Air Pollution Exposure and Interstitial Lung Features in SPIROMICS Participants with COPD.

RATIONALE: It is unknown whether air pollution is associated with radiographic features of interstitial lung disease in individuals with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine whether air pollution increases prevalence of interstitial lung abnormalities (ILA) or percent high-attenuation area (HAA) on computed tomography (CT) in individuals with a heavy smoking history and COPD. METHODS: We performed a cross-sectional study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), focused on current or former smokers with COPD. 10-year exposure to particulate matter < 2.5 µm (PM2.5), nitrogen oxides (NOx), nitrogen dioxide (NO2), and ozone (O3) prior to enrollment CTs (completed between 2010-2015) were estimated with validated spatiotemporal models at residential addresses. We applied adjusted multivariable modified Poisson regression and linear regression to investigate associations between pollution exposure and relative risk of ILA or increased percent HAA (between -600 and -250 Hounsfield units) respectively. We assessed for effect modification by MUC5B-promoter polymorphism (GT/TT vs GG at rs3705950), smoking status, sex, and percent emphysema. RESULTS: Among 1272 participants with COPD assessed for HAA, 424 were current smokers, 249 were carriers of the variant MUC5B allele (GT/TT). 519 participants were assessed for ILA. We found no association between pollution exposure and ILA or HAA. Associations between pollutant exposures and risk of ILA were modified by the presence of MUC5B polymorphism (p-value interaction term for NOx = 0.04 and PM2.5 = 0.05) and smoking status (p-value interaction term for NOx = 0.05, NO2 = 0.01, and O3 = 0.05). With higher exposure to NOx and PM2.5, MUC5B variant carriers had increased risk of ILA (Relative Risk [RR] per 26ppb NOx 2.41; 95% Confidence Interval [CI] 0.97 to 6.0) and RR per 4 µg·m-3 PM2.5 1.43; 95% CI 0.93 to 2.2). With higher exposure to NO2, former smokers had increased risk of ILA (RR per 10ppb 1.64; 95% CI 1.0 to 2.7). CONCLUSIONS: Exposure to ambient air pollution was not associated with interstitial features on CT in this population of heavy smokers with COPD. MUC5B modified the association between pollution and ILA, suggesting that gene-environment interactions may influence prevalence of interstitial lung features in COPD.

Leveraging low-cost sensors to predict nitrogen dioxide for epidemiologic exposure assessment.

BACKGROUND: Statistical models of air pollution enable intra-urban characterization of pollutant concentrations, benefiting exposure assessment for environmental epidemiology. The new generation of low-cost sensors facilitate the deployment of dense monitoring networks and can potentially be used to improve intra-urban models of air pollution. OBJECTIVE: Develop and evaluate a spatiotemporal model for nitrogen dioxide (NO2) in the Puget Sound region of WA, USA for the Adult Changes in Thought Air Pollution (ACT-AP) study and assess the contribution of low-cost sensor data to the model's performance through cross-validation. METHODS: We developed a spatiotemporal NO2 model for the study region incorporating data from 11 agency locations, 364 supplementary monitoring locations, and 117 low-cost sensor (LCS) locations for the 1996-2020 time period. Model features included long-term time trends and dimension-reduced land use regression. We evaluated the contribution of LCS network data by comparing models fit with and without sensor data using cross-validated (CV) summary performance statistics. RESULTS: The best performing model had one time trend and geographic covariates summarized into three partial least squares components. The model, fit with LCS data, performed as well as other recent studies (agency cross-validation: CV- root mean square error (RMSE) = 2.5 ppb NO2; CV- coefficient of determination ( R 2 ) = 0.85). Predictions of NO2 concentrations developed with LCS were higher at residential locations compared to a model without LCS, especially in recent years. While LCS did not provide a strong performance gain at agency sites (CV-RMSE = 2.8 ppb NO2; CV- R 2 = 0.82 without LCS), at residential locations, the improvement was substantial, with RMSE = 3.8 ppb NO2 and R 2 = 0.08 (without LCS), compared to CV-RMSE = 2.8 ppb NO2 and CV- R 2 = 0.51 (with LCS). IMPACT: We developed a spatiotemporal model for nitrogen dioxide (NO2) pollution in Washington's Puget Sound region for epidemiologic exposure assessment for the Adult Changes in Thought Air Pollution study. We examined the impact of including low-cost sensor data in the NO2 model and found the additional spatial information the sensors provided predicted NO2 concentrations that were higher than without low-cost sensors, particularly in recent years. We did not observe a clear, substantial improvement in cross-validation performance over a similar model fit without low-cost sensor data; however, the prediction improvement with low-cost sensors at residential locations was substantial. The performance gains from low-cost sensors may have been attenuated due to spatial information provided by other supplementary monitoring data.

Integrating traffic pollution dispersion into spatiotemporal NO2 prediction.

Accurately predicting ambient NO2 concentrations has great public health importance, as traffic-related air pollution is of major concern in urban areas. In this study, we present a novel approach incorporating traffic contribution to NO2 prediction in a fine-scale spatiotemporal model. We used nationally available traffic estimate dataset in a scalable dispersion model, Research LINE source dispersion model (RLINE). RLINE estimates then served as an additional input for a validated spatiotemporal pollution modeling approach. Our analysis uses measurement data collected by the Multi-Ethnic Study of Atherosclerosis and Air Pollution in the greater Los Angeles area between 2006 and 2009. We predicted road-type-specific annual average daily traffic (AADT) on road segments via national-level spatial regression models with nearest-neighbor Gaussian processes (spNNGP); the spNNGP models were trained based on over half a million point-level traffic volume measurements nationwide. AADT estimates on all highways were combined with meteorological data in RLINE models. We evaluated two strategies to integrate RLINE estimates into spatiotemporal NO2 models: 1) incorporating RLINE estimates as a space-only covariate and, 2) as a spatiotemporal covariate. The results showed that integrating the RLINE estimates as a space-only covariate improved overall cross-validation R2 from 0.83 to 0.84, and root mean squared error (RMSE) from 3.58 to 3.48 ppb. Incorporating the estimates as a spatiotemporal covariate resulted in similar model improvement. The improvement of our spatiotemporal model was more profound in roadside monitors alongside highways, with R2 increasing from 0.56 to 0.66 and RMSE decreasing from 3.52 to 3.11 ppb. The observed improvement indicates that the RLINE estimates enhanced the model's predictive capabilities for roadside NO2 concentration gradients even after considering a comprehensive list of geographic covariates including the distance to roads. Our proposed modeling framework can be generalized to improve high-resolution prediction of NO2 exposure - especially near major roads in the U.S.

Evaluating low-cost monitoring designs for PM2.5 exposure assessment with a spatiotemporal modeling approach.

Determining the most feasible and cost-effective approaches to improving PM2.5 exposure assessment with low-cost monitors (LCMs) can considerably enhance the quality of its epidemiological inferences. We investigated features of fixed-site LCM designs that most impact PM2.5 exposure estimates to be used in long-term epidemiological inference for the Adult Changes in Thought Air Pollution (ACT-AP) study. We used ACT-AP collected and calibrated LCM PM2.5 measurements at the two-week level from April 2017 to September 2020 (N of monitors [measurements] = 82 [502]). We also acquired reference-grade PM2.5 measurements from January 2010 to September 2020 (N = 78 [6186]). We used a spatiotemporal modeling approach to predict PM2.5 exposures with either all LCM measurements or varying subsets with reduced temporal or spatial coverage. We evaluated the models based on a combination of cross-validation and external validation at locations of LCMs included in the models (N = 82), and also based on an independent external validation with a set of LCMs not used for the modeling (N = 30). We found that the model's performance declined substantially when LCM measurements were entirely excluded (spatiotemporal validation R2 [RMSE] = 0.69 [1.2 µg/m3]) compared to the model with all LCM measurements (0.84 [0.9 µg/m3]). Temporally, using the farthest apart measurements (i.e., the first and last) from each LCM resulted in the closest model's performance (0.79 [1.0 µg/m3]) to the model with all LCM data. The models with only the first or last measurement had decreased performance (0.77 [1.1 µg/m3]). Spatially, the model's performance decreased linearly to 0.74 (1.1 µg/m3) when only 10% of LCMs were included. Our analysis also showed that LCMs located in densely populated, road-proximate areas improved the model more than those placed in moderately populated, road-distant areas.

Exposure Disparities by Income, Race and Ethnicity, and Historic Redlining Grade in the Greater Seattle Area for Ultrafine Particles and Other Air Pollutants.

BACKGROUND: Growing evidence shows ultrafine particles (UFPs) are detrimental to cardiovascular, cerebrovascular, and respiratory health. Historically, racialized and low-income communities are exposed to higher concentrations of air pollution. OBJECTIVES: Our aim was to conduct a descriptive analysis of present-day air pollution exposure disparities in the greater Seattle, Washington, area by income, race, ethnicity, and historical redlining grade. We focused on UFPs (particle number count) and compared with black carbon, nitrogen dioxide, and fine particulate matter (PM2.5) levels. METHODS: We obtained race and ethnicity data from the 2010 U.S. Census, median household income data from the 2006-2010 American Community Survey, and Home Owners' Loan Corporation (HOLC) redlining data from the University of Richmond's Mapping Inequality. We predicted pollutant concentrations at block centroids from 2019 mobile monitoring data. The study region encompassed much of urban Seattle, with redlining analyses restricted to a smaller region. To analyze disparities, we calculated population-weighted mean exposures and regression analyses using a generalized estimating equation model to account for spatial correlation. RESULTS: Pollutant concentrations and disparities were largest for blocks with median household income of <$20,000, Black residents, HOLC Grade D, and ungraded industrial areas. UFP concentrations were 4% lower than average for non-Hispanic White residents and higher than average for racialized groups (Asian, 3%; Black, 15%; Hispanic, 6%; Native American, 8%; Pacific Islander, 11%). For blocks with median household incomes of <$20,000, UFP concentrations were 40% higher than average, whereas blocks with incomes of >$110,000 had UFP concentrations 16% lower than average. UFP concentrations were 28% higher for Grade D and 49% higher for ungraded industrial areas compared with Grade A. Disparities were highest for UFPs and lowest for PM2.5 exposure levels. DISCUSSION: Our study is one of the first to highlight large disparities with UFP exposures compared with multiple pollutants. Higher exposures to multiple air pollutants and their cumulative effects disproportionately impact historically marginalized groups. https://doi.org/10.1289/EHP11662.

Black carbon content in airway macrophages is associated with increased severe exacerbations and worse COPD morbidity in SPIROMICS.

BACKGROUND: Airway macrophages (AM), crucial for the immune response in chronic obstructive pulmonary disease (COPD), are exposed to environmental particulate matter (PM), which they retain in their cytoplasm as black carbon (BC). However, whether AM BC accurately reflects environmental PM2.5 exposure, and can serve as a biomarker of COPD outcomes, is unknown. METHODS: We analyzed induced sputum from participants at 7 of 12 sites SPIROMICS sites for AM BC content, which we related to exposures and to lung function and respiratory outcomes. Models were adjusted for batch (first vs. second), age, race (white vs. non-white), income (<$35,000, $35,000~$74,999, ≥$75,000, decline to answer), BMI, and use of long-acting beta-agonist/long-acting muscarinic antagonists, with sensitivity analysis performed with inclusion of urinary cotinine and lung function as covariates. RESULTS: Of 324 participants, 143 were current smokers and 201 had spirometric-confirmed COPD. Modeled indoor fine (< 2.5 µm in aerodynamic diameter) particulate matter (PM2.5) and urinary cotinine were associated with higher AM BC. Other assessed indoor and ambient pollutant exposures were not associated with higher AM BC. Higher AM BC was associated with worse lung function and odds of severe exacerbation, as well as worse functional status, respiratory symptoms and quality of life. CONCLUSION: Indoor PM2.5 and cigarette smoke exposure may lead to increased AM BC deposition. Black carbon content in AMs is associated with worse COPD morbidity in current and former smokers, which remained after sensitivity analysis adjusting for cigarette smoke burden. Airway macrophage BC, which may alter macrophage function, could serve as a predictor of experiencing worse respiratory symptoms and impaired lung function.

Within-City Variation in Ambient Carbon Monoxide Concentrations: Leveraging Low-Cost Monitors in a Spatiotemporal Modeling Framework.

BACKGROUND: Based on human and animal experimental studies, exposure to ambient carbon monoxide (CO) may be associated with cardiovascular disease outcomes, but epidemiological evidence of this link is limited. The number and distribution of ground-level regulatory agency monitors are insufficient to characterize fine-scale variations in CO concentrations. OBJECTIVES: To develop a daily, high-resolution ambient CO exposure prediction model at the city scale. METHODS: We developed a CO prediction model in Baltimore, Maryland, based on a spatiotemporal statistical algorithm with regulatory agency monitoring data and measurements from calibrated low-cost gas monitors. We also evaluated the contribution of three novel parameters to model performance: high-resolution meteorological data, satellite remote sensing data, and copollutant (PM2.5, NO2, and NOx) concentrations. RESULTS: The CO model had spatial cross-validation (CV) R2 and root-mean-square error (RMSE) of 0.70 and 0.02 parts per million (ppm), respectively; the model had temporal CV R2 and RMSE of 0.61 and 0.04 ppm, respectively. The predictions revealed spatially resolved CO hot spots associated with population, traffic, and other nonroad emission sources (e.g., railroads and airport), as well as sharp concentration decreases within short distances from primary roads. DISCUSSION: The three novel parameters did not substantially improve model performance, suggesting that, on its own, our spatiotemporal modeling framework based on geographic features was reliable and robust. As low-cost air monitors become increasingly available, this approach to CO concentration modeling can be generalized to resource-restricted environments to facilitate comprehensive epidemiological research. https://doi.org/10.1289/EHP10889.

Ambient ozone effects on respiratory outcomes among smokers modified by neighborhood poverty: An analysis of SPIROMICS AIR.

BACKGROUND: Neighborhood poverty has been associated with poor health outcomes. Previous studies have also identified adverse respiratory effects of long-term ambient ozone. Factors associated with neighborhood poverty may accentuate the adverse impact of ozone on respiratory health. OBJECTIVES: To evaluate whether neighborhood poverty modifies the association between ambient ozone exposure and respiratory morbidity including symptoms, exacerbation risk, and radiologic parameters, among participants of the SPIROMICS AIR cohort study. METHODS: Spatiotemporal models incorporating cohort-specific monitoring estimated 10-year average outdoor ozone concentrations at participants' homes. Adjusted regression models were used to determine the association of ozone exposure with respiratory outcomes, accounting for demographic factors, education, individual income, body mass index (BMI), and study site. Neighborhood poverty rate was defined by percentage of families living below federal poverty level per census tract. Interaction terms for neighborhood poverty rate with ozone were included in covariate-adjusted models to evaluate for effect modification. RESULTS: 1874 participants were included in the analysis, with mean (± SD) age 64 (± 8.8) years and FEV1 (forced expiratory volume in one second) 74.7% (±25.8) predicted. Participants resided in neighborhoods with mean poverty rate of 9.9% (±10.3) of families below the federal poverty level and mean 10-year ambient ozone concentration of 24.7 (±5.2) ppb. There was an interaction between neighborhood poverty rate and ozone concentration for numerous respiratory outcomes, including COPD Assessment Test score, modified Medical Research Council Dyspnea Scale, six-minute walk test, and odds of COPD exacerbation in the year prior to enrollment, such that adverse effects of ozone were greater among participants in higher poverty neighborhoods. CONCLUSION: Individuals with COPD in high poverty neighborhoods have higher susceptibility to adverse respiratory effects of ambient ozone exposure, after adjusting for individual factors. These findings highlight the interaction between exposures associated with poverty and their effect on respiratory health.

Publicly available low-cost sensor measurements for PM2.5 exposure modeling: Guidance for monitor deployment and data selection.

High-resolution, high-quality exposure modeling is critical for assessing the health effects of ambient PM2.5 in epidemiological studies. Using sparse regulatory PM2.5 measurements as principal model inputs may result in two issues in exposure prediction: (1) they may affect the models' accuracy in predicting PM2.5 spatial distribution; (2) the internal validation based on these measurements may not reliably reflect the model performance at locations of interest (e.g., a cohort's residential locations). In this study, we used the PM2.5 measurements from a publicly available commercial low-cost PM2.5 network, PurpleAir, with an external validation dataset at the residential locations of a representative sample of participants from the Adult Changes in Thought - Air Pollution (ACT-AP) study, to improve the accuracy of exposure prediction at the cohort participant locations. We also proposed a metric based on principal component analysis (PCA) - the PCA distance - to assess the similarity between monitor and cohort locations to guide monitor deployment and data selection. The analysis was based on a spatiotemporal modeling framework with 51 "gold-standard" monitors and 58 PurpleAir monitors for model development, as well as 105 home monitors at the cohort locations for model validation, in the Puget Sound region of Washington State from June 2017 to March 2019. After including calibrated PurpleAir measurements as part of the dependent variable, the external spatiotemporal validation R2 and root-mean-square error, RMSE, for two-week concentration averages improved from 0.84 and 2.22 µg/m3 to 0.92 and 1.63 µg/m3, respectively. The external spatial validation R2 and RMSE for long-term averages over the modeling period improved from 0.72 and 1.01 µg/m3 to 0.79 and 0.88 µg/m3, respectively. The exposure predictions incorporating PurpleAir measurements demonstrated sharper urban-suburban concentration gradients. The PurpleAir monitors with shorter PCA distances improved the model's prediction accuracy more substantially than the monitors with longer PCA distances, supporting the use of this similarity metric.

Deployment, Calibration, and Cross-Validation of Low-Cost Electrochemical Sensors for Carbon Monoxide, Nitrogen Oxides, and Ozone for an Epidemiological Study.

We designed and built a network of monitors for ambient air pollution equipped with low-cost gas sensors to be used to supplement regulatory agency monitoring for exposure assessment within a large epidemiological study. This paper describes the development of a series of hourly and daily field calibration models for Alphasense sensors for carbon monoxide (CO; CO-B4), nitric oxide (NO; NO-B4), nitrogen dioxide (NO2; NO2-B43F), and oxidizing gases (OX-B431)-which refers to ozone (O3) and NO2. The monitor network was deployed in the Puget Sound region of Washington, USA, from May 2017 to March 2019. Monitors were rotated throughout the region, including at two Puget Sound Clean Air Agency monitoring sites for calibration purposes, and over 100 residences, including the homes of epidemiological study participants, with the goal of improving long-term pollutant exposure predictions at participant locations. Calibration models improved when accounting for individual sensor performance, ambient temperature and humidity, and concentrations of co-pollutants as measured by other low-cost sensors in the monitors. Predictions from the final daily models for CO and NO performed the best considering agreement with regulatory monitors in cross-validated root-mean-square error (RMSE) and R2 measures (CO: RMSE = 18 ppb, R2 = 0.97; NO: RMSE = 2 ppb, R2 = 0.97). Performance measures for NO2 and O3 were somewhat lower (NO2: RMSE = 3 ppb, R2 = 0.79; O3: RMSE = 4 ppb, R2 = 0.81). These high levels of calibration performance add confidence that low-cost sensor measurements collected at the homes of epidemiological study participants can be integrated into spatiotemporal models of pollutant concentrations, improving exposure assessment for epidemiological inference.

Modeling residential indoor concentrations of PM2.5 , NO2 , NOx , and secondhand smoke in the Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) Air study.

Increased outdoor concentrations of fine particulate matter (PM2.5 ) and oxides of nitrogen (NO2 , NOx ) are associated with respiratory and cardiovascular morbidity in adults and children. However, people spend most of their time indoors and this is particularly true for individuals with chronic obstructive pulmonary disease (COPD). Both outdoor and indoor air pollution may accelerate lung function loss in individuals with COPD, but it is not feasible to measure indoor pollutant concentrations in all participants in large cohort studies. We aimed to understand indoor exposures in a cohort of adults (SPIROMICS Air, the SubPopulations and Intermediate Outcome Measures in COPD Study of Air pollution). We developed models for the entire cohort based on monitoring in a subset of homes, to predict mean 2-week-measured concentrations of PM2.5 , NO2 , NOx , and nicotine, using home and behavioral questionnaire responses available in the full cohort. Models incorporating socioeconomic, meteorological, behavioral, and residential information together explained about 60% of the variation in indoor concentration of each pollutant. Cross-validated R2 for best indoor prediction models ranged from 0.43 (NOx ) to 0.51 (NO2 ). Models based on questionnaire responses and estimated outdoor concentrations successfully explained most variation in indoor PM2.5 , NO2 , NOx , and nicotine concentrations.

Contribution of Individual and Neighborhood Factors to Racial Disparities in Respiratory Outcomes.

Rationale: Black adults have worse health outcomes compared with white adults in certain chronic diseases, including chronic obstructive pulmonary disease (COPD).Objectives: To determine to what degree disadvantage by individual and neighborhood socioeconomic status (SES) may contribute to racial disparities in COPD outcomes.Methods: Individual and neighborhood-scale sociodemographic characteristics were determined in 2,649 current or former adult smokers with and without COPD at recruitment into SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). We assessed whether racial differences in symptom, functional, and imaging outcomes (St. George's Respiratory Questionnaire, COPD Assessment Test score, modified Medical Research Council dyspnea scale, 6-minute-walk test distance, and computed tomography [CT] scan metrics) and severe exacerbation risk were explained by individual or neighborhood SES. Using generalized linear mixed model regression, we compared respiratory outcomes by race, adjusting for confounders and individual-level and neighborhood-level descriptors of SES both separately and sequentially.Measurements and Main Results: After adjusting for COPD risk factors, Black participants had significantly worse respiratory symptoms and quality of life (modified Medical Research Council scale, COPD Assessment Test, and St. George's Respiratory Questionnaire), higher risk of severe exacerbations and higher percentage of emphysema, thicker airways (internal perimeter of 10 mm), and more air trapping on CT metrics compared with white participants. In addition, the association between Black race and respiratory outcomes was attenuated but remained statistically significant after adjusting for individual-level SES, which explained up to 12-35% of racial disparities. Further adjustment showed that neighborhood-level SES explained another 26-54% of the racial disparities in respiratory outcomes. Even after accounting for both individual and neighborhood SES factors, Black individuals continued to have increased severe exacerbation risk and persistently worse CT outcomes (emphysema, air trapping, and airway wall thickness).Conclusions: Disadvantages by individual- and neighborhood-level SES each partly explain disparities in respiratory outcomes between Black individuals and white individuals. Strategies to narrow the gap in SES disadvantages may help to reduce race-related health disparities in COPD; however, further work is needed to identify additional risk factors contributing to persistent disparities.

The Association Between Neighborhood Socioeconomic Disadvantage and Chronic Obstructive Pulmonary Disease.

Rationale: Individual socioeconomic status has been shown to influence the outcomes of patients with chronic obstructive pulmonary disease (COPD). However, contextual factors may also play a role. The objective of this study is to evaluate the association between neighborhood socioeconomic disadvantage measured by the area deprivation index (ADI) and COPD-related outcomes. Methods: Residential addresses of SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) subjects with COPD (FEV1/FVC <0.70) at baseline were geocoded and linked to their respective ADI national ranking score at the census block group level. The associations between the ADI and COPD-related outcomes were evaluated by examining the contrast between participants living in the most-disadvantaged (top quintile) to the least-disadvantaged (bottom quintile) neighborhood. Regression models included adjustment for individual-level demographics, socioeconomic variables (personal income, education), exposures (smoking status, packs per year, occupational exposures), clinical characteristics (FEV1% predicted, body mass index) and neighborhood rural status. Results: A total of 1800 participants were included in the analysis. Participants residing in the most-disadvantaged neighborhoods had 56% higher rate of COPD exacerbation (P<0.001), 98% higher rate of severe COPD exacerbation (P=0.001), a 1.6 point higher CAT score (P<0.001), 3.1 points higher SGRQ (P<0.001), and 24.6 meters less six-minute walk distance (P=0.008) compared with participants who resided in the least disadvantaged neighborhoods. Conclusion: Participants with COPD who reside in more-disadvantaged neighborhoods had worse COPD outcomes compared to those residing in less-disadvantaged neighborhoods. Neighborhood effects were independent of individual-level socioeconomic factors, suggesting that contextual factors could be used to inform intervention strategies targeting high-risk persons with COPD.

Association of Long-term Ambient Ozone Exposure With Respiratory Morbidity in Smokers.

Importance: Few studies have investigated the association of long-term ambient ozone exposures with respiratory morbidity among individuals with a heavy smoking history. Objective: To investigate the association of historical ozone exposure with risk of chronic obstructive pulmonary disease (COPD), computed tomography (CT) scan measures of respiratory disease, patient-reported outcomes, disease severity, and exacerbations in smokers with or at risk for COPD. Design, Setting, and Participants: This multicenter cross-sectional study, conducted from November 1, 2010, to July 31, 2018, obtained data from the Air Pollution Study, an ancillary study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). Data analyzed were from participants enrolled at 7 (New York City, New York; Baltimore, Maryland; Los Angeles, California; Ann Arbor, Michigan; San Francisco, California; Salt Lake City, Utah; and Winston-Salem, North Carolina) of the 12 SPIROMICS clinical sites. Included participants had historical ozone exposure data (n = 1874), were either current or former smokers (≥20 pack-years), were with or without COPD, and were aged 40 to 80 years at baseline. Healthy persons with a smoking history of 1 or more pack-years were excluded from the present analysis. Exposures: The 10-year mean historical ambient ozone concentration at participants' residences estimated by cohort-specific spatiotemporal modeling. Main Outcomes and Measures: Spirometry-confirmed COPD, chronic bronchitis diagnosis, CT scan measures (emphysema, air trapping, and airway wall thickness), 6-minute walk test, modified Medical Research Council (mMRC) Dyspnea Scale, COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), postbronchodilator forced expiratory volume in the first second of expiration (FEV1) % predicted, and self-report of exacerbations in the 12 months before SPIROMICS enrollment, adjusted for demographics, smoking, and job exposure. Results: A total of 1874 SPIROMICS participants were analyzed (mean [SD] age, 64.5 [8.8] years; 1479 [78.9%] white; and 1013 [54.1%] male). In adjusted analysis, a 5-ppb (parts per billion) increase in ozone concentration was associated with a greater percentage of emphysema (ß = 0.94; 95% CI, 0.25-1.64; P = .007) and percentage of air trapping (ß = 1.60; 95% CI, 0.16-3.04; P = .03); worse scores for the mMRC Dyspnea Scale (ß = 0.10; 95% CI, 0.03-0.17; P = .008), CAT (ß = 0.65; 95% CI, 0.05-1.26; P = .04), and SGRQ (ß = 1.47; 95% CI, 0.01-2.93; P = .048); lower FEV1% predicted value (ß = -2.50; 95% CI, -4.42 to -0.59; P = .01); and higher odds of any exacerbation (odds ratio [OR], 1.37; 95% CI, 1.12-1.66; P = .002) and severe exacerbation (OR, 1.37; 95% CI, 1.07-1.76; P = .01). No association was found between historical ozone exposure and chronic bronchitis, COPD, airway wall thickness, or 6-minute walk test result. Conclusions and Relevance: This study found that long-term historical ozone exposure was associated with reduced lung function, greater emphysema and air trapping on CT scan, worse patient-reported outcomes, and increased respiratory exacerbations for individuals with a history of heavy smoking. The association between ozone exposure and adverse respiratory outcomes suggests the need for continued reevaluation of ambient pollution standards that are designed to protect the most vulnerable members of the US population.

Calibration of low-cost particulate matter sensors: Model development for a multi-city epidemiological study.

Low-cost air monitoring sensors are an appealing tool for assessing pollutants in environmental studies. Portable low-cost sensors hold promise to expand temporal and spatial coverage of air quality information. However, researchers have reported challenges in these sensors' operational quality. We evaluated the performance characteristics of two widely used sensors, the Plantower PMS A003 and Shinyei PPD42NS, for measuring fine particulate matter compared to reference methods, and developed regional calibration models for the Los Angeles, Chicago, New York, Baltimore, Minneapolis-St. Paul, Winston-Salem and Seattle metropolitan areas. Duplicate Plantower PMS A003 sensors demonstrated a high level of precision (averaged Pearson's r = 0.99), and compared with regulatory instruments, showed good accuracy (cross-validated R2 = 0.96, RMSE = 1.15 µg/m3 for daily averaged PM2.5 estimates in the Seattle region). Shinyei PPD42NS sensor results had lower precision (Pearson's r = 0.84) and accuracy (cross-validated R2 = 0.40, RMSE = 4.49 µg/m3). Region-specific Plantower PMS A003 models, calibrated with regulatory instruments and adjusted for temperature and relative humidity, demonstrated acceptable performance metrics for daily average measurements in the other six regions (R2 = 0.74-0.95, RMSE = 2.46-0.84 µg/m3). Applying the Seattle model to the other regions resulted in decreased performance (R2 = 0.67-0.84, RMSE = 3.41-1.67 µg/m3), likely due to differences in meteorological conditions and particle sources. We describean approach to metropolitan region-specific calibration models for low-cost sensors that can be used with cautionfor exposure measurement in epidemiological studies.

Estimating ambient-origin PM2.5 exposure for epidemiology: observations, prediction, and validation using personal sampling in the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES: We aim to characterize the qualities of estimation approaches for individual exposure to ambient-origin fine particulate matter (PM2.5), for use in epidemiological studies. METHODS: The analysis incorporates personal, home indoor, and home outdoor air monitoring data and spatio-temporal model predictions for 60 participants from the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). We compared measurement-based personal PM2.5 exposure with several measured or predicted estimates of outdoor, indoor, and personal exposures. RESULTS: The mean personal 2-week exposure was 7.6 (standard deviation 3.7) µg/m3. Outdoor model predictions performed far better than outdoor concentrations estimated using a nearest-monitor approach (R = 0.63 versus R = 0.43). Incorporating infiltration indoors of ambient-derived PM2.5 provided better estimates of the measurement-based personal exposures than outdoor concentration predictions (R = 0.81 versus R = 0.63) and better scaling of estimated exposure (mean difference 0.4 versus 5.4 µg/m3 higher than measurements), suggesting there is value to collecting data regarding home infiltration. Incorporating individual-level time-location information into exposure predictions did not increase correlations with measurement-based personal exposures (R = 0.80) in our sample consisting primarily of retired persons. CONCLUSIONS: This analysis demonstrates the importance of incorporating infiltration when estimating individual exposure to ambient air pollution. Spatio-temporal models provide substantial improvement in exposure estimation over a nearest monitor approach.

Ambient air pollution and lung cancer risk among never-smokers in the Women's Health Initiative.

BACKGROUND: Ambient air pollution is classified as a human carcinogen by the International Agency for Research on Cancer (IARC). However, epidemiologic studies supporting this classification have focused on lung cancer mortality rather than incidence, and spatial and temporal resolutions of exposure estimates have varied considerably across studies. METHODS: We evaluated the association of outdoor air pollution and lung cancer incidence among never-smoking participants of the Women's Health Initiative (WHI) study, a large, US-based cohort of postmenopausal women (N = 65,419; 265 cases). We used geospatial models to estimate exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) based on residential addresses at baseline and throughout follow-up. We also characterized exposures to traffic-related air pollution by proximity to major roadways. We estimated hazard ratios (HRs) for the risk of lung cancer in association with these exposure metrics using Cox proportional hazards regression models. RESULTS: No compelling associations of PM2.5 and NO2 exposures with lung cancer risk were observed. An increased risk of lung cancer was observed when comparing those individuals with residences <50 versus ≥200 meters from a primary limited access highway (HR = 5.23; 95% confidence interval = 1.94, 14.13). CONCLUSIONS: Our results do not exclude lung cancer risk estimates observed in association with PM2.5 and NO2 exposures identified in previous studies. Our results suggest that residential proximity to major roadways may be a proxy for carcinogenic exposures not correlated with PM2.5 or NO2 levels. New studies of air pollution and lung cancer incidence should characterize additional aspects of proximity to major roadways.

Ultrasound carotid plaque features, cardiovascular disease risk factors and events: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: It is not known if ultrasound carotid plaque features are associated with cardiovascular disease (CVD) risk factors or if they predict future CVD events. METHODS: We measured total carotid plaque area (TPA) and grayscale plaque features (grayscale median, black areas, and discrete white areas) by B-mode carotid ultrasound among 2205 participants who participated in the first (baseline) visit of the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used to examine relationships between ultrasound plaque features and CVD risk factors at baseline. Cox proportional hazards models were used to assess if TPA, grayscale features, and carotid plaque score (number of arterial segments with a plaque) could predict incident coronary heart disease and cerebrovascular disease events over a mean follow-up of 13.3 years. RESULTS: Participants were mean (standard deviation [SD]) 65.4 (9.6) years, 49% male, 39% White, 11% Chinese, 28% Black, and 22% Hispanic. Mean TPA 27.7 (24.7) mm2, but no grayscale plaque features, was associated with CVD risk factors. In fully adjusted models, TPA but no grayscale features predicted incident coronary heart disease (CHD) events (HR 1.23; 95%CI 1.11-1.36; p<0.001), however, C-statistics for CHD were similar to carotid plaque score but less than for coronary artery calcium (CAC) scoring. Neither TPA nor grayscale features independently predicted cerebrovascular events. CONCLUSIONS: In middle-aged adults free of known cardiovascular disease, TPA but not grayscale plaque features was associated with CVD risk factors and predicted incident CHD events. For CHD, prediction indices for TPA were similar to carotid plaque score but less than for CAC.

Rural Residence and Chronic Obstructive Pulmonary Disease Exacerbations. Analysis of the SPIROMICS Cohort.

Rationale: Rural residence is associated with poor outcomes in several chronic diseases. The association between rural residence and chronic obstructive pulmonary disease (COPD) exacerbations remains unclear.Objectives: In this work, we sought to determine the independent association between rural residence and COPD-related outcomes, including COPD exacerbations, airflow obstruction, and symptom burden.Methods: A total of 1,684 SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) participants with forced expiratory volume in 1 second/forced vital capacity < 0.70 had geocoding-defined rural-urban residence status determined (N = 204 rural and N = 1,480 urban). Univariate and multivariate logistic and negative binomial regressions were performed to assess the independent association between rurality and COPD outcomes, including exacerbations, lung function, and symptom burden. The primary exposure of interest was rural residence, determined by geocoding of the home address to the block level at the time of study enrollment. Additional covariates of interest included demographic and clinical characteristics, occupation, and occupational exposures. The primary outcome measures were exacerbations determined over a 1-year course after enrollment by quarterly telephone calls and at an annual research clinic visit. The odds ratio (OR) and incidence rate ratio (IRR) of exacerbations that required treatment with medications, including steroids or antibiotics (total exacerbations), and exacerbations leading to hospitalization (severe exacerbations) were determined after adjusting for relevant covariates.Results: Rural residence was independently associated with a 70% increase in the odds of total exacerbations (OR, 1.70 [95% confidence interval (CI), 1.13-2.56]; P = 0.012) and a 46% higher incidence rate of total exacerbations (IRR 1.46 [95% CI, 1.02-2.10]; P = 0.039). There was no association between rural residence and severe exacerbations. Agricultural occupation was independently associated with increased odds and incidence of total and severe exacerbations. Inclusion of agricultural occupation in the analysis attenuated the association between rural residence and the odds and incidence rate of total exacerbations (OR, 1.52 [95% CI, 1.00-2.32]; P = 0.05 and IRR 1.39 [95% CI, 0.97-1.99]; P = 0.07). There was no difference in symptoms or airflow obstruction between rural and urban participants.Conclusions: Rural residence is independently associated with increased odds and incidence of total, but not severe, COPD exacerbations. These associations are not fully explained by agriculture-related exposures, highlighting the need for future research into potential mechanisms of the increased risk of COPD exacerbations in the rural population.

Exposure to ambient air pollution and calcification of the mitral annulus and aortic valve: the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: Long-term exposure to high ambient air pollution has been associated with coronary artery calcium (CAC), a marker of cardiovascular disease (CVD). Calcifications of left-sided heart valves are also markers of CVD risk. We investigated whether air pollution was associated with valvular calcification and its progression. METHODS: We studied 6253 MESA participants aged 45-84 years who underwent two cardiac CT scans 2.5 years apart to quantify aortic valve calcium (AVC) and mitral annular calcium (MAC). CAC was included for the same timeframe for comparison with AVC/MAC. Ambient particulate matter <2.5 µm (PM2.5) and oxides of nitrogen (NOx) concentrations were predicted from residence-specific spatio-temporal models. RESULTS: The mean age (SD) of the study sample was 62 (10) years, 39% were white, 27% black, 22% Hispanic, and 12% Chinese. The prevalence of AVC and MAC at baseline were 13% and 9% respectively, compared to 50% prevalence of CAC. The adjusted prevalence ratios of AVC and MAC for each 5 µg/m3 higher PM2.5 was 1.19 (95% CI 0.87, 1.62) and 1.20 (0.81, 1.77) respectively, and for CAC was 1.14 (1.01, 1.27). Over 2.5 years, the mean change in Agatston units/year for each 5 µg/m3 higher PM2.5 concentration was 0.29 (-5.05, 5.63) for AVC and 4.38 (-9.13, 17.88) for MAC, compared to 8.66 (0.61, 16.71) for CAC. We found no significant associations of NOx with AVC and MAC. CONCLUSION: Our findings suggest a trend towards increased 2.5-year progression of MAC with exposure to outdoor PM2.5, although this association could not be confirmed. Additional well-powered studies with longer periods of follow-up are needed to further study associations of air pollution with valvular calcium. TRIAL REGISTRATION: Although MESA is not a clinical trial, this cohort is registered at ClinicalTrials.gov Identifier: NCT00005487; Date of registration May 25, 2000.