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

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

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

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

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

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.

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

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

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

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.

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

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.

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

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.

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

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.

Occupational and environmental bronchiolar disorders.

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.

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

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.

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

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.

Styrene-associated health outcomes at a windblade manufacturing plant.

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.

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

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

Work-related spirometric restriction in flavoring manufacturing workers.

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.

Respiratory and olfactory cytotoxicity of inhaled 2,3-pentanedione in Sprague-Dawley rats.

Flavorings-related lung disease is a potentially disabling disease of food industry workers associated with exposure to the α-diketone butter flavoring, diacetyl (2,3-butanedione). To investigate the hypothesis that another α-diketone flavoring, 2,3-pentanedione, would cause airway damage, rats that inhaled air, 2,3-pentanedione (112, 241, 318, or 354 ppm), or diacetyl (240 ppm) for 6 hours were sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis comparable to diacetyl-induced injury. To investigate delayed toxicity, additional rats inhaled 318 (range, 317.9-318.9) ppm 2,3-pentanedione for 6 hours and were sacrificed 0 to 2, 12 to 14, or 18 to 20 hours after exposure. Respiratory epithelial injury in the upper nose involved both apoptosis and necrosis, which progressed through 12 to 14 hours after exposure. Olfactory neuroepithelial injury included loss of olfactory neurons that showed reduced expression of the 2,3-pentanedione-metabolizing enzyme, dicarbonyl/L-xylulose reductase, relative to sustentacular cells. Caspase 3 activation occasionally involved olfactory nerve bundles that synapse in the olfactory bulb (OB). An additional group of rats inhaling 270 ppm 2,3-pentanedione for 6 hours 41 minutes showed increased expression of IL-6 and nitric oxide synthase-2 and decreased expression of vascular endothelial growth factor A in the OB, striatum, hippocampus, and cerebellum using real-time PCR. Claudin-1 expression increased in the OB and striatum. We conclude that 2,3-pentanedione is a respiratory hazard that can also alter gene expression in the brain.

Obliterative bronchiolitis in fibreglass workers: a new occupational disease?

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.

Long-term efficacy of a program to prevent beryllium disease.

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.

Markers of upper airway inflammation associated with microbial exposure and symptoms in occupants of a water-damaged building.

BACKGROUND: Water damage in buildings has been associated with reports of upper airway inflammation among occupants. METHODS: This survey included a questionnaire, allergen skin testing, nasal nitric oxide, and nasal lavage on 153 participants. We conducted exposure assessments of 297 workstations and analyzed collected dust for fungi, endotoxin, and (1 → 3)-ß-D-glucan to create floor-specific averages. RESULTS: Males had higher levels of nasal inflammatory markers, and females reported more symptoms. ECP, IL-8, and MPO were significantly associated with nasal symptoms, flu-like achiness, or chills. Fungi and glucan were positively associated with blowing out thick mucus. Endotoxin was significantly associated with ECP in overall models, and with ECP, IL-8, MPO, and neutrophils among non-atopic females. CONCLUSIONS: In this study, we documented an association between endotoxin and nasal inflammatory markers among office workers. The results of our study suggest that a non-allergic response may contribute to symptoms occurring among occupants in this water-damaged building.

Serial evaluations at an indium-tin oxide production facility.

BACKGROUND: We evaluated the effectiveness of workplace changes to prevent indium lung disease, using 2002-2010 surveillance data collected by an indium-tin oxide production facility. METHODS: We assessed pulmonary function using lower limits of normal. Blood indium concentration and personal air sampling data were used to estimate exposure. RESULTS: Abnormalities were uncommon at hire. After hire, prevalence of spirometric restriction was 31% (n = 14/45), about fourfold higher than expected. Excessive decline in FEV1 was elevated at 29% (n = 12/41). Half (n = 21/42) had blood indium ≥5 µg/l. More recent hires had fewer abnormalities. There was a suggestion that abnormalities were more common among workers with blood indium ≥5 µg/l, but otherwise an exposure-response relationship was not evident. Peak dust concentrations were obscured by time averaging. CONCLUSIONS: Evolving lung function abnormalities consistent with subclinical indium lung disease appeared common and merit systematic investigation. Traditional measures of exposure and response were not illustrative, suggesting fresh approaches will be needed. Workplace changes seemed to have had a positive though incomplete impact; novel preventive interventions are warranted.

Consensus Statements on Deployment-Related Respiratory Disease, Inclusive of Constrictive Bronchiolitis: A Modified Delphi Study.

BACKGROUND: The diagnosis of constrictive bronchiolitis (CB) in previously deployed individuals, and evaluation of respiratory symptoms more broadly, presents considerable challenges, including using consistent histopathologic criteria and clinical assessments. RESEARCH QUESTION: What are 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 an a priori definition of consensus. Additionally, rank-order voting on the recommended diagnostic approach and terminology was performed. RESULTS: Twenty-five of 28 statements reached consensus, including the definition of CB as a histologic 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 noninvasive evaluation or when surgical lung biopsy reveals evidence of multicompartmental lung injury that 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 postdeployment respiratory findings. Additional follow-up of individuals with DRRD is needed to assess disease progression and to define other features of its natural history, which could inform physicians better and lead to evolution in this nosology.