Short term exposure to low level ambient fine particulate matter and natural cause, cardiovascular, and respiratory morbidity among US adults with health insurance: case time series study.

OBJECTIVE: To estimate the excess relative and absolute risks of hospital admissions and emergency department visits for natural causes, cardiovascular disease, and respiratory disease associated with daily exposure to fine particulate matter (PM2.5) at concentrations below the new World Health Organization air quality guideline limit among adults with health insurance in the contiguous US. DESIGN: Case time series study. SETTING: US national administrative healthcare claims database. PARTICIPANTS: 50.1 million commercial and Medicare Advantage beneficiaries aged ≥18 years between 1 January 2010 and 31 December 2016. MAIN OUTCOME MEASURES: Daily counts of hospital admissions and emergency department visits for natural causes, cardiovascular disease, and respiratory disease based on the primary diagnosis code. RESULTS: During the study period, 10.3 million hospital admissions and 24.1 million emergency department visits occurred for natural causes among 50.1 million adult enrollees across 2939 US counties. The daily PM2.5 levels were below the new WHO guideline limit of 15 µg/m3 for 92.6% of county days (7 360 725 out of 7 949 713). On days when daily PM2.5 levels were below the new WHO air quality guideline limit of 15 µg/m3, an increase of 10 µg/m3 in PM2.5 during the current and previous day was associated with higher risk of hospital admissions for natural causes, with an excess relative risk of 0.91% (95% confidence interval 0.55% to 1.26%), or 1.87 (95% confidence interval 1.14 to 2.59) excess hospital admissions per million enrollees per day. The increased risk of hospital admissions for natural causes was observed exclusively among adults aged ≥65 years and was not evident in younger adults. PM2.5 levels were also statistically significantly associated with relative risk of hospital admissions for cardiovascular and respiratory diseases. For emergency department visits, a 10 µg/m3 increase in PM2.5 during the current and previous day was associated with respiratory disease, with an excess relative risk of 1.34% (0.73% to 1.94%), or 0.93 (0.52 to 1.35) excess emergency department visits per million enrollees per day. This association was not found for natural causes or cardiovascular disease. The higher risk of emergency department visits for respiratory disease was strongest among middle aged and young adults. CONCLUSIONS: Among US adults with health insurance, exposure to ambient PM2.5 at concentrations below the new WHO air quality guideline limit is statistically significantly associated with higher rates of hospital admissions for natural causes, cardiovascular disease, and respiratory disease, and with emergency department visits for respiratory diseases. These findings constitute an important contribution to the debate about the revision of air quality limits, guidelines, and standards.

Exposure-response associations between chronic exposure to fine particulate matter and risks of hospital admission for major cardiovascular diseases: population based cohort study.

OBJECTIVE: To estimate exposure-response associations between chronic exposure to fine particulate matter (PM2.5) and risks of the first hospital admission for major cardiovascular disease (CVD) subtypes. DESIGN: Population based cohort study. SETTING: Contiguous US. PARTICIPANTS: 59 761 494 Medicare fee-for-service beneficiaries aged ≥65 years during 2000-16. Calibrated PM2.5 predictions were linked to each participant's residential zip code as proxy exposure measurements. MAIN OUTCOME MEASURES: Risk of the first hospital admission during follow-up for ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, valvular heart disease, thoracic and abdominal aortic aneurysms, or a composite of these CVD subtypes. A causal framework robust against confounding bias and bias arising from errors in exposure measurements was developed for exposure-response estimations. RESULTS: Three year average PM2.5 exposure was associated with increased relative risks of first hospital admissions for ischemic heart disease, cerebrovascular disease, heart failure, cardiomyopathy, arrhythmia, and thoracic and abdominal aortic aneurysms. For composite CVD, the exposure-response curve showed monotonically increased risk associated with PM2.5: compared with exposures ≤5 µg/m3 (the World Health Organization air quality guideline), the relative risk at exposures between 9 and 10 µg/m3, which encompassed the US national average of 9.7 µg/m3 during the study period, was 1.29 (95% confidence interval 1.28 to 1.30). On an absolute scale, the risk of hospital admission for composite CVD increased from 2.59% with exposures ≤5 µg/m3 to 3.35% at exposures between 9 and 10 µg/m3. The effects persisted for at least three years after exposure to PM2.5. Age, education, accessibility to healthcare, and neighborhood deprivation level appeared to modify susceptibility to PM2.5. CONCLUSIONS: The findings of this study suggest that no safe threshold exists for the chronic effect of PM2.5 on overall cardiovascular health. Substantial benefits could be attained through adherence to the WHO air quality guideline.

Long-term exposure to ambient PM2.5, particulate constituents and hospital admissions from non-respiratory infection.

The association between PM2.5 and non-respiratory infections is unclear. Using data from Medicare beneficiaries and high-resolution datasets of PM2.5 and its constituents across 39,296 ZIP codes in the U.S between 2000 and 2016, we investigated the associations between annual PM2.5, PM2.5 constituents, source-specific PM2.5, and hospital admissions from non-respiratory infections. Each standard deviation (3.7-µg m-3) increase in PM2.5 was associated with a 10.8% (95%CI 10.8-11.2%) increase in rate of hospital admissions from non-respiratory infections. Sulfates (30.8%), Nickel (22.5%) and Copper (15.3%) contributed the largest weights in the observed associations. Each standard deviation increase in PM2.5 components sourced from oil combustion, coal burning, traffic, dirt, and regionally transported nitrates was associated with 14.5% (95%CI 7.6-21.8%), 18.2% (95%CI 7.2-30.2%), 20.6% (95%CI 5.6-37.9%), 8.9% (95%CI 0.3-18.4%) and 7.8% (95%CI 0.6-15.5%) increases in hospital admissions from non-respiratory infections. Our results suggested that non-respiratory infections are an under-appreciated health effect of PM2.5.

Modification of the PM2.5- and extreme heat-mortality relationships by historical redlining: a case-crossover study in thirteen U.S. states.

BACKGROUND: Redlining has been associated with worse health outcomes and various environmental disparities, separately, but little is known of the interaction between these two factors, if any. We aimed to estimate whether living in a historically-redlined area modifies the effects of exposures to ambient PM2.5 and extreme heat on mortality by non-external causes. METHODS: We merged 8,884,733 adult mortality records from thirteen state departments of public health with scanned and georeferenced Home Owners Loan Corporation (HOLC) maps from the University of Richmond, daily average PM2.5 from a sophisticated prediction model on a 1-km grid, and daily temperature and vapor pressure from the Daymet V4 1-km grid. A case-crossover approach was used to assess modification of the effects of ambient PM2.5 and extreme heat exposures by redlining and control for all fixed and slow-varying factors by design. Multiple moving averages of PM2.5 and duration-aware analyses of extreme heat were used to assess the most vulnerable time windows. RESULTS: We found significant statistical interactions between living in a redlined area and exposures to both ambient PM2.5 and extreme heat. Individuals who lived in redlined areas had an interaction odds ratio for mortality of 1.0093 (95% confidence interval [CI]: 1.0084, 1.0101) for each 10 µg m-3 increase in same-day ambient PM2.5 compared to individuals who did not live in redlined areas. For extreme heat, the interaction odds ratio was 1.0218 (95% CI 1.0031, 1.0408). CONCLUSIONS: Living in areas that were historically-redlined in the 1930's increases the effects of exposures to both PM2.5 and extreme heat on mortality by non-external causes, suggesting that interventions to reduce environmental health disparities can be more effective by also considering the social context of an area and how to reduce disparities there. Further study is required to ascertain the specific pathways through which this effect modification operates and to develop interventions that can contribute to health equity for individuals living in these areas.

Long-term exposure to PM2.5 species and all-cause mortality among Medicare patients using mixtures analyses.

BACKGROUND: The relationship between long-term exposure to PM2.5 and mortality is well-established; however, the role of individual species is less understood. OBJECTIVES: In this study, we assess the overall effect of long-term exposure to PM2.5 as a mixture of species and identify the most harmful of those species while controlling for the others. METHODS: We looked at changes in mortality among Medicare participants 65 years of age or older from 2000 to 2018 in response to changes in annual levels of 15 PM2.5 components, namely: organic carbon, elemental carbon, nickel, lead, zinc, sulfate, potassium, vanadium, nitrate, silicon, copper, iron, ammonium, calcium, and bromine. Data on exposure were derived from high-resolution, spatio-temporal models which were then aggregated to ZIP code. We used the rate of deaths in each ZIP code per year as the outcome of interest. Covariates included demographic, temperature, socioeconomic, and access-to-care variables. We used a mixtures approach, a weighted quantile sum, to analyze the joint effects of PM2.5 species on mortality. We further looked at the effects of the components when PM2.5 mass levels were at concentrations below 8 µg/m3, and effect modification by sex, race, Medicaid status, and Census division. RESULTS: We found that for each decile increase in the levels of the PM2.5 mixture, the rate of all-cause mortality increased by 1.4% (95% CI: 1.3%-1.4%), the rate of cardiovascular mortality increased by 2.1% (95% CI: 2.0%-2.2%), and the rate of respiratory mortality increased by 1.7% (95% CI: 1.5%-1.9%). These effects estimates remained significant and slightly higher when we restricted to lower concentrations. The highest weights for harmful effects were due to organic carbon, nickel, zinc, sulfate, and vanadium. CONCLUSIONS: Long-term exposure to PM2.5 species, as a mixture, increased the risk of all-cause, cardiovascular, and respiratory mortality.

Long-term association of air pollution and incidence of lung cancer among older Americans: A national study in the Medicare cohort.

BACKGROUND: Despite strong evidence of the association of fine particulate matter (PM2.5) exposure with an increased risk of lung cancer mortality, few studies had investigated associations of multiple pollutants simultaneously, or with incidence, or using causal methods. Disparities were also understudied. OBJECTIVES: We investigated long-term effects of PM2.5, nitrogen dioxide (NO2), warm-season ozone, and particle radioactivity (PR) exposures on lung cancer incidence in a nationwide cohort. METHODS: We conducted a cohort study with Medicare beneficiaries (aged ≥ 65 years) continuously enrolled in the fee-for-service program in the contiguous US from 2001 to 2016. Air pollution exposure was averaged across three years and assigned based on ZIP code of residence. We fitted Cox proportional hazards models to estimate the hazard ratio (HR) for lung cancer incidence, adjusted for individual- and neighborhood-level confounders. As a sensitivity analysis, we evaluated the causal relationships using inverse probability weights. We further assessed effect modifications by individual- and neighborhood-level covariates. RESULTS: We identified 166,860 lung cancer cases of 12,429,951 studied beneficiaries. In the multi-pollutant model, PM2.5 and NO2 exposures were statistically significantly associated with increased lung cancer incidence, while PR was marginally significantly associated. Specifically, the HR was 1.008 (95% confidence interval [CI]: 1.005, 1.011) per 1-µg/m3 increase in PM2.5, 1.013 (95% CI: 1.012, 1.013) per 1-ppb increase in NO2, and 1.005 (0.999, 1.012) per 1-mBq/m3 increase in PR. At low exposure levels, all pollutants were associated with increased lung cancer incidence. Men, older individuals, Blacks, and residents of low-income neighborhoods experienced larger effects of PM2.5 and PR. DISCUSSION: Long-term PM2.5, NO2, and PR exposures were independently associated with increased lung cancer incidence among the national elderly population. Low-exposure analysis indicated that current national standards for PM2.5 and NO2 were not restrictive enough to protect public health, underscoring the need for more stringent air quality regulations.

Seasonal Temperature Variability and Mortality in the Medicare Population.

BACKGROUND: Seasonal temperature variability remains understudied and may be modified by climate change. Most temperature-mortality studies examine short-term exposures using time-series data. These studies are limited by regional adaptation, short-term mortality displacement, and an inability to observe longer-term relationships in temperature and mortality. Seasonal temperature and cohort analyses allow the long-term effects of regional climatic change on mortality to be analyzed. OBJECTIVES: We aimed to carry out one of the first investigations of seasonal temperature variability and mortality across the contiguous United States. We also investigated factors that modify this association. Using adapted quasi-experimental methods, we hoped to account for unobserved confounding and to investigate regional adaptation and acclimatization at the ZIP code level. METHODS: We examined the mean and standard deviation (SD) of daily temperature in the warm (April-September) and cold (October-March) season in the Medicare cohort from 2000 to 2016. This cohort comprised 622,427,230 y of person-time in all adults over the age of 65 y from 2000 to 2016. We used daily mean temperature obtained from gridMET to develop yearly seasonal temperature variables for each ZIP code. We used an adapted difference-in-difference approach model with a three-tiered clustering approach and meta-analysis to observe the relationship between temperature variability and mortality within ZIP codes. Effect modification was assessed with stratified analyses by race and population density. RESULTS: For every 1°C increase in the SD of warm and cold season temperature, the mortality rate increased by 1.54% [95% confidence interval (CI): 0.73%, 2.15%] and 0.69% (95% CI: 0.22%, 1.15%) respectively. We did not see significant effects for seasonal mean temperatures. Participants who were classified by Medicare into an "other" race group had smaller effects than those classified as White for Cold and Cold SD and areas with lower population density had larger effects for Warm SD. DISCUSSION: Warm and cold season temperature variability were significantly associated with increased mortality rates in U.S. individuals over the age of 65 y, even after controlling for seasonal temperature averages. Warm and cold season mean temperatures showed null effects on mortality. Cold SD had a larger effect size for those who were in the racial subgroup other, whereas Warm SD was more harmful for those living in lower population density areas. This study adds to the growing calls for urgent climate mitigation and environmental health adaptation and resiliency. https://doi.org/10.1289/EHP11588.

Association of Long-term Exposure to Air Pollution With Late-Life Depression in Older Adults in the US.

Importance: Emerging evidence has suggested harmful associations of air pollutants with neurodegenerative diseases among older adults. However, little is known about outcomes regarding late-life mental disorders, such as geriatric depression. Objective: To investigate if long-term exposure to air pollution is associated with increased risk of late-life depression diagnosis among older adults in the US. Design, Setting, and Participants: This population-based longitudinal cohort study consisted of US Medicare enrollees older than 64 years. Data were obtained from the US Centers for Medicare and Medicaid Services Chronic Conditions Warehouse. The participants were continuously enrolled in the Fee-for-Service program and both Medicare Part A and Part B. After the 5-year washout period at entry, a total of 8 907 422 unique individuals were covered over the study period of 2005 to 2016, who contributed to 1 526 690 late-onset depression diagnoses. Data analyses were performed between March 2022 and November 2022. Exposures: The exposures consisted of residential long-term exposure to fine particulate matter (PM2.5), measured in micrograms per cubic meter; nitrogen dioxide (NO2), measured in parts per billion; and ozone (O3), measured in parts per billion. Main Outcomes and Measures: Late-life depression diagnoses were identified via information from all available Medicare claims (ie, hospital inpatient, skilled nursing facility, home health agency, hospital outpatient, and physician visits). Date of the first occurrence was obtained. Hazard ratios and percentage change in risk were estimated via stratified Cox proportional hazards models accounting for climate coexposures, neighborhood greenness, socioeconomic conditions, health care access, and urbanicity level. Results: A total of 8 907 422 Medicare enrollees were included in this study with 56.8% being female individuals and 90.2% being White individuals. The mean (SD) age at entry (after washout period) was 73.7 (4.8) years. Each 5-unit increase in long-term mean exposure to PM2.5, NO2, and O3 was associated with an adjusted percentage increase in depression risk of 0.91% (95% CI, 0.02%-1.81%), 0.61% (95% CI, 0.31%- 0.92%), and 2.13% (95% CI, 1.63%-2.64%), respectively, based on a tripollutant model. Effect size heterogeneity was found among subpopulations by comorbidity condition and neighborhood contextual backgrounds. Conclusions and Relevance: In this cohort study among US Medicare enrollees, harmful associations were observed between long-term exposure to air pollution and increased risk of late-life depression diagnosis.

Measurement error correction for ambient PM2.5 exposure using stratified regression calibration: Effects on all-cause mortality.

BACKGROUND: Previous studies on the impact of measurement error for PM2.5 were mostly simulation studies, did not control for other pollutants, or used a single regression calibration model to correct for measurement error. However, the relationship between actual and error-prone PM2.5 concentration may vary by time and region. We aim to correct the measurement error of PM2.5 predictions using stratified regression calibration and investigate how the measurement error biases the association between PM2.5 and mortality in the Medicare Cohort. METHODS: The "gold-standard" measurements of PM2.5 were defined as daily monitoring data. We regressed daily monitoring PM2.5 on modeled PM2.5 using the simple linear regression by strata of season, elevation, census division and time period. Calibrated PM2.5 was calculated with stratum-specific calibration parameters ß0 (intercept) and ß1 (slope) for each strata and aggregated to annual level. Associations between calibrated and error-prone annual PM2.5 and all-cause mortality among Medicare beneficiaries were estimated with Quasi-Poisson regression models. RESULTS: Across 208 strata, the median of ß0 and ß1 were 0.62 (25% 0.0.20, 75% 1.06) and 0.93 (25% 0.87, 75% 0.99). From calibrated and error-prone PM2.5 data, we estimated that each 10 µg/m3 increase in PM2.5 was respectively associated with 4.9% (95%CI 4.6-5.2) and 4.6% (95%CI 4.4-4.9) increases in the mortality rate among Medicare beneficiaries, conditional on confounders. CONCLUSIONS: Regression calibration parameters of PM2.5 varied by time and region. Using error-prone measures of PM2.5 underestimated the association between PM2.5 and all-cause mortality. Modern exposure models produce relatively small bias.

The effect of long-term exposure to air pollution and seasonal temperature on hospital admissions with cardiovascular and respiratory disease in the United States: A difference-in-differences analysis.

BACKGROUND: Few studies have simultaneously examined the effect of long-term exposure to air pollution and ambient temperature on the rate of hospital admissions with cardiovascular and respiratory disease using causal inference methods. METHODS: We used a variation of a difference-in-difference (DID) approach to assess the effects of long-term exposure to warm-season temperature, cold-season temperature, NO2, O3, and PM2.5 on the rate of hospital admissions for cardiovascular disease (CVD), myocardial infarction (MI), ischemic stroke, and respiratory diseases from 2001 to 2016 among Medicare beneficiaries who use fee-for-service programs. We computed the rate of admissions by zip code and year. Covariates included demographic and socioeconomic variables which were obtained from the decennial Census, the American Community Survey, the Behavioral Risk Factor Surveillance System, and the Dartmouth Health Atlas. As a secondary analysis, we restricted the analysis to zip code-years that had exposure to low concentrations of our pollutants. RESULTS: PM2.5 was associated with a significant increase in the absolute rate of annual admissions with cardiovascular disease by 47.71 admissions (95 % CI: 41.25-56.05) per 100,000 person-years, myocardial infarction by 7.44 admissions (95 % CI: 5.53-9.63) per 100,000 person-years, and 18.58 respiratory admissions (95 % CI: 12.42-23.72) for each one µg/m3 increase in two-year average levels. O3 significantly increased the rates of all the studied outcomes. NO2 was associated with a decreased rate of admissions with MI by 0.83 admissions (95 % CI: 0.10-1.55) per 100,000 person-years but increased rate of admissions for respiratory disease by 3.16 admissions (95 % CI: 1.34-5.24) per 100,000 person-years. Warmer cold-season temperature was associated with a decreased admissions rate for all outcomes. CONCLUSION: Air pollutants, particularly PM2.5 and O3, increased the rate of hospital admissions with cardiovascular and respiratory disease among the elderly, while higher cold-season temperatures decreased the rate of admissions with these conditions.

Associations of short-term exposure to air pollution and increased ambient temperature with psychiatric hospital admissions in older adults in the USA: a case-crossover study.

BACKGROUND: Little is known about the associations between ambient environmental exposures and the risk of acute episodes of psychiatric disorders. We aimed to estimate the link between short-term exposure to atmospheric pollutants, temperature, and acute psychiatric hospital admissions in adults aged 65 years and older in the USA. METHODS: For this study, we included all people (aged ≥65 years) enrolled in the Medicare programme in the USA who had an emergency or urgent hospital admission for a psychiatric disorder recorded between Jan 31, 2000, and Dec 31, 2016. We applied a case-crossover design to study the associations between short-term exposure to air pollution (fine particulate matter [PM2·5], ozone, and nitrogen dioxide [NO2]), ambient temperature, and the risk of acute hospital admissions for depression, schizophrenia, and bipolar disorder in this population. The percentage change in the risk of hospital admission and annual absolute risk differences were estimated. FINDINGS: For each 5°C increase in short-term exposure to cold season temperature, the relative risk of acute hospital admission increased by 3·66% (95% CI 3·06-4·26) for depression, by 3·03% (2·04-4·02) for schizophrenia, and by 3·52% (2·38-4·68) for bipolar disorder in the US Medicare population. Increased short-term exposure to PM2·5 and NO2 was also associated with a significant increase in the risk of acute hospital admissions for psychiatric disorders. Each 5 µg/m3 increase in PM2·5 was associated with an increase in hospital admission rates of 0·62% (95% CI 0·23-1·02) for depression, 0·77% (0·11-1·44) for schizophrenia, and 1·19% (0·49-1·90) for bipolar disorder; each 5 parts per billion (ppb) increase in NO2, meanwhile, was linked to an increase in hospital admission rates of 0·35% (95% CI 0·03-0·66) for depression and 0·64% (0·20-1·08) for schizophrenia. No such associations were found with warm season temperature. INTERPRETATION: In the US Medicare population, short-term exposure to elevated concentrations of PM2·5 and NO2 and cold season ambient temperature were significantly associated with an increased risk of hospital admissions for psychiatric disorders. Considering the increasing burden of psychiatric disorders in the US population, these findings suggest that intervening on air pollution and ambient temperature levels through stricter environmental regulations or climate mitigation could help ease the psychiatric health-care burden. FUNDING: US National Institute of Environmental Health Sciences, US Environmental Protection Agency, and US National Institute on Aging.

Air Pollutants and Asthma Hospitalization in the Medicaid Population.

Rationale: Risk of asthma hospitalization and its disparities associated with air pollutant exposures are less clear within socioeconomically disadvantaged populations, particularly at low degrees of exposure. Objectives: To assess effects of short-term exposures to fine particulate matter (particulate matter with an aerodynamic diameter of ⩽2.5 µm [PM2.5]), warm-season ozone (O3), and nitrogen dioxide (NO2) on risk of asthma hospitalization among national Medicaid beneficiaries, the most disadvantaged population in the United States, and to test whether any subpopulations were at higher risk. Methods: We constructed a time-stratified case-crossover dataset among 1,627,002 hospitalizations during 2000-2012 and estimated risk of asthma hospitalization associated with short-term PM2.5, O3, and NO2 exposures. We then restricted the analysis to hospitalizations with degrees of exposure below increasingly stringent thresholds. Furthermore, we tested effect modifications by individual- and community-level characteristics. Measurements and Main Results: Each 1-µg/m3 increase in PM2.5, 1-ppb increase in O3, and 1-ppb increase in NO2 was associated with 0.31% (95% confidence interval [CI], 0.24-0.37%), 0.10% (95% CI, 0.05 - 0.15%), and 0.28% (95% CI, 0.24 - 0.32%) increase in risk of asthma hospitalization, respectively. Low-level PM2.5 and NO2 exposures were associated with higher risk. Furthermore, beneficiaries with only one asthma hospitalization during the study period or in communities with lower population density, higher average body mass index, longer distance to the nearest hospital, or greater neighborhood deprivation experienced higher risk. Conclusions: Short-term air pollutant exposures increased risk of asthma hospitalization among Medicaid beneficiaries, even at concentrations well below national standards. The subgroup differences suggested individual and contextual factors contributed to asthma disparities under effects of air pollutant exposures.

Long-term effect of exposure to lower concentrations of air pollution on mortality among US Medicare participants and vulnerable subgroups: a doubly-robust approach.

BACKGROUND: Long-term exposure to air pollution has been linked with an increase in risk of mortality. Whether existing US Environmental Protection Agency standards are sufficient to protect health is unclear. Our study aimed to examine the relationship between exposure to lower concentrations of air pollution and the risk of mortality. METHODS: Our nationwide cohort study investigated the effect of annual average exposure to air pollutants on all-cause mortality among Medicare enrolees from the beginning of 2000 to the end of 2016. Patients entered the cohort in the month of January following enrolment and were followed up until the end of the study period in 2016 or death. We restricted our analyses to participants who had only been exposed to lower concentrations of pollutants over the study period, specifically particulate matter less than 2·5 µg/m3 in diameter (PM2·5) at a concentration of up to 12 µg/m3, nitrogen dioxide (NO2) at a concentration of up to 53 parts per billion (ppb), and summer ozone (O3) at concentrations of up to 50 ppb. We adjusted for two types of covariates, which were individual level and postal code-level variables. We used a doubly-robust additive model to estimate the change in risk. We further looked at effect-measure modification by stratification on the basis of demographic and socioeconomic characteristics. FINDINGS: We found an increased risk of mortality with all three pollutants. Each 1 µg/m3 increase in annual PM2·5 concentrations increased the absolute annual risk of death by 0·073% (95% CI 0·071-0·076). Each 1 ppb increase in annual NO2 concentrations increased the annual risk of death by 0·003% (0·003-0·004), and each 1 ppb increase in summer O3 concentrations increased the annual risk of death by 0·081% (0·080-0·083). This increase translated to approximately 11 540 attributable deaths (95% CI 11 087-11 992) for PM2·5, 1176 attributable deaths (998-1353) for NO2, and 15 115 attributable deaths (14 896-15 333) for O3 per year for each unit increase in pollution concentrations. The effects were higher in certain subgroups, including individuals living in areas of low socioeconomic status. Long-term exposure to permissible concentrations of air pollutants increases the risk of mortality. FUNDING: The US Environmental Protection Agency, National Institute of Environmental Health Services, and Health Effects Institute.

Emulating causal dose-response relations between air pollutants and mortality in the Medicare population.

BACKGROUND: Fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) are major air pollutants that pose considerable threats to human health. However, what has been mostly missing in air pollution epidemiology is causal dose-response (D-R) relations between those exposures and mortality. Such causal D-R relations can provide profound implications in predicting health impact at a target level of air pollution concentration. METHODS: Using national Medicare cohort during 2000-2016, we simultaneously emulated causal D-R relations between chronic exposures to fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) and all-cause mortality. To relax the contentious assumptions of inverse probability weighting for continuous exposures, including distributional form of the exposure and heteroscedasticity, we proposed a decile binning approach which divided each exposure into ten equal-sized groups by deciles, treated the lowest decile group as reference, and estimated the effects for the other groups. Binning continuous exposures also makes the inverse probability weights robust against outliers. RESULTS: Assuming the causal framework was valid, we found that higher levels of PM2.5, O3, and NO2 were causally associated with greater risk of mortality and that PM2.5 posed the greatest risk. For PM2.5, the relative risk (RR) of mortality monotonically increased from the 2nd (RR, 1.022; 95% confidence interval [CI], 1.018-1.025) to the 10th decile group (RR, 1.207; 95% CI, 1.203-1.210); for O3, the RR increased from the 2nd (RR, 1.050; 95% CI, 1.047-1.053) to the 9th decile group (RR, 1.107; 95% CI, 1.104-1.110); for NO2, the DR curve wiggled at low levels and started rising from the 6th (RR, 1.005; 95% CI, 1.002-1.018) till the highest decile group (RR, 1.024; 95% CI, 1.021-1.027). CONCLUSIONS: This study provided more robust evidence of the causal relations between air pollution exposures and mortality. The emulated causal D-R relations provided significant implications for reviewing the national air quality standards, as they inferred the number of potential early deaths prevented if air pollutants were reduced to specific levels; for example, lowering each air pollutant concentration from the 70th to 60th percentiles would prevent 65,935 early deaths per year.

Assessing additive effects of air pollutants on mortality rate in Massachusetts.

BACKGROUND: We previously found additive effects of long- and short-term exposures to fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) on all-cause mortality rate using a generalized propensity score (GPS) adjustment approach. The study addressed an important question of how many early deaths were caused by each exposure. However, the study was computationally expensive, did not capture possible interactions and high-order nonlinearities, and omitted potential confounders. METHODS: We proposed two new methods and reconducted the analysis using the same cohort of Medicare beneficiaries in Massachusetts during 2000-2012, which consisted of 1.5 million individuals with 3.8 billion person-days of follow-up. The first method, weighted least squares (WLS), leveraged large volume of data by aggregating person-days, which gave equivalent results to the linear probability model (LPM) method in the previous analysis but significantly reduced computational burden. The second method, m-out-of-n random forests (moonRF), implemented scaling random forests that captured all possible interactions and nonlinearities in the GPS model. To minimize confounding bias, we additionally controlled relative humidity and health care utilizations that were not included previously. Further, we performed low-level analysis by restricting to person-days with exposure levels below increasingly stringent thresholds. RESULTS: We found consistent results between LPM/WLS and moonRF: all exposures were positively associated with mortality rate, even at low levels. For long-term PM2.5 and O3, the effect estimates became larger at lower levels. Long-term exposure to PM2.5 posed the highest risk: 1 µg/m3 increase in long-term PM2.5 was associated with 1053 (95% confidence interval [CI]: 984, 1122; based on LPM/WLS methods) or 1058 (95% CI: 988, 1127; based on moonRF method) early deaths each year among the Medicare population in Massachusetts. CONCLUSIONS: This study provides more rigorous causal evidence between PM2.5, O3, and NO2 exposures and mortality, even at low levels. The largest effect estimate for long-term PM2.5 suggests that reducing PM2.5 could gain the most substantial benefits. The consistency between LPM/WLS and moonRF suggests that there were not many interactions and high-order nonlinearities. In the big data context, the proposed methods will be useful for future scientific work in estimating causality on an additive scale.

Long-Term Association of Air Pollution and Hospital Admissions Among Medicare Participants Using a Doubly Robust Additive Model.

BACKGROUND: Studies examining the nonfatal health outcomes of exposure to air pollution have been limited by the number of pollutants studied and focus on short-term exposures. METHODS: We examined the relationship between long-term exposure to fine particulate matter with an aerodynamic diameter <2.5 micrometers (PM2.5), NO2, and tropospheric ozone and hospital admissions for 4 cardiovascular and respiratory outcomes (myocardial infarction, ischemic stroke, atrial fibrillation and flutter, and pneumonia) among the Medicare population of the United States. We used a doubly robust method for our statistical analysis, which relies on both inverse probability weighting and adjustment in the outcome model to account for confounding. The results from this regression are on an additive scale. We further looked at this relationship at lower pollutant concentrations, which are consistent with typical exposure levels in the United States, and among potentially susceptible subgroups. RESULTS: Long-term exposure to fine PM2.5 was associated with an increased risk of all outcomes with the highest effect seen for stroke with a 0.0091% (95% CI, 0.0086-0.0097) increase in the risk of stroke for each 1-µg/m3 increase in annual levels. This translated to 2536 (95% CI, 2383-2691) cases of hospital admissions with ischemic stroke per year, which can be attributed to each 1-unit increase in fine particulate matter levels among the study population. NO2 was associated with an increase in the risk of admission with stroke by 0.00059% (95% CI, 0.00039-0.00075) and atrial fibrillation by 0.00129% (95% CI, 0.00114-0.00148) per ppb and tropospheric ozone was associated with an increase in the risk of admission with pneumonia by 0.00413% (95% CI, 0.00376-0.00447) per parts per billion. At lower concentrations, all pollutants were consistently associated with an increased risk for all our studied outcomes. CONCLUSIONS: Long-term exposure to air pollutants poses a significant risk to cardiovascular and respiratory health among the elderly population in the United States, with the greatest increase in the association per unit of exposure occurring at lower concentrations.

Long-term effects of PM2·5 on neurological disorders in the American Medicare population: a longitudinal cohort study.

BACKGROUND: Accumulating evidence links fine particulate matter (PM2·5) to premature mortality, cardiovascular disease, and respiratory disease. However, less is known about the influence of PM2·5 on neurological disorders. We aimed to investigate the effect of long-term PM2·5 exposure on development of Parkinson's disease or Alzheimer's disease and related dementias. METHODS: We did a longitudinal cohort study in which we constructed a population-based nationwide open cohort including all fee-for-service Medicare beneficiaries (aged ≥65 years) in the contiguous United States (2000-16) with no exclusions. We assigned PM2·5 postal code (ie, ZIP code) concentrations based on mean annual predictions from a high-resolution model. To accommodate our very large dataset, we applied Cox-equivalent Poisson models with parallel computing to estimate hazard ratios (HRs) for first hospital admission for Parkinson's disease or Alzheimer's disease and related dementias, adjusting for potential confounders in the health models. FINDINGS: Between Jan 1, 2000, and Dec 31, 2016, of 63 038 019 individuals who were aged 65 years or older during the study period, we identified 1·0 million cases of Parkinson's disease and 3·4 million cases of Alzheimer's disease and related dementias based on primary and secondary diagnosis billing codes. For each 5 µg/m3 increase in annual PM2·5 concentrations, the HR was 1·13 (95% CI 1·12-1·14) for first hospital admission for Parkinson's disease and 1·13 (1·12-1·14) for first hospital admission for Alzheimer's disease and related dementias. For both outcomes, there was strong evidence of linearity at PM2·5 concentrations less than 16 µg/m3 (95th percentile of the PM2·5 distribution), followed by a plateaued association with increasingly larger confidence bands. INTERPRETATION: We provide evidence that exposure to annual mean PM2·5 in the USA is significantly associated with an increased hazard of first hospital admission with Parkinson's disease and Alzheimer's disease and related dementias. For the ageing American population, improving air quality to reduce PM2·5 concentrations to less than current national standards could yield substantial health benefits by reducing the burden of neurological disorders. FUNDING: The Health Effects Institute, The National Institute of Environmental Health Sciences, The National Institute on Aging, and the HERCULES Center.

Causal Effects of Air Pollution on Mortality Rate in Massachusetts.

Air pollution epidemiology studies have primarily investigated long- and short-term exposures separately, have used multiplicative models, and have been associational studies. Implementing a generalized propensity score adjustment approach with 3.8 billion person-days of follow-up, we simultaneously assessed causal associations of long-term (1-year moving average) and short-term (2-day moving average) exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5), ozone, and nitrogen dioxide with all-cause mortality on an additive scale among Medicare beneficiaries in Massachusetts (2000-2012). We found that long- and short-term PM2.5, ozone, and nitrogen dioxide exposures were all associated with increased mortality risk. Specifically, per 10 million person-days, each 1-µg/m3 increase in long- and short-term PM2.5 exposure was associated with 35.4 (95% confidence interval (CI): 33.4, 37.6) and 3.04 (95% CI: 2.17, 3.94) excess deaths, respectively; each 1-part per billion (ppb) increase in long- and short-term ozone exposure was associated with 2.35 (95% CI: 1.08, 3.61) and 2.41 (95% CI: 1.81, 2.91) excess deaths, respectively; and each 1-ppb increase in long- and short-term nitrogen dioxide exposure was associated with 3.24 (95% CI: 2.75, 3.77) and 5.60 (95% CI: 5.24, 5.98) excess deaths, respectively. Mortality associated with long-term PM2.5 and ozone exposure increased substantially at low levels. The findings suggested that air pollution was causally associated with mortality, even at levels below national standards.

Inverse probability weighted distributed lag effects of short-term exposure to PM2.5 and ozone on CVD hospitalizations in New England Medicare participants - Exploring the causal effects.

BACKGROUND: Although many studies have established significant associations between short-term air pollution and the risk of getting cardiovascular diseases, there is a lack of evidence based on causal distributed lag modeling. METHODS: Inverse probability weighting (ipw) propensity score models along with conditional logistic outcome regression models based on a case-crossover study design were applied to get the causal unconstrained distributed (lag0-lag5) as well as cumulative lag effect of short-term exposure to PM2.5/Ozone on hospital admissions of acute myocardial infarction (AMI), congestive heart failure (CHF) and ischemic stroke (IS) among New England Medicare participants during 2000-2012. Effect modification by gender, race, secondary diagnosis of Chronic Obstructive Pulmonary Diseases (COPD) and Diabetes (DM) was explored. RESULTS: Each 10 µg/m3 increase in lag0-lag5 cumulative PM2.5 exposure was associated with an increase of 4.3% (95% confidence interval: 2.2%, 6.4%, percentage change) in AMI hospital admission rate, an increase of 3.9% (2.4%, 5.5%) in CHF rate and an increase of 2.6% (0.4%, 4.7%) in IS rate. A weakened lagging effect of PM2.5 from lag0 to lag5 could be observed. No cumulative short-term effect of ozone on CVD was found. People with secondary diagnosis of COPD, diabetes, female gender and black race are sensitive population. CONCLUSIONS: Based on our causal distributed lag modeling, we found that short-term exposure to an increased ambient PM2.5 level had the potential to induce higher risk of CVD hospitalization in a causal way. More attention should be paid to population of COPD, diabetes, female gender and black race.

Short term exposure to fine particulate matter and hospital admission risks and costs in the Medicare population: time stratified, case crossover study.

OBJECTIVE: To assess risks and costs of hospital admission associated with short term exposure to fine particulate matter with diameter less than 2.5 µm (PM2.5) for 214 mutually exclusive disease groups. DESIGN: Time stratified, case crossover analyses with conditional logistic regressions adjusted for non-linear confounding effects of meteorological variables. SETTING: Medicare inpatient hospital claims in the United States, 2000-12 (n=95 277 169). PARTICIPANTS: All Medicare fee-for-service beneficiaries aged 65 or older admitted to hospital. MAIN OUTCOME MEASURES: Risk of hospital admission, number of admissions, days in hospital, inpatient and post-acute care costs, and value of statistical life (that is, the economic value used to measure the cost of avoiding a death) due to the lives lost at discharge for 214 disease groups. RESULTS: Positive associations between short term exposure to PM2.5 and risk of hospital admission were found for several prevalent but rarely studied diseases, such as septicemia, fluid and electrolyte disorders, and acute and unspecified renal failure. Positive associations were also found between risk of hospital admission and cardiovascular and respiratory diseases, Parkinson's disease, diabetes, phlebitis, thrombophlebitis, and thromboembolism, confirming previously published results. These associations remained consistent when restricted to days with a daily PM2.5 concentration below the WHO air quality guideline for the 24 hour average exposure to PM2.5. For the rarely studied diseases, each 1 µg/m3 increase in short term PM2.5 was associated with an annual increase of 2050 hospital admissions (95% confidence interval 1914 to 2187 admissions), 12 216 days in hospital (11 358 to 13 075), US$31m (£24m, €28m; $29m to $34m) in inpatient and post-acute care costs, and $2.5bn ($2.0bn to $2.9bn) in value of statistical life. For diseases with a previously known association, each 1 µg/m3 increase in short term exposure to PM2.5 was associated with an annual increase of 3642 hospital admissions (3434 to 3851), 20 098 days in hospital (18 950 to 21 247), $69m ($65m to $73m) in inpatient and post-acute care costs, and $4.1bn ($3.5bn to $4.7bn) in value of statistical life. CONCLUSIONS: New causes and previously identified causes of hospital admission associated with short term exposure to PM2.5 were found. These associations remained even at a daily PM2.5 concentration below the WHO 24 hour guideline. Substantial economic costs were linked to a small increase in short term PM2.5.