Lisa Marie Kauri

Associations between personal exposure to air pollutants and lung function tests and cardiovascular indices among children with asthma living near an industrial complex and petroleum refineries

OBJECTIVE The acute cardiorespiratory effects of air quality among children living in areas with considerable heavy industry have not been well investigated. We conducted a panel study of children with asthma living in proximity to an industrial complex housing two refineries in Montreal, Quebec, in order to assess associations between their personal daily exposure to air pollutants and changes in pulmonary function and selected indicators of cardiovascular health. METHODS Seventy-two children with asthma age 7-12 years in 2009-2010 participated in this panel study for a period of 10 consecutive days. They carried a small backpack for personal monitoring of sulphur dioxide (SO2), benzene, fine particles (PM2.5), nitrogen dioxide (NO2) and polycyclic aromatic hydrocarbons (PAHs) and underwent daily spirometry and cardiovascular testing (blood pressure, pulse rate and oxygen saturation). To estimate these associations, we used mixed regression models, adjusting for within-subject serial correlation, and for the effects of a number of personal and environmental variables (e.g., medication use, ethnicity, temperature). RESULTS Children with asthma involved in the study had relatively good pulmonary function test results (mean FEV1 compared to standard values: 89.8%, mean FVC: 97.6%, mean FEF25-75: 76.3%). Median diastolic, systolic blood pressures and oxygen saturation were 60/94 mmHg and 99%, respectively. Median personal concentrations of pollutants were NO2, 5.5 ppb; benzene, 2.1 µg/m(3); PM2.5, 5.7 µg/m(3); and total PAH, 130 µg/m(3). Most personal concentrations of SO2 were below the level of detection. No consistent associations were observed between cardio-pulmonary indices and personal exposure to PM2.5, NO2 and benzene, although there was a suggestion for a small decrease in respiratory function with total concentrations of PAHs (e.g., adjusted association with FVC: -9.9 ml per interquartile range 95%CI: -23.4, 3.7). CONCLUSIONS This study suggests that at low daily average levels of exposure to industrial emissions, effects on pulmonary and cardiovascular functions in children with asthma may be difficult to detect over 10 consecutive days.

Global transcriptional characterization of a mouse pulmonary epithelial cell line for use in genetic toxicology

Prior to its application for in vitro toxicological assays, thorough characterization of a cell line is essential. The present study uses global transcriptional profiling to characterize a lung epithelial cell line (FE1) derived from MutaMouse [White, P.A., Douglas, G.R., Gingerich, J., Parfett, C., Shwed, P., Seligy, V., Soper, L., Berndt, L., Bayley, J., Wagner, S., Pound, K., Blakey, D., 2003. Development and characterization of a stable epithelial cell line from Muta Mouse lung. Environmental and Molecular Mutagenesis 42, 166-184]. Results presented here demonstrate the origin of the FE1 lung cell line as epithelial, presenting both type I and type II alveolar phenotype. An assessment of toxicologically-relevant genes, including those involved in the response to stress and stimuli, DNA repair, cellular metabolism, and programmed cell death, revealed changes in expression of 22-27% of genes in one or more culture type (proliferating and static FE1 cultures, primary epithelial cultures) compared with whole lung isolates. Gene expression analysis at 4 and 24h following benzo(a)pyrene exposure revealed the induction of cyp1a1, cyp1a2, and cyp1b1 in FE1 cells and lung isolates. The use of DNA microarrays for gene expression profiling allows an improved understanding of global, coordinated cellular events arising in cells under different physiological conditions. Taken together, these data indicate that the FE1 cell line is derived from a cell type relevant to toxic responses in vivo, and shows some similarity in response to chemical insult as the original tissue.

Residential exposure to volatile organic compounds and lung function: Results from a population-based cross-sectional survey

Exposure to residential volatile organic compounds (VOCs) is ubiquitous in homes, and may influence respiratory health with important public health implications. To investigate the association between VOCs measured in residential indoor air and lung function in the Canadian population Cycle 2 of the Canadian Health Measures Survey - a population based cross-sectional survey designed to be representative of the Canadian population - was carried out between 2009 and 2011. Of the 84 VOCs measured, 47 were detectable in at least 50% of homes and ten were negatively associated with lung function: decanal, 2-furancarboxaldehyde, hexanal, nonanal, octanal, benzene, styrene, α-pinene, 2-methyl-1,2-butadiene and naphthalene. Differences were observed between males and females, as well as by age, and significant associations were most frequent in those under 17 years. These results provide evidence that some VOCs measured indoors are negatively associated with lung function in the Canadian population.

Exposure to air pollution near a steel plant and effects on cardiovascular physiology: A randomized crossover study

BACKGROUND Iron and steel industry is an important source of air pollution emissions. Few studies have investigated cardiovascular effects of air pollutants emitted from steel plants. OBJECTIVE We examined the influence of outdoor air pollution in the vicinity of a steel plant on cardiovascular physiology in Sault Ste. Marie, Canada. METHODS Sixty-one healthy, non-smoking subjects (females/males=33/28, median age 22 years) spent 5 consecutive 8-hour days outdoors in a residential area neighbouring a steel plant, or on a college campus approximately 5 kilometres away from the plant, and then crossed over to the other site with a 9-day washout. Mid day, subjects underwent daily 30-minute moderate intensity exercise. Blood pressure (BP) and pulse rate were determined daily and post exercise at both sites. Flow-mediated vasodilation (FMD) was determined at the site near the plant. Air pollution was monitored at both sites. Mixed-effects regressions were run for statistical associations, adjusting for weather variables. RESULTS Concentrations of ultrafine particles, sulphur dioxide (SO2), nitrogen dioxide (NO2) and carbon monoxide (CO) were 50-100% higher at the site near the plant than at the college site, with minor differences in temperature, humidity, and concentrations of particulate matter ≤2.5 μm in size (PM2.5) and ozone (O3). Resting pulse rate [mean (95% confidence interval)] was moderately higher near the steel plant [+1.53 bpm (0.31, 2.78)] than at the college site, male subjects having the highest pulse rate elevation [+2.77 bpm (0.78, 4.76)]. Resting systolic and diastolic BP and pulse pressure, and post-exercise BP and pulse rate were not significantly different between two sites. Interquartile range concentrations of SO2 (2.9 ppb), NO2 (5.0 ppb) and CO (0.2 ppm) were associated with increased pulse rate [0.19 bpm (-0.00, 0.38), 0.86 bpm (0.03, 1.68), and 0.11 bpm (0.00, 0.22), respectively], ultrafine particles (10,256 count/cm(3)) associated with increased pulse pressure [0.85 mmHg (0.23, 1.48)], and NO2 and CO inversely associated with FMD [-0.14% (-0.31, 0.02), -0.02% (-0.03, -0.00), respectively]. SO2 during exercise was associated with increased pulse rate [0.26 bpm (0.01, 0.51)]. CONCLUSION Air quality in residential areas near steel plants may influence cardiovascular physiology.

The association between ambient air quality and cardiac rate and rhythm in ambulatory subjects

BACKGROUND Acute increases in ambient air pollution have been associated with increased hospitalization for cardiac diseases and stroke. Triggering of cardiac arrhythmia by changes in air quality could theoretically predispose individuals to cardiac arrest or heart failure, or stroke through precipitation of atrial fibrillation. We investigated the association between air quality and cardiac rate and rhythm characteristics measured by ambulatory cardiac monitoring. METHODS AND RESULTS Daily ambient 3-h maximum concentrations of ozone, nitrogen dioxide and fine particulate matter, and an index summarizing these pollutants called the Air Quality Health Index (AQHI) were compared to the results of 24-h ambulatory cardiac monitoring performed for clinical purposes in 8662 patients and analyzed at the University of Ottawa Heart Institute, Canada, between 2004 and 2009. An interquartile increase in the daily 3 h- maximum AQHI was associated with a 0.9% (95% CI 0.3%, 1.5%) increase in the daily maximum heart rate and a 1.17% (95% CI 1.07%, 1.29%) increase in heart block frequency. An interquartile increase in NO2 was associated with an increase in the percentage of time in atrial fibrillation of 4.39% (-0.15, 9.15) among those ≤50 years old, and 7.1% (0.24, 14.5) among males. CONCLUSIONS We found evidence that air pollution may affect cardiac rate and rhythm. This may be one mechanism partially explaining the increase in strokes and cardiac events observed on days of higher air pollution.

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.

The associations between phthalate exposure and insulin resistance, β-cell function and blood glucose control in a population-based sample

In developed countries, phthalate exposure is ubiquitous. Previous studies have shown an association between phthalate levels and health effects. To test associations between phthalate exposures, estimated from urinary phthalate metabolites, and insulin resistance, β-cell function and glucose control. Data were obtained from a cross-sectional, nationally representative study; the Canadian Health Measures Survey (CHMS, 2009-2011). Participants under the age of 12, those with diabetes, who were pregnant or who had not fasted overnight were excluded. Fasting blood glucose, insulin, and glycosylated hemoglobin (HbA1C) levels were measured in a subset of participants, and urine was collected for creatinine and phthalate metabolites. We tested associations between these variables using linear regression analysis. Of 4437 participants (12-79years old), 2119 had fasting glucose measurements and at least one phthalate metabolite above detection limits. MBzP, MCPP, MEHP, MEHHP, MiBP, and the sum of DEHP metabolites were positively associated with increased HbA1C (p<0.05). DEHP metabolites were positively associated with increased fasting glucose, insulin, HOMA-IR and HOMA-β. An interquartile increase in the sum of log transformed DEHP metabolites was associated with increases in HOMA-IR and HOMA-β of 0.15 (95% CI 0.04, 0.26) and 10.24 (95% CI 3.71, 16.77) respectively. Increased concentrations of all measured phthalate metabolites were associated with reduced blood glucose control. DEHP metabolites were also associated with increased glucose concentrations, and indicators of β-cell function and insulin resistance. Our results suggest that exposure to phthalates may possibly impair control of blood glucose and thereby predispose to pre-diabetes.

Cardiovascular and inflammatory mechanisms in healthy humans exposed to air pollution in the vicinity of a steel mill

BackgroundThere is a paucity of mechanistic information that is central to the understanding of the adverse health effects of source emission exposures. To identify source emission-related effects, blood and saliva samples from healthy volunteers who spent five days near a steel plant (Bayview site, with and without a mask that filtered many criteria pollutants) and at a well-removed College site were tested for oxidative stress, inflammation and endothelial dysfunction markers.MethodsBiomarker analyses were done using multiplexed protein-array, HPLC-Fluorescence, EIA and ELISA methods. Mixed effects models were used to test for associations between exposure, biological markers and physiological outcomes. Heat map with hierarchical clustering and Ingenuity Pathway Analysis (IPA) were used for mechanistic analyses.ResultsMean CO, SO2 and ultrafine particles (UFP) levels on the day of biological sampling were higher at the Bayview site compared to College site. Bayview site exposures “without” mask were associated with increased (p < 0.05) pro-inflammatory cytokines (e.g IL-4, IL-6) and endothelins (ETs) compared to College site. Plasma IL-1β, IL-2 were increased (p < 0.05) after Bayview site “without” compared to “with” mask exposures. Interquartile range (IQR) increases in CO, UFP and SO2 were associated with increased (p < 0.05) plasma pro-inflammatory cytokines (e.g. IL-6, IL-8) and ET-1(1–21) levels. Plasma/saliva BET-1 levels were positively associated (p < 0.05) with increased systolic BP. C-reactive protein (CRP) was positively associated (p < 0.05) with increased heart rate. Protein network analyses exhibited activation of distinct inflammatory mechanisms after “with” and “without” mask exposures at the Bayview site relative to College site exposures.ConclusionsThese findings suggest that air pollutants in the proximity of steel mill site can influence inflammatory and vascular mechanisms. Use of mask and multiple biomarker data can be valuable in gaining insight into source emission-related health impacts.

The Oakville Oil Refinery Closure and Its Influence on Local Hospitalizations: A Natural Experiment on Sulfur Dioxide

Background: An oil refinery in Oakville, Canada, closed over 2004–2005, providing an opportunity for a natural experiment to examine the effects on oil refinery-related air pollution and residents’ health. Methods: Environmental and health data were collected for the 16 years around the refinery closure. Toronto (2.5 million persons) and the Greater Toronto Area (GTA, 6.3 million persons) were used as control and reference populations, respectively, for Oakville (160,000 persons). We compared sulfur dioxide and age- and season-standardized hospitalizations, considering potential factors such as changes in demographics, socio-economics, drug prescriptions, and environmental variables. Results: The closure of the refinery eliminated 6000 tons/year of SO2 emissions, with an observed reduction of 20% in wind direction-adjusted ambient concentrations in Oakville. After accounting for trends, a decrease in cold-season peak-centered respiratory hospitalizations was observed for Oakville (reduction of 2.2 cases/1000 persons per year, p=0.0006) but not in Toronto (p = 0.856) and the GTA (p = 0.334). The reduction of respiratory hospitalizations in Oakville post closure appeared to have no observed link to known confounders or effect modifiers. Conclusion: The refinery closure allowed an assessment of the change in community health. This natural experiment provides evidence that a reduction in emissions was associated with improvements in population health. This study design addresses the impact of a removed source of air pollution.