Journal List > Allergy Asthma Respir Dis > v.4(2) > 1059162

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

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.

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.

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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.

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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.

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Fig. 4

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

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Table 1

Baseline characteristics of study subjects

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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

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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

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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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