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.

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.

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.

Population-wide preventive interventions for reducing the burden of chronic respiratory disease.

Chronic obstructive pulmonary disease and asthma impose a substantial burden of disease. This narrative review focuses on potential population-wide interventions that are likely to have an impact on these diseases. The developmental origins of adult disease commence in utero, with maternal nutrition being of particular interest. However, to date, trials of maternal allergen avoidance, dietary supplementation or probiotics have not shown consistent protective effects against asthma. Poor indoor air quality, especially from biomass fuels as well as second-hand tobacco smoke, is a well-recognised risk factor for chronic respiratory diseases. This can be modified by cleaner fuels, cooking stoves or heaters, and improved ventilation. Although allergens are a risk factor for childhood asthma, the results of interventions to reduce exposures have been disappointing. Traffic-related air pollution is associated with an increased incidence of asthma in children. Primary prevention of the adverse effects of air pollution has focused on the development of ambient air quality guidelines, but enforcement remains a challenge in many countries. Occupational asthma may be induced by sensitisers or irritants in the workplace. Prevention involves eliminating the agent or reducing exposure as far as possible, which is more effective than respiratory protective equipment. Smoking cessation remains a key proven preventive strategy for chronic respiratory diseases. There is now an international framework for tobacco control, and recent innovations include plain packaging of tobacco. Chronic respiratory diseases can be substantially prevented by the above population-wide interventions.

Occupational diseases in individuals exposed to metal working fluids.

PURPOSE OF REVIEW: To examine the current occurrence of respiratory and skin disease in workers who do metal machining with metal working fluids (MWFs), a common work process in manufacturing. RECENT FINDINGS: A summary of the 27 recognized outbreaks of respiratory disease in workers exposed to MWFs was published. New studies have identified irritative symptoms among workers with low-level exposures. There were review articles discussing the content, measurement and control of microbial agents in MWFs. SUMMARY: The occurrence of work-related asthma and hypersensitivity pneumonitis appears to have diminished in the last 10 years. This is presumed to be secondary to lower air levels from the use of newer machining equipment, which are enclosed and have local ventilation as well as better control of microbial contaminants. However, clinicians need to be aware that at the minimum irritative symptoms of the upper respiratory tract are still being reported at these lower exposure levels and there remains the possibility of the development of asthma and hypersensitivity pneumonitis. Given the widespread use of MWFs in manufacturing facilities, clinicians need to consider the possibility that MWFs are the cause or are aggravating the respiratory and dermatologic conditions of their patients.

[Need for occupational and environmental allergology in occupational health - the 45th Japanese society of Occupational and Environmental Allergy Annual Meeting 2014 in Fukuoka].

The 45th Japanese Society of Occupational and Environmental Allergy (OEA) Annual Meeting 2014 was held in Fukuoka city in conjunction with a technical course for occupational health physicians to learn occupational and environmental diseases more deeply. Allergic reaction due to low concentrations of chemical and biological materials is important in toxicological diseases due to highly concentrated chemical materials in the field of occupational and environmental medicine. In this paper we describe the activities of the OEA, which was established in 1970 and has completely cured patients with severe occupational asthma, such as the regional Konjac asthma in Gunma prefecture and Sea Squirt asthma in Hiroshima prefecture. Regard for the occupational environment will prevent the onset and/or exacerbation of allergic occupational disease in individual employees with allergy. Occupational cancer of the bile duct and asbestosis are also current, serious issues that should be resolved as soon as possible. It is desirable for the occupational health physician to have a large stock of knowledge about toxicological and allergic diseases in various occupational settings to maintain the health and safety of workers.

Evolution of occupational asthma: does cessation of exposure really improve prognosis?

AIM: To assess the evolution of occupational asthma (OA) depending on whether the patient avoids or continues with exposure to the offending agent. METHODS: Study in patients diagnosed with OA using a specific inhalation challenge. Patients underwent the following examinations on the same day: clinical interview, physical examination, forced spirometry, methacholine test and determination of total IgE. Clinical improvement, deterioration or no change were defined according to the changes seen on the GINA severity scale at the time of diagnosis. RESULTS: Of the 73 patients finally included, 55 had totally ended exposure and 18 continued to be exposed at work. Clinical improvement was observed in 47% of those who had terminated exposure and in 22% of those who remained exposed; clinical deterioration was observed in 14% and 17% respectively (p = 0.805). Logistical regression analysis, including the type of agent and the persistence or avoidance of exposure among the variables, did not show any predictive factors of clinical evolution. Similarly, the changes in FEV1 and in bronchial hyperresponsiveness were not associated with the avoidance or continuation of exposure to the causative agent. CONCLUSIONS: Avoiding exposure to the causative agent in patients with OA does not seem to improve prognosis in this disease. Despite these findings, there is insufficient evidence to recommend a change in current management guidelines.

What are the benefits of medical screening and surveillance?

Pre-employment examination is considered to be an important practice and is commonly performed in several countries within the European Union. The benefits of medical surveillance programmes are not generally accepted and their structure is often inconsistent. The aim of this review was to evaluate, on the basis of the available literature, the usefulness of medical screening and surveillance. MEDLINE was searched from its inception up to March 2010. Retrieved literature was evaluated in a peer-review process and relevant data was collected following a systematic extraction schema. Pre-placement screening identifies subjects who are at an increased risk for developing work-related allergic disease, but pre-employment screening is too low to be used as exclusion criteria. Medical surveillance programmes can identify workers who have, or who are developing, work-related asthma. These programmes can also be used to avoid worsening of symptoms by implementing preventive measures. A combination of different tools within the surveillance programme, adjusted for the risk of the individual worker, improves the predictive value. Medical surveillance programmes provide medical as well as socioeconomic benefits. However, pre-employment screening cannot be used to exclude workers. They may act as a starting point for surveillance strategies. A stratified approach can increase the effectiveness and reduce the costs for such programmes.

May the reduction of exposure to specific sensitizers be an alternative to work cessation in occupational asthma? Results from a follow-up study.

BACKGROUND: Few data are reported on the effects of a reduction of exposure to specific sensitizers in occupational asthma (OA). The objective of this study was to evaluate the clinical outcome of subjects with OA, comparing the effect of a reduction with that of the persistence or cessation of occupational exposure to the specific sensitizer. SUBJECTS AND METHODS: Forty-one subjects with OA due to different sensitizers were diagnosed via a specific inhalation challenge. After a follow-up interval of 3.5 years, subjects were reexamined by clinical assessment, bronchial hyperresponsiveness (BH) and induced sputum. RESULTS: At follow-up, subjects who had reduced occupational exposure (n = 22) showed a significant improvement in BH and a nonsignificant improvement in sputum eosinophilia (from 5.3 to 1.1%, n.s.), while subjects still exposed (n = 10) showed a significant decrease in FEV(1). Subjects who ceased work (n = 9) showed a trend of improvement in BH and sputum eosinophilia. Logistic analysis showed that the major determinant of improvement in BH at follow-up was the severity of BH at diagnosis, with a minimal contribution from the duration of exposure and treatment with inhaled corticosteroids during follow-up; reduction of work exposure did not enter into any model. CONCLUSION: The reduction of occupational exposure could not be considered to be as effective as work cessation, which remained the best treatment for OA. However, it was not associated with a deterioration of FEV(1) as observed in subjects with persistent exposure.