Jennifer M. Cavallari

PM2.5 metal exposures and nocturnal heart rate variability: a panel study of boilermaker construction workers.

BackgroundTo better understand the mechanism(s) of particulate matter (PM) associated cardiovascular effects, research priorities include identifying the responsible PM characteristics. Evidence suggests that metals play a role in the cardiotoxicity of fine PM (PM2.5) and in exposure-related decreases in heart rate variability (HRV). We examined the association between daytime exposure to the metal content of PM2.5 and night HRV in a panel study of boilermaker construction workers exposed to metal-rich welding fumes.MethodsTwenty-six male workers were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of the mean squared differences of successive intervals) was summarized over the night (0:00–7:00). Workday, gravimetric PM2.5 samples were analyzed by x-ray fluorescence to determine metal content. We used linear mixed effects models to assess the associations between night rMSSD and PM2.5 metal exposures both with and without adjustment for total PM2.5. Matched ECG measurements from the non-workday were used to control for individual cardiac risk factors and models were also adjusted for smoking status. To address collinearity between PM2.5 and metal content, we used a two-step approach that treated the residuals from linear regression models of each metal on PM2.5 as surrogates for the differential effects of metal exposures in models for night rMSSD.ResultsThe median PM2.5 exposure was 650 μg/m3; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 μg/m3 to non-detectable. We found inverse linear associations in exposure-response models with increased metal exposures associated with decreased night rMSSD. A statistically significant association for manganese was observed, with a decline of 0.130 msec (95% CI: -0.162, -0.098) in night rMSSD for every 1 μg/m3 increase in manganese. However, even after adjusting for individual metals, increases in total PM2.5 exposures were associated with declines in night rMSSD.ConclusionThese results support the cardiotoxicity of PM2.5 metal exposures, specifically manganese. However the metal component alone did not account for the observed declines in night HRV. Therefore, results suggest the importance of other PM elemental components.

Obesity is a modifier of autonomic cardiac responses to fine metal particulates.

Background Increasing evidence suggests that obesity may impart greater susceptibility to adverse effects of air pollution. Particulate matter, especially PM2.5 (particulate matter with aero-dynamic diameter ≤2.5 μm), is associated with increased cardiac events and reduction of heart rate variability (HRV). Objectives Our goal was to investigate whether particle-mediated autonomic modulation is aggravated in obese individuals. Methods We examined PM2.5-mediated acute effects on HRV and heart rate (HR) using 10 24-hr and 13 48-hr ambulatory electrocardiogram recordings collected from 18 boilermakers (39.5 ± 9.1 years of age) exposed to high levels of metal particulates. Average HR and 5-min HRV [SDNN: standard deviation of normal-to-normal intervals (NN); rMSSD: square-root of mean squared-differences of successive NN intervals; HF: high-frequency power 0.15–0.4 Hz] and personal PM2.5 exposures were continuously monitored. Subjects with body mass index ≥ 30 kg/m2 were classified as obese. Mixed-effect models were used for statistical analyses. Results Half (50%) of the study subjects were obese. After adjustment for confounders, each 1-mg/m3 increase in 4-hr moving average PM2.5 was associated with HR increase of 5.9 bpm [95% confidence interval (CI), 4.2 to 7.7] and with 5-min HRV reduction by 6.5% (95% CI, 1.9 to 11.3%) for SDNN, 1.7% (95% CI, –4.9 to 8.4%) for rMSSD, and 8.8% (95% CI, –3.8 to 21.3%) for HF. Obese individuals had greater PM2.5-mediated HRV reductions (2- to 3-fold differences) than nonobese individuals, and had more PM2.5-mediated HR increases (9-bpm vs. 4-bpm increase in HR for each 1-mg/m3 increase in PM2.5; p < 0.001). Conclusions Our study revealed greater autonomic cardiac responses to metal particulates in obese workers, supporting the hypothesis that obesity may impart greater susceptibility to acute cardiovascular effects of fine particles.

Toenail, Blood, and Urine as Biomarkers of Manganese Exposure

Objective: This study examined the correlation between manganese exposure and manganese concentrations in different biomarkers. Methods: Air measurement data and work histories were used to determine manganese exposure over a work shift and cumulative exposure. Toenail samples (n = 49), as well as blood and urine before (n = 27) and after (urine, n = 26; blood, n = 24) a work shift were collected. Results: Toenail manganese, adjusted for age and dietary manganese, was significantly correlated with cumulative exposure in 7 to 9, 10 to 12, and 7 to 12 months before toenail clipping date, but not 1 to 6 months. Manganese exposure over a work shift was not correlated with changes in blood nor urine manganese. Conclusions: Toenails appeared to be a valid measure of cumulative manganese exposure 7 to 12 months earlier. Neither change in blood nor urine manganese appeared to be suitable indicators of exposure over a typical work shift.

Traffic-related air pollution exposures and changes in heart rate variability in Mexico City: A panel study

BackgroundWhile air pollution exposures have been linked to cardiovascular outcomes, the contribution from acute gas and particle traffic-related pollutants remains unclear. Using a panel study design with repeated measures, we examined associations between personal exposures to traffic-related air pollutants in Mexico City and changes in heart rate variability (HRV) in a population of researchers aged 22 to 56 years.MethodsParticipants were monitored for approximately 9.5 hours for eight days while operating a mobile laboratory van designed to characterize traffic pollutants while driving in traffic and “chasing” diesel buses. We examined the association between HRV parameters (standard deviation of normal-to-normal intervals (SDNN), power in high frequency (HF) and low frequency (LF), and the LF/HF ratio) and the 5-minute maximum (or average in the case of PM2.5) and 30-, 60-, and 90-minute moving averages of air pollutants (PM2.5, O3, CO, CO2, NO2, NOx, and formaldehyde) using single- and two-pollutant linear mixed-effects models.ResultsShort-term exposure to traffic-related emissions was associated with statistically significant acute changes in HRV. Gaseous pollutants – particularly ozone – were associated with reductions in time and frequency domain components (α = 0.05), while significant positive associations were observed between PM2.5 and SDNN, HF, and LF. For ozone and formaldehyde, negative associations typically increased in magnitude and significance with increasing averaging periods. The associations for CO, CO2, NO2, and NOx were similar with statistically significant associations observed for SDNN, but not HF or LF. In contrast, PM2.5 increased these HRV parameters.ConclusionsResults revealed an association between traffic-related PM exposures and acute changes in HRV in a middle-aged population when PM exposures were relatively low (14 μ g/m3) and demonstrate heterogeneity in the effects of different pollutants, with declines in HRV – especially HF – with ozone and formaldehyde exposures, and increases in HRV with PM2.5 exposure. Given that exposure to traffic-related emissions is associated with increased risk of cardiovascular morbidity and mortality, understanding the mechanisms by which traffic-related emissions can cause cardiovascular disease has significant public health relevance.

Vascular Function, Inflammation, and Variations in Cardiac Autonomic Responses to Particulate Matter Among Welders

Patients with health conditions associated with impaired vascular function and inflammation may be more susceptible to the adverse health effects of fine particulate (particulate matter with a mass median aerodynamic diameter of </=2.5 mum (PM(2.5))) exposure. In 2006, the authors conducted a panel study to investigate directly whether vascular function and inflammation (assessed by C-reactive protein) modify PM(2.5)-associated reductions in heart rate variability among 23 young male workers (mean age, 40 years) from Massachusetts. Concurrent 24-hour ambulatory electrocardiogram and personal PM(2.5) exposure information was collected over a total of 36 person-days, including either or both welding and nonwelding days. Linear mixed models were used to examine the 5-minute standard deviation of normal-to-normal intervals (SDNN) in relation to the moving PM(2.5) averages in the preceding 1-4 hours. C-reactive protein levels and 3 measures of vascular function (augmentation index, mean arterial pressure, and pulse pressure) were determined at baseline. The authors observed an inverse association between the 1-hour PM(2.5) and 5-minute SDNN. Greater SDNN declines were observed among those with C-reactive protein (P(interaction) < 0.001) and augmentation index (P = 0.06) values at or above the 75th percentile and pulse pressure values below the 75th percentile (P < 0.001). Systemic inflammation and poorer vascular function appear to aggravate particle-related declines in heart rate variability among workers.

Acute changes in vascular function among welders exposed to metal-rich particulate matter.

Background: Although welding fume exposure is associated with adverse cardiovascular outcomes, the mechanisms remain unclear. To investigate the role of vascular function, we assessed levels of the augmentation index (a correlate of arterial stiffness) after short-term exposure to welding-derived fine particulate matter (PM2.5). Methods: In a panel study, we monitored 26 male welders over 24 hours on a welding day (n = 25), a nonwelding day (n = 15), or both (n = 14). Augmentation index (expressed as a percent) was obtained in the morning before exposure (baseline) and after exposure in the afternoon and the following morning. Personal PM2.5 exposure was measured over 6 hours of welding or an equivalent nonwelding period. We used linear mixed models adjusting for baseline augmentation index, smoking, age, and time to evaluate the effects of welding (binary) and PM2.5 (continuous) on augmentation index levels. We also assessed modification by welding exposure the day before monitoring (binary). Results: Welding was associated with a 2.8% increase in afternoon augmentation index (95% confidence interval = −1.4 to 7.0) and a 2.4% decrease (−6.9 to 2.2) in next-morning augmentation index. Additional exposure the day prior to monitoring was associated with a greater afternoon increase (5.1%; 0.8 to 9.5). Using PM2.5 concentration, a positive association was observed in the afternoon and an inverse association the next morning; results differed by previous days welding status after excluding outliers. Conclusions: Subsequent to welding fume exposure, there is an increase in afternoon augmentation index and a decrease in next-morning augmentation index, with greater changes after consecutive days of exposure. These results suggest that exposure to the PM2.5 component of welding fume elicits acute adverse vascular responses.

Dermal Exposure and Urinary 1-Hydroxypyrene among Asphalt Roofing Workers

The primary objective of this study was to identify significant determinants of dermal exposure to polycyclic aromatic compounds (PACs) among asphalt roofing workers and use urinary 1-hydroxyprene (1-OHP) measurements to evaluate the effect of dermal exposure on total absorbed dose. The study population included 26 asphalt roofing workers who performed three primary tasks: tearing off old roofs (tear-off), putting down new roofs (put-down), and operating the kettle at ground level (kettle). During multiple consecutive work shifts (90 workerdays), dermal patch samples were collected from the underside of each workers wrists and were analyzed for PACs, pyrene, and benzo(a)pyrene (BAP). During the same work week, urine samples were collected at pre-shift, post-shift, and bedtime each day and were analyzed for 1-OHP (205 urine samples). Linear mixed effects models were used to evaluate the dermal measurements for the purpose of identifying important determinants of exposure, and to evaluate urinary 1-OHP measurements for the purpose of identifying important determinants of total absorbed dose. Dermal exposures to PAC, pyrene, and BAP were found to vary significantly by roofing task (tear-off > put-down > kettle) and by the presence of an old coal tar pitch roof (pitch > no pitch). For each of the three analytes, the adjusted mean dermal exposures associated with tear-off (812 ng PAC/cm 2 , 14.9 ng pyrene/cm 2 , 4.5 ng BAP/cm 2 ) were approximately four times higher than exposures associated with operating the kettle (181 ng PAC/cm 2 , 4.1 ng pyrene/cm 2 , 1.1 ng BAP/cm 2 ). Exposure to coal tar pitch was associated with a 6-fold increase in PAC exposure (p = 0.0005), an 8-fold increase in pyrene exposure (p < 0.0001), and a 35-fold increase in BAP exposure (p < 0.0001). Similarly, urinary 1-OHP levels were found to be significantly higher on days when an old pitch roof was removed, accounting for a 3.7-fold difference at pre-shift (p = 0.01), a 5.0-fold difference at post-shift (p = 0.004), and a 7.2-fold difference at bedtime (p = 0.002). The pyrene measurements obtained during the work shift were found to be strongly correlated with urinary 1-OHP measurements obtained at the end of that shift (r = 0.8, p < 0.001) as well as at bedtime (r = 0.7, p < 0.001). Ultimately, the results of a distributed lag model indicated that dermal exposure during the preceding 40 hours had a statistically significant effect on urinary 1-OHP. The presence of coal tar pitch was the primary determinant of dermal exposure, particularly for exposure to BAP. However, the task-based differences that were observed while controlling for pitch suggest that exposure to asphalt also contributes to dermal exposures. We found that dermal exposure was a significant determinant of total absorbed dose, suggesting that control strategies aimed at reducing occupational exposure to PACs should include an effort to minimize dermal exposure.

Time Course of Heart Rate Variability Decline Following Particulate Matter Exposures in an Occupational Cohort

Although research suggests that particles influence cardiac autonomic response as evidenced by decreases in heart rate variability (HRV), the time course of the response remains unclear. Using a crossover panel study, we monitored 36 male boilermaker welders, occupationally exposed to metal-rich particulate matter (PM) to investigate the temporal trend of hourly HRV subsequent to PM exposure. Ambulatory electrocardiograms were collected over work (exposure) and non-work (control) periods and the mean of the standard deviations of all normal-to-normal intervals for all 5-min segments (SDNNi) was calculated hourly for up to 14-hrs post-work. The exposure-response relationship was examined with linear mixed effects regression models to account for participants monitored over multiple occasions. Models were adjusted for non-work HRV to control for diurnal fluctuations and individual predictors of HRV. The mean (SD) work PM2. 5 concentration was 1.12 (0.76) mg/m3. Hourly SDNNi was consistently lower post-work as compared to the same time period on a non-work day. HRV was inversely associated with work PM2. 5 exposures in each of the 14-hrs post-work. The hourly associations suggested an early and later phase response, with the largest regression coefficients observed 2–3 hrs (β = −6.86 (95% CI: −11.91, −1.81) msec/1 mg/m3 at 3-hrs), and then 9–13 hrs (β = −8.60 (95% CI: −17.45, 0.24) msec/1 mg/m3 at 11-hrs), after adjusting for non-work HRV, smoking status, and age. This investigation demonstrates declines in HRV for up to 14 hours following PM exposure and a multiphase cardiovascular autonomic response with immediate (2 hrs) and delayed (9–13 hrs) responses.

Traffic-related exposures and biomarkers of systemic inflammation, endothelial activation and oxidative stress: a panel study in the US trucking industry.

BackgroundExperimental evidence suggests that inhaled particles from vehicle exhaust have systemic effects on inflammation, endothelial activation and oxidative stress. In the present study we assess the relationships of short-term exposures with inflammatory endothelial activation and oxidative stress biomarker levels in a population of trucking industry workers.MethodsBlood and urine samples were collected pre and post-shift, at the beginning and end of a workweek from 67 male non-smoking US trucking industry workers. Concurrent measurements of microenvironment concentrations of elemental and organic carbon (EC & OC), and fine particulate matter (PM2.5) combined with time activity patterns allowed for calculation of individual exposures. Associations between daily and first and last-day average levels of exposures and repeated measures of intercellular and vascular cell adhesion molecule-1 (ICAM-1 & VCAM-1), interleukin 6 (IL-6) and C-reactive protein (CRP) blood levels and urinary 8-Hydroxy-2′-Deoxyguanosine (8-OHdG) were assessed using linear mixed effects models for repeated measures.ResultsThere was a statistically significant association between first and last-day average PM2.5 and 8-OHdG (21% increase, 95% CI: 2, 42%) and first and last-day average OC and IL-6 levels (18% increase 95% CI: 1, 37%) per IQR in exposure. There were no significant findings associated with EC or associations suggesting acute cross-shift effects.ConclusionOur findings suggest associations between weekly average exposures of PM2.5 on markers of oxidative stress and OC on IL-6 levels.

Night heart rate variability and particulate exposures among boilermaker construction workers.

Background Although studies have documented the association between heart rate variability (HRV) and ambient particulate exposures, the association between HRV, especially at night, and metal-rich, occupational particulate exposures remains unclear. Objective Our goal in this study was to investigate the association between long-duration HRV, including nighttime HRV, and occupational PM2.5 exposures. Methods We used 24-hr ambulatory electrocardiograms (ECGs) to monitor 36 male boilermaker welders (mean age of 41 years) over a workday and nonworkday. ECGs were analyzed for HRV in the time domain; rMSSD (square root of the mean squared differences of successive intervals), SDNN (SD of normal-to-normal intervals over entire recording), and SDNNi (SDNN for all 5-min segments) were summarized over 24-hr, day (0730–2130 hours), and night (0000–0700 hours) periods. PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) exposures were monitored over the workday, and 8-hr time-weighted average concentrations were calculated. We used linear regression to assess the associations between HRV and workday particulate exposures. Matched measurements from a nonworkday were used to control for individual cardiac risk factors. Results Mean (± SD) PM2.5 exposure was 0.73 ± 0.50 mg/m3 and ranged from 0.04 to 2.70 mg/m3. We observed a consistent inverse exposure–response relationship, with a decrease in all HRV measures with increased PM2.5 exposure. However, the decrease was most pronounced at night, where a 1-mg/m3 increase in PM2.5 was associated with a change of −8.32 [95% confidence interval (CI), −16.29 to −0.35] msec nighttime rMSSD, −14.77 (95% CI, −31.52 to 1.97) msec nighttime SDNN, and −8.37 (95% CI, −17.93 to 1.20) msec nighttime SDNNi, after adjusting for nonworking nighttime HRV, age, and smoking. Conclusion Metal-rich particulate exposures were associated with decreased long-duration HRV, especially at night. Further research is needed to elucidate which particulate metal constituent is responsible for decreased HRV.