Asthma and lower airway disease
Levels of nitric oxide oxidation products are increased in the epithelial lining fluid of children with persistent asthma

https://doi.org/10.1016/j.jaci.2009.08.039Get rights and content

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.

Section snippets

Sample

Children 5 to 17 years of age with symptomatic asthma attending an asthma clinic at Emory University were invited to participate in this study. Asthmatic children met published criteria for persistent asthma14 and had a history of at least a 12% change in FEV1 after albuterol administration.15 Severe asthma was diagnosed according to criteria developed by the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program,1 which were adapted from the

Results

Initially, 49 asthmatic children (severe asthma, n = 32), 7 pediatric control subjects, and 20 healthy adult control subjects were recruited for this study. However, 6 children, including 2 pediatric control subjects, 2 subjects with mild-to-moderate asthma, and 2 subjects with severe asthma, were infected with Streptococcus pneumoniae, Haemophilus influenzae, and/or Moraxella catarrhalis and were excluded from data analysis because of potential denitrification.23 The features of the excluded

Discussion

To our knowledge, this is the first study to directly measure NO oxidation products in the ELF of children with persistent asthma. Compared with control subjects, children with mild-to-moderate and severe allergic asthma had increased concentrations of nitrite, nitrate, and nitrotyrosine in the ELF that were consistently higher in the proximal versus the distal airways. Contrary to our hypothesis, we did not detect significant differences in concentrations of NO oxidation products between

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  • Cited by (0)

    Supported with funds from National Institutes of Health/National Institute of Nursing Research KO1 NR010548, National Institutes of Health/National Center for Research Resources K12 RR017643, and National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program RO1 HL69170.

    Disclosure of potential conflict of interest: W. G. Teague is on the speakers' bureau for Merck and Co; receives research support from the National Institutes of Health/National Heart, Lung, and Blood Institute, the American Lung Association, and the Centers for Disease Control and Prevention; is on the review panel for the American Thoracic Society; and is on the advisory board for WESTAT–Children's Health Study. The rest of the authors have declared that they have no conflict of interest.

    See the acknowledgments for a complete listing of the Severe Asthma Research Program contributors.

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