Levels of nitric oxide oxidation products are increased in the epithelial lining fluid of children with persistent asthma

Background

Children with severe allergic asthma have persistent airway inflammation and oxidant stress.

Objectives

We hypothesized that children with severe allergic asthma would have increased concentrations of the nitric oxide (NO) oxidation products nitrite, nitrate, and nitrotyrosine in the proximal and distal airway epithelial lining fluid (ELF). We further hypothesized that NO oxidation products would be associated with higher exhaled NO values (fraction of exhaled nitric oxide [FENO]), greater allergic sensitization, and lower pulmonary function.

Methods

Bronchoalveolar lavage fluid was obtained from 15 children with mild-to-moderate asthma, 30 children with severe allergic asthma, 5 nonasthmatic children, and 20 nonsmoking adults. The bronchoalveolar lavage fluid was divided into proximal and distal portions and nitrite, nitrate, and nitrotyrosine values were quantified.

Results

Children with mild-to-moderate and severe allergic asthma had increased concentrations of nitrite (adult control subjects, 15 ± 3 μmol/L; pediatric control subjects, 23 ± 4 μmol/L; subjects with mild-to-moderate asthma, 56 ± 26 μmol/L; subjects with severe asthma, 74 ± 18 μmol/L), nitrate (37 ± 13 vs 145 ± 38 vs 711 ± 155 vs 870 ± 168 μmol/L, respectively) and nitrotyrosine (2 ± 1 vs 3 ± 1 vs 9 ± 3 vs 10 ± 4 μmol/L, respectively) in the proximal ELF. Similar results were seen in the distal ELF, although the concentrations were significantly lower (P < .05 for each). Although univariate analyses revealed no associations between NO oxidation products and clinical features, multivariate analyses revealed FENO values to be a significant predictor of NO oxidation in asthmatic children.

Conclusions

NO oxidation products are increased in the ELF of asthmatic children. The relationship between FENO values and airway nitrosative stress is complicated and requires further study.

Key words: Asthma, children, nitric oxide, nitrogen oxides, nitrosation, nitrosative stress, reactive nitrogen species

Abbreviations used: BAL, Bronchoalveolar lavage, ELF, Epithelial lining fluid, FENO, Fraction of exhaled nitric oxide, ICS, Inhaled corticosteroid, NO, Nitric oxide, NOS, Nitric oxide synthase