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Abstract
Purpose
Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. Several BHR studies comparing groups of atopic and nonatopic asthmatics have reported conflicting results. The aim of this study was to compare BHR to indirect
Methods
We performed a retrospective analysis of data from 110 children with asthma, aged 6–18 years using skin prick tests, and serum total and specific IgE levels. Atopy degree was measured using the sum of graded wheal size or the sum of the allergen-spe-cific IgE. Bronchial provocation tests (BPTs) using methacholine were performed on all subjects. BPTs using indirect simuli, including exercise and mannitol, were also performed.
Results
Asthma cases were classified as atopic asthma (n=83) or nonatopic asthma (n=27) from skin prick or allergen-specific IgE test results. There was no significant difference in the prevalence of BHR to mannitol or exercise between atopic and nonatopic asthmatics. Atopic asthma had a significantly lower postexercise maximum decrease in % forced expiratory volume in 1 second (FEV1) (geometric mean [95% confidence interval]: 31.9 [22.9–40.9] vs. 14.0 [9.4–18.6], P=0.015) and a methacholine PC20 (provocative concentration of methacholine inducing a 20% fall in FEV1) than nonatopic asthmatics (geometric mean [95% confidence interval]: 1.24 [0.60–1.87] ng/mL vs. 4.97 [3.47–6.47]) ng/mL, P=0.001), whereas mannitol PD15 (cumulative provocative dose causing a 15% fall in FEV1) was not significantly different between the 2 groups.
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 | Fig. 1.Number of study subjects who underwent that bronchial provocation tests in atopic asthma group (n=83) (A) and nonaopic asthma group (n=27) (B). |
 | Fig. 2.Correlations between mannitol PD15, postexercise maximum decrease in FEV1, and methacholine PC20. The manntiol challenge was completed when a ≥15% fall in FEV1 from baseline occurred, which was considered to be a positive response, or when the maximum cumulative dose of mannitol (635 mg) was administered. An exercise bronchoprovocation test was used for EIB diagnosis, which was considered positive with a 10% or greater decrease in FEV1 after exercise. (A) Mannitol PD15 was significantly correlated with methacholine PC20 in asthmatic subjects (n=59, r=0.538, P<0.001). (B) Postexercise maximum decrease in FEV1 in asthmatic subjects was significantly correlated with methacholine PC20 in asthmatic subjects (n=69, r=-0.294, P=0.014). (C) Postexercise maximum decrease in FEV1 was significantly correlated with mannitol PD15 in asthmatic subjects (n=14, r=-0.474, P=0.030). PD15, cumulative provocative dose causing a 15% fall in FEV1; PC20, provocative concentration of methacholine inducing a 20% fall in FEV1; FEV1, forced expiratory volume in 1 second; EIB, exercise induced bronchoconstriction. r=Spearman correlation coefficients. |
Table 1.
Characteristics of the subjects included in the study
| Characteristic | Atopic asthma (n=83) | Nonatopic asthma (n=27 ) | P-value∗ |
|---|---|---|---|
| Age (yr) | 9.50±3.11 | 9.11±2.44 | 0.955 |
| Height (cm) | 136.50±18.95 | 138.48±18.24 | 0.274 |
| Weight (kg) | 38.52±17.33 | 39.00±14.92 | 0.424 |
| Body mass index (kg/m2) | 20.25±3.50 | 19.27±3.82 | 0.925 |
| Male sex (%) | 63.9 | 66.7 | 0.491† |
| Prior ICS use (%) | 48.2 | 44.4 | 0.463 |
| Total IgE (IU/mL) | 394.93 (192.02–597.84) | 176.78 (92.41–445.94) | 0.041 |
| PB eosinophil (/μL) | 552.5 (134.8–970.2) | 230.0 (71.78–577.78) | 0.006 |
| ECP (ng/mL) | 83.53 (19.49–147.56) | 26.55 (7.47–243.25) | 0.011 |
Table 2.
Lung function, bronchial hyperresponsiveness, and exhaled nitric oxide measurements among the 2 study groups BHR
| Variable | Atopic asthma (n=83) | Nonatopic asthma (n=27) | P-value∗ |
|---|---|---|---|
| Baseline | |||
| FEV1 (pred%) | 86.00±14.44 | 88.24±12.09 | 0.168 |
| FVC (pred%) | 94.67±14.15 | 93.96±12.69 | 0.344 |
| FEV1/FVC ratio | 81.17±6.09 | 82.68±8.00 | 0.775 |
| Postbronchodilator | |||
| ∆FEV1 (pred%) | 12.00±8.32 | 10.36±7.75 | 0.905 |
| FeNO (ppb) | 33.9 (27.8–40.0) | 16.6 (9.7–23.6) | 0.036 |
| PC20 (mg/mL) | 1.24 (0.60–1.87) | 4.97 (3.47–6.47) | 0.001 |
| BHR to mannitol | 32/48 (66.7) | 11/15 (73.3) | 0.737† |
| PD15 (mg) | 161.36 (96.12–226.59) | 225.34 (169.50–281.18) | 0.590 |
| RDR (%/mg) | 0.120 (0.043–0.198) | 0.074 (0.035 –0.144) | 0.744 |
| BHR to exercise | 45/55 (81.8) | 11/18 (61.1) | 0.091† |
| Postexcercise maximum decrease in FEV1 (%) | 31.9 (22.9–40.9) | 14.0 (9.4–18.6) | 0.015 |
Values are presented as mean±standard deviation, geometric mean (95% confidence interval), or number (%).
BHR, bronchial hyperresponsiveness; FEV1, forced expiratory volume in 1 second; pred%, predicted %; FVC, forced vital capacity; FeNO, fractional exhaled nitric oxide; PC20, provocative concentration of methacholine inducing a 20% fall in FEV1; PD15, cumulative provocative dose causing a 15% fall in FEV1; RDR, response–dose ratio (% fall in FEV1/cu-mulative dose of mannitol).
Table 3.
Correlation coefficients between bronchial hyperresponsiveness and lung function or markers of atopy
PD15, cumulative provocative dose causing a 15% fall in FEV1; PC20, provocative concentration of methacholine inducing a 20% fall in FEV1; FEV1, forced expiratory volume in 1 second; pred%, predicted %; FVC, forced vital capacity; FeNO, fractional exhaled nitric oxide; PB, peripheral blood; ECP, eosinophilc cationic protein.
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