Nitric Oxide Oxidation Products are Increased in the Epithelial Lining Fluid of Children with Persistent Asthma

• Type of Material: Article
• Authors: Anne M Fitzpatrick, Emory University; Lou Ann Brown, Emory University; Fernando Holguin, Emory University; W. Gerald Teague, Emory University
• Language: English
• Date: 2009-11
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jaci.2009.08.039
• Title of Journal or Parent Work: Journal of Allergy and Clinical Immunology: In Practice
• ISSN: 2213-2201
• Volume: 124
• Issue: 5
• Start Page: 990
• End Page: 6.e1-9
• Grant/Funding Information: This study was supported with funds from NIH/NINR KO1 NR010548, NIH/NCRR K12 RR017643, and NIH/NHLBI SARP RO1 HL69170.; The Severe Asthma Research Program is a multicenter asthma research group funded by the National Heart Lung Blood Institute (NHLBI)
• Keywords: Asthma; Reactive nitrogen species; Children; Nitrosative Stress; Nitrosation; Nitrogen oxides; Nitric oxide
• Research Categories: Health Sciences, Medicine and Surgery

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 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 nitric oxide (FENO), greater allergic sensitization, and lower pulmonary function. Methods Bronchoalveolar lavage (BAL) was obtained from 15 children with mild-to-moderate asthma, 30 children with severe allergic asthma, 5 non-asthmatic children and 20 non-smoking adults. The BAL was divided into proximal and distal portions and nitrite, nitrate, and nitrotyrosine were quantified. Results Children with mild-to-moderate and severe allergic asthma had increased concentrations of nitrite (adult control: 15 ± 3; pediatric control: 23 ± 4; mild-to-moderate asthma: 56 ± 26; severe asthma: 74 ± 18 µM), nitrate (37 ± 13 vs. 145 ± 38 vs. 711 ± 155 vs. 870 ± 168 µM) and nitrotyrosine (2 ± 1 vs. 3 ± 1 vs. 9 ± 3 vs. 10 ± 4 µM) in the proximal ELF. Similar results were seen in the distal ELF although the concentrations were significantly lower (p < 0.05 for each). Although univariate analyses revealed no associations between NO oxidation products and clinical features, multivariate analyses revealed FENO 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 and airway nitrosative stress is complicated and requires further study.