Exercise-induced bronchoconstriction (EIB) is a key clinical problem for asthmatic children. Exercise challenge tests, used to confirm EIB, are time consuming and require patient cooperation. The aim of this study was to investigate the diagnostic values of fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and plethysmography for prediction of EIB in children with well-controlled asthma. Fifty-nine children with allergic asthma aged 6–18 years were included in the study. FeNO was measured and all patients underwent spirometry, IOS, and plethysmography. An exercise challenge test was performed to assess EIB. EIB was confirmed with an exercise challenge test in 20 (33.9%) patients. Baseline FeNO levels were significantly higher in the group with EIB (P = 0.003). Resistance at 5 Hz (R5) and frequency dependence of resistance (R5–R20) in IOS and total specific airway resistance (SRtot), residual volume (RV), and the ratio of RV to total lung capacity in plethysmography were significantly higher in the group with EIB. In the logistic regression analysis, the higher baseline FeNO, R5–R20, and SRtot values were found to be significantly related to EIB [Odds ratios (OR):1.35 and P = 0.046, OR:1.80, and P = 0.016, and OR:1.10, P = 0.035, respectively]. To differentiate asthmatic children with EIB from those without EIB, the optimal cutoff point for FeNO was 28 ppb [negative predictive value (NPV):86% and positive predictive value (PPV):52%]. An SRtot level lower than 207.6% (NPV:96% and PPV:54%) can be used to exclude EIB. R5–R20 values higher than 15.5% (NPV: 81% and PPV:71%) were associated with EIB in asthmatic children. Baseline SRtot in plethysmography provided the best sensitivity, whereas the baseline R5–R20 in IOS offered the best specificity for EIB. This study suggested that FeNO, IOS, and plethysmography are valuable tools for the assessment of EIB in children with controlled asthma and EIB is strongly correlated to small airway disease markers.
YoshikawaT, ShojiS, FujiiT, KanazawaH, KudohS, HirataK, et al.Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma. Eur Respir J, 1998; 12:879–884.
3.
NishioK, OdajimaH, MotomuraC, NakaoF, NishimaS. Exhaled nitric oxide and exercise-induced bronchospasm assessed by FEV1, FEF25–FEF75% in childhood asthma. J Asthma, 2007; 44:475–478.
4.
LexC, DymekS, HeyingR, KovacevicA, KrammCM, SchusterA. Value of surrogate tests to predict exercise-induced bronchoconstriction in atopic childhood asthma. Pediatr Pulmonol, 2007; 42:225–230.
5.
ScolloM, ZanconatoS, OngaroR, ZaramellaC, ZacchelloF, BaraldiE. Exhaled nitric oxide and exercise-induced bronchoconstriction in asthmatic children. Am J Respir Crit Care Med, 2000; 161:1047–1050.
FrantzS, NihlénU, DenckerM, EngströmG, LöfdahlCG, WollmerP. Impulse oscillometry may be of value in detecting early manifestations of COPD. Respir Med, 2012; 106:1116–1123.
8.
SchulzeJ, SmithHJ, FuchsJ, HerrmannE, DresslerM, RoseMA, et al.Methacholine challenge in young children as evaluated by spirometry and impulse oscillometry. Respir Med, 2012; 106:627–634.
9.
KomarowHD, MylesIA, UzzamanA, MetcalfeDD. Impulse oscillometry in the evaluation of diseases of the airways in children. Ann Allergy Asthma Immunol, 2011; 106:191–199.
10.
KaminskyDA. What does airway resistance tell us about lung function?. Respir Care, 2012; 57:85–96.
11.
NajiN, KeungE, KaneJ, WatsonRM, KillianKJ, GauvreauGM. Comparison of changes in lung function measured by plethymography and IOS after bronchoprovocation. Respir Med, 2013; 107:503–510.
12.
From National Heart, Lung, and Blood Institute. Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma-full report. 2007. Avaialable at: www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm Accessed November1, 2016.
13.
DweikRA, BoggsPB, ErzurumSC, IrvinCG, LeighMW, LundbergJO; American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. 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.
14.
MillerMR, CrapoR, HankinsonJ, BrusascoV, BurgosF, CasaburiR, et al.General considerations for lung function testing. Eur Respir J, 2005; 26:153–161.
15.
PellegrinoR, ViegiG, BrusascoV, CrapoRO, BurgosF, CasaburiR, et al.Interpretative strategies for lung function tests. Eur Respir J, 2005; 26:948–968.
16.
ZapletalA, SamanekM, PaulT, et al.Lung function in children and adolescents: methods, reference values. Basel: Karger, 1997.
17.
BeydonN, DavisSD, LombardiE, AllenJL, AretsHG, AuroraP, et al.An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children. Am J Respir Crit Care Med, 2007; 175:1304–1345.
18.
StocksJ, GodfreyS, BeardsmoreC, Bar-YishayE, CastileR; ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society. Plethysmographic measurements of lung volume and airway resistance. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society. Eur Respir J, 2001; 17:302–312.
19.
ParsonsJP, HallstrandTS, MastronardeJG, KaminskyDA, RundellKW, HullJH, et al.An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med, 2013; 187:1016–1027.
20.
HosmerDW, LemeshowS. Multiple logistic regression, in applied logistic regression, 2nd Edition. John Wiley & Sons, New York, 2000, p. 375.
21.
CockcroftD, DavisB. Direct and indirect challenges in the clinical assessment of asthma. Ann Allergy Asthma Immunol, 2009; 103:363–369.
AndersonSD. Indirect challenge tests: airway hyperresponsiveness in asthma: its measurement and clinical significance. Chest, 2010; 138:25–30.
24.
BuchvaldF, HermansenMN, NielsenKG, BisgaardH. Exhaled nitric oxide predicts exercise-induced bronchoconstriction in asthmatic school children. Chest, 2005; 128:1964–1967.
25.
WarkeTJ, FitchPS, BrownV, TaylorR, LyonsJD, EnnisM, et al.Exhaled nitric oxide correlates with airway eosinophils in childhood asthma. Thorax, 2002; 57:383–387.
26.
BarretoM, ZambardiR, VillaMP. Exhaled nitric oxide and other exhaled biomarkers in bronchial challenge with exercise in asthmatic children: current knowledge. Paediatr Respir Rev, 2015; 16:68–74.
27.
MuñozX, Sanchez-VidaurreS, RocaO, TorresF, MorellF, CruzMJ. Bronchial inflammation and hyperresponsiveness in well controlled asthma. Clin Exp Allergy, 2012; 42:1321–1328.
28.
HuangJ, ZhangM, ZhangX, WangL. Airway hyper-responsiveness and small airway function in children with well-controlled asthma. Pediatr Res, 2015; 77:819–822.
29.
ElHalawaniSM, LyNT, MahonRT, AmundsonDE. Exhaled nitric oxide as a predictor of exercise-induced bronchoconstriction. Chest, 2003; 124:639–643.
30.
RamserM, HammerJ, AmacherA, TrachselD. The value of exhaled nitric oxide in predicting bronchial hyperresponsiveness in children. J Asthma, 2008; 45:191–195.
MergetR, NensaF, HeinzeE, TaegerD, BrueningT. Spirometry or body plethysmography for the assessment of bronchial hyperresponsiveness?. Adv Exp Med Biol, 2016; 921:1–10.
33.
CriéeCP, SorichterS, SmithHJ, KardosP, MergetR, HeiseD, et al; Working Group for Body Plethysmography of the German Society for Pneumology and RespiratoryCare. Body plethysmography—its principles and clinical use. Respir Med, 2011; 105:959–971.
34.
DesirajuK, AgrawalA. Impulse oscillometry: the state-of-art for lung function testing. Lung India, 2016; 33:410–416.
35.
PerezT, ChanezP, DusserD, DevillierP. Small airway impairment in moderate to severe asthmatics without significant proximal airway obstruction. Respir Med, 2013; 107:1667–1674.
36.
JainVV, AbejieB, BashirMH, TynerT, VempillyJ. Lung volume abnormalities and its correlation to spirometric and demographic variables in adult asthma. J Asthma, 2013; 50:600–605.
37.
KraftM, PakJ, MartinRJ, KaminskyD, IrvinCG. Distal lung dysfunction at night in nocturnal asthma. Am J Respir Crit Care Med, 2001; 163:1551–1556.
38.
BrashierB, SalviS. Measuring lung function using sound waves: role of the forced oscillation technique and impulse oscillometry system. Breathe(Sheff), 2015; 11:57–65.
39.
AlfieriV, AielloM, PisiR, TzaniP, MarianiE, MarangioE, et al.Small airway dysfunction is associated to excessive bronchoconstriction in asthmatic patients. Respir Res, 2014; 15:86.
40.
BjermerL. The role of small airway disease in asthma. Curr Open Pulm Med, 2014; 20:23–30.
41.
ShortPM, AndersonWJ, ManoharanA, LipworthBJ. Usefulness of impulse oscillometry for the assessment of airway hyperresponsiveness in mild-to-moderate adult asthma. Ann Allergy Asthma Immunol, 2015; 115:17–20.
42.
RandolphC. An update on exercise-induced bronchoconstriction with and without asthma. Curr Allergy Asthma Rep, 2009; 9:433–438.
43.
GrzelewskiT, GrzelewskaA, MajakP, StelmachW, KowalskaA, StelmachR, et al.Fractional exhaled nitric oxide (FeNO) may predict exercise-induced bronchoconstriction (EIB) in schoolchildren with atopic asthma. Nitric Oxide, 2012; 27:82–87.
44.
WeilerJM, BoniniS, CoifmanR, CraigT, DelgadoL, Capão-FilipeM, et al.American Academy of Allergy, Asthma & Immunology Work Group report: exercise-induced asthma. J Allergy Clin Immunol, 2007; 119:1349–1358.
