Within-City Variation in Reactive Oxygen Species from Fine Particle Air Pollution and COVID-19.

Rationale: Evidence linking outdoor air pollution with coronavirus disease (COVID-19) incidence and mortality is largely based on ecological comparisons between regions that may differ in factors such as access to testing and control measures that may not be independent of air pollution concentrations. Moreover, studies have yet to focus on key mechanisms of air pollution toxicity such as oxidative stress. Objectives: To conduct a within-city analysis of spatial variations in COVID-19 incidence and the estimated generation of reactive oxygen species (ROS) in lung lining fluid attributable to fine particulate matter (particulate matter with an aerodynamic diameter ⩽2.5 µm [PM2.5]). Methods: Sporadic and outbreak-related COVID-19 case counts, testing data, population data, and sociodemographic data for 140 neighborhoods were obtained from the City of Toronto. ROS estimates were based on a mathematical model of ROS generation in lung lining fluid in response to iron and copper in PM2.5. Spatial variations in long-term average ROS were predicted using a land-use regression model derived from measurements of iron and copper in PM2.5. Data were analyzed using negative binomial regression models adjusting for covariates identified using a directed acyclic graph and accounting for spatial autocorrelation. Measurements and Main Results: A significant positive association was observed between neighborhood-level ROS and COVID-19 incidence (incidence rate ratio = 1.07; 95% confidence interval, 1.01-1.15 per interquartile range ROS). Effect modification by neighborhood-level measures of racialized group membership and socioeconomic status was also identified. Conclusions: Examination of neighborhood characteristics associated with COVID-19 incidence can identify inequalities and generate hypotheses for future studies.

Associations between air pollution and cardio-respiratory physiological measures in older adults exercising outdoors.

We examined whether exercising indoors vs. outdoors reduced the cardio-respiratory effects of outdoor air pollution. Adults ≥55 were randomly assigned to exercise indoors when the Air Quality Health Index was ≥5 and outdoors on other days (intervention group, n = 37), or outdoors everyday (control group, n = 35). Both groups completed cardio-respiratory measurements before and after exercise for up to 10 weeks. Data were analyzed using linear mixed effect regression models. In the control group, an interquartile range increase in fine particulate matter (PM2.5) was associated with increases of 1.4% in heart rate (standard error (SE) = 0.7%) and 5.6% (SE = 2.6%) in malondialdehyde, and decreases of 5.6% (SE = 2.5%) to 16.5% (SE = 7.5%) in heart rate variability measures. While the hypothesized benefit of indoor vs. outdoor exercise could not be demonstrated due to an insufficient number of intervention days (n = 2), the study provides evidence of short-term effects of air pollution in older adults. ISRCTN #26552763.

Associations between incident breast cancer and ambient concentrations of nitrogen dioxide from a national land use regression model in the Canadian National Breast Screening Study.

BACKGROUND: Air pollution has been classified as a human carcinogen based largely on epidemiological studies of lung cancer. Recent research suggests that exposure to ambient air pollution increases the risk of female breast cancer especially in premenopausal women. METHODS: Our objective was to determine the association between residential exposure to ambient nitrogen dioxide (NO2) and newly diagnosed cases of invasive breast cancer in a cohort of 89,247 women enrolled in the Canadian National Breast Screening Study between 1980 and 1985. Vital status and incident breast cancers through 2005 were determined through record linkage to the Canadian national mortality and cancer registries. Estimates of exposures to NO2 using participants' addresses at time of entry into the study were derived from a national land use regression model. We classified women as reaching menopause according to information obtained at baseline. In addition, as we had no information from women on their menopausal status during the observation period, we conducted analyses using different cut-points for defining postmenopausal status (i.e., at 50 or at 52 years of age), and hence we had four non-independent cohorts. We computed rate ratios for the incidence of breast cancer and their 95% confidence intervals (CI) separately for premenopausal and postmenopausal women. Our Cox models used attained age as the time axis and the rate ratios were adjusted for several individual-level risk factors, including reproductive history, as well as census-based neighborhood-level characteristics. RESULTS: The median concentration of NO2 was about 15 parts per billion (ppb). After adjusting for personal risk factors and contextual variables, we found no evidence of associations for the incidence of breast cancer in the postmenopausal cohorts. In premenopausal women, the rate ratio for an increase of 9.7 ppb (about the interquartile range) was 1.13 (95%CI: 0.94-1.37) for the 50 years of age cut-off for menopausal status and it was 1.17 (95%CI: 1.00-1.38) for the 52 years of age cut-off. CONCLUSIONS: Our findings suggest that exposure to low concentrations of NO2, a marker for traffic-related air pollution, increases the risk of premenopausal breast cancer, but not postmenopausal breast cancer.

Low concentrations of fine particle air pollution and mortality in the Canadian Community Health Survey cohort.

BACKGROUND: Approximately 2.9 million deaths are attributed to ambient fine particle air pollution around the world each year (PM2.5). In general, cohort studies of mortality and outdoor PM2.5 concentrations have limited information on individuals exposed to low levels of PM2.5 as well as covariates such as smoking behaviours, alcohol consumption, and diet which may confound relationships with mortality. This study provides an updated and extended analysis of the Canadian Community Health Survey-Mortality cohort: a population-based cohort with detailed PM2.5 exposure data and information on a number of important individual-level behavioural risk factors. We also used this rich dataset to provide insight into the shape of the concentration-response curve for mortality at low levels of PM2.5. METHODS: Respondents to the Canadian Community Health Survey from 2000 to 2012 were linked by postal code history from 1981 to 2016 to high resolution PM2.5 exposure estimates, and mortality incidence to 2016. Cox proportional hazard models were used to estimate the relationship between non-accidental mortality and ambient PM2.5 concentrations (measured as a three-year average with a one-year lag) adjusted for socio-economic, behavioural, and time-varying contextual covariates. RESULTS: In total, 50,700 deaths from non-accidental causes occurred in the cohort over the follow-up period. Annual average ambient PM2.5 concentrations were low (i.e. 5.9 µg/m3, s.d. 2.0) and each 10 µg/m3 increase in exposure was associated with an increase in non-accidental mortality (HR = 1.11; 95% CI 1.04-1.18). Adjustment for behavioural covariates did not materially change this relationship. We estimated a supra-linear concentration-response curve extending to concentrations below 2 µg/m3 using a shape constrained health impact function. Mortality risks associated with exposure to PM2.5 were increased for males, those under age 65, and non-immigrants. Hazard ratios for PM2.5 and mortality were attenuated when gaseous pollutants were included in models. CONCLUSIONS: Outdoor PM2.5 concentrations were associated with non-accidental mortality and adjusting for individual-level behavioural covariates did not materially change this relationship. The concentration-response curve was supra-linear with increased mortality risks extending to low outdoor PM2.5 concentrations.

The influence of three e-cigarette models on indoor fine and ultrafine particulate matter concentrations under real-world conditions.

Electronic cigarette (e-cigarette) use has steadily increased since 2010. Indoor e-cigarette use exposes bystanders to a new source of particulate matter (PM) air pollution. Elevated short-term exposures to PM with a lower measuremented aerodynamic diameter (≤2.5 µm), PM2.5 and ultrafine particles (UFPs) have been linked to increased risk of adverse respiratory and cardiac events. This exposure study estimated concentrations of PM2.5 and UFPs from indoor e-cigarette use at 0.5 meters (m) and 1 m away from an e-cigarette user and investigated whether these indoor concentrations varied across three common e-cigarette models. One e-cigarette user tested three different e-cigarettes containing the same nicotine solution on three separate occasions and measured concentrations on PM2.5 and UFPs at 0.5 and 1 m in a ∼38 m3 office. Continuous measures of PM2.5 and UFPs were taken for 5.5 min before e-cigarette use, then the user puffed seven times for 6.5 min (exposure), and for 10 min after ceasing e-cigarette use. Following the initiation of e-cigarette use, levels of PM2.5 increased 160-fold at a distance of 0.5 m, and 103-fold at 1 m. The corresponding increases in UFP counts were 5.2, and 3.0-fold higher, respectively. The PM2.5 concentrations and UFP counts between e-cigarette models were statistically significantly different at 1 m, but not at 0.5 m. There was substantial variability between distances, e-cigarettes, and replicates. This study indicates that e-cigarette vapors influence PM2.5 and UFPs concentrations/counts at close proximity distances indoors; additional research is needed to characterize the composition of those particles and evaluate the impacts of other e-cigarette solutions on indoor air quality.

Cardiorespiratory Effects of Air Pollution in a Panel Study of Winter Outdoor Physical Activity in Older Adults.

OBJECTIVE: The aim of this study was to assess cardiorespiratory effects of air pollution in older adults exercising outdoors in winter. METHODS: Adults 55 years of age and older completed daily measurements of blood pressure, peak expiratory flow and oximetry, and weekly measurements of heart rate variability, endothelial function, spirometry, fraction of exhaled nitric oxide and urinary oxidative stress markers, before and after outdoor exercise, for 10 weeks. Data were analyzed using linear mixed effect models. RESULTS: Pooled estimates combining 2014 (n = 36 participants) and 2015 (n = 34) indicated that an interquartile increase in the Air Quality Health Index was associated with a significant (P < 0.05) increase in heart rate (0.33%) and significant decreases in forced expiratory volume (0.30%), and systolic (0.28%) and diastolic blood pressure (0.39%). CONCLUSION: Acute subclinical effects of air pollution were observed in older adults exercising outdoors in winter.

Cardio-Respiratory Effects of Air Pollution in a Panel Study of Outdoor Physical Activity and Health in Rural Older Adults.

OBJECTIVE: To examine cardio-respiratory effects of air pollution in rural older adults exercising outdoors. METHODS: Adults 55 and over completed measurements of blood pressure, peak expiratory flow and oximetry daily, and of heart rate variability, endothelial function, spirometry, fraction of exhaled nitric oxide and urinary oxidative stress markers weekly, before and after outdoor exercise, for 10 weeks. Data were analyzed using linear mixed effect models. RESULTS: Pooled estimates combining 2013 (n = 36 participants) and 2014 (n = 41) indicated that an interquartile increase in the air quality health index (AQHI) was associated with a significant (P < 0.05) increase in heart rate (2.1%) and significant decreases in high frequency power (-19.1%), root mean square of successive differences (-9.5%), and reactive hyperemia index (-6.5%). CONCLUSIONS: We observed acute subclinical adverse effects of air pollution in rural older adults exercising outdoors.

Long-term exposure to fine particulate matter air pollution and the risk of lung cancer among participants of the Canadian National Breast Screening Study.

Recently, air pollution has been classified as a carcinogen largely on the evidence of epidemiological studies of lung cancer. However, there have been few prospective studies that have evaluated associations between fine particulate matter (PM2.5 ) and cancer at lower concentrations. We conducted a prospective analysis of 89,234 women enrolled in the Canadian National Breast Screening Study between 1980 and 1985, and for whom residential measures of PM2.5 could be assigned. The cohort was linked to the Canadian Cancer Registry to identify incident lung cancers through 2004. Surface PM2.5 concentrations were estimated using satellite data. Cox proportional hazards models were used to characterize associations between PM2.5 and lung cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) computed from these models were adjusted for several individual-level characteristics, including smoking. The cohort was composed predominantly of Canadian-born (82%), married (80%) women with a median PM2.5 exposure of 9.1 µg/m(3) . In total, 932 participants developed lung cancer. In fully adjusted models, a 10 µg/m(3) increase in PM2.5 was associated with an elevated risk of lung cancer (HR: 1.34; 95% CI = 1.10, 1.65). The strongest associations were observed with small cell carcinoma (HR: 1.53; 95% CI = 0.93, 2.53) and adenocarcinoma (HR: 1.44; 95% CI = 1.06, 1.97). Stratified analyses suggested increased PM2.5 risks were limited to those who smoked cigarettes. Our findings are consistent with previous epidemiological investigations of long-term exposure to PM2.5 and lung cancer. Importantly, they suggest associations persist at lower concentrations such as those currently found in Canadian cities.

Fine Particulate Matter and Emergency Room Visits for Respiratory Illness. Effect Modification by Oxidative Potential.

RATIONALE: Fine particulate air pollution (PM2.5; particulate matter 2.5 µm or less in diameter) is thought to contribute to acute respiratory morbidity in part through oxidative stress. OBJECTIVES: To examine the association between PM2.5 oxidative burden and emergency room visits for respiratory illnesses. METHODS: We conducted a case-crossover study in Ontario, Canada between 2004 and 2011, including 127,836 cases of asthma, 298,751 cases of chronic obstructive pulmonary disease, and more than 1.1 million cases of all respiratory illnesses. Daily air pollution data were collected from ground monitors, and city-level PM2.5 oxidative potential was measured on the basis of a synthetic respiratory tract lining fluid containing the antioxidants glutathione and ascorbate. Conditional logistic regression was used to estimate associations between air pollution concentrations and emergency room visits, adjusting for time-varying covariates. MEASUREMENTS AND MAIN RESULTS: Three-day mean PM2.5 concentrations were consistently associated with emergency room visits for all respiratory illnesses. Among children (<9 yr), each interquartile change (5.92 µg/m(3)) in 3-day mean PM2.5 was associated with a 7.2% (95% confidence interval, 4.2-10) increased risk of emergency room visits for asthma. Glutathione-related oxidative potential modified the impact of PM2.5 on emergency room visits for respiratory illnesses (P = 0.001) but only at low concentrations (≤10 µg/m(3)). Between-city differences in ascorbate-related oxidative potential did not modify the impact of PM2.5 on respiratory outcomes. CONCLUSIONS: Between-city differences in glutathione-related oxidative potential may modify the impact of PM2.5 on acute respiratory illnesses at low PM2.5 concentrations. This may explain in part how small changes in ambient PM2.5 mass concentrations can contribute to acute respiratory morbidity in low-pollution environments.

Long-term Exposure to Fine Particulate Matter Air Pollution and Mortality Among Canadian Women.

BACKGROUND: Long-term exposure to fine particulate matter (PM2.5) has been associated with increased mortality, especially from cardiovascular disease. There are, however, uncertainties about the nature of the exposure-response relation at lower concentrations. In Canada, where ambient air pollution levels are substantially lower than in most other countries, there have been few attempts to study associations between long-term exposure to PM2.5 and mortality. METHODS: We present a prospective cohort analysis of 89,248 women who enrolled in the Canadian National Breast Screening Study between 1980 and 1985, and for whom residential measures of PM2.5 could be assigned. We derived individual-level estimates of long-term exposure to PM2.5 from satellite observations. We linked cohort records to national mortality data to ascertain mortality between 1980 and 2005. We used Cox proportional hazards models to characterize associations between PM2.5 and several causes of death. The hazard ratios (HRs) and 95% confidence intervals (CIs) computed from these models were adjusted for several individual and neighborhood-level characteristics. RESULTS: The cohort was composed predominantly of Canadian-born (82%) and married (80%) women. The median residential concentration of PM2.5 was 9.1 µg/m(3) (standard deviation = 3.4). In fully adjusted models, a 10 µg/m(3) increase in PM2.5 exposure was associated with elevated risks of nonaccidental (HR: 1.12; 95% CI = 1.04, 1.19), and ischemic heart disease mortality (HR: 1.34; 95% CI = 1.09, 1.66). CONCLUSIONS: The findings from this study provide additional support for the hypothesis that exposure to very low levels of ambient PM2.5 increases the risk of cardiovascular mortality.

PM2.5, oxidant defence and cardiorespiratory health: a review.

Airborne fine particle mass concentrations (PM2.5) are used for ambient air quality management worldwide based in part on known cardiorespiratory health effects. While oxidative stress is generally thought to be an important mechanism in determining these effects, relatively few studies have specifically examined how oxidant defence may impact susceptibility to particulate air pollution. Here we review studies that explore the impact of polymorphisms in anti-oxidant related genes or anti-oxidant supplementation on PM2.5-induced cardiorespiratory outcomes in an effort to summarize existing evidence related to oxidative stress defence and the health effects of PM2.5. Recent studies of PM-oxidative burden were also examined. In total, nine studies were identified and reviewed and existing evidence generally suggests that oxidant defence may modify the impact of PM2.5 exposure on various health outcomes, particularly heart rate variability (a measure of autonomic function) which was the most common outcome examined in the studies reviewed. Few studies examined interactions between PM2.5 and oxidant defence for respiratory outcomes, and in general studies focused primarily on acute health effects. Therefore, further evaluation of the potential modifying role of oxidant defence in PM2.5-induced health effects is required, particularly for chronic outcomes. Similarly, while an exposure metric that captures the ability of PM2.5 to cause oxidative stress may offer advantages over traditional mass concentration measurements, little epidemiological evidence is currently available to evaluate the potential benefits of such an approach. Therefore, further evaluation is required to determine how this metric may be incorporated in ambient air quality management.

Acute changes in lung function associated with proximity to a steel plant: a randomized study.

BACKGROUND: Steel production is a major industry worldwide yet there is relatively little information on the pulmonary effects of air quality near steel manufacturing plants. OBJECTIVES: The aim of this study was to examine how lung function changes acutely when healthy subjects are situated near a steel plant which is adjacent to a residential area. METHODS: Sixty-one subjects were randomly assigned to spend 5 consecutive, 8-hour days in a residential neighborhood approximately 0.9km from a steel plant, or approximately 4.5km away at a college campus. Subjects crossed-over between sites after a nine-day washout period. Lung function was measured daily at both sites along with air pollutants including SO2, NO2, O3, PM2.5, and ultrafine particles. Diffusion capacity and pulse oximetry were also examined. RESULTS: Compared with the college site, the forced expiratory volume in 1-second/forced vital capacity, forced expiratory flow between 25% and 75% of the FVC, total lung capacity, functional residual capacity, and residual volume were lower near the steel plant by 0.67% (95% CI: 0.28, 1.06),1.62% (95% CI: 0.50, 2.75), 1.54% (95% CI: 0.68, 2.39), 3.54% (95% CI: 1.95, 5.13) and 11.3% (95% CI: 4.92, 17.75), respectively. Diffusion capacity, forced expiratory volume in 1s, and pulse oximetry were also lower near the plant but these effects were not statistically significant. Sulfur dioxide, ultrafine particulates, and oxides of nitrogen were greater near the steel plant site compared to the college site. CONCLUSIONS: Spending short periods of time near a steel plant is associated with a decrease in lung function.