Publications by authors named "Kathleen Kreiss"

99 Publications

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

Am J Respir Crit Care Med 2020 12;202(12):1678-1688

Department of Medicine and.

Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease. 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. 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. effects of MWF exposure on murine B cells were assessed. 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 , the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation , a hallmark cell subtype found in the pathology of index cases. 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.
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http://dx.doi.org/10.1164/rccm.202001-0197OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737585PMC
December 2020

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

Occup Environ Med 2020 06 4;77(6):386-392. Epub 2020 Mar 4.

Respiratory Health Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA

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 (FEV) 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 FEV 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/m) 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 FEV 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/m) 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.
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http://dx.doi.org/10.1136/oemed-2019-106296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404615PMC
June 2020

Flavorings-Related Lung Disease: A Brief Review and New Mechanistic Data.

Toxicol Pathol 2019 12 23;47(8):1012-1026. Epub 2019 Oct 23.

Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, USA.

Flavorings-related lung disease is a potentially disabling and sometimes fatal lung disease of workers making or using flavorings. First identified almost 20 years ago in microwave popcorn workers exposed to butter-flavoring vapors, flavorings-related lung disease remains a concern today. In some cases, workers develop bronchiolitis obliterans, a severe form of fixed airways disease. Affected workers have been reported in microwave popcorn, flavorings, and coffee production workplaces. Volatile α-dicarbonyl compounds, particularly diacetyl (2,3-butanedione) and 2,3-pentanedione, are implicated in the etiology. Published studies on diacetyl and 2,3-pentanedione document their ability to cause airway epithelial necrosis, damage biological molecules, and perturb protein homeostasis. With chronic exposure in rats, they produce airway fibrosis resembling bronchiolitis obliterans. To add to this knowledge, we recently evaluated airway toxicity of the 3-carbon α-dicarbonyl compound, methylglyoxal. Methylglyoxal inhalation causes epithelial necrosis at even lower concentrations than diacetyl. In addition, we investigated airway toxicity of mixtures of diacetyl, acetoin, and acetic acid, common volatiles in butter flavoring. At ratios comparable to workplace scenarios, the mixtures or diacetyl alone, but not acetic acid or acetoin, cause airway epithelial necrosis. These new findings add to existing data to implicate α-dicarbonyl compounds in airway injury and flavorings-related lung disease.
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http://dx.doi.org/10.1177/0192623319879906DOI Listing
December 2019

Associations of Metrics of Peak Inhalation Exposure and Skin Exposure Indices With Beryllium Sensitization at a Beryllium Manufacturing Facility.

Ann Work Expo Health 2019 10;63(8):856-869

National Institute for Occupational Safety and Health, Respiratory Health Division, Morgantown, WV, USA.

Objectives: Peak beryllium inhalation exposures and exposure to the skin may be relevant for developing beryllium sensitization (BeS). The objective of this study was to identify risk factors associated with BeS to inform the prevention of sensitization, and the development of chronic beryllium disease (CBD).

Methods: In a survey of short-term workers employed at a primary beryllium manufacturing facility between the years 1994-1999, 264 participants completed a questionnaire and were tested for BeS. A range of qualitative and quantitative peak inhalation metrics and skin exposure indices were created using: personal full-shift beryllium exposure measurements, 15 min to 24 h process-specific task and area exposure measurements, glove measurements as indicator of skin exposure, process-upset information gleaned from historical reports, and self-reported information on exposure events. Hierarchical clustering was conducted to systematically group participants based on similarity of patterns of 16 exposure variables. The associations of the exposure metrics with BeS and self-reported skin symptoms (in work areas processing beryllium salts as well as in other work areas) were evaluated using correlation analysis, log-binomial and logistic regression models with splines.

Results: Metrics of peak inhalation exposure, indices of skin exposure, and using material containing beryllium salts were significantly associated with skin symptoms and BeS; skin symptoms were a strong predictor of BeS. However, in this cohort, we could not tease apart the independent effects of skin exposure from inhalation exposure, as these exposures occurred simultaneously and were highly correlated. Hierarchical clustering identified groups of participants with unique patterns of exposure characteristics resulting in different prevalence of BeS and skin symptoms. A cluster with high skin exposure index and use of material containing beryllium salts had the highest prevalence of BeS and self-reported skin symptoms, followed by a cluster with high inhalation and skin exposure index and a very small fraction of jobs in which beryllium salts were used. A cluster with low inhalation and skin exposure and no workers using beryllium salts had no cases of BeS.

Conclusion: Multiple pathways and types of exposure were associated with BeS and may be important for informing BeS prevention. Prevention efforts should focus on controlling airborne beryllium exposures with attention to peaks, use of process characteristics (e.g. the likelihood of upset conditions to design interventions) minimize skin exposure to beryllium particles, and in particular, eliminate skin contact with beryllium salts to interrupt potential exposure pathways for BeS risk.
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http://dx.doi.org/10.1093/annweh/wxz064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788944PMC
October 2019

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

Am J Ind Med 2019 11 28;62(11):927-937. Epub 2019 Aug 28.

Respiratory Health Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia.

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 FEV  = 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.
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http://dx.doi.org/10.1002/ajim.23038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561037PMC
November 2019

Animal production, insecticide use and self-reported symptoms and diagnoses of COPD, including chronic bronchitis, in the Agricultural Health Study.

Environ Int 2019 06 25;127:764-772. Epub 2019 Apr 25.

Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, United States of America. Electronic address:

Background: Occupational exposure to animal production is associated with chronic bronchitis symptoms; however, few studies consider associations with chronic obstructive pulmonary disease (COPD). We estimated associations between animal production activities and prevalence of self-reported COPD among farmers in the Agricultural Health Study.

Methods: During a 2005-2010 interview, farmers self-reported information about: their operations (i.e., size, type, number of animals, insecticide use), respiratory symptoms, and COPD diagnoses (i.e., COPD, chronic bronchitis, emphysema). Operations were classified as small or medium/large based on regulatory definitions. Farmers were classified as having a COPD diagnosis, chronic bronchitis symptoms (cough and phlegm for ≥3 months during 2 consecutive years), or both. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).

Results: Of 22,491 participating farmers (median age: 59 years), 922 (4%) reported a COPD diagnosis only, 254 (1%) reported a diagnosis and symptoms, and 962 (4%) reported symptoms only. Compared to raising no commercial animals, raising animals on a medium/large operation was positively associated with chronic bronchitis symptoms with (OR: 1.59; 95% CI: 1.16, 2.18) and without a diagnosis (OR: 1.69; 95% CI: 1.42, 2.01). Ever use of multiple organophosphates, carbaryl, lindane, and permethrin were positively associated with chronic bronchitis symptoms.

Conclusion: Animal production work, including insecticide use, was positively associated with chronic bronchitis symptoms; but not consistently with COPD diagnosis alone. Our results support the need for further investigation into the role of animal production-related exposures in the etiology of COPD and better respiratory protection for agricultural workers.
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http://dx.doi.org/10.1016/j.envint.2019.02.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800065PMC
June 2019

Non-malignant respiratory disease among workers in industries using styrene-A review of the evidence.

Am J Ind Med 2017 Feb;60(2):163-180

Respiratory Health Division, Centers for Disease Control and Prevention (CDC), National Institute for Occupational Safety and Health (NIOSH), Morgantown, West Virginia.

Background: Asthma and obliterative bronchiolitis (OB) cases have occurred among styrene-exposed workers. We aimed to investigate styrene as a risk factor for non-malignant respiratory disease (NMRD).

Methods: From a literature review, we identified case reports and assessed cross-sectional and mortality studies for strength of evidence of positive association (i.e., strong, intermediate, suggestive, none) between styrene exposure and NMRD-related morbidity and mortality.

Results: We analyzed 55 articles and two unpublished case reports. Ten OB cases and eight asthma cases were identified. Six (75%) asthma cases had abnormal styrene inhalation challenges. Thirteen (87%) of 15 cross-sectional studies and 12 (50%) of 24 mortality studies provided at least suggestive evidence that styrene was associated with NMRD-related morbidity or mortality. Six (66%) of nine mortality studies assessing chronic obstructive pulmonary disease-related mortality indicated excess mortality.

Conclusions: Available evidence suggests styrene exposure is a potential risk factor for NMRD. Additional studies of styrene-exposed workers are warranted. Am. J. Ind. Med. 60:163-180, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ajim.22655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379121PMC
February 2017

Research to Practice Implications of High-Risk Genotypes for Beryllium Sensitization and Disease.

J Occup Environ Med 2016 09;58(9):855-60

Respiratory Health Division (Drs Kreiss, Fechter-Leggett, Schuler [former affiliation], Weston), Health Effects Laboratory Division (Drs McCanlies, Weston [former affiliation]), and Division of Safety Research, National Institute for Occupational Safety and Health, Morgantown, West Virginia (Dr Schuler).

Objective: Beryllium workers may better understand their genetic susceptibility to chronic beryllium disease (CBD) expressed as population-based prevalence, rather than odds ratios from case-control studies.

Methods: We calculated CBD prevalences from allele-specific DNA sequences of 853 workers for Human Leukocyte Antigen (HLA)-DPB1 genotypes and groups characterized by number of E69-containing alleles and by calculated surface electronegativity of HLA-DPB1.

Results: Of 18 groups of at least 10 workers with specific genotypes, CBD prevalence was highest, 72.7%, for the HLA-DPB102:01:02/DPB117:01 genotype. Population-based grouped genotypes with two E69 alleles wherein one allele had -9 surface charge had a beryllium sensitization (BeS) of 52.6% and a CBD prevalence of 42.1%.

Conclusions: The high CBD and BeS prevalences associated with -9-charged E69 alleles and two E69s suggest that workers may benefit from knowing their genetic susceptibility in deciding whether to avoid future beryllium exposure.
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http://dx.doi.org/10.1097/JOM.0000000000000805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339739PMC
September 2016

Recognizing occupational effects of diacetyl: What can we learn from this history?

Authors:
Kathleen Kreiss

Toxicology 2017 08 17;388:48-54. Epub 2016 Jun 17.

Division of Respiratory Health, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown WV, United States. Electronic address:

For half of the 30-odd years that diacetyl-exposed workers have developed disabling lung disease, obliterative bronchiolitis was unrecognized as an occupational risk. Delays in its recognition as an occupational lung disease are attributable to the absence of a work-related temporal pattern of symptoms; failure to recognize clusters of cases; complexity of exposure environments; and absence of epidemiologic characterization of workforces giving rise to case clusters. Few physicians are familiar with this rare disease, and motivation to investigate the unknown requires familiarity with what is known and what is anomalous. In pursuit of the previously undescribed risk, investigators benefited greatly from multi-disciplinary collaboration, in this case including physicians, epidemiologists, environmental scientists, toxicologists, industry representatives, and worker advocates. In the 15 years since obliterative bronchiolitis was described in microwave popcorn workers, α-dicarbonyl-related lung disease has been found in flavoring manufacturing workers, other food production workers, diacetyl manufacturing workers, and coffee production workers, alongside case reports in other industries. Within the field of occupational health, impacts include new ventures in public health surveillance, attention to spirometry quality for serial measurements, identifying other indolent causes of obliterative bronchiolitis apart from accidental over-exposures, and broadening the spectrum of diagnostic abnormalities in the disease. Within toxicology, impacts include new attention to appropriate animal models of obliterative bronchiolitis, pertinence of computational fluid dynamic-physiologically based pharmacokinetic modeling, and contributions to mechanistic understanding of respiratory epithelial necrosis, airway fibrosis, and central nervous system effects. In these continuing efforts, collaboration between laboratory scientists, clinicians, occupational public health practitioners in government and industry, and employers remains critical for improving the health of workers inhaling volatile α-dicarbonyl compounds.
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http://dx.doi.org/10.1016/j.tox.2016.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323392PMC
August 2017

Respirable indium exposures, plasma indium, and respiratory health among indium-tin oxide (ITO) workers.

Am J Ind Med 2016 07 24;59(7):522-31. Epub 2016 May 24.

National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia.

Background: Workers manufacturing indium-tin oxide (ITO) are at risk of elevated indium concentration in blood and indium lung disease, but relationships between respirable indium exposures and biomarkers of exposure and disease are unknown.

Methods: For 87 (93%) current ITO workers, we determined correlations between respirable and plasma indium and evaluated associations between exposures and health outcomes.

Results: Current respirable indium exposure ranged from 0.4 to 108 μg/m(3) and cumulative respirable indium exposure from 0.4 to 923 μg-yr/m(3) . Plasma indium better correlated with cumulative (rs  = 0.77) than current exposure (rs  = 0.54) overall and with tenure ≥1.9 years. Higher cumulative respirable indium exposures were associated with more dyspnea, lower spirometric parameters, and higher serum biomarkers of lung disease (KL-6 and SP-D), with significant effects starting at 22 μg-yr/m(3) , reached by 46% of participants.

Conclusions: Plasma indium concentration reflected cumulative respirable indium exposure, which was associated with clinical, functional, and serum biomarkers of lung disease. Am. J. Ind. Med. 59:522-531, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
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http://dx.doi.org/10.1002/ajim.22585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915590PMC
July 2016

Environmental characterization of a coffee processing workplace with obliterative bronchiolitis in former workers.

J Occup Environ Hyg 2016 10;13(10):770-81

a Centers for Disease Control and Prevention (CDC), National Institute for Occupational Safety and Health (NIOSH), Respiratory Health Division , Morgantown , West Virginia.

Obliterative bronchiolitis in five former coffee processing employees at a single workplace prompted an exposure study of current workers. Exposure characterization was performed by observing processes, assessing the ventilation system and pressure relationships, analyzing headspace of flavoring samples, and collecting and analyzing personal breathing zone and area air samples for diacetyl and 2,3-pentanedione vapors and total inhalable dust by work area and job title. Mean airborne concentrations were calculated using the minimum variance unbiased estimator of the arithmetic mean. Workers in the grinding/packaging area for unflavored coffee had the highest mean diacetyl exposures, with personal concentrations averaging 93 parts per billion (ppb). This area was under positive pressure with respect to flavored coffee production (mean personal diacetyl levels of 80 ppb). The 2,3-pentanedione exposures were highest in the flavoring room with mean personal exposures of 122 ppb, followed by exposures in the unflavored coffee grinding/packaging area (53 ppb). Peak 15-min airborne concentrations of 14,300 ppb diacetyl and 13,800 ppb 2,3-pentanedione were measured at a small open hatch in the lid of a hopper containing ground unflavored coffee on the mezzanine over the grinding/packaging area. Three out of the four bulk coffee flavorings tested had at least a factor of two higher 2,3-pentanedione than diacetyl headspace measurements. At a coffee processing facility producing both unflavored and flavored coffee, we found the grinding and packaging of unflavored coffee generate simultaneous exposures to diacetyl and 2,3-pentanedione that were well in excess of the NIOSH proposed RELs and similar in magnitude to those in the areas using a flavoring substitute for diacetyl. These findings require physicians to be alert for obliterative bronchiolitis and employers, government, and public health consultants to assess the similarities and differences across the industry to motivate preventive intervention where indicated by exposures above the proposed RELs for diacetyl and 2,3-pentanedione.
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http://dx.doi.org/10.1080/15459624.2016.1177649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836548PMC
October 2016

Bronchiolitis by Any Other Name: Describing Bronchiolar Disorders from Inhalational Exposures.

Ann Am Thorac Soc 2016 Jan;13(1):143-4

2 Duke University School of Medicine Durham, North Carolina.

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http://dx.doi.org/10.1513/AnnalsATS.201510-714LEDOI Listing
January 2016

Respiratory morbidity in a coffee processing workplace with sentinel obliterative bronchiolitis cases.

Am J Ind Med 2015 Dec 2;58(12):1235-45. Epub 2015 Nov 2.

Centers for Disease Control and Prevention (CDC), National Institute for Occupational Safety and Health (NIOSH), Respiratory Health Division, Field Studies Branch, Morgantown, WV.

Rationale: Obliterative bronchiolitis in former coffee workers prompted a cross-sectional study of current workers. Diacetyl and 2,3-pentanedione levels were highest in areas for flavoring and grinding/packaging unflavored coffee.

Methods: We interviewed 75 (88%) workers, measured lung function, and created exposure groups based on work history. We calculated standardized morbidity ratios (SMRs) for symptoms and spirometric abnormalities. We examined health outcomes by exposure groups.

Results: SMRs were elevated 1.6-fold for dyspnea and 2.7-fold for obstruction. The exposure group working in both coffee flavoring and grinding/packaging of unflavored coffee areas had significantly lower mean ratio of forced expiratory volume in 1 s to forced vital capacity and percent predicted mid-expiratory flow than workers without such exposure.

Conclusion: Current workers have occupational lung morbidity associated with high diacetyl and 2,3-pentanedione exposures, which were not limited to flavoring areas.
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http://dx.doi.org/10.1002/ajim.22533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715657PMC
December 2015

Styrene-associated health outcomes at a windblade manufacturing plant.

Am J Ind Med 2015 Nov 25;58(11):1150-9. Epub 2015 Aug 25.

Field Studies Branch, Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia.

Background: Health risks of using styrene to manufacture windblades for the green energy sector are unknown.

Methods: Using data collected from 355 (73%) current windblade workers and regression analysis, we investigated associations between health outcomes and styrene exposure estimates derived from urinary styrene metabolites.

Results: The median current styrene exposure was 53.6 mg/g creatinine (interquartile range: 19.5-94.4). Color blindness in men and women (standardized morbidity ratios 2.3 and 16.6, respectively) was not associated with exposure estimates, but was the type previously reported with styrene. Visual contrast sensitivity decreased and chest tightness increased (odds ratio 2.9) with increasing current exposure. Decreases in spirometric parameters and FeNO, and increases in the odds of wheeze and asthma-like symptoms (odds ratios 1.3 and 1.2, respectively) occurred with increasing cumulative exposure.

Conclusions: Despite styrene exposures below the recommended 400 mg/g creatinine, visual and respiratory effects indicate the need for additional preventative measures in this industry.
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http://dx.doi.org/10.1002/ajim.22516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618383PMC
November 2015

Occupational and environmental bronchiolar disorders.

Semin Respir Crit Care Med 2015 Jun 29;36(3):366-78. Epub 2015 May 29.

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia.

Occupational and environmental causes of bronchiolar disorders are recognized on the basis of case reports, case series, and, less commonly, epidemiologic investigations. Pathology may be limited to the bronchioles or also involve other components of the respiratory tract, including the alveoli. A range of clinical, functional, and radiographic findings, including symptomatic disease lacking abnormalities on noninvasive testing, poses a diagnostic challenge and highlights the value of surgical biopsy. Disease clusters in workplaces and communities have identified new etiologies, drawn attention to indolent disease that may otherwise have been categorized as idiopathic, and expanded the spectrum of histopathologic responses to an exposure. More sensitive noninvasive diagnostic tools, evidence-based therapies, and ongoing epidemiologic investigation of at-risk populations are needed to identify, treat, and prevent exposure-related bronchiolar disorders.
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http://dx.doi.org/10.1055/s-0035-1549452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610354PMC
June 2015

Work-related asthma cluster at a syntactic foam manufacturing facility - Massachusetts 2008-2013.

MMWR Morb Mortal Wkly Rep 2015 Apr;64(15):411-4

Work-related asthma is asthma that is caused or exacerbated by exposure to specific substances in the workplace. Approximately 10%-16% of adult-onset asthma cases are attributable to occupational factors, and estimates of asthma exacerbated by work range from 13% to 58%. During 2008-2012, the Massachusetts Department of Public Health received nine reports of work-related asthma among workers at a facility that manufactured syntactic foam used for flotation in the offshore oil and gas industry. These reports and a request from facility employees led to a CDC health hazard evaluation during 2012-2013 in which CDC reviewed records, toured the facility, and administered a questionnaire to current employees. Investigators found that workers' risk for asthma increased substantially after hire, possibly because of known asthma triggers (i.e., asthmagens) used in production. The company has since initiated efforts to reduce employee exposures to these substances. This cluster of work-related asthma was identified through CDC-funded, state-based surveillance and demonstrates complementary state and federal investigations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779556PMC
April 2015

Remediating buildings damaged by dampness and mould for preventing or reducing respiratory tract symptoms, infections and asthma.

Cochrane Database Syst Rev 2015 Feb 25(2):CD007897. Epub 2015 Feb 25.

Finnish Institute of Occupational Health, P.O.Box 486, Tampere, Finland,

Background: Dampness and mould in buildings have been associated with adverse respiratory symptoms, asthma and respiratory infections of inhabitants. Moisture damage is a very common problem in private houses, workplaces and public buildings such as schools.

Objectives: To determine the effectiveness of repairing buildings damaged by dampness and mould in order to reduce or prevent respiratory tract symptoms, infections and symptoms of asthma.

Search Methods: We searched CENTRAL (2014, Issue 10), MEDLINE (1951 to November week 1, 2014), EMBASE (1974 to November 2014), CINAHL (1982 to November 2014), Science Citation Index (1973 to November 2014), Biosis Previews (1989 to June 2011), NIOSHTIC (1930 to March 2014) and CISDOC (1974 to March 2014).

Selection Criteria: Randomised controlled trials (RCTs), cluster-RCTs (cRCTs), interrupted time series studies and controlled before-after (CBA) studies of the effects of remediating dampness and mould in a building on respiratory symptoms, infections and asthma.

Data Collection And Analysis: Two authors independently extracted data and assessed the risk of bias in the included studies.

Main Results: We included 12 studies (8028 participants): two RCTs (294 participants), one cRCT (4407 participants) and nine CBA studies (3327 participants). The interventions varied from thorough renovation to cleaning only.Repairing houses decreased asthma-related symptoms in adults (among others, wheezing (odds ratio (OR) 0.64; 95% confidence interval (CI) 0.55 to 0.75) and respiratory infections (among others, rhinitis (OR 0.57; 95% CI 0.49 to 0.66), two studies, moderate-quality evidence). For children, we did not find a difference between repaired houses and receiving information only, in the number of asthma days or emergency department visits because of asthma (one study, moderate-quality evidence).One CBA study showed very low-quality evidence that after repairing a mould-damaged office building, asthma-related and other respiratory symptoms decreased. In another CBA study, there was no difference in symptoms between full or partial repair of houses.For children in schools, the evidence of an effect of mould remediation on respiratory symptoms was inconsistent and out of many symptom measures only respiratory infections might have decreased after the intervention. For staff in schools, there was very low-quality evidence that asthma-related and other respiratory symptoms in mould-damaged schools were similar to those of staff in non-damaged schools, both before and after intervention.

Authors' Conclusions: We found moderate to very low-quality evidence that repairing mould-damaged houses and offices decreases asthma-related symptoms and respiratory infections compared to no intervention in adults. There is very low-quality evidence that although repairing schools did not significantly change respiratory symptoms in staff, pupils' visits to physicians due to a common cold were less frequent after remediation of the school. Better research, preferably with a cRCT design and with more validated outcome measures, is needed.
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http://dx.doi.org/10.1002/14651858.CD007897.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769180PMC
February 2015

Silicosis Appears Inevitable Among Former Denim Sandblasters: A 4-Year Follow-up Study.

Chest 2015 Sep;148(3):647-654

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV.

Background: The course of denim sandblasting silicosis is unknown. We aimed to reevaluate former sandblasters studied in 2007 for incident silicosis, radiographic progression, pulmonary function loss, and mortality and to examine any associations between these outcomes and previously demonstrated risk factors for silicosis.

Methods: We defined silicosis on chest radiograph as category 1/0 small opacity profusion using the International Labor Organization classification. We defined radiographic progression as a profusion increase of two or more subcategories, development of a new large opacity, or an increase in large opacity category. We defined pulmonary function loss as a ≥ 12% decrease in FVC.

Results: Among the 145 former sandblasters studied in 2007, 83 were reassessed in 2011. In the 4-year follow-up period, nine (6.2%) had died at a mean age of 24 years. Of the 74 living sandblasters available for reexamination, the prevalence of silicosis increased from 55.4% to 95.9%. Radiographic progression, observed in 82%, was associated with younger age, never smoking, foreman work, and sleeping at the workplace. Pulmonary function loss, seen in 66%, was positively associated with never smoking and higher initial FVC % predicted. Death was associated with never smoking, foreman work, number of different denim-sandblasting places of work, sleeping at the workplace, and lower pulmonary function, of which only the number of different places worked remained in multivariate analyses.

Conclusions: This 4-year follow-up suggests that almost all former denim sandblasters may develop silicosis, despite short exposures and latency.
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http://dx.doi.org/10.1378/chest.14-2848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556121PMC
September 2015

Comment on Farsalinos et al., "Evaluation of Electronic Cigarette Liquids and Aerosol for the Presence of Selected Inhalation Toxins".

Nicotine Tob Res 2015 Oct 12;17(10):1288-9. Epub 2015 Jan 12.

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV;

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http://dx.doi.org/10.1093/ntr/ntu338DOI Listing
October 2015

Early changes in clinical, functional, and laboratory biomarkers in workers at risk of indium lung disease.

Ann Am Thorac Soc 2014 Nov;11(9):1395-403

1 Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia.

Rationale: Occupational exposure to indium compounds, including indium-tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood.

Objectives: To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities.

Methods: Among indium-tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models.

Measurements And Main Results: Eighty-seven (93%) of 94 indium-tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures.

Conclusions: In indium-tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung disease.
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http://dx.doi.org/10.1513/AnnalsATS.201407-346OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4645993PMC
November 2014

The authors respond to Egilman.

Am J Ind Med 2014 Aug 25;57(8):972. Epub 2014 Jun 25.

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia.

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http://dx.doi.org/10.1002/ajim.22358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584392PMC
August 2014

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

Occup Environ Med 2014 Aug 2;71(8):549-54. Epub 2014 Jun 2.

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia, USA.

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.
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http://dx.doi.org/10.1136/oemed-2013-101927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623303PMC
August 2014

Nonmalignant respiratory disease mortality in styrene-exposed workers.

Epidemiology 2014 Jan;25(1):160-1

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV.

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http://dx.doi.org/10.1097/EDE.0b013e3182a70b0fDOI Listing
January 2014

Work-related spirometric restriction in flavoring manufacturing workers.

Authors:
Kathleen Kreiss

Am J Ind Med 2014 Feb 22;57(2):129-37. Epub 2013 Nov 22.

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia.

Background: Flavoring-exposed workers are at risk for occupational lung disease.

Methods: We examined serial spirometries from corporate medical surveillance of flavoring production workers to assess abnormality compared to the U.S. population; mean decline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC); and excessive declines in FEV1.

Results: Of 106 workers, 30 had spirometric restriction, 3 had obstruction, 1 had both, and 13 (of 70, 19%) had excessive declines in FEV1. The adjusted prevalence of restriction was 3.7 times expected. Employees with higher potential for flavorings exposure had 3.0 times and 2.4 times greater average annual declines in FEV1 and FVC respectively, and had 5.8 times higher odds of having excessive FEV1 declines than employees with lower potential for exposure.

Conclusion: Exposure-related spirometric abnormalities consistent with a restrictive process evolved during employment, suggesting that exposures in flavoring production are associated with a range of pathophysiology.
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http://dx.doi.org/10.1002/ajim.22282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586123PMC
February 2014

Vocal cord dysfunction related to water-damaged buildings.

J Allergy Clin Immunol Pract 2013 Jan 2;1(1):46-50. Epub 2012 Dec 2.

Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WVa. Electronic address:

Background: Vocal cord dysfunction (VCD) is the intermittent paradoxical adduction of the vocal cords during respiration, resulting in variable upper airway obstruction. Exposure to damp indoor environments is associated with adverse respiratory health outcomes, including asthma, but its role in the development of VCD is not well described.

Objective: We describe the spectrum of respiratory illness in occupants of 2 water-damaged office buildings.

Methods: The National Institute for Occupational Safety and Health conducted a health hazard evaluation that included interviews with managers, a maintenance officer, a remediation specialist who had evaluated the 2 buildings, employees, and consulting physicians. In addition, medical records and reports of building evaluations were reviewed. Diagnostic evaluations for VCD had been conducted at the Asthma and Allergy Center of the Medical College of Wisconsin.

Results: Two cases of VCD were temporally related to occupancy of water-damaged buildings. The patients experienced cough, chest tightness, dyspnea, wheezing, and hoarseness when in the buildings. Spirometry was normal. Methacholine challenge did not show bronchial hyperreactivity but did elicit symptoms of VCD and inspiratory flow-volume loop truncation. Direct laryngoscopy revealed vocal cord adduction during inspiration. Coworkers developed upper and lower respiratory symptoms; their diagnoses included sinusitis and asthma, consistent with recognized effects of exposure to indoor dampness. Building evaluations provided evidence of water damage and mold growth.

Conclusion: VCD can occur with exposure to water-damaged buildings and should be considered in exposed patients with asthma-like symptoms.
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http://dx.doi.org/10.1016/j.jaip.2012.10.001DOI Listing
January 2013

Factors associated with fatal mining injuries among contractors and operators.

J Occup Environ Med 2013 Nov;55(11):1337-44

From the Division of Pulmonary, Allergy, and Critical Care Medicine (Dr Muzaffar) and Department of Sociology (Dr Allison), University of Pennsylvania, Philadelphia; National Institute for Occupational Safety and Health (Drs Cummings and Kreiss), Morgantown; and Department of Statistics (Dr Hobbs), West Virginia University, Morgantown.

Objective: To explore factors associated with fatal accidents among contractors and operators by using the Mine Safety and Health Administration database.

Methods: Cross-sectional data on 157,410 miners employed by operators or contractors during 1998-2007 were analyzed using logistic regression and multiple imputation.

Results: Univariate odds of fatal versus nonfatal accident were 2.8 (95% confidence interval, 2.3 to 3.4) times higher for contractors than operators. In a multivariable model, fatality was associated with contractor, less experience at the current mine, and occurrence at more than 8 hours into the workday (P < 0.05 for each). Differences in odds of fatality by employment type were more pronounced in surface mines.

Conclusions: Contractors had a higher proportion of fatal injuries. Fatality also varied by mine experience, the number of hours worked before injury, work location, and mine type.
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http://dx.doi.org/10.1097/JOM.0b013e3182a2a5a2DOI Listing
November 2013

Dampness and mould in schools and respiratory symptoms.

Authors:
Kathleen Kreiss

Occup Environ Med 2013 Oct 12;70(10):679-80. Epub 2013 Aug 12.

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http://dx.doi.org/10.1136/oemed-2013-101641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539563PMC
October 2013

Remediating buildings damaged by dampness and mould for preventing or reducing respiratory tract symptoms, infections and asthma (Review).

Evid Based Child Health 2013 May;8(3):944-1000

Finnish Institute of Occupational Health, Tampere, Finland.

Background: Dampness and mould in buildings have been associated with adverse respiratory symptoms, asthma and respiratory infections of inhabitants. Moisture damage is a very common problem in private houses, workplaces and public buildings such as schools.

Objectives: To determine the effectiveness of remediating buildings damaged by dampness and mould in order to reduce or prevent respiratory tract symptoms, infections and symptoms of asthma.

Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1951 to June week 1, 2011), EMBASE (1974 to June 2011), CINAHL (1982 to June 2011), Science Citation Index (1973 to June 2011), Biosis Previews (1989 to June 2011), NIOSHTIC (1930 to November 2010) and CISDOC (1974 to November 2010).

Selection Criteria: Randomised controlled trials (RCTs), cluster-RCTs (cRCTs), interrupted time series studies and controlled before-after (CBA) studies of the effects of remediating dampness and mould in a building on respiratory symptoms, infections and asthma.

Data Collection And Analysis: Two authors independently extracted data and assessed the risk of bias in the included studies.

Main Results: We included eight studies (6538 participants); two RCTs (294 participants), one cRCT (4407 participants) and five CBA studies (1837 participants). The interventions varied from thorough renovation to cleaning only. We found moderate-quality evidence in adults that repairing houses decreased asthma-related symptoms (among others, wheezing (odds ratio (OR) 0.64; 95% confidence interval (CI) 0.55 to 0.75) and respiratory infections (among others, rhinitis (OR 0.57; 95% CI 0.49 to 0.66)). For children, we found moderate-quality evidence that the number of acute care visits (among others mean difference (MD) -0.45; 95% CI -0.76 to -0.14)) decreased in the group receiving thorough remediation. One CBA study showed very low-quality evidence that after repairing a mould-damaged office building, asthma-related and other respiratory symptoms decreased. For children and staff in schools, there was very low-quality evidence that asthma-related and other respiratory symptoms in mould-damaged schools were similar to those of children and staff in non-damaged schools, both before and after intervention. For children, respiratory infections might have decreased after the intervention.

Authors' Conclusions: We found moderate to very low-quality evidence that repairing mould-damaged houses and offices decreases asthma-related symptoms and respiratory infections compared to no intervention in adults. There is very low-quality evidence that although repairing schools did not significantly change respiratory symptoms in staff or children, pupils' visits to physicians due to a common cold were less frequent after remediation of the school. Better research, preferably with a cRCT design and with more validated outcome measures, is needed.
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http://dx.doi.org/10.1002/ebch.1914DOI Listing
May 2013

Occupational lung disease: from case reports to prevention.

Authors:
Kathleen Kreiss

Chest 2013 Jun;143(6):1529-1531

Field Studies Branch, Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV. Electronic address:

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http://dx.doi.org/10.1378/chest.12-3001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673658PMC
June 2013

Increased respiratory disease mortality at a microwave popcorn production facility with worker risk of bronchiolitis obliterans.

PLoS One 2013 28;8(2):e57935. Epub 2013 Feb 28.

Epidemic Intelligence Service Program, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

Background: Bronchiolitis obliterans, an irreversible lung disease, was first associated with inhalation of butter flavorings (diacetyl) in workers at a microwave popcorn company. Excess rates of lung-function abnormalities were related to cumulative diacetyl exposure. Because information on potential excess mortality would support development of permissible exposure limits for diacetyl, we investigated respiratory-associated mortality during 2000-2011 among current and former workers at this company who had exposure to flavorings and participated in cross-sectional surveys conducted between 2000-2003.

Methods: We ascertained workers' vital status through a Social Security Administration search. Causes of death were abstracted from death certificates. Because bronchiolitis obliterans is not coded in the International Classification of Disease 10(th) revision (ICD-10), we identified respiratory mortality decedents with ICD-10 codes J40-J44 which encompass bronchitis (J40), simple and mucopurulent chronic bronchitis (J41), unspecified chronic bronchitis (J42), emphysema (J43), and other chronic obstructive pulmonary disease (COPD) (J44). We calculated expected number of deaths and standardized mortality ratios (SMRs) with 95% confidence intervals (CI) to determine if workers exposed to diacetyl experienced greater respiratory mortality than expected.

Results: We identified 15 deaths among 511 workers. Based on U.S. population estimates, 17.39 deaths were expected among these workers (SMR = 0.86; CI:0.48-1.42). Causes of death were available for 14 decedents. Four deaths among production and flavor mixing workers were documented to have a multiple cause of 'other COPD' (J44), while 0.98 'other COPD'-associated deaths were expected (SMR = 4.10; CI:1.12-10.49). Three of the 4 'other COPD'-associated deaths occurred among former workers and workers employed before the company implemented interventions reducing diacetyl exposure in 2001.

Conclusion: Workers at the microwave popcorn company experienced normal rates of all-cause mortality but higher rates of COPD-associated mortality, especially workers employed before the company reduced diacetyl exposure. The demonstrated excess in COPD-associated mortality suggests continued efforts to lower flavoring exposure are prudent.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057935PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585235PMC
August 2013