Variable Pulmonary Responses from Exposure to Concentrated Ambient Air Particles in a Rat Model of Bronchitis

Abstract

Chronic bronchitis may be considered a risk factor in particulate matter (PM)-induced morbidity. We hypothesized that a rat model of human bronchitis would be more susceptible to the pulmonary effects of concentrated ambient particles (CAPs) from Research Triangle Park, NC. Bronchitis was induced in male Sprague-Dawley rats (90-100 days of age) by exposure to 200 ppm sulfur dioxide (SO2), 6 h/day x 5 days/week x 6 weeks. One day following the last SO2 exposure, both healthy (air-exposed) and bronchitic (SO2-exposed) rats were exposed to filtered air (three healthy; four bronchitic) or CAPs (five healthy; four bronchitic) by whole-body inhalation, 6 h/day x 2 or 3 days. Pulmonary injury was determined either immediately (0h) or 18 h following final CAPs exposure. The study protocol involving 0 h time point was repeated four times (study #A, November, 1997; #B, February, 1998; #C and #D, May, 1998), whereas the study protocol involving 18 h time point was done only once (#F). In an additional study (#E), rats were exposed to residual oil fly ash (ROFA), approximately 1 mg/ m(3)x6 h/day x 3 days to mimic the CAPs protocol (February, 1998). The rats allowed 18 h recovery following CAPs exposure (#F) did not depict any CAPs-related differences in bronchoalveolar lavage fluid (BALF) injury markers. Of the four CAPs studies conducted (0 h time point), the first (#A) study (approximately 650 microg/m3 CAPs) revealed significant changes in the lungs of CAPs-exposed bronchitic rats compared to the clean air controls. These rats had increased BALF protein, albumin, N-acetyl glutaminidase (NAG) activity and neutrophils. The second (#B) study (approximately 475 microg/m3 CAPs) did not reveal any significant effects of CAPs on BALF parameters. Study protocols #C (approximately 869 microg/m3 CAPs) and #D (approximately 907 microg/m3 CAPs) revealed only moderate increases in the above mentioned BALF parameters in bronchitic rats exposed to CAPs. Pulmonary histologic evaluation of studies #A, #C, #D, and #F revealed marginally higher congestion and perivascular cellularity in CAPs-exposed bronchitic rats. Healthy and bronchitic rats exposed to ROFA (approximately 1 mg/m3) did not show significant pulmonary injury (#E). Analysis of leachable elemental components of CAPs revealed the presence of sulfur, zinc, manganese, and iron. There was an apparent lack of association between pulmonary injury and CAPs concentration, or its leachable sulfate or elemental content. In summary, real-time atmospheric PM may result in pulmonary injury, particularly in susceptible models. However, the variability observed in pulmonary responses to CAPs emphasizes the need to conduct repeated studies, perhaps in relation to the season, as composition of CAPs may vary. Additionally, potential variability in pathology of induced bronchitis or other lung disease may decrease the ability to distinguish toxic injury due to PM.

Concentrated Ambient Air Particles Induce Vasoconstriction of Small Pulmonary Arteries in Rats

“…Recently, this rat model of chronic bronchitis (CB) was used to study the effects of inhaled ambient particles (8,9) using the Harvard Ambient Particle Concentrator (HAPC). This device concentrates ambient outdoor particles in the fine particle range (0.1-2.5 µm) for subsequent direct delivery for animal exposure (10,11).…”

“…This device concentrates ambient outdoor particles in the fine particle range (0.1-2.5 µm) for subsequent direct delivery for animal exposure (10,11). These studies demonstrated that concentrated ambient particles (CAPs) induced changes in pulmonary breathing parameters and elicited variable degrees of pulmonary inflammation (8,9).…”

Toxicological Evaluation of Realistic Emissions of Source Aerosols (Teresa): Application to Power Plant-Derived PM2.5

“…In the associations observed in this study between neutral sulfate and flow parameters (PEF and EF50), neutral sulfate concentrations ranged from 5.6 -139 g/m studies have not shown any association with sulfate. Indeed, while a number of CAPs studies in our laboratory and others have shown biological responses (Kodavanti et al 2000;Gurgiera et al 2002;Wellenius et al 2003;Urch et al 2004;Maciejczyk & Chen, 2005), these studies did not find associations between these effects and either measured sulfate or a sulfate factor. Kodavanti et al (2000) found that the leachable sulfate in CAPs from Research Triangle Park, NC, was not related to inflammatory responses in rats.…”

“…Indeed, while a number of CAPs studies in our laboratory and others have shown biological responses (Kodavanti et al 2000;Gurgiera et al 2002;Wellenius et al 2003;Urch et al 2004;Maciejczyk & Chen, 2005), these studies did not find associations between these effects and either measured sulfate or a sulfate factor. Kodavanti et al (2000) found that the leachable sulfate in CAPs from Research Triangle Park, NC, was not related to inflammatory responses in rats. Increased activation of nuclear factor (NF)-κB in human bronchial epithelial cells did not correlate with sulfate from CAPs from the New York area (where sulfate constituted 65% of the PM mass) (Maciejczyk & Chen, 2005).…”

“…These CAPs investigations have used factor analysis to determine the contribution of source factors. To date, factors related to sulfate and other products of coal combustion have not been identified among the most toxic factors Kodavanti et al, 2000;Wellenius et al, 2003;Saldiva et al, 2002). The CAPs approach differs from the TERESA approach in that CAPs represent the full and complex ambient environment; these particles contain contributions from a variety of pollutant sources.…”