Am. J. Respir. Crit. Care Med., Vol 151, No. 5, 05 1995, 1512-1518.
Restrictive lung disease in rats exposed chronically to an urban profile of ozone
DL Costa, JS Tepper, MA Stevens, WP Watkinson, DL Doerfler, TR Gelzleichter and JA Last
Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
The potential for irreversible lung impairment resulting from life-long
ozone (O3) exposure remains uncertain. To address this question, young
adult rats (male, F-344) were exposed to a simulated urban profile of O3
for 1, 3, 13, 52, or 78 wk, after which pulmonary function tests were
performed. To assess reversibility of effects, cohorts from the 13- , 52-,
and 78-wk groups were evaluated, respectively, after an additional 6, 27,
and 17 wk of clean air. Static and dynamic lung properties were based on
measurements of lung volume apportionment, respiratory system compliance
(Crs), DLCO, multibreath N2 washout, and maximum expiratory flow-volume
relationships. Electrocardiography was also performed in unanesthetized,
restrained rats after 52 and 78 wk, as were determinations of wet and dry
lung weights, lung collagen, and associated connective tissue crosslinks.
Small (< 10%) but significant reductions in TLC and RV were noted after
13, 52, and 78 wk of O3 exposure. At 13 and 52 wk, N2 washout was enhanced,
though at 78 wk it was similar to control. None of these changes appeared
progressive with continued O3 exposure. Post exposure to clean air did not
completely reverse the reduction in TLC. Additionally, Crs, though not
affected during O3 exposure, decreased during the air recovery. No
O3-related changes in collagen were apparent, however. Thus, near life-long
exposure of F-344 rats to a worse-case, urban profile of O3 appears to have
led to a functionally restrictive, i.e. "stiffened," lung without overt
fibrosis. Furthermore, certain aspects of the O3-induced effect were not
fully reversible.
