Effects of Short-Term Exposure to 0.2 ppm Ozone on Biomarkers of Inflammation in Sputum, Exhaled Nitric Oxide, and Lung Function in Subjects With Mild Atopic Asthma

Abstract

To gain further insight into the kinetics of airway inflammatory response and explore the possibility of nitric oxide as a surrogate marker of the lower airway inflammatory response to ozone, nine subjects with mild atopic asthma were exposed to filtered air or 0.2 ppm ozone for 2 hours with intermittent exercise. Lung function was measured at baseline and immediately after exposures. Sputum induction was performed at 6 hours and at 24 hours after exposures, and exhaled nitric oxide levels were measured at baseline, immediately, 6, and 24 hours after both exposures. A significant decline in forced expiratory volume in one second and inspiratory capacity was detectable following exposure to ozone. In addition, a 2-fold increase was observed in the percentage of polymorphonuclear leukocytes 6 hours after exposure to ozone, with no changes in other biomarkers at this time point. By 24 hours after ozone exposure, the neutrophilia had subsided but there was an increase in albumin, total protein, myeloperoxidase, and eosinophil cationic protein. Exhaled nitric oxide levels, histamine, interleukin-8, and growth-related oncogene-alpha in sputum did not change significantly following ozone exposure. It was concluded that short-term ozone exposure induces an acute inflammatory response in asthmatic airways, characterized by early polymorphonuclear leukocyte influx followed by plasma extravasation and activation of eosinophils and neutrophils. Exhaled nitric oxide is not a useful marker for detecting inflammatory response to ozone in persons with mild asthma.

Ozone exposure enhances mast-cell inflammation in asthmatic airways despite inhaled corticosteroid therapy

“…Certain ozone exposure studies in mild asthmatics not on anti-inflammatory treatment have reported increases in BAL ECP and eosinophils (Hiltermann 1999;Newson 2000;Peden 1997) as well as the upregulation of pro-eosinophilic cytokines such as IL-5 and GM-CSF in the bronchial mucosa (Bosson 2003). However, in the present study the asthmatic subjects were on inhaled corticosteroid treatment, which decreases airway tissue eosinophils (Djukanovic 1992) and dampens allergeninduced BAL eosinophilia (Becky Kelly 2000).…”

“…It has been repeatedly demonstrated that ozone exposure decreases lung function (Holz 1999;Horstman 1995;Jorres 1996;Koenig 1987;Kreit 1989;Nightingale 1999;Scannell 1996) and increases bronchial hyperresponsiveness in asthmatic subjects (Gong, Jr. 1997;Hiltermann 1995;Hiltermann 1998;Jenkins 1999;Jorres 1996;Kehrl 1999;Linn 1994). In induced sputum, ozone exposure induces airway inflammation in asthmatics 1-24 h post challenge, with increases in neutrophils, lymphocytes, interleukin (IL)-8, myeloperoxidase (MPO), albumin, protein, eosinophilic cationic protein (ECP), and elastase (Hiltermann 1999;Hiltermann 1995;Holz 1999;Newson 2000;Nightingale 1999;Vagaggini 1999). In both asthmatic and healthy subjects, exposure to relatively high doses of ozone has been shown to induce airway inflammation with increases in IL-6, IL-8, protein, and neutrophils in bronchoalveolar lavages (BAL) 16-18 h after ozone exposure (Basha 1994;Hiltermann 1999;Peden 1997;Scannell 1996).…”

Measurement of offline exhaled nitric oxide in a study of community exposure to air pollution.

“…Newson et al (2000) also found that eNO values did not change after exposure of subjects with mild atopic disease to 0.2 ppm ozone for 2 hr. A similar study was reported by Nightingale et al (1999), who found no change in eNO after exposure of subjects with asthma to 0.2 ppm ozone for 2 hr, even though forced expiratory volume in 1 sec (FEV 1 ) decreased 9%.…”

Associations between Health Effects and Particulate Matter and Black Carbon in Subjects with Respiratory Disease

“…In contrast, no increase in FE NO was seen in adult subjects with asthma after exposure to concentrated coarse particles (Gong et al 2003) or ultrafine particles (Pietropaoli et al 2004). Several controlled ozone exposure studies have assessed FE NO in atopic subjects with asthma (Newson et al 2000; Nightingale et al 1999) and healthy subjects (Olin et al 2001), but none has found an association.…”