Rachel Broadwin

Fine Particulate Air Pollution and Mortality in Nine California Counties: Results from CALFINE

Many epidemiologic studies provide evidence of an association between daily counts of mortality and ambient particulate matter < 10 μm in diameter (PM10). Relatively few studies, however, have investigated the relationship of mortality with fine particles [PM < 2.5 μm in diameter (PM2.5)], especially in a multicity setting. We examined associations between PM2.5 and daily mortality in nine heavily populated California counties using data from 1999 through 2002. We considered daily counts of all-cause mortality and several cause-specific subcategories (respiratory, cardiovascular, ischemic heart disease, and diabetes). We also examined these associations among several subpopulations, including the elderly (> 65 years of age), males, females, non-high school graduates, whites, and Hispanics. We used Poisson multiple regression models incorporating natural or penalized splines to control for covariates that could affect daily counts of mortality, including time, seasonality, temperature, humidity, and day of the week. We used meta-analyses using random-effects models to pool the observations in all nine counties. The analysis revealed associations of PM2.5 levels with several mortality categories. Specifically, a 10-μg/m3 change in 2-day average PM2.5 concentration corresponded to a 0.6% (95% confidence interval, 0.2–1.0%) increase in all-cause mortality, with similar or greater effect estimates for several other subpopulations and mortality subcategories, including respiratory disease, cardiovascular disease, diabetes, age > 65 years, females, deaths out of the hospital, and non-high school graduates. Results were generally insensitive to model specification and the type of spline model used. This analysis adds to the growing body of evidence linking PM2.5 with daily mortality.

Coarse and fine particles and daily mortality in the Coachella Valley, California: a follow-up study.

Many epidemiological studies provide evidence of an association between ambient particles, measured as PM10, and daily mortality. Most of these studies have been conducted in urban areas where PM10 is highly correlated with and dominated by fine particles less than 2.5 μm in diameter (PM2.5). Fewer studies have investigated impacts associated with the fraction of coarse mode particles (between 2.5 and 10 μm in diameter). In a previous study using data from 1989 through 1992 in the Coachella Valley, a desert resort and retirement area east of Los Angeles, we reported associations between PM10 and several different measures of mortality [Ostro B.D., Hurley S., and Lipsett M.J. Air pollution and daily mortality in the Coachella Valley, California: a study of PM10 dominated by coarse particles. Environ. Res. 1999: 81: 231–238]. In this arid environment, coarse particles of geologic origin are highly correlated with and comprise approximately 60% of PM10, increasing to >90% during wind events. This study was intended to repeat the earlier investigation using 10 years (1989–1998) of daily data on mortality and PM10. The last 2.5 years of data also included daily measures of PM2.5, allowing examination of size-specific impacts. To ensure adequate statistical power, we attempted to develop predictive models for both fine and coarse particles to use in analyses of the full 10-year period. An acceptable fit was found only for coarse particles, which were found to be a cubic function of PM10 (R2=0.95). Outcome variables included several measures of daily mortality, including all-cause (minus accidents and homicides), cardiovascular and respiratory mortality. Multivariate Poisson regression analyses using generalized additive models were employed to explain the variation in these endpoints, controlling for temperature, humidity, day of the week, season, and time, using locally weighted smoothing techniques. Pollution lags of up to 4 days were examined. Several pollutants were associated with all-cause mortality, including PM2.5, carbon monoxide and nitrogen dioxide. More consistent results were found for cardiovascular-specific mortality, for which associations were found for coarse particles (RR=1.02; 95% C.I., 1.01–1.04), PM10 (RR=1.03; 95% C.I., 1.01–1.05). None of the pollutants was associated with respiratory-specific mortality. Ozone was not associated with any of the mortality outcomes. These findings are generally consistent with those we previously reported for the Coachella Valley for the period 1989–1992, demonstrating associations between several measures of particulate matter and daily mortality in an environment in which particulate concentrations are dominated by the coarse fraction.

Developing Asthma in Childhood from Exposure to Secondhand Tobacco Smoke: Insights from a Meta-Regression

Objective Studies have identified associations between household secondhand tobacco smoke (SHS) exposure and induction of childhood asthma. However, the true nature and strength of this association remains confounded in many studies, producing inconsistent evidence. To look for sources of potential bias and try to uncover consistent patterns of relative risk estimates (RRs), we conducted a meta-analysis of studies published between 1970 and 2005. Data sources Through an extensive literature search, we identified 38 epidemiologic studies of SHS exposure and the development of childhood asthma (that also controlled for atopy history) from 300 potentially relevant articles. Data synthesis We observed substantial heterogeneity within initial summary RRs of 1.48 [95% confidence interval (CI), 1.32–1.65], 1.25 (1.21–1.30), and 1.21 (1.08–1.36), for ever, current, and incident asthma, respectively. Lack of control for type of atopy history (familial or child) and child’s own smoking status within studies and age category altered summary RRs in separate meta-regressions. After adjusting for these confounding characteristics, consistent patterns of association emerged between SHS exposure and childhood asthma induction. Our summary RR of 1.33 (95% CI, 1.14–1.56) from studies of incident asthma among older children (6–18 years of age) is 1.27 times the estimate from studies of younger children and higher than estimates reported in earlier meta-analyses. Conclusions This new finding indicates that exposure duration may be a more important factor in the induction of asthma than previously understood, and suggests that SHS could be a more fundamental and widespread cause of childhood asthma than some previous meta-analyses have indicated.

The effect of high ambient temperature on emergency room visits.

Background: The association between temperature and mortality has been widely researched, although the association between temperature and morbidity has been less studied. We examined the association between mean daily apparent temperature and emergency room (ER) visits in California. Methods: We used a time-stratified case-crossover design, restricting our data to the warm seasons of 2005–2008 in 16 climate zones. The study population included cases residing within 10 km of meteorologic monitors. Conditional logistic regression models with apparent temperature were applied by climate zone; these models were then combined in meta-analyses to estimate overall effects. Our analyses considered the effects by disease subgroup, race/ethnic group, age group, and potential confounding by air pollutants. Results: More than 1.2 million ER visits were included. Positive associations were found for same-day apparent temperature and ischemic heart disease (% excess risk per 10°F = 1.7 [95% confidence interval = 0.2 to 3.3]), ischemic stroke (2.8 [0.9 to 4.7]), cardiac dysrhythmia (2.8 [0.9 to 4.9]), hypotension (12.7 [8.3 to 17.4]), diabetes (4.3 [2.8 to 5.9]), intestinal infection (6.1 [3.3 to 9.0]), dehydration (25.6 [21.9 to 29.4]), acute renal failure (15.9 [12.7 to 19.3]), and heat illness (393.3 [331.2 to 464.5]). Negative associations were found for aneurysm, hemorrhagic stroke, and hypertension. Most of these estimates remained relatively unchanged after adjusting for air pollutants. Risks often varied by age or racial/ethnic group. Conclusions: Increased temperatures were found to have same-day effects on ER admission for several outcomes. Age and race/ethnicity seemed to modify some of these impacts.

Evaluation and Application of the RD50 for Determining Acceptable Exposure Levels of Airborne Sensory Irritants for the General Public

Background The RD50 (exposure concentration producing a 50% respiratory rate decrease) test evaluates airborne chemicals for sensory irritation and has become an American Society for Testing and Materials (ASTM) standard method. Past studies reported good correlations (R2) between RD50s and the occupational exposure limits, particularly threshold limit values (TLVs). Objective The main purpose of this study was to examine the relationship between RD50s and human sensory irritation responses in a quantitative manner, particularly for chemicals that produce burning sensation of the eyes, nose, or throat, based on lowest observed adverse effect levels (LOAELs) reported for human subjects. Methods We compared RD50s with LOAELs and acute reference exposure levels (RELs). RELs, developed by the California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment, represent a level at which no adverse effects are anticipated after exposure. We collected RD50s from the published literature and evaluated them for consistency with ASTM procedures. We identified LOAELs for human irritation and found 25 chemicals with a corresponding RD50 in mice. Discussion We found the relationship between RD50s and LOAELs as log RD50 = 1.16 (log LOAEL) + 0.77 with an R2 value of 0.80. This strong correlation supports the use of the RD50 in establishing exposure limits for the public. We further identified 16 chemical irritants with both RD50s and corresponding acute RELs, and calculated the relationship as log RD50 = 0.71 (log REL) + 2.55 with an R2 value of 0.71. This relationship could be used to identify health protective values for the public to prevent respiratory or sensory irritation. Conclusion Consequently, we believe that the RD50 has benefits for use in setting protective levels for the health of both workers and the general population.

Effects of fine particulate matter and its constituents on low birth weight among full-term infants in California.

Relationships between prenatal exposure to fine particles (PM2.5) and birth weight have been observed previously. Few studies have investigated specific constituents of PM2.5, which may identify sources and major contributors of risk. We examined the effects of trimester and full gestational prenatal exposures to PM2.5 mass and 23 PM2.5 constituents on birth weight among 646,296 term births in California between 2000 and 2006. We used linear and logistic regression models to assess associations between exposures and birth weight and risk of low birth weight (LBW; <2500g), respectively. Models were adjusted for individual demographic characteristics, apparent temperature, month and year of birth, region, and socioeconomic indicators. Higher full gestational exposures to PM2.5 mass and several PM2.5 constituents were significantly associated with reductions in term birth weight. The largest reductions in birth weight were associated with exposure to vanadium, sulfur, sulfate, iron, elemental carbon, titanium, manganese, bromine, ammonium, zinc, and copper. Several of these PM2.5 constituents were associated with increased risk of term LBW. Reductions in birth weight were generally larger among younger mothers and varied by race/ethnicity. Exposure to specific constituents of PM2.5, especially traffic-related particles, sulfur constituents, and metals, were associated with decreased birth weight in California.

Chronic PM2.5 exposure and inflammation: determining sensitive subgroups in mid-life women.

BACKGROUND Several cohort studies report associations between chronic exposure to ambient fine particles (PM2.5) and cardiovascular mortality. Uncertainty exists about biological mechanisms responsible for this observation, but systemic inflammation has been postulated. In addition, the subgroups susceptible to inflammation have not been fully elucidated. METHODS We investigated whether certain subgroups are susceptible to the effects of long-term exposure to PM2.5 on C-reactive protein (CRP), a marker of inflammation directly linked to subsequent cardiovascular disease. We used data from the SWAN cohort of 1923 mid-life women with up to five annual repeated measures of CRP. Linear mixed and GEE models accounting for repeated measurements within an individual were used to estimate the effects of prior-year PM2.5 exposure on CRP. We examined CRP as a continuous and as binary outcome for CRP greater than 3mg/l, a level of clinical significance. RESULTS We found strong associations between PM2.5 and CRP among several subgroups. For example a 10 µg/m(3) increase in annual PM2.5 more than doubled the risk of CRP greater than 3mg/l in older diabetics, smokers and the unmarried. Larger effects were also observed among those with low income, high blood pressure, or who were using hormone therapy, with indications of a protective effects for those using statins or consuming moderate amounts of alcohol. CONCLUSIONS In this study, we observed significant associations between long-term exposure to PM2.5 and CRP in several susceptible subgroups. This suggests a plausible pathway by which exposure to particulate matter may be associated with increased risk of cardiovascular disease.

Coarse Particles and Respiratory Emergency Department Visits in California

Although respiratory disease has been strongly connected to fine particulate air pollution (particulate matter <2.5 μm in diameter (PM2.5)), evidence has been mixed regarding the effects of coarse particles (particulate matter from 2.5 to 10 μm in diameter), possibly because of the greater spatial heterogeneity of coarse particles. In this study, we evaluated the relationship between coarse particles and respiratory emergency department visits, including common subdiagnoses, from 2005 to 2008 in 35 California counties. A time-stratified case-crossover design was used to help control for time-invariant confounders and seasonal influences, and the study population was limited to those residing within 20 km of pollution monitors to mitigate the influence of spatial heterogeneity. Significant associations between respiratory emergency department visits and coarse particle levels were observed. Asthma visits showed associations (for 2-day lag, excess risk per 10 μg/m³ = 3.3%, 95% confidence interval: 2.0, 4.6) that were robust to adjustment by other common air pollutants (particles <2.5 μm in diameter, ozone, nitrogen dioxide, carbon monoxide, and sulfur dioxide). Pneumonia and acute respiratory infection visits were not associated, although some suggestion of a relationship with chronic obstructive pulmonary disease visits was present. Our results indicate that coarse particle exposure may trigger asthma exacerbations requiring emergency care, and reducing exposures among asthmatic persons may provide benefits.

A Time-Stratified Case-Crossover Study of Ambient Ozone Exposure and Emergency Department Visits for Specific Respiratory Diagnoses in California (2005-2008).

Background: Studies have explored ozone’s connection to asthma and total respiratory emergency department visits (EDVs) but have neglected other specific respiratory diagnoses despite hypotheses relating ozone to respiratory infections and allergic responses. Objective: We examined relationships between ozone and EDVs for respiratory visits, including specifically acute respiratory infections (ARI), asthma, pneumonia, chronic obstructive pulmonary disease (COPD), and upper respiratory tract inflammation (URTI). Methods: We conducted a multi-site time-stratified case-crossover study of ozone exposures for approximately 3.7 million respiratory EDVs from 2005 through 2008 among California residents living within 20 km of an ozone monitor. Conditional logistic regression was used to estimate associations by climate zone. Random effects meta-analysis was then applied to estimate pooled excess risks (ER). Effect modification by season, distance from the monitor and individual demographic characteristics (i.e., age, race/ethnicity, sex, and payment method), and confounding by other gaseous air pollutants were also investigated. Meta-regression was utilized to explore how climate zone–level meteorological, demographic, and regional differences influenced estimates. Results: We observed ozone-associated increases in all respiratory, asthma, and ARI visits, which were slightly larger in the warm season [asthma ER per 10-ppb increase in mean of same and previous 3 days ozone exposure (lag03) = 2.7%, 95% CI: 1.5, 3.9; ARI ERlag03 = 1.4%, 95% CI: 0.8, 1.9]. EDVs for pneumonia, COPD, and URTI were also significantly associated with ozone exposure over the whole year, but typically more consistently so during the warm season. Conclusions: Short-term ozone exposures among California residents living near an ozone monitor were positively associated with EDVs for asthma, ARI, pneumonia, COPD, and URTI from 2005 through 2008. Those associations were typically larger and more consistent during the warm season. Our findings suggest that these outcomes should be considered when evaluating the potential health benefits of reducing ozone concentrations. Citation: Malig BJ, Pearson DL, Chang YB, Broadwin R, Basu R, Green RS, Ostro B. 2016. A time-stratified case-crossover study of ambient ozone exposure and emergency department visits for specific respiratory diagnoses in California (2005–2008). Environ Health Perspect 124:745–753; http://dx.doi.org/10.1289/ehp.1409495

Long- and Short-term Exposure to Air Pollution and Inflammatory/Hemostatic Markers in Midlife Women.

Background: Studies have reported associations between long-term air pollution exposures and cardiovascular mortality. The biological mechanisms connecting them remain uncertain. Methods: We examined associations of fine particles (PM2.5) and ozone with serum markers of cardiovascular disease risk in a cohort of midlife women. We obtained information from women enrolled at six sites in the multi-ethnic, longitudinal Study of Women’s Health Across the Nation, including repeated measurements of high-sensitivity C-reactive protein, fibrinogen, tissue-type plasminogen activator antigen, plasminogen activator inhibitor type 1, and factor VIIc (factor VII coagulant activity). We obtained residence-proximate PM2.5 and ozone monitoring data for a maximum five annual visits, calculating prior year, 6-month, 1-month, and 1-day exposures and their relations to serum markers using longitudinal mixed models. Results: For the 2,086 women studied from 1999 to 2004, PM2.5 exposures were associated with all blood markers except factor VIIc after adjusting for age, race/ethnicity, education, site, body mass index, smoking, and recent alcohol use. Adjusted associations were strongest for prior year exposures for high-sensitivity C-reactive protein (21% increase per 10 &mgr;g/m3 PM2.5, 95% confidence interval [CI]: 6.6, 37), tissue-type plasminogen activator antigen (8.6%, 95% CI: 1.8, 16), and plasminogen activator inhibitor (35%, 95% CI: 19, 53). An association was also observed between year prior ozone exposure and factor VIIc (5.7% increase per 10 ppb ozone, 95% CI: 2.9, 8.5). Conclusions: Our findings suggest that prior year exposures to PM2.5 and ozone are associated with adverse effects on inflammatory and hemostatic pathways for cardiovascular outcomes in midlife women.