BACKGROUND: The diagnosis of constrictive bronchiolitis (CB) in previously deployed individuals, and evaluation of respiratory symptoms more broadly, presents considerable challenges, including utilizing consistent histopathologic criteria and clinical assessments. RESEARCH QUESTION: What is the recommended diagnostic workup, and associated terminology, of respiratory symptoms in previously deployed individuals STUDY DESIGN AND METHODS: Nineteen experts participated in a three-round modified Delphi study, ranking their level of agreement for each statement with a priori definition of consensus. Additionally, rank-order voting on the recommended diagnostic approach and terminology was performed. RESULTS: 25 of 28 statements reached consensus, including the definition of CB as a histological pattern of lung injury that occurs in some previously deployed individuals while recognizing the importance of considering alternative diagnoses. Consensus statements also identified a diagnostic approach for the previously deployed individual with respiratory symptoms distinguishing assessments best performed at a local or specialty referral center. Also, 'deployment-related respiratory disease' (DRRD) was proposed as a broad term to subsume a wide range of potential syndromes and conditions identified through non-invasive evaluation, or when surgical lung biopsy reveals evidence of multi-compartmental lung injury which may include CB. INTERPRETATION: Using a modified Delphi technique, consensus statements provide a clinical approach to possible CB in previously deployed individuals. Use of DRRD provides a broad descriptor encompassing a range of post-deployment respiratory findings. Additional follow-up of individuals with DRRD is needed to assess disease progression and define other features of its natural history, which could better inform and lead to evolution in this nosology.

INTRODUCTION: 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 paired environmental and human sampling to evaluate cross-pollination of microbes between environment and host and possible effects on lung pathology present among workers. METHODS: Workplace environmental microbiota was evaluated in air and MWF samples. Human microbiota was evaluated in lung tissue samples from workers with respiratory symptoms found to have lymphocytic bronchiolitis and alveolar ductitis with B-cell follicles and emphysema, lung tissue controls, 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. RESULTS: Increased similarity of microbial composition was found between MWF samples and lung tissue samples of case workers compared to controls. Among workers in different locations within the facility, those that worked in machine shop area had skin, nasal and oral microbiota more closely related to the microbiota present in MWF samples. Lung samples from four index cases, and skin and nasal samples from workers in 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 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.

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/m(3)) 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/m(3)) 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.

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 alpha-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 alpha-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 alpha-dicarbonyl compounds in airway injury and flavorings-related lung disease.

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.

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.

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 >/=3months 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: 59years), 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.

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.

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.

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, alpha-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 alpha-dicarbonyl compounds.

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 mug/m3 and cumulative respirable indium exposure from 0.4 to 923 mug-yr/m3 . 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 mug-yr/m3 , 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. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

INTRODUCTION: Obliterative bronchiolitis in five former coffee processing employees at a single workplace prompted an exposure study of current workers. METHODS: 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. RESULTS: 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-minute 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. CONCLUSIONS: 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.

We read with interest the recent article by Ryerson and colleagues about the potential reversibility of a bronchiolar disorder they termed “fibrosing bronchiolitis” (1). The three cases described by the authors are unrelated and of unclear etiology, but may have infectious or inhalational causes. The patients had centrilobular nodularity on chest computed tomography and bronchiolar luminal narrowing by granulation tissue on biopsy. They were treated with immunosuppressive agents, including corticosteroids, and subsequently had clinical and functional improvement. The authors speculated that without immunosuppressive therapy, the disease may have progressed to constrictive bronchiolitis. | The finding of polypoid granulation tissue within bronchioles has been described historically under the nonspecific term “bronchiolitis obliterans” (2). Lowry and Schuman’s classic report of an inhalational bronchiolar disease, silo-fillers’ disease, from exposure to oxides of nitrogen, was notable for a diffuse nodular infiltrate on chest imaging “that cannot be distinguished from acute miliary tuberculosis,” and a microscopic pattern of bronchiolar filling by “a rather cellular fibrinous exudate” (3). Lowry and Schuman noted that “organization of this adherent plug of fibrin by ingrowth of fibroblasts from the bronchial walls tends eventually to occlude the lumen” (3).

We examined microbial correlates of health outcomes in building occupants with a sarcoidosis cluster and excess asthma. We offered employees a questionnaire and pulmonary function testing and collected floor dust and liquid/sludge from drain tubing traps of heat pumps that were analyzed for various microbial agents. Forty-nine percent of participants reported any symptom reflecting possible granulomatous disease (shortness of breath on exertion, flu-like achiness, or fever and chills) weekly in the last 4 weeks. In multivariate regressions, thermophilic actinomycetes (median=529 CFU/m2 ) in dust were associated with FEV1 /FVC [coefficient=-2.8 per inter-quartile range change, p=0.02], percent predicted FEF25-75% (coefficient=-12.9, p=0.01), and any granulomatous disease-like symptom [odds ratio (OR)=3.1, 95% confidence interval (CI)=1.45-6.73]. Mycobacteria (median=658 CFU/m2 ) were positively associated with asthma symptoms (OR=1.5, 95% CI=0.97-2.43). Composite score (median=11.5) of total bacteria from heat pumps was negatively associated with asthma (0.8, 0.71-1.00) and positively associated with FEV1 /FVC (coefficient=0.44, p=0.095). Endotoxin (median score=12.0) was negatively associated with two or more granulomatous disease-like symptoms (OR=0.8, 95% CI=0.67-0.98) and asthma (0.8, 0.67-0.96). Fungi or (1-->3)-beta-D-glucan in dust or heat pump traps were not associated with any health outcomes. Thermophilic actinomycetes and nontuberculous mycobacteria may have played a role in the occupants' respiratory outcomes in this water-damaged building.

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.

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.

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.

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.

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.

We read with great interest the recent publication, Evaluation of electronic cigarette liquids and aerosol for the presence of selected inhalation toxins.1 We are particularly grateful to the authors for recognizing the high rate of chronic obstructive pulmonary disease and of bronchiolitis, specifically, in smokers and for measuring the concentrations of diacetyl (DA) and acetyl propionyl (AP, also known as 2,3-pentanedione) in electronic cigarette (e-cigarette) liquids and aerosols. However, we would like to clarify two issues: | The National Institute for Occupational Safety and Health (NIOSH) draft document, Criteria for a Recommended Standard: Occupational Exposure to Diacetyl and 2,3-Pentanedione, proposes recommended exposure limits (RELs) to reduce the risk of respiratory impairment (decreased lung function) and the severe irreversible lung disease, constrictive bronchiolitis obliterans, associated with occupational exposure to these chemicals. As noted by Farsalinos and co-workers in their limitations section, it is not intended to establish “safe” exposure concentrations for consumers or the general public.1 | The exposure comparisons between e-cigarette users and traditional cigarette smokers and workers use values that are not widely accepted.

RATIONALE: Occupational exposure to indium compounds including indium-tin oxide (ITO) 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 development of early lung abnormalities. METHODS: Among ITO production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. The 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 ITO facility workers (median tenure=2 years; median plasma indium=1.0 mcg/L) participated in the study. Spirometric abnormalities were not in excess and few had radiographic evidence of alveolar proteinosis (n=0), fibrosis (n=2), or emphysema (n=4). Compared to participants with plasma indium concentrations <1.0 mcg/L, those with values ≥1.0 mcg/L had more dyspnea, lower mean FEV1% and FVC%, and higher median serum KL-6 and SP-D levels. Spline regression demonstrated non-linear exposure-response, with significant differences occurring at plasma indium concentrations as low as 1.0 mcg/L for FEV1%, FVC%, KL-6, and SP-D compared to the reference. Associations between health outcomes and plasma indium were evident in linear regression models and not explained by age, smoking status, or facility tenure. CONCLUSIONS: In ITO facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, abnormal spirometry, and increased serum biomarkers of lung disease.

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.

Collins and colleagues1 focus on cancer risk in their study of more than 15,000 workers at 30 US reinforced-plastic facilities. Yet their demonstration of excess mortality from nonmalignant respiratory disease warrants further discussion. For this cohort of styrene workers, the standardized mortality ratio (SMR) for “bronchitis, emphysema, and asthma” was elevated at 1.35 (95% confidence interval [CI] = 1.17–1.56). | The authors attribute this excess of deaths to smoking. Certainly, smoking is a recognized contributor to obstructive lung diseases. Furthermore, the observed inverse relationship with employment duration may appear to be inconsistent with an occupational cause of disease. However, previous studies have demonstrated excess mortality from nonmalignant respiratory disease in short-term styrene workers. An earlier examination of this same cohort found excess mortality (SMR = 1.40 [95% CI = 1.04–1.84]) from “other nonmalignant respiratory diseases,” with the highest risk (SMR 1.79) in those with less than 1 year of styrene exposure.2 Similarly, among US fiberglass boat builders employed between 1959 to 1978 and followed to 1998, those with high styrene exposures had elevated mortality (SMR = 2.54 [95% CI = 1.31–4.44]) from “pneumoconioses and other respiratory diseases”; the excess mortality was associated with short (<1 year) employment duration.3 | How could occupational styrene exposure be responsible for an excess of mortality from obstructive lung disease among mostly short-term workers? A recent report of obliterative bronchiolitis in styrene-exposed workers is informative.4 Obliterative bronchiolitis is a disabling lung disease that follows, with short latency, certain inhalational exposures. Obliterative bronchiolitis is likely under-recognized and confused with other obstructive lung diseases. Hence the excess mortality due to “bronchitis, emphysema, and asthma” described by Collins et al may represent not a consequence of smoking but a burden of misdiagnosed obliterative bronchiolitis in workers who were disabled by styrene exposure early in their tenure and thus left employment.

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.

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.

Flock worker’s lung disease presents a useful paradigm for identifying new occupational causes of lung disease. It is an unusual interstitial lung disease characterized by lymphocytic bronchiolitis and peribronchiolitis in workers exposed to flock fibers in manufacturing velvet-like fabrics, fuzzy greeting cards and wall papers, and automotive gaskets and glove box surfaces. Flock is made by cutting short synthetic fibers from bundles of parallel monofilaments of nylon or other polymers for application to adhesive-coated substrates. Unlike respirable mineral fibers such as asbestos, synthetic flock is visible, as illustrated in its typical applications. Since 1975, published case reports have raised suspicion of a respiratory hazard associated with various synthetic fibers, including polyester, nylon, and acrylic dust.1-3 With regard to synthetic flock, early reports in 1974 and 1981 of workplace evaluations by National Institute of Occupational Safety and Health (NIOSH) investigators attributed respiratory symptoms among workers to irritant properties of nonrespirable flock fibers on the upper airways but did not pursue the possibility of lung disease associated with flock work.4,5 Systematic workplace investigation of lung disease in workers that flock with synthetic fibers awaited the recognition of case clusters of interstitial disease in small workforces, first in Kingston, Ontario, Canada, and then in Rhode Island, as detailed in the background of the follow-up study by Turcotte et al6 published in this issue of CHEST (see page 1642). Subsequently, additional cases or subclinical morbidity have been found in relation to nylon flock in two Massachusetts plants, to polyethylene flock in Spain, to polypropylene flock in Turkey, and to rayon flock in Kansas.6

RATIONALE AND OBJECTIVES: Obliterative bronchiolitis (OB) is a rare disease with a small number of established occupational aetiologies. We describe a case series of severe OB in workers making glass-reinforced plastics. METHODS: Workplace exposures were the likely cause after the independent diagnosis of OB in two workers laying up the fibreglass hulls of yachts; the second worker took over the job of the first after he left following a lung transplant. Presentation of these two cases at international meetings led to others identifying similar workers. MAIN RESULTS: We identified six workers with good evidence of OB. All were involved in preparing fibreglass with styrene resins, five as boat builders laying up fibreglass hulls and one during cooling-tower fabrication. The disease came on rapidly without unusual acute exposures. Two patients had lung transplants, while another died while waiting for one. Histology confirmed OB in the four with biopsies/post-mortem examinations or explanted lungs. CONCLUSIONS: A rare, potentially fatal disease occurring in six workers laying up fibreglass with styrene resins from five different worksites suggests that work exposures were the cause of their OB. The precise agent responsible awaits identification.

BACKGROUND: Working in damp conditions is associated with asthma, but few studies have used objective testing to document work-related patterns.AimsTo describe the relationship of peak flow measurements to work-related asthma (WRA) symptoms and WRA among occupants in a damp office building. METHODS: At the beginning of the study, all workers were offered a questionnaire and methacholine challenge testing. Participants were then instructed to perform serial spirometry using handheld spirometers five times per day over a 3 week period. Peak flow data were analysed using OASYS-2 software. We calculated the area between the curves (ABC score) using hours from waking. We considered a score >5.6 L/min/h to be indicative of a work-related pattern. RESULTS: All 24 employees participated in the questionnaire. Seven participants (29%) reported physician-diagnosed asthma with onset after starting work in the building. Almost two-thirds (63%) of participants reported at least one lower respiratory symptom (LRS) occurring one or more times per week in the last 4 weeks. Twenty-two (92%) consented to participate in serial spirometry. Fourteen participants had adequate quality of serial spirometry, five of whom had ABC scores >5.6, ranging from 5.9-23.0. Of these five, two had airways responsiveness, three had current post-hire onset physician-diagnosed asthma and four reported work-related LRS. CONCLUSIONS: We found evidence of work-related changes in serial peak flows among some occupants of an office building with a history of dampness. Serial peak flows may be a useful measure to determine WRA in office settings.

BACKGROUND: In 2000, a manufacturer of beryllium materials and products introduced a comprehensive program to prevent beryllium sensitization and chronic beryllium disease (CBD). We assessed the program's efficacy in preventing sensitization 9 years after implementation. METHODS: Current and former workers hired since program implementation completed questionnaires and provided blood samples for the beryllium lymphocyte proliferation test (BeLPT). Using these data, as well as company medical surveillance data, we estimated beryllium sensitization prevalence. RESULTS: Cross-sectional prevalence of sensitization was 0.7% (2/298). Combining survey results with surveillance results, a total of seven were identified as sensitized (2.3%). Early Program workers were more likely to be sensitized than Late Program workers; one of the latter was newly identified. All sensitization was identified while participants were employed. One worker was diagnosed with CBD during employment. CONCLUSIONS: The combination of increased respiratory and dermal protection, enclosure and improved ventilation of high-risk processes, dust migration control, improved housekeeping, and worker and management education showed utility in reducing sensitization in the program's first 9 years. The low rate (0.6%, 1/175) among Late Program workers suggests that continuing refinements have provided additional protection against sensitization compared to the program's early years. (Am. J. Ind. Med. (c) 2013 Wiley Periodicals, Inc.)

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 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.