O3-induced change in bronchial reactivity to methacholine and airway inflammation in humans

Abstract

The increase in airway responsiveness induced by O3 exposure in dogs is associated with airway epithelial inflammation, as evidenced by an increase in the number of neutrophils (polymorphonuclear leukocytes) found in epithelial biopsies and in bronchoalveolar lavage fluid. We investigated in 10 healthy, human subjects whether O3-induced hyperresponsiveness was similarly associated with airway inflammation by examining changes in the types of cells recovered in bronchoalveolar lavage fluid obtained after exposure to air or to O3 (0.4 or 0.6 ppm). We also measured the concentrations of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in lavage fluid. We measured airway responsiveness to inhaled methacholine aerosol before and after each exposure and performed bronchoalveolar lavage 3 h later. We found more neutrophils in the lavage fluid from O3-exposed subjects, especially in those in whom O3 exposure produced an increase in airway responsiveness. We also found significant increases in the concentrations of prostaglandins E2, F2 alpha, and thromboxane B2 in lavage fluid from O3-exposed subjects. These results show that in human subjects O3-induced hyperresponsiveness to methacholine is associated with an influx of neutrophils into the airways and with changes in the levels of some cyclooxygenase metabolites of arachidonic acid.

Role of cathepsin S in ozone-induced airway hyperresponsiveness and inflammation

“…Experimental ozone exposure induces oxidative stress, airways hyperresponsiveness (AHR) and lung neutrophilia (1)(2)(3)(4)(5)(6). The mechanisms underlying ozone-induced AHR and inflammation are unclear, although the influx of neutrophils may be due to their recruitment by ozone-induced release of pro-inflammatory cytokines and chemokines.…”

Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone‐exposed guinea‐pigs: effects of dexamethasone and rolipram

“…Anti-oxidant and scavenger enzymes normally sequester increased levels of ROS after ozone exposure, however, oxidative stress occurs if the level of ozone exceeds the capacity of the anti-oxidative mechanisms (Cardile et al, 1995). In animals and humans, inhaled ozone (O 3 ) induces AHR to various spasmogens (Schultheis, et al, 1994;Seltzer et al, 1986;Arakida et al, 2000), decreases expiratory¯ow and volume (Hazucha, 1987;Joad et al, 1994) and bronchial biopsies and lavage exhibit evidence of leukocyte in¯ux, oedema and epithelial damage (Murlas & Roum, 1985;Aris et al, 1993). Thus, oxidant stress arising after ozone inhalation shares many features associated with COPD and asthma.…”

Importance of Impairment of the Airway Epithelium for Ozone-Induced Airway Hyperresponsiveness in Guinea Pigs

“…Some researchers (17)(18)(19) have emphasized the association between 03-induced AHR and infiltration of inflammatory cells, especially neutrophils. Weideman and Schlesinger (21) reported that neutrophils in humans and rabbits were activated to change eicosanoid metabolism following 03 exposure in vitro.…”

“…Because some reports suggested that 03-induced AHR is associated with infiltration of inflammatory cells including neutrophils in the airway (17)(18)(19), we first examined the time course of AHR after 03 exposure. In this study, the AHR was observed up to 5 hr, and it was already diminished from 24 hr (Fig.…”

“…It is said that 03-induced AHR is due to 5-lipoxygenase metabolites (15), endogenous tachykinin (16) and other factors. On the other hand, some reports indicated that infiltration of neutrophils into the airway lumen was associated with 03-induced AHR (17)(18)(19), but another reports have denied this (13,20).…”