Health consequences of exposure to aircraft contaminated air and fume events: a narrative review and medical protocol for the investigation of exposed aircrew and passengers.

Thermally degraded engine oil and hydraulic fluid fumes contaminating aircraft cabin air conditioning systems have been well documented since the 1950s. Whilst organophosphates have been the main subject of interest, oil and hydraulic fumes in the air supply also contain ultrafine particles, numerous volatile organic hydrocarbons and thermally degraded products. We review the literature on the effects of fume events on aircrew health. Inhalation of these potentially toxic fumes is increasingly recognised to cause acute and long-term neurological, respiratory, cardiological and other symptoms. Cumulative exposure to regular small doses of toxic fumes is potentially damaging to health and may be exacerbated by a single higher-level exposure. Assessment is complex because of the limitations of considering the toxicity of individual substances in complex heated mixtures.There is a need for a systematic and consistent approach to diagnosis and treatment of persons who have been exposed to toxic fumes in aircraft cabins. The medical protocol presented in this paper has been written by internationally recognised experts and presents a consensus approach to the recognition, investigation and management of persons suffering from the toxic effects of inhaling thermally degraded engine oil and other fluids contaminating the air conditioning systems in aircraft, and includes actions and investigations for in-flight, immediately post-flight and late subsequent follow up.

A case of welder's lung with end-stage pulmonary fibrosis.

BACKGROUND: Welding, performed regularly by more than a million workers worldwide, is associated with exposures to irritative, fibrogenic and carcinogenic fumes and gases. METHODS AND RESULTS: We present the case of a welder who had worked under extremely poor hygiene conditions for nearly 20 years and had developed end-stage lung fibrosis, finally requiring lung transplantation. Detailed histopathology and scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS) analyses of his lungs showed advanced interstitial fibrosis and dust deposits in the lungs and in peribronchial lymph nodes containing welding type bodies, Fe, Si (silica), Ti (titanium), SiAl (aluminum silicates), Fe with Cr (Steel), and Zr (Zirkonium). CONCLUSION: In the absence of a systemic disorder and the failure to meet the criteria for diagnosis of idiopathic pulmonary fibrosis (IPF), these findings suggest welder's lung fibrosis as the most likely diagnosis.

Malignant mesothelioma: Ongoing controversies about its etiology in females.

Malignant mesothelioma (MM) is one of the most aggressive cancers with the poorest of outcomes. There is no doubt that mesothelioma in males is related to asbestos exposure, but some authors suggest that most of the cases diagnosed in females are "idiopathic." In our assessment of the science, the "low risk" of mesothelioma in females is because of the nonsystematic recording of exposure histories among females. Indeed, asbestos exposure is mentioned in only some of the studies that include females. We estimate the risk of MM among females to be close to that in males. The absence of detailed exposure histories should be rectified in future studies involving ​women. As a matter of social justice, the ongoing failure to recognize asbestos as the cause of a majority of cases of MM in females does them, and their kin, a profound disservice.

Immunological methods for diagnosis and monitoring of IgE-mediated allergy caused by industrial sensitizing agents (IMExAllergy).

Industrial sensitizing agents (allergens) in living and working environments play an important role in eliciting type 1 allergic disorders including asthma and allergic rhinitis. Successful management of allergic diseases necessitates identifying their specific causes (ie, identify the causative agent(s) and the route of contact to allergen: airborne, or skin contact) to avoid further exposure. Identification of sensitization by a sensitive and validated measurement of specific IgE is an important step in the diagnosis. However, only a limited number of environmental and occupational allergens are available on the market for use in sIgE testing. Accordingly, specific in-house testing by individual diagnostic and laboratory centers is often required. Currently, different immunological tests are in use at various diagnostic centers that often produce considerably divergent results, mostly due to lack of standardized allergen preparation and standardized procedures as well as inadequate quality control. Our review and meta-analysis exhibited satisfactory performance of sIgE detection test for most high molecular weight (HMW) allergens with a pooled sensitivity of 0.74 and specificity of 0.71. However, for low molecular weight (LMW) allergens, pooled sensitivity is generally lower (0.28) and specificity higher (0.89) than for HMW tests. Major recommendations based on the presented data include diagnostic use of sIgE to HMW allergens. A negative sIgE result for LMW agents does not exclude sensitization. In addition, the requirements for full transparency of the content of allergen preparations with details on standardization and quality control are underlined. Development of standard operating procedures for in-house sIgE assays, and clinical validation, centralized quality control and audits are emphasized. There is also a need for specialized laboratories to provide a custom service for the development of tests for the measurement of putative novel occupational allergens that are not commercially available.

Performance of specific immunoglobulin E tests for diagnosing occupational asthma: a systematic review and meta-analysis.

OBJECTIVES: To determine the test performance parameters for the retrievable range of high-molecular-weight (HMW) and low-molecular-weight (LMW) occupational allergens and to evaluate the impact of allergenic components and the implementation of measures for test validation. METHODS: A protocol with predefined objectives and inclusion criteria was the basis of an electronic literature search of MEDLINE and EMBASE (time period 1967-2016). The specific inhalation challenge and serial peak flow measurements were the reference standards for the specific IgE (sIgE) test parameters. All of the review procedures were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: Seventy-one studies were selected, and 62 entered meta-analysis. Pooled pairs analysis indicated a sensitivity of 0.74(95% CI 0.66 to 0.80) and specificity of 0.71(95% CI 0.63 to 0.77) for HMW allergens and a sensitivity of 0.28(95% CI 0.18 to 0.40) and specificity of 0.89(95% CI 0.77 to 0.95) for LMW allergens. Component-specific analysis improved the test parameters for some allergens. Test validation was handled heterogeneously among studies. CONCLUSION: sIgE test performance is rather satisfactory for a wide range of HMW allergens with the potential for component-specific approaches, whereas sensitivity for LMW allergens is considerably lower, indicating methodological complications and/or divergent pathomechanisms. A common standard for test validation is needed.

How can the integrity of occupational and environmental health research be maintained in the presence of conflicting interests?

BACKGROUND: The sciences, and especially the research subspecialties of occupational and environmental health, are being misused. The misuse serves to interfere with the advancement of policies that depend on rational evidence needed for policies to protect public health. METHODS: We selectively surveyed the independent scientific literature. In addition, the efforts of respected international professional organizations of scientists whose focus is on maintaining and improving public health have been considered. This commentary is unique in assembling not only the factual basis for sounding alarms about significant bias in occupational and environmental health research, but also about the manipulative mechanisms used, and, in turn, the methods needed to keep science honest. RESULTS: Scientific integrity is based on the principle that research is conducted as objectively as possible; it cannot be compromised by special interests whose primary goals are neither to seek truth nor to protect human health. Evidence demonstrates a significant risk of bias in research reports sponsored by financial interests. Practices of corporate malfeasance include the orchestrated contamination of editorial boards of peer-reviewed scientific journals with industry apologists; interference with activities of national regulatory bodies and international review panels engaged in safeguarding occupational and public health; constructing roadblocks by capitalizing on uncertainty to undermine scientific consensus for much-needed government regulation of carcinogenic, endocrine-disrupting and/or immunotoxic agents; promoting "causation" criteria that lack foundation and effectively block workers' access to legal remedies for harms from occupational exposures resulting in morbidity and premature mortality; and, violating standards of professional conduct by seducing reputable scientists with financial incentives that make them beholden to corporate agendas. CONCLUSIONS: Well-orchestrated assaults on science continue unabated and must now be met head-on. Success could be achieved by promoting and protecting the integrity of research. Furthermore, avoiding influence by conflicted corporate affiliates in occupational and public health regulations is needed. Identifying, managing and, ideally, eliminating corporate influence on science and science policy are needed to protect research integrity. Protecting the public's health, preventing disease, and promoting well-being must be the unambiguous goals of research in occupational and environmental health.

Review on the adverse health effects of asbestiform antigorite, a non-regulated asbestiform serpentine mineral.

BACKGROUND: Although antigorite is generally described as platy, its fibrous (asbestiform) variant is present widespread in serpentinite rocks. In addition to its primarily fibrous occurrence, asbestiform antigorite may also be formed from serpentinite with massive appearance during tunneling and mining. It is not of commercial interest, but exposure may occur in the certain environments. METHODS AND RESULTS: Detailed studies of the structural features of this antigorite type revealed characteristics closely related to those of chrysotile. Therefore, it is plausible that this serpentine mineral may present a similar health risk for exposed subjects. This is in agreement with results from clinical and animal studies, as well as in vitro experiments showing the cytotoxic, fibrogenic, and carcinogenic potential of antigorite, similar to that of chrysotile and amphibole asbestos. CONCLUSIONS: Current evidence supports a need for an update to existing regulations to include unregulated asbestiform antigorite, similar to regulatory measures taken for asbestos.

Sensitising effects of genetically modified enzymes used in flavour, fragrance, detergence and pharmaceutical production: cross-sectional study.

OBJECTIVES: The use of genetically engineered enzymes in the synthesis of flavourings, fragrances and other applications has increased tremendously. There is, however, a paucity of data on sensitisation and/or allergy to the finished products. We aimed to review the use of genetically modified enzymes and the enormous challenges in human biomonitoring studies with suitable assays of specific IgE to a variety of modified enzyme proteins in occupational settings and measure specific IgE to modified enzymes in exposed workers. METHODS: Specific IgE antibodies against workplace-specific individual enzymes were measured by the specific fluorescence enzyme-labelled immunoassay in 813 exposed workers seen in cross-sectional surveys. RESULTS: Twenty-three per cent of all exposed workers showed type I sensitisation with IgE antibodies directed against respective workplace-specific enzymes. The highest sensitisation frequencies observed were for workers exposed enzymes derived from α-amylase (44%), followed by stainzyme (41%), pancreatinin (35%), savinase (31%), papain (31%), ovozyme (28%), phytase (16%), trypsin (15%) and lipase (4%). The highest individual antibody levels (up to 110 kU/L) were detected in workers exposed to phytase, xylanase and glucanase. In a subgroup comprising 134 workers, detailed clinical diagnostics confirmed work-related symptoms. There was a strong correlation (r=0.75, p<0.0001) between the symptoms and antibody levels. Workers with work-related respiratory symptoms showed a higher prevalence for the presence of specific IgE antibodies against workplace-specific enzymes than asymptomatic exposed workers (likelihood ratio 2.32, sensitivity 0.92, specificity 0.6). CONCLUSIONS: Our data confirm the previous findings showing that genetically engineered enzymes are potent allergens eliciting immediate-type sensitisation. Owing to lack of commercial diagnostic tests, few of those exposed receive regular surveillance including biomonitoring with relevant specific IgE assays.

Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement.

This consensus statement provides practical recommendations for specific inhalation challenge (SIC) in the diagnosis of occupational asthma. They are derived from a systematic literature search, a census of active European centres, a Delphi conference and expert consensus. This article details each step of a SIC, including safety requirements, techniques for delivering agents, and methods for assessing and interpreting bronchial responses. The limitations of the procedure are also discussed. Testing should only be carried out in hospitals where physicians and healthcare professionals have appropriate expertise. Tests should always include a control challenge, a gradual increase of exposure to the suspected agent, and close monitoring of the patient during the challenge and for at least 6 h afterwards. In expert centres, excessive reactions provoked by SIC are rare. A positive response is defined by a fall in forced expiratory volume in 1 s ≥ 15% from baseline. Equivocal reactions can sometimes be clarified by finding changes in nonspecific bronchial responsiveness, sputum eosinophils or exhaled nitric oxide. The sensitivity and specificity of SIC are high but not easily quantified, as the method is usually used as the reference standard for the diagnosis of occupational asthma.

Accidental exposure to gas emissions from transit goods treated for pest control.

BACKGROUND: International phytosanitary standards ISPM 15 require (since 2007) fumigation or heat treatment for shipping and storage. Those dealing with fumigated freight might be accidentally exposed. In this paper we report a series of three accidents of six storage room workers in a medium sized company regularly importing electronic production parts from abroad. METHODS: Patients (n=6, aged from 32-54 yrs.) and control group (n=30, mean 40 yrs.) donated blood and urine samples. The fumigants: ethylene oxide, methyl bromide, chloropicrin, ethylene dichloride, other halo-alkanes and solvents were analyzed by headspace gas chromatography/mass spectrometry (GCMS). For the quantitation of long term exposure/s, macromolecular reaction products (hemoglobin adducts) were used (with GCMS) as molecular dosimeter; additionally 8-OHdG and circulating mtDNA (cmtDNA) were analyzed as nonspecific biological effect markers. RESULTS: The hemoglobin adducts N-methyl valine (MEV) and N-(2-hydroxy ethyl) valine (HEV) were elevated after exposure to the alkylating chemicals methyl bromide and ethylene oxide. Under the consideration of known elimination kinetics and the individual smoking status (biomonitored with nicotine metabolite cotinine and tobacco specific hemoglobin adduct: N-(2 cyan ethyl) valines, CEV), the data allow theoretical extrapolation to the initial protein adduct concentrations at the time of the accident (the MEV/CEV levels were from 1,616 pmol/g globin to 1,880 pmol/g globin and HEV/CEV levels from 1,407 pmol/g globin to 5,049 pmol/g globin, and correlated with inhaled 0.4-1.5 ppm ethylene oxide. These integrated, extrapolated internal doses, calculated on the basis of biological exposure equivalents, confirmed the clinical diagnosis for three patients, showing severe intoxication symptoms. Both, cmtDNA and 8-OHdG, as non-specific biomarkers of toxic effects, were elevated in four patients. CONCLUSION: The cases reported here, stress the importance of a suitable risk assessment and control measures. We put emphasis on the necessity of human biomonitoring guidelines and the urgency for the relevant limit values.

Allergens causing occupational asthma: an evidence-based evaluation of the literature.

PURPOSE: The aim of this work is to provide an evidence-based evaluation and overview of causative substances in order to improve disease management. METHODS: We conducted a database search with MEDLINE via PubMed, screened reference lists of relevant reviews and matched our findings with a list of agents denoted as "may cause sensitisation by inhalation" by the phrase H334 (till 2011 R42). After exclusion of inappropriate publications, quality of the selected studies was rated with the Scottish Intercollegiate Guideline Network (SIGN) grading system. The evidence level for each causative agent was graded using the modified Royal College of General Practitioners (RCGP) three-star system. RESULTS: A total of 865 relevant papers were identified, which covered 372 different causes of allergic work-related asthma. The highest level achieved using the SIGN grading system was 2++ indicating a high-quality study with a very low risk of confounding or bias and a high probability of a causal relationship. According to the modified RCGP three-star grading system, the strongest evidence of association with an individual agent, profession or worksite ("***") was found to be the co-exposure to various laboratory animals. An association with moderate evidence level ("**") was obtained for α-amylase from Aspergillus oryzae, various enzymes from Bacillus subtilis, papain, bakery (flour, amylase, storage mites), western red cedar, latex, psyllium, farming (animals, cereal, hay, straw and storage mites), storage mites, rat, carmine, egg proteins, atlantic salmon, fishmeal, norway lobster, prawn, snow crab, seafood, trout and turbot, reactive dyes, toluene diisocyanates and platinum salts. CONCLUSION: This work comprises the largest list of occupational agents and worksites causing allergic asthma. For the first time, these agents are assessed in an evidence-based manner. The identified respiratory allergic agents or worksites with at least moderate evidence for causing work-related asthma may help primary care physicians and occupational physicians in diagnostics and management of cases suffering from work-related asthma. Furthermore, this work may possibly provide a major contribution to prevention and may also initiate more detailed investigations for broadening and updating these evidence-based evaluations.

Less work: more burnout? A comparison of working conditions and the risk of burnout by German physicians before and after the implementation of the EU Working Time Directive.

OBJECTIVES: The present study is a 10-year comparison (1997 vs. 2007) of occupational and health aspects before and after the implementation of the European Working Time Directive on German hospital physicians. A major focus is whether the changes in working conditions are accompanied by a lower risk for burnout. METHODS: Three hundred and twenty-eight physicians from the Medical Register of the city of Hamburg completed the survey in 1997 and 994 physicians in 2007. The response rates were 55.4 and 46.5 %, respectively. All participants filled in a 22-item version of the German translation of the Maslach Burnout Inventory. Results of multivariate covariance analyses are reported. RESULTS: The work of physicians has changed significantly within the 10-year period, for example, work time decreased by 4.5 h on average to 55.8 h per week in 2007. Junior physicians profited more from this development, but on-call duties increased for senior physicians in particular. The reduced hours were at the expense of fewer rests. Junior, as well as senior, physicians reported significantly higher rates on the burnout scale for emotional exhaustion (mean 21.8, SD 10.7) in the latter survey and senior physicians also on the depersonalization scale (mean 9.7, SD 6.3). CONCLUSIONS: Changes in working conditions in accordance with the European Working Time Directive are not accompanied by reduced strain and risk of burnout for physicians. Rather, our data argue for greater intensification in work, especially for senior physicians. Further studies are suggested in order to explore interventions for a sustainable improvement in the working conditions of physicians.

Accidental exposure to polychlorinated biphenyls (PCB) in waste cargo after heavy seas. Global waste transport as a source of PCB exposure.

OBJECTIVES: After cargo with PCB-containing transformer oil waste was damaged in heavy seas, the vessel crew exposed to PCB developed itching and acne-form eruption of the skin. The objective of our study was to analyse this work-related incident and its effects on health. METHODS: Air and wipe test samples were taken in the ship for analysis of PCB (28/52/101/138/153/180); clinical investigations of all seafarers (n = 6) included lung function, chest X-ray, clinical chemistry and biomonitoring (plasma PCBs, chlorophenols in urine) measured after a latency of 7 weeks. The biomonitoring data were adjusted according to age-related reference values and validated against controls (n = 96). RESULTS: Biomonitoring showed elevated PCB-28-/52/-102/-138 congeners (mean 1.16/0.91/136, ∑PCB: 5.82 µg/l), which correlates with the dust samples from the cargo hold (∑PCB. 9,440 mg/m(2)) and with 6.1 and 5.0 µg/m(3) in stern and bow cargo air samples. IgE elevation in two seafarers and substantial blood sedimentation rate increase with anaemia or pulmonary emphysema were unlikely to be caused by PCB exposure. Although two members showed slightly elevated airway resistance values, other lung function parameters were normal and reactive airways dysfunction syndrome due to PCBs could be excluded. Elevated chlorophenols in urine could contribute to the manifestation of chloracne. CONCLUSIONS: PCB-52/-101/-138 found in plasma and in air samples confirm exposure to PCB. Acne-form skin eruptions were from occupational exposure to polychlorinated biphenyls in the spilt transformer oil. There were no other abnormal findings in medical and clinical examinations that could be attributed to PCBs. This does not exclude possible long-term effects.

Is specific IgE antibody analysis feasible for the diagnosis of methylenediphenyl diisocyanate-induced occupational asthma?

PURPOSE: Early recognition improves the prognosis of isocyanate asthma. A major unanswered question is whether IgE-dependent mechanisms are of diagnostic value? Our objective was to appraise serological methods using various methylenediphenyl diisocyanate (MDI)-albumin conjugates and weigh up the data versus the outcome of standardized comprehensive clinical diagnostics to evaluate the viability of immunological analysis in supportive MDI-asthma diagnosis (OAI). METHODS: Specific IgE (sIgE) and IgG (sIgG) binding was measured with fluorescence enzyme immunoassay in 43 study subjects (using conjugates prepared in-vapor, in-solution and commercial preparations). The differential clinical diagnosis included standardized measurement of pulmonary function, non-specific bronchial hyper-responsiveness, specific MDI-prick test (MDI-SPT) and specific inhalation challenge (MDI-SIC). RESULTS: Detailed diagnostic scheme allows the differential OAI and MDI-induced hypersensitivity pneumonitis (PI). The presumed OAI diagnoses were confirmed in 84 % (45 % cases having demonstrable sIgE antibodies) with RR 5.7, P > 0.001, when OAI diagnosis is correlated with MDI-SIC/MDI-SPT (RR 1.28 for MDI-SIC alone); sIgG antibodies were clinically relevant for PI and not for the OA diagnosis. MDI-specific IgE data generated with commercial ImmunoCAP preparations show high correlation with our in-vapor generated MDI conjugates. CONCLUSIONS: Isocyanate-specific IgE antibodies are not always detectable but their presence is strongly predictive of OAI and supportive for the diagnosis. MDI-SPT can be a valuable parameter differentiating OAI and PI. We have confirmed and extended published data showing that isocyanate-albumin conjugates perform better in specific antibody assays when prepared with volatile phase formulations and would like to stress additionally the necessity for further refinements and standardization in clinical diagnostics procedures.

Allergic asthma caused by exposure to bacterial alpha-amylase Termamyl®.

BACKGROUND: Airborne enzymes behave as potent respiratory allergens. Till date, allergic disorders caused by genetically engineered enzymes widely used in the industry, have not been reported. RESULTS AND CONCLUSIONS: We describe a worker employed in the detergent industry who developed asthma and rhinitis from IgE-mediated sensitization to the thermostable endo-alpha-amylase Termamyl® and to the protease Savinase®. This is the first report showing that Termamyl® elicits allergic respiratory disorders in humans.

The Relationship Between Potential Occupational Sensitizing Exposures and Asthma: An Overview of Systematic Reviews.

OBJECTIVES: The aim was to identify, appraise, and synthesize the scientific evidence of the relationship between potential occupational sensitizing exposures and the development of asthma based on systematic reviews. METHODS: The study was conducted as an overview of systematic reviews. A systematic literature search was conducted for systematic reviews published up to 9 February 2020. Eligibility study criteria included persons in or above the working age, potential occupational sensitizing exposures, and outcomes defined as asthma. Potential occupational sensitizing exposures were divided into 23 main groups comprising both subgroups and specific exposures. Two reviewers independently selected studies, extracted study data, assessed study quality, and evaluated confidence in study results and level of evidence of the relationship between potential occupational sensitizing exposures and asthma. RESULTS: Twenty-seven systematic reviews were included covering 1242 studies and 486 potential occupational sensitizing exposures. Overall confidence in study results was rated high in three systematic reviews, moderate in seven reviews, and low in 17 reviews. Strong evidence for the main group of wood dusts and moderate evidence for main groups of mites and fish was found. For subgroups/specific exposures, strong evidence was found for toluene diisocyanates, Aspergillus, Cladosporium, Penicillium, and work tasks involving exposure to laboratory animals, whereas moderate evidence was found for 52 subgroups/specific exposures. CONCLUSIONS: This overview identified hundreds of potential occupational sensitizing exposures suspected to cause asthma and evaluated the level of evidence for each exposure. Strong evidence was found for wood dust in general and for toluene diisocyanates, Aspergillus, Cladosporium, Penicillium, and work tasks involving exposure to laboratory animals.

Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.

The aim of the Task Force was to derive continuous prediction equations and their lower limits of normal for spirometric indices, which are applicable globally. Over 160,000 data points from 72 centres in 33 countries were shared with the European Respiratory Society Global Lung Function Initiative. Eliminating data that could not be used (mostly missing ethnic group, some outliers) left 97,759 records of healthy nonsmokers (55.3% females) aged 2.5-95 yrs. Lung function data were collated and prediction equations derived using the LMS method, which allows simultaneous modelling of the mean (mu), the coefficient of variation (sigma) and skewness (lambda) of a distribution family. After discarding 23,572 records, mostly because they could not be combined with other ethnic or geographic groups, reference equations were derived for healthy individuals aged 3-95 yrs for Caucasians (n=57,395), African-Americans (n=3,545), and North (n=4,992) and South East Asians (n=8,255). Forced expiratory value in 1 s (FEV(1)) and forced vital capacity (FVC) between ethnic groups differed proportionally from that in Caucasians, such that FEV(1)/FVC remained virtually independent of ethnic group. For individuals not represented by these four groups, or of mixed ethnic origins, a composite equation taken as the average of the above equations is provided to facilitate interpretation until a more appropriate solution is developed. Spirometric prediction equations for the 3-95-age range are now available that include appropriate age-dependent lower limits of normal. They can be applied globally to different ethnic groups. Additional data from the Indian subcontinent and Arabic, Polynesian and Latin American countries, as well as Africa will further improve these equations in the future.