Person:

Garshick, Eric

Background: Occupational and population-based studies have related exposure to fine particulate air pollution, and specifically particulate matter from vehicle exhausts, to cardiovascular diseases and lung cancer. Objectives: We have established a large retrospective cohort to assess mortality in the unionized U.S. trucking industry. To provide insight into mortality patterns associated with job-specific exposures, we examined rates of cause-specific mortality compared with the general U.S. population. Methods: We used records from four national trucking companies to identify 54,319 male employees employed in 1985. Cause-specific mortality was assessed through 2000 using the National Death Index. Expected numbers of all and cause-specific deaths were calculated stratifying by race, 10-year age group, and calendar period using U.S. national reference rates. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated for the entire cohort and by job title. Results: As expected in a working population, we found a deficit in overall and all-cancer mortality, likely due to the healthy worker effect. In contrast, compared with the general U.S. population, we observed elevated rates for lung cancer, ischemic heart disease, and transport-related accidents. Lung cancer rates were elevated among all drivers (SMR = 1.10; 95% CI, 1.02–1.19) and dockworkers (SMR = 1.10; 95% CI, 0.94–1.30); ischemic heart disease was also elevated among these groups of workers [drivers, SMR = 1.49 (95% CI, 1.40–1.59); dockworkers, SMR = 1.32 (95% CI, 1.15–1.52)], as well as among shop workers (SMR = 1.34; 95% CI, 1.05–1.72). Conclusions: In this detailed assessment of specific job categories in the U.S. trucking industry, we found an excess of mortality due to lung cancer and ischemic heart disease, particularly among drivers.

Diesel exhaust is a mixture of combustion gases and ultrafine particles coated with organic compounds. There is concern whether exposure can result in or worsen obstructive airway diseases, but there is only limited information to assess this risk. U.S. railroad workers have been exposed to diesel exhaust since diesel locomotives were introduced after World War II, and by 1959, 95% of the locomotives were diesel. We conducted a case–control study of railroad worker deaths between 1981 and 1982 using U.S. Railroad Retirement Board job records and next-of-kin smoking, residential, and vitamin use histories. There were 536 cases with chronic obstructive pulmonary disease (COPD) and 1,525 controls with causes of death not related to diesel exhaust or fine particle exposure. After adjustment for age, race, smoking, U.S. Census region of death, vitamin use, and total years off work, engineers and conductors with diesel-exhaust exposure from operating trains had an increased risk of COPD mortality. The odds of COPD mortality increased with years of work in these jobs, and those who had worked ≥ 16 years as an engineer or conductor after 1959 had an odds ratio of 1.61 (95% confidence interval, 1.12–2.30). These results suggest that diesel-exhaust exposure contributed to COPD mortality in these workers. Further study is needed to assess whether this risk is observed after exposure to exhaust from later-generation diesel engines with modern emission controls.

Background: COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs). Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations. Methods: In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count. We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St. George's Respiratory Questionnaire Activity Score (SGRQ-AS). AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months. Results: Mean daily step count was 5804±3141 steps. Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year). Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003–1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08–1.42). There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003). Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01–1.14) for AEs and 1.18 (95%CI = 1.07–1.30) for COPD-related hospitalizations. Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01–1.09) for AEs and 1.10 (95%CI = 1.02–1.17) for COPD-related hospitalizations. Conclusions: Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD–related hospitalizations, independent of pulmonary function and previous AE history. These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies.

Background: Previous studies have suggested associations of adult exposures to secondhand smoke (SHS) with respiratory symptoms, but no study has focused on blue-collar industrial environments. We assessed the association between SHS and respiratory symptoms in 1,562 non-current smoking U.S. trucking industry workers. Methods: Information on SHS exposure and respiratory health was obtained by questionnaire. Multiple logistic regression analyses were used to assess the associations of recent and lifetime exposures to SHS with chronic phlegm, chronic cough, and any wheeze, defined by American Thoracic Society criteria. Results: In analyses adjusted for age, gender, race, childhood SHS exposure, former smoking, pack-years of smoking and years since quitting, body mass index, job title, region of the country, and urban residence, recent exposures to SHS were associated with all three respiratory symptoms (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.00-2.13) for chronic cough, 1.55 (95% CI = 1.08-2.21) for chronic phlegm, and 1.76 (95% CI = 1.41-2.21) for any wheeze). Workplace exposure was the most important recent exposure. Childhood exposure to SHS was also associated with all three symptoms, but only statistically significantly for chronic phlegm (OR = 1.84; 95% CI = 1.24-2.75). Additional years of living with a smoker were associated with an increased risk, but there was no evidence of a dose–response, except for chronic phlegm. Conclusions: In this group of trucking industry workers, childhood and recent exposures to SHS were related to respiratory symptoms.

Background: Diesel exhaust has been considered to be a probable lung carcinogen based on studies of occupationally exposed workers. Efforts to define lung cancer risk in these studies have been limited in part by lack of quantitative exposure estimates. Objective: We conducted a retrospective cohort study to assess lung cancer mortality risk among U.S. trucking industry workers. Elemental carbon (EC) was used as a surrogate of exposure to engine exhaust from diesel vehicles, traffic, and loading dock operations. Methods: Work records were available for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. A statistical model based on a national exposure assessment was used to estimate historical work-related exposures to EC. Lung cancer mortality was ascertained through the year 2000, and associations with cumulative and average EC were estimated using proportional hazards models. Results: Duration of employment was inversely associated with lung cancer risk consistent with a healthy worker survivor effect and a cohort composed of prevalent hires. After adjusting for employment duration, we noted a suggestion of a linear exposure–response relationship. For each 1,000-µg/m3 months of cumulative EC, based on a 5-year exposure lag, the hazard ratio (HR) was 1.07 [95% confidence interval (CI): 0.99, 1.15] with a similar association for a 10-year exposure lag [HR = 1.09 (95% CI: 0.99, 1.20)]. Average exposure was not associated with relative risk. Conclusions: Lung cancer mortality in trucking industry workers increased in association with cumulative exposure to EC after adjusting for negative confounding by employment duration.

Abstract In patients with chronic obstructive pulmonary disease (COPD), moderate or severe pulmonary hypertension (COPD-PH) is associated with increased rates of morbidity and mortality. Despite this, approaches to treatment and the efficacy of phosphodiesterase type 5 inhibition (PDE-5i) in COPD-PH are unresolved. We present the clinical rationale and study design to assess the effect of oral tadalafil on exercise capacity, cardiopulmonary hemodynamics, and clinical outcome measures in COPD-PH patients. Male and female patients 40–85 years old with GOLD stage 2 COPD or higher and pulmonary hypertension diagnosed on the basis of invasive cardiac hemodynamic assessment (mean pulmonary artery pressure [mPAP] >30 mmHg, pulmonary vascular resistance [PVR] >2.5 Wood units, and pulmonary capillary wedge pressure ≤18 mmHg at rest) will be randomized at a 1∶1 ratio to receive placebo or oral PDE-5i with tadalafil (40 mg daily for 12 months). The primary end point is change from baseline in 6-minute walk distance at 12 months. The secondary end points are change from baseline in PVR and mPAP at 6 months and change from baseline in peak volume of oxygen consumption () during exercise at 12 months. Changes in systemic blood pressure and/or oxyhemoglobin saturation (Sao2) at rest and during exercise will function as safety outcome measures. TADA-PHiLD (TADAlafil for Pulmonary Hypertension assocIated with chronic obstructive Lung Disease) is the first sufficiently powered randomized clinical trial testing the effect of PDE-5i on key clinical and drug safety outcome measures in patients with at least moderate PH due to COPD.

Background: Experimental 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. Methods: Blood 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. Results: There 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. Conclusion: Our findings suggest associations between weekly average exposures of PM2.5 on markers of oxidative stress and OC on IL-6 levels.

Background: Diesel engine exhaust (DEE) has recently been classified as a known human carcinogen. Objective: We derived a meta-exposure–response curve (ERC) for DEE and lung cancer mortality and estimated lifetime excess risks (ELRs) of lung cancer mortality based on assumed occupational and environmental exposure scenarios. Methods: We conducted a meta-regression of lung cancer mortality and cumulative exposure to elemental carbon (EC), a proxy measure of DEE, based on relative risk (RR) estimates reported by three large occupational cohort studies (including two studies of workers in the trucking industry and one study of miners). Based on the derived risk function, we calculated ELRs for several lifetime occupational and environmental exposure scenarios and also calculated the fractions of annual lung cancer deaths attributable to DEE. Results: We estimated a lnRR of 0.00098 (95% CI: 0.00055, 0.0014) for lung cancer mortality with each 1-μg/m3-year increase in cumulative EC based on a linear meta-regression model. Corresponding lnRRs for the individual studies ranged from 0.00061 to 0.0012. Estimated numbers of excess lung cancer deaths through 80 years of age for lifetime occupational exposures of 1, 10, and 25 μg/m3 EC were 17, 200, and 689 per 10,000, respectively. For lifetime environmental exposure to 0.8 μg/m3 EC, we estimated 21 excess lung cancer deaths per 10,000. Based on broad assumptions regarding past occupational and environmental exposures, we estimated that approximately 6% of annual lung cancer deaths may be due to DEE exposure. Conclusions: Combined data from three U.S. occupational cohort studies suggest that DEE at levels common in the workplace and in outdoor air appear to pose substantial excess lifetime risks of lung cancer, above the usually acceptable limits in the United States and Europe, which are generally set at 1/1,000 and 1/100,000 based on lifetime exposure for the occupational and general population, respectively. Citation: Vermeulen R, Silverman DT, Garshick E, Vlaanderen J, Portengen L, Steenland K. 2014. Exposure-response estimates for diesel engine exhaust and lung cancer mortality based on data from three occupational cohorts. Environ Health Perspect 122:172–177; http://dx.doi.org/10.1289/ehp.1306880

Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30–1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort.