Modeling spatial effects of PM₂.₅ on term low birth weight in Los Angeles County

Air pollution epidemiological studies suggest that elevated exposure to fine particulate matter (PM₂.₅) is associated with higher prevalence of term low birth weight (TLBW). Previous studies have generally assumed the exposure–response of PM₂.₅ on TLBW to be the same throughout a large geographical area. Health effects related to PM₂.₅ exposures, however, may not be uniformly distributed spatially, creating a need for studies that explicitly investigate the spatial distribution of the exposure–response relationship between individual-level exposure to PM₂.₅ and TLBW. Here, we examine the overall and spatially varying exposure–response relationship between PM₂.₅ and TLBW throughout urban Los Angeles (LA) County, California. We estimated PM₂.₅ from a combination of land use regression (LUR), aerosol optical depth from remote sensing, and atmospheric modeling techniques. Exposures were assigned to LA County individual pregnancies identified from electronic birth certificates between the years 1995-2006 (N=1,359,284) provided by the California Department of Public Health. We used a single pollutant multivariate logistic regression model, with multilevel spatially structured and unstructured random effects set in a Bayesian framework to estimate global and spatially varying pollutant effects on TLBW at the census tract level. Overall, increased PM₂.₅ level was associated with higher prevalence of TLBW county-wide. The spatial random effects model, however, demonstrated that the exposure–response for PM₂.₅ and TLBW was not uniform across urban LA County. Rather, the magnitude and certainty of the exposure–response estimates for PM₂.₅ on log odds of TLBW were greatest in the urban core of Central and Southern LA County census tracts. These results suggest that the effects may be spatially patterned, and that simply estimating global pollutant effects obscures disparities suggested by spatial patterns of effects. Studies that incorporate spatial multilevel modeling with random coefficients allow us to identify areas where air pollutant effects on adverse birth outcomes may be most severe and policies to further reduce air pollution might be most effectiveKEYWORDS: Multilevel modeling, Term low birth weight, Air pollution, PM2.5, Spatial effects, PM₂.₅This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Elsevier. The published article can be found at: http://www.journals.elsevier.com/environmental-research

Spiral ligament fibrocyte-derived MCP-1/CCL2 contributes to inner ear inflammation secondary to nontypeable H. influenzae-induced otitis media

<p>Abstract</p> <p>Background</p> <p>Otitis media (OM), one of the most common pediatric infectious diseases, causes inner ear inflammation resulting in vertigo and sensorineural hearing loss. Previously, we showed that spiral ligament fibrocytes (SLFs) recognize OM pathogens and up-regulate chemokines. Here, we aim to determine a key molecule derived from SLFs, contributing to OM-induced inner ear inflammation.</p> <p>Methods</p> <p>Live NTHI was injected into the murine middle ear through the tympanic membrane, and histological analysis was performed after harvesting the temporal bones. Migration assays were conducted using the conditioned medium of NTHI-exposed SLFs with and without inhibition of MCP-1/CCL2 and CCR2. qRT-PCR analysis was performed to demonstrate a compensatory up-regulation of alternative genes induced by the targeting of MCP-1/CCL2 or CCR2.</p> <p>Results</p> <p>Transtympanic inoculation of live NTHI developed serous and purulent labyrinthitis after clearance of OM. THP-1 cells actively migrated and invaded the extracellular matrix in response to the conditioned medium of NTHI-exposed SLFs. This migratory activity was markedly inhibited by the viral CC chemokine inhibitor and the deficiency of MCP-1/CCL2, indicating that MCP-1/CCL2 is a main attractant of THP-1 cells among the SLF-derived molecules. We further demonstrated that CCR2 deficiency inhibits migration of monocyte-like cells in response to NTHI-induced SLF-derived molecules. Immunolabeling showed an increase in MCP-1/CCL2 expression in the cochlear lateral wall of the NTHI-inoculated group. Contrary to the <it>in vitro </it>data, deficiency of MCP-1/CCL2 or CCR2 did not inhibit OM-induced inner ear inflammation <it>in vivo</it>. We demonstrated that targeting MCP-1/CCL2 enhances NTHI-induced up-regulation of MCP-2/CCL8 in SLFs and up-regulates the basal expression of CCR2 in the splenocytes. We also found that targeting CCR2 enhances NTHI-induced up-regulation of MCP-1/CCL2 in SLFs.</p> <p>Conclusions</p> <p>Taken together, we suggest that NTHI-induced SLF-derived MCP-1/CCL2 is a key molecule contributing to inner ear inflammation through CCR2-mediated recruitment of monocytes. However, deficiency of MCP-1/CCL2 or CCR2 alone was limited to inhibit OM-induced inner ear inflammation due to compensation of alternative genes.</p

Modeling spatial effects of PM2.5 on term low birth weight in Los Angeles County

Air pollution epidemiological studies suggest that elevated exposure to fine particulate matter (PM2.5) is associated with higher prevalence of term low birth weight (TLBW). Previous studies have generally assumed the exposure–response of PM2.5 on TLBW to be the same throughout a large geographical area. Health effects related to PM2.5 exposures, however, may not be uniformly distributed spatially, creating a need for studies that explicitly investigate the spatial distribution of the exposure–response relationship between individual-level exposure to PM2.5 and TLBW. Here, we examine the overall and spatially varying exposure–response relationship between PM2.5 and TLBW throughout urban Los Angeles (LA) County, California. We estimated PM2.5 from a combination of land use regression (LUR), aerosol optical depth from remote sensing, and atmospheric modeling techniques. Exposures were assigned to LA County individual pregnancies identified from electronic birth certificates between the years 1995-2006 (N=1,359,284) provided by the California Department of Public Health. We used a single pollutant multivariate logistic regression model, with multilevel spatially structured and unstructured random effects set in a Bayesian framework to estimate global and spatially varying pollutant effects on TLBW at the census tract level. Overall, increased PM2.5 level was associated with higher prevalence of TLBW county-wide. The spatial random effects model, however, demonstrated that the exposure–response for PM2.5 and TLBW was not uniform across urban LA County. Rather, the magnitude and certainty of the exposure–response estimates for PM2.5 on log odds of TLBW were greatest in the urban core of Central and Southern LA County census tracts. These results suggest that the effects may be spatially patterned, and that simply estimating global pollutant effects obscures disparities suggested by spatial patterns of effects. Studies that incorporate spatial multilevel modeling with random coefficients allow us to identify areas where air pollutant effects on adverse birth outcomes may be most severe and policies to further reduce air pollution might be most effective.Research described in this article was conducted under contract to the Health Effects Institute (HEI), an organization jointly funded by the United States Environmental Protection Agency (EPA) (Assistance Award No. R-82811201) and certain motor vehicle and engine manufacturers