based corticosteroid use.

Keywords

eosinophils / oral corticosteroids / wheeze / asthma / preschool wheeze / precision medicine

References

[1] Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention (2025 update) [Internet]. [cited 2026 May 01]. Available from: https://ginasthma.org/wp-content/uploads/2025/11/GINA-2025-Update-25_11_08-WMS.pdf

[2] Bloom CI, Franklin C, Bush A, Saglani S, Quint JK. Burden of preschool wheeze and progression to asthma in the UK: Population-based cohort 2007 to 2017. J Allergy Clin Immunol. 2021; 147: 1949-58.

[3] Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995; 332: 133-8.

[4] Kallis C, Maslova E, Morgan AD, Sinha I, Roberts G, van der Valk RJP, et al. Recent trends in asthma diagnosis, preschool wheeze diagnosis and asthma exacerbations in English children and adolescents: a SABINA Jr study. Thorax. 2023; 78: 1175-80.

[5] Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002; 360: 1715-21.

[6] Ramakrishnan S, Russell REK, Mahmood HR, Krassowska K, Melhorn J, Mwasuku C, et al. Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): a double-blind, double-dummy, active placebo-controlled randomised trial. Lancet Respir Med. 2025; 13: 59-68.

[7] Makrinioti H, Fainardi V, Bonnelykke K, Custovic A, Cicutto L, Coleman C, et al. European Respiratory Society statement on preschool wheezing disorders: updated definitions, knowledge gaps and proposed future research directions. Eur Respir J. 2024; 64: 2400624.

[8] Perikleous A, Bowen S, Griffiths C, Pavord I, Rosenthal M, Fleming L, et al. Preschool wheeze endotypes and their association with asthma attacks and inhaled corticosteroid response. ERJ Open Res. 2026; 12: 01183-2025.

[9] Hillson K, Fontanella S, Almeida H, Pavlou B, Lajunen K, Irving S, et al. Point-of-Care Blood Eosinophils to Predict Preschool Wheeze Attacks. Allergy. 2025; 80: 1038-46.

[10] Lee B, Turner S, Borland M, Csonka P, Grigg J, Guilbert TW, et al. Efficacy of oral corticosteroids for acute preschool wheeze: a systematic review and individual participant data meta-analysis of randomised clinical trials. Lancet Respir Med. 2024; 12: 444-56.

[11] Bush A. Basic clinical management of preschool wheeze. Pediatr Allergy Immunol. 2023; 34: e13988.

[12] Panickar J, Lakhanpaul M, Lambert PC, Kenia P, Stephenson T, Smyth A, et al. Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med. 2009; 360: 329-38.

[13] Wallace A, Sinclair O, Shepherd M, Neutze J, Trenholme A, Tan E, et al. Impact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trial. Arch Dis Child. 2021; 106: 339-44.

[14] Foster SJ, Cooper MN, Oosterhof S, Borland ML. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018; 6: 97-106.

[15] Jartti T, Nieminen R, Vuorinen T, Lehtinen P, Vahlberg T, Gern J, et al. Short- and long-term efficacy of prednisolone for first acute rhinovirus-induced wheezing episode. J Allergy Clin Immunol. 2015; 135: 691-8.e9.

[16] Jartti T, Lehtinen P, Vanto T, Hartiala J, Vuorinen T, Mäkelä MJ, et al. Evaluation of the efficacy of prednisolone in early wheezing induced by rhinovirus or respiratory syncytial virus. Pediatr Infect Dis J. 2006; 25: 482-8.

[17] Aljebab F, Choonara I, Conroy S. Systematic review of the toxicity of short-course oral corticosteroids in children. Arch Dis Child. 2016; 101: 365-70.

[18] Heatley H, Tran TN, Bourdin A, Menzies-Gow A, Jackson DJ, Maslova E, et al. Observational UK cohort study to describe intermittent oral corticosteroid prescribing patterns and their association with adverse outcomes in asthma. Thorax. 2023; 78: 860-7.

[19] Yao T, Wang J, Chang S, Chang Y, Tsai Y, Wu AC, et al. Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children. JAMA Pediatr. 2021; 175: 723-9.

[20] Fitzpatrick AM, Jackson DJ, Mauger DT, Boehmer SJ, Phipatanakul W, Sheehan WJ, et al. Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol. 2016; 138: 1608-18.e12.

[21] Fitzpatrick AM, Grunwell JR, Cottrill KA, Mutic AD, Mauger DT. Blood Eosinophils for Prediction of Exacerbation in Preschool Children With Recurrent Wheezing. J Allergy Clin Immunol Pract. 2023; 11: 1485-93.e8.

[22] Just J, Saf S, Guiddir T, Cottel N, Amat F, Lambert N, et al. Determinants of blood eosinophilia in moderate and severe asthmatic patients during childhood: Evidence from the severe asthma molecular phenotype (SAMP) cohort. Pediatr Allergy Immunol. 2021; 32: 1217-25.

[23] Hartl S, Breyer M, Burghuber OC, Ofenheimer A, Schrott A, Urban MH, et al. Blood eosinophil count in the general population: typical values and potential confounders. Eur Respir J. 2020; 55: 1901874.

[24] Peters MDJ, Godfrey CM, Khalil H, McInerney P, Parker D, Soares CB. Guidance for conducting systematic scoping reviews. Int J Evid Based Healthc. 2015; 13: 141-6.

[25] Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018; 169: 467-73.

[26] Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016; 5: 210.

[27] Holden KA, Roland D, Welsh KG, Gaillard EA. Comparison of Blood Eosinophil Numbers Between Acute Asthma and Stable Disease in Children with Preschool Wheeze. Pediatr Allergy Immunol Pulmonol. 2017; 30: 210-7.

[28] Kocak AK, Bor O, Yildiz B, Erdogan L, Us T. T-lymphocyte activation and the levels of eosinophilic cationic protein and interleukin-5 in asthmatic children with acute exacerbation and effect of glucocorticoid treatment. Allergy Asthma Proc. 2006; 27: 371-7.

[29] Elkharwili DA, Ibrahim OM, Elazab GA, Elrifaey SM. Two regimens of dexamethasone versus prednisolone for acute exacerbations in asthmatic Egyptian children. Eur J Hosp Pharm. 2020; 27: 151-6.

[30] Li S, Dong J, Li A, Yang Q, Xiong X, Xie X, et al. The role of 14-3-3β in acute asthma in children and analysis of the risk factors for asthma exacerbation. J Asthma. 2024; 61: 1422-31.

[31] Gileles-Hillel A, Guttman S, Breuer O, Reiter J, Leshem R, Shoseyov D, et al. Betamethasone versus dexamethasone for inpatient preschool wheezing-A case-control study. Pediatr Pulmonol. 2021; 56: 875-82.

[32] Kim HS, Yang H, Song DJ, Lee YJ, Suh DI, Shim JY, et al. Eosinophil-derived neurotoxin: An asthma exacerbation biomarker in children. Allergy Asthma Proc. 2022; 43: 133-9.

[33] Perikleous A, Bowen S, Griffiths C, Pavord I, Rosenthal M, Fleming L, et al. Blood Eosinophil Count: Lack of Stability and Association with Wheeze Attacks in Preschool Children. Am J Respir Crit Care Med. 2025; 211: 263-5.

[34] Baumann A, Gönnenwein S, Bischoff SC, Sherman H, Chapnik N, Froy O, et al. The circadian clock is functional in eosinophils and mast cells. Immunology. 2013; 140: 465-74.

[35] Busby J, Khoo E, Pfeffer PE, Mansur AH, Heaney LG. The effects of oral corticosteroids on lung function, type-2 biomarkers and patient-reported outcomes in stable asthma: A systematic review and meta-analysis. Respir Med. 2020; 173: 106156.

[36] Kato M, Yamada Y, Maruyama K, Hayashi Y. Differential effects of corticosteroids on serum eosinophil cationic protein and cytokine production in rhinovirus- and respiratory syncytial virus-induced acute exacerbation of childhood asthma. Int Arch Allergy Immunol. 2011; 155 Suppl 1: 77-84.