Abstract
Purpose
The measurement of fraction of nitric oxide (FeNO) is a noticeable tool that reflects airway inflammation in asthmatic patients. We wanted to find out the relationship between pulmonary function, bronchial hyperresponsiveness (AHR), blood eosinophilic inflammatory markers and FeNO level before and after methacholine bronchoprovocation test in asthmatic patients.
Methods
Fifty-five children, who visited the Allergy Clinic of Korea University Anam Hospital from March 2011 to February 2012, due to asthmatic symptoms, such as history of episodic wheezing or dyspnea during the previous year and resolved after using bronchodilators, were enrolled. We performed the baseline pulmonary function and methacholine bronchoprovocation test in the enrolled patients. Blood eosinophil counts and blood eosinophil cationic protein (ECP) were measured. FeNO levels were measured before and after the methacholine bronchoprovocation test.
Results
The mean FeNO levels (36.3 ppb) fell after methacholine bronchoprovocation test (25.7 ppb). Forced expiratory volume in one second (FEV1) %pred inversely correlated both with FeNO level before (R2=0.07, P=0.029) and after (R2=0.059, P=0.01) methacholine bronchoprovocation test. The provocative concentration, causing a 20% decrease in FEV1 to methacholine (methacholine PC20) inversely correlated both with FeNO levels before (R2=0.086, P=0.001) and after (R2=0.141, P=0.001) the challenge. FeNO level measured at bronchoconstriction state significantly correlated with blood eosinophil counts (R2=0.112, P=0.028). Serum ECP levels correlated FeNO level, neither before nor after bronchoprovocation.
Conclusion
The baseline FeNO levels were higher in asthmatic children. However, FeNO levels rather decreased after methacholine induced bronchoconstriction. Repeated spirometry maneuver was considered to have an effect on reducing FeNO levels. FeNO correlated with pulmonary function, airway AHR and blood eosinophil counts.
References
1. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987. 327:524–526.
2. Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax. 1998. 53:91–95.
3. Mattes J, Storm van's Gravesande K, Reining U, Alving K, Ihorst G, Henschen M, et al. NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma. Eur Respir J. 1999. 13:1391–1395.
4. Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med. 2001. 163:1693–1722.
5. Tsujino I, Nishimura M, Kamachi A, Makita H, Munakata M, Miyamoto K, et al. Exhaled nitric oxide--is it really a good marker of airway inflammation in bronchial asthma? Respiration. 2000. 67:645–651.
6. Lanz MJ, Leung DY, White CW. Comparison of exhaled nitric oxide to spirometry during emergency treatment of asthma exacerbations with glucocorticoids in children. Ann Allergy Asthma Immunol. 1999. 82:161–164.
7. Stirling RG, Kharitonov SA, Campbell D, Robinson DS, Durham SR, Chung KF, et al. Asthma and Allergy Group. Increase in exhaled nitric oxide levels in patients with difficult asthma and correlation with symptoms and disease severity despite treatment with oral and inhaled corticosteroids. Thorax. 1998. 53:1030–1034.
8. Yates DH, Kharitonov SA, Barnes PJ. Effect of short- and long-acting inhaled beta2-agonists on exhaled nitric oxide in asthmatic patients. Eur Respir J. 1997. 10:1483–1488.
9. Baek HS, Park YR, Kim JH, Oh JW, Lee HB. Nitric oxide correlates with exercise-induced bronchoconstriction in asthmatic children. Pediatr Allergy Respir Dis. 2011. 21:99–107.
10. Steerenberg PA, Janssen NA, de Meer G, Fischer PH, Nierkens S, van Loveren H, et al. Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children. Thorax. 2003. 58:242–245.
11. Louis R, Sele J, Henket M, Cataldo D, Bettiol J, Seiden L, et al. Sputum eosinophil count in a large population of patients with mild to moderate steroid-naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness. Allergy. 2002. 57:907–912.
12. Van Den Berge M, Meijer RJ, Kerstjens HA, de Reus DM, Koeter GH, Kauffman HF, et al. PC (20) adenosine 5'-monophosphate is more closely associated with airway inflammation in asthma than PC(20) methacholine. Am J Respir Crit Care Med. 2001. 163:1546–1550.
13. Brusasco V, Crimi E, Pellegrino R. Airway hyperresponsiveness in asthma: not just a matter of airway inflammation. Thorax. 1998. 53:992–998.
14. Silvestri M, Sabatini F, Spallarossa D, Fregonese L, Battistini E, Biraghi MG, et al. Exhaled nitric oxide levels in non-allergic and allergic mono- or polysensitised children with asthma. Thorax. 2001. 56:857–862.
15. Choi BS, Kim KW, Lee YJ, Baek J, Park HB, Kim YH, et al. Exhaled nitric oxide is associated with allergic inflammation in children. J Korean Med Sci. 2011. 26:1265–1269.
16. Gelb AF, Flynn Taylor C, Shinar CM, Gutierrez C, Zamel N. Role of spirometry and exhaled nitric oxide to predict exacerbations in treated asthmatics. Chest. 2006. 129:1492–1499.
17. Beydon N, Davis SD, Lombardi E, Allen JL, Arets HG, Aurora P, 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. Chai H, Farr RS, Froehlich LA, Mathison DA, McLean JA, Rosenthal RR, et al. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol. 1975. 56:323–327.
19. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, 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.
20. Ho LP, Wood FT, Robson A, Innes JA, Greening AP. Atopy influences exhaled nitric oxide levels in adult asthmatics. Chest. 2000. 118:1327–1331.
21. 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. 112:883–892.
22. Saito J, Inoue K, Sugawara A, Yoshikawa M, Watanabe K, Ishida T, et al. Exhaled nitric oxide as a marker of airway inflammation for an epidemiologic study in schoolchildren. J Allergy Clin Immunol. 2004. 114:512–516.
23. Colon-Semidey AJ, Marshik P, Crowley M, Katz R, Kelly HW. Correlation between reversibility of airway obstruction and exhaled nitric oxide levels in children with stable bronchial asthma. Pediatr Pulmonol. 2000. 30:385–392.
24. Ko HS, Chung SH, Choi YS, Choi SH, Rha YH. Relationship between exhaled nitric oxide and pulmonary function test in children with asthma. Korean J Pediatr. 2008. 51:181–187.
25. Mehta V, Stokes JR, Berro A, Romero FA, Casale TB. Time-dependent effects of inhaled corticosteroids on lung function, bronchial hyperresponsiveness, and airway inflammation in asthma. Ann Allergy Asthma Immunol. 2009. 103:31–37.
26. Venge P, Bystrom J, Carlson M, Hakansson L, Karawacjzyk M, Peterson C, et al. Eosinophil cationic protein (ECP): molecular and biological properties and the use of ECP as a marker of eosinophil activation in disease. Clin Exp Allergy. 1999. 29:1172–1186.
27. Wolthers OD. Eosinophil granule proteins in the assessment of airway inflammation in pediatric bronchial asthma. Pediatr Allergy Immunol. 2003. 14:248–254.
28. Covar RA, Szefler SJ, Martin RJ, Sundstrom DA, 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. 142:469–475.
29. Choi BS, Jee HM, Park YH, Kim KW, Sohn MH, Kim KE. Relationship between exhaled nitric oxide concentration and pulmonary function/airway hyperresponsiveness in asthmatic children. Pediatr Allergy Respir Dis. 2009. 19:291–299.