Journal List > Allergy Asthma Respir Dis > v.3(4) > 1059111

Seo, Lee, Cho, Baek, Lee, Shin, Jee, Jung, and Han: Relationship between exhaled nitric oxide and small-airway dysfunction in children with asthma using spirometry and the impulse oscillometry system

Abstract

Purpose

Fractional exhaled nitric oxide (FeNO) is a maker of airway inflammation, and impedance of low frequency in the impulse oscillometry system (IOS) reflects small-airway obstruction. We investigated the association of the FeNO level with IOS parameters and spirometry results in asthma patients.

Methods

Fifty-eight children with asthma (60.3%, male), mean age 8.3 years (range, 4.5–16.0 years), were enrolled in the study. Reactance and resistance at 5 Hz with IOS, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow 25%–75% of the vital capacity (FEF25%-75%) with spirometry and FeNO were measured in all patients. The Z-score of spirometry and IOS parameters and the mean level of FeNO were used for correlation and regression analysis.

Results

FeNO was not significantly associated with height, age, or other demographic parameters. There was a statistically significant correlation between spirometry results and IOS measurements. The FeNO level was not significantly correlated with IOS variables. After adjusting for height, sex, atopic status, and the use of inhaled corticosteroid, the FeNO level showed significant correlations with Z-score of FEV1/FVC (P=0.037, adjusted R2 =0.234).

Conclusion

FeNO was significantly correlated with Z-scores of FEV1/FVC, but not with IOS variables. Therefore, FeNO may be used to detect whole airway obstruction, but not small-airway obstruction.

References

1. Olaguibel Rivera JM, Alvarez Puebla MJ, Arroabarren Aleman E, Cambra K, Uribe San Martin MP, De Esteban Chocarro B. Spirometric and exhaled nitric oxide reference values in preschool children from the community of Navarra. J Investig Allergol Clin Immunol. 2014; 24:169–76.
2. 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; 184:602–15.
crossref
3. 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; 169:473–8.
4. van der Wiel E, ten Hacken NH, Postma DS, van den Berge M. Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: a systematic review. J Allergy Clin Immunol. 2013; 131:646–57.
crossref
5. Scichilone N, Contoli M, Paleari D, Pirina P, Rossi A, Sanguinetti CM, et al. Assessing and accessing the small airways; implications for asthma management. Pulm Pharmacol Ther. 2013; 26:172–9.
crossref
6. Komarow HD, Myles IA, Uzzaman A, Metcalfe DD. Impulse oscillometry in the evaluation of diseases of the airways in children. Ann Allergy Asthma Immunol. 2011; 106:191–9.
crossref
7. Fujisawa T, Yasui H, Akamatsu T, Hashimoto D, Enomoto N, Inui N, et al. Alveolar nitric oxide concentration reflects peripheral airway obstruction in stable asthma. Respirology. 2013; 18:522–7.
crossref
8. Ko HS, Chung SH, Choi YS, Choi SH, Rha YH. Relationship between exhaled nitric oxdie and pulmonary function test in children with asthma. Korean J Pediatr. 2008; 51:181–7.
9. del Giudice MM, Brunese FP, Piacentini GL, Pedulla M, Capristo C, Deci-mo F, et al. Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in naïve atopic asthmatic children. J Asthma. 2004; 41:759–65.
crossref
10. Spergel JM, Fogg MI, Bokszczanin-Knosala A. Correlation of exhaled nitric oxide, spirometry and asthma symptoms. J Asthma. 2005; 42:879–83.
crossref
11. Malmberg LP, Petays T, Haahtela T, Laatikainen T, Jousilahti P, Vartiainen E, et al. Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference values. Pediatr Pulmonol. 2006; 41:635–42.
crossref
12. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005; 26:319–38.
13. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multiethnic reference values for spirometry for the 3–95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012; 40:1324–43.
crossref
14. Seo HK, Chang SJ, Jung DW, Wee YS, Jee HM, Han MY, et al. The quality control and acceptability of spirometry in preschool children. Korean J Pediatr. 2009; 52:1267–72.
crossref
15. Oostveen E, MacLeod D, Lorino H, Farre R, Hantos Z, Desager K, et al. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003; 22:1026–41.
crossref
16. Larsen GL, Morgan W, Heldt GP, Mauger DT, Boehmer SJ, Chinchilli VM, et al. Impulse oscillometry versus spirometry in a longterm study of controller therapy for pediatric asthma. J Allergy Clin Immunol. 2009; 123:861–7.e1.
crossref
17. Quanjer PH, Weiner DJ. Interpretative consequences of adopting the Global Lungs 2012 reference equations for spirometry for children and adolescents. Pediatr Pulmonol. 2014; 49:118–25.
crossref
18. 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; 30:385–92.
19. 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; 170:426–32.
20. Ramsey CD, Celedon JC, Sredl DL, Weiss ST, Cloutier MM. Predictors of disease severity in children with asthma in Hartford, Connecticut. Pediatr Pulmonol. 2005; 39:268–75.
crossref

Table 1.
Clinical characteristics of the study group (n=58)
Characteristic Value
Age (yr) 8.27±2.53
Male sex 35 (60.3)
Height (cm) 130.7±18.7
Atopic status 43 (74.1)
Parental asthma 8 (13.8)
FeNO (ppb) 18.74±14.59
Spirometry  
FEV1/FVC (%) 79.90±7.26
FEV1/FVC, Z-score –1.42±1.02
FEV1, Z-score –1.16±1.62
FVC, Z-score –0.42±1.60
FEF25%-75%, Z-score –1.36±1.19
Impulse oscillometry system  
Rrs5, Z-score 0.81±1.06
Xrs5, Z-score –0.04±0.65
AX, Z-score –0.09±0.84

Values are presented as mean±standard deviation or number (%).

FeNO, fractional exhaled nitric oxide; ppb, parts per billion; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; FEF25%-75%, forced expiratory flow at 25%–75% of vital capacity; IOS, impulse oscillometry system; Rrs5, resistance at 5 Hz; Xrs5, reactance at 5 Hz; AX, reactance area.

Table 2.
Correlation matrix of spirometry and ISO value, FeNO
  FEV1 FVC FEV1/FVC FEF25%-75% Rrs5 Xrs5 AX FeNO
FEV1 1 0.896** 0.596** 0.883** 0.469** 0.560** 0.518** –0.065
FVC   1 0.224 0.629** 0.318* 0.463** 0.375* 0.023
FEV1/FVC     1 0.842** 0.476** 0.452** 0.427* –0.283
FEF25%-75%       1 0.516** 0.584** 0.577** –0.195
Rrs5         1 0.634** 0.799** –0.141
Xrs5           1 0.874** 0.021
AX             1 0.030
FeNO               1

IOS, impulse oscillometry system; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; FEF25%-75%, forced expiratory flow at 25%–75% of vital capacity; Rrs5, resistance at 5 Hz; Xrs5, reactance at 5 Hz; AX, reactance area. *P<0.05. **P<0.001; spirometrc and IOS value represents the Z-score.

Table 3.
Multiple linear regression with determinant of fractional exhaled nitric oxide
  Intercept (SE) R2 B P-value
FEV1 Z-score 29.38 (16.61) 0.168 –0.365 0.749
FVC Z-score –30.84 (16.65) 0.170 0.493 0.664
FEV1/FVC pred. –31.93 (15.89) 0.167 –24.085 0.929
FEV1/FVC Z-score –29.02 (16.38) 0.234 –3.839 0.037
FEF25%-75% Z-score –34.14 (17.01) 0.185 –1.697 0.278
Rrs5 Z-score –31.04 (17.17) 0.180 1.527 0.350
Xrs5 Z-score –32.41 (18.09) 0.167 0.689 0.806
AX Z-score –29.38 (16.61) 0.168 0.800 0.734

Adjusting the confounding factor; height, sex, atopic status, and inhaled corticosteroid. SE, standard error; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; FEV1/FVC pred., predicted value of FEV1/FVC; FEF25%-75%, forced expiratory flow at 25%–75% of vital capacity; Rrs5, resistance at 5 Hz; Xrs5, reactance at 5 Hz; AX, reactance area.

TOOLS
Similar articles