Faculty Bibliography

BACKGROUND: Long-term exposure to ambient particulate matter (PM) air pollution is associated with increased cardiovascular disease (CVD); however, the impact of PM on clinical risk factors for CVD in healthy subjects is unclear. We examined the relationship of PM with levels of circulating lipids and blood pressure in the Third National Health and Nutrition Examination Survey (NHANES III), a large nationally-representative US survey. METHODS: This study was based on 11,623 adult participants of NHANES III (1988-1994; median age 41.0). Serum lipids and blood pressure were measured during the NHANES III examination. Average exposure for 1988-1994 to particulate matter <10microm in aerodynamic diameter (PM10) at the residences of participants was estimated based on measurements from U.S. Environmental Protection Agency monitors. Multivariate linear regression was used to estimate the associations of PM10 with lipids and blood pressure. RESULTS: An interquartile range width (IQRw) increase in PM10 exposure (11.1 microg/m) in the study population was associated with 2.42 percent greater serum triglycerides (95% confidence interval [CI]: 1.09-3.76); multivariate adjusted means of triglycerides according to increasing quartiles of PM10 were 137.6, 142.5, 142.6, and 148.9 mg/dL, respectively. An IQRw increase in PM10 was associated with 1.43 percent greater total cholesterol (95% CI: 1.21-1.66). These relationships with triglycerides and total cholesterol did not differ by age or region. Associations of PM10 with blood pressure were modest. CONCLUSIONS: Findings from this large diverse study indicate that greater long-term PM10 exposure is associated with elevated serum triglycerides and total cholesterol, potentially mediating air pollution-related effects on CVD.

BACKGROUND: Outdoor fine particulate matter (PM2.5) has been identified as a global health threat, but the number of large U.S. prospective cohort studies with individual participant data remains limited, especially at lower recent exposures. OBJECTIVES: To test the relationship between long-term exposure PM2.5 and death risk from all non-accidental causes, cardiovascular (CVD), and respiratory diseases in 517,041 men and women enrolled in the National Institutes of Health-AARP cohort. METHODS: Individual participant data were linked with residence PM2.5 exposure estimates across the continental U.S for a 2000-2009 follow up period when matching census-tract level PM2.5 exposure data were available. Participants enrolled ranged from 50-71 yrs. of age, residing in 6 U.S. States and 2 cities. Cox Proportional Hazard models yielded Hazard Ratio (HR) estimates per 10 microg/m3 of PM2.5 exposure. RESULTS: PM2.5 exposure was significantly associated with total mortality (HR= 1.03, 95% CI =1.00, 1.05) and CVD mortality (HR=1.10, 95% CI=1.05, 1.15), but the association with respiratory mortality was not statistically significant (HR=1.05, 95% CI=0.98,1.13). A significant association was found with respiratory mortality only among never smokers (HR=1.27; 95% CI: 1.03, 1.56). Associations with 10 microg/m3 PM2.5 exposures in yearly participant residential annual mean, or in metropolitan area-wide mean, were consistent with baseline exposure model results. Associations with PM2.5 were similar when adjusted for ozone exposures. Analyses of California residents alone also yielded statistically significant PM2.5 mortality HR's for total and CVD mortality. CONCLUSIONS: Long-term exposure to PM2.5 air pollution was associated with an increased risk of total and CVD mortality, providing an independent test of the PM2.5 - mortality relationship in a new large U.S. prospective cohort experiencing lower post-2000 PM2.5 exposure levels.

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines, including interleukin (IL)-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], tumor necrosis factor (TNF) receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1alpha and IL-1beta), promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1alpha, IL-1beta, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin, yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indices of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1alpha, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient as compared to wild-type mice, no genotype-related differences in the other indices existed following O3 exposure. O3 caused AHR to acetyl-beta-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were non-existent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.