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Levels of nitric oxide oxidation products are increased in the epithelial lining fluid of children with persistent asthma - 15/08/11

Doi : 10.1016/j.jaci.2009.08.039 
Anne M. Fitzpatrick, PhD a, , Lou Ann S. Brown, PhD a, Fernando Holguin, MD b, W. Gerald Teague, MD a

National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program

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

a Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga 
b Department of Medicine, Emory University School of Medicine, Atlanta, Ga 

Reprint requests: Anne M. Fitzpatrick, PhD. 2015 Uppergate Dr, Atlanta, GA 30322.

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 [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.

El texto completo de este artículo está disponible en PDF.

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

Abbreviations used : BAL, ELF, FENO, ICS, NO, NOS


Esquema


 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.


© 2009  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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Vol 124 - N° 5

P. 990 - novembre 2009 Regresar al número
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