The Role of FENO in Comparison to Spirometry and ACT in Control of Children Asthma Symptoms

  • Abbas Dabbaghzadeh Department of Immunology and Allergy, Pediatrics Infectious Diseases Research Center, Bou Ali Sina Hospital, Mazandaran University of Medical Sciences, Sari, Iran
  • Marzieh Tavakol Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
  • Mohammad Gharagozlou Mail Department of Allergy and Clinical Immunology, Children’s Hospital Center, Tehran University of Medical Sciences, Tehran, Iran
Asthma, Child, Nitric oxide, Spirometry


Fractional exhaled nitric oxide (FeNO) is a noninvasive marker of inflammation, used for monitoring asthma. The aim of this study was to compare FeNO, asthma control test (ACT), and lung function test (spirometry) in children aged 8-15 years. This observational, cross-sectional study was performed on76 asthmatic children (age, 8-15 years), who were referred to the Department of Immunology and Allergy, Children's Medical Center, Tehran, Iran during 2012-2013. Patients were matched for sex and age. The recruited patients were selected via consecutive sampling. FeNO was measured with a portable electrochemical analyzer and forced spirometry was performed according to the American Thoracic Society (ATS) guidelines. The ACT questionnaire was used and completed for all the patients. The mean FeNO was 28.5±29.1 ppb, and the mean ACT score was 19.8±3.6. FeNO was significantly correlated with forced expiratory volume (FEV1) (r, 0.232; p=0.049) or 25-75% maximum expiratory flow (MEF 25-75) (r, -0.304; p=0.009). FeNO showed no significant correlation with ACT score or FEV1/forced vital capacity (FVC) (p>0.05). Additionally, there was no significant correlation between FeNO and changes in FEV1 and MEF 25-75% before and after the administration of bronchodilators (p>0.05). To improve asthma control, childhood ACT, FeNO, and spirometric tests can be used as complementary tools in clinical practice to detect children with poorly controlled asthma.


1. Global Strategy for Asthma Management and Prevention 2016 update. Available from: www.
2. Koshak EA. Classification of asthma according to revised 2006 GINA: Evolution from severity to control. Ann Thorac Med 2007; 2(2):45-6.
3. Gustafsson LE, Leone A, Persson M, Wiklund N, Moncada S. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem Biophys Res Commun 1991; 181(2):852-7.
4. Guo FH, Comhair SA, Zheng S, Dweik RA, Eissa NT, Thomassen MJ, 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):5970-80.
5. Kharitonov S, Yates D, Robbins R, Barnes P, Logan-Sinclair R, Shinebourne E. Increased nitric oxide in exhaled air of asthmatic patients. Lancet 1994; 343(8890):133-5.
6. Kharitonov SA, Yates DH, Barnes PJ. Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Am J Respir Crit Care Med 1996; 153(1):454-7.
7. Pijnenburg M, Hofhuis W, Hop W, De Jongste JC. Exhaled nitric oxide predicts asthma relapse in
children with clinical asthma remission. Thorax 2005; 60(3):215-8.
8. Strunk RC, Szefler SJ, Phillips BR, Zeiger RS, Chinchilli VM, Larsen G, et al. Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J Allergy Clin Immunol 2003; 112(5):
9. Pijnenburg MW, Bakker EM, Hop WC, De Jongste JC. Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trial. Am J Respir Crit Care Med 2005; 172(7):831-6.
10. Shaw DE, Berry MA, Thomas M, Green RH, Brightling CE, Wardlaw AJ, et al. The use of exhaled nitric oxide to guide asthma management: a randomized controlled trial. Am J Respir Crit Care Med 2007; 176(3):231-7.
11. Franklin PJ, Stick SM. The value of FeNO measurement in asthma management: the motion against FeNO to help manage childhood asthma–reality bites. Paediatr Respir Rev 2008; 9(2):122-6.
12. Global Strategy for Asthma Management and Prevention. Updated 2011 [January 13, 2012]. Available from:
13. Liu AH, Zeiger R, Sorkness C, Mahr T, Ostrom N, Burgess S, et al. Development and cross-sectional validation of the Childhood Asthma Control Test. J Allergy Clin Immunol 2007; 119(4):817-25.
14. Nathan RA, Sorkness CA, Kosinski M, Schatz M, Li JT, Marcus P, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol 2004; 113(1):59-65.
15. Vega J, Badia X, Badiola C, López-Viña A, Olaguíbel J, Picado C, et al. Validation of the Spanish version of the Asthma Control Test (ACT). J Asthma 2007; 44(10):867-72.
16. Ito Y, Adachi Y, Itazawa T, Okabe Y, Adachi YS, Higuchi O, et al. Association between the results of the childhood asthma control test and objective parameters in asthmatic children. J Asthma 2011; 48(10):1076-80.
17. National AE, Prevention P. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. The J Allergy Clin Immunol 2007; 120(5 Suppl):S94.
18. Global Strategy for Asthma Management and Prevention Updated 2007. Available from:
19. A national clinical guideline. British Thoracic Society. Scottish Intercollegiate Guidelines Network SIGN Updated Mayo 2008. Available from:
20. American Thoracic Society;EuropeanRespiratorySociety. 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):912-30.
21. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J 2005; 26(2):319-38.
22. National Institutes of Health. National Asthma Education and Prevention Program 2007. Available from:
23. Szefler SJ, Wenzel S, Brown R, Erzurum SC, Fahy JV, Hamilton RG, et al. Asthma outcomes: biomarkers. J Allergy Clin Immunol 2012; 129(3):S9-S23.
24. Morton J, Henry RL, Thomas PS. Exhaled breath condensate nitrite/nitrate and pH in relation to pediatric asthma control and exhaled nitric oxide. Pediatr Pulmonol 2006; 41(10):929-36.
25. Spergel JM, Fogg MI, Bokszczanin-Knosala A. Correlation of exhaled nitric oxide, spirometry and asthma symptoms. J Asthma 2005; 42(10):879-83.
26. Robroeks C, Van De Kant K, Jöbsis Q, Hendriks H, Van Gent R, Wouters E, et al. Exhaled nitric oxide and biomarkers in exhaled breath condensate indicate the presence, severity and control of childhood asthma. Clin Exp Allergy 2007; 37(9):1303-11.
27. Khalili B, Boggs PB, Shi R, Bahna SL. Discrepancy between clinical asthma control assessment tools and fractional exhaled nitric oxide. Ann Allergy Asthma Immunol 2008; 101(2):124-9.
28. Piacentini G, Peroni D, Bodini A, Bonafiglia E, Rigotti E, Baraldi E, et al. Childhood Asthma Control Test and airway inflammation evaluation in asthmatic children. Allergy 2009; 64(12):1753-7.
29. Paro‐Heitor MLZ, Bussamra MHC, Saraiva‐Romanholo BM, Martins MA, Okay TS, Rodrigues JC. Exhaled nitric oxide for monitoring childhood asthma inflammation compared to sputum analysis, serum interleukins and pulmonary function. Pediatric pulmonology. Pediatr Pulmonol 2008; 43(2):134-41.
30. Covar RA, Szefler SJ, Martin RJ, Sundstrom D, Silkoff PE, Murphy J, et al. Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma. J Pediatr 2003; 142(5):469-75.
31. Prasad A, Langford B, Stradling JR, Ho L-P. Exhaled nitric oxide as a screening tool for asthma in school children. Respir Med 2006; 100(1):167-73.
32. Dweik R, Boggs P, Erzurum S, Irvin C, Leigh M, Lundberg J, et al. American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels for Clinical A. 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):602-15.
33. Spanier AJ, Kahn RS, Hornung R, Lierl M, Lanphear BP. Associations of fraction of exhaled nitric oxide with beta agonist use in children with asthma. Pediatr Allergy Immunol Pulmonol 2011; 24(1):45-50.
34. Petsky H, Cates C, Lasserson T, Li A, Turner C, Kynaston J, et al. A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils). Thorax 2012; 67(3):199-208.
35. Mitra A, Ogston S, Crighton A, Mukhopadhyay S. Lung function and asthma symptoms in children: relationships and response to treatment. Acta Paediatr 2002; 91(7):789-92.
36. De Jongste JC, Carraro S, Hop WC, Group CS, Baraldi E. Daily telemonitoring of exhaled nitric oxide and symptoms in the treatment of childhood asthma. Am J Respir Crit Care Med 2009; 179(2):93-7.
37. Berkman N, Avital A, Breuer R, Bardach E, Springer C, Godfrey S. Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests. Thorax 2005; 60(5):383-8.
38. Smith AD, Cowan JO, Filsell S, McLachlan C, Monti-Sheehan G, Jackson P, et al. Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests. Am J Respir Crit Care Med 2004; 169(4):473-8.
39. Deykin A, Massaro AF, Drazen JM, Israel E. Exhaled nitric oxide as a diagnostic test for asthma: online versus offline techniques and effect of flow rate. Am J Respir Crit Care Med 2002; 165(12):1597-601.
How to Cite
Dabbaghzadeh A, Tavakol M, Gharagozlou M. The Role of FENO in Comparison to Spirometry and ACT in Control of Children Asthma Symptoms. Iran J Allergy Asthma Immunol. 18(5):479-486.
Original Article(s)