• Ivana Filipović Clinical Hospital Center “Dr Dragiša Mišović - Dedinje”, Children’s Hospital for Lung Diseases and Tuberculosis, Belgrade,
  • Vesna Veković Medical Center „Dr Dragiša Mišović“, Children's Hospital for Lung Diseases and Tuberculosis, Belgrade, Serbia
  • Đorđe Filipović Institute for Cardiovascular Diseases “Dedinje”, Belgrade, Serbia
  • Zorica Živković Clinical Hospital Center “Dr Dragiša Mišović - Dedinje”, Children’s Hospital for Lung Diseases and Tuberculosis, Belgrade, University Business Academy in Novi Sad, Faculty of Pharmacy, Novi Sad, Serbia


pediatric asthma, diagnosis, monitoring


In routine clinical practice, the diagnosis of asthma in children is mainly based on clinical criteria. Recently the assessment of physiological and pathological processes through biomarkers can support the diagnosis of asthma, help in monitoring and improving the treatment outcomes and prevention of the morbidity rate. The identification and validation of biomarkers in pediatric asthma has emerged as a top priority among leading experts, researchers, and clinicians. The use of non-invasive biomarkers is highly supported in recent guidelines for the diagnosis of asthma in adult patients, on the other hand, when it comes to the pediatric population, data are still quite limited. The most studied biomarkers include spirometry, markers of allergic sensitization and fractional exhaled nitric oxide (FeNO). Newer markers measured in exhaled air and "omics" approaches provide information on specific asthma phenotypes, however, their clinical applicability is still insufficiently elucidated. This review aims to summarize and discuss the available data on the use of non-invasive biomarkers in the diagnosis and monitoring of children with asthma.


Caminati M, Durić-Filipović I, Arasi S, Peroni DG, Živković Z, Senna G. Respiratory allergies in childhood: Recent advances and future challenges. Pediatr Allergy Immunol. 2015;26(8):702-710. doi:10.1111/pai.12509

Filipović I, Caminati M, Kase Tanno L, Lackovic L, Simonović S, Živković Z .Asthma in Adolescent’s Ages. Prev Ped, 2020; 6(1-2): 61 - 64.

Papadopoulos N.G., Custovic A., Cabana M.D., et al. Pediatric asthma: an unmet need for more effective, focused treatments. Pediatr Allergy Immunol: official publication of the European Society of Pediatric Allergy and Immunology. 2019;30:7–16. doi: 10.1111/pai.12990.

Ferraro V., Carraro S., Bozzetto S., Zanconato S., Baraldi E. Exhaled biomarkers in childhood asthma: old and new approaches. Asthma research and practice. 2018;4:9. doi: 10.1186/s40733-018-0045-6.

Xepapadaki P., Korovessi P., Bachert C., et al. Evolution of airway inflammation in preschoolers with asthma-results of a two-year longitudinal study. J Clin Med. 2020;9

James A., Hedlin G. Biomarkers for the phenotyping and monitoring of asthma in children. Current treatment options in allergy. 2016;3:439–452.

Xepapadaki P, Adachi Y, Pozo… Filipovic I et al. Utility of biomarkers in the diagnosis and monitoring of asthmatic children. World Allergy Organ J. 2022 Dec 15;16(1):100727. doi: 10.3390/jcm9010187.

Pellegrino R., Viegi G., Brusasco V., et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26:948–968.

Levin M., Ansotegui I.J., Bernstein J., et al. Acute asthma management during SARS-CoV2-pandemic 2020. The World Allergy Organization journal. 2020;13.

Dobra R., Equi A. How to use peak expiratory flow rate. Archives of disease in childhood Education and practice edition. 2018;103:158–162

Antalffy T., De Simoni A., Griffiths C.J. Promising peak flow diary compliance with an electronic peak flow meter and linked smartphone app. NPJ primary care respiratory medicine. 2020;30:19.

Graham B.L., Steenbruggen I., Miller M.R., et al. Standardization of spirometry 2019 update. An official American thoracic society and European respiratory society technical statement. Am J Respir Crit Care Med. 2019;200:e70–e88.

Gaillard E.A., Kuehni C.E., Turner S., et al. European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years. Eur Respir J. 2021;58(5):2004173.

Elenius V., Chawes B., Malmberg P.L., et al. Lung function testing and inflammation markers for wheezing preschool children: a systematic review for the EAACI Clinical Practice Recommendations on Diagnostics of Preschool Wheeze. Pediatr Allergy Immunol. 2021;32:501–513.

Komarow H.D., Myles I.A., Uzzaman A., Metcalfe D.D. Impulse oscillometry in the evaluation of diseases of the airways in children. Ann Allergy Asthma Immunol. 2011;106:191–199.

Duiverman E.J., Den Boer J.A., Roorda R.J., Rooyackers C.M., Valstar M., Kerrebijn K.F. Lung function and bronchial responsiveness measured by forced oscillometry after bronchopulmonary dysplasia. Arch Dis Child. 1988;63:727–732.

Gangell C.L., Horak F., Jr., Patterson H.J., Sly P.D., Stick S.M., Hall G.L. Respiratory impedance in children with cystic fibrosis using forced oscillations in clinic. Eur Respir J. 2007;30:892–897.

Kim Y.H., Kim K.W., Baek J., et al. Usefulness of impulse oscillometry and fractional exhaled nitric oxide in children with Eosinophilic bronchitis. Pediatr Pulmonol. 2013;48:221–228.

Guan W.J., Yuan J.J., Gao Y.H., et al. Impulse oscillometry and spirometry small-airway parameters in mild to moderate bronchiectasis. Respir Care. 2016;61:1513–1522.

Komarow H.D., Young M., Nelson C., Metcalfe D.D. Vocal cord dysfunction as demonstrated by impulse oscillometry. J Allergy Clin Immunol Pract. 2013;1:387–393.

Kim H.Y., Shin Y.H., Jung D.W., Jee H.M., Park H.W., Han M.Y. Resistance and reactance in oscillation lung function reflect basal lung function and bronchial hyperresponsiveness respectively. Respirology. 2009;14:1035–1041.

Nieto A., Pamies R., Oliver F., Medina A., Caballero L., Mazon A. Montelukast improves pulmonary function measured by impulse oscillometry in children with asthma (Mio study) Respir Med. 2006;100:1180–1185.

Diong B., Singh K., Menendez R. Effects of two inhaled corticosteroid/long-acting beta-agonist combinations on small-airway dysfunction in mild asthmatics measured by impulse oscillometry. J Asthma Allergy. 2013;6:109–116.

Di Cicco M., Peroni D.G., Ragazzo V., Comberiati P. Application of exhaled nitric oxide (FeNO) in pediatric asthma. Curr Opin Allergy Clin Immunol. 2021;21:151–158. doi: 10.1097/ACI.0000000000000726.

Rupani H., Kent B.D. Using fractional exhaled nitric oxide measurement in clinical asthma management. Chest. 2022;161:906–917. doi: 10.1016/j.chest.2021.10.015.

Elliott M., Heltshe S.L., Stamey D.C., Cochrane E.S., Redding G.J., Debley J.S. Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers. Clin Exp Allergy : journal of the British Society for Allergy and Clinical Immunology. 2013;43:1351–1361.

Caudri D., Wijga A.H., Hoekstra M.O., et al. Prediction of asthma in symptomatic preschool children using exhaled nitric oxide, Rint and specific IgE. Thorax. 2010;65:801–807.

Dweik R.A., Boggs P.B., Erzurum S.C., et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184:602–615. doi: 10.1164/rccm.9120-11ST.

Moeller A., Carlsen K.H., Sly P.D., et al. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation. Eur Respir Rev. 2015;24:204–215.

Xepapadaki P., Papadopoulos N.G., Bossios A., Manoussakis E., Manousakas T., Saxoni-Papageorgiou P. Duration of postviral airway hyperresponsiveness in children with asthma: effect of atopy. J Allergy Clin Immunol. 2005;116:299–304. doi: 10.1016/j.jaci.2005.04.007.

Golan-Lagziel T., Mandelberg A., Wolfson Y., Ater D., Armoni Domany K. Can bronchial challenge test with adenosine or methacholine at preschool age predict school-age asthma? Pediatr Pulmonol. 2021;56:3200–3208.

Kaiser S.V., Huynh T., Bacharier L.B., et al. Preventing exacerbations in preschoolers with recurrent wheeze: a meta-analysis. Pediatrics. 2016;137

Akar-Ghibril N., Casale T., Custovic A., Phipatanakul W. Allergic endotypes and phenotypes of asthma. J Allergy Clin Immunol Pract. 2020;8:429–440.

FitzGerald J.M., Bleecker E.R., Menzies-Gow A., et al. Predictors of

Gaillard E.A., McNamara P.S., Murray C.S., Pavord I.D., Shields M.D. Blood eosinophils as a marker of likely corticosteroid response in children with preschool wheeze: time for an eosinophil guided clinical trial? Clin Exp Allergy. 2015;45:1384–1395.

Saglani S., Fleming L., Sonnappa S., Bush A. Advances in the aetiology, management, and prevention of acute asthma attacks in children. Lancet Child Adolesc Health. 2019;3:354–364.

Buzzulini F., Da Re M., Scala E., et al. Evaluation of a new multiplex assay for allergy diagnosis. Clin Chim Acta. 2019;493:73–78.

Steering Committee A., Review Panel M. A WAO - ARIA - GA(2)LEN consensus document on molecular-based allergy diagnosis (PAMD@): update 2020. World Allergy Organ J. 2020;13

Walsh C.J., Zaihra T., Benedetti A., et al. Exacerbation risk in severe asthma is stratified by inflammatory phenotype using longitudinal measures of sputum eosinophils. Clin Exp Allergy. 2016;46:1291–1302. doi: 10.1111/cea.12762.

Marc-Malovrh M., Camlek L., Skrgat S., et al. Elevated eosinophils, IL5 and IL8 in induced sputum in asthma patients with accelerated FEV1 decline. Respir Med. 2020;162

Bush A. Which child with asthma is a candidate for biological therapies? J Clin Med. 2020;9

Demarche S.F., Schleich F.N., Paulus V.A., Henket M.A., Van Hees T.J., Louis R.E. Asthma control and sputum eosinophils: a longitudinal study in daily practice. J Allergy Clin Immunol Pract. 2017;5:1335–13343 e5.doi: 10.1016/j.jaip.2017.01.026.

Hossny E., El-Awady H., Bakr S., Labib A. Vascular endothelial growth factor overexpression in induced sputum of children with bronchial asthma. Pediatr Allergy Immunol. 2009;20:89–96. doi: 10.1111/j.1399-3038.2008.00730.

Kim M.J., Lee H.S., Sol I.S., et al. Increased sputum levels of thymus and activation-regulated chemokine in children with asthma not eosinophilic bronchitis. Allergol Immunopathol. 2017;45:220–226.

Thomas P.S., Lowe A.J., Samarasinghe P., et al. Exhaled breath condensate in pediatric asthma: promising new advance or pouring cold water on a lot of hot air? a systematic review. Pediatr Pulmonol. 2013;48:419–442.

Bannier M., Rosias P.P.R., Jobsis Q., Dompeling E. Exhaled breath condensate in childhood asthma: a review and current perspective. Front Pediatr. 2019;7:150.

Ivanova O., Richards L.B., Vijverberg S.J., et al. What did we learn from multiple omics studies in asthma? Allergy. 2019;74:2129–2145.

Golebski K., Kabesch M., Melen E., et al. Childhood asthma in the new omics era: challenges and perspectives. Curr Opin Allergy Clin Immunol.2020;20:155–161. doi: 10.1097/ACI.0000000000000626.

McGeachie M.J., Dahlin A., Qiu W., et al. The metabolomics of asthma control: a promising link between genetics and disease. Immun Inflamm Dis. 2015;3:224–238. doi: 10.1002/iid3.61.

Tyler S.R., Bunyavanich S. Leveraging -omics for asthma endotyping. J Allergy Clin Immunol. 2019;144:13–23.






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