Comparison between exhaled nitric oxide and bronchial challenge with methacholine or adenosine-5'-monophosphate in the diagnosis of childhood asthma

Jisun Yoon; Jun-Sung Park; Hyun-Ju Cho; Eun Lee; Song-I Yang; Soo-Jong Hong; Jinho Yu

doi:10.4168/aard.2016.4.2.100

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Yoon, Park, Cho, Lee, Yang, Hong, and Yu: Comparison between exhaled nitric oxide and bronchial challenge with methacholine or adenosine-5'-monophosphate in the diagnosis of childhood asthma

Original Article

Allergy, Asthma & Respiratory Disease 2016; 4(2): 100-106.

Published online: 31 March 2016

DOI: https://doi.org/10.4168/aard.2016.4.2.100

Comparison between exhaled nitric oxide and bronchial challenge with methacholine or adenosine-5'-monophosphate in the diagnosis of childhood asthma

Jisun Yoon¹, Jun-Sung Park¹, Hyun-Ju Cho¹, Eun Lee¹, Song-I Yang², Soo-Jong Hong¹, Jinho Yu¹

¹Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

²Department of Pediatrics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.

Correspondence to: Jinho Yu. Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Tel: +82-2-3010-3922, Fax: +82-2-473-3725, jyu3922@gmail.com

Received 16 July 2015 Revised 9 September 2015 Accepted 25 September 2015

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).

Abstract

Purpose

Asthma is a chronic airway inflammatory disease characterized by bronchial hyperresponsiveness and reversible airway obstruction. Bronchial challenge with methacholine or adenosine-5'-monophosphate (AMP) has been used to diagnose asthma. Recently, measurement of exhaled nitric oxide (eNO) can also be used for the diagnosis of asthma. The aim of this study was to compare the diagnostic value for asthma between challenge with methacholine or AMP and eNO in children with chronic nonspecific respiratory symptoms.

Methods

One hundred thirty-three children who have chronic nonspecific respiratory symptoms were enrolled. Bronchial challenge with methacholin and AMP were performed, and eNO was measured in all subjects. Subjects were defined as asthma based on the clinical symptoms and bronchodilator response during follow-up of at least 3 months after test.

Results

Thirty-three subjects (34%) were finally diagnosed as asthma among 97 patients after 3-month follow-up. The area under the receiver operating characteristic curves for the diagnosis of asthma were 0.903 (95% confidence interval [CI], 0.838-0.969; P<0.001) for methacholline challenge, 0.867 (95% CI, 0.783-0.950; P<0.001) for AMP challenge, and 0.588 (95% CI, 0.467-0.709, P=0.156) for eNO measurement. The cutoff values of these tests were methacholine PC₂₀ (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second) 12.0 mg/mL (sensitivity, 87.9%; specificity, 82.8%), AMP PC₂₀ 566.2 mg/mL (sensitivity, 84.8%; specificity, 85.9%), and eNO 18.5 ppb (sensitivity, 45.5%; specificity, 71.9%).

Conclusion

Measurement of eNO may be inferior to challenge with methacholine and AMP for the diagnosis of asthma in children.

Keywords: Asthma, Child, Nitric oxide, Bronchial challenge tests

Figures and Tables

Fig. 1

Recruitment and follow-up of study subjects. PFT, pulmonary function test; Mch, methacholine; AMP, adenosine 5'-monophosphate; eNO, exhaled nitric oxide; SPT, skin prick test. ^*Bronchopulmonary dysplasia, bronchiolitis obliterans, congenital heart disease.

Fig. 2

Receiver operation characteristic curve for methacholine PC₂₀. PC₂₀, provocative concentration causing a 20% fall in the forced expiratory volume in one second decrease; AUC, area under curve; CI, confidence interval.

Fig. 3

Receiver operation characteristic curve for AMP PC₂₀. AMP, adenosine-5'-monophosphate; PC₂₀, provocative concentration causing a 20% fall in the forced expiratory volume in one second decrease; AUC, area under curve; CI, confidence interval.

Fig. 4

Receiver operation characteristic curve for exhaled nitric oxide. AUC, area under curve; CI, confidence interval.

Table 1

Baseline characteristics of study subjects

Characteristic	Asthma (n = 33)	Nonasthma (n = 64)
Sex
Male:female	18:15	36:28
Age (yr)	6.7 ± 2.3^**	9.2 ± 3.1
Height (cm)	119.7 ± 15.9^**	135.3 ± 19.0
Weight (kg)	25.2 ± 14.0^**	35.2 ± 15.3
Body mass index (kg/m²)	16.4 ± 1.2^*	18.1 ± 1.2
Total IgE (kU/L)	295.0 (93.5-930.2)^**	71.3 (18.8-270.6)
Blood eosinophil (%)	3.6 (1.5-8.5)	2.6 (1.1-6.2)
Atopy	28 (84.8)^**	28 (44.8)
Atopic dermatitis	24 (72.7)^**	8 (12.5)
Allergic rhinitis	18 (54.5)	33 (51.6)
Family history of asthma	5 (15.2)	1 (1.6)

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

^*P<0.05, compared to nonasthma group. ^**P<0.001, compared to nonasthma group.

Table 2

Lung function, bronchial hyperresponsiveness, and exhaled nitric oxide between asthmatic and nonasthmatic children

Variable	Asthma (n = 33)	Nonasthma (n = 64)
FEV₁ %pred	104.5 ± 12.0	108.1 ± 13.1
FVC %pred	109.4 ± 12.1	106.1 ± 11.5
FEV₁/FVC	0.87 ± 0.08	0.90 ± 0.06
Mch PC₂₀ (mg/mL)	3.8 (1.3-11.6)^**	30.9 (12.2-78.5)
Mch PC₂₀ ≤ 16 mg/mL	30 (90.9)^**	13 (20.3)
AMP PC₂₀ (mg/mL)	68.1 (15.0-309.3)^**	566.3 (225.5-1,422.1)
AMP PC₂₀ ≤ 200 mg/mL	27 (81.8)^**	8 (12.5)
eNO (ppb)	17.0 (8.7-33.1)	13.8 (7.5-25.6)

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

FEV₁, forced expiratory volume in one second; %pred, percentage predicted; FVC, forced vital capacity; Mch, methacholine; PC₂₀, provocative concentration causing a 20% fall in the FEV₁; AMP, adenosine-5'-monophosphate; eNO, exhaled nitric oxide.

^**P<0.001, compared to nonasthma group.

Table 3

Cutoff values of eNO measurement and bronchial challenge with methacholine and AMP for the diagnosis of asthma

Variable	Cutoff value	Sensitivity (%)	Specificity (%)
Mch (mg/mL)	≤ 12.0	87.9	82.8
AMP (mg/mL)	≤ 566.2	84.8	85.9
eNO (ppb)	> 18.5	45.5	71.9

eNO, exhaled nitric oxide; Mch, methacholine; AMP, adenosine 5'-monophosphate.

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ORCID iDs: Jinho Yu
https://orcid.org/http://orcid.org/0000-0002-1226-8077
Similar articles

Comparison between exhaled nitric oxide and bronchial challenge with methacholine or adenosine-5'-monophosphate in the diagnosis of childhood asthma

Abstract

Purpose

Methods

Results

Conclusion

Figures and Tables

Fig. 1

Recruitment and follow-up of study subjects. PFT, pulmonary function test; Mch, methacholine; AMP, adenosine 5'-monophosphate; eNO, exhaled nitric oxide; SPT, skin prick test. *Bronchopulmonary dysplasia, bronchiolitis obliterans, congenital heart disease.

Fig. 2

Receiver operation characteristic curve for methacholine PC20. PC20, provocative concentration causing a 20% fall in the forced expiratory volume in one second decrease; AUC, area under curve; CI, confidence interval.

Fig. 3

Receiver operation characteristic curve for AMP PC20. AMP, adenosine-5'-monophosphate; PC20, provocative concentration causing a 20% fall in the forced expiratory volume in one second decrease; AUC, area under curve; CI, confidence interval.

Fig. 4

Receiver operation characteristic curve for exhaled nitric oxide. AUC, area under curve; CI, confidence interval.

Table 1

Baseline characteristics of study subjects

Table 2

Lung function, bronchial hyperresponsiveness, and exhaled nitric oxide between asthmatic and nonasthmatic children

Table 3

Cutoff values of eNO measurement and bronchial challenge with methacholine and AMP for the diagnosis of asthma

References

Recruitment and follow-up of study subjects. PFT, pulmonary function test; Mch, methacholine; AMP, adenosine 5'-monophosphate; eNO, exhaled nitric oxide; SPT, skin prick test. ^*Bronchopulmonary dysplasia, bronchiolitis obliterans, congenital heart disease.

Receiver operation characteristic curve for methacholine PC₂₀. PC₂₀, provocative concentration causing a 20% fall in the forced expiratory volume in one second decrease; AUC, area under curve; CI, confidence interval.

Receiver operation characteristic curve for AMP PC₂₀. AMP, adenosine-5'-monophosphate; PC₂₀, provocative concentration causing a 20% fall in the forced expiratory volume in one second decrease; AUC, area under curve; CI, confidence interval.