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Abstract
Purpose
Exercise-induced bronchoconstriction (EIB) affects daily activities as well as school performance in children. Exhaled nitric oxide (eNO) is a noninvasive test that measures airway inflammation in asthmatics. The aim of this study was to address the relationship between eNO and childhood EIB.
Methods
Our study consisted of 101 children aged 6 to 18 years belonging to one of three groups, asthmatic children with EIB (n=31), asthmatic children without EIB (n=28), or healthy controls (n=42). After children were taken off drugs that treated their asthma, baseline (pre-exercise) eNO and biomarkers of inflammation were measured. All subjects underwent spirometry and the bronchial challenge by methacholine inhalation and outdoor free running.
Results
eNO levels in asthmatic children with EIB were significantly greater than those in both asthmatic children without EIB (P=0.012) and controls (P<0.001). The median eNO (interquartile range) levels were 26.0 (15.0 to 46.0) parts per billion (ppb) in asthmatic children with EIB, 16.0 (12.5 to 28.0) ppb in asthmatic children without EIB, and 12.0 (10.0 to 15.3) ppb in controls. Postexercise decrease of forced expiratory volume in 1 second correlated positively with eNO (r=0.637, P<0.001; r, partial correlation coefficient adjusted for age and height). The cutoff value for prediction of significant EIB was 20 ppb, and the overall sensitivity, specificity, positive predictive value, and negative predictive values were 61.3%, 80.0%, 57.6%, and 82.4%, respectively. The area under the receiver operating characteristic curve was 0.767 (95% confidence interval, 0.661 to 0.874).
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 | Fig. 1.(A) Exhaled nitric oxide (eNO) levels of study subjects. (B) Association between post-exercise decrease of forced expiratory volume in 1 second (FEV1) and eNO levels (r=0.637, r=partial correlation coefficient adjusted for age and height, P <0.001). ppb, parts per billion; EIB, exercise-induced bronchoconstriction. |
 | Fig. 2.Receiver operating characteristic curve for exhaled nitric oxide (eNO) predicting exercise-induced bronchoconstriction with representative values. AUC, area under curve; SE, standard error; CI, confidence interval. |
Table 1.
Characteristics of Children Studied, Baseline Values and Biomarkers
| Asthmatics | Healthy controls (n=42) | P -value∗ | ||
|---|---|---|---|---|
| With EIB (n=31) | Without EIB (n=28) | |||
| Age (yr) | 10.3 2.0 ± | 9.6 2.6 ± | 9.9 2.2 ± | 0.970 |
| Sex, male (%) | 68.4 | 69.6 | 56.4 | 0.312† |
| Parental smoking (%) | 19.3 | 16.7 | 14.3 | 0.124‡ |
| Clinical features (%) | ||||
| Prior ICS use | 54.8 | 46.4 | NA | 0.078‡ |
| Allergic rhinitis | 61.3 | 50.0 | NA | 0.097‡ |
| Atopy | 84.2 | 82.6 | NA | 0.707‡ |
| Baseline | ||||
| FEV1, pred % | 86.2 14.9 ± | 84.3 21.1 ± | 99.3 11.8 ± | 0.548 |
| FVC, pred % | 98.7 9.5 ± | 95.5 11.3 ± | 97.5 12.4 ± | 0.029 |
| FEV1/FVC ratio | 80.0 9.2 ± | 83.8 16.5 ± | 92.0 5.3 ± | 0.019 |
| FEF25-75, pred % | 68.3 23.2 ± | 72.0 27.2 ± | 92.5 15.0 ± | <0.001 |
| Postbronchodilator FEV ∆ 1, pred % | 11.2 5.3 ± | 11.7 5.9 ± | NA | 0.964§ |
| PC20, mg/mL | 4.8 4.9 ± | 11.7 5.9 ∫ | NA | <0.001§ |
| Post-exercise decrease in FEV1 | 27.7 (19.6–32.9)∫ | 9.0 (4.7–10.6) | 7.7 (5.1–10.0) | <0.001 |
| PB eosinophil, /mL | 480 (245–780) | 300 (140–467) | 125 (95–175) | 0.002 |
| ECP, ng/mL | 33.2 (23.5–63.4) | 23.7 (14.1–51.2) | 11.1 (5.6–23.1) | <0.001 |
| Total IgE, IU/mL | 446.9 (205.3–995.0) | 225.0 (80.0–394.3) | 55.9 (28.2–141.5) | 0.002 |
EIB, exercise-induced bronchoconstriction; ICS, inhaled corticosteroid; FEV1, forced expiratory volume in 1 second; pred %, predicted %; FVC, forced vital capacity; FEF, forced expiratory flow, midexpiratory phase; PC20, provocative concentration of methacholine inducing a 20% fall in FEV1; PB, peripheral blood; ECP, eosinophil cationic protein; NA, not applicable.
Table 2.
Partial Correlation Coefficients in Asthma Subject
| Exhaled nitric oxide (ppb) | ||
|---|---|---|
| r∗ | P -value | |
| FEV1, pred % | 0.160 | 0.227 |
| FVC, pred % | –0.111 | 0.537 |
| FEV1/FVC ratio | –0.307 | 0.018 |
| FEF25-75, pred % | –0.369 | 0.002 |
| Postbronchodilator FEV ∆ 1, pred % | 0.322 | 0.029 |
| Methacholine PC20, mg/mL | –0.223 | 0.132 |
| PB eosinophil, /mL | 0.508 | <0.001 |
| ECP, ng/mL | 0.202 | 0.138 |
| Total IgE, IU/mL | 0.475 | <0.001 |
ppb, parts per billion; FEV1, forced expiratory volume in 1 second; pred %, predicted %; FVC, forced vital capacity; FEF25–75, forced expiratory flow, midexpiratory phase; PC20, provocative concentration of methacholine inducing a 20% fall in FEV1; PB, Peripheral blood; ECP, eosinophil cationic protein.
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