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.

Work-related adverse respiratory health outcomes at a machine manufacturing facility with a cluster of bronchiolitis, alveolar ductitis and emphysema (BADE).

OBJECTIVES: Four machine manufacturing facility workers had a novel occupational lung disease of uncertain aetiology characterised by lymphocytic bronchiolitis, alveolar ductitis and emphysema (BADE). We aimed to evaluate current workers' respiratory health in relation to job category and relative exposure to endotoxin, which is aerosolised from in-use metalworking fluid. METHODS: We offered a questionnaire and spirometry at baseline and 3.5 year follow-up. Endotoxin exposures were quantified for 16 production and non-production job groups. Forced expiratory volume in one second (FEV1) decline ≥10% was considered excessive. We examined SMRs compared with US adults, adjusted prevalence ratios (aPRs) for health outcomes by endotoxin exposure tertiles and predictors of excessive FEV1 decline. RESULTS: Among 388 (89%) baseline participants, SMRs were elevated for wheeze (2.5 (95% CI 2.1 to 3.0)), but not obstruction (0.5 (95% CI 0.3 to 1.1)). Mean endotoxin exposures (range: 0.09-28.4 EU/m3) were highest for machine shop jobs. Higher exposure was associated with exertional dyspnea (aPR=2.8 (95% CI 1.4 to 5.7)), but not lung function. Of 250 (64%) follow-up participants, 11 (4%) had excessive FEV1 decline (range: 403-2074 mL); 10 worked in production. Wheeze (aPR=3.6 (95% CI 1.1 to 12.1)) and medium (1.3-7.5 EU/m3) endotoxin exposure (aPR=10.5 (95% CI 1.3 to 83.1)) at baseline were associated with excessive decline. One production worker with excessive decline had BADE on subsequent lung biopsy. CONCLUSIONS: Lung function loss and BADE were associated with production work. Relationships with relative endotoxin exposure indicate work-related adverse respiratory health outcomes beyond the sentinel disease cluster, including an incident BADE case. Until causative factors and effective preventive strategies for BADE are determined, exposure minimisation and medical surveillance of affected workforces are recommended.

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.

Fatal chlorine gas exposure at a metal recycling facility: Case report.

At least four workers at a metal recycling facility were hospitalized and one died after exposure to chlorine gas when it was accidentally released from an intact, closed-valved cylinder being processed for scrap metal. This unintentional chlorine gas release marks at least the third such incident at a metal recycling facility in the United States since 2010. We describe the fatal case of the worker whose clinical course was consistent with acute respiratory distress syndrome (ARDS) following exposure to high concentrations of chlorine gas. This case report emphasizes the potential risk of chlorine gas exposure to metal recycling workers by accepting and processing intact, closed-valved containers. The metal recycling industry should take steps to increase awareness of this established risk to prevent future chlorine gas releases. Additionally, public health practitioners and clinicians should be aware that metal recycling workers are at risk for chlorine gas exposure.

Elemental properties of copper slag and measured airborne exposures at a copper slag processing facility.

In 1974, the National Institute for Occupational Safety and Health recommended a ban on the use of abrasives containing >1% silica, giving rise to abrasive substitutes like copper slag. We present results from a National Institute for Occupational Safety and Health industrial hygiene survey at a copper slag processing facility that consisted of the collection of bulk samples for metals and silica; and full-shift area and personal air samples for dust, metals, and respirable silica. Carcinogens, suspect carcinogens, and other toxic elements were detected in all bulk samples, and area and personal air samples. Area air samples identified several areas with elevated levels of inhalable and respirable dust, and respirable silica: quality control check area (236 mg/m3 inhalable; 10.3 mg/m3 respirable; 0.430 mg/m3 silica), inside the screen house (109 mg/m3 inhalable; 13.8 mg/m3 respirable; 0.686 mg/m3 silica), under the conveyor belt leading to the screen house (19.8 mg/m3 inhalable), and inside a conveyor access shack (11.4 mg/m3 inhalable; 1.74 mg/m3 respirable; 0.067 mg/m3 silica). Overall, personal dust samples were lower than area dust samples and did not exceed published occupational exposure limits. Silica samples collected from a plant hand and a laborer exceeded the American Conference of Governmental Industrial Hygienist Threshold Limit Value of 0.025 µg/m3. All workers involved in copper slag processing (n = 5) approached or exceeded the Occupational Safety and Health Administration permissible exposure limit of 10 µg/m3 for arsenic (range: 9.12-18.0 µg/m3). Personal total dust levels were moderately correlated with personal arsenic levels (Rs = 0.70) and personal respirable dust levels were strongly correlated with respirable silica levels (Rs = 0.89). We identified multiple areas with elevated levels of dust, respirable silica, and metals that may have implications for personal exposure at other facilities if preventive measures are not taken. To our knowledge, this is the first attempt to characterize exposures associated with copper slag processing. More in-depth air monitoring and health surveillance is needed to understand occupational exposures and health outcomes in this industry.

Elemental properties of coal slag and measured airborne exposures at two coal slag processing facilities.

In 1974, the National Institute for Occupational Safety and Health recommended a ban on the use of silica sand abrasives containing >1% silica due to the risk of silicosis. This gave rise to substitutes including coal slag. An Occupational Safety and Health Administration investigation in 2010 uncovered a case cluster of suspected pneumoconiosis in four former workers at a coal slag processing facility in Illinois, possibly attributable to occupational exposure to coal slag dust. This article presents the results from a National Institute for Occupational Safety and Health industrial hygiene survey at the same coal slag processing facility and a second facility. The industrial hygiene survey consisted of the collection of: (a) bulk samples of unprocessed coal slag, finished granule product, and settled dust for metals and silica; (b) full-shift area air samples for dust, metals, and crystalline silica; and (c) full-shift personal air samples for dust, metals, and crystalline silica. Bulk samples consisted mainly of iron, manganese, titanium, and vanadium. Some samples had detectable levels of arsenic, beryllium, cadmium, and cobalt. Unprocessed coal slags from Illinois and Kentucky contained 0.43-0.48% (4,300-4,800 mg/kg) silica. Full-shift area air samples identified elevated total dust levels in the screen (2-38 mg/m3) and bag house (21 mg/m3) areas. Full-shift area air samples identified beryllium, chromium, cobalt, copper, iron, nickel, manganese, and vanadium. Overall, personal air samples for total and respirable dust (0.1-6.6 mg/m3 total; and 0.1-0.4 mg/m3 respirable) were lower than area air samples. All full-shift personal air samples for metals and silica were below published occupational exposure limits. All bulk samples of finished product granules contained less than 1% silica, supporting the claim coal slag may present less risk for silicosis than silica sand. We note that the results presented here are solely from two coal slag processing facilities, and more in-depth air monitoring is needed to better characterize occupational exposure to coal slag dust, metals, and silica at similar facilities.

Respiratory symptoms and lung function abnormalities related to work at a flavouring manufacturing facility.

OBJECTIVES: To better understand respiratory symptoms and lung function in flavouring manufacturing workers. METHODS: We offered a questionnaire and lung function testing to the current workforce of a flavouring manufacturing facility that had transitioned away from diacetyl and towards substitutes in recent years. We examined symptoms, spirometric parameters and diffusing capacity measurements by exposure variables, including facility tenure and time spent daily in production areas. We used linear and logistic regression to develop final models adjusted for age and smoking status. RESULTS: A total of 367 (93%) current workers participated. Shortness of breath was twice as common in those with tenure ≥ 7 years (OR 2.0, 95% CI 1.1 to 3.6). Other chest symptoms were associated with time spent daily in production. Participants who spent ≥ 1 h daily in production areas had twice the odds of any spirometric abnormality (OR 2.3; 95% CI 1.1 to 5.3) and three times the odds of low diffusing capacity (OR 2.8; 95% CI 0.9 to 9.4) than other participants. Mean spirometric parameters were significantly lower in those with tenure ≥ 7 years and those who spent ≥ 1 h daily in production. Mean diffusing capacity parameters were significantly lower in those with tenure ≥ 7 years. Differences in symptoms and lung function could not be explained by age, smoking status or employment at another flavouring plant. CONCLUSIONS: Symptoms and lung function findings were consistent with undiagnosed or subclinical obliterative bronchiolitis and associated with workplace exposures. Further efforts to lower exposures to flavouring chemicals, including diacetyl substitutes, are warranted.

Correcting diacetyl concentrations from air samples collected with NIOSH method 2557.

Diacetyl (2,3-butanedione), a diketone chemical used to impart a buttery taste in many flavoring mixtures, has been associated with bronchiolitis obliterans in several industrial settings. For workplace evaluations in 2000-2006, National Institute for Occupational Safety and Health (NIOSH) investigators used NIOSH Method 2557, a sampling and analytical method for airborne diacetyl utilizing carbon molecular sieve sorbent tubes. The method was subsequently suspected to progressively underestimate diacetyl concentrations with increasing sampling site humidity. Since underestimation of worker exposure may lead to overestimation of respiratory health risk in quantitative exposure-effect analyses, correction of the diacetyl concentrations previously reported with Method 2557 is essential. We studied the effects of humidity and sample storage duration on recovery of diacetyl from experimental air samples taken from a dynamically generated controlled test atmosphere that allowed control of diacetyl concentration, temperature, relative humidity, sampling duration, and sampling flow rate. Samples were analyzed with Method 2557, and results were compared with theoretical test atmosphere diacetyl concentration. After fitting nonlinear models to the experimental data, we found that absolute humidity, diacetyl concentration, and days of sample storage prior to extraction affected diacetyl recovery as did sampling flow rate to a much smaller extent. We derived a mathematical correction procedure to more accurately estimate historical workplace diacetyl concentration based on laboratory-reported concentrations of diacetyl using Method 2557, and sample site temperature and relative humidity (to calculate absolute humidity), as well as days of sample storage prior to extraction in the laboratory. With this correction procedure, quantitative risk assessment for diacetyl can proceed using corrected exposure levels for air samples previously collected and analyzed using NIOSH Method 2557 for airborne diacetyl.

Evaluation of flavorings-related lung disease risk at six microwave popcorn plants.

OBJECTIVE: After investigating fixed airways obstruction in butter flavoring-exposed workers at a microwave popcorn plant, we sought to further characterize lung disease risk from airborne butter-flavoring chemicals. METHODS: We analyzed data from medical and environmental surveys at six microwave popcorn plants (including the index plant). RESULTS: Respiratory symptom and airways obstruction prevalences were higher in oil and flavorings mixers with longer work histories and in packaging-area workers near nonisolated tanks of oil and flavorings. Workers were affected at five plants, one with mixing-area exposure to diacetyl (a butter-flavoring chemical with known respiratory toxicity potential) as low as 0.02 ppm. CONCLUSIONS: Microwave popcorn workers at many plants are at risk for flavoring-related lung disease. Peak exposures may be hazardous even when ventilation maintains low average exposures. Respiratory protection and engineering controls are necessary to protect workers.

Diacetyl emissions and airborne dust from butter flavorings used in microwave popcorn production.

In microwave popcorn workers, exposure to butter flavorings has been associated with fixed obstructive lung disease resembling bronchiolitis obliterans. Inhalation toxicology studies have shown severe respiratory effects in rats exposed to vapors from a paste butter flavoring, and to diacetyl, a diketone found in most butter flavorings. To gain a better understanding of worker exposures, we assessed diacetyl emissions and airborne dust levels from butter flavorings used by several microwave popcorn manufacturing companies. We heated bulk samples of 40 different butter flavorings (liquids, pastes, and powders) to approximately 50 degrees C and used gas chromatography, with a mass selective detector, to measure the relative abundance of volatile organic compounds emitted. Air sampling was conducted for diacetyl and for total and respirable dust during the mixing of powder, liquid, or paste flavorings with heated soybean oil at a microwave popcorn plant. To further examine the potential for respiratory exposures to powders, we measured dust generated during different simulated methods of manual handling of several powder butter flavorings. Powder flavorings were found to give off much lower diacetyl emissions than pastes or liquids. The mean diacetyl emissions from liquids and pastes were 64 and 26 times larger, respectively, than the mean of diacetyl emissions from powders. The median diacetyl emissions from liquids and pastes were 364 and 72 times larger, respectively, than the median of diacetyl emissions from powders. Fourteen of 16 powders had diacetyl emissions that were lower than the diacetyl emissions from any liquid flavoring and from most paste flavorings. However, simulated handling of powder flavorings showed that a substantial amount of the airborne dust generated was of respirable size and could thus pose its own respiratory hazard. Companies that use butter flavorings should consider substituting flavorings with lower diacetyl emissions and the use of ventilation and enclosure engineering controls to minimize exposures. Until controls are fully implemented, companies should institute mandatory respiratory protection for all exposed workers.

Characterization of respiratory exposures at a microwave popcorn plant with cases of bronchiolitis obliterans.

Eight former workers from a microwave popcorn packaging plant were reported to have severe obstructive lung disease consistent with bronchiolitis obliterans. Investigations into respiratory exposures at this plant were done during August through November of 2000. Samples were collected to assess airborne particulate concentrations, particle size distributions, endotoxins, oxides of nitrogen, organic gases and vapors, and other analytes. Bulk corn and flavoring components were also analyzed for endotoxins and culturable bacteria and fungi. Workers in the microwave production areas of the plant were exposed to particulates and a range of organic vapors from flavorings. The particles were comprised largely of salt and oil/grease particles. Respirable dust concentrations (area plus personal) in the microwave mixer job category, the highest job exposure category in the plant, ranged from 0.13 milligrams per cubic meter of air (mg/m3) to a high of 0.77 mg/m3. Endotoxin concentrations were below 60 endotoxin units per cubic meter of air (EU/m3). Qualitative sampling for volatile organic compounds (VOCs) in the air detected over 100 different VOCs in the microwave area. The predominant compounds identified in the microwave mixing room included the ketones diacetyl, methyl ethyl ketone, acetoin, and 2-nonanone, and acetic acid. Diacetyl, the predominant ketone in the plant, was present in concentrations ranging from below detectable limits to 98 parts per million parts air by volume (ppm), with a mean of 8.1 ppm (standard deviation 18.5 ppm). The average ketone concentrations were highest in the microwave mixing room where the 10 area samples had a mean diacetyl concentration of 37.8 ppm (SD 27.6 ppm) and a mean acetoin concentration of 3.9 ppm (SD 4.3 ppm). These data show that workers involved in microwave popcorn packaging can be exposed to a complex mixture of VOCs from flavoring ingredients; animal studies show that diacetyl can cause airway epithelial injury, although the contributions of other specific compound(s) associated with obstructive respiratory disease in these workers is still unresolved.