Person:

Coull, Brent

Results from air pollution exposure assessment studies suggest that ambient fine particles [particulate matter with aerodynamic diameter ≤ 2.5 μg (PM2.5)], but not ambient gases, are strong proxies of corresponding personal exposures. For particles, the strength of the personal–ambient association can differ by particle component and level of home ventilation. For gases, however, such as ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2), the impact of home ventilation on personal–ambient associations is untested. We measured 24-hr personal exposures and corresponding ambient concentrations to PM2.5, sulfate (SO42−), elemental carbon, O3, NO2, and SO2 for 10 nonsmoking older adults in Steubenville, Ohio. We found strong associations between ambient particle concentrations and corresponding personal exposures. In contrast, although significant, most associations between ambient gases and their corresponding exposures had low slopes and R2 values; the personal–ambient NO2 association in the fall season was moderate. For both particles and gases, personal–ambient associations were highest for individuals spending most of their time in high- compared with low-ventilated environments. Cross-pollutant models indicated that ambient particle concentrations were much better surrogates for exposure to particles than to gases. With the exception of ambient NO2 in the fall, which showed moderate associations with personal exposures, ambient gases were poor proxies for both gas and particle exposures. In combination, our results suggest that a) ventilation may be an important modifier of the magnitude of effect in time-series health studies, and b) results from time-series health studies based on 24-hr ambient concentrations are more readily interpretable for particles than for gases.

Introduction: Ambient particulate pollution and traffic have been linked to myocardial infarction and cardiac death risk. Possible mechanisms include autonomic cardiac dysfunction. Methods: In a repeated-measures study of 46 patients 43–75 years of age, we investigated associations of central-site ambient particulate pollution, including black carbon (BC) (a marker for regional and local traffic), and report of traffic exposure with changes in half-hourly averaged heart rate variability (HRV), a marker of autonomic function measured by 24-hr Holter electrocardiogram monitoring. Each patient was observed up to four times within 1 year after a percutaneous intervention for myocardial infarction, acute coronary syndrome without infarction, or stable coronary artery disease (4,955 half-hour observations). For each half-hour period, diary data defined whether the patient was home or not home, or in traffic. Results: A decrease in high frequency (HF; an HRV marker of vagal tone) of −16.4% [95% confidence interval (CI), −20.7 to −11.8%] was associated with an interquartile range of 0.3-μg/m3 increase in prior 5-day averaged ambient BC. Decreases in HF were independently associated both with the previous 2-hr averaged BC (−10.4%; 95% CI, −15.4 to −5.2%) and with being in traffic in the previous 2 hr (−38.5%; 95% CI, −57.4 to −11.1%). We also observed independent responses for particulate air matter with aerodynamic diameter ≤ 2.5 μm and for gases (ozone or nitrogen dioxide). Conclusion: After hospitalization for coronary artery disease, both particulate pollution and being in traffic, a marker of stress and pollution, were associated with decreased HRV.

Introduction: Systemic inflammation may be one of the mechanisms mediating the association between ambient air pollution and cardiovascular morbidity and mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic inflammation that are independent risk factors for cardiovascular disease. Objective: We investigated the association between ambient air pollution and systemic inflammation using baseline measurements of IL-6 and fibrinogen from controlled human exposure studies. Methods: In this retrospective analysis we used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5). Linear mixed-model regression determined the effects of the pollutants on systemic IL-6 and fibrinogen. Effect modification by season was considered. Results: We observed a positive association between IL-6 and O3 [0.31 SD per O3 interquartile range (IQR); 95% confidence interval (CI), 0.08–0.54] and between IL-6 and SO2 (0.25 SD per SO2 IQR; 95% CI, 0.06–0.43). We observed the strongest effects using 4-day moving averages. Responses to pollutants varied by season and tended to be higher in the summer, particularly for O3 and PM2.5. Fibrinogen was not associated with pollution. Conclusions: This study demonstrates a significant association between ambient pollutant levels and baseline levels of systemic IL-6. These findings have potential implications for controlled human exposure studies. Future research should consider whether ambient pollution exposure before chamber exposure modifies IL-6 response.

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61–88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During post-exercise rest, an elevated BC level was associated with −0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression ≥0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic.

Background: Altered heart rate variability (HRV), a marker of poor cardiac autonomic function, has been associated with sudden cardiac death and heart failure. Objective: We examined the association of low-level lead exposure measured in bone by K-X-ray fluorescence with alterations in HRV, and whether metabolic syndrome (MetS) or its individual components modify those associations. Methods: HRV measures [power in high-frequency (HF({norm})) and low-frequency (LF({norm})) in normalized units, and LF/HF] were taken among 413 elderly men from the Normative Aging Study. MetS was defined as subjects having three or more of the following criteria: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein, high blood pressure, and high fasting glucose. Results: Of the subjects, 32% were identified as having MetS. Inverse but nonstatistically significant associations of both tibia and patella lead levels with HF({norm}) and nonstatistically significant positive relations with LF({norm}) and LF/HF were found in the entire cohort. There was a graded, statistically significant reduction in HF({norm}) and increases in LF({norm}) and LF/HF in association with an increase in patella lead as the number of metabolic abnormalities increased. We also observed that higher patella lead was consistently associated with lower HFnorm and higher LF(_{norm}) and LF/HF among subjects with MetS or its individual components. No statistically significant interaction between MetS and tibia lead was observed. Conclusion: The results suggest that elderly men with MetS were more susceptible to autonomic dysfunction in association with chronic lead exposure as measured in patella. The modification by MetS is consistent with a role for oxidative stress in lead toxicity on the cardiovascular system.

Airborne particulate matter (PM) may lead to increased cardiac risk through an inflammatory pathway. Therefore, we investigated associations between ambient PM and markers of systemic inflammation among repeated measures from 44 senior citizens (≥ 60 years of age) and examined susceptibility by conditions linked to chronic inflammation. Mixed models were used to identify associations between concentrations of fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] averaged over 1–7 days and measures of C-reactive protein (CRP), interleukin-6 (IL-6), and white blood cells (WBCs). Effect modification was investigated for diabetes, obesity, hypertension, and elevated mean inflammatory markers. We found positive associations between longer moving averages of PM2.5 and WBCs across all participants, with a 5.5% [95% confidence interval (CI), 0.10 to 11%] increase per interquartile increase (5.4 μg/m3) of PM2.5 averaged over the previous week. PM2.5 and CRP also exhibited positive associations among all individuals for averages longer than 1 day, with the largest associations for persons with diabetes, obesity, and hypertension. For example, an interquartile increase in the 5-day mean PM2.5 (6.1 μg/m3) was associated with a 14% increase in CRP (95% CI, −5.4 to 37%) for all individuals and an 81% (95% CI, 21 to 172%) increase for persons with diabetes, obesity, and hypertension. Persons with diabetes, obesity, and hypertension also exhibited positive associations between PM2.5 and IL-6. Individuals with elevated mean inflammatory markers exhibited enhanced associations with CRP, IL-6, and WBCs. We found modest positive associations between PM2.5 and indicators of systemic inflammation, with larger associations suggested for individuals with diabetes, obesity, hypertension, and elevated mean inflammatory markers.

Objectives: Airborne particles have been linked to pulmonary oxidative stress and inflammation. Because these effects may be particularly great for traffic-related particles, we examined associations between particle exposures and exhaled nitric oxide (FENO) in a study of 44 senior citizens, which involved repeated trips aboard a diesel bus. Methods: Samples of FENO collected before and after the trips were regressed against microenvironmental and ambient particle concentrations using mixed models controlling for subject, day, trip, vitamins, collection device, mold, pollen, room air nitric oxide, apparent temperature, and time to analysis. Although ambient concentrations were collected at a fixed location, continuous group-level personal samples characterized microenvironmental exposures throughout facility and trip periods. Results: In pre-trip samples, both microenvironmental and ambient exposures to fine particles were positively associated with FENO. For example, an interquartile increase of 4 μg/m3 in the daily microenvironmental PM2.5 concentration was associated with a 13% [95% confidence interval (CI), 2–24%) increase in FENO. After the trips, however, FENO concentrations were associated pre-dominantly with microenvironmental exposures, with significant associations for concentrations measured throughout the whole day. Associations with exposures during the trip also were strong and statistically significant with a 24% (95% CI, 15–34%) increase in FENO predicted per interquartile increase of 9 μg/m3 in PM2.5. Although pre-trip findings were generally robust, our post-trip findings were sensitive to several influential days. Conclusions: Fine particle exposures resulted in increased levels of FENO in elderly adults, suggestive of increased airway inflammation. These associations were best assessed by microenvironmental exposure measurements during periods of high personal particle exposures.

Background: Long-term exposure to particulate air pollution has been associated with an increased risk of dying from cardiopulmonary and ischemic heart disease, yet few studies have evaluated cardiovascular end points other than mortality. We investigated the relationship between long-term exposure to traffic and occurrence of acute myocardial infarction (AMI) in a case–control study. Methods: A total of 5,049 confirmed cases of AMI were identified between 1995 and 2003 as part of the Worcester Heart Attack Study, a community-wide study examining changes over time in the incidence of AMI among greater Worcester, Massachusetts, residents. Population controls were selected from Massachusetts resident lists. We used cumulative traffic within 100 m of subjects’ residence and distance from major roadway as proxies for exposure to traffic-related air pollution. We estimated the relationship between exposure to traffic and occurrence of AMI using logistic regression, and we adjusted for the following potential confounders: age, sex, section of the study area, point sources emissions of particulate matter with aerodynamic diameter < 2.5 μm, area socioeconomic characteristics, and percentage of open space. Results: An increase in cumulative traffic near the home was associated with a 4% increase in the odds of AMI per interquartile range [95% confidence interval (CI), 2–7%], whereas living near a major roadway was associated with a 5% increase in the odds of AMI per kilometer (95% CI, 3–6%). Conclusions: These results provide support for an association between long-term exposure to traffic and the risk of AMI.

Background: Many studies have shown that airborne particles are associated with increased risk of death, but attention has more recently focused on the differential toxicity of particles from different sources. Geographic information system (GIS) approaches have recently been used to improve exposure assessment, particularly for traffic particles, but only for long-term exposure. Objectives: We analyzed approximately 100,000 deaths from all, cardiovascular, and respiratory causes for the years 1995–2002 using a case–crossover analysis. Methods: Estimates of exposure to traffic particles were geocoded to the address of each decedent on the day before death and control days, with these estimates derived from a GIS-based exposure model incorporating deterministic covariates, such as traffic density and meteorologic factors, and a smooth function of latitude and longitude. Results: We estimate that an IQR increase in traffic particle exposure on the day before death is associated with a 2.3% increase [95% confidence interval (CI), 1.2 to 3.4%] in all-cause mortality risk. Stroke deaths were particularly elevated (4.4%; 95% CI, −0.2 to 9.3%), as were diabetes deaths (5.7%; 95% CI, −1.7 to 13.7%). Sulfate particles are spatially homogeneous, and using a central monitor, we found that an IQR increase in sulfate levels on the day before death is associated with a 1.1% (95% CI, 0.1 to 2.0%) increase in all-cause mortality risk. Conclusions: Both traffic and powerplant particles are associated with increased deaths in Boston, with larger effects for traffic particles.

BACKGROUND: Understanding the shape of the concentration–response curve for particles is important for public health, and lack of such understanding was recently cited by U.S. Environmental Protection Agency (EPA) as a reason for not tightening the standards. Similarly, the delay between changes in exposure and changes in health is also important in public health decision making. We addressed these issues using an extended follow-up of the Harvard Six Cities Study. METHODS: Cox proportional hazards models were fit controlling for smoking, body mass index, and other covariates. Two approaches were used. First, we used penalized splines, which fit a flexible functional form to the concentration response to examine its shape, and chose the degrees of freedom for the curve based on Akaike’s information criterion. Because the uncertainties around the resultant curve do not reflect the uncertainty in model choice, we also used model averaging as an alternative approach, where multiple models are fit explicitly and averaged, weighted by their probability of being correct given the data. We examined the lag relationship by model averaging across a range of unconstrained distributed lag models. RESULTS: We found that the concentration–response curve is linear, clearly continuing below the current U.S. standard of 15 μg/m3, and that the effects of changes in exposure on mortality are seen within two years. CONCLUSIONS: Reduction in particle concentrations below U.S. EPA standards would increase life expectancy.