Ozone-induced lung function decrements do not correlate with early airway inflammatory or antioxidant responses

Abstract

To obtain information on the real-time events occurring within human respiratory tract lining fluids (RTLFs) during ozone exposure, sequential nasal lavage was performed on 13 human volunteers exposed on separate occasions to 0.2 parts per million O 3 and filtered air (2-h exposures, with intermittent exercise).Nasal lavage was performed and blood samples obtained at four time points throughout each exposure: pre-exposure (Pre-E), 1 h into exposure (1h-E), immediately postexposure (0h-PE) and 1 h post-exposure (1h-PE). Endobronchial mucosal biopsies were obtained at 1.5 h-post exposure (1.5 h-PE).Nasal RTLF neutrophilia was not apparent during, or 1.5 h after, O 3 exposure. Furthermore, activation of the pre-existing neutrophil population did not occur. Airway permeability was not altered by this O 3 exposure regimen. Sequential lavage resulted in significant washout of RTLF ascorbic acid, reduced glutathione, extracellular superoxide dismutase and myeloperoxidase at 1h-E, 0h-PE and 1.5h-PE relative to baseline Pre-E values. In contrast, RTLF uric acid (UA), total protein and albumin concentrations did not display washout kinetics. Of the antioxidants examined, only UA was clearly depleted by O 3 , concentrations, falling by 6.22 mmol . L -1 at 1h-E, compared with 1.61 mmol . L -1 (p<0.01) during control air exposure. The establishment of a new pseudo-steady-state concentration of RTLF UA (70% of Pre-E values) during the second hour of O 3 exposure was coincident with a small but significant increase in plasma UA concentration (19.27 (O 3 ) versus 1.95 mmol . L -1 (air), p<0.05).These data demonstrate that inhalation of 0.2 parts per million O 3 results in the depletion of nasal respiratory tract lining fluid uric acid and that this regional loss of uric acid leads to a small increase in plasma uric acid concentration. Whilst the reaction of uric acid with inspired O 3 may confer protection locally, the role of upper airway uric acid as a sink for inhaled O 3 is not supported by these findings.

Antioxidant Responsiveness in BALB/c Mice Exposed to Ozone

“…Retinol has been investigated in pulmonary disease [21, 22]. MDA has been known as an oxidative damage marker in BAL fluid [15]. In this study retinol was increased in the group exposed to 2-ppm ozone but the level of retinol regardless of the ozone concentration was not statistically different.…”

“…Antioxidant vitamins may play a role in respiratory health, and vitamin E and β-cryptoxanthin appear to be stronger correlates of lung function than other antioxidant vitamins. There is still considerable uncertainty about the association of BAL fluid antioxidants with lung function [15, 26]. In this study airway responsiveness to acute ozone exposure increased in a concentration-dependent manner, and antioxidant responses increased in higher ozone concentrations, suggesting that antioxidant responses be related to airway responsiveness after ozone exposure in BALB/c mice.…”

“…Only few studies have investigated BAL fluid levels of antioxidants in relation to lung function [15, 24, 25]. Antioxidant vitamins may play a role in respiratory health, and vitamin E and β-cryptoxanthin appear to be stronger correlates of lung function than other antioxidant vitamins.…”

“…Uric acid and ascorbic acid were determined simultaneously using reverse phase high-performance liquid chromatography (HPLC) with electrochemical detection, based on the method of Mudway et al [13]. HPLC determinations of retinol, α-tocopherol, and γ-tocopherol were based on the method of Bieri et al [14]and have been described in detail for BAL fluid [15]. …”

Pulmonary Epithelial Integrity in Children: Relationship to Ambient Ozone Exposure and Swimming Pool Attendance

“…Human experimental exposure to O 3 has demonstrated a spectrum of acute airway responses. Among these are decrements in forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV 1 ), increased airway resistance (Blomberg et al 1999; Seal 1993), altered airway permeability, and antioxidant defenses (Blomberg et al 1999; Mudway et al 2001), as well as a neutrophilic airway inflammation (Schelegle et al 1991; Stenfors et al 2002). Most of these studies were short-term exposures on healthy adults.…”