Synergy of Biostatistics and Epidemiology in Air Pollution Health Effects Studies.

The extraordinary advances in quantifying the health effects of ambient air pollution over the last five decades have led to dramatic improvement in air quality in the United States. This work has been possible through innovative epidemiologic study designs coupled with advanced statistical analytic methods. This paper presents a historical perspective on the coordinated developments of epidemiologic designs and statistical methods for air pollution health effects studies at the Harvard School of Public Health.

Antenatal depressive symptoms and adverse perinatal outcomes.

BACKGROUND: The association of antenatal depression with adverse pregnancy, birth, and postnatal outcomes has been an item of scientific interest over the last decades. However, the evidence that exists is controversial or limited. We previously found that one in five women in Kuwait experience antenatal depressive symptoms. Therefore, the aim of this study was to examine whether antenatal depressive symptoms are associated with preterm birth (PTB), small for gestational age (SGA), or large for gestational age (LGA) babies in this population. METHODS: This was a secondary analysis based on data collected in the Transgenerational Assessment of Children's Environmental Risk (TRACER) Study that was conducted in Kuwait. Logistic regression analysis was used to examine whether antenatal depressive symptoms assessed using the Edinburgh Depression Scale (EDS) were associated with preterm birth, small for gestational age, and large for gestational age babies. RESULTS: A total of 1694 women had complete information about the outcomes of interest. Women with depressive symptoms in pregnancy had increased, albeit non-significant, odds of having PTB (OR = 1.41; 95%CI: 0.81, 2.45), SGA babies (OR = 1.26; 0.80, 1.98), or LGA babies (OR = 1.27; 0.90, 1.79). Antenatal depressive symptoms had similar increased odds for the three outcomes even after adjusting for several covariates though none of these reached statistical significance. CONCLUSIONS: In the present study, the depressive symptoms in pregnancy did not predict adverse birth outcomes, such as PTB, SGA, and LGA, which adds to the currently non-conclusive literature. However, further research is needed to examine these associations, as the available evidence is quite limited.

Mortality Benefits and Control Costs of Improving Air Quality in Mexico City: The Case of Heavy Duty Diesel Vehicles.

Diesel vehicles are significant contributors to air pollution in Mexico City. We estimate the costs and mortality benefits of retrofitting heavy-duty vehicles with particulate filters and oxidation catalysts. The feasibility and cost-effectiveness of controls differ by vehicle model-year and type. We evaluate 1985 to 2014 model-year vehicles from 10 vehicle classes and five model-year groups. Our analysis shows that retrofitting all vehicles with the control that maximizes expected net benefits for that vehicle type and model-year group has the potential to reduce emissions of primary fine particles (PM2.5 ) by 950 metric tons/year; cut the population-weighted annual mean concentration of PM2.5 in Mexico City by 0.90 µg/m3 ; reduce the annual number of deaths attributable to air pollution by over 80; and generate expected annual health benefits of close to 250 million US$. These benefits outweigh expected costs of 92 million US$ per year. Diesel retrofits are but one step that should viewed in the context of other efforts--such as development of an integrated public transportation system, promotion of the rational use of cars, reduction of emissions from industrial sources and fires, and redesign of the Mexico City Metropolitan Area to reduce urban sprawl--that must be analyzed and implemented to substantially control air pollution and protect public health. Even if considering other potential public health interventions, which would offer greater benefits at the same or lower costs, only by conducting, promoting, and publishing this sort of analyses, we can make strides to improve public health cost-effectively.

Guidance to Reduce the Cardiovascular Burden of Ambient Air Pollutants: A Policy Statement From the American Heart Association.

In 2010, the American Heart Association published a statement concluding that the existing scientific evidence was consistent with a causal relationship between exposure to fine particulate matter and cardiovascular morbidity and mortality, and that fine particulate matter exposure is a modifiable cardiovascular risk factor. Since the publication of that statement, evidence linking air pollution exposure to cardiovascular health has continued to accumulate and the biological processes underlying these effects have become better understood. This increasingly persuasive evidence necessitates policies to reduce harmful exposures and the need to act even as the scientific evidence base continues to evolve. Policy options to mitigate the adverse health impacts of air pollutants must include the reduction of emissions through action on air quality, vehicle emissions, and renewable portfolio standards, taking into account racial, ethnic, and economic inequality in air pollutant exposure. Policy interventions to improve air quality can also be in alignment with policies that benefit community and transportation infrastructure, sustainable food systems, reduction in climate forcing agents, and reduction in wildfires. The health care sector has a leadership role in adopting policies to contribute to improved environmental air quality as well. There is also potentially significant private sector leadership and industry innovation occurring in the absence of and in addition to public policy action, demonstrating the important role of public-private partnerships. In addition to supporting education and research in this area, the American Heart Association has an important leadership role to encourage and support public policies, private sector innovation, and public-private partnerships to reduce the adverse impact of air pollution on current and future cardiovascular health in the United States.

Exposure to Air Pollution and Particle Radioactivity With the Risk of Ventricular Arrhythmias.

BACKGROUND: Individuals are exposed to air pollution and ionizing radiation from natural sources through inhalation of particles. This study investigates the association between cardiac arrhythmias and short-term exposures to fine particulate matter (particulate matter ≤2.5 µm aerodynamic diameter; PM2.5) and particle radioactivity. METHODS: Ventricular arrhythmic events were identified among 176 patients with dual-chamber implanted cardioverter-defibrillators in Boston, Massachusetts between September 2006 and June 2010. Patients were assigned exposures based on residential addresses. Daily PM2.5 levels were estimated at 1-km×1-km grid cells from a previously validated prediction model. Particle gross ß activity was used as a surrogate for particle radioactivity and was measured from several monitoring sites by the US Environmental Protection Agency's monitoring network. The association of the onset of ventricular arrhythmias (VA) with 0- to 21-day moving averages of PM2.5 and particle radioactivity (2 single-pollutant models and a 2-pollutant model) before the event was examined using time-stratified case-crossover analyses, adjusted for dew point and air temperatures. RESULTS: A total of 1,050 VA were recorded among 91 patients, including 123 sustained VA among 25 of these patients. In the single-pollutant model of PM2.5, each interquartile range increase in daily PM2.5 levels for a 21-day moving average was associated with 39% higher odds of a VA event (95% CI, 12%-72%). In the single-pollutant model of particle radioactivity, each interquartile range increase in particle radioactivity for a 2-day moving average was associated with 13% higher odds of a VA event (95% CI, 1%-26%). In the 2-pollutant model, for the same averaging window of 21 days, each interquartile range increase in daily PM2.5 was associated with an 48% higher odds of a VA event (95% CI, 15%-90%), and each interquartile range increase of particle radioactivity with a 10% lower odds of a VA event (95% CI, -29% to 14%). We found that with higher levels of particle radioactivity, the effect of PM2.5 on VAs is reduced. CONCLUSIONS: In this high-risk population, intermediate (21-day) PM2.5 exposure was associated with higher odds of a VA event onset among patients with known cardiac disease and indication for implanted cardioverter-defibrillator implantation independently of particle radioactivity.

Postnatal depressive symptoms in women with and without antenatal depressive symptoms: results from a prospective cohort study.

Evidence exists that the risk factors for depression in the antenatal and postnatal period may differ, but only a handful of studies looked at depression longitudinally. The aims of this study were (1) to estimate the prevalence of postnatal depressive symptoms in Kuwait where data about postnatal depression are scarce and identify its determinants and (2) to compare these risk factors between women who had experienced antenatal depressive symptoms and those that did not. Data collected in the TRansgenerational Assessment of Children's Environmental Risk (TRACER) Study in Kuwait were used in this analysis. The sample was restricted to the 1348 women who answered the Edinburgh Postnatal Depression Scale (EPDS) both antenatally and postnatally. The prevalence of postnatal depressive symptoms, defined by an EPDS score ≥ 10, was 11.7%. Overall, antenatal depressive symptoms were the strongest determinant of postnatal depressive symptoms. Multivariable logistic regression analysis showed that in women with depressive symptoms in pregnancy, having a lower household income was the most significant risk factor for postnatal depressive symptoms. Among women without antenatal depressive symptoms, those who had lower income, were Kuwaitis, experienced other problems in pregnancy such as perceived stress, PTSD symptoms and social isolation, and those who delivered a boy had higher odds of postnatal depressive symptoms. Antenatal depressive symptoms and other psychosocial characteristics can predict postnatal depressive symptoms. Therefore, maternal mental health issues should be detected during the antenatal period and support should be provided in order to lower the risk of postnatal depression and its sequelae.

Depressive symptoms and comorbid problems in pregnancy - results from a population based study.

OBJECTIVE: To estimate the prevalence of antenatal depressive symptoms, identify relevant risk factors, and assess comorbid mental health problems, among pregnant women enrolled in a population based study. METHODS: This was a secondary analysis of data collected from 1916 pregnant women who participated in the TRansgenerational Assessment of Children's Environmental Risk (TRACER) study in Kuwait, and had answered the Baseline Questionnaire and completed the Edinburgh Depression Scale (EDS). Logistic regression models were used to examine the association of depressive symptoms with baseline socio-demographic characteristics and psychosocial indicators. RESULTS: The prevalence of antenatal depressive symptoms, using a cut-off of EDS score ≥ 10, was 20.1%. Depressive symptoms were reported more by women of lower family income and had self-reported history of depression prior to pregnancy, with women in the third trimester having higher odds of antenatal depressive symptoms compared to those in the second trimester. Pregnancy-related anxiety, higher perceived stress levels, and post-traumatic stress disorder symptoms were comorbid with the presence of depressive symptoms. CONCLUSION: The findings showed that one in five pregnant women in Kuwait experiences antenatal depressive symptoms and that these symptoms are comorbid with other mental health problems. Screening for antenatal depression and providing support to pregnant women should be considered.

Coupling external with internal exposure metrics of trihalomethanes in young females from Kuwait and Cyprus.

The Eastern Mediterranean and the Middle Eastern regions are both understudied in terms of possible environmental health risks for their populations. Water scarcity and desalination treatment provide the general population of countries from these regions (e.g., Kuwait and Cyprus) with unique tap water characteristics. This study investigated the association between external (tap water and 24 h personal air samples) and internal (urine) THM exposure metrics that reflected information about THM-related habits and activities collected using questionnaires and time activity diaries. The study population comprised of young females residing in either Kuwait (n=13) or Cyprus (n=22). First morning urine voids were collected on 2 consecutive days. Urinary creatinine-adjusted total THM (TTHM) levels were higher in Kuwait (median (interquartile range): 1044 (814, 1270) ng/g) than in Cyprus (691 (510, 919) ng/g, P<0.05). Median personal air TTHM levels in Kuwait (1.4 (0.7, 1.7) µg/m3) were higher than those in Cyprus (0.9 (0.5, 1.4) µg/m3), but did not reach statistical significance (P=0.17). Median tap water TTHM in Kuwait (6.7 (5.4, 11.6) µg/l) did not correlate with urinary or air THM and they were lower than those in Cyprus (29.5 (20.1, 48.0) µg/l; P<0.01). Despite that tap water did not contain chloroform (TCM), TCM was detected in both air and urine samples in Kuwait, suggesting other TCM exposure sources, such as household cleaning activities. Total duration of activities and mopping were significantly correlated with air and urine THM in Kuwait, as reported in the time activity diary. Personal air and urine exposure metrics were correlated in Kuwait (TTHM ρ=0.62, P<0.05), but not in Cyprus (TTHM ρ=-0.32, P>0.05). Time-activity diaries and urinary THM seemed to be useful measures of THM exposures in Kuwait. Coupling both external with internal exposure metrics could find use in population health studies towards further refining the association between environmental exposures and health outcomes.

Countervailing effects of income, air pollution, smoking, and obesity on aging and life expectancy: population-based study of U.S. Counties.

BACKGROUND: Income, air pollution, obesity, and smoking are primary factors associated with human health and longevity in population-based studies. These four factors may have countervailing impacts on longevity. This analysis investigates longevity trade-offs between air pollution and income, and explores how relative effects of income and air pollution on human longevity are potentially influenced by accounting for smoking and obesity. METHODS: County-level data from 2,996 U.S. counties were analyzed in a cross-sectional analysis to investigate relationships between longevity and the four factors of interest: air pollution (mean 1999-2008 PM2.5), median income, smoking, and obesity. Two longevity measures were used: life expectancy (LE) and an exceptional aging (EA) index. Linear regression, generalized additive regression models, and bivariate thin-plate smoothing splines were used to estimate the benefits of living in counties with higher incomes or lower PM2.5. Models were estimated with and without controls for smoking, obesity, and other factors. RESULTS: Models which account for smoking and obesity result in substantially smaller estimates of the effects of income and pollution on longevity. Linear regression models without these two variables estimate that a $1,000 increase in median income (1 µg/m(3) decrease in PM2.5) corresponds to a 27.39 (33.68) increase in EA and a 0.14 (0.12) increase in LE, whereas models that control for smoking and obesity estimate only a 12.32 (20.22) increase in EA and a 0.07 (0.05) increase in LE. Nonlinear models and thin-plate smoothing splines also illustrate that, at higher levels of income, the relative benefits of the income-pollution tradeoff changed-the benefit of higher incomes diminished relative to the benefit of lower air pollution exposure. CONCLUSIONS: Higher incomes and lower levels of air pollution both correspond with increased human longevity. Adjusting for smoking and obesity reduces estimates of the benefits of higher income and lower air pollution exposure. This adjustment also alters the tradeoff between income and pollution: increases in income become less beneficial relative to a fixed reduction in air pollution-especially at higher levels of income.

Particulate Air Pollution, Exceptional Aging, and Rates of Centenarians: A Nationwide Analysis of the United States, 1980-2010.

BACKGROUND: Exceptional aging, defined as reaching age 85 years, shows geographic inequalities that may depend on local environmental conditions. Links between particulate pollution-a well-recognized environmental risk factor-and exceptional aging have not been investigated. OBJECTIVES: We conducted a nationwide analysis of ~28 million adults in 3,034 United States counties to determine whether local PM2.5 levels (particulate matter < 2.5 µm in aerodynamic diameter) affected the probability of becoming 85- to 94-year-olds or centenarians (100- to 104-year-olds) in 2010 for individuals who were 55-64 or 70-74 years old, respectively, in 1980. METHODS: We used population-weighted regression models including county-level PM2.5 from hybrid land-use regression and geostatistical interpolation, smoking, obesity, sociodemographic, and age-specific migration variables. RESULTS: On average, 2,295 and 71.4 per 10,000 of the 55- to 64- and 70- to 74-year-olds in 1980, respectively, remained in the 85- to 94- and 100- to 104-year-old population in 2010. An interquartile range (4.19 µg/m3) increase in PM2.5 was associated with 93.7 fewer 85- to 94-year-olds (p < 0.001) and 3.5 fewer centenarians (p < 0.05). These associations were nearly linear, were stable to model specification, and were detectable below the annual PM2.5 national standard. Exceptional aging was strongly associated with smoking, with an interquartile range (4.77%) increase in population who smoked associated with 181.9 fewer 85- to 94-year-olds (p < 0.001) and 6.4 fewer centenarians (p < 0.001). Exceptional aging was also associated with obesity rates and median income. CONCLUSIONS: Communities with the most exceptional aging have low ambient air pollution and low rates of smoking, poverty, and obesity. Improvements in these determinants may contribute to increasing exceptional aging. Citation: Baccarelli AA, Hales N, Burnett RT, Jerrett M, Mix C, Dockery DW, Pope CA III. 2016. Particulate air pollution, exceptional aging, and rates of centenarians: a nationwide analysis of the United States, 1980-2010. Environ Health Perspect 124:1744-1750; http://dx.doi.org/10.1289/EHP197.

Birth Outcomes in a Prospective Pregnancy-Birth Cohort Study of Environmental Risk Factors in Kuwait: The TRACER Study.

BACKGROUND: Rapid development and westernisation in Kuwait and other Gulf states have been accompanied by rising rates of obesity, diabetes, asthma, and other chronic conditions. Prenatal experiences and exposures may be important targets for intervention. We undertook a prospective pregnancy-birth cohort study in Kuwait, the TRansgenerational Assessment of Children's Environmental Risk (TRACER) Study, to examine prenatal risk factors for early childhood obesity. This article describes the methodology and results of follow-up through birth. METHODS: Women were recruited at antenatal clinical visits. Interviewers administered questionnaires during the pregnancy and collected and banked biological samples. Children are being followed up with quarterly maternal interviews, annual anthropometric measurements, and periodic collection of biosamples. Frequencies of birth outcomes (i.e. stillbirth, preterm birth, small and large for gestational age, and macrosomia) were calculated as a function of maternal characteristics and behaviours. RESULTS: Two thousand four hundred seventy-eight women were enrolled, and 2254 women were followed to delivery. Overall, frequencies of stillbirth (0.6%), preterm birth (9.3%), and small for gestational age (7.4%) were comparable to other developed countries, but not strongly associated with maternal characteristics or behaviours. Macrosomia (6.1%) and large for gestational age (23.0%) were higher than expected and positively associated with pre-pregnancy maternal overweight/obesity. CONCLUSIONS: A large birth cohort has been established in Kuwait. The collected risk factors and banked biosamples will allow examination of the effects of prenatal exposures on the development of chronic disease in children. Initial results suggest that maternal overweight/obesity before pregnancy should be targeted to prevent macrosomia and its associated sequelae of childhood overweight/obesity.

Occupational vehicle-related particulate exposure and inflammatory markers in trucking industry workers.

BACKGROUND: Previous studies have suggested an association between particulate air pollution and cardiovascular disease, but the mechanism is still unclear. OBJECTIVE: We examined the association between workplace exposure to vehicle-related particles and cardiovascular disease related systemic inflammatory markers, C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and interleukin-6 (IL-6) in 137 trucking terminal workers (non-drivers) in the U.S. trucking industry. METHODS: We visited two large trucking terminals in 2009 and measured vehicle-related elemental carbon (EC), organic carbon (OC), and particulate matter with aerodynamic diameter ≤2.5µm (PM2.5), for 5 days consecutively at the main work areas. Each participant provided a blood sample and completed a health questionnaire during the sampling period. Individual workplace exposure level was calculated by 12-h time weighted moving averages based on work shift. The association between each blood marker and exposure to each pollutant during 0-12, 12-24, 24-36, and 36-48h before the blood draw was examined by multivariable regression analyses. RESULTS: In general, OC and EC had a positive association with sICAM-1, especially for exposure periods 12-24 (lag12-24) and 24-36 (lag24-36)h prior to blood draw [ß=54.9 (95%CI: 12.3-97.5) for lag12-24 and ß=46.5 (95%CI: 21.2-71.8) for lag12-24; change in sICAM-1 (in ng/mL) corresponding to an IQR increase in OC]. A similar pattern was found for EC and PM2.5. We did not find an association between measured pollutants up to 48h before blood draw and hs-CRP or IL-6. CONCLUSION: In this group of healthy workers, short-term exposure to vehicle-related air pollutants may be associated with sICAM-1. Our findings may be dependent on the exposure period studied.

"What We Breathe Impacts Our Health: Improving Understanding of the Link between Air Pollution and Health".

Air pollution contributes to the premature deaths of millions of people each year around the world, and air quality problems are growing in many developing nations. While past policy efforts have succeeded in reducing particulate matter and trace gases in North America and Europe, adverse health effects are found at even these lower levels of air pollution. Future policy actions will benefit from improved understanding of the interactions and health effects of different chemical species and source categories. Achieving this new understanding requires air pollution scientists and engineers to work increasingly closely with health scientists. In particular, research is needed to better understand the chemical and physical properties of complex air pollutant mixtures, and to use new observations provided by satellites, advanced in situ measurement techniques, and distributed micro monitoring networks, coupled with models, to better characterize air pollution exposure for epidemiological and toxicological research, and to better quantify the effects of specific source sectors and mitigation strategies.

Daily indoor-to-outdoor temperature and humidity relationships: a sample across seasons and diverse climatic regions.

The health consequences of heat and cold are usually evaluated based on associations with outdoor measurements collected at a nearby weather reporting station. However, people in the developed world spend little time outdoors, especially during extreme temperature events. We examined the association between indoor and outdoor temperature and humidity in a range of climates. We measured indoor temperature, apparent temperature, relative humidity, dew point, and specific humidity (a measure of moisture content in air) for one calendar year (2012) in a convenience sample of eight diverse locations ranging from the equatorial region (10 °N) to the Arctic (64 °N). We then compared the indoor conditions to outdoor values recorded at the nearest airport weather station. We found that the shape of the indoor-to-outdoor temperature and humidity relationships varied across seasons and locations. Indoor temperatures showed little variation across season and location. There was large variation in indoor relative humidity between seasons and between locations which was independent of outdoor airport measurements. On the other hand, indoor specific humidity, and to a lesser extent dew point, tracked with outdoor, airport measurements both seasonally and between climates, across a wide range of outdoor temperatures. These results suggest that, in general, outdoor measures of actual moisture content in air better capture indoor conditions than outdoor temperature and relative humidity. Therefore, in studies where water vapor is among the parameters of interest for examining weather-related health effects, outdoor measurements of actual moisture content can be more reliably used as a proxy for indoor exposure than the more commonly examined variables of temperature and relative humidity.

Tradeoffs between income, air pollution and life expectancy: Brief report on the US experience, 1980-2000.

During the period of 1980-2000, the US obtained substantial reductions in air pollution and improvements in life expectancy (LE). Multiple factors contributed to improved health. This report explores and illustrates trade-offs between income, air pollution, and LE. Both improved air quality and income growth contributed to LE gains - without evidence of substantial negative tradeoffs between air pollution and income. Cleaner air may be considered an "economic good" with contributions to health, wellbeing, and human capital.

Chemical Composition of Fine Particulate Matter and Life Expectancy: In 95 US Counties Between 2002 and 2007.

BACKGROUND: In a previous study, we provided evidence that a decline in fine particulate matter (PM2.5) air pollution during the period between 2000 and 2007 was associated with increased life expectancy in 545 counties in the United States. In this article, we investigated which chemical constituents of PM2.5 were the main drivers of the observed association. METHODS: We estimated associations between temporal changes in seven major components of PM2.5 (ammonium, sulfate, nitrate, elemental carbon matter, organic carbon matter, sodium, and silicon) and temporal changes in life expectancy in 95 counties between 2002 and 2007. We included US counties that had adequate chemical components of PM2.5 mass data across all seasons. We fitted single pollutant and multiple pollutant linear models, controlling for available socioeconomic, demographic, and smoking variables and stratifying by urban and nonurban counties. RESULTS: In multiple pollutant models, we found that: (1) a reduction in sulfate was associated with an increase in life expectancy; and (2) reductions in ammonium and sodium ion were associated with increases in life expectancy in nonurban counties only. CONCLUSIONS: Our findings suggest that recent reductions in long-term exposure to sulfate, ammonium, and sodium ion between 2002 and 2007 are associated with improved public health.