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Published ahead of print on June 3, 2005, doi:10.1164/rccm.200502-272OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 4, August 2005, 427-432

A more recent version of this article appeared on August 15, 2005
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Submitted on February 18, 2005
Accepted on May 11, 2005

Repeated Exposure to Ozone Increases Alveolar Macrophage Recruitment into Asthmatic Airways

Mehrdad Arjomandi1, Allyson Witten1, Emilio Abbritti1, Kurt Reintjes1, Isabelle Schmidlin1, Wenwu Zhai1, Colin Solomon1, and John R Balmes2*

1 Lung Biology Center, Department of Medicine, University of California, San Francisco, CA, USA, 2 Lung Biology Center, Department of Medicine, University of California, San Francisco, CA, USA; Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA

* To whom correspondence should be addressed. E-mail: jbalmes{at}itsa.ucsf.edu.

Rationale: Repeated, short-term exposures to ozone (O3) lead to attenuation of the acute lung function and airway inflammatory responses seen after a single exposure in healthy subjects, but it is unclear whether these acute responses also attenuate in asthmatic subjects. Objective: To address this question by exposing 14 asthmatic subjects to 0.2 ppm O3 for either 4 h on a single day (1-D) or 4 h on four consecutive days [multi-day (MD)]. At least 3 weeks later, subjects underwent the alternate exposure. Methods: Spirometry was performed immediately pre- and post-exposure and bronchoalveolar lavage (BAL) was obtained 18 h after each exposure. Main Results: The decrease in FEV1 was greatest across day 2 of the MD (MD2) exposure and then gradually declined on successive days of the MD exposure (mean±SD decrease in FEV1 of 25.4±18.0% across MD2 compared to 4.2±6.5% across MD4). Respiratory symptoms followed a similar pattern to that of FEV1. While the concentration of neutrophils in BAL after the MD4 exposure was not significantly different from that after the 1-D exposure (1.7±1.3 x104cells/ml versus 1.2±0.8 x104cells/ml; p=0.20), the concentration of alveolar macrophages did significantly increase in BAL after the MD exposure (19.9±9.7 x104cells/ml after MD4 versus 12.1±6.4 x104cells/ml after 1-D). Conclusions: Alveolar macrophages are recruited to the airways of asthmatic subjects with repeated short-term exposures to ozone, suggesting a possible role for these cells in the chronic response to oxidant-induced injury.


Key words: Ozone, asthma, airway inflammation, alveolar macrophage, multi-day exposure




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