Journal List > Allergy Asthma Respir Dis > v.3(6) > 1059142

Park, Lee, Yang, Yoon, Cho, Hong, and Yu: Exhaled nitric oxide and bronchial hyperresponsiveness in atopic asthmatic children with and without allergic rhinitis

Abstract

Purpose

Children with asthma frequently have allergic rhinitis (AR) as a comorbidity. Asthmatic children with AR have a higher exhaled nitric oxide (eNO) level and bronchial hyperresponsiveness (BHR) than those without. The purpose of this study is to investigate the difference in lung function, eNO, and BHR between atopic asthma with and without AR, and the association of eNO and BHR with atopic intensity in total asthmatics.

Methods

We recruited 69 atopic asthmatic children with AR, 19 atopic asthmatic children without AR, 38 children with AR, and 43 nonatopic controls. We measured forced expiratory volume in one second (FEV1) and forced expiratory flow at 25% to 75% of forced vital capacity (FEF25%-75%), dose response slope (DRS) of bronchial challenge with methacholine and adenosine 5'-monophosphate (AMP), the levels of eNO, and the ratio of sum of allergen wheal diameter to histamine using skin prick tests.

Results

Atopic asthmatic children with AR had a higher eNO level compared to those without AR (P<0.05). However, there was no difference in FEV1 %predicted, FEF25%-75% %predicted, methacholine DRS, and AMP DRS between asthmatic children with and without AR. In total asthmatics, methacholine DRS and AMP DRS significantly correlated with eNO levels (r=0.338, P<0.001; r=0.365, P<0.001), but not with total IgE levels. However, eNO significantly correlated with total IgE levels (r=0.479, P<0.001).

Conclusion

These results suggest that AR may enhance airway inflammation but may not lead to enhanced BHR in children with asthma.

Figures and Tables

Fig. 1

Venn diagram of study subjects.

aard-3-425-g001
Table 1

Baseline characteristics of study participants

aard-3-425-i001
Characteristic NAC AR Atopic asthma without AR Atopic asthma+AR
No. of patients 43 (25.4) 38 (22.5) 19 (11.2) 69 (40.8)
Sex
 Male:female 25:18 25:13 10:09 47:22
Age (mo) 108.6 ± 34.5 126.26 ± 38.2 86.89 ± 27.2 105.71 ± 38.9
Height (cm) 135.21 ± 17.8 143.13 ± 19.71 121.79 ± 15.25§ 131.62 ± 19.01
Weight (kg) 33.51 ± 12.7 41.76 ± 18.1 26.42 ± 12.3 32.29 ± 15.1
Blood eosinophil (%)* 2.43 (1.27-4.64) 3.34 (1.66-6.71) 4.63 (2.25-9.55) 5.29 (2.46-11.37)‡¶
Total IgE (IU/mL)* 48.89 (15.46-154.56) 163.09 (53.32-498.82) 195.34 (60.34-632.42) 418.45 (161.76-1,082.46)§¶**
SOW/H* 0.74 (0.64-0.86) 3.66 (2.37-5.65) 3.31 (2.08-5.28) 3.71 (2.51-5.5)
Asthma severity
 Mild intermittent - - 16 (84.2) 52 (75.4)
 Mild persistent - - 2 (10.5) 6 (8.7)
 Moderate persistent - - 1 (5.3) 10 (14.5)
 Severe persistent - - 0 (0.0) 1 (1.4)
Inhaled steroid use - - - -
 None - - 12 (63.2) 32 (46.4)
 Any use - - 7 (36.8) 37 (53.6)
Systemic steroid use - -
 None - - 18 (94.7) 67 (97.1)
 Any use - - 1 (5.3) 2 (2.9)

Values are presented as number (%), mean±standard deviation (SD), or geometric mean (range of 1SD).

NAC, nonatopic control; AR, allergic rhinitis; SOW/H, sum of wheal size in each allergen/histamine wheal size.

*P-values were adjusted for weight and for multiple comparisons by Bonferroni. P<0.01, compared to AR group. P<0.05, compared to AR group. §P<0.001, compared to AR group. P<0.05, compared to NAC group. P<0.001, compared to NAC group. **P<0.05, compared to atopic asthma without AR group.

Table 2

Lung function, bronchial hyperresponsiveness, and exhaled nitric oxide among the study groups

aard-3-425-i002
Variable NAC AR Atopic asthma without AR Atopic asthma+AR
No. of patients 43 (25.4) 38 (22.5) 19 (11.2) 69 (40.8)
FEV1 (%predicted) 106.81 ± 13.6 110.6 ± 11.1 100.62 ± 12.1 98.11 ± 12.7‡§
FVC (% predicted) 104.52 ± 13.2 108.61 ± 10.9 100.99 ± 16.2 102.38 ± 13.2
FEF25%-75% (% predicted) 110.1 ± 23.7 112.76 ± 25.7 92.89 ± 20.8∥† 85.98 ± 22.1§¶
DRS methacholine* 0.62 ± 0.15 0.62 ± 0.12 1.02 ± 0.35§¶ 1.04 ± 0.37§¶
DRS AMP* 0.51 ± 0.01 0.52 ± 0.01 0.72 ± 0.18†‡ 0.72 ± 0.27§¶
eNO (ppb)* 10.81 (6.26-18.67) 16.87 (8.74-32.55) 17.5 (9.38-32.63) 28.53 (14.84-54.86)§¶**

Values are presented as number (%), mean±standard deviation (SD), or geometric mean (range of 1SD).

NAC, nonatopic control; AR, allergic rhinitis; FEV1, forced expiratory volume in one second; FVC, functional vital capacity; FEF25%-75%, forced expiratory flow during 25%-75%; DRS, dose-response slope; AMP, adenosine 5'-monophosphate; eNO, exhaled nitric oxide.

*P-values were adjusted for weight and for multiple comparisons by Bonferroni. P<0.05, compared to AR group. P<0.01, compared to NAC group. §P<0.001, compared to AR group. P<0.05, compared to NAC group. P<0.001, compared to NAC group. **P<0.05, compared to atopic asthma without AR group.

Table 3

Correlation between lung function, bronchial hyperresponsiveness, and exhaled nitric oxide in subjects with atopic asthma

aard-3-425-i003
Variable FEV1 (%predicted) FEF25%-75% (%predicted) DRS methacholine DRS AMP eNO Total IgE SOW/H
FEF25%-75% 0.663*** - - - - - -
DRS methacholine -0.397*** -0.398*** - - - - -
DRS AMP -0.33*** -0.308** 0.667*** - - - -
eNO -0.277** -0.286** 0.338*** 0.365*** - - -
Total IgE -0.209* -0.122 0.168 0.146 0.479*** - -
SOW/H 0.094 0.100 0.116 0.281** 0.317*** 0.358*** -

Data are correlation coefficient (Pearson r) with controls for weight.

FEV1, forced expiratory volume in one second; FVC, functional vital capacity; FEF25%-75%, forced expiratory flow during 25%-75%; DRS, dose-response slope; AMP, adenosine 5'-monophosphate; eNO, exhaled nitric oxide; SOW/H, sum of wheal size in each allergen/histamine wheal size.

*P<0.05. **P<0.01. ***P<0.001.

References

1. Shim E, Yu J. Relationship between duration of disease and bronchial responsiveness in 6-8 years old children with asthma. Allergy Asthma Respir Dis. 2014; 2:23–28.
2. Pawankar R, Bunnag C, Khaltaev N, Bousquet J. Allergic rhinitis and its impact on asthma in asia pacific and the ARIA Update 2008. World Allergy Organ J. 2012; 5:Suppl 3. S212–S217.
3. Arga M, Bakirtas A, Topal E, Turktas I. Can exhaled nitric oxide be a surrogate marker of bronchial hyperresponsiveness to adenosine 5'-monophosphate in steroid-naive asthmatic children? Clin Exp Allergy. 2015; 45:758–766.
4. 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.
5. Hovland V, Riiser A, Mowinckel P, Carlsen KH, Carlsen KC. Asthma with allergic comorbidities in adolescence is associated with bronchial responsiveness and airways inflammation. Pediatr Allergy Immunol. 2014; 25:351–359.
6. Shim E, Lee E, Yang SI, Jung YH, Park GM, Kim HY, et al. The association of lung function, bronchial hyperresponsiveness, and exhaled nitric oxide differs between atopic and non-atopic asthma in children. Allergy Asthma Immunol Res. 2015; 7:339–345.
7. Kumar R, Gupta N, Goel N. Correlation of atopy and FeNO in allergic rhinitis: an Indian study. Indian J Chest Dis Allied Sci. 2013; 55:79–83.
8. 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.
9. Chawes BL, Bonnelykke K, Kreiner-Moller E, Bisgaard H. Children with allergic and nonallergic rhinitis have a similar risk of asthma. J Allergy Clin Immunol. 2010; 126:567–573.e1-8.
10. Suh DI, Lee JK, Kim CK, Koh YY. Bronchial hyperresponsiveness to methacholine and adenosine 5'-monophosphate, and the presence and degree of atopy in young children with asthma. Clin Exp Allergy. 2011; 41:338–345.
11. Urbano FL. Review of the NAEPP 2007 Expert Panel Report (EPR-3) on Asthma Diagnosis and Treatment Guidelines. J Manag Care Pharm. 2008; 14:41–49.
12. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012; 40:1324–1343.
13. Chinn S. Methodology of bronchial responsiveness. Thorax. 1998; 53:984–988.
14. L'Hermite N, Peyrat JF, Alami M, Brion JD. Synthesis and characterization of low generation halogenated linear poly(arylpropargyl)ether (PAPE) branches via selective palladium catalyzed coupling reactions. Tetrahedron Lett. 2005; 46:8987–8991.
15. Ciprandi G, Tosca MA, Capasso M. Exhaled nitric oxide in children with allergic rhinitis and/or asthma: a relationship with bronchial hyperreactivity. J Asthma. 2010; 47:1142–1147.
16. Baptist AP, Li L, Dichiaro CA. The importance of atopy on exhaled nitric oxide levels in African American children. Ann Allergy Asthma Immunol. 2015; 114:399–403.
17. Gemicioglu B, Musellim B, Dogan I, Guven K. Fractional exhaled nitric oxide (FeNo) in different asthma phenotypes. Allergy Rhinol (Providence). 2014; 5:157–161.
18. Mappa L, Cardinale F, Camodeca R, Tortorella ML, Pietrobelli A, Armenio L, et al. Exaled nitric oxide and air trapping correlation in asthmatic children. Allergy. 2005; 60:1436–1439.
19. Pin I, Godard P. Mechanisms of bronchial hyperreactivity: role of airway inflammation and atopy. Rev Mal Respir. 1994; 11:111–122.
20. Langley EW, Gebretsadik T, Hartert TV, Peebles RS Jr, Arnold DH. Exhaled nitric oxide is associated with severity of pediatric acute asthma exacerbations. J Allergy Clin Immunol Pract. 2014; 2:618–620.e1.
21. Takeyama K, Kondo M, Tagaya E, Kirishi S, Ishii M, Ochiai K, et al. Budesonide/formoterol maintenance and reliever therapy in moderate-to-severe asthma: effects on eosinophilic airway inflammation. Allergy Asthma Proc. 2014; 35:141–147.
22. Perzanowski MS, Yoo Y. Exhaled nitric oxide and airway hyperresponsiveness to adenosine 5'-monophosphate and methacholine in children with asthma. Int Arch Allergy Immunol. 2015; 166:107–113.
23. 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, 2005. Am J Respir Crit Care Med. 2005; 171:912–930.

Supplementary Material

Supplement Table 1

Lung function, bronchial hyperresponsiveness, and exhaled nitric oxide among the study groups after correction with IgE