Background: The effect of corticosteroids on the ozone (O3)-induced airway inflammation is still debated. Objective: The aim of the study was to confirm the effect of a short-term treatment with oral glucocorticosteroids on O3-induced airway inflammation, detected by induced sputum analysis, and on functional response in glucocorticosteroid-naive subjects. Methods: A randomized, placebo-controlled study using oral prednisone (25 mg o.d. for 4 days) was carried out. Nine mild persistent asthmatics were exposed for 2 h, on separatedays, to 0.27 ppm O3 and to air in random order, after 4 days of treatment with prednisone (25 mg o.d.) and after 4 days of placebo.Before and after exposure, pulmonary function test was measured; 6 h afterexposure, sputum induction was done. Results: Oral glucorticosteroids did not prevent pulmonary function decrement due to O3. After placebo, the percentage of neutrophils in induced sputum was significantly higher after O3 than after air [52.1 (15.7–77.3) vs. 17.8 (1.7–58.4), p = 0.02, O3 vs. air]. This difference was lost after 4 days of treatment with prednisone [35.2% (10–96.2) vs. 30.9% (6.1–75.6), n.s., O3 vs. air]. Neutrophil elastase in sputum supernatant increased after O3 exposure in the sample obtained after placebo, but not after prednisone treatment. Conclusions: This study confirms that glucocorticosteroids reduce inflammatory airway response, but do not prevent the airway functional impairment after O3 exposure.

Keywords:
Asthma, Induced sputum, Neutrophils, Ozone, Oral corticosteroid, Pulmonary function
1.
Ito K, De Leon SF, Lippmann M: Association between ozone exposure and daily mortality: analysis and meta-analysis. Epidemiology 2005;16:446–457.
2.
Segala C, Fauroux B, Just J, et al: Short-term effect of winter air pollution on respiratory health of asthmatic children in Paris. Eur Respir J 1998;11:677–685.
3.
Gent FJ, Triche EW, Holford TR, et al: Association of low-level ozone and fine particles with respiratory symptoms in children with asthma. JAMA 2003;290:1859–1867.
4.
Boutin-Forzano S, Adel N, Gratecos J, et al: Visits to the emergency room for asthma attacks and short-term variations in air pollution. A cross-over study. Respiration 2004;71:134–137.
5.
McConnell R, Berhane K, Glilliand F, et al: Asthma in exercising children exposed to ozone: a cohort study. Lancet 2002;139:386–391.
6.
Stenfors N, Pourazar J, Blomberg A, et al: Effects of ozone on bronchial mucosal inflammation in asthmatic and healthy subjects. Respir Med 2002;96:352–358.
7.
Basha MA, Gross KB, Gwizdala CJ, et al: Bronchoalveolar lavage neutrophilia in asthmatic and healthy volunteers after controlled exposure to ozone and filtered purified air. Chest 1994;106:757–1765.
8.
Fahy JV, Wong HH, Liu JT, Boushey HA: Analysis of induced sputum after air and ozone exposures in healthy subjects. Environ Res 1996;70:77–83.
9.
Vagaggini B, Carnevali S, Macchioni P, et al: Airway inflammatory response to ozone in subjects with different asthma severity. Eur Respir J 1999;13:274–280.
10.
Ying RL, Gross KB, Terzo TS, Eschenbacher WL: Indomethacin does not inhibit the ozone-induced increase in bronchial responsiveness in human subjects. Am Rev Respir Dis 1990;142:817–821.
11.
Samet JM, Hatch GE, Horstman D, et al: Effect of antioxidant supplementation on ozone-induced lung injury in human subjects. Am J Respir Crit Care Med 2001;164:819–825.
12.
Romieu I, Sienra-Monge JJ, Martinez-Aguilar M, et al: Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Am J Respir Crit Care Med 2002;166:703–709.
13.
Bottei GM, Devlin RB, Bromberg PA, Peden DB: The effect of corticosteroids on lower airways inflammation and pulmonary function after ozone exposure (abstract). Am J Respir Crit Care Med1995;151:A28.
14.
Nightingale J, Rogers DF, Chung KF, Barnes PJ: No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Am J Respir Crit Care Med 2000;161:479–486.
15.
Vagaggini B, Taccola M, Cianchetti S, et al: Budesonide reduces neutrophilic but not functional airway response to ozone in mild asthmatics. Am J Respir Crit Care Med 2001;164:2172–2176.
16.
Balmes JR, Chen LL, Scannel C, et al: Ozone-induced decrements in FEV1 and FVC do not correlate with measures of inflammation. Am J Respir Crit Care Med 1996;153:904–909.
17.
Global Initiative for Asthma: NIH Publication 1995;95:3659.
18.
Vagaggini B, Taccola M, Cianchetti S, et al: Ozone exposure increases eosinophilic airway response induced by previous allergen challenge. Am J Respir Crit Care Med 2002;166:1073–1077.
19.
Bacci E, Cianchetti S, Ruocco L, et al: Comparison between eosinophilic markers in induced sputum and blood in asthmatic patients. Clin Exp Allergy 1998;28:1237–1243.
20.
Cianchetti S, Bacci E, Ruocco L, et al: Granulocyte markers in hypertonic and isotonic saline-induced sputum of asthmatic subjects. Eur Respir J 2004;24:1018–1024.
21.
Weinmann GG, Liu MC, Proud D, et al: Ozone exposure in humans: inflammatory, small and peripheral airway response. Am J Respir Crit Care Med 1995;152:1175–1182.
22.
Bosson J, Stenfors N, Bucht A, et al: Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects. Clin Exp Allergy 2003;33:777–782.
23.
Krishna MT, Madden J, Teran ML, et al: Effects of 0.2 ppm ozone on biomarkers of inflammation in bronchoalveolar lavage fluid and bronchial mucosa of healthy subjects. Eur Respir J 1998;11:1294–1300.
24.
Barnes PJ, Pedersen S, Busse WW: Efficacy and safety of inhaled corticosteroids. Am J Respir Crit Care Med 1998;157:S1–S53.
25.
Adcock IM, Ito K, Barnes PJ: Glucocorticoids: effects on gene transcription. Proc Am Thorac Soc 2004;1:247–254.
26.
Nocker RE, Weller FR, Out TA, et al: A double-blind study on the effect of corticosteroids on plasma exudation in asthma. Am J Respir Crit Care Med 1999;159:1499–1505.
27.
Stevens WHM, Adelroth E, Woolley MJ, et al: The effects of an inhaled corticosteroid on oxygen radical production by bronchoalveolar cells after allergen or ozone in dogs. Eur J Pharmacol 1995;293:251–257.
28.
Hotchkiss JA, Hilaski R, Cho H, et al: Fluticasone propionate attenuates ozone-induced rhinitis and mucous cell metaplasia in rat nasal airway epithelium. Am J Respir Cell Mol Biol 1998;18:91–99.
29.
Haddad ED, Liu SF, Salmon M: Expression of inducible nitric oxide synthase mRNA in Brown Norway rats exposed to ozone: effects of dexamethasone. Eur J Pharmacol 1995;293:287–290.
30.
Hiltermann JT, Lapperre TS, Van Breer L, et al: Ozone-induced inflammation assessed in sputum and in bronchial lavage fluid from asthmatics: a new noninvasive tool in epidemiologic studies on air pollution and asthma. Free Radic Biol Med 1999;27:1448–1454.
31.
Hazucha MJ, Bates DV, Bromberg PA: Mechanism of action of ozone on the human lung. J ApplPhysiol 1989;67:1535–1541.
32.
DeLorme MT, Yang H, Elbon-Copp C, et al: Hyperresponsive airways correlate with lung tissue inflammatory cell changes in ozone exposed rats. J Toxicol Environ Health A 2002;65:1453–1470.
33.
Foster MW, Braun RH, Macri K, Mitchell CS: Bronchial reactivity of healthy subjects: 18–20 h post-exposure to ozone. J Appl Phys 2000;89:1804–1813.
© 2007 S. Karger AG, Basel
2006
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.