BACKGROUND: The Diesel Exhaust in Miners Study (DEMS) was an important contributor to the International Agency for Research on Cancer reclassification of diesel exhaust as a Group I carcinogen and subsequent risk assessment. We extended the DEMS cohort follow-up by 18 y and the nested case-control study to include all newly identified lung cancer deaths and matched controls (DEMS II), nearly doubling the number of lung cancer deaths. OBJECTIVE: Our purpose was to characterize the exposure-response relationship with a focus on the effects of timing of exposure and exposure cessation. METHODS: We conducted a case-control study of lung cancer nested in a cohort of 12,315 workers in eight nonmetal mines (376 lung cancer deaths, 718 controls). Controls were selected from workers who were alive when the case died, individually matched on mine, sex, race/ethnicity, and birth year (within 5 y). Based on an extensive historical exposure assessment, we estimated respirable elemental carbon (REC), an index of diesel exposure, for each cohort member. Odds ratios (ORs) were estimated by conditional regression analyses controlling for smoking and other confounders. To evaluate time windows of exposure, we evaluated the joint OR patterns for cumulative REC within each of four preselected exposure time windows,  < 5, 5-9, 10-19, and  ≥ 20 y prior to death/reference date, and we evaluated the interaction of cumulative exposure across time windows under additive and multiplicative forms for the joint association. RESULTS: ORs increased with increasing 15-y lagged cumulative exposure, peaking with a tripling of risk for exposures of  ∼ 950 to < 1,700 μg/m3-y [OR = 3.23; 95% confidence interval (CI): 1.47, 7.10], followed by a plateau/decline among the heavily exposed (OR = 1.85; 95% CI: 0.85, 4.04). Patterns of risk by cumulative REC exposure varied across four exposure time windows (phomogeneity < 0.001), with ORs increasing for exposures accrued primarily 10-19 y prior to death (ptrend < 0.001). Results provided little support for a waning of risk among workers whose exposures ceased for  ≥ 20 y. CONCLUSION: DEMS II findings provide insight into the exposure-response relationship between diesel exhaust and lung cancer mortality. The pronounced effect of exposures occurring in the window 10-19 y prior to death, the sustained risk 20 or more years after exposure ceases, and the plateau/decline in risk among the most heavily exposed provide direction for future research on the mechanism of diesel-induced carcinogenesis in addition to having important implications for the assessment of risk from diesel exhaust by regulatory agencies. https://doi.org/10.1289/EHP11980.

E-cigarettes are battery-operated devices that heat a liquid mixture to make an aerosol that is inhaled, or vaped, by the user. Vape shops are retail environments for customer demand of diverse e-liquid flavors and hardware options, which create unique worker exposure concerns. To characterize exposures to vape shop workers, especially to flavoring chemicals associated with known respiratory toxicity, this study recruited vape shops from the San Francisco Bay Area. In six shops, air concentrations were measured for volatile organic compounds, formaldehyde, flavoring chemicals, and nicotine in personal and/or area samples; analyzed components of e-liquids vaped during field visits; and assessed metals on surface wipe samples. Interviews and observations were conducted over the course of a workday in the same six shops and performed interviews only in an additional six where sampling was not conducted. Detections of the alpha-diketone butter flavoring chemicals diacetyl and/or 2,3-pentanedione were common: in the headspace of purchased e-liquids (18 of 26 samples), in personal air samples (five of 16), and in area air samples (two of six shops). Two exceedances of recommended exposure limits for 2,3-pentanedione (a short-term exposure limit and an eight-hour time weighted average) were measured in personal air samples. Other compounds detected in area and personal air samples included substitutes for diacetyl and 2,3-pentanedione (acetoin and 2,3-hexanedione) and compounds that may be contaminants or impurities. Furthermore, a large variety (82) of other flavoring chemicals were detected in area air samples. None of the 12 shops interviewed had a health and safety program. Six shops reported no use of any personal protective equipment (PPE) (e.g., gloves, chemical resistant aprons, eye protection) and the others stated occasional use; however, no PPE use was observed during any field investigation day. Recommendations were provided to shops that included making improvements to ventilation, hygiene, use of personal protective equipment, and, if possible, avoidance of products containing the alpha-diketone flavoring chemicals. Future research is needed to evaluate the long-term health risks among workers in the vape shop retail industry and for e-cigarette use generally. Specific areas include further characterizing e-liquid constituents and emissions, evaluating ingredient health risks, evaluating the contributions of different routes of exposure (dermal, inhalation, and ingestion) and determining effective exposure mitigation measures.

E-cigarettes utilize a wide range of flavoring chemicals with respiratory health effects that are not well understood. In this study, we used pulmonary-associated cell lines to assess the in vitro cytotoxic effects of 30 flavoring chemicals. Human bronchial epithelial cells (BEAS-2B) and both naïve and activated macrophages (THP-1) were treated with 10, 100, and 1000 µM of flavoring chemicals and analyzed for changes in viability, cell membrane damage, reactive oxygen species (ROS) production, and inflammatory cytokine release. Viability was unaffected for all chemicals at the 10 and 100 µM concentrations. At 1000 µM, the greatest reductions in viability were seen with decanal, hexanal, nonanal, cinnamaldehyde, eugenol, vanillin, alpha-pinene, eugenol, and limo-nene. High amounts of ROS were elicited by vanillin, ethyl maltol, and the diketones (2,3-pentane-dione, 2,3-heptanedione, and 2,3-hexanedione) from both cell lines. Naïve THP-1 cells produced significantly elevated levels of IL-1β, IL-8, and TNF-α when exposed to ethyl maltol and hexanal. Activated THP-1 cells released increased IL-1β and TNF-α when exposed to ethyl maltol, but many flavoring chemicals had an apparent suppressive effect on inflammatory cytokines released by activated macrophages, some with varying degrees of accompanying cytotoxicity. The diketones, L-carvone, and linalool suppressed cytokine release in the absence of cytotoxicity. These findings pro-vide insight into lung cell cytotoxicity and inflammatory cytokine release in response to flavorings commonly used in e-cigarettes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Importance: Since August 2019, more than 2700 patients have been hospitalized with e-cigarette, or vaping, product use-associated lung injury (EVALI) across the United States. This report describes the outbreak in California, a state with one of the highest case counts and with a legal adult-use (recreational) cannabis market. Objective: To present clinical characteristics and vaping product exposures of patients with EVALI in California. Design, Setting, and Participants: Case series describing epidemiologic and laboratory data from 160 hospitalized patients with EVALI reported to the California Department of Public Health by local health departments, who received reports from treating clinicians, from August 7 through November 8, 2019. Exposures: Standardized patient interviews were conducted to assess vaping products used, frequency of use, and method of product acquisition. Vaping products provided by a subset of patients were tested for active ingredients and other substances. Main Outcomes and Measures: Demographic and clinical characteristics, level of care, and outcomes of hospitalization were obtained from medical record review. Results: Among 160 patients with EVALI, 99 (62%) were male, and the median age was 27 years (range, 14-70 years). Of 156 patients with data available, 71 (46%) were admitted to an intensive care unit, and 46 (29%) required mechanical ventilation. Four in-hospital deaths occurred. Of 86 patients interviewed, 71 (83%) reported vaping tetrahydrocannabinol (THC)-containing products, 36 (43%) cannabidiol (CBD)-containing products, and 39 (47%) nicotine-containing products. Sixty-five of 87 (75%) THC-containing products were reported as obtained from informal sources, such as friends, acquaintances, or unlicensed retailers. Of 87 vaping products tested from 24 patients, 49 (56%) contained THC. Vitamin E or vitamin E acetate was found in 41 (84%) of the THC-containing products and no nicotine products. Conclusions and Relevance: Patients' clinical outcomes and vaping behaviors, including predominant use of THC-containing products from informal sources, are similar to those reported by other states, despite California's legal recreational cannabis market. While most THC products tested contained vitamin E or vitamin E acetate, other underlying cause(s) of injury remain possible. The California Department of Public Health recommends that individuals refrain from using any vaping or e-cigarette products, particularly THC-containing products from informal sources, while this investigation is ongoing.

OBJECTIVE: The 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 1987-2018. 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-1990 s, the number of B Readers has declined and the mean age and years certified has 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.

BACKGROUND: Age at female puberty is associated with adult morbidities, including breast cancer and diabetes. Hormonally active chemicals are suspected of altering pubertal timing. We examined whether persistent organic pollutants (POPs) are associated with age at menarche in a longitudinal study. METHODS: We analyzed data for females enrolled at age 6-8 years in the Breast Cancer and Environment Research Program from California and Ohio. Participants were followed annually 2004-2013 and provided serum (mean age 7.8 years) for measurement of polychlorinated biphenyl (PCB), organochlorine pesticide (OCP), and polybrominated diphenyl ether (PBDE) concentrations. Age of menarche was assigned based on parental and participant reported dates and ages of menarche. Adjusted hazard ratios (aHRs) for menarchal onset were calculated with Cox proportional regression. Body mass index (BMI), potentially on the causal pathway, was added to parallel analyses. RESULTS: Age of menarche was later with higher summed PCB levels (median 11.9 years in quartile 1 [Q1] versus 12.7 in quartile 4 [Q4]) and OCP levels (12.1 years versus 12.4, respectively). When adjusting for all covariates except BMI, higher POP concentrations were associated with later age at menarche (Q4 versus Q1 aHRs: PBDEs 0.75 [95% CI 0.58, 0.97], PCBs 0.67 [95% CI 0.5, 0.89], and OCPs 0.66 [95% CI 0.50, 0.89]). Additional adjustment for BMI attenuated aHRs; PCB aHR approached the null. CONCLUSION: Findings revealed later onset of menarche with higher concentrations of certain POPs, possibly through an association with BMI. Altered pubertal timing may have long lasting effects on reproductive health and disease risk, so continued attention is important for understanding the biological processes affected by hormonally active chemicals.

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 (DEMS) cohort. METHODS: We analyzed data on 10,779 male miners from 8 non-metal, non-coal 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 non-metal miners, are consistent with the hypothesis that interventions to eliminate exposures to diesel exhaust and respirable dust would reduce IHD mortality risk.

The use of electronic nicotine delivery systems continues to gain popularity, and there is concern for potential health risks from inhalation of aerosol and vapor produced by these devices. An analytical method was developed that provided quantitative and qualitative chemical information for characterizing the volatile constituents of bulk electronic cigarette liquids (e-liquids) using a static headspace technique. Volatile organic compounds (VOCs) were screened from a convenience sample of 146 e-liquids by equilibrating 1 g of each e-liquid in amber vials for 24 h at room temperature. Headspace was transferred to an evacuated canister and quantitatively analyzed for 20 VOCs as well as tentatively identified compounds using a preconcentrator/gas chromatography/mass spectrometer system. The e-liquids were classified into flavor categories including brown, fruit, hybrid dairy, menthol, mint, none, tobacco, and other. 2,3-Butanedione was found at the highest concentration in brown flavor types, but was also found in fruit, hybrid dairy, and menthol flavor types. Benzene was observed at concentrations that are concerning given the carcinogenicity of this compound (max 1.6 ppm in a fruit flavor type). The proposed headspace analysis technique coupled with partition coefficients allows for a rapid and sensitive prediction of the volatile content in the liquid. The technique does not require onerous sample preparation, dilution with organic solvents, or sampling at elevated temperatures. Static headspace screening of e-liquids allows for the identification of volatile chemical constituents which is critical for identifying and controlling emission of potentially hazardous constituents in the workplace.

Persons who died of Ebola virus disease at home in rural communities in Liberia and Guinea resulted in more secondary infections than persons admitted to Ebola treatment units. Intensified monitoring of contacts of persons who died of this disease in the community is an evidence-based approach to reduce virus transmission in rural communities.

We measured the reproduction number before and after interventions were implemented to reduce Ebola transmission in 9 outbreaks in Liberia during 2014. We evaluated risk factors for secondary cases and the association between patient admission to an Ebola treatment unit (ETU) and survival. The reproduction number declined 94% from 1.7 (95% CI 1.1-2.6) to 0.1 (95% CI 0.02-0.6) after interventions began. The risk for secondary infections was 90% lower for patients admitted to an ETU (risk ratio 0.1, 95% CI 0.04-0.3) than for those who died in the community. The case-fatality rate was 68% (95% CI 60-74), and ETU admission was associated with a 50% reduction in death (hazard ratio 0.5, 95% CI 0.4-0.8). Isolation and treatment of Ebola patients had the dual benefit of interrupting community transmission and improving survival.

On August 24, 2014, at 3:20 a.m., a magnitude 6.0 earthquake struck California, with its epicenter in Napa County (1). The earthquake was the largest to affect the San Francisco Bay area in 25 years and caused significant damage in Napa and Solano counties, including widespread power outages, five residential fires, and damage to roadways, waterlines, and 1,600 buildings (2). Two deaths resulted (2). On August 25, Napa County Public Health asked the California Department of Public Health (CDPH) for assistance in assessing postdisaster health effects, including earthquake-related injuries and effects on mental health. On September 23, Solano County Public Health requested similar assistance. A household-level Community Assessment for Public Health Emergency Response (CASPER) was conducted for these counties in two cities (Napa, 3 weeks after the earthquake, and Vallejo, 6 weeks after the earthquake). Among households reporting injuries, a substantial proportion (48% in Napa and 37% in western Vallejo) reported that the injuries occurred during the cleanup period, suggesting that increased messaging on safety precautions after a disaster might be needed. One fifth of respondents overall (27% in Napa and 9% in western Vallejo) reported one or more traumatic psychological exposures in their households. These findings were used by Napa County Mental Health to guide immediate-term mental health resource allocations and to conduct public training sessions and education campaigns to support persons with mental health risks following the earthquake. In addition, to promote community resilience and future earthquake preparedness, Napa County Public Health subsequently conducted community events on the earthquake anniversary and provided outreach workers with psychological first aid training.

West Africa is experiencing its first epidemic of Ebola virus disease (Ebola). As of February 9, Liberia has reported 8,864 Ebola cases, of which 3,147 were laboratory-confirmed. Beginning in August 2014, the Liberia Ministry of Health and Social Welfare (MOHSW), supported by CDC, the World Health Organization (WHO), and others, began systematically investigating and responding to Ebola outbreaks in remote areas. Because many of these areas lacked mobile telephone service, easy road access, and basic infrastructure, flexible and targeted interventions often were required. Development of a national strategy for the Rapid Isolation and Treatment of Ebola (RITE) began in early October. The strategy focuses on enhancing capacity of county health teams (CHT) to investigate outbreaks in remote areas and lead tailored responses through effective and efficient coordination of technical and operational assistance from the MOHSW central level and international partners. To measure improvements in response indicators and outcomes over time, data from investigations of 12 of 15 outbreaks in remote areas with illness onset dates of index cases during July 16-November 20, 2014, were analyzed. The times to initial outbreak alerts and durations of the outbreaks declined over that period while the proportions of patients who were isolated and treated increased. At the same time, the case-fatality rate in each outbreak declined. Implementation of strategies, such as RITE, to rapidly respond to rural outbreaks of Ebola through coordinated and tailored responses can successfullyreduce transmission and improve outcomes.

We commend the overall evaluation by Cherrie et al. (2013) of the current occupational exposure limits (OELs) for respirable poorly-soluble low toxicity (PSLT) particles. As described in that paper, the epidemiological studies provide compelling evidence that exposure to PSLT at the current OELs has been associated with adverse health effects, including pulmonary fibrosis and lung function deficits. In contrast to Cherrie et al. (2013), we discuss here that the chronic inhalation studies in animals also provide evidence of the adverse pulmonary effects of PSLT. | For example, we would like to clarify or correct the following statements (p. 688, 2nd column): | (1) …the phenomenon of rat lung overload has little relevance for human lung response at high lung burden of low-toxicity dust. | This statement is not entirely supported by the scientific evidence. While it is correct that differences have been observed in the rat and human lung clearance and retention kinetics for respirable particles, these differences have been well described, and can be accounted for, using lung dosimetry models in humans (Kuempel et al., 2001a,b; Gregoratto et al., 2010, 2011) and rats (Tran et al., 1999, 2000; Anjilvel and Asgharian, 1995). Because of the slower pulmonary clearance in humans, particles can build up in the lungs at exposures below those that would cause overloading in rats (Snipes, 1989; Kuempel et al., 2000; Kuempel and Tran, 2002). This build up is associated with the movement of particles into the alveolar interstitium of the mammalian lungs (Nikula et al., 1997, 2001). Only at overloading do the particle lung burdens in rats reach the higher levels that have been reported in coal miners, i.e., up to 10 mg g−1 lungs or more in rats (Morrow, 1988; Muhle et al., 1990; Bellmann et al., 1991; Oberdörster et al., 1992) and in humans (Attfield et al., 1994; Kuempel et al., 1997; Tran and Buchanan, 2000).

Because our original publication (1) generated considerable interest over the past two years, we now provide additional data from our nested case-control study that are valuable in evaluating the relation between diesel exhaust exposure and lung cancer. Here we include results based on alternative exposure metrics (Table 1) and alternative approaches for adjusting for cigarette smoking as a confounder (Table 2), for comparison with results that appeared in Table 3 of Silverman et al. (1).

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 ever 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.

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. (Am J Public Health. Published online ahead of print May 16, 2013: e1-e6. doi:10.2105/AJPH.2012.301051).

We read with interest the recent report by Kirchner et al [1] in BJR, which describes the results of the International Labour Office (ILO) classifications of routine digital chest radiographs as well as readings of contrast-enhanced chest CT images among a convenience-based sample of 85 tobacco smokers who were clinically referred for chest imaging, primarily for known or suspected cancer. Chest radiographs for the study were obtained using a storage phosphor digital system, and hard copies were printed from the digital image files via a laser printer. Transparencies were then displayed and classified by two board-certified radiologists. It was not described whether or not the classifications were made independently, and if so, how the readings were summarised. The data were presented as a correlation (see Figure 2) between pack-years and the ILO classification scores, which was found to be significant. Only slightly more than half of the data points were visible in this figure, leaving the reader to infer that some of the points presented represented more than one value. However, the actual distribution of the data cannot be inferred with the presentation of the results in this format. Additionally, there was no mention of how recognised confounding factors, such as age or occupational exposures, were accounted for in the correlation. | A number of previous studies have shown that, in the absence of occupational dust exposures, cigarette smoking and increasing age may lead to a one- or two-subcategory increase in the profusion of irregular type opacities. However, our reading of this report raised a number of concerns regarding study methods, including image acquisition and classification, as well as conclusions.

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. (Am J Public Health. Published online ahead of print March 8, 2012: e1-e5. doi:10.2105/AJPH.2011.300427).

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 mcg/m(3)-y category compared with the reference category (0 to <20 mcg/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 mcg/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.

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 mcg/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 mcg/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.

Exposure to respirable elemental carbon (REC), a component of diesel exhaust (DE), was assessed for an epidemiologic study investigating the association between DE and mortality, particularly from lung cancer, among miners at eight mining facilities from the date of dieselization (1947-1967) through 1997. To provide insight into the quality of the estimates for use in the epidemiologic analyses, several approaches were taken to evaluate the exposure assessment process and the quality of the estimates. An analysis of variance was conducted to evaluate the variability of 1998-2001 REC measurements within and between exposure groups of underground jobs. Estimates for the surface exposure groups were evaluated to determine if the arithmetic means (AMs) of the REC measurements increased with increased proximity to, or use of, diesel-powered equipment, which was the basis on which the surface groups were formed. Estimates of carbon monoxide (CO) (another component of DE) air concentrations in 1976-1977, derived from models developed to predict estimated historical exposures, were compared to 1976-1977 CO measurement data that had not been used in the model development. Alternative sets of estimates were developed to investigate the robustness of various model assumptions. These estimates were based on prediction models using: (i) REC medians rather AMs, (ii) a different CO:REC proportionality than a 1:1 relation, and (iii) 5-year averages of historical CO measurements rather than modeled historical CO measurements and DE-related determinants. The analysis of variance found that in three of the facilities, most of the between-group variability in the underground measurements was explained by the use of job titles. There was relatively little between-group variability in the other facilities. The estimated REC AMs for the surface exposure groups rose overall from 1 to 5 mcg/m(3) as proximity to, and use of, diesel equipment increased. The alternative estimates overall were highly correlated (~0.9) with the primary set of estimates. The median of the relative differences between the 1976-1977 CO measurement means and the 1976-1977 estimates for six facilities was 29%. Comparison of estimated CO air concentrations from the facility-specific prediction models with historical CO measurement data found an overall agreement similar to that observed in other epidemiologic studies. Other evaluations of components of the exposure assessment process found moderate to excellent agreement. Thus, the overall evidence suggests that the estimates were likely accurate representations of historical personal exposure levels to DE and are useful for epidemiologic analyses.

BACKGROUND: Digital radiography systems are replacing traditional film for chest radiographic monitoring in the recognition of pneumoconiosis. METHODS: To further investigate previous findings regarding the equivalence of film screen radiographs (FSR) and storage phosphor computed radiographs (CR), FSR and CR from 172 underground coal miners were classified independently by seven NIOSH-approved B Readers, using the International Labour Office (ILO) classification of radiographs of pneumoconiosis. RESULTS: More CR were classified as "good" quality compared to FSR (prevalence ratio (PR) =1.5; 95% CI, 1.4-1.6; P<0.001). B Readers showed good overall agreement on scoring small opacity profusion using CR versus FSR, (weighted kappa =0.58, 95% CI 0.54-0.62). Significantly more irregular opacities (compared to rounded) were classified using CR images compared to FSR (PR=1.3; 95% CI=1.1-1.6; P=0.01). Similarly, the smallest size opacities (width <1.5 mm, p and s-type) were reported more frequently using CR vs. FSR images (PR=1.3; 95% CI= 1.1-1.5; P<0.001). Inter- and intra-reader agreement was lower with respect to the classification of shape/size than for small opacity profusion. Overall, inter- and intra-reader variability did not significantly differ using CR versus FSR. CONCLUSIONS: Under optimal conditions using standardized methods and equipment, reader visualization of small pneumoconiotic opacities does not appear to meaningfully differ whether using CR or FSR. Variability in ILO classifications between imaging modalities appears considerably less than variability between readers. The well-documented challenge of reader variability does not appear to be resolved through the use of digital imaging alone, and additional approaches must be evaluated.

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 US coal miners using dust exposure, tenure, miner's age and coal rank as predictors. chi(2) 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.

This report provides an overview of the exposure assessment process for an epidemiologic study that investigated mortality, with a special focus on lung cancer, associated with diesel exhaust (DE) exposure among miners. Details of several components are provided in four other reports. A major challenge for this study was the development of quantitative estimates of historical exposures to DE. There is no single standard method for assessing the totality of DE, so respirable elemental carbon (REC), a component of DE, was selected as the primary surrogate in this study. Air monitoring surveys at seven of the eight study mining facilities were conducted between 1998 and 2001 and provided reference personal REC exposure levels and measurements for other agents and DE components in the mining environment. (The eighth facility had closed permanently prior to the surveys.) Exposure estimates were developed for mining facility/department/job/year combinations. A hierarchical grouping strategy was developed for assigning exposure levels to underground jobs [based on job titles, on the amount of time spent in various areas of the underground mine, and on similar carbon monoxide (CO, another DE component) concentrations] and to surface jobs (based on the use of, or proximity to, diesel-powered equipment). Time trends in air concentrations for underground jobs were estimated from mining facility-specific prediction models using diesel equipment horsepower, total air flow rates exhausted from the underground mines, and, because there were no historical REC measurements, historical measurements of CO. Exposures to potentially confounding agents, i.e. respirable dust, silica, radon, asbestos, and non-diesel sources of polycyclic aromatic hydrocarbons, also were assessed. Accuracy and reliability of the estimated REC exposures levels were evaluated by comparison with several smaller datasets and by development of alternative time trend models. During 1998-2001, the average measured REC exposure level by facility ranged from 40 to 384 mu g m(-3) for the underground workers and from 2 to 6 mu g m(-3) for the surface workers. For one prevalent underground job, 'miner operator', the maximum annual REC exposure estimate by facility ranged up to 685% greater than the corresponding 1998-2001 value. A comparison of the historical CO estimates from the time trend models with 1976-1977 CO measurements not used in the modeling found an overall median relative difference of 29%. Other comparisons showed similar levels of agreement. The assessment process indicated large differences in REC exposure levels over time and across the underground operations. Method evaluations indicated that the final estimates were consistent with those from alternative time trend models and demonstrated moderate to high agreement with external data.

Air monitoring surveys were conducted between 1998 and 2001 at seven non-metal mining facilities to assess exposure to respirable elemental carbon (REC), a component of diesel exhaust (DE), for an epidemiologic study of miners exposed to DE. Personal exposure measurements were taken on workers in a cross-section of jobs located underground and on the surface. Air samples taken to measure REC were also analyzed for respirable organic carbon (ROC). Concurrent measurements to assess exposure to nitric oxide (NO) and nitrogen dioxide (NO2), two gaseous components of DE, were also taken. The REC measurements were used to develop quantitative estimates of average exposure levels by facility, department, and job title for the epidemiologic analysis. Each underground job was assigned to one of three sets of exposure groups from specific to general: (i) standardized job titles, (ii) groups of standardized job titles combined based on the percentage of time in the major underground areas, and (iii) larger groups based on similar area carbon monoxide (CO) air concentrations. Surface jobs were categorized based on their use of diesel equipment and proximity to DE. A total of 779 full-shift personal measurements were taken underground. The average REC exposure levels for underground jobs with five or more measurements ranged from 31 to 58 mu g m(-3) at the facility with the lowest average exposure levels and from 313 to 488 mu g m(-3) at the facility with the highest average exposure levels. The average REC exposure levels for surface workers ranged from 2 to 6 mu g m(-3) across the seven facilities. There was much less contrast in the ROC compared with REC exposure levels measured between surface and underground workers within each facility, as well as across the facilities. The average ROC levels underground ranged from 64 to 195 mu g m(-3), while on the surface, the average ROC levels ranged from 38 to 71 mu g m(-3) by facility, an similar to 2- to 3-fold difference. The average NO and NO2 levels underground ranged from 0.20 to 1.49 parts per million (ppm) and from 0.10 to 0.60 ppm, respectively, and were similar to 10 times higher than levels on the surface, which ranged from 0.02 to 0.11 ppm and from 0.01 to 0.06 ppm, respectively. The ROC, NO, and NO2 concentrations underground were correlated with the REC levels (r = 0.62, 0.71, and 0.62, respectively). A total of 80% of the underground jobs were assigned an exposure estimate based on measurements taken for the specific job title or for other jobs with a similar percentage of time spent in the major underground work areas. The average REC exposure levels by facility were from 15 to 64 times higher underground than on the surface. The large contrast in exposure levels measured underground versus on the surface, along with the differences between the mining facilities and between underground jobs within the facilities resulted in a wide distribution in the exposure estimates for evaluation of exposure-response relationships in the epidemiologic analyses.

Diesel exhaust (DE) has been implicated as a potential lung carcinogen. However, the exact components of DE that might be involved have not been clearly identified. In the past, nitrogen oxides (NOx) and carbon oxides (COx) were measured most frequently to estimate DE, but since the 1990s, the most commonly accepted surrogate for DE has been elemental carbon (EC). We developed quantitative estimates of historical exposure levels of respirable elemental carbon (REC) for an epidemiologic study of mortality, particularly lung cancer, among diesel-exposed miners by back-extrapolating 1998-2001 REC exposure levels using historical measurements of carbon monoxide (CO). The choice of CO was based on the availability of historical measurement data. Here, we evaluated the relationship of REC with CO and other current and historical components of DE from side-by-side area measurements taken in underground operations of seven non-metal mining facilities. The Pearson correlation coefficient of the natural log-transformed (Ln)REC measurements with the Ln(CO) measurements was 0.4. The correlation of REC with the other gaseous, organic carbon (OC), and particulate measurements ranged from 0.3 to 0.8. Factor analyses indicated that the gaseous components, including CO, together with REC, loaded most strongly on a presumed 'Diesel exhaust' factor, while the OC and particulate agents loaded predominantly on other factors. In addition, the relationship between Ln(REC) and Ln(CO) was approximately linear over a wide range of REC concentrations. The fact that CO correlated with REC, loaded on the same factor, and increased linearly in log-log space supported the use of CO in estimating historical exposure levels to DE.

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 m(3) 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.

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.

Traditional film-screen radiography (FSR) has been useful in the recognition and evaluation of interstitial lung diseases, but is becoming increasingly obsolete. To evaluate the applicability of storage phosphor digital computed radiography (CR) images in the recognition of small lung opacities, we compared image quality and the profusion of small opacities between FSR and CR radiographs.We screened 1388 working coal miners during the course of the study with FSR and CR images obtained on the same day from all participants. Each traditional chest film was independently interpreted by two of eight experienced readers using the International Labour Office (ILO) classification of radiographs of pneumoconiosis, as were CR images displayed on medical-grade computer monitors.The prevalence of small opacities (ILO category 1/0 or greater) did not differ between the two imaging modalities (5.2%, for FSR and 4.8% for soft copy CR, p>0.50). Inter-reader agreement was also similar between FSR and CR. Significant differences between image modalities were observed in the shape of small opacities, and in the proportion of miners demonstrating high opacity profusion (category ≥2/1).Our results indicate that, with appropriate attention to image acquisition and soft copy display, CR digital radiography can be equivalent to FSR in the identification of small interstitial lung opacities.

OBJECTIVES: Epidemiologic 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 Office Classification of Radiographs of Pneumoconioses. CXRs from 1980-2008 of 90,973 participating miners were studied, focusing 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 in the 1990s (PR=2.5; 95% CI=1.7-3.7) and after 1999 (PR=4.1; 95% CI=3.0-5.6), 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 1980's (PR=4.4; 95% CI=3.1-6.3) and 1990's (PR=3.8; 95% CI=2.1-6.8) 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 U.S. coal miners are being exposed to excessive amounts of respirable crystalline silica.