Estimating the associations of apparent temperature and inflammatory, hemostatic, and lipid markers in a cohort of midlife women.

Associations between temperature and cardiovascular (CVD) mortality have been reported, but the underlying biological mechanisms remain uncertain. We explored the association between apparent temperature and serum biomarkers for CVD. Using linear mixed effects models, we examined the relationships between residence-proximate apparent temperature (same day and 1, 7, and 30 days prior) and several inflammatory, hemostatic, and lipid biomarkers for midlife women from 1999 through 2004. Our study population consisted of 2,306 women with mean age of 51 years (± 3 years) enrolled in Study of Women's Health Across the Nation (SWAN) in Chicago, Illinois; Detroit, Michigan; Los Angeles and Oakland, California; Newark, New Jersey; and Pittsburgh, Pennsylvania. Mean daily apparent temperature was calculated using temperature and relative humidity data provided by the National Climatic Data Center and the US Environmental Protection Agency, while daily data for fine particles, ozone, carbon monoxide, and nitrogen dioxide from the US Environmental Protection Agency Air Quality Data Mart were considered as confounders. All analyses were stratified by warm and cold seasons. More significant (p < 0.10) negative associations were found during the warm season for various lag times, including hs-CRP, fibrinogen, tissue plasminogen activator antigen (tPA-ag), tissue plasminogen activator antigen (PAI-1), Factor VIIc, high-density lipoprotein (HDL), and total cholesterol. During the cold season, significant negative associations for fibrinogen and HDL, but significant positive associations for tPA-ag, PAI-1, and triglycerides were observed for various lag times. With the exception of ozone, pollutants did not confound these associations. Apparent temperature was associated with several serum biomarkers of CVD risk in midlife women, shedding light on potential mechanisms.

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 µg/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.

Introducing the Medical Ethics Bowl.

Although ethics is an essential component of undergraduate medical education, research suggests that current medical ethics curricula face considerable challenges in improving students' ethical reasoning. This article discusses these challenges and introduces a promising new mode of graduate and professional ethics instruction for overcoming them. We begin by describing common ethics curricula, focusing in particular on established problems with current approaches. Next, we describe a novel method of ethics education and assessment for medical students that we have devised: the Medical Ethics Bowl (MEB). Finally, we suggest the pedagogical advantages of the MEB when compared to other ethics curricula.

Association of stillbirth with ambient air pollution in a California cohort study.

Recent studies have suggested an association between air pollution and stillbirth. In this California study, we examined the records of 13,999 stillbirths and 3,012,270 livebirths occurring between 1999 and 2009. Using a retrospective cohort design and logistic regression models, we calculated the odds of stillbirth associated with each pollutant exposure by trimester and throughout the entire pregnancy. Covariates considered in the model included infant sex, maternal demographic characteristics, season of last menstrual period, apparent temperature, air basin of mother's residence, and year of conception. In single-pollutant models, we found that a 10-µg/m(3) increase in particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (odds ratio (OR) = 1.06, 95% confidence interval (CI): 0.99, 1.13) and a 10-ppb increase in nitrogen dioxide (OR = 1.08, 95% CI: 1.03, 1.13) during the entire pregnancy were associated with stillbirth. A 10-ppb increase in ozone exposure during the third trimester was also associated with a slightly elevated risk (OR = 1.03, 95% CI: 1.01, 1.05). These ozone and nitrogen dioxide findings were fairly stable after adjustment in 2-pollutant models. However, adjustment for nitrogen dioxide attenuated the full-pregnancy-particulate matter relationship. No significant associations were found for sulfur dioxide or carbon monoxide. These findings support growing evidence of an association between air pollution and adverse birth outcomes.

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.

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.

The effects of temperature and use of air conditioning on hospitalizations.

Several investigators have documented the effect of temperature on mortality, although fewer have studied its impact on morbidity. In addition, little is known about the effectiveness of mitigation strategies such as use of air conditioners (ACs). The authors investigated the association between temperature and hospital admissions in California from 1999 to 2005. They also determined whether AC ownership and usage, assessed at the zip-code level, mitigated this association. Because of the unique spatial pattern of income and climate in California, confounding of AC effects by other local factors is less likely. The authors included only persons who had a temperature monitor within 25 km of their residential zip code. Using a time-stratified case-crossover approach, the authors observed a significantly increased risk of hospitalization for multiple diseases, including cardiovascular disease, ischemic heart disease, ischemic stroke, respiratory disease, pneumonia, dehydration, heat stroke, diabetes, and acute renal failure, with a 10°F increase in same-day apparent temperature. They also found that ownership and usage of ACs significantly reduced the effects of temperature on these health outcomes, after controlling for potential confounding by family income and other socioeconomic factors. These results demonstrate important effects of temperature on public health and the potential for mitigation.

Estimating the mortality effect of the July 2006 California heat wave.

OBJECTIVE: As a result of the California heat wave in July 2006, county coroners reported that the high temperatures during that period caused approximately 147 deaths. However, heat wave-related deaths are likely to be underreported due to a lack of a clear case definition and the multi-factorial nature of heat-related mortality. Public health policy suggests a need for a careful assessment of mortality following a heat wave. In addition, it is useful to provide a comparison of the mortality impact per degree change during heat waves versus high temperatures observed during non-heat wave periods. DESIGN: Daily data were collected for mortality, weather and ozone in seven California counties impacted by the July 2006 heat wave. The association between apparent temperature and daily mortality was assessed using a Poisson regression model and combined across counties in a meta-analysis. These results were then used to estimate the increases in the number of deaths during the heat wave. RESULTS: Our analysis indicated that during the July heat wave, there was a 9% (95% CI = 1.6, 16.3) increase in daily mortality per 10 degrees Fahrenheit (F) change in apparent temperature for all counties combined. This estimate is almost 3 times larger than the effect estimated for the full warm season of May-September, during the non-heat wave years. Our estimates also determined that actual mortality during the July 2006 heat wave was 2-3 times greater than the coroner estimates. CONCLUSION: This multi-county analysis provides additional evidence that the attributable risk of mortality following a heat wave may be underestimated by examining only direct heat-related deaths. In addition, we have found that the mortality effect per degrees F is several times higher than that reported during non-heat wave periods.

Association between gaseous air pollutants and inflammatory, hemostatic and lipid markers in a cohort of midlife women.

BACKGROUND: Exposures to ambient gaseous pollutants have been linked to cardiovascular diseases (CVDs), but the biological mechanisms remain uncertain. OBJECTIVES: This study examined the changes in CVD marker levels resulting from elevated exposure to ambient gaseous pollutants in midlife women. METHODS: Annual repeated measurements of several inflammatory, hemostatic and lipid makers were obtained from 2306 midlife women enrolled in the longitudinal Study of Women's Health Across the Nation (SWAN) between 1999 and 2004. Ambient carbon monoxide (CO), nitrogen dioxide (NO2), and sulfur dioxide (SO2) data were assigned to each woman based on proximity of the monitoring station to her residential address. Short- and long-term exposures were calculated, and their associations with markers were examined using linear mixed-effects regression models, adjusted for demographic, health and other factors. RESULTS: Short-term CO exposure was associated with increased fibrinogen, i.e., every interquartile increase of average prior one-week exposure to CO was associated with 1.3% (95% CI: 0.6%, 2.0%) increase in fibrinogen. Long-term exposures to NO2 and SO2 were associated with reduced high-density lipoproteins and apolipoprotein A1, e.g., 4.0% (1.7%, 6.3%) and 4.7% (2.8%, 6.6%) decrease per interquartile increment in prior one-year average NO2 concentration, respectively. Fine particle (PM2.5) exposure confounded associations between CO/NO2 and inflammatory/hemostatic markers, while associations with lipoproteins were generally robust to PM2.5 adjustment. CONCLUSIONS: Exposures to these gas pollutants at current ambient levels may increase thrombotic potential and disrupt cholesterol metabolism, contributing to greater risk of CVDs in midlife women. Caution should be exercised in evaluating the confounding by PM2.5 exposure.

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.

The relation of occupational organic solvent exposure to symptom reporting in a sample of white and Chinese midlife women.

OBJECTIVE: This study examined the relation of occupational solvent exposure to menopausal and other symptoms in midlife women. METHODS: We conducted a cross-sectional study of 480 Chinese and 494 white women, aged 40-55 years, in Northern California. Levels of exposure to organic solvents (none, low, medium, or high) were assigned to each current job using a job-exposure matrix. RESULTS: A lower proportion of women with low occupational organic solvent exposure reported hot flashes or night sweats than working women with no solvent exposure (adjusted prevalence odds ratio [APOR] = 0.48, 95% confidence interval [CI] = 0.19-1.21). A greater proportion of women with high solvent exposure reported forgetfulness than women with no exposure (APOR = 2.51, 95% CI = 1.12-5.63). CONCLUSIONS: Some symptom reporting in midlife women was related to their occupational organic solvent exposure.

Agricultural dust exposure and respiratory symptoms among California farm operators.

OBJECTIVE: To study whether dust exposure in California agriculture is a risk factor for respiratory symptoms. METHODS: A population-based survey of 1947 California farmers collected respiratory symptoms, occupational and personal exposures. Associations between dust and respiratory symptoms were assessed by logistic regression models. RESULTS: The prevalence of persistent wheeze was 8.6%, chronic bronchitis 3.8%, chronic cough 4.2%, and asthma 7.8%. Persistent wheeze was independently associated with dust in a dose-response fashion odds ratio, 1.2 (95% confidence interval[CI]=0.8-2.0) and 1.8 (95% CI=1.1-3.2) for low and high time in dust. A borderline significant association between chronic bronchitis and dust exposure was found. Asthma was associated with keeping livestock, but not with dust exposure. CONCLUSIONS: Occupational dust exposure among California farmers, only one third of whom tended animals, was independently associated with chronic respiratory symptoms.

Proximity of California public schools to busy roads.

Residential proximity to busy roads has been associated with adverse health outcomes, and school location may also be an important determinant of children's exposure to traffic-related pollutants. The goal of this study was to examine the characteristics of public schools (grades K-12) in California (n = 7,460) by proximity to major roads. We determined maximum daily traffic counts for all roads within 150 m of the school using a statewide road network and a geographic information system. Statewide, 173 schools (2.3%) with a total enrollment of 150,323 students were located within 150 m of high-traffic roads (greater than or equal to 50,000 vehicles/day); 536 schools (7.2%) were within 150 m of medium-traffic roads (25,000-49,999 vehicles/day). Traffic exposure was related to race/ethnicity. For example, the overall percentage of nonwhite students was 78% at the schools located near high-traffic roads versus 60% at the schools with very low exposure (no streets with counted traffic data within 150 m). As the traffic exposure of schools increased, the percentage of both non-Hispanic black and Hispanic students attending the schools increased substantially. Traffic exposure was also related to school-based and census-tract-based socioeconomic indicators, including English language learners. The median percentage of children enrolled in free or reduced-price meal programs increased from 40.7% in the group with very low exposure to 60.5% in the highest exposure group. In summary, a substantial number of children in California attend schools close to major roads with very high traffic counts, and a disproportionate number of those students are economically disadvantaged and nonwhite.

The effect of temperature on hospital admissions in nine California counties.

OBJECTIVES: This study examined the association between mean daily apparent temperature and hospital admissions for several diseases in nine California counties from May to September, 1999 to 2005. METHODS: We conducted a time-stratified case-crossover study limited to cases with residential zip codes located within 10 km of a temperature monitor. County-specific estimates were combined, using a random effects meta-analysis. The analyses also considered the effects of ozone and particulate matter (PM(2.5)). RESULTS: We found that a 10 degrees F increase in mean apparent temperature was associated with a 3.5% [95% confidence interval (CI) 1.5-5.6] increase in ischemic stroke and increases in several other disease-specific outcomes including all respiratory diseases (2.0%, 95% CI 0.7-3.2), pneumonia (3.7%, 95% CI 1.7-3.7), dehydration (10.8%, 95% CI 8.3-13.6), diabetes (3.1%, 95% CI 0.4-5.9), and acute renal failure (7.4%, 95% CI 4.0-10.9). There was little evidence that the temperature effects we found were due to confounding by either PM(2.5) or ozone. CONCLUSION: Our results indicate that increases in ambient temperature have important public health impacts on morbidity.

Residential exposure to traffic and spontaneous abortion.

BACKGROUND: Studies have shown associations between air pollution or traffic exposure and adverse birth outcomes, such as low birth weight. However, very few studies have examined the effect of traffic emissions on spontaneous abortion (SAB). OBJECTIVE: The goal of this study was to determine whether residential exposure to vehicular traffic was associated with SAB. METHODS: Pregnant women from a prepaid health plan in California were recruited into a prospective cohort study in 1990-1991. Three measures of traffic exposure were constructed for the 4,979 participants using annual average daily traffic (AADT) counts near each residence and distance from residence to major roads. SAB was examined in relation to the traffic exposure measures using logistic regression adjusting for a number of demographic and lifestyle variables. RESULTS: Of the traffic measures, maximum annual average traffic within 50 m showed the strongest association with SAB, although it was not statistically significant. The adjusted odds ratio (AOR) for the top 90th percentile (AADT greater than 15,199) versus the bottom 75th percentile (AADT = 0-1,089) was 1.18 [95% confidence interval (CI), 0.87-1.60]. However, subgroup analyses showed statistically significant associations for traffic with SAB among African Americans (AOR = 3.11; 95% CI, 1.26-7.66) and nonsmokers (AOR = 1.47; 95% CI, 1.07-2.04). CONCLUSION: In this cohort, living within 50 m of a road with AADT of 15,200 or more was significantly associated with SAB among African Americans and nonsmokers. Further research is needed to confirm these results and possibly elucidate the mechanisms responsible for the findings.