Lung function testing and inflammation markers for wheezing preschool children: A systematic review for the EAACI Clinical Practice Recommendations on Diagnostics of Preschool Wheeze.
asthma
child
diagnosis
lung function
prediction
preschool
wheezing
Journal
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
ISSN: 1399-3038
Titre abrégé: Pediatr Allergy Immunol
Pays: England
ID NLM: 9106718
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
06
11
2020
received:
25
07
2020
accepted:
13
11
2020
pubmed:
23
11
2020
medline:
19
8
2021
entrez:
22
11
2020
Statut:
ppublish
Résumé
Preschool wheeze is highly prevalent; 30%-50% of children have wheezed at least once before age six. Wheezing is not a disorder; it is a symptom of obstruction in the airways, and it is essential to identify the correct diagnosis behind this symptom. An increasing number of studies provide evidence for novel diagnostic tools for monitoring and predicting asthma in the pediatric population. Several techniques are available to measure airway obstruction and airway inflammation, including spirometry, impulse oscillometry, whole-body plethysmography, bronchial hyperresponsiveness test, multiple breath washout test, measurements of exhaled NO, and analyses of various other biomarkers. We systematically reviewed all the existing techniques available for measuring lung function and airway inflammation in preschool children to assess their potential and clinical value in the routine diagnostics and monitoring of airway obstruction. If applicable, measuring FEV1 using spirometry is considered useful. For those unable to perform spirometry, whole-body plethysmography and IOS may be useful. Bronchial reversibility to beta2-agonist and hyperresponsiveness test with running exercise challenge may improve the sensitivity of these tests. The difficulty of measuring lung function and the lack of large randomized controlled trials makes it difficult to establish guidelines for monitoring asthma in preschool children.
Sections du résumé
BACKGROUND
Preschool wheeze is highly prevalent; 30%-50% of children have wheezed at least once before age six. Wheezing is not a disorder; it is a symptom of obstruction in the airways, and it is essential to identify the correct diagnosis behind this symptom. An increasing number of studies provide evidence for novel diagnostic tools for monitoring and predicting asthma in the pediatric population. Several techniques are available to measure airway obstruction and airway inflammation, including spirometry, impulse oscillometry, whole-body plethysmography, bronchial hyperresponsiveness test, multiple breath washout test, measurements of exhaled NO, and analyses of various other biomarkers.
METHODS
We systematically reviewed all the existing techniques available for measuring lung function and airway inflammation in preschool children to assess their potential and clinical value in the routine diagnostics and monitoring of airway obstruction.
RESULTS
If applicable, measuring FEV1 using spirometry is considered useful. For those unable to perform spirometry, whole-body plethysmography and IOS may be useful. Bronchial reversibility to beta2-agonist and hyperresponsiveness test with running exercise challenge may improve the sensitivity of these tests.
CONCLUSIONS
The difficulty of measuring lung function and the lack of large randomized controlled trials makes it difficult to establish guidelines for monitoring asthma in preschool children.
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Review
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
501-513Informations de copyright
© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Références
Bisgaard H, Szefler S. Prevalence of asthma-like symptoms in young children. Pediatr Pulmonol. 2007;42(8):723-728.
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(3):133-138.
Garner R, Kohen D. Changes in the prevalence of asthma among Canadian children. Health Rep. 2008;19(2):45-50.
Beydon N, Davis SD, Lombardi E, et al. An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children. Am J Respir Crit Care Med. 2007;175(12):1304-1345.
Rosenfeld M, Allen J, Arets BH, et al. An official American Thoracic Society workshop report: optimal lung function tests for monitoring cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheezing in children less than 6 years of age. Ann Am Thorac Soc. 2013;10(2):S1-S11.
Zapletal A, Hladíková M, Chalupová J, Svobodová T, Vávrová V. Area under the maximum expiratory flow-volume curve - a sensitive parameter in the evaluation of airway patency. Respiration. 2008;75(1):40-47.
Francisco B, Ner Z, Ge B, Hewett J, König P. Sensitivity of different spirometric tests for detecting airway obstruction in childhood asthma. J Asthma. 2015;52(5):505-511.
Quanjer PH, Weiner DJ, Pretto JJ, Brazzale DJ, Boros PW. Measurement of FEF25-75% and FEF75% does not contribute to clinical decision making. Eur Respir J. 2014;43(4):1051-1058.
Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med. 2013;187(9):1016-1027.
Weiler JM, Brannan JD, Randolph CC, et al. Exercise-induced bronchoconstriction update-2016. J Allergy Clin Immunol. 2016;138(5):1292-1295.e1236.
Arianto L, Hallas HW, Stokholm J, Bønnelykke K, Bisgaard H, Chawes BL. Sensitivity of multiple breath washout to detect mild-to-moderate asthma in adolescence. J Allergy Clin Immunol Pract. 2019.
Hellinckx J, De Boeck K, Bande-Knops J, van der Poel M, Demedts M. Bronchodilator response in 3-6.5 years old healthy and stable asthmatic children. Eur Respir J. 1998;12(2):438-443.
Malmberg LP, Pelkonen A, Poussa T, Pohianpalo A, Haahtela T, Turpeinen M. Determinants of respiratory system input impedance and bronchodilator response in healthy Finnish preschool children. Clin Physiol Funct Imaging. 2002;22(1):64-71.
Thamrin C, Gangell CL, Udomittipong K, et al. Assessment of bronchodilator responsiveness in preschool children using forced oscillations. Thorax. 2007;62(9):814-819.
Dweik RA, Boggs PB, Erzurum SC, 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(5):602-615.
Robinson PD, Latzin P, Ramsey KA, et al. Preschool multiple-breath washout testing. an official american thoracic society technical statement. Am J Respir Crit Care Med. 2018;197(5):e1-e19.
Palmer LJ, Rye PJ, Gibson NA, Burton PR, Landau LI, Lesouëf PN. Airway responsiveness in early infancy predicts asthma, lung function, and respiratory symptoms by school age. Am J Respir Crit Care Med. 2001;163(1):37-42.
Turner SW, Palmer LJ, Rye PJ, et al. Infants with flow limitation at 4 weeks: outcome at 6 and 11 years. Am J Respir Crit Care Med. 2002;165(9):1294-1298.
Håland G, Carlsen KCL, Sandvik L, et al. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med. 2006;355(16):1682-1689.
Hallas HW, Chawes BL, Rasmussen MA, et al. Airway obstruction and bronchial reactivity from age 1 month until 13 years in children with asthma: A prospective birth cohort study. PLoS Med. 2019;16(1):e1002722.
Arianto L, Hallas H, Stokholm J, Bønnelykke K, Bisgaard H, Chawes BL. Multiple breath washout for diagnosing asthma and persistent wheeze in young children. Ann Am Thorac Soc. 2019;16(5):599-605.
Society AT, Society ER. ATS/ERS statement: raised volume forced expirations in infants: guidelines for current practice. Am J Respir Crit Care Med. 2005;172(11):1463-1471.
Loland L, Bisgaard H. Feasibility of repetitive lung function measurements by raised volume rapid thoracoabdominal compression during methacholine challenge in young infants. Chest. 2008;133(1):115-122.
Chawes BL, Poorisrisak P, Johnston SL, Bisgaard H. Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants. J Allergy Clin Immunol. 2012;130(2):354-361.e353.
Bisgaard H, Jensen SM, Bønnelykke K. Interaction between asthma and lung function growth in early life. Am J Respir Crit Care Med. 2012;185(11):1183-1189.
Bisgaard H, Klug B. Lung function measurement in awake young children. Eur Respir J. 1995;8(12):2067-2075.
Nielsen KG, Bisgaard H. Lung function response to cold air challenge in asthmatic and healthy children of 2-5 years of age. Am J Respir Crit Care Med. 2000;161(6):1805-1809.
Sonnappa S, Bastardo CM, Wade A, et al. Symptom-pattern phenotype and pulmonary function in preschool wheezers. J Allergy Clin Immunol. 2010;126(3):pp. 519-526.e511-517.
Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med. 2006;354(19):1998-2005.
Belgrave DC, Buchan I, Bishop C, Lowe L, Simpson A, Custovic A. Trajectories of lung function during childhood. Am J Respir Crit Care Med. 2014;189(9):1101-1109.
Sorkness RL, Teague WG, Penugonda M, Fitzpatrick AM. National Institutes of Health NH, L.ng, and Blood Institute's Severe Asthma Research Program. Sex dependence of airflow limitation and air trapping in children with severe asthma. J Allergy Clin Immunol. 2011;127(4):1073-1074.
Moeller A, Carlsen K-H, Sly PD, et al. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation. Eur Respir Rev. 2015;24(136):204-215.
Komarow HD, Myles IA, Uzzaman A, Metcalfe DD. Impulse oscillometry in the evaluation of diseases of the airways in children. Ann Allergy Asthma Immunol. 2011;106(3):191-199.
Komarow HD, Skinner J, Young M, et al. A study of the use of impulse oscillometry in the evaluation of children with asthma: analysis of lung parameters, order effect, and utility compared with spirometry. Pediatr Pulmonol. 2012;47(1):18-26.
Bickel S, Popler J, Lesnick B, Eid N. Impulse oscillometry: interpretation and practical applications. Chest. 2014;146(3):841-847.
Marchal F, Schweitzer C, Thuy LV. Forced oscillations, interrupter technique and body plethysmography in the preschool child. Paediatr Respir Rev. 2005;6(4):278-284.
De Assumpcao MS, da Silva GE, Oliveira MS, et al. Impulse oscillometry system and anthropometric variables of preschoolers, children and adolescents systematic review. Curr Pediatr Rev. 2017;13(2):126-135.
Goldman MD, Saadeh C, Ross D. Clinical applications of forced oscillation to assess peripheral airway function. Respir Physiol Neurobiol. 2005;148(1-2):179-194.
Oostveen E, MacLeod D, Lorino H, et al. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003;22(6):1026-1041.
Malmberg LP, Pelkonen AS, Haahtela T, Turpeinen M. Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma. Thorax. 2003;58(6):494-499.
Oostveen E, Dom S, Desager K, Hagendorens M, De Backer W, Weyler J. Lung function and bronchodilator response in 4-year-old children with different wheezing phenotypes. Eur Respir J. 2010;35(4):865-872.
Dom S, Weyler JJ, Droste JHJ, et al. Determinants of baseline lung function and bronchodilator response in 4-year-old children. Eur Respir J. 2014;44(2):371-381.
Konstantinou GN, Papadopoulos NG, Manousakis E, Xepapadaki P. Virus-induced asthma/wheeze in preschool children: longitudinal assessment of airflow limitation using impulse oscillometry. J Clin Med. 2019;8(9).
Jpers C, Cuijpers GJ, Kessels A, et al. Low diagnostic value of respiratory impedance measurements in children. Eur Respir J. 1997;10(1):88-93.
Shi Y, Aledia AS, Tatavoosian AV, Vijayalakshmi S, Galant SP, George SC. Relating small airways to asthma control by using impulse oscillometry in children. J Allergy Clin Immunol. 2012;129(3):671-678.
Shi Y, Aledia AS, Galant SP, George SC. Peripheral airway impairment measured by oscillometry predicts loss of asthma control in children. J Allergy Clin Immunol. 2013;131(3):718-723.
Delacourt C, Lorino H, Herve-Guillot M, Reinert P, Harf A, Housset B. Use of the forced oscillation technique to assess airway obstruction and reversibility in children. Am J Respir Crit Care Med. 2000;161(3 Pt 1):730-736.
Nielsen KG, Bisgaard H. Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years. Am J Respir Crit Care Med. 2001;164(4):554-559.
Marotta A, Klinnert MD, Price MR, Larsen GL, Liu AH. Impulse oscillometry provides an effective measure of lung dysfunction in 4-year-old children at risk for persistent asthma. J Allergy Clin Immunol. 2003;112(2):317-322.
Malmberg LP, Mäkelä MJ, Mattila PS, Hammarén-Malmi S, Pelkonen AS. Exercise-induced changes in respiratory impedance in young wheezy children and nonatopic controls. Pediatr Pulmonol. 2008;43(6):538-544.
Lee JH, Lee YW, Shin YS, Jung YH, Hong CS, Park JW. Exercise-induced airway obstruction in young asthmatics measured by impulse oscillometry. J Investig Allergol Clin Immunol. 2010;20(7):575-581.
Schulze J, Smith H-J, Fuchs J, et al. Methacholine challenge in young children as evaluated by spirometry and impulse oscillometry. Respir Med. 2012;106(5):627-634.
Kalliola S, Malmberg LP, Kajosaari M, Mattila PS, Pelkonen AS, Mäkelä MJ. Assessing direct and indirect airway hyperresponsiveness in children using impulse oscillometry. Ann Allergy Asthma Immunol. 2014;113(2):166-172.
Larsen GL, Morgan W, Heldt GP, et al. Impulse oscillometry versus spirometry in a long-term study of controller therapy for pediatric asthma. J Allergy Clin Immunol. 2009;123(4):861-867.e861.
Brooke E, Lucas JS, Collins SA, et al. Infant lung function and wheeze in later childhood in the Southampton Women's Survey. Eur Respir J. 2014;43(3):919-921.
Guilbert TW, Singh AM, Danov Z, et al. Decreased lung function after preschool wheezing rhinovirus illnesses in children at risk to develop asthma. J Allergy Clin Immunol. 2011;128(3):532-538.e531-510.
Lajunen K, Kalliola S, Kotaniemi-Syrjänen A, et al. Abnormal lung function at preschool age asthma in adolescence? Ann Allergy Asthma Immunol. 2018;120(5):520-526.
Lauhkonen E, Riikonen R, Törmänen S, et al. Impulse oscillometry at preschool age is a strong predictor of lung function by flow-volume spirometry in adolescence. Pediatr Pulmonol. 2018;53(5):552-558.
Knihtilä H, Kotaniemi-Syrjänen A, Pelkonen AS, Kalliola S, Mäkelä MJ, Malmberg LP. Sensitivity of newly defined impulse oscillometry indices in preschool children. Pediatr Pulmonol. 2017;52(5):598-605.
Kattan M, Bacharier LB, O'Connor GT, et al. Spirometry and impulse oscillometry in preschool children: acceptability and relationship to maternal smoking in pregnancy. J Allergy Clin Immunol Pract. 2018;6(5):1596-1603.e1596.
Alblooshi AS, Simpson SJ, Stick SM, Hall GL. The safety and feasibility of the inhaled mannitol challenge test in young children. Eur Respir J. 2013;42(5):1420-1423.
Dinakar C, Chipps BE, IMMUNOLOGY SOAA, MEDICINE SOPPAS. Clinical tools to assess asthma control in children. Pediatrics. 2017;139(1).
Macleod KA, Horsley AR, Bell NJ, Greening AP, Innes JA, Cunningham S. Ventilation heterogeneity in children with well controlled asthma with normal spirometry indicates residual airways disease. Thorax. 2009;64(1):33-37.
Downing B, Irving S, Bingham Y, Fleming L, Bush A, Saglani S. Feasibility of lung clearance index in a clinical setting in pre-school children. Eur Respir J. 2016;48(4):1074-1080.
Vilmann L, Buchvald F, Green K, Nielsen KG. Fractional exhaled nitric oxide and multiple breath nitrogen washout in preschool healthy and asthmatic children. Respir Med. 2017;133:42-47.
Chawes BL, Bønnelykke K, Stokholm J, et al. Effect of vitamin D3 supplementation during pregnancy on risk of persistent wheeze in the offspring: a randomized clinical trial. JAMA. 2016;315(4):353-361.
Society AT, Society ER. 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. 2005;171(8):912-930.
Malmberg LP, Petäys T, Haahtela T, et al. Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference values. Pediatr Pulmonol. 2006;41(7):635-642.
Malmberg LP, Pelkonen AS, Mattila PS, Hammarén-Malmi S, Mäkelä MJ. Exhaled nitric oxide and exercise-induced bronchoconstriction in young wheezy children - interactions with atopy. Pediatr Allergy Immunol. 2009;20(7):673-678.
Chawes BLK, Buchvald F, Bischoff AL, et al. Elevated exhaled nitric oxide in high-risk neonates precedes transient early but not persistent wheeze. Am J Respir Crit Care Med. 2010;182(2):138-142.
Debley JS, Stamey DC, Cochrane ES, Gama KL, Redding GJ. Exhaled nitric oxide, lung function, and exacerbations in wheezy infants and toddlers. J Allergy Clin Immunol. 2010;125(6):1228-1234.e1213.
Elliott M, Heltshe SL, Stamey DC, Cochrane ES, Redding GJ, Debley JS. Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers. Clin Exp Allergy. 2013;43(12):1351-1361.
Kotaniemi-Syrjänen A, Malmberg LP, Malmström K, Pelkonen AS, Mäkelä MJ. Factors associated with elevated exhaled nitric oxide fraction in infants with recurrent respiratory symptoms. Eur Respir J. 2013;41(1):189-194.
Moeller A, Franklin P, Hall GL, et al. Inhaled fluticasone dipropionate decreases levels of nitric oxide in recurrenty wheezy infants. Pediatr Pulmonol. 2004;38(3):250-255.
Straub DA, Moeller A, Minocchieri S, et al. The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma. Eur Respir J. 2005;25(2):289-294.
Petsky HL, Cates CJ, Li A, Kynaston JA, Turner C, Chang AB. Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults. Cochrane Database Syst Rev. 2009(4):CD006340.
Petsky HL, Cates CJ, Kew KM, Chang AB. Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis. Thorax. 2018;73(12):1110-1119.
Schoos AM, Christiansen CF, Stokholm J, Bønnelykke K, Bisgaard H, Chawes BL. FeNO and exercise testing in children at risk of asthma. J Allergy Clin Immunol Pract. 2018;6(3):855-862.e852.
Gibson PG, Grootendorst DC, Henry RL, et al. Sputum induction in children. Eur Respir J Suppl. 2002;37:44s-46s.
Fleming L, Bush A. Use of sputum eosinophil counts to guide management in children with severe asthma. Thorax. 2012;67(11):1015-1016. author reply 1016.
Lex C, Payne DNR, Zacharasiewicz A, et al. Sputum induction in children with difficult asthma: safety, feasibility, and inflammatory cell pattern. Pediatr Pulmonol. 2005;39(4):318-324.
Thomas PS, Lowe AJ, 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(5):419-442.
Baraldi E, Ghiro L, Piovan V, Carraro S, Zacchello F, Zanconato S. Safety and success of exhaled breath condensate collection in asthma. Arch Dis Child. 2003;88(4):358-360.
Carraro S, Giordano G, Reniero F, et al. Asthma severity in childhood and metabolomic profiling of breath condensate. Allergy. 2013;68(1):110-117.
Trischler J, Merkel N, Könitzer S, Müller CM, Unverzagt S, Lex C. Fractionated breath condensate sampling: H2O2 concentrations of the alveolar fraction may be related to asthma control in children. Respir Res. 2012;13:14.
Moeller A, Franklin P, Hall GL, Horak F, Wildhaber JH, Stick SM. Measuring exhaled breath condensates in infants. Pediatr Pulmonol. 2006;41(2):184-187.
Klaassen EMM, van de Kant KDG, Jöbsis Q, et al. Exhaled biomarkers and gene expression at preschool age improve asthma prediction at 6 years of age. Am J Respir Crit Care Med. 2015;191(2):201-207.
van Vliet D, Alonso A, Rijkers G, et al. Prediction of asthma exacerbations in children by innovative exhaled inflammatory markers: results of a longitudinal study. PLoS One. 2015;10(3):e0119434.
Garcia-Marcos L, Edwards J, Kennington E, et al. Priorities for future research into asthma diagnostic tools: a PAN-EU consensus exercise from the European asthma research innovation partnership (EARIP). Clin Exp Allergy. 2018;48(2):104-120.
van der Schee MP, Paff T, Brinkman P, van Aalderen WMC, Haarman EG, Sterk PJ. Breathomics in lung disease. Chest. 2015;147(1):224-231.
Fens N, van der Schee MP, Brinkman P, Sterk PJ. Exhaled breath analysis by electronic nose in airways disease. Established issues and key questions. Clin Exp Allergy. 2013;43(7):705-715.
Dallinga JW, Robroeks CM, van Berkel JJ, et al. Volatile organic compounds in exhaled breath as a diagnostic tool for asthma in children. Clin Exp Allergy. 2010;40(1):68-76.
van der Schee MP, Hashimoto S, Schuurman AC, et al. Altered exhaled biomarker profiles in children during and after rhinovirus-induced wheeze. Eur Respir J. 2015;45(2):440-448.
Robroeks CM, van Berkel JJ, Jöbsis Q, et al. Exhaled volatile organic compounds predict exacerbations of childhood asthma in a 1-year prospective study. Eur Respir J. 2013;42(1):98-106.
van de Kant KD, van Berkel JJ, Jöbsis Q, et al. Exhaled breath profiling in diagnosing wheezy preschool children. Eur Respir J. 2013;41(1):183-188.
Fuglsbjerg MG, Rasmussen MA, Hansen KS, et al. Limited clinical value of exhaled volatile organic compound measurements in childhood asthma. ERJ Open Res. 2018;4(4).
van Vliet D, Smolinska A, Jöbsis Q, et al. Can exhaled volatile organic compounds predict asthma exacerbations in children? J Breath Res. 2017;11(1):016016.
Smolinska A, Klaassen EM, Dallinga JW, et al. Profiling of volatile organic compounds in exhaled breath as a strategy to find early predictive signatures of asthma in children. PLoS One. 2014;9(4):e95668.
Lauhkonen E, Cooper BG, Iles R. Mini review shows that structured light plethysmography provides a non-contact method for evaluating breathing patterns in children. Acta Paediatr. 2019;108(8):1398-1405.
Hmeidi H, Motamedi-Fakhr S, Chadwick E, et al. Tidal breathing parameters measured using structured light plethysmography in healthy children and those with asthma before and after bronchodilator. Physiol Rep. 2017;5(5).
Hmeidi H, Motamedi-Fakhr S, Chadwick EK, et al. Tidal breathing parameters measured by structured light plethysmography in children aged 2-12 years recovering from acute asthma/wheeze compared with healthy children. Physiol Rep. 2018;6(12):e13752.
Vuorela T, Seppä VP, Vanhala J, Hyttinen J. Design and implementation of a portable long-term physiological signal recorder. IEEE Trans Inf Technol Biomed. 2010;14(3):718-725.
Usemann J, Suter A, Zannin E, et al. Variability of tidal breathing parameters in preterm infants and associations with respiratory morbidity during infancy: a cohort study. J Pediatr. 2019;205(61-69):e61.
Malmberg LP, Seppä V-P, Kotaniemi-Syrjänen A, et al. Measurement of tidal breathing flows in infants using impedance pneumography. Eur Respir J. 2017;49(2).
Seppä V-P, Paassilta M, Kivistö J, et al. Reduced expiratory variability index (EVI) is associated with controller medication withdrawal and symptoms in wheezy children aged 1-5 years. Pediatr Allergy Immunol. 2020.