Diesel Exhaust, Respirable Dust, and Ischemic Heart Disease: An Application of the Parametric g-formula.

BACKGROUND: Although general population studies of air pollution suggest that particulate matter-diesel exhaust emissions in particular-is a potential risk factor for cardiovascular disease, direct evidence from occupational cohorts using quantitative metrics of exposure is limited. In this study, we assess counterfactual risk of ischemic heart disease (IHD) mortality under hypothetical scenarios limiting exposure levels of diesel exhaust and of respirable mine/ore dust in the Diesel Exhaust in Miners Study cohort. METHODS: We analyzed data on 10,779 male miners from 8 nonmetal, noncoal mines-hired after diesel equipment was introduced in the respective facilities-and followed from 1948 to 1997, with 297 observed IHD deaths in this sample. We applied the parametric g-formula to assess risk under hypothetical scenarios with various limits for respirable elemental carbon (a surrogate for diesel exhaust), and respirable dust, separately and jointly. RESULTS: The risk ratio comparing the observed risk to cumulative IHD mortality risk at age 80 under a hypothetical scenario where exposures to elemental carbon and respirable dust are eliminated was 0.79 (95% confidence interval [CI]: 0.64, 0.97). The corresponding risk difference was -3.0% (95% CI: -5.7, -0.3). CONCLUSION: Our findings, based on data from a cohort of nonmetal miners, are consistent with the hypothesis that interventions to eliminate exposures to diesel exhaust and respirable dust would reduce IHD mortality risk.

Ischemic Heart Disease Mortality and Diesel Exhaust and Respirable Dust Exposure in the Diesel Exhaust in Miners Study.

Diesel exhaust is a suggested risk factor for ischemic heart disease (IHD), but evidence from cohorts using quantitative exposure metrics is limited. We examined the impact of respirable elemental carbon (REC), a key surrogate for diesel exhaust, and respirable dust (RD) on IHD mortality, using data from the Diesel Exhaust in Miners Study in the United States. Using data from a cohort of male workers followed from 1948-1968 until 1997, we fitted Cox proportional hazards models to estimate hazard ratios for IHD mortality for cumulative and average intensity of exposure to REC and RD. Segmented linear regression models allowed for nonmonotonicity. Hazard ratios for cumulative and average REC exposure declined relative to the lowest exposure category before increasing to 0.79 and 1.25, respectively, in the highest category. Relative to the category containing the segmented regression change points, hazard ratios for the highest category were 1.69 and 1.54 for cumulative and average REC exposure, respectively. Hazard ratios for RD exposure increased across the full exposure range to 1.33 and 2.69 for cumulative and average RD exposure, respectively. Tests for trend were statistically significant for cumulative REC exposure (above the change point) and for average RD exposure. Our findings suggest excess risk of IHD mortality in relation to increased exposure to REC and RD.

Examination of potential sources of bias in the US Coal Workers' Health Surveillance Program.

OBJECTIVES: We examined the potential influences of certain selection factors on the utility of the Coal Workers' Health Surveillance Program (CWHSP) data for tracking disease distribution and trends. METHODS: We combined data from the CWHSP and the Energy Information Administration to examine any influence of variable worker participation on observed disease prevalence. We evaluated effects of differential participation by coal mining region, temporal changes in employment, and active surveillance efforts. RESULTS: The published findings of pneumoconiosis distribution and trends from the CWHSP were robust compared with the various participation factors that might have affected their validity for population-based estimates of disease burden. Exploration of factors that could potentially bias the findings generally led to small increases in the primary estimates, mostly for the early years of the program. CONCLUSIONS: We confirmed previously reported findings that there was a high prevalence of coal worker pneumoconiosis (CWP) around 1970-1974, a substantial decline in 1995-1999, and indications of an increase since then. Overall our findings suggest that the previously reported distribution and trends in CWP prevalence were broadly accurate.

Respiratory disease mortality among US coal miners; results after 37 years of follow-up.

OBJECTIVES: To evaluate respiratory related mortality among underground coal miners after 37 years of follow-up. METHODS: Underlying cause of death for 9033 underground coal miners from 31 US mines enrolled between 1969 and 1971 was evaluated with life table analysis. Cox proportional hazards models were fitted to evaluate the exposure-response relationships between cumulative exposure to coal mine dust and respirable silica and mortality from pneumoconiosis, chronic obstructive pulmonary disease (COPD) and lung cancer. RESULTS: Excess mortality was observed for pneumoconiosis (SMR=79.70, 95% CI 72.1 to 87.67), COPD (SMR=1.11, 95% CI 0.99 to 1.24) and lung cancer (SMR=1.08; 95% CI 1.00 to 1.18). Coal mine dust exposure increased risk for mortality from pneumoconiosis and COPD. Mortality from COPD was significantly elevated among never [corrected] smokers and former smokers (HR=1.84, 95% CI 1.05 to 3.22; HRK=1.52, 95% CI 0.98 to 2.34, respectively) but not current smokers (HR=0.99, 95% CI 0.76 to 1.28). Respirable silica was positively associated with mortality from pneumoconiosis (HR=1.33, 95% CI 0.94 to 1.33) and COPD (HR=1.04, 95% CI 0.96 to 1.52) in models controlling for coal mine dust. We saw a significant relationship between coal mine dust exposure and lung cancer mortality (HR=1.70; 95% CI 1.02 to 2.83) but not with respirable silica (HR=1.05; 95% CI 0.90 to 1.23). In the most recent follow-up period (2000-2007) both exposures were positively associated with lung cancer mortality, coal mine dust significantly so. CONCLUSIONS: Our findings support previous studies showing that exposure to coal mine dust and respirable silica leads to increased mortality from malignant and non-malignant respiratory diseases even in the absence of smoking.

Potential determinants of coal workers' pneumoconiosis, advanced pneumoconiosis, and progressive massive fibrosis among underground coal miners in the United States, 2005-2009.

OBJECTIVES: We better defined the distribution and determinants of coal workers' pneumoconiosis (CWP) among US underground coal miners. METHODS: We obtained chest radiographs from the mobile unit of an enhanced surveillance program begun in 2005 by the National Institute for Occupational Safety and Health for underground coal miners. B Readers classified them for presence of pneumoconiosis. RESULTS: Miners from 15 states participated (n = 6658). The prevalence of CWP was higher in 3 states (Kentucky, 9.0%; Virginia, 8.0%; West Virginia, 4.8%) than in 12 other states (age-adjusted risk ratio [RR] = 4.5; 95% confidence interval [CI] = 3.3, 6.1). Miners in these 3 states were younger and had less mining tenure, but advanced CWP (category ≥ 2/1; RR = 8.1; 95% CI = 3.9, 16.9) and progressive massive fibrosis (RR = 10.5; 95% CI = 3.8, 29.1) was more prevalent among them. Advanced CWP and progressive massive fibrosis were more prevalent among workers at mines with fewer than 155 miners, irrespective of mining region, than among workers at larger mines. CONCLUSIONS: Enhanced surveillance results confirmed the persistence of severe CWP among US coal miners and documented the health consequences of inadequate dust control for miners in parts of Appalachia and at smaller mines.

Coal workers' pneumoconiosis in the United States: regional differences 40 years after implementation of the 1969 Federal Coal Mine Health and Safety Act.

OBJECTIVE: To assess whether the recent increases in the prevalence of coal workers' pneumoconiosis (CWP) in the USA reflect increased measured exposures over recent decades, and to identify other potential causative factors. METHODS: The observed CWP prevalence was calculated for 12,408 underground coal miner participants in the Coal Workers' Health Surveillance Program for the period 2005-2009, stratified by the Mine Safety and Health Administration (MSHA) geographical districts. The predicted prevalence was estimated using a published exposure-response model from a large epidemiological study among U.S. coal miners using dust exposure, tenure, miner's age and coal rank as predictors. χ2 Testing was performed to compare the observed versus predicted CWP prevalence. RESULTS: Observed prevalence was significantly higher than predicted prevalence in MSHA districts 4-7 (central Appalachian region) (10.1% vs. 4.2%; prevalence ratio (PR) 2.4; p<0.001) and significantly lower than predicted in other regions (1.6% vs. 3.6%; PR 0.4; p<0.001). The central Appalachian region had a significantly older workforce with greater mining tenure, a lower proportion of mines with 200 or more employees, and lower seam heights. Significant lower average compliance dust concentrations were reported for this region. CONCLUSION: The observed CWP prevalence substantially exceeded predicted levels in central Appalachia. However, the increased prevalence was not explained by the measured levels of dust exposures. Likely contributing factors include mine size and low seam mining, which may be associated with higher exposure to silica. Further study is needed to characterise the responsible factors for the elevated CWP rates in central Appalachia.

Coal workers' pneumoconiosis and progressive massive fibrosis are increasingly more prevalent among workers in small underground coal mines in the United States.

OBJECTIVE: To determine whether the prevalence of coal workers' pneumoconiosis (CWP) or progressive massive fibrosis (PMF) among United States underground miners is associated with mine size. METHODS: We examined chest radiographs from 1970 to 2009 of working miners who participated in the National Coal Workers Health Surveillance Program for the presence of small and large opacities consistent with pneumoconiosis, based upon the International Labour Organization classification system. RESULTS: A total of 145 512 miners contributed 240 067 radiographs for analysis. From the 1990s to the 2000s, the prevalence of radiographic CWP increased among miners in mines of all sizes, while miners working in mines with fewer than 50 employees had a significantly higher prevalence of CWP compared to miners who worked in mines with 50 or more employees (p<0.0001). When adjusted for age and within-miner correlation, the difference in prevalence of CWP by mine size was significant for all decades. Since 1999, miners from small mines were five times more likely to have radiographic evidence of PMF (1.0% of miners) compared to miners from larger mines (0.2% of miners) with a prevalence ratio of 5.0 and 95% CI 3.3 to 7.5. CONCLUSION: The prevalence of CWP among United States coal miners is increasing in mines of all sizes, while CWP and PMF are much more prevalent among workers from underground mines with fewer than 50 workers.

Pneumoconiosis among underground bituminous coal miners in the United States: is silicosis becoming more frequent?

OBJECTIVES: Epidemiological reports since 2000 have documented increased prevalence and rapid progression of pneumoconiosis among underground coal miners in the United States. To investigate a possible role of silica exposure in the increase, we examined chest x-rays (CXRs) for specific abnormalities (r-type small opacities) known to be associated with silicosis lung pathology. METHODS: Underground coal miners are offered CXRs every 5 years. Abnormalities consistent with pneumoconiosis are recorded by National Institute for Occupational Safety and Health (NIOSH) B Readers using the International Labour Organization Classification of Radiographs of Pneumoconioses. CXRs from 1980 to 2008 of 90 973 participating miners were studied, focussing on reporting of r-type opacities (small rounded opacities 3-10 mm in diameter). Log binomial regression was used to calculate prevalence ratios adjusted for miner age and profusion category. RESULTS: Among miners from Kentucky, Virginia and West Virginia, the proportion of radiographs showing r-type opacities increased during the 1990s (prevalence ratio (PR) 2.5; 95% CI 1.7 to 3.7) and after 1999 (PR 4.1; 95% CI 3.0 to 5.6), compared to the 1980s (adjusted for profusion category and miner age). The prevalence of progressive massive fibrosis in 2000-2008 was also elevated compared to the 1980s (PR 4.4; 95% CI 3.1 to 6.3) and 1990s (PR 3.8; 95% CI 2.1 to 6.8) in miners from Kentucky, Virginia and West Virginia. CONCLUSIONS: The increasing prevalence of pneumoconiosis over the past decade and the change in the epidemiology and disease profile documented in this and other recent studies imply that US coal miners are being exposed to excessive amounts of respirable crystalline silica.

The Diesel Exhaust in Miners Study: IV. Estimating historical exposures to diesel exhaust in underground non-metal mining facilities.

We developed quantitative estimates of historical exposures to respirable elemental carbon (REC) for an epidemiologic study of mortality, including lung cancer, among diesel-exposed miners at eight non-metal mining facilities [the Diesel Exhaust in Miners Study (DEMS)]. Because there were no historical measurements of diesel exhaust (DE), historical REC (a component of DE) levels were estimated based on REC data from monitoring surveys conducted in 1998-2001 as part of the DEMS investigation. These values were adjusted for underground workers by carbon monoxide (CO) concentration trends in the mines derived from models of historical CO (another DE component) measurements and DE determinants such as engine horsepower (HP; 1 HP = 0.746 kW) and mine ventilation. CO was chosen to estimate historical changes because it was the most frequently measured DE component in our study facilities and it was found to correlate with REC exposure. Databases were constructed by facility and year with air sampling data and with information on the total rate of airflow exhausted from the underground operations in cubic feet per minute (CFM) (1 CFM = 0.0283 m³ min⁻¹), HP of the diesel equipment in use (ADJ HP), and other possible determinants. The ADJ HP purchased after 1990 (ADJ HP1990(+)) was also included to account for lower emissions from newer, cleaner engines. Facility-specific CO levels, relative to those in the DEMS survey year for each year back to the start of dieselization (1947-1967 depending on facility), were predicted based on models of observed CO concentrations and log-transformed (Ln) ADJ HP/CFM and Ln(ADJ HP1990(+)). The resulting temporal trends in relative CO levels were then multiplied by facility/department/job-specific REC estimates derived from the DEMS surveys personal measurements to obtain historical facility/department/job/year-specific REC exposure estimates. The facility-specific temporal trends of CO levels (and thus the REC estimates) generated from these models indicated that CO concentrations had been generally greater in the past than during the 1998-2001 DEMS surveys, with the highest levels ranging from 100 to 685% greater (median: 300%). These levels generally occurred between 1970 and the early 1980s. A comparison of the CO facility-specific model predictions with CO air concentration measurements from a 1976-1977 survey external to the modeling showed that our model predictions were slightly lower than those observed (median relative difference of 29%; range across facilities: 49 to -25%). In summary, we successfully modeled past CO concentration levels using selected determinants of DE exposure to derive retrospective estimates of REC exposure. The results suggested large variations in REC exposure levels both between and within the underground operations of the facilities and over time. These REC exposure estimates were in a plausible range and were used in the investigation of exposure-response relationships in epidemiologic analyses.

The impact of alternative historical extrapolations of diesel exhaust exposure and radon in the Diesel Exhaust in Miners Study (DEMS).

BACKGROUND: Previous results from the Diesel Exhaust in Miners Study (DEMS) demonstrated a positive exposure-response relation between lung cancer and respirable elemental carbon (REC), a key surrogate for diesel exhaust exposure. Two issues have been raised regarding DEMS: (i) the use of historical carbon monoxide (CO) measurements to calibrate models used for estimating historical exposures to REC in the DEMS exposure assessment; and (ii) potential confounding by radon. METHODS: We developed alternative REC estimates using models that did not rely on CO for calibration, but instead relied on estimated use of diesel equipment, mine ventilation rates and changes in diesel engine emission rates over time. These new REC estimates were used to quantify cumulative REC exposure for each subject in the nested case-control study. We conducted conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals for lung cancer. To evaluate the impact of including radon as a potential confounder, we estimated ORs for average REC intensity adjusted for cumulative radon exposure in underground miners. RESULTS: Validation of the new REC exposure estimates indicated that they overestimated historical REC by 200-400%, compared with only 10% for the original estimates. Effect estimates for lung cancer using these alternative REC exposures or adjusting for radon typically changed by <10% when compared with the original estimates. CONCLUSIONS: These results emphasize the robustness of the DEMS findings, support the use of CO for model calibration and confirm that radon did not confound the DEMS estimates of the effect of diesel exposure on lung cancer mortality.

The National Institute for Occupational Safety and Health B Reader Certification Program-An Update Report (1987 to 2018) and Future Directions.

OBJECTIVE: The National Institute for Occupational Safety and Health (NIOSH) B Reader Program provides the opportunity for physicians to demonstrate proficiency in the International Labour Office (ILO) system for classifying radiographs of pneumoconioses. We summarize trends in participation and examinee attributes and performance during 1987 to 2018. METHODS: Since 1987, NIOSH has maintained details of examinees and examinations. Attributes of examinees and their examination performance were summarized. Simple linear regression was used in trend analysis of passing rates over time. RESULTS: The mean passing rate for certification and recertification for the study period was 40.4% and 82.6%, respectively. Since the mid-1990s, the number of B Readers has declined and the mean age and years certified have increased. CONCLUSIONS: To address the declining B Reader population, NIOSH is currently taking steps to modernize the program and offer more opportunities for training and testing.

Silicosis mortality among young adults in the United States, 1968-2004.

BACKGROUND: To describe silicosis deaths in young (aged 15-44) adults in the U.S. during 1968-2004. METHODS: We analyzed the National Center for Health Statistics multiple cause-of-death records. RESULTS: Compared with silicosis decedents aged >or=45 years (n = 15,643), young decedents (n = 237) were more likely to have silicosis listed as the underlying cause of death (74.3% vs. 48.2%, P < 0.001), to be female (9.3% vs. 2.2%, P < 0.001) and black (37.1% vs. 11.7%, P < 0.001). Twenty-nine young silicosis decedents had industry and occupation information available. Occupations in construction and manufacturing industries were associated with significantly elevated proportionate mortality ratios for young silicosis deaths. CONCLUSIONS: Silicosis deaths occur among young adults. Because these deaths are likely to reflect more intense and recent exposures, the follow-back investigations into the work sites where these individuals were exposed to silica should be conducted.

National trends in silicosis mortality in the United States, 1981-2004.

BACKGROUND: This article describes trends in mortality with silicosis and identifies industries and occupations with elevated silicosis mortality. METHODS: A total of 6,326 deaths with silicosis for 1981-2004 were analyzed for trends and association with occupation and industry. Annual mortality rates were age-adjusted to the U.S. Year 2000 population. A linear regression model was used for analyzing mortality trends. Proportionate mortality ratios (PMRs) were based on 1,440 deaths with information on usual industry and occupation. RESULTS: Overall age-adjusted mortality rates per million declined from 2.4 in 1981 to 0.7 in 2004. Industries having significantly elevated PMRs for silicosis included mining and quarrying. Occupations with elevated PMRs included those associated with metal and mineral processing. CONCLUSIONS: The results suggest that considerable progress has been made towards elimination of this preventable disease. However, about 30 silicosis deaths per year have been recorded since 1995 among those of working age, warranting continued efforts to effectively limit workplace exposures.

Mapping and prediction of coal workers' pneumoconiosis with bioavailable iron content in the bituminous coals.

Based on the first National Study of Coal Workers' Pneumoconiosis (CWP) and the U.S. Geological Survey database of coal quality, we show that the prevalence of CWP in seven coal mine regions correlates with levels of bioavailable iron (BAI) in the coals from that particular region (correlation coefficient r = 0.94, p < 0.0015). CWP prevalence is also correlated with contents of pyritic sulfur (r = 0.91, p < 0.0048) or total iron (r = 0.85, p < 0.016) but not with coal rank (r = 0.59, p < 0.16) or silica (r = 0.28, p < 0.54). BAI was calculated using our model, taking into account chemical interactions of pyrite, sulfuric acid, calcite, and total iron. That is, iron present in coals can become bioavailable by pyrite oxidation, which produces ferrous sulfate and sulfuric acid. Calcite is the major component in coals that neutralizes the available acid and inhibits iron's bioavailability. Therefore, levels of BAI in the coals are determined by the available amounts of acid after neutralization of calcite and the amount of total iron in the coals. Using the linear fit of CWP prevalence and the calculated BAI in the seven coal mine regions, we have derived and mapped the pneumoconiotic potencies of 7,000 coal samples. Our studies indicate that levels of BAI in the coals may be used to predict coal's toxicity, even before large-scale mining.

[Early change of pulmonary ventilation in new coal miners].

OBJECTIVE: To study the early effects of coal dust on lung function in new underground coal miners. METHODS: Two hundred and eighty-seven male miners were selected from new employees at the Xuzhou Mining Group Company as study group, and 132 male students at a mining technical school were selected as control. Data collection included: individual demographic parameters, family medical history, occupational history, and smoking history, measurement of dust concentrations in work areas, and lung function tests. This prospective cohort study took place over 3 years during which time total dust and respirable dust concentrations in the new coal miners' work areas were measured twice each month. For both miner and student groups, FVC and FEV(1) were tested initially before dust exposure, and then 15 times over the 3 years. RESULTS: The average total dust and respirable dust concentrations in the miners' work areas were 23.8 mg/m(3) and 8.9 mg/m(3) respectively, which greatly exceeded national health criteria. During the first year of dust exposure, the miners's average FVC was higher than that of the controls (5.19 L vs 4.92 L, P < 0.01). During the 2nd and 3rd year the difference in average FVC between miners and control group was not significant (5.14 L vs 5.12 L, P > 0.05). Before dust exposure, the miners' FEV(1) was significantly higher than that of the control group (4.48 L vs 4.28 L). In the miners group, FEV(1) declined rapidly during the first year following dust exposure (from 4.48 L to 4.25 L), and in the 2nd and the 3rd year the average FEV(1) of the miners was significantly lower than that of controls (4.34 L vs 4.56 L, P < 0.01), although there were some fluctuations during the follow-up period. Overall, the average FEV(1) of miners group showed a significant decline during the study. There were significant correlations between FVC or FEV(1) and age, height, weight, and smoking. The three-year total loss of FVC and FEV(1) in smoking miners (154 ml, 184 ml) were greater than in non-smoking miners (83 ml, 91 ml). CONCLUSION: There are apparent effects of coal dust on lung function in new underground coal miners, with FEV(1) being more impacted than FVC. Smoking may aggravate the effect of dust exposure on reducing lung function.

Malignant mesothelioma surveillance: a comparison of ICD 10 mortality data with SEER incidence data in nine areas of the United States.

With the implementation in 1999 of ICD-10 death certificate coding in the United States, mortality data specific to malignant mesothelioma became readily available on a national basis. To evaluate the accuracy and completeness of diagnosis and coding for mesothelioma on the death certificate, mortality information was compared with incidence data. A mortality/incidence ratio was calculated for each of the nine areas covered by the SEER Program, using National Vital Statistics mortality data from 1999 and 2000, and the SEER incidence data for 1998 and 1999. The mortality/incidence ratio for the two years combined for all areas was 0.82. Only two areas (Connecticut and Atlanta) had ratios <80%. The overall correlation coefficient between mortality and incidence rates was 0.96. Thus, mortality data coded using ICD-10 can be a valid source for mesothelioma surveillance and can be instituted without major cost if a national mortality statistics program based on ICD-10 is in place, making it feasible even for developing countries.

The Diesel Exhaust in Miners study: a cohort mortality study with emphasis on lung cancer.

BACKGROUND: Current information points to an association between diesel exhaust exposure and lung cancer and other mortality outcomes, but uncertainties remain. METHODS: We undertook a cohort mortality study of 12 315 workers exposed to diesel exhaust at eight US non-metal mining facilities. Historical measurements and surrogate exposure data, along with study industrial hygiene measurements, were used to derive retrospective quantitative estimates of respirable elemental carbon (REC) exposure for each worker. Standardized mortality ratios and internally adjusted Cox proportional hazard models were used to evaluate REC exposure-associated risk. Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death. RESULTS: Standardized mortality ratios for lung cancer (1.26, 95% confidence interval [CI] = 1.09 to 1.44), esophageal cancer (1.83, 95% CI = 1.16 to 2.75), and pneumoconiosis (12.20, 95% CI = 6.82 to 20.12) were elevated in the complete cohort compared with state-based mortality rates, but all-cause, bladder cancer, heart disease, and chronic obstructive pulmonary disease mortality were not. Differences in risk by worker location (ever-underground vs surface only) initially obscured a positive diesel exhaust exposure-response relationship with lung cancer in the complete cohort, although it became apparent after adjustment for worker location. The hazard ratios (HRs) for lung cancer mortality increased with increasing 15-year lagged cumulative REC exposure for ever-underground workers with 5 or more years of tenure to a maximum in the 640 to less than 1280 µg/m(3)-y category compared with the reference category (0 to <20 µg/m(3)-y; 30 deaths compared with eight deaths of the total of 93; HR = 5.01, 95% CI = 1.97 to 12.76) but declined at higher exposures. Average REC intensity hazard ratios rose to a plateau around 32 µg/m(3). Elevated hazard ratios and evidence of exposure-response were also seen for surface workers. The association between diesel exhaust exposure and lung cancer risk remained after inclusion of other work-related potentially confounding exposures in the models and were robust to alternative approaches to exposure derivation. CONCLUSIONS: The study findings provide further evidence that exposure to diesel exhaust increases risk of mortality from lung cancer and have important public health implications.

The Diesel Exhaust in Miners study: a nested case-control study of lung cancer and diesel exhaust.

BACKGROUND: Most studies of the association between diesel exhaust exposure and lung cancer suggest a modest, but consistent, increased risk. However, to our knowledge, no study to date has had quantitative data on historical diesel exposure coupled with adequate sample size to evaluate the exposure-response relationship between diesel exhaust and lung cancer. Our purpose was to evaluate the relationship between quantitative estimates of exposure to diesel exhaust and lung cancer mortality after adjustment for smoking and other potential confounders. METHODS: We conducted a nested case-control study in a cohort of 12 315 workers in eight non-metal mining facilities, which included 198 lung cancer deaths and 562 incidence density-sampled control subjects. For each case subject, we selected up to four control subjects, individually matched on mining facility, sex, race/ethnicity, and birth year (within 5 years), from all workers who were alive before the day the case subject died. We estimated diesel exhaust exposure, represented by respirable elemental carbon (REC), by job and year, for each subject, based on an extensive retrospective exposure assessment at each mining facility. We conducted both categorical and continuous regression analyses adjusted for cigarette smoking and other potential confounding variables (eg, history of employment in high-risk occupations for lung cancer and a history of respiratory disease) to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death (case subjects)/reference date (control subjects). All statistical tests were two-sided. RESULTS: We observed statistically significant increasing trends in lung cancer risk with increasing cumulative REC and average REC intensity. Cumulative REC, lagged 15 years, yielded a statistically significant positive gradient in lung cancer risk overall (P (trend) = .001); among heavily exposed workers (ie, above the median of the top quartile [REC ≥ 1005 µg/m(3)-y]), risk was approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that among workers in the lowest quartile of exposure. Among never smokers, odd ratios were 1.0, 1.47 (95% CI = 0.29 to 7.50), and 7.30 (95% CI = 1.46 to 36.57) for workers with 15-year lagged cumulative REC tertiles of less than 8, 8 to less than 304, and 304 µg/m(3)-y or more, respectively. We also observed an interaction between smoking and 15-year lagged cumulative REC (P (interaction) = .086) such that the effect of each of these exposures was attenuated in the presence of high levels of the other. CONCLUSION: Our findings provide further evidence that diesel exhaust exposure may cause lung cancer in humans and may represent a potential public health burden.