Journal List > Allergy Asthma Respir Dis > v.4(1) > 1059168

Lim, Kim, Lim, Park, Choung, and Yoo: Relationships between fractional exhaled nitric oxide levels and FEF25%–75% in children with asthma

Abstract

Purpose

Fractional exhaled nitric oxide (FeNO) is considered an indirect marker of airway inflammation, and forced expiratory flow between 25% and 75% of vital capacity (FEF25%–75%) is widely used as a sensitive indicator of small airway obstruction in asthma. The aim of this study was to investigate relationships between FeNO and FEF25%–75% in children with asthma.

Methods

A total of 118 children with asthma underwent spirometry and measurement of eosinophil markers. FeNO levels were measured, and skin prick tests to 13 common allergens were done. Study subjects were divided into 2 groups according to FEF25%–75% values (group 1, normal FEF25%–75%≥65%pred, n=90; group 2, impaired FEF25%–75%<65%pred, n=28).

Results

The mean (±standard deviation, SD) age was not significantly different between groups 1 and 2 (10.3±2.8 years vs. 11.1±3.4 years), and the sex ratio was also not significantly different between 2 groups. The geometric mean (range of 1 SD) concentration of FeNO was significantly higher in group 2 than in group 1 (25.8 ppb [14.2–46.9 ppb] vs. 37.2 ppb [24.2–57.2 ppb], P=0.008). A significant inverse correlation between FeNO and FEF25%–75% was observed in group 2 (r=–0.493, P=0.038), but not in group 1 (r=–0.037, P=0.749) after adjustment for confounders, such as atopy, age, sex, weight, and height.

Conclusion

FeNO levels were higher in group of asthmatic children with impaired FEF25%–75% level. FeNO levels were inversely correlated with FEF25%–75% only in impaired small-airway obstruction group after adjustment for atopy. These results suggest that small-airway obstruction may relate more closely to airway inflammation in asthmatic children with impaired small-airway function.

Figures and Tables

Fig. 1

FeNO values do not correlate with FEV1 %pred (r=–0.144, P=0.154; A), FVC %pred (r=–0.049, P=0.627; B) and FEV1/FVC (r=–0.195, P=0.053; C), but show significantly inverse correlation with FEF25%–75% %pred (r=–0.211, P=0.035; D) in total asthmatic children. FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF25%–75%, forced expiratory flow between 25% and 75% of vital capacity.

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Fig. 2

FeNO values show significant correlation with neither FEV1 %pred (r=–0.018, P=0.878; A), FVC %pred (r=–0.072, P=0.534; B), FEV1/FVC (r=–0.104, P=0.367; C) nor FEF25%–75% %pred (r=–0.037, P=0.749; D) in children with group 1 (normal FEF25%–75%, ≥65%pred). FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF25%–75%, forced expiratory flow between 25% and 75% of vital capacity.

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Fig. 3

FeNO values do not correlate with inversely correlate with with FEV1 %pred (r=–0.066, P=0.795; A) or FVC %pred (r=0.179, P=0.477; B), but show significant FEV1/FVC (r=–0.566, P=0.014; C), and FEF25%–75% %pred (r=–0.493, P=0.038; D) in children with group 2 (impaired FEF25%–75%, <65%pred). FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF25%–75%, forced expiratory flow between 25% and 75% of vital capacity.

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Table 1

Clinical characteristics in children with asthma

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Characteristic Group 1 (n = 90) Group 2 (n = 28) Total (n = 118) P-value
Age (yr) 10.3 ± 2.8 11.1 ± 3.4 10.5 ± 2.9 0.229
Boys 58 (64.4) 19 (67.9) 77 (65.3) 0.823
Atopy 65 (79.3) 20 (86.9) 85 (80.9) 0.553
Body mass index (kg/m2) 19.4 ± 3.9 20.8 ± 3.9 19.7 ± 3.9 0.108
FEV1 %pred 93.6 ± 10.6 71.2 ± 15.9 88.3 ± 15.3 <0.001
FVC %pred 97.7 ± 12.1 88.2 ± 18.9 95.5 ± 14.5 0.017
FEV1/FVC 88.2 ± 4.9 74.5 ± 8.2 84.9 ± 14.5 <0.001
FEF25%-75% %pred 97.5 ± 17.7 47.8 ± 13.4 85.7 ± 27.0 <0.001
Eosinophil (%) 3.6 (1.3–9.8) 4.2 (2.5–7.3) 3.7 (1.5–9.3) 0.783
ECP (µg/L) 17.6 (5.9–52.0) 17.2 (7.6–39.4) 17.5 (6.3–48.8) 0.320
FeNO (ppb) 25.8 (14.2–46.9) 37.2 (24.2–57.2) 28.2 (15.7–50.4) 0.006

Valus are presented as mean±standard deviation, number (%), or geometric mean (range).

Group 1, normal FEF25%–75% group (FEF25%–75%≥65%pred); group 2, impaired FEF25%–75% group (FEF25%–75%<65%pred); FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF25%–75%, forced expiratory flow between 25% and 75% of vital capacity; ECP, eosinophil cationic protein; FeNO, fractional exhaled nitric oxide.

Table 2

Comparison of clinical characteristics between atopy and nonatopy group

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Characteristic Atopy group (n = 85) Nonatopy group (n = 20) P-value
Age (yr) 10.7 ± 2.8 10.0 ± 2.9 0.338
Boys 55 (67.0) 10 (50.0) 0.154
Body mass index (kg/m2) 19.8 ± 3.7 19.6 ± 4.8 0.843
FEV1 %pred 88.0 ± 14.8 90.9 ± 12.8 0.432
FVC %pred 95.5 ± 14.5 98.0 ± 13.3 0.500
FEV1/FVC 94.8 ± 7.7 85.3 ± 8.6 0.821
FEF25%-75% %pred 85.1 ± 27.1 88.8 ± 22.3 0.575
Eosinophil (%) 2.4 (2.25–2.47) 1.5 (1.36–1.57) 0.001
ECP (µg/L) 20.6 (8.3–51.1) 7.9 (2.7–23.5) <0.001
FeNO (ppb) 31.7 (20.1–49.9) 17.8 (8.7–36.4) 0.003

Valus are presented as mean±standard deviation, number (%), or geometric mean (range).

FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FEF25%–75%, forced expiratory flow between 25% and 75% of vital capacity; ECP, eosinophil cationic protein; FeNO, fractional exhaled nitric oxide.

Notes

This study was supported in part by grants from the Environmental Health Center for Childhood Asthma (2014) and the Allergy Immunology Center, Korea University, Korea.

References

1. International consensus report on diagnosis and treatment of asthma. National Heart, Lung, and Blood Institute, National Institutes of Health. Bethesda, Maryland 20892. Publication no. 92-3091, March 1992. Eur Respir J. 1992; 5:601–641.
2. Pyun BY. Guideline for the management of childhood asthma. J Korean Pediatr Soc. 2001; 44:727–731.
3. Bacharier LB, Strunk RC, Mauger D, White D, Lemanske RF Jr, Sorkness CA. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med. 2004; 170:426–432.
4. McFadden ER Jr, Linden DA. A reduction in maximum mid-expiratory flow rate. a spirographic manifestation of small airway disease. Am J Med. 1972; 52:725–737.
5. Gibb ER, Thyne SM, Kaplan DN, Ly NP. Asthma, FEF25–75, and hospitalizations in children. Pediatr Allergy Immunol Pulmonol. 2013; 26:115–121.
6. Barnes PJ, Liew FY. Nitric oxide and asthmatic inflammation. Immunol Today. 1995; 16:128–130.
crossref
7. Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993; 6:1368–1370.
8. 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.
crossref
9. 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.
crossref
10. 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.
crossref
11. 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.
12. 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.
crossref
13. 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.
crossref
14. Kim JO, Woo SI, Hahn YS. Relevance of exhaled nitric oxide levels to asthma control test scores and spirometry values in children with atopic asthma. Pediatr Allergy Respir Dis. 2011; 21:24–31.
crossref
15. National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol. 2007; 120:5 Suppl. S94–S138.
16. Cockcroft DW. Bronchoprovocation methods: direct challenges. Clin Rev Allergy Immunol. 2003; 24:19–26.
crossref
17. Ciprandi G, Tosca MA, Cirillo I, Lionetti E, Leonardi S, Miraglia Del Giudice M, et al. Impaired FEF25-75 may predict high exhaled nitric oxide values in children with allergic rhinitis and/or asthma. J Biol Regul Homeost Agents. 2012; 26:1 Suppl. S27–S33.
18. Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med. 1995; 152:1107–1136.
19. Park CH, Kim HB, Jung YH, Lee E, Yang SI, Seo JH, et al. Predicted normal values of pulmonary function tests in normal Korean children. Allergy Asthma Respir Dis. 2014; 2:187–193.
crossref
20. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005; 26:319–338.
crossref
21. 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.
crossref
22. Johansson SG, Yman L. In vitro assays for immunoglobulin E. Methodology, indications, and interpretation. Clin Rev Allergy. 1988; 6:93–139.
23. del Giudice MM, Brunese FP, Piacentini GL, Pedulla M, Capristo C, Decimo F, et al. Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in naïve atopic asthmatic children. J Asthma. 2004; 41:759–765.
crossref
24. 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.
crossref
25. Sampson AP. The role of eosinophils and neutrophils in inflammation. Clin Exp Allergy. 2000; 30:Suppl 1. 22–27.
crossref
26. Prasad A, Langford B, Stradling JR, Ho LP. Exhaled nitric oxide as a screening tool for asthma in school children. Respir Med. 2006; 100:167–173.
crossref
27. Joseph-Bowen J, de Klerk N, Holt PG, Sly PD. Relationship of asthma, atopy, and bronchial responsiveness to serum eosinophil cationic proteins in early childhood. J Allergy Clin Immunol. 2004; 114:1040–1045.
crossref
28. Paredi P, Kharitonov SA, Meah S, Barnes PJ, Usmani OS. A novel approach to partition central and peripheral airway nitric oxide. Chest. 2014; 145:113–119.
crossref
29. Pedroletti C, Zetterquist W, Nordvall L, Alving K. Evaluation of exhaled nitric oxide in schoolchildren at different exhalation flow rates. Pediatr Res. 2002; 52:393–398.
crossref
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Young Yoo
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