Restricted accessResearch articleFirst published online 2014-09
The Interpretation of Exhaled Nitric Oxide Values in Children With Asthma Depends on the Degree of Bronchoconstriction and the Levels of Asthma Severity
The clinical implications of fractional exhaled nitric oxide (FENO) measurements in childhood asthma are unclear. We aimed to evaluate the relationship between the level of exhaled nitric oxide and pre-bronchodilator FEV1 and the change in FEV1 after bronchodilator in children with asthma.
METHODS:
This was a retrospective, cross-sectional study. We evaluated data from medical documentation of children with asthma with special attention to FENO results, asthma severity, FEV1 (% predicted), and bronchial reversibility test.
RESULTS:
Four hundred and five subjects (age 6–18 y) completed the study. Median levels of FENO increased linearly with subjects' age (P = .03). We found a nonlinear trend of pre-bronchodilator FEV1 across 4 quartiles of FENO in episodic and mild asthma; we observed lower pre-bronchodilator FEV1 in children with higher FENO, but only up to the FENO value of 35.4 ppb; in children with FENO value > 35.4 ppb, pre-bronchodilator FEV1 was increased. We found a linear increasing trend of change from baseline (after 400 μg of salbutamol) in FEV1 across FENO categories in children with moderate asthma.
CONCLUSIONS:
Our results suggest a need to measure FENO before as well as after spirometry. Consequently, in children with asthma with bronchial obstruction, we suggest assessing FENO after short-acting β2 agonists as well. (ClinicalTrials.gov registration NCT00815984.)
GINA Report, Global Strategy for Asthma Management and Prevention, 2012http://www.ginasthma.org/. Accessed November 2013.
2.
DweikRA, BoggsPB, ErzurumSC, IrvinCG, LeighMW, LundbergJO, et al. 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(5):602–615.
3.
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(2):82–87.
4.
GrzelewskiT, MajakP, JerzyńskaJ, CichalewskiL, KrakowiakJ, StelmachW, et al. The association between fractional exhaled nitric oxide (FeNO) and cat dander in asthmatic children. Nitric Oxide, 2011; 25(3):288–293.
5.
HamidQ, SpringallDR, Riveros-MorenoV, ChanezP, HowarthP, RedingtonA, et al. Induction of nitric oxide synthase in asthma. Lancet, 1993; 342(8886-8887):1510–1513.
6.
RedingtonAE, MengQH, SpringallDR, EvansTJ, CréminonC, MacloufJ, et al. Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatment. Thorax, 2001; 56(5):351–357.
7.
GuoFH, ComhairSA, ZhengS, DweikRA, EissaNT, ThomassenMJ, et al. Molecular mechanisms of increased nitric oxide (NO) in asthma: evidence for transcriptional and post-translational regulation of NO synthesis. J Immunol, 2000; 164(11):5970–5980.
8.
GreenRJ, KleinM, BeckerP, HalkasA, LewisH, KitchinO, et al. Disagreement among common measures of asthma control in children. Chest, 2013; 143(1):117–122.
9.
StrunkRC, SzeflerSJ, PhillipsBR, ZeigerRS, ChinchilliVM, LarsenG, et al. Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute: Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J Allergy Clin Immunol, 2003; 112(5):883–892.
10.
Miraglia del GiudiceM, PiacentiniGL, CapassoM, CapristoC, MaielloN, BonerAL, CapristoAF. Formoterol, montelukast, and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide. Respir Med, 2007; 101(8):1809–1813.
11.
RamserM, HammerJ, AmacherA, TrachselD. The value of exhaled nitric oxide in predicting bronchial hyperresponsiveness in children. J Asthma, 2008; 45(3):191–195.
12.
del GiudiceMM, BruneseFP, PiacentiniGL, PedullàM, CapristoC, DecimoF, CapristoAF. Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in naïve atopic asthmatic children. J Asthma, 2004; 41(7):759–765.
13.
BousquetJ, KhaltaevN, CruzAA, DenburgJ, FokkensWJ, TogiasA, et al. World Health Organization; GA(2)LEN; AllerGen. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy, 2008; 63(Suppl 86):8–160.
14.
Recommendations for standardized procedures for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, Jul 1999. Am J Respir Crit Care Med, 1999; 160(6):2104–2117.
15.
QuanjerPH, TammelingGJ, CotesJE, FabbriLM, MatthysH, PedersenOF, et al. Symbols abbreviations and units. Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Eur Respir J Suppl. 1993Mar; 16:85–100.
16.
QuanjerPhH, HelmsP, BjureJ, GaultierC. Standardization of lung function tests in paediatrics. Eur Respir J, 1989; 2(Suppl 4):184s–261s.
17.
MillerMR, HankinsonJ, BrusascoV, BurgosF, CasaburiR, CoatesA, et al. ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J, 2005; 26(2):319–338.
18.
PellegrinoR, ViegiG, BrusascoV, CrapoRO, BurgosF, CasaburiR, et al. Interpretative strategies for lung function tests. Eur Respir J, 2005; 26(5):948–968.
19.
CordeiroD, RudolphusA, SnoeyE, BraunstahlGJ. Utility of nitric oxide for the diagnosis of asthma in an allergy clinic population. Allergy Asthma Proc, 2011; 32(2):119–126.
20.
MahutB, PeyrardS, DelclauxC. Exhaled nitric oxide and clinical phenotypes of childhood asthma. Respir Res, 2011; 12(1):65–73.
DweikRA, ComhairSA, GastonB, ThunnissenFB, FarverC, ThomassenMJ, et al. NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response. Proc Natl Acad Sci USA, 2001; 98(5):2622–2627.
23.
RicciardoloFL. Multiple roles of nitric oxide in the airways. Thorax, 2003; 58(2):175–182.
24.
KhatriSB, HammelJ, KavuruMS, ErzurumSC, DweikRA. Temporal association of nitric oxide levels and airflow in asthma after whole lung allergen challenge. J Appl Physiol, 2003; 95(1):436–440.
25.
KhatriSB, OzkanM, McCarthyK, LaskowskiD, HammelJ, DweikRA, ErzurumSC. Alterations in exhaled gas profile during allergen-induced asthmatic response. Am J Respir Crit Care Med, 2001; 164(10 Pt 1):1844–1848.
26.
SpergelJM, FoggMI, Bokszczanin-KnosalaA. Correlation of exhaled nitric oxide, spirometry and asthma symptoms. J Asthma, 2005; 42(10):879–883.
27.
VahlkvistS, SindingM, SkamstrupK, BisgaardH. Daily home measurements of exhaled nitric oxide in asthmatic children during natural birch pollen exposure. J Allergy Clin Immunol, 2006; 117(6):1272–1276.
28.
Paro-HeitorML, BussamraMH, Saraiva-RomanholoBM, MartinsMA, OkayTS, RodriguesJC. Exhaled nitric oxide for monitoring childhood asthma inflammation compared to sputum analysis, serum interleukins and pulmonary function. Pediatr Pulmonol, 2008; 43(2):134–141.
29.
PiacentiniGL, PeroniDG, BodiniA, BonafigliaE, RigottiE, BaraldiE, et al. Childhood Asthma Control Test and airway inflammation evaluation in asthmatic children. Allergy, 2009; 64(12):1753–1757.
30.
StelmachI, Kaluzińska-ParzyszekI, JerzynskaJ, StelmachP, StelmachW, MajakP. Comparative effect of pre-coseasonal and continuous grass sublingual immunotherapy in children. Allergy, 2012; 67(3):312–320.
31.
American Thoracic Society, European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med, 2005; 171(8):912–930.
32.
BaraldiE, de JongsteJC, European Respiratory Society/American Thoracic Society (ERS/ATS) Task Force. Measurement of exhaled nitric oxide in children. Eur Respir J, 2002; 20(1):223–237.
33.
Colon-SemideyAJ, MarshikP, CrowleyM, KatzR, KellyHW. Correlation between reversibility of airway obstruction and exhaled nitric oxide levels in children with stable bronchial asthma. Pediatr Pulmonol, 2000; 30(5):385–392.
34.
PapakostaD, LatsiosD, ManikaK, PorpodisK, KontakiotiE, GioulekasD. Asthma control test is correlated to FEV1 and nitric oxide in Greek asthmatic patients: influence of treatment. J Asthma, 2011; 48(9):901–906.
35.
YasuiH, FujisawaT, InuiN, KatoM, HashimotoD, EnomotoN, et al. Impact of add-on pranlukast in stable asthma; the additive effect on peripheral airway inflammation. Respir Med, 2012; 106(4):508–514.
36.
BanovcinP, JesenakM, MichnovaZ, BabusikovaE, NosalS, MiklerJ, et al. Factors attributable to the level of exhaled nitric oxide in asthmatic children. Eur J Med Res, 2009; 14(Suppl 4):9–13.
