Age-related differences in pulmonary effects of acute and subchronic episodic ozone exposures in Brown Norway rats

Ozone (O-3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O-3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O-3 are uncertain. In this study, we examined age-related susceptibility to O-3 using 1mo (adolescent), 4mo (young adult), 12mo (adult) and 24mo (senescent) male Brown Norway rats exposed to filtered air or O-3 (0.25 and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O-3-induced pulmonary effects. Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O-3 exposures. PenH was increased in all groups with an augmented response in the 4mo rats following the subchronic O-3 exposures. O-3 led to increased breathing frequency and minute volume in the 1 and 4mo animals. Markers of pulmonary permeability were increased in all age groups. Elevations in BALF gamma-glutamyl transferase activity and lung inflammation following an acute O-3 exposure were noted in only the 1 and 4mo rats, which likely received an increased effective O-3 dose. These data demonstrate that adolescent and young adult animals are more susceptible to changes in ventilation and pulmonary injury/inflammation caused by acute and episodic O-3 exposure.