Accelerated silicosis in sandblasters: Pathology, mineralogy, and clinical correlates.

BACKGROUND: With increasing reports of accelerated and acute silicosis, PMF, and autoimmune disease among coal miners and silica-exposed countertop workers, we present previously incompletely-described pulmonary pathology of accelerated silicosis and correlations with mineralogy, radiography, and disease progression in 46 Texas oilfield pipe sandblasters who were biopsied between 1988 and 1995. METHODS: Worker examinations included pulmonary function tests, chest X-ray (CXR), high-resolution computed tomography (HRCT), and Gallium-67 scans. Quantitative mineralogic analysis of pulmonary parenchymal burden of silica, silicates, and metal particles used scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM EDS). RESULTS: Workers had clinical deterioration after <10 years exposure in dusty workplaces. Although initial CXR was normal in 54%, Gallium-67 scans were positive in 68% of those with normal CXR, indicating pulmonary inflammation. The histology of accelerated silicosis is diffuse interstitial infiltration of macrophages filled with weakly birefringent particles with or without silicotic nodules or alveolar proteinosis. Lung silica concentrations were among the highest in our database, showing a dose-response relationship with CXR, HRCT, and pathologic changes (macrophages, fibrosis, and silicotic nodules). Radiographic scores and diffusing capacity worsened during observation. Silica exposure was intensified, patients presented younger, with shorter exposure, more severe clinical abnormalities, higher lung particle burdens, and more rapid progression in a subset of patients exposed to recycled blasting sand. CONCLUSIONS: Accelerated silicosis may present with a normal CXR despite significant histopathology. Multivariable analyses showed silica, and not other particles, is the driver of observed radiologic, physiologic, and histologic outcomes. Eliminating this preventable disease requires higher physician, public health, and societal awareness.

Interstitial pulmonary disease and aluminum trihydrate exposure: A single case report and detailed workplace analysis.

Exposure to aluminum compounds is clearly associated with pulmonary function decrements, and several animal models document possible mechanisms of aluminum- compound-induced pulmonary toxicity. Nevertheless, disagreements remain about the precise mechanism by which exposures lead to damage. We present a strong case for attributing a case of interstitial pulmonary disease to occupational exposure to aluminum trihydrate. This report follows a 2014 publication of another case of interstitial pulmonary disease following a similar exposure. Our patient eventually underwent double lung transplantation nearly 5 years postexposure. Detailed pulmonary particulate elemental analysis suggested that aluminum metal, including aluminum trihydrate, was the most likely cause. A detailed assessment of the worker's relevant occupational exposures accompanies this case report.

Evidence for Environmental-Human Microbiota Transfer at a Manufacturing Facility with Novel Work-related Respiratory Disease.

Rationale: Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease.Objectives: As part of a public health investigation of a manufacturing facility, we performed a cross-sectional study using paired environmental and human sampling to evaluate the cross-pollination of microbes between the environment and the host and possible effects on lung pathology present among workers.Methods: Workplace environmental microbiota were evaluated in air and MWF samples. Human microbiota were evaluated in lung tissue samples from workers with respiratory symptoms found to have lymphocytic bronchiolitis and alveolar ductitis with B-cell follicles and emphysema, in lung tissue samples from control subjects, and in skin, nasal, and oral samples from 302 workers from different areas of the facility. In vitro effects of MWF exposure on murine B cells were assessed.Measurements and Main Results: An increased similarity of microbial composition was found between MWF samples and lung tissue samples of case workers compared with control subjects. Among workers in different locations within the facility, those that worked in the machine shop area had skin, nasal, and oral microbiota more closely related to the microbiota present in the MWF samples. Lung samples from four index cases and skin and nasal samples from workers in the machine shop area were enriched with Pseudomonas, the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation in vitro, a hallmark cell subtype found in the pathology of index cases.Conclusions: Evaluation of a manufacturing facility with a cluster of workers with respiratory disease supports cross-pollination of microbes from MWF to humans and suggests the potential for exposure to these microbes to be a health hazard.

Severe lung disease characterized by lymphocytic bronchiolitis, alveolar ductitis, and emphysema (BADE) in industrial machine-manufacturing workers.

BACKGROUND: A cluster of severe lung disease occurred at a manufacturing facility making industrial machines. We aimed to describe disease features and workplace exposures. METHODS: Clinical, functional, radiologic, and histopathologic features were characterized. Airborne concentrations of thoracic aerosol, metalworking fluid, endotoxin, metals, and volatile organic compounds were measured. Facility airflow was assessed using tracer gas. Process fluids were examined using culture, polymerase chain reaction, and 16S ribosomal RNA sequencing. RESULTS: Five previously healthy male never-smokers, ages 27 to 50, developed chest symptoms from 1995 to 2012 while working in the facility's production areas. Patients had an insidious onset of cough, wheeze, and exertional dyspnea; airflow obstruction (mean FEV1 = 44% predicted) and reduced diffusing capacity (mean = 53% predicted); and radiologic centrilobular emphysema. Lung tissue demonstrated a unique pattern of bronchiolitis and alveolar ductitis with B-cell follicles lacking germinal centers, and significant emphysema for never-smokers. All had chronic dyspnea, three had a progressive functional decline, and one underwent lung transplantation. Patients reported no unusual nonoccupational exposures. No cases were identified among nonproduction workers or in the community. Endotoxin concentrations were elevated in two air samples; otherwise, exposures were below occupational limits. Air flowed from areas where machining occurred to other production areas. Metalworking fluid primarily grew Pseudomonas pseudoalcaligenes and lacked mycobacterial DNA, but 16S analysis revealed more complex bacterial communities. CONCLUSION: This cluster indicates a previously unrecognized occupational lung disease of yet uncertain etiology that should be considered in manufacturing workers (particularly never-smokers) with airflow obstruction and centrilobular emphysema. Investigation of additional cases in other settings could clarify the cause and guide prevention.

Gadolinium released from MR contrast agents is deposited in brain tumors: in situ demonstration using scanning electron microscopy with energy dispersive X-ray spectroscopy.

BACKGROUND: gadolinium (Gd)-containing MRI contrast agents (GdCA) are widely used in studies of brain tumors, and a number of reports suggest that under certain conditions, such as renal failure, Gd may be released from GdCA into patient's tissues. Whether this may happen in abnormal tissues in the absence of renal failure has not been studied. PURPOSE: to test the hypothesis that the local retention of GdCA resulting from brain tumor-associated alterations in the blood-brain barrier (BBB) may result in the deposition of Gd released from the GdCA, depending on stability. MATERIAL AND METHODS: in this retrospective study, 30 selected brain tumor biopsies from 28 patients (taken before and after an institutional switch from a less stable to an intermediate stable GdCA) were searched for Gd-containing deposits using scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS). Relevant histories and laboratory results were obtained through institutional electronic records. Associations between the presence of deposits and other variables were tested for statistical significance using the two-tailed Fisher's exact test. RESULTS: insoluble deposits containing Gd associated with phosphorus and calcium were found in seven biopsies from five patients. These deposits were found in patients with estimated GFRs above 53 ml/min, and were detected more often in those receiving GdCA before the switch from a less stable to an intermediate stable GdCA (P = 0.04), and may be more frequent in patients receiving more than one contrast-enhanced MR scan (P = 0.15). CONCLUSION: Gd-containing deposits are present in brain tumors following contrast-enhanced MR scans in patients without severe renal disease. Further studies are needed to assess the clinical importance of the deposits we observed and to determine whether they are also found in other conditions that alter the integrity of the BBB.

Indicators of airborne fungal concentrations in urban homes: understanding the conditions that affect indoor fungal exposures.

Indoor fungal exposure can compromise respiratory health. Low-income urban areas are of concern because of high asthma and allergy rates and housing disrepair. Understanding the conditions that affect indoor fungal exposures is important for assessing health risks and for developing mitigation strategies. We examined the types and concentrations of airborne fungi inside and outside of homes in low-income areas of Syracuse, NY as well as the effect of snow cover on fungal levels. At 103 homes, air samples for viable fungi were collected, occupants were interviewed and homes were inspected for visible mold, musty odors, water problems and other factors. Multivariable logistic regression was used to relate high fungal levels to home conditions. Predominant indoor fungi included Cladosporium, Penicillium, Aspergillus, Alternaria and hyaline unknowns. Basidiomycetes and an uncommon genus Acrodontium were also found frequently due to analysis methods developed for this project. With snow cover, outdoor total fungal levels were depressed and indoor concentrations were three times higher than outdoor on average with a maximum of 29 times higher. Visible mold was related to elevated levels of Penicillium (OR 4.11 95% CI 1.37-14.0) and bacteria (OR 3.79 95% CI 1.41-11.2). Musty, moldy odors were associated with elevated concentrations of total fungi (OR 3.48 95% CI 1.13-11.6) and basidiomycetes. Cockroaches, an indicator of moisture, were associated with elevated levels of Penicillium (OR 3.66 95% CI 1.16-13.1) and Aspergillus (OR 4.36 95% CI 1.60-13.4). Increasing relative humidity was associated with higher concentrations of Penicillium, yeasts and basidiomycetes. Visible mold, musty odors, indoor humidity and cockroaches are modifiable factors that were important determinants of indoor fungal exposures. Indoor air investigators should interpret indoor:outdoor fungal ratios cautiously when snow cover is present.

Indoor airborne fungi and wheeze in the first year of life among a cohort of infants at risk for asthma.

In studies worldwide, respiratory outcomes such as cough, wheeze and asthma have been consistently linked to mold exposure. Young children spend most of their time indoors and may be particularly vulnerable. We evaluated the associations between exposure to airborne fungal levels and episodes of wheezing in a cohort of 103 infants at risk for asthma (due to maternal history of asthma), living primarily in low-income urban settings. Using a new protocol that facilitates identification of rare and slow-growing fungi, we measured the type and concentration of cultured fungi in home air samples taken early in the infant's first year of life. We also inspected the homes for visible mold, water damage and other housing and environmental conditions. All homes had measurable indoor airborne fungi and 73%, had some sign of mold, water damage, dampness or a musty odor. One or more episodes of wheeze during the first year of life were observed in 38% of infants. Multiple logistic regression showed high indoor levels of Penicillium were a significant risk factor for wheeze (OR 6.18; 95% CI: 1.34-28.46) in the first year of life after controlling for season of sampling, smoking, endotoxin levels, day care attendance and confounders. Acrodontium, a rarely reported fungal genus, was detected in 18% of study homes, and was associated with wheeze in unadjusted models (OR 2.75; 95% CI 0.99-7.61), but not after adjustment for confounders. Total fungal levels, visually observed mold, dampness, water damage or musty odors were not significantly associated with wheeze.

Issues in design and implementation in an urban birth cohort study: the Syracuse AUDIT project.

The Syracuse AUDIT (Assessment of Urban Dwellings for Indoor Toxics) project is a birth cohort study of wheezing in the first year of life in a low-income urban setting. Such studies are important because of the documented serious risks to children's health and the lack of attention and published work on asthma development and intervention in communities of this size. We studied 103 infants of mothers with asthma, living predominantly in inner-city households. Our study combines measurements of a large panel of indoor environmental agents, in-home infant assessments, and review of all prenatal and postnatal medical records through the first year of life. We found multiple environmental pollution sources and potential health risks in study homes including high infant exposure to tobacco smoke. The prevalence of maternal smoking during pregnancy was 54%; postnatal environmental tobacco smoke (ETS) exposure was nearly 90%. The majority (73%) of homes showed signs of dampness. Participants' lives were complicated by poverty, unemployment and single-parenthood. Thirty-three percent of fathers were not involved with their children, and 62% of subjects moved at least once during the study period. These socioeconomic issues had an impact on project implementation and led to modification of study eligibility criteria. Extensive outreach, follow up, and relationship-building were required in order to recruit and retain families and resulted in considerable work overload for study staff. Our experiences implementing the project will inform further studies on this and other similar populations. Future reports on this cohort will address the role of multiple environmental variables and their effects on wheezing outcome during the first year of life.