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

Abstract

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 [F(ENO)]), 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 micromol/L; pediatric control subjects, 23 +/- 4 micromol/L; subjects with mild-to-moderate asthma, 56 +/- 26 micromol/L; subjects with severe asthma, 74 +/- 18 micromol/L), nitrate (37 +/- 13 vs 145 +/- 38 vs 711 +/- 155 vs 870 +/- 168 micromol/L, respectively) and nitrotyrosine (2 +/- 1 vs 3 +/- 1 vs 9 +/- 3 vs 10 +/- 4 micromol/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 F(ENO) 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 F(ENO) values and airway nitrosative stress is complicated and requires further study.

Figure 1

Diagram of nitric oxide (NO) metabolite formation in the airways.

Figure 2

(A) Total nitrite + nitrate, (B) nitrite, (C) nitrate, and (D) nitrotyrosine concentrations (µM) in the proximal (dark bars) and distal (light bars) airway ELF. Data represent the mean ± SEM with AC = adult control, PC = pediatric control, MA= mild-to-moderate asthma, and SA = severe asthma. ^ap < 0.05 versus AC, ^bp < 0.05 versus PC.

Figure 3

Scatterplot depicting the relationship between total nitrite + nitrate and nitrotyrosine concentrations (µM) in the proximal (dark circles) and distal (light circles) airway ELF. Data were logarithmically transformed.