Mechanistic and Therapeutic Approaches to Occupational Exposure-Associated Allergic and Non-Allergic Asthmatic Disease.

PURPOSE OF REVIEW: Occupational lung disease, including asthma, is a significant cause of disability worldwide. The dose, exposure frequency, and nature of the causal agent influence the inflammatory pathomechanisms that inform asthma disease phenotype and progression. While surveillance, systems engineering, and exposure mitigation strategies are essential preventative considerations, no targeted medical therapies are currently available to ameliorate lung injury post-exposure and prevent chronic airway disease development. RECENT FINDINGS: This article reviews contemporary understanding of allergic and non-allergic occupational asthma mechanisms. In addition, we discuss the available therapeutic options, patient-specific susceptibility and prevention measures, and recent scientific advances in post-exposure treatment conception. The course of occupational lung disease that follows exposure is informed by individual predisposition, immunobiologic response, agent identity, overall environmental risk, and preventative workplace practices. When protective strategies fail, knowledge of underlying disease mechanisms is necessary to inform targeted therapy development to lessen occupational asthma disease severity and occurrence.

[Allergy and immunotoxicology in preventive and clinical medicine from theory to practice: Occupational allergy and isocyanate-induced asthma].

Genetic and environmental factors and their interactions cause diseases and deteriorate health (Genetic and Environmental Interaction). Exposure to environmental factors plays a major role in the deterioration of health in the workplace.Occupational asthma (OA) is a common disorder in the workplace. Approaches to OA are well described and discussed in "Japanese Guideline for Diagnosis and Management of Occupational Allergic Diseases" by the Japanese Society of Occupational and Environmental Allergy. According to the guideline, OA and work-aggravated asthma comprise work-related asthma, and OA can be further divided into two disease entities: sensitizer-induced OA and irritant-induced OA. The guidelines also describe diagnostic and therapeutic strategies for OA. Since a definitive diagnosis of OA requires a comprehensive decision based on a detailed interview on clinical symptoms related to employment status and clinical tests, including inhalation tests of suspected substances as needed, the possibility of OA should be considered as the first step toward diagnosis of the patient. Otherwise, OA may not be diagnosed. Therapeutic strategies include exposure avoidance, environmental arrangements in the workplace, utilization of social resources for workers, and conventional pharmacotherapy for asthma.Artificially synthesized small compounds are used in various industries and can cause allergies. For example, isocyanates are small compounds in the -NCO group, which have been toxicologically studied. It was later shown that isocyanate could cause various nontoxic adverse health effects, including allergic reactions. Since small agents with low molecular weights bind to proteins, detecting their specific immunoglobulin E (IgE) antibodies targeting small compounds is generally difficult. In contrast, isocyanate-specific IgE antibodies are detectable in individuals with isocyanate allergies.Suspecting OA is essential in cases exposed to newly synthesized compounds, or to those that are already known but applied to new uses, which can be better understood and predicted by studying the health effects of isocyanates.Academic interest in various issues related to allergies, immunology, and toxicology in the workplace includes clinical medicine, epidemiology, and epigenetics related to environmental exposure. Further advanced research in these areas is necessary and promising.

Main Causal Agents of Occupational Asthma in France, Reported to the National Network for Occupational Disease Vigilance and Prevention (RNV3P) 2001-2018.

OBJECTIVES: The definition of work-related Asthma (WRA) has changed in recent years and new etiologies and agents have been identified. The aim of this study is to describe the main causal agents of WRA in France in the period 2001-2018 in the main work sectors. METHODS: Data were collected from the French national network of occupational health surveillance and prevention [Réseau National de Vigilance et de Prévention des Pathologies Professionnelles (RNV3P)], Data between 2001 and 2018 with at least a probable or certain association with one occupational agent, were included. RESULTS: Work sectors with more cases OF WRA included personal service activities (10.6%), food industry (10.2%) and healthcare activities (7.6%). WRA cases were most frequently related to flour (10%), quaternary ammoniums compounds (5.3%), isocyanates (5.1%) and cleaning products (4.8%). CONCLUSION: Occupational exposure to specific agents capable of causing WRA is still present, and four agents represent more than 25% of the cases. Actions to prevent respiratory exposure are still relevant.

Occupational chronic obstructive pulmonary disorder: prevalence and prevention.

INTRODUCTION: Occupational chronic obstructive pulmonary disorder, i.e. work-related asthma (WRA) and occupational chronic obstructive pulmonary disease (COPD), are the most common occupational lung diseases in the last decades worldwide. As in the case of the other occupational disorders, these diseases may be prevented. AREAS COVERED: WRA is a heterogeneous entity that includes three subtypes, immunologic occupational asthma (OA), irritant-induced asthma (IIA), and work-exacerbated asthma (WEA), depending on the role of occupational exposures as a causing or aggravating factor of the disease. In addition, there is consistent evidence that a substantial proportion of COPD cases can be explained by exposure to noxious particles and gases other than tobacco smoke, such as workplace dusts, gases, fumes, and vapors. The articles cited in this paper were searched by keywords in several databases in the period up to May-July 2021. EXPERT OPINION: The development of occupational chronic obstructive disorder is a matter of prevention. WRA and occupational COPD contribute significantly to the overall burden of asthma and COPD. Activities and measures targeted to elimination or reduction of harmful workplace exposures, as well as to early detection and early intervention in the course of the lung damage, can significantly reduce the burden caused by these diseases.

Practical learnings from an epidemiology study on TDI-related occupational asthma: Part II-Exposure without respiratory protection to TWA-8 values indicative of peak events is a good indicator of risk.

The anonymized data of an epidemiology study on the incidence of toluene diisocyanate (TDI)-related occupational asthma in three US-based TDI production facilities have been reanalyzed to identify where to best focus exposure reduction efforts in industrial practice in order to reduce the risk of sensitization to TDI. In Part I, it was demonstrated that cumulative exposure is not a good indicator of the risk of developing TDI-related occupational asthma. In this Part II, an alternative model was developed based on net exposure parameters (i.e. samples taken when no respiratory protection was used). A statistically significant relationship was determined between asthma incidence and the frequency of exposure to TDI levels indicative of peak events that are expressed as time-weighted average-8 (TWA-8) values greater than 3 ppb during which no respiratory protection was used. This relationship suggests a threshold to induction of TDI-related asthma. The findings also highlight the importance of a comprehensive program for controlling workplace atmosphere in the plant by technical measures (e.g. selection of equipment, cleaning procedures) and controlling exposure by organizational measures and situational awareness (e.g. training, use of in-the-field direct reading indicators) during high potential exposure scenarios (e.g. line breaking, spills) to encourage or enforce the appropriate use of respiratory protection.

A scoping review to identify strategies that work to prevent four important occupational diseases.

BACKGROUND: Despite being largely preventable, many occupational diseases continue to be highly prevalent and extremely costly. Effective strategies are required to reduce their human, economic, and social impacts. METHODS: To better understand which approaches are most likely to lead to progress in preventing noise-related hearing loss, occupational contact dermatitis, occupational cancers, and occupational asthma, we undertook a scoping review and consulted with a number of key informants. RESULTS: We examined a total of 404 articles and found that various types of interventions are reported to contribute to occupational disease prevention but each has its limitations and each is often insufficient on its own. Our principal findings included: legislation and regulations can be an effective means of primary prevention, but their impact depends on both the nature of the regulations and the degree of enforcement; measures across the hierarchy of controls can reduce the risk of some of these diseases and reduce exposures; monitoring, surveillance, and screening are effective prevention tools and for evaluating the impact of legislative/policy change; the effect of education and training is context-dependent and influenced by the manner of delivery; and, multifaceted interventions are often more effective than ones consisting of a single activity. CONCLUSIONS: This scoping review identifies occupational disease prevention strategies worthy of further exploration by decisionmakers and stakeholders and of future systematic evaluation by researchers. It also identified important gaps, including a lack of studies of precarious workers and the need for more studies that rigorously evaluate the effectiveness of interventions.

Assessing the health impact of interventions for baker's allergy and asthma in supermarket bakeries: a group randomised trial.

PURPOSE: To assess the impact of an intervention for baker's allergy and asthma in supermarket bakeries. METHODS: A group randomised trial conducted in 31 bakeries (n = 337 bakers) that were randomly assigned to one of two intervention groups (n = 244 bakers) and a control group (n = 93 bakers). Health data collected prior to and 1-year after the intervention included information obtained from an ECRHS questionnaire; tests for atopy and serum-specific IgE to cereal flours; fractional exhaled nitric oxide (FeNO). Data from the two intervention groups were combined to form one intervention group for purposes of the statistical analysis. RESULTS: At 1 year of follow-up, the incidence and level of decline of work-related ocular-nasal and chest symptoms, sensitisation status and elevated FeNO (FeNO > 25 ppb) was similar in both intervention and control groups. The mean FeNO difference was also similar across both groups (2.2 ppb vs 1.7 ppb, p = 0.86). In those with FeNO > 25 ppb at baseline, the decline was greater in the intervention compared to control group (16.9 ppb vs 7.7 ppb, p = 0.24). Multivariate logistic regression models (adjusting for smoking, baseline sensitisation to cereal flour, baseline FeNO > 25 ppb) did not demonstrate an appreciable FeNO decline (≥ 10%) in the intervention compared to control group. However, stratification by the presence of work-related ocular-nasal symptoms in bakers at baseline demonstrated a significant FeNO decline (≥ 10%) in the intervention compared to the control group (OR 3.73, CI 1.22-11.42). CONCLUSION: This study demonstrates some evidence of an intervention effect on FeNO 1 year after an intervention, particularly in bakers with work-related ocular-nasal symptoms.

Prevention of baker's asthma.

PURPOSE OF REVIEW: Baker's allergy and asthma continue to represent an important contributor of occupational asthma globally. This review identified recent studies related to the prevention of baker's allergy and asthma. RECENT FINDINGS: Studies with respect to regulatory exposure standards, workplace control measures aimed at reduction of flour dust exposures, surveillance programmes (exposure monitoring, medical surveillance) and workplace information, education and training programmes were identified. SUMMARY: Detailed knowledge on risk factors and detection methods to assess exposure and early identification of high-risk workers exist, but workplace control measures remain sub-optimal because they are rarely multifaceted. This is compounded by the lack of health-based exposure standards globally. Exposure level monitoring and medical surveillance are integral to assessing effectiveness of preventive strategies. Triage systems for optimizing the efficiency of medical surveillance programmes show promise, but need replication in different contexts. Future studies need to focus on evaluating the relevance and quantification of peak exposures in increasing risk; developing standardized respiratory questionnaires for medical surveillance; and further exploration of serial fractional exhaled nitric oxide (FeNO) measurements as an adjunct to allergic sensitization for the early identification of baker's asthma and assessing the long-term impact of interventions.

Occupational asthma; the limited role of air-fed respiratory protective equipment.

BACKGROUND: Evidence-based reviews have found that evidence for the efficacy of respiratory protective equipment (RPE) in the management of occupational asthma (OA) is lacking. AIMS: To quantify the effectiveness of air-fed RPE in workers with sensitizer-induced OA exposed to metal-working fluid aerosols in a car engine and transmission manufacturing facility. METHODS: All workers from an outbreak of metal-working fluid-induced OA who had continuing peak expiratory flow (PEF) evidence of sensitizer-induced OA after steam cleaning and replacement of all metal-working fluid were included. Workers kept 2-hourly PEF measurements at home and work, before and after a strictly enforced programme of RPE with air-fed respirators with charcoal filters. The area-between-curve (ABC) score from the Oasys plotter was used to assess the effectiveness of the RPE. RESULTS: Twenty workers met the inclusion criteria. Records were kept for a mean of 24.6 day shifts and rest days before and 24.7 after the institution of RPE. The ABC score improved from 26.6 (SD 16.2) to 17.7 (SD 25.4) l/min/h (P > 0.05) post-RPE; however, work-related decline was <15 l/min/h in only 12 of 20 workers, despite increased asthma treatment in 5 workers. CONCLUSIONS: Serial PEF measurements assessed with the ABC score from the Oasys system allowed quantification of the effect of RPE in sensitized workers. The RPE reduced falls in PEF associated with work exposure, but this was rarely complete. This study suggests that RPE use cannot be relied on to replace source control in workers with OA, and that monitoring post-RPE introduction is needed.

An educational intervention to improve knowledge about prevention against occupational asthma and allergies using targeted maximum likelihood estimation.

PURPOSE: Occupational asthma and allergies are potentially preventable diseases affecting 5-15% of the working population. However, the use of preventive measures is often insufficient. The aim of this study was to estimate the average treatment effect of an educational intervention designed to improve the knowledge of preventive measures against asthma and allergies in farm apprentices from Bavaria (Southern Germany). METHODS: Farm apprentices at Bavarian farm schools were asked to complete a questionnaire evaluating their knowledge about preventive measures against occupational asthma and allergies (use of personal protective equipment, personal and workplace hygiene measures). Eligible apprentices were randomized by school site to either a control or an intervention group. The intervention consisted of a short educational video about use of preventive measures. Six months after the intervention, subjects were asked to complete a post-intervention questionnaire. Of the 116 apprentices (70 intervention group, 46 control group) who answered the baseline questionnaire, only 47 subjects (41%; 17 intervention group, 30 control group) also completed the follow-up questionnaire. We, therefore, estimated the causal effect of the intervention using targeted maximum likelihood estimation. Models were controlled for potential confounders. RESULTS: Based on the targeted maximum likelihood estimation, the intervention would have increased the proportion of correct answers on all six preventive measures by 18.4% (95% confidence interval 7.3-29.6%) had all participants received the intervention vs. had they all been in the control group. CONCLUSIONS: These findings indicate the improvement of knowledge by the educational intervention.

Andrographolide prevented toluene diisocyanate-induced occupational asthma and aberrant airway E-cadherin distribution via p38 MAPK-dependent Nrf2 induction.

Toluene diisocyanate (TDI) is a major cause of chemical-induced occupational asthma, which contributes about 15% of global asthma burden. Resistance and compounded side effects associated with the use of corticosteroid in asthma necessitate the search for alternative drugs. Andrographolide (AGP), a naturally occurring diterpene lactone is known to exhibit various bioactivities. Its ability to ameliorate cardinal features of allergic asthma was previously suggested in an eosinophilic asthma endotype. However, its potential antiasthma activity and mechanism of action in a neutrophilic occupational asthma model, as well as its effect on epithelial dysfunction remain unknown. BALB/c mice were dermally sensitised with 0.3% TDI or acetone olive oil (AOO) vehicle on day 1 and 8, followed by 0.1% TDI intranasal challenge on days 15, 18 and 21. Endpoints were evaluated via bronchoalveolar lavage fluid (BALF) cell analysis, 2',7'-dichlorofluorescein diacetate (DCFDA) assays, immunoblotting, immunohistochemistry and methacholine challenge test. Decreases in total and differential leukocyte counts of BALF were recorded in AGP-treated animals. The compound dose-dependently reduced intracellular de-esterification of DCFDA, thus suggesting AGP's potential to inhibit intracellular reactive oxygen species (ROS). Mechanistically, the treatment prevented TDI-induced aberrant E-cadherin distribution and restored airway epithelial ß-catenin at cell to cell contact site. Furthermore, AGP ameliorated TDI induced pulmonary collagen deposition. In addition, the treatment significantly upregulated pulmonary HO-1, Nrf2 and phospho-p38 levels. Airway hyperresponsiveness was markedly suppressed among AGP-treated animals. Collectively, these findings suggest AGP's protective function against TDI-induced airway epithelial barrier dysfunction and oxidative lung damage possibly through the upregulation of adherence junction proteins and the activation of p38/Nrf2 signalling. This study elucidates the therapeutic potential of AGP in the control and management of chemical-induced allergic asthma. To the best of our knowledge, the potential anti-asthma activity of AGP in TDI-induced occupational asthma has not been reported previously.

Comprehensive Biological Monitoring to Assess Isocyanates and Solvents Exposure in the NSW Australia Motor Vehicle Repair Industry.

Urethane products that contain isocyanates are extensively used in the motor vehicle repair (MVR) industry and other industries such as furniture and cabinet-making as two-pack spray paints, clears, and adhesives. Attention has recently been refocussed on isocyanate-containing chemicals, particularly in paints. The spray painters in the MVR industry had a propensity to develop industrial asthma at a rate 80 times higher than the general public, which was previously reported in the UK. To track workers exposure to isocyanates, urine samples were collected from 196 spray painters who worked mainly in 78 MVR shops across 54 New South Wales (NSW) towns and suburbs. The biological monitoring also covered exposure testing to a wide variety of solvents including aromatic hydrocarbons, ketones, and alcohols. The main finding of the study was that 2.6% of the spray painters surveyed in the MVR industry in NSW that handled isocyanate-containing paints showed exposure to isocyanates; with 1.0% being moderately exposed, which is more than twice the current UK's Health and Safety Executive (HSE) Biological Monitoring Guidance Value (BMGV) of 1 µmol mol-1 creatinine. Potential exposures to toluene (a solvent often found in paint thinners) was monitored via hippuric acid (HA) urine levels and showed 2.6% of the spray painters surveyed to be over the US' American Conference of Government Industrial Hygienists (ACGIH) Biological Exposure Index (BEI) of 1010 mmol/mole creatinine for HA. The other solvents or their metabolites were all below their respective BEI; these comprised benzene, xylene, ethyl benzene, methyl ethyl ketone, acetone, methanol, and ethanol. These findings indicate that isocyanates and certain solvents exposure were occurring in the NSW Australia vehicle repair industry, albeit at lower levels than previous occupational biological monitoring studies that showed higher exposure levels, particularly for isocyanates. One reason for this could be the increasing use of water-based paints in the industry, resulting in lower than expected isocyanate and solvent metabolite levels detected in this more recent study. Further, the completion of sample context form, along with spot urine collection in relation to the isocyanate exposure monitoring work details will provide crucial information to interpret the biological analysis results. The development of new biomarkers of isocyanate oligomer-derived triamines should be incorporated in the assessment of isocyanate exposure in the MVR industry to provide a more complete picture of isocyanate exposure.

Management and prevention of occupational asthma.

Occupational asthma is a potential preventable form of asthma. This review of diagnosis, management and prevention focuses mainly on publications from the past three years. Early suspicion of the diagnosis is essential for a timely diagnosis and management and the possibility may first be raised by the patient or may need to be elicited by careful history by the health care provider. Objective diagnostic steps are needed, as have been detailed in consensus statements and guidelines. A combination of tests is often needed for diagnosis and these are most easily obtained while the patient is still employed. Management includes consideration of safe future workplace accommodation and of preventive measures for the patient and for other workers.

Occupational asthma: diagnostic challenges and management dilemmas.

PURPOSE OF REVIEW: Work-related asthma encompasses both sensitizer-induced and irritant-induced occupational asthma as well as work-exacerbated asthma. This review summarizes current diagnostic and management strategies for occupational asthma. RECENT FINDINGS: Occupational asthma is the most common occupational lung disease in the industrialized world. Over 400 agents have been described to cause occupational asthma. Specific inhalation challenge is often considered the reference method for diagnosis of occupational asthma but specific inhalation challenge as well as other diagnostic tests all generate false positive or false negative results. Definitive avoidance of the inciting agent is the preferred strategy for sensitizer-induced occupational asthma and reduction of exposure is the next best step. Immunotherapy is not currently well established and can cause systemic reactions. SUMMARY: An accurate diagnosis made in a timely fashion can positively impact the health and socioeconomic burden associated with occupational asthma. Newer diagnostic tools are promising, but much work needs to be done to standardize and validate these testing methods. Primary, secondary, and tertiary prevention strategies are crucial for effective management of sensitizer-induced occupational asthma.

Medical surveillance and long-term prognosis of occupational allergy due to platinum salts.

PURPOSE: Medical surveillance of workers in precious metals refineries and catalyst production plants is well established in many countries as a measure to prevent occupational asthma due to platinum (Pt) salts. It was the aim of this study to evaluate the impact of medical surveillance and to define prognostic factors with an emphasis on exposure determinants. METHODS: As part of an observational longitudinal study, 96 workers from German precious metals refineries and catalyst production plants with Pt salt allergy underwent a second examination several years (median 67 months) after the initial diagnosis was made. RESULTS: When the second examination was conducted, 92 subjects (96 %) had already been transferred to jobs with very low or no exposure to Pt salts. The number of subjects with sensitization to Pt salt as assessed by skin prick test (SPTPt) decreased from 86 to 52 %, and there was a clear improvement for rhinitis, conjunctivitis and contact urticaria between both examinations. Although the number of subjects with asthma symptoms decreased significantly, at the second examination 74 subjects (77 %) continued to suffer from asthma and 51 subjects (53 %) received asthma medication. Airway obstruction or bronchial hyperresponsiveness persisted in 83 subjects (86 %). CONCLUSIONS: Secondary prevention in subjects with occupational exposure to Pt salts, as practiced for over 25 years in Germany could not avoid persistent asthma in the majority of cases, although improvements occurred. This study reveals the limitations of the concept that removal from exposure after the occurrence of respiratory symptoms may prevent chronic asthma. It is recommended that removal from exposure should be done immediately after the occurrence of a positive SPTPt, irrespective of symptoms.

Asma ocupacional por doble agente causal / Occupational asthma caused byt wo different agents

Se describe el caso de una trabajadora con asma ocupacional en el que se detecta un doble agente etiológico condicionado por la exposición mixta en distintas áreas de trabajo. Los isocianatos y resinas epoxi se han descrito como responsables de enfermedad profesional y se ha confirmado su relevancia en las pruebas de función pulmonar tanto de manera inmediata como tardía y en la prueba de provocación bronquial específica. Se destaca la necesidad de evaluar exhaustivamente la exposición a sustancias en el ambiente laboral y comprobar la mejoría clínica tras el cese permanente de la exposición a los agentes implicados

We describe a case of a worker with occupational asthma caused by two separate etiologic agents, resulting from mixed exposures in different work areas. Isocyanates and epoxy resins are established causes of occupational disease, and their role in this case was confirmed by immediate and delayed pulmonary function testing, together with a specific bronchial challenge. A thorough evaluation of exposure to harmful substances in the workplace is essential, together with continued clinical monitoring following cessation of exposure in order to verify clinical improvement

Career Advice for Young Allergy Patients.

BACKGROUND: One-third of all young persons entering the work force have a history of atopic disease. Occupationally induced allergy and asthma generally arise in the first few months on the job, while pre-existing symptoms tend to worsen. Young persons with a history of an atopic disease should receive evidence-based advice before choosing a career. METHODS: We systematically searched PubMed for cohort studies investigating the new onset of asthma, rhinitis, or hand eczema among job trainees from before the start of training and onward into the first few years on the job. The search revealed 514 articles; we read their abstracts and selected 85 full-text articles for further analysis. 24 of these met the inclusion criteria. RESULTS: According to present evidence, atopy and a history of allergic disease (allergic rhinitis, atopic dermatitis) are the main risk factors for occupationally induced disease. The predictive value of a personal history of allergic diseases for the later development of an occupationally induced disease varies from 9% to 64% in the studies we analyzed. It follows that only young people with severe asthma or severe atopic eczema should be advised against choosing a job that is associated with a high risk of allergy, e.g., hairdressing or working with laboratory animals. Young people with a history of other atopic diseases should be counseled about their individual risk profile. CONCLUSION: In view of the relatively poor predictive value of pre-existing atopic disease, secondary prevention is particularly important. This includes frequent medical follow-up of the course of symptoms over the first few years on the job. If sensitization or allergic symptoms arise, it should be carefully considered whether exposure reduction will enable the apprentice to stay on the job.

Update on work-exacerbated asthma.

Work-exacerbated asthma (WEA) is the term used to describe the worsening of asthma related to work but not the causation of asthma by work. It is common and has been reported to occur for 21.5% of working asthmatics on average. The frequency and severity may range from a single mild exacerbation that may lead to no time lost at work up to daily or severe exacerbations that may require a permanent change in work. Reports from general population surveys and primary care settings include more patients with short-term or mild exacerbations while those from tertiary care settings reflect the more severe end of the spectrum of severity or frequency, with socioeconomic outcomes that are similar to those of occupational asthma. In the minority of patients with the WEA, whose asthma starts while working, the differential diagnosis includes sensitizer-induced or possible irritant-induced occupational asthma. Optimizing work exposures and asthma management may improve outcome and prevent exacerbations. Worker education and screening of working asthmatics by primary health care workers may also prevent morbidity.