Resting diffusing capacity and severity of radiographic disease predict gas exchange abnormalities with exercise in former US coal miners.

BACKGROUND: The US Department of Labor (DOL) does not fund diffusing capacity (DLCO) or metabolic measurements from cardiopulmonary exercise testing (CPET) for coal miners' disability evaluations. Although exercise arterial blood gas testing is covered, many miners are unable to perform maximal tests, and sampling at peak exercise can be challenging. We explored the relationship between resting DLCO, radiographic disease severity, and CPET abnormalities in former US coal miners. METHODS: We analyzed data from miners evaluated between 2005 and 2015. Multivariable linear and logistic regression analyses were used to examine relationships between percent predicted (pp) forced expiratory volume in 1 s (FEV1pp), DLCOpp, VO2maxpp, A-a oxygen gradient (A-a)pp, dead space fraction (Vd/Vt), disabling oxygen tension (PO2), and radiographic findings of pneumoconiosis. RESULTS: Data from 2015 male coal miners was analyzed. Mean tenure was 28 years (SD 8.6). Thirty-twopercent had an abnormal A-a gradient (>150 pp), 20% had elevated Vd/Vt (>0.33), and 34% a VO2max < 60 pp. DLCOpp strongly predicted a disabling PO2, with an odds ratio (OR) of 2.33 [2.09-2.60], compared to 1.18 [1.08-1.29] for FEV1. Each increase in subcategory of small opacity (simple) pneumoconiosis increased the odds of a disabling PO2 by 42% [1.29-1.57], controlling for age, body mass index, pack-years of tobacco smoke exposure, and years of coal mine employment. CONCLUSIONS: DLCO is the best resting pulmonary function test predictor of CPET abnormalities. Radiographic severity of pneumoconiosis was also associated with CPET abnormalities. These findings support funding DLCO testing for impairment and suggest the term "small opacity" should replace "simple" pneumoconiosis to reflect significant associations with impairment.

Longitudinal changes in lung function following post-9/11 military deployment in symptomatic veterans.

RATIONALE: Exposure to burn pit smoke, desert and combat dust, and diesel exhaust during military deployment to Southwest Asia and Afghanistan (SWA) can cause deployment-related respiratory diseases (DRRDs) and may confer risk for worsening lung function after return. METHODS: Study subjects were SWA-deployed veterans who underwent occupational lung disease evaluation (n = 219). We assessed differences in lung function by deployment exposures and DRRD diagnoses. We used linear mixed models to assess changes in lung function over time. RESULTS: Most symptomatic veterans reported high intensity deployment exposure to diesel exhaust and burn pit particulates but had normal post-deployment spirometry. The most common DRRDs were deployment-related distal lung disease involving small airways (DDLD, 41%), deployment-related asthma (DRA, 13%), or both DRA/DDLD (24%). Those with both DDLD/DRA had the lowest estimated mean spirometry measurements five years following first deployment. Among those with DDLD alone, spirometry measurements declined annually, adjusting for age, sex, height, weight, family history of lung disease, and smoking. In this group, the forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) ratio declined 0.2% per year. Those with more intense inhalational exposure had more abnormal lung function. We found significantly lower estimated FVC and total lung capacity five years following deployment among active duty participants (n = 173) compared to those in the reserves (n = 26). CONCLUSIONS: More intense inhalational exposures were linked with lower post-deployment lung function. Those with distal lung disease (DDLD) experienced significant longitudinal decline in FEV1/FVC ratio, but other DRRD diagnosis groups did not.

Particle Morphology and Elemental Analysis of Lung Tissue from Post-9/11 Military Personnel with Biopsy-Proven Lung Disease.

The relationship between exposure to inhaled inorganic particulate matter and risk for deployment-related lung disease in military personnel is unclear due in part to difficulties characterizing individual exposure to airborne hazards. We evaluated the association between self-reported deployment exposures and particulate matter (PM) contained in lung tissue from previously deployed personnel with lung disease ("deployers"). The PM in deployer tissues was compared to normal lung tissue PM using the analytical results of scanning electron microscopy and inductively coupled plasma mass spectrometry. The majority of PM phases for both the deployers and the controls were sub-micrometer in size and were compositionally classified as aluminum and zirconium oxides, carbonaceous particles, iron oxides, titanium oxides, silica, other silicates, and other metals. The proportion of silica and other silicates was significantly higher in the retained dust from military veterans with biopsy-confirmed deployment-related lung disease compared to the control subjects. Within the deployer population, those who had combat jobs had a higher total PM burden, though the difference was not statistically significant. These findings have important implications for understanding the role of inhaled inorganic dusts in the risk for lung injury in previously deployed military veterans.

Characterizing Lung Particulates Using Quantitative Microscopy in Coal Miners With Severe Pneumoconiosis.

CONTEXT.­: Current approaches for characterizing retained lung dust using pathologists' qualitative assessment or scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS) have limitations. OBJECTIVE.­: To explore polarized light microscopy coupled with image-processing software, termed quantitative microscopy-particulate matter (QM-PM), as a tool to characterize in situ dust in lung tissue of US coal miners with progressive massive fibrosis. DESIGN.­: We developed a standardized protocol using microscopy images to characterize the in situ burden of birefringent crystalline silica/silicate particles (mineral density) and carbonaceous particles (pigment fraction). Mineral density and pigment fraction were compared with pathologists' qualitative assessments and SEM/EDS analyses. Particle features were compared between historical (born before 1930) and contemporary coal miners, who likely had different exposures following changes in mining technology. RESULTS.­: Lung tissue samples from 85 coal miners (62 historical and 23 contemporary) and 10 healthy controls were analyzed using QM-PM. Mineral density and pigment fraction measurements with QM-PM were comparable to consensus pathologists' scoring and SEM/EDS analyses. Contemporary miners had greater mineral density than historical miners (186 456 versus 63 727/mm3; P = .02) and controls (4542/mm3), consistent with higher amounts of silica/silicate dust. Contemporary and historical miners had similar particle sizes (median area, 1.00 versus 1.14 µm2; P = .46) and birefringence under polarized light (median grayscale brightness: 80.9 versus 87.6; P = .29). CONCLUSIONS.­: QM-PM reliably characterizes in situ silica/silicate and carbonaceous particles in a reproducible, automated, accessible, and time/cost/labor-efficient manner, and shows promise as a tool for understanding occupational lung pathology and targeting exposure controls.

First Annual PACT Act Research Symposium on Veterans Health: A Colorado PACT Act Collaboration (CoPAC) Initiative.

In response to the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act being signed into law, several research groups in Colorado organized the First Annual PACT Act Research Symposium for Veteran Health. The 2-day symposium was interested in research relevant to military exposures with a primary focus on respiratory and mental health. Information on the PACT Act, data sources in the Department of Veteran Affairs and DOD, and research opportunities at the Veteran Affairs were presented. The morning session centered on respiratory health, highlighting research conducted over the last two decades regarding deployment-related respiratory diseases. Despite the high prevalence of mental health disorders among Veterans, information presented during the afternoon sessions on mental health highlighted the dearth of research to date regarding psychological health and military-related exposures. Policymakers, clinicians, and researchers were encouraged to adopt a life-course approach when conceptualizing physical and psychological exposures. On the second day of meetings, a smaller group of participants discussed next steps in military exposure research, as well as priorities for future research. Per the latter, recommendations for future research were made regarding the need for more precise exposure characterization, longitudinal data collection, and efforts to increase understanding regarding disease pathogenesis, as well as the impact of exposures across multiple organs. Such efforts will require interdisciplinary collaboration.

Racial Differences in Respiratory Impairment, Pneumoconiosis, and Federal Compensation for Western U.S. Indigenous Coal Miners.

Rationale: Indigenous populations in the United States face numerous health disparities, but the health of Indigenous workers is less well understood. In a recent surveillance study of active Indigenous coal miners, 3% had coal workers' pneumoconiosis/black lung, and 9% had respiratory impairment. However, occupational lung disease prevalence among Indigenous coal miners has not been directly compared with that among other race/ethnicity groups. Coal miners who are totally disabled from black lung may qualify for U.S. Department of Labor (DOL) compensation benefits, but it is unclear how current federal spirometry criteria affect qualification for Indigenous coal miners.Objectives: To compare findings of pneumoconiosis and respiratory impairment in Indigenous and non-Indigenous coal miners in the western United States and assess federal compensation qualification for Indigenous miners using different spirometry standards.Methods: We used voluntary medical surveillance data from 2002 to 2023 to compare the adjusted odds of pneumoconiosis and respiratory impairment between Indigenous/non-Indigenous coal miners. We examined the proportion of Indigenous miners meeting DOL criteria for federal compensation using different spirometry standards.Results: We identified 691 western U.S. coal miners with at least one year of coal mining employment, 289 Indigenous and 402 non-Indigenous (96% White/Hispanic). Indigenous miners had a greater odds ratio for pneumoconiosis for each additional decade of life (2.47 [95% confidence interval (CI), 1.66-3.68]) compared with non-Indigenous coal miners (1.48 [95% CI, 1.19-1.85]). For each decade, Indigenous coal miners also had a greater adjusted odds ratio for respiratory impairment (1.67 [95% CI, 1.25-2.24]) than non-Indigenous miners (1.06 [95% CI, 0.90-1.25]). Indigenous miners had an additional decline of 71 ml (95% CI, 6-136 ml) in forced expiratory volume in 1 second for each decade of life compared with non-Indigenous coal miners. Using the DOL-mandated Knudson (1976) spirometry standard rather than an Indigenous-specific standard, 6 of 18 (33%) Indigenous miners would not qualify for federal compensation.Conclusions: Indigenous coal miners experience greater adjusted odds for pneumoconiosis and respiratory impairment per decade of life and greater decline in forced expiratory volume in 1 second despite lower smoking rates. Structural inequities exist in federal spirometry requirements for Indigenous miners seeking DOL black lung benefits. Regulatory reform is needed to address barriers to compensation for these underrepresented workers.

Pathologic Findings in Severe Coal Workers' Pneumoconiosis in Contemporary US Coal Miners.

CONTEXT.­: The pathology of coal workers' pneumoconiosis (CWP) and its most severe form-progressive massive fibrosis (PMF)-in US coal miners has changed in recent years. Severe disease is occurring in younger miners and has been linked to an increase in silica dust exposure. OBJECTIVE.­: To update the description of the pathologic features of CWP in contemporary miners compared to historical miners. DESIGN.­: This study is a retrospective expert classification of lung tissue from 85 historical and contemporary coal miners with PMF. Significant pathologic features were scored by using a standardized instrument with consensus achieved for major findings, including newly defined categories of PMF as coal-type, mixed-type, and silica-type. RESULTS.­: Pathologic features associated with silica dust exposure, including silica-type PMF, mineral dust alveolar proteinosis (MDAP), and immature (early stage) silicotic nodules were increased in contemporary miners. Detailed descriptions of the pathology of contemporary CWP with illustrative figures are provided. CONCLUSIONS.­: Silica-related pathologies are more common in contemporary miners. Severe forms of CWP can be detected by subtyping PMF lesions (if present) or by identification of mature and immature silicotic nodules, coal mine dust-related alveolar proteinosis, and severe inflammation in coal miners' lungs. Silica-type PMF cases showed significantly higher levels of MDAP than either mixed- or coal-type PMF (P < .001). High profusion of birefringent silica/silicate particles was observed more frequently in cases with immature (early stage) silicotic nodules (P = .04). Severe inflammation was also significantly increased in contemporary miners (P = .03). Our findings underscore the urgent need to revise current exposure limits and monitoring of respirable crystalline silica in US coal mines.

Findings on High Resolution Computed Tomography in Symptomatic Veterans with Deployment-Related Lung Disease.

PURPOSE: Military deployment to dusty, austere environments in Southwest Asia and Afghanistan is associated with symptomatic airways diseases including asthma and bronchiolitis. The utility of chest high-resolution computed tomographic (HRCT) imaging in lung disease diagnosis in this population is poorly understood. We investigated visual assessment of HRCT for identifying deployment-related lung disease compared with healthy controls. MATERIALS AND METHODS: Chest HRCT images from 46 healthy controls and 45 symptomatic deployed military personnel with clinically confirmed asthma and/or biopsy-confirmed distal lung disease were scored by 3 independent thoracic radiologists. We compared demographic and clinical characteristics and frequency of imaging findings between deployers and controls, and between deployers with asthma and those with biopsy-confirmed distal lung disease, using χ2, Fisher exact or t tests, and logistic regression where appropriate. We also analyzed inter-rater agreement for imaging findings. RESULTS: Expiratory air trapping was the only chest CT imaging finding that was significantly more frequent in deployers compared with controls. None of the 24 deployers with biopsy-confirmed bronchiolitis and/or granulomatous pneumonitis had HRCT findings of inspiratory mosaic attenuation or centrilobular nodularity. Only 2 of 21 with biopsy-proven emphysema had emphysema on HRCT. CONCLUSIONS: Compared with surgical lung biopsy, visual assessment of HRCT showed few abnormalities in this small cohort of previously deployed symptomatic veterans with normal or near-normal spirometry.

Historical shift in pathological type of progressive massive fibrosis among coal miners in the USA.

BACKGROUND: Pneumoconiosis among coal miners in the USA has been resurgent over the past two decades, despite modern dust controls and regulatory standards. Previously published studies have suggested that respirable crystalline silica (RCS) is a contributor to this disease resurgence. However, evidence has been primarily indirect, in the form of radiographic features. METHODS: We obtained lung tissue specimens and data from the National Coal Workers' Autopsy Study. We evaluated specimens for the presence of progressive massive fibrosis (PMF) and used histopathological classifications to type these specimens into coal-type, mixed-type and silica-type PMF. Rates of each were compared by birth cohort. Logistic regression was used to assess demographic and mining characteristics associated with silica-type PMF. RESULTS: Of 322 cases found to have PMF, study pathologists characterised 138 (43%) as coal-type, 129 (40%) as mixed-type and 55 (17%) as silica-type PMF. Among earlier birth cohorts, coal-type and mixed-type PMF were more common than silica-type PMF, but their rates declined in later birth cohorts. In contrast, the rate of silica-type PMF did not decline in cases from more recent birth cohorts. More recent year of birth was significantly associated with silica-type PMF. CONCLUSIONS: Our findings demonstrate a shift in PMF types among US coal miners, from a predominance of coal- and mixed-type PMF to a more commonly encountered silica-type PMF. These results are further evidence of the prominent role of RCS in the pathogenesis of pneumoconiosis among contemporary US coal miners.

Global Trends in Occupational Lung Disease.

Lung diseases caused by workplace exposure are too often mis- or underdiagnosed due in part to nonexistent or inadequate health surveillance programs for workers. Many of these diseases are indistinguishable from those that occur in the general population and are not recognized as being caused at least in part by occupational exposures. More than 10% of all lung diseases are estimated to result from workplace exposures. This study reviews recent estimates of the burden of the most important occupational lung diseases using data published by United Nations specialized agencies as well as the Global Burden of Disease studies. We focus on occupational chronic respiratory disease of which chronic obstructive lung disease and asthma are the most significant. Among occupational cancers, lung cancer is the most common, and is associated with more than 10 important workplace carcinogens. Classic occupational interstitial lung diseases such as asbestosis, silicosis, and coal workers' pneumoconiosis still comprise a substantial burden of disease in modern industrial societies, while other occupational causes of pulmonary fibrosis and granulomatous inflammation are frequently misclassified as idiopathic. Occupational respiratory infections gained prominence during the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic, eclipsing influenza and tuberculosis and other less common workplace infectious agents. The most significant risks are workplace exposures to particulate matter, gases, and fumes as well as occupational carcinogens and asthmagens. We present data on the burden of disease measured by deaths attributable to occupational respiratory disease as well as disability-adjusted years of life lost. Where available, prevalence and incidence data are also presented. These diseases are unique in that they are theoretically 100% preventable if appropriate exposure controls and workplace medical surveillance are implemented. This remains a continuing challenge globally and requires steadfast commitment on the part of government, industry, organized labor, and the medical profession.

Mining Tenure and Job Duties Differ Among Contemporary and Historic Underground Coal Miners With Progressive Massive Fibrosis.

OBJECTIVE: To characterize differences in mining jobs and tenure between contemporary (born 1930+, working primarily with modern mining technologies) and historic coal miners with progressive massive fibrosis (PMF). METHODS: We classified jobs as designated occupations (DOs) and non-DOs based on regulatory sampling requirements. Demographic, occupational characteristics, and histopathological PMF type were compared between groups. RESULTS: Contemporary miners ( n = 33) had significantly shorter mean total (30.4 years vs 37.1 years, P = 0.0006) and underground (28.8 years vs 35.8 years, P = 0.001) mining tenure compared with historic miners ( n = 289). Silica-type PMF was significantly more common among miners in non-DOs (30.1% vs 15.8%, P = 0.03) and contemporary miners (58.1% vs 15.2%, P < 0.0001). CONCLUSIONS: Primary jobs changed over time with the introduction of modern mining technologies and likely changed exposures for workers. Elevated crystalline silica exposures are likely in non-DOs and require attention.

Increased odds of mortality from non-malignant respiratory disease and lung cancer are highest among US coal miners born after 1939.

OBJECTIVES: Coal miners suffer increased mortality from non-malignant respiratory diseases (NMRD), including pneumoconioses and chronic obstructive pulmonary disease, compared with the US population. We characterised mortality trends from NMRD, lung cancer and ischaemic heart disease (IHD) using data from the Federal Black Lung Program, National Coal Workers' Health Surveillance Program and the National Death Index. METHODS: We compared mortality ORs (MORs) for NMRD, lung cancer and IHD in former US coal miners to US white males. MORs were computed for the study period 1979-2017 by birth cohort (<1920, 1920-1929, 1930-1939, ≥1940), with a subanalysis restricted to Central Appalachia. RESULTS: The study population totalled 235 550 deceased miners, aged >45 years. Odds of death from NMRD and lung cancer across all miner birth cohorts averaged twice those of US males. In Central Appalachia, MORs significantly increased across birth cohorts. There was an eightfold increase in odds of death from NMRD among miners born after 1940 (MORBC≥1940 8.25; 95% CI 7.67 to 8.87). Miners with progressive massive fibrosis (PMF) were younger at death than those without PMF (74 vs 78 years; p<0.0001). We observed a pattern of reduced MORs from IHD in coal miners compared with national and regional counterparts. CONCLUSION: US coal miners have excess mortality from NMRD and lung cancer compared with total US and Appalachian populations. Mortality is highest in the most recent birth cohorts, perhaps reflecting increased rates of severe pneumoconiosis.

Unexplained dyspnea linked to mitochondrial myopathy following military deployment to Southwest Asia and Afghanistan.

We identified a case of probable mitochondrial myopathy (MM) in a soldier with dyspnea and reduced exercise tolerance through cardiopulmonary exercise testing (CPET) following Southwest Asia (SWA) deployment. Muscle biopsy showed myopathic features. We compared demographic, occupational exposure, and clinical characteristics in symptomatic military deployers with and without probable MM diagnosed by CPET criteria. We evaluated 235 symptomatic military personnel who deployed to SWA and/or Afghanistan between 2010 and 2021. Of these, 168 underwent cycle ergometer maximal CPET with an indwelling arterial line. We defined probable MM based on five CPET criteria: arterial peak exercise lactate >12 mEq/L, anaerobic threshold (AT) ≤50%, maximum oxygen consumption (VO2max ) <95% predicted, oxygen (O2) pulse percent predicted (pp) at least 10% lower than heart rate pp, and elevated ventilatory equivalent for O2 at end exercise (VE/VO2 ≥ 40). We characterized demographics, smoking status/pack-years, spirometry, and deployment exposures, and used descriptive statistics to compare findings in those with and without probable MM. We found 9/168 (5.4%) deployers with probable MM. Compared to symptomatic deployers without probable MM, they were younger (p = 0.0025) and had lower mean BMI (p = 0.02). They had a higher mean forced expiratory volume (FEV1)pp (p = 0.02) and mean arterial oxygen partial pressure (PaO2) at maximum exercise (p = 0.0003). We found no significant differences in smoking status, deployment frequency/duration, or inhalational exposures. Our findings suggest that mitochondrial myopathy may be a cause of dyspnea and reduced exercise tolerance in a subset of previously deployed military personnel. CPET with arterial line may assist with MM diagnosis and management.

Consensus Statements on Deployment-Related Respiratory Disease, Inclusive of Constrictive Bronchiolitis: A Modified Delphi Study.

BACKGROUND: The diagnosis of constrictive bronchiolitis (CB) in previously deployed individuals, and evaluation of respiratory symptoms more broadly, presents considerable challenges, including using consistent histopathologic criteria and clinical assessments. RESEARCH QUESTION: What are the recommended diagnostic workup and associated terminology of respiratory symptoms in previously deployed individuals? STUDY DESIGN AND METHODS: Nineteen experts participated in a three-round modified Delphi study, ranking their level of agreement for each statement with an a priori definition of consensus. Additionally, rank-order voting on the recommended diagnostic approach and terminology was performed. RESULTS: Twenty-five of 28 statements reached consensus, including the definition of CB as a histologic pattern of lung injury that occurs in some previously deployed individuals while recognizing the importance of considering alternative diagnoses. Consensus statements also identified a diagnostic approach for the previously deployed individual with respiratory symptoms, distinguishing assessments best performed at a local or specialty referral center. Also, deployment-related respiratory disease (DRRD) was proposed as a broad term to subsume a wide range of potential syndromes and conditions identified through noninvasive evaluation or when surgical lung biopsy reveals evidence of multicompartmental lung injury that may include CB. INTERPRETATION: Using a modified Delphi technique, consensus statements provide a clinical approach to possible CB in previously deployed individuals. Use of DRRD provides a broad descriptor encompassing a range of postdeployment respiratory findings. Additional follow-up of individuals with DRRD is needed to assess disease progression and to define other features of its natural history, which could inform physicians better and lead to evolution in this nosology.

Demographic, exposure and clinical characteristics in a multinational registry of engineered stone workers with silicosis.

OBJECTIVES: To investigate differences in workplace exposure, demographic and clinical findings in engineered stone (ES) workers from a multinational consortium using the Engineered Stone Silicosis Investigators (ESSI) Global Silicosis Registry. METHODS: With ethics board approval in Israel, Spain, Australia and the USA, ES workers ages 18+ with a physician diagnosis of work-related silicosis were enrolled. Demographic, occupational, radiologic, pulmonary function and silica-related comorbidity data were compared cross-sectionally among countries using analysis of variance, Fisher's exact tests and logistic regression. RESULTS: Among 169 ES workers with silicosis, most were men, with mean age 51.7 (±11.4) years. Mean work tenure in stone fabrication or masonry was 19.9 (±9.8) years. Different methods of case ascertainment explained some inter-country differences, for example, workers in Queensland, Australia with a state-based surveillance program were likely to be identified earlier and with shorter work tenure. Overall, 32.5% of workers had progressive massive fibrosis, the most severe form of dust-related pneumoconiosis, of whom 18.5% reported ≤10 years of work tenure. Lung function impairment including restriction, reduced diffusion capacity and hypoxaemia was common, as was autoimmunity. CONCLUSIONS: Findings from a multinational registry represent a unique effort to compare demographic, exposure and clinical information from ES workers with silicosis, and suggest a substantial emerging population of workers worldwide with severe and irreversible silica-associated diseases. This younger worker population is at high risk for disease progression, multiple comorbidities and severe disability. The ESSI registry provides an ongoing framework for investigating epidemiological trends and developing prospective studies for prevention and treatment of these workers.