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Research Advance Publication

Environ Health Perspect; DOI:10.1289/ehp.1307240

Repeated Nitrogen Dioxide Exposures and Eosinophilic Airway Inflammation in Asthmatics: A Randomized Crossover Study

Véronique Ezratty,1 Gaëlle Guillossou,1 Catherine Neukirch,2 Monique Dehoux,3 Serge Koscielny,4 Marcel Bonay,5 Pierre-André Cabanes,1 Jonathan M. Samet,6 Patrick Mure,7 Luc Ropert,7 Sandra Tokarek,7 Jacques Lambrozo,1 and Michel Aubier2
Author Affiliations close
1Service des Etudes Médicales (SEM), EDF, Levallois-Perret, France; 2Service de Pneumologie A, Clinical Center of Investigation, Inserm U700, Bichat Hospital, Université Paris Diderot, DHU FIRE, Paris, France; 3Laboratoire de Biochimie, Bichat Hospital, Paris, France; 4Service de biostatistiques et épidémiologie, Gustave Roussy, Villejuif, France; 5Department of Physiology, Bichat Hospital, Paris, France; 6Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, and Director, Institute for Global Health, University of Southern California, Los Angeles, California, USA; 7Center for Research & Innovation in Gas and New Energy Sources, CRIGEN, GDF SUEZ, St-Denis, France
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This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

Citation: Ezratty V, Guillossou G, Neukirch C, Dehoux M, Koscielny S, Bonay M, Cabanes PA, Samet JM, Mure P, Ropert L, Tokarek S, Lambrozo J, Aubier M. Repeated Nitrogen Dioxide Exposures and Eosinophilic Airway Inflammation in Asthmatics: A Randomized Crossover Study. Environ Health Perspect;

Received: 18 June 2013
Accepted: 15 April 2014
Advance Publication: 18 April 2014

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Background: Nitrogen dioxide (NO2), a ubiquitous atmospheric pollutant, has been reported to enhance the asthmatic response to allergen through eosinophilic activation in the airways. The effect of NO2 on inflammation without exposure to allergen is poorly studied.

Objectives: We investigated whether repeated peaks of NO2, at various realistic concentrations, induce changes in airway inflammation in asthmatics.

Methods: 19 nonsmoker asthmatics were exposed at rest in a double-blind, crossover study, in randomized order, to 200 ppb NO2, or 600 ppb NO2, or clean air for 1×30 min day 1, and 2×30 min day 2. The three series of exposures were separated by 2 weeks. Inflammatory response in sputum was measured 6 hours (day 1), 32 hours (day 2), and 48 hours (day 3) after first exposure and compared to baseline measured twice 10 to 30 days before.

Results: Compared to baseline, the percentage of eosinophils in sputum increased by 57% after 600 ppb NO2 (P=0.003) but did not change significantly after 200 ppb. The slope of the association between the percentage of eosinophils and NO2 exposure level was significant (p=0.04). Eosinophil cationic protein (ECP) in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO2 (p=0.001). Lung function assessed daily was not affected by NO2.

Conclusions: To our knowledge, this is the first study on repeated NO2 peaks performed without allergen exposure that demonstrates a dose-related effect on airway eosinophilic inflammation in asthmatics.

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