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.

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.

Prenatal Exposure to Poly- and Perfluoroalkyl Substances (2009-2014) and Vaccine Antibody Titers of Measles, Mumps, Rubella, and Varicella in Children Four to Eight Years Old from the Healthy Start Cohort.

BACKGROUND: Prenatal exposures to certain poly- and perfluoroalkyl substances (PFAS) are associated with reduced humoral responses to some childhood immunizations. OBJECTIVE: We estimated associations between prenatal PFAS exposure and child antibody titers for measles, mumps, rubella (MMR), and varicella after immunization. METHODS: We measured serum antibody titers of 145 children (4-8 y old) enrolled in the Healthy Start cohort in Colorado, whose mothers had PFAS quantified mid-pregnancy (2009-2014). We used linear and logistic regression models to assess the relationship between five PFAS detected in >65% of mothers and continuous or non-high-censored ("low") antibody titers and quantile g-computation to evaluate the overall effect of the PFAS mixture. RESULTS: Median concentrations of individual PFAS were at or below the median reported among females in the United States. After receiving two vaccine doses, seropositive levels of antibodies were detected among most (93%-100%) children. Each log-unit increase in perfluorononanoate was associated with 2.09 [95% confidence interval (CI): 1.13, 3.87] times higher odds of a low measles titer, and each log-unit increase in perfluorooctanoate was associated with 2.46 (95% CI: 1.28, 4.75) times higher odds of a low mumps titer. Odds ratios for all other PFAS were elevated, but CIs included the null. Each quartile increase in the PFAS mixture was associated with 1.35 (95% CI: 0.80, 2.26) times higher odds of a low measles titer and 1.44 (95% CI: 0.78, 2.64) times higher odds of a low mumps titer. No significant associations were observed between PFAS and varicella or rubella antibodies. In stratified analyses, associations were negative among female children, except for perfluorohexane sulfonate and varicella, whereas they were positive among males. DISCUSSION: Some prenatal PFAS were associated with lower antibody titers among fully immunized children. The potential for immunotoxic effects of PFAS requires further investigation in a larger study, because exposure is ubiquitous globally. https://doi.org/10.1289/EHP12863.

Prenatal exposure to poly- and perfluoroalkyl substances and the incidence of asthma in early childhood.

EXPOSURE TO POLY: and perfluoroalkyl substances (PFAS) in early life may increase the risk of childhood asthma, but evidence has been inconsistent. We estimated associations between maternal serum concentrations of PFAS during pregnancy and clinician-diagnosed asthma incidence in offspring through age eight. We included 597 mother-child pairs with PFAS quantified in mid-pregnancy serum and childhood medical records reviewed for asthma diagnoses. We used separate Cox proportional hazards models to assess the relationship between log-transformed concentrations of five PFAS and the incidence of asthma. We estimated associations between the PFAS mixture and clinician-diagnosed asthma incidence using quantile-based g-computation. PFAS concentrations were similar to those among females in the US general population. Seventeen percent of children (N = 104) were diagnosed with asthma during follow-up. Median (interquartile range) duration of follow-up was 4.7 (4.0, 6.2) years, and median age at asthma diagnosis was 1.7 (0.9, 2.8) years. All adjusted hazard ratios (HRs) were elevated, but all 95% confidence intervals (CI) included the null. The HR (95% CI) of asthma for a one-quartile increase in the PFAS mixture was 1.17 (0.86, 1.61). In this cohort of children followed to eight years of age, prenatal PFAS concentrations were not significantly associated with incidence of clinician-diagnosed asthma.

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.

Deployment-Related Respiratory Disease: Where Are We?

Military personnel and veterans who have deployed to Afghanistan, Iraq, and parts of Southwest Asia (SWA) since 1990 are at risk of developing a host of respiratory symptoms and deployment-related respiratory diseases (DRRDs). This review aims to summarize our current understanding of DRRD and inform pulmonary practitioners of recent updates to DRRD screening, diagnosis, evaluation, and management. The most common respiratory diseases in these patients include asthma, chronic sinonasal disease, laryngeal disease/dysfunction, and distal lung disease. Pulmonary function testing and chest imaging are the most commonly used diagnostic tools, but techniques such as lung clearance index testing via multiple breath washout, forced oscillation testing/impulse oscillometry, and quantitative chest computed tomography (CT) assessment appear promising as noninvasive modalities to aid in lung disease detection in this population. We also summarize guidance on conducting an occupational and deployment exposure history as well as recommendations for testing. Finally, we discuss the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act of 2022 (PACT Act) that includes a list of health conditions that are "presumptively" considered to be related to SWA military deployment toxic exposures, and provide resources for clinicians who evaluate and treat patients with DRRD.

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.

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.

Vaccination Trends and Family-Level Characteristics Associated With Incomplete or Delayed Childhood Immunizations: The Healthy Start Study.

PURPOSE: Assess family-level factors associated with childhood immunization schedule adherence. DESIGN: Prospective cohort; Setting; The Healthy Start study enrolled 1,410 pregnant women in Denver, Colorado 2009-2014. SUBJECTS: Children with available vaccination data in medical records (0-6 years old). MEASURES: Vaccine schedule completion and compliance. ANALYSIS: Logistic regression comparing family-level factors that differ based on vaccine schedule adherence. RESULTS: Most immunizations required in Colorado for school entry were below national completion goals with 61.8% of participants (n = 532/861) completing the full vaccination series. Most participants received the first dose of individual vaccines on time (73.5% - 90.7%), but fewer received all doses on time (21.0% - 39.5%). Factors associated with not completing the vaccination series (OR [95% CI]) included: in-utero exposure to cigarette smoke (1.97 [1.41, 2.75]), single parent household (1.70 [1.21, 2.38]), children identified as non-White (Hispanic 1.40 [1.01, 1.94]; Black 1.88 [1.24, 2.85]; Other 2.17 [1.34, 3.49]), mothers not working outside the home (1.98 [1.46, 2.67]), and household income <$70,000 per year (<$40,000 1.93 [1.35, 2.75]; $40,000-$70,000 1.64 [1.09, 2.46]). Conversely, families with more educated mothers (0.47 [0.29, 0.76]) and older parents (0.97 [0.94, 0.99]) were significantly more likely to complete the series. CONCLUSIONS: These findings may help identify groups at risk of immunization schedule non-adherence and may be used to target education/advocacy campaigns to reduce hesitancy and increase access in these populations.

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.

Quantitative imaging analysis detects subtle airway abnormalities in symptomatic military deployers.

BACKGROUND: Exposure to inhalational hazards during post-9/11 deployment to Southwest Asia and Afghanistan puts military personnel at risk for respiratory symptoms and disease. Pulmonary function and qualitative chest high resolution computed tomography (HRCT) are often normal in "deployers" with persistent respiratory symptoms. We explored the utility of quantitative HRCT imaging markers of large and small airways abnormalities, including airway wall thickness, emphysema, and air trapping, in symptomatic deployers with clinically-confirmed lung disease compared to controls. METHODS: Chest HRCT images from 45 healthy controls and 82 symptomatic deployers with asthma, distal lung disease or both were analyzed using Thirona Lung quantification software to calculate airway wall thickness (by Pi10), emphysema (by percentage of lung volume with attenuation < -950 Hounsfield units [LAA%-950]), and three parameters of air trapping (expiratory/inspiratory total lung volume and mean lung density ratios, and LAA%-856). SAS v.9.4 was used to compare demographic and clinical characteristics between deployers and controls using Chi-Square, Fisher Exact or t-tests. Linear regression was used to assess relationships between pulmonary function and quantitative imaging findings. RESULTS: Gender and smoking status were not statistically significantly different between groups, but deployers were significantly younger than controls (42 vs 58 years, p < 0.0001), had higher body mass index (31 vs 28 kg/m2, p = 0.01), and had fewer total smoking pack-years (8 vs. 26, p = 0.007). Spirometric measures were not statistically significantly different between groups. Pi10 and LAA%-950 were significantly elevated in deployers compared to controls in unadjusted analyses, with the emphysema measure remaining significantly higher in deployers after adjustment for age, sex, smoking, BMI, and expiratory total lung volume. Air trapping parameters were more common in control images, likely due to differences in age and smoking between groups. Among deployers, LAA%-950 and Pi10 were significantly correlated with spirometric markers of obstruction based on ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) and/or percent predicted FEV1. CONCLUSIONS: Quantitative chest HRCT imaging analysis identifies emphysema in deployers with asthma and distal lung disease, and may be useful in detecting and monitoring deployment-related lung disease in a population where spirometry is typically normal.

Small airways and airspace inflammation and injury distinguish lung histopathology in deployed military personnel from healthy and diseased lungs.

The link between military deployment to Southwest Asia and Afghanistan, and the risk for lung disease, including bronchiolitis, is increasingly well-recognized. However, histopathologic features that distinguish deployment-related lung diseases from other diseases affecting the small airways and airspaces are uncertain. A computer-based scoring system was developed to characterize surgical lung biopsy findings in 65 soldiers with persistent respiratory symptoms following military deployment ("deployers"). Deployer lung biopsies were compared to those from 8 patients with chronic hypersensitivity pneumonitis (cHP), 10 with smoking-related respiratory bronchiolitis, 11 with autoimmune or post-transplant obliterative bronchiolitis, and 10 normal donor lungs. Upper, middle, and lower lobe-specific findings in deployer samples were analyzed to inform optimum biopsy location choice for future patients. Surgical lung biopsies from symptomatic deployed military service members were distinguished by a combination of small airways abnormalities including smooth muscle hypertrophy (SMH), peribronchiolar metaplasia (PBM), and lymphocytic inflammation, often with constrictive/obliterative (C/O) and/or respiratory bronchiolitis (43.1%), granulomatous inflammation (38.5%), and moderate/severe emphysema (46.2%, mainly in nonsmokers). Lymphocytic pleural inflammation was common (89.2%), and vascular abnormalities occurred in nearly one-third. Histopathologic features in deployers were most strongly overlapping with cases of cHP, both showing granulomatous inflammation, PBM, and emphysema. SMH along with C/O and respiratory bronchiolitis were common in deployers but not in cHP cases. In deployers, there were significantly higher odds of small airways injury in the lower lobe compared with upper lobe samples.

Pathology and Mineralogy Demonstrate Respirable Crystalline Silica Is a Major Cause of Severe Pneumoconiosis in U.S. Coal Miners.

Rationale: The reasons for resurgent coal workers' pneumoconiosis and its most severe forms, rapidly progressive pneumoconiosis and progressive massive fibrosis (PMF), in the United States are not yet fully understood. Objectives: To compare the pathologic and mineralogic features of contemporary coal miners with severe pneumoconiosis with those of their historical counterparts. Methods: Lung pathology specimens from 85 coal miners with PMF were included for evaluation and analysis. We compared the proportion of cases with pathologic and mineralogic findings in miners born between 1910 and 1930 (historical) with those in miners born in or after 1930 (contemporary). Results: We found a significantly higher proportion of silica-type PMF (57% vs. 18%; P < 0.001) among contemporary miners compared with their historical counterparts. Mineral dust alveolar proteinosis was also more common in contemporary miners compared with their historical counterparts (70% vs. 37%; P < 0.01). In situ mineralogic analysis showed that the percentage (26.1% vs. 17.8%; P < 0.01) and concentration (47.3 × 108 vs. 25.8 × 108 particles/cm3; P = 0.036) of silica particles were significantly greater in specimens from contemporary miners compared with their historical counterparts. The concentration of silica particles was significantly greater when silica-type PMF, mineral dust alveolar proteinosis, silicotic nodules, or immature silicotic nodules were present (P < 0.05). Conclusions: Exposure to respirable crystalline silica appears causal in the unexpected surge of severe disease in contemporary miners. Our findings underscore the importance of controlling workplace silica exposure to prevent the disabling and untreatable adverse health effects afflicting U.S. coal miners.