Chest
Volume 124, Issue 1, July 2003, Pages 25-31
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Clinical Investigations
Asthma
Increased Exhaled 8-Isoprostane in Childhood Asthma

https://doi.org/10.1378/chest.124.1.25Get rights and content

Study objectives

To quantify lung oxidative stress in asthmatic children by measuring concentrations of 8-isoprostane, a marker of oxidative stress, in exhaled breath condensate (EBC), which is a noninvasive method of sampling airway secretions. Secondary objectives were as follows: (1) to measure levels of exhaled prostaglandin (PG) E2, since impaired PGE2 production has been implicated in the pathogenesis of asthma in adults; and (2) to measure levels of fractional exhaled nitric oxide (FeNO), which is a marker of airway inflammation.

Design

Single-center, cross-sectional study.

Patients

Twelve healthy children, 12 steroid-nai¨ve asthmatic children, and 30 children in stable condition with mild-to-moderate persistent asthma who were being treated with inhaled corticosteroids (ICSs) [average dose, 300 μg per day] were studied.

Interventions

Subjects attended the outpatient clinic on one occasion for the collection of EBC and FeNO measurements.

Measurements and results

8-Isoprostane and PGE2 concentrations in EBC were measured with specific radioimmunoassays. FeNO was measured online by a chemiluminescence analyzer. 8-Isoprostane was detectable in the EBC of healthy children (mean [± SEM], 34.2 ± 4.5 pg/mL), and its concentrations were increased in both steroid-nai¨ve asthmatic children (mean, 56.4 ± 7.7 pg/mL; p < 0.01) and steroid-treated asthmatic children (mean, 47.2 ± 2.3 pg/mL; p < 0.05). There was no difference in exhaled 8-isoprostane concentrations between the two groups of asthmatic children (p = 0.14). By contrast, exhaled PGE2 concentrations were similar among the three study groups (p = 0.56). FeNO levels were higher in steroid-nai¨ve children with asthma (49.2 ± 9.6 parts per billion [ppb]; p < 0.05) and, to a lesser extent, in steroid-treated asthmatic children (37.8 ± 6.6 ppb; p < 0.05) compared with healthy children (15.2 ± 1.7 ppb).

Conclusions

Lung oxidative stress is increased in children who are in stable condition with asthma, as reflected by increased exhaled 8-isoprostane concentrations. This increase seems to be relatively resistant to treatment with ICSs. Decreased PGE2 lung production is unlikely to play a pathophysiologic role in childhood asthma.

Section snippets

Study Subjects

The following three groups of white subjects were studied: 12 healthy children; 12 steroid-nai¨ve asthmatic children; and 30 children in stable condition with mild-to-moderate persistent asthma who were treated with ICSs (Table 1). The asthmatic children (age range, 5 to 16 years) and healthy children (age range, 6 to 13 years) were matched for age.

The diagnosis and classification of asthma was based on clinical history, physical examination, and pulmonary function parameters, which were

Results

8-Isoprostane concentrations were detectable in EBC in healthy children (34.2 ± 4.5 pg/mL; 95% confidence interval [CI], 24.3 to 44.0) and were increased in both steroid-nai¨ve children with asthma (56.4 ± 7.7 pg/mL; p < 0.01; 95% CI, 39.4 to 73.4) and steroid-treated children with asthma (47.2 ± 2.3 pg/mL; p < 0.05; 95% CI, 42.4 to 52.0) [Fig 1, top]. There was no difference in exhaled 8-isoprostane concentrations between the two groups of asthmatic children (p = 0.14). In contrast, exhaled PGE

Discussion

Recently, attention has focused on analyzing EBC for studying the composition of the fluid that lines the respiratory tract.4 As the measurement of EBC is completely noninvasive, this method is potentially useful for the long-term monitoring of lung inflammation in patients with inflammatory airway diseases, including children.30

In this study, we have shown that 8-isoprostane, a marker of free radical-induced lipid peroxidation, is detectable in the EBC of healthy children, indicating that ROS

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    This work was supported by the Catholic University of the Sacred Heart, Rome, Italy, and by the University of Padova, Padova, Italy.

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