Recent developments in occupational asthma.

PURPOSE OF REVIEW: Occupational asthma (OA) is a complex condition that can be difficult to diagnose. The purpose of this review is to describe some recent findings regarding the epidemiology of OA, the occupational sensitizing agents, the prognosis of OA, and its primary prevention. RECENT FINDINGS: The risk of developing OA varies according to the geographic localization of the worker, the type of industry and the type of sensitizing agents. New findings have been reported for several known sensitizing agents, such as isocyanates, seafood & cleaning agents, and their related industries, such as hairdressing salons and schools. Moreover, a few new sensitizing agents, such as cannabis, have been identified in the past few years. The prognosis of OA seems worse than that of nonwork-related asthma. It is mainly determined by the duration and the level of exposure. Primary prevention is crucial to reduce the number of new cases of OA. Complete avoidance of exposure to the causal agent remains the optimal treatment of sensitizer-induced OA. SUMMARY: Improving our knowledge regarding OA and its causative agents is key to enable an early recognition of this condition and improve its prognosis. Further research is still needed to improve primary prevention.

Multivariate analysis and data mining help predict asthma exacerbations.

BACKGROUND: Work-related asthma has become a highly prevalent occupational lung disorder. OBJECTIVE: Our study aims to evaluate occupational exposure as a predictor for asthma exacerbation. METHOD: We performed a retrospective evaluation of 584 consecutive patients diagnosed and treated for asthma between October 2017 and December 2019 in four clinics from Western Romania. We evaluated the enrolled patients for their asthma control level by employing the Asthma Control Test (ACT < 20 represents uncontrolled asthma), the medical record of asthma exacerbations, occupational exposure, and lung function (i.e. spirometry). Then, we used statistical and data mining methods to explore the most important predictors for asthma exacerbations. RESULTS: We identified essential predictors by calculating the odds ratios (OR) for the exacerbation in a logistic regression model. The average age was 45.42 ± 11.74 years (19-85 years), and 422 (72.26%) participants were females. 42.97% of participants had exacerbations in the past year, and 31.16% had a history of occupational exposure. In a multivariate model analysis adjusted for age and gender, the most important predictors for exacerbation were uncontrolled asthma (OR 4.79, p < .001), occupational exposure (OR 4.65, p < .001), and lung function impairment (FEV1 < 80%) (OR 1.15, p = .011). The ensemble machine learning experiments on combined patient features harnessed by our data mining approach reveal that the best predictor is professional exposure, followed by ACT. CONCLUSIONS: Machine learning ensemble methods and statistical analysis concordantly indicate that occupational exposure and ACT < 20 are strong predictors for asthma exacerbation.

Identification of true chemical respiratory allergens: Current status, limitations and recommendations.

Asthma in the workplace is an important occupational health issue. It comprises various subtypes: occupational asthma (OA; both allergic asthma and irritant-induced asthma) and work-exacerbated asthma (WEA). Current regulatory paradigms for the management of OA are not fit for purpose. There is therefore an important unmet need, for the purposes of both effective human health protection and appropriate and proportionate regulation, that sub-types of work-related asthma can be accurately identified and classified, and that chemical respiratory allergens that drive allergic asthma can be differentiated according to potency. In this article presently available strategies for the diagnosis and characterisation of asthma in the workplace are described and critically evaluated. These include human health studies, clinical investigations and experimental approaches (structure-activity relationships, assessments of chemical reactivity, experimental animal studies and in vitro methods). Each of these approaches has limitations with respect to providing a clear discrimination between OA and WEA, and between allergen-induced and irritant-induced asthma. Against this background the needs for improved characterisation of work-related asthma, in the context of more appropriate regulation is discussed.

Fatal Occupational Asthma in Cannabis Production - Massachusetts, 2022.

Multiple respiratory hazards have been identified in the cannabis cultivation and production industry, in which occupational asthma and work-related exacerbation of preexisting asthma have been reported. An employee working in a Massachusetts cannabis cultivation and processing facility experienced progressively worsening work-associated respiratory symptoms, which culminated in a fatal asthma attack in January 2022. This report represents findings of an Occupational Safety and Health Administration inspection, which included a worksite exposure assessment, coworker and next-of-kin interviews, medical record reviews, and collaboration with the Massachusetts Department of Public Health. Respiratory tract or skin symptoms were reported by four of 10 coworkers with similar job duties. Prevention is best achieved through a multifaceted approach, including controlling asthmagen exposures, such as cannabis dust, providing worker training, and conducting medical monitoring for occupational allergy. Evaluation of workers with new-onset or worsening asthma is essential, along with prompt diagnosis and medical management, which might include cessation of work and workers' compensation when relation to work exposures is identified. It is important to recognize that work in cannabis production is potentially causative.

Occupational asthma induced by fish exposure.

Occupational asthma triggered by inhaling fish-derived aerosols is estimated to affect 2-8% of exposed individuals. This primarily affects workers in the fish processing industry. Fishmongers, rarely experience this issue, as recent research found no significant difference in asthma rates compared to a control group. We report the case of a fishmonger who presented with a 1-year history of rhinoconjunctivitis and asthma. The patient attributed these symptoms to his occupational exposure within the fish market environment, which worsened in the cold storage warehouse. Symptoms improved during holidays. Diagnosis involved skin-prick tests, sIgE (ImmunoCAP-specific IgE) measurements, and bronchial challenge tests, confirming occupational asthma from fish bioaerosol exposure. Parvalbumins, common fish proteins, share structural similarities, leading to cross-reactivity in fish allergy sufferers. In this case, sensitivity to rGad c1 (cod parvalbumin) was identified as the primary trigger for the patient's asthma, and responsible for sensitizations observed across various tested fish species.

Occupational Respiratory Allergy: Risk Factors, Diagnosis, and Management.

Occupational allergies are among the most common recorded occupational diseases. The skin and the upper and lower respiratory tract are the classical manifestation organs. More than 400 occupational agents are currently documented as being potential "respiratory sensitizers" and new reported causative agents are reported each year. These agents may induce occupational rhinitis (OR) or occupational asthma (OA) and can be divided into high-molecular weight (HMW) and low-molecular weight (LMW) agents. The most common occupational HMW agents are (glycol)proteins found in flour and grains, enzymes, laboratory animals, fish and seafood, molds, and Hevea brasiliensis latex. Typical LMW substances are isocyanates, metals, quaternary ammonium persulfate, acid anhydrides, and cleaning products/disinfectants. Diagnosis of occupational respiratory allergy is made by a combination of medical history, physical examination, positive methacholine challenge result or bronchodilator responsiveness, determination of IgE-mediated sensitization, and specific inhalation challenge tests as the gold standard. Accurate diagnosis of asthma is the first step to managing OA as shown above. Removal from the causative agent is of central importance for the management of OA. The best strategy to avoid OA is primary prevention, ideally by avoiding the use of and exposure to the sensitizer or substituting safer substances for these agents.

Severe asthma and death in a worker using methylene diphenyl diisocyanate MDI asthma death.

Diisocyanates are well-recognized to cause occupational asthma, yet diisocyanate asthma can be challenging to diagnose and differentiate from asthma induced by other allergens. The present study assesses the potential contribution of methylene diphenyl diisocyanate (MDI) to a workplace fatality. Examination of medical records, tissue, and blood from the deceased worker were undertaken. Formalin-fixed paraffin-embedded lung tissue sections were assessed through histologic and immunochemical stains. Serum MDI-specific IgE and IgG, and total IgE, were measured by enzyme-linked immunosorbent assays and/or Western blot. Information about potential chemical exposures and industrial processes in the workplace were provided by the employer and through interviews with co-workers. Review of the worker's medical records, occupational history, and autopsy findings were consistent with severe asthma as the cause of death, and ruled out cardiac disease, pulmonary embolism, or stroke. Lung pathology revealed hallmarks of asthma including smooth muscle hypertrophy, eosinophilia, basement membrane thickening, and mucus plugging of bronchioles. Immunochemical staining for MDI was positive in the thickened basement membrane of inflamed airways. MDI-specific serum IgE and IgG were significantly elevated and demonstrated specificity for MDI versus other diisocyanates, however, total serum IgE was normal (24 IU/ml). The workplace had recently introduced MDI into the foundry as part of a new process, but MDI air levels had not been measured. Respirators were not required. In summary, post-mortem findings support the diagnosis of diisocyanate asthma and a severe asthma attack at work as the cause of death in a foundry worker.

Occupational asthma in office workers.

BACKGROUND: Office work has a relative perception of safety for the worker. Data from surveillance schemes and population-based epidemiological studies suggest that office work carries a low risk of occupational asthma (OA). Office workers are frequently used as comparators in studies of occupational exposure and respiratory disease. AIMS: We aimed to describe and illustrate our tertiary clinical experience of diagnosing OA in office workers. METHODS: We searched the Birmingham NHS Occupational Lung Disease Service clinical database for cases of occupational respiratory disease diagnosed between 2002 and 2020, caused by office work or in office workers. For patients with OA, we gathered existing data on demographics, diagnostic tests including Occupational Asthma SYStem (OASYS) analysis of serial peak expiratory flow and specific inhalational challenge, and employment outcome. We summarised data and displayed them alongside illustrative cases. RESULTS: There were 47 cases of OA (5% of all asthma) confirmed using OASYS analysis of PEFs in the majority. Sixty percent of cases occurred in healthcare, education and government sectors. The most frequently implicated causative exposures or agents were: indoor air (9), printing, copying and laminating (7), cleaning chemicals (4), mould and damp (4), and acrylic flooring and adhesives (4). Exposures were grouped into internal office environment, office ventilation-related and adjacent environment. CONCLUSIONS: Clinicians should be vigilant for exposures associated with OA in office workers who present with work-related symptoms, where respiratory sensitizing agents may be present. A structured approach to assessment of the workplace is recommended.

Novel approaches in occupational asthma diagnosis and management.

PURPOSE OF REVIEW: To describe the recent findings of the last 2 years on the epidemiology and phenotypes of occupational asthma, as well as new developments in its diagnosis and management. RECENT FINDINGS: Data from nine longitudinal studies showed a population attributable fraction for the occupational contribution to incident asthma of 16%. The main phenotypes of occupational asthma are: occupational asthma caused by high-molecular-weight (HMW) or low-molecular-weight (LMW) agents, irritant-induced asthma and occupational asthma-chronic obstructive pulmonary disease overlap. Among the variety of causative agents of occupational asthma, food-derived components are increasingly being reported, accounting for up to 25% cases of occupational asthma and/or occupational rhinitis. Recently, a specific inhalation challenge (SIC)-independent model has been developed to calculate the probability of occupational asthma diagnosis in workers exposed to HMW agents. In this model, work-specific sensitization, bronchial hyperresponsiveness, inhaled corticosteroid use, rhinoconjunctivitis and age 40 years or less were the most relevant predictive factors. Specific IgE measurements showed a pooled sensitivity of 0.74 and a specificity of 0.71 in the diagnosis of occupational asthma for HMW agents, while a lower sensitivity (0.28) and a higher specificity (0.89) was shown for LMW agents. Cessation of exposure to workplace sensitizers is the cornerstone of management of work-related conditions. SUMMARY: An early and precise diagnosis of occupational asthma is crucial, allowing appropriate management and implementation of preventive strategies.

Occupational Exposure to Metals and Solvents: Allergy and Airway Diseases.

PURPOSE OF REVIEW: Occupational allergic diseases (OAD) such as occupational contact dermatitis (OCD), occupational asthma (OA), and occupational rhinitis (OR) are the most prevalent occupational diseases in industrialized countries. The purpose of this review is to provide an update about the main occupational metal and solvent exposures related to allergy and airway diseases and to discuss newly defined causative agents and industries in this field. RECENT FINDINGS: Currently for over 400 causative agents for OA and OCD, several hundreds of agents for OR have been identified. Although many studies have reported an overall decline in OAD related to known agents after implementation of efficient and effective workplace preventive measures, the constant development of new products continuously introduces to the market potential unknown respiratory hazards. Workplace allergens are often high molecular weight (HMW) agents that are > 10 kDa molecular weight and capable of eliciting IgE sensitization. Sensitizing low molecular weight (LMW) agents are often reactive chemicals. Metals and solvents are two large causative agent groups related to OADs that mainly behave as LMW (< 10 kDa) sensitizers and/or irritants. Avoidance of causative exposures through control strategies is the primary prevention approach for OADs. These strategies must be applied and covered for all known and newly defined causative agents. This review aims to summarize current status of known occupational metal and solvent exposures related to allergy and airway diseases and to discuss newly defined causative agents and industries in this field.

Prevalence of COPD among workers with work-related asthma.

Objective: Concurrent asthma and chronic obstructive pulmonary disease (COPD) diagnoses occur in 15%-20% of patients, and have been associated with worse health outcomes than asthma or COPD alone. Work-related asthma (WRA), asthma that is caused or made worse by exposures in the workplace, is characterized by poorly controlled asthma. The objective of this study was to assess the proportion of ever-employed adults (≥18 years) with current asthma who have been diagnosed with COPD, by WRA status.Methods: Data from 23 137 respondents to the 2012-2014 Behavioral Risk Factor Surveillance System Asthma Call-back Survey from 31 states and the District of Columbia were examined. Logistic regression was used to calculate adjusted prevalence ratios (PRs), examining six disjoint categories of WRA-COPD overlap with non-WRA/no COPD as the referent category.Results: An estimated 51.9% of adults with WRA and 25.6% of adults with non-WRA had ever been diagnosed with COPD. Adults with WRA/COPD were more likely than those with non-WRA/no COPD to have an asthma attack (PR = 1.77), urgent treatment for worsening asthma (PR = 2.85), an asthma-related emergency room visit (PR = 4.21), overnight stay in a hospital because of asthma (PR = 6.57), an activity limitation on 1-13 days (PR = 2.01) or ≥14 days (PR = 5.02), and very poorly controlled asthma (PR = 3.22).Conclusions: COPD was more frequently diagnosed among adults with WRA than those with non-WRA, and adults diagnosed with both WRA and COPD appear to have more severe adverse asthma outcomes than those with non-WRA and no COPD.

Follow-up survey of patients with occupational asthma.

BACKGROUND: Occupational asthma (OA) is often associated with a poor prognosis and the impact of a diagnosis on an individual's career and income can be significant. AIMS: We sought to understand the consequences of a diagnosis of OA to patients attending our clinic. METHODS: Using a postal questionnaire, we surveyed all patients attending our specialist occupational lung disease clinic 1 year after having received a diagnosis of OA due to a sensitizer (n = 125). We enquired about their current health and employment status and impact of their diagnosis on various aspects of their life. Additional information was collected by review of clinical records. RESULTS: We received responses from 71 (57%) patients; 77% were referred by an occupational health (OH) provider. The median duration of symptoms prior to referral was 18 months (interquartile range (IQR) 8-48). At 1 year, 79% respondents were no longer exposed to the causal agent. Whilst the unexposed patients reported an improvement in symptoms compared with those still exposed (82% versus 53%; P = 0.023), they had poorer outcomes in terms of career, income and how they felt treated by their employer; particularly those not currently employed. Almost all (>90%) of those still employed had been referred by an OH provider compared with 56% of those currently unemployed (P = 0.002)x. CONCLUSIONS: The negative impact of OA on people's careers, livelihood and quality of life should not be underestimated. However, with early detection and specialist care, the prognosis is often good and particularly so for those with access to occupational health.

Are high- and low-molecular-weight sensitizing agents associated with different clinical phenotypes of occupational asthma?

BACKGROUND: High-molecular-weight (HMW) proteins and low-molecular-weight (LMW) chemicals can cause occupational asthma (OA) although few studies have thoroughly compared the clinical, physiological, and inflammatory patterns associated with these different types of agents. The aim of this study was to determine whether OA induced by HMW and LMW agents shows distinct phenotypic profiles. METHODS: Clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge response to HMW (n = 544) and LMW (n = 635) agents. RESULTS: Multivariate logistic regression analysis showed significant associations between OA caused by HMW agents and work-related rhinitis (OR [95% CI]: 4.79 [3.28-7.12]), conjunctivitis (2.13 [1.52-2.98]), atopy (1.49 [1.09-2.05]), and early asthmatic reactions (2.86 [1.98-4.16]). By contrast, OA due to LMW agents was associated with chest tightness at work (2.22 [1.59-3.03]), daily sputum (1.69 [1.19-2.38]), and late asthmatic reactions (1.52 [1.09-2.08]). Furthermore, OA caused by HMW agents showed a higher risk of airflow limitation (1.76 [1.07-2.91]), whereas OA due to LMW agents exhibited a higher risk of severe exacerbations (1.32 [1.01-1.69]). There were no differences between the two types of agents in the baseline sputum inflammatory profiles, but OA caused by HMW agents showed higher baseline blood eosinophilia and a greater postchallenge increase in fractional nitric oxide. CONCLUSION: This large cohort study describes distinct phenotypic profiles in OA caused by HMW and LMW agents. There is a need to further explore differences in underlying pathophysiological pathways and outcome after environmental interventions.

Claudins, VEGF, Nrf2, Keap1, and Nonspecific Airway Hyper-Reactivity Are Increased in Mice Co-Exposed to Allergen and Acrolein.

Acrolein, an α/ß-unsaturated aldehyde, is volatile at room temperature. It is a respiratory irritant found in environmental tobacco smoke, which can be generated during cooking or endogenously at sites of injury. An acute high concentration of uncontrolled irritant exposure can lead to an asthma-like syndrome known as reactive airways dysfunction syndrome (RADS). However, whether acrolein can induce RADS remains poorly understood. The aim of study is to develop a RADS model of acrolein inhalation in mice and to clarify the mechanism of RADS. Mice were treated with ovalbumin (OVA) and exposed to acrolein (5 ppm/10 min). Airway hyper-responsiveness (AHR) was measured on days 24 and 56, and samples were collected on days 25 and 57. Tight junction protein, antioxidant-associated protein, and vascular endothelial growth factor (VEGF) levels were estimated by Western blotting and immunohistochemical staining. Reactive oxygen species (ROS) was calculated using enzyme linked immunosorbent assays. Acrolein or OVA groups exhibited an increase in airway inflammatory cells and AHR compared to a sham group. These effects were further increased in mice in the OVA + acrolein exposure group than in the OVA exposure group and persisted in the acrolein exposure group for 8 weeks. CLDNs, carbonyls, VEGF, Nrf2, and Keap1 were observed in the lungs. Our data demonstrate that acrolein induces RADS and that ROS, angiogenesis, and tight junction proteins are involved in RADS in a mouse model.

Occupational asthma: clinical phenotypes, biomarkers, and management.

PURPOSE OF REVIEW: This review focuses on new findings in the clinical and inflammatory aspects that can help to better identify the different phenotypes of work-related asthma and the development of specific biomarkers useful in diagnosis and follow-up. RECENT FINDINGS: Studies on phenotyping of occupational asthma, a subtype of work-related asthma, have mainly compared the clinical, physiological, and inflammatory patterns associated with the type of agent causing occupational asthma, namely, high-molecular-weight and low-molecular-weight agents. Most of this research has found that patients with occupational asthma due to high-molecular-weight agents have an associated presence of rhinitis, conjunctivitis, atopy, and a pattern of early asthmatic reactions during specific inhalation challenge. The inflammatory profile (blood eosinophils, sputum cell count, or exhaled nitric oxide) may be similar when occupational asthma is caused by either type of agent. In some studies, severity of asthma and exacerbations have been associated with exposure to low-molecular-weight agents. The most reliable biomarkers in diagnosis and follow-up are eosinophilia in induced sputum and exhaled nitric oxide. SUMMARY: There are several phenotypes, characterized by its pathogenesis and inflammatory profile. Avoidance of the causative agents does not warrant complete recovery of occupational asthma. Treatment with biologic agents may be considered in severe occupational asthma.

Circulating miRs-183-5p, -206-3p and -381-3p may serve as novel biomarkers for 4,4'-methylene diphenyl diisocyanate exposure.

BACKGROUND: Occupational exposure to the most widely used diisocyanate, 4,4'-methylene diphenyl diisocyanate (MDI), is a cause of occupational asthma (OA). Early recognition of MDI exposure and sensitization is essential for the prevention of MDI-OA. OBJECTIVE: Identify circulating microRNAs (miRs) as novel biomarkers for early detection of MDI exposure and prevention of MDI-OA. MATERIALS AND METHODS: Female BALB/c mice were exposed to one of three exposure regimens: dermal exposure to 1% MDI in acetone; nose-only exposure to 4580 ± 1497 µg/m3 MDI-aerosol for 60 minutes; or MDI dermal exposure/sensitization followed by MDI-aerosol inhalation challenge. Blood was collected and miRCURY™ miRs qPCR Profiling Service was used to profile circulate miRs from dermally exposed mice. Candidate miRs were identified and verified from mice exposed to three MDI-exposure regimens by TaqMan® miR assays. RESULTS: Up/down-regulation patterns of circulating mmu-miRs-183-5p, -206-3p and -381-3p were identified and verified. Circulating mmu-miR-183-5p was upregulated whereas mmu-miRs-206-3p and -381-3p were downregulated in mice exposed via all three MDI exposure regimens. DISCUSSION AND CONCLUSION: Upregulation of circulating miR-183-5p along with downregulation of circulating miRs-206-3p and -381-3p may serve as putative biomarkers of MDI exposure and may be considered as potential candidates for validation in exposed human worker populations.

Emerging trends in the UK incidence of occupational asthma: should we be worried?

While 15% of adult-onset asthma is estimated to have an occupational cause, there has been evidence of a downward trend in occupational asthma incidence in several European countries since the start of this millennium. However, recent data from The Health and Occupation Reporting network in the UK have suggested a possible reversal of this downward trend since 2014. We present these data and discuss possible explanations for this observed change in incidence trend. A high index of suspicion of occupational causation in new-onset asthma cases continues to be important, whether or not the recently observed increase in occupational asthma incidence in the UK is real or artefactual.

Novel clinical scores for occupational asthma due to exposure to high-molecular-weight agents.

OBJECTIVE: Specific inhalation challenge (SIC) as the reference diagnostic test for occupational asthma (OA) is not widely available worldwide. We aimed to develop non-SIC-based models for OA. METHODS: Of 427 workers who were exposed to high-molecular-weight agents and referred to OA clinic at Montréal Sacré-Cœur Hospital between 1983 and 2016, we analysed 160 workers who completed non-specific bronchial hyper-responsiveness (NSBHR) tests and still worked 1 month before SIC. OA was defined as positive SIC. Logistic regression models were developed. The accuracy of the models was quantified using calibration and discrimination measures. Their internal validity was evaluated with bootstrapping procedures. The final models were translated into clinical scores and stratified into probability groups. RESULTS: The final model, which included age ≤40 years, rhinoconjunctivitis, inhaled corticosteroid use, agent type, NSBHR, and work-specific sensitisation had a reasonable internal validity. The area under the receiver operating characteristics curve (AUC) was 0.91 (95% CI 0.86 to 0.95), statistically significantly higher than the combination of positive NSBHR and work-specific sensitisation (AUC=0.84). The top 70% of the clinical scores (ie, the high probability group) showed a significantly higher sensitivity (96.4%vs86.9%) and negative predictive value (93.6%vs84.1%) than the combination of positive NSBHR and work-specific sensitisation (p value <0.001). CONCLUSIONS: We developed novel scores for OA induced by high-molecular-weight agents with excellent discrimination. It could be helpful for secondary-care physicians who have access to pulmonary function test and allergy testing in identifying subjects at a high risk of having OA and in deciding on appropriate referral to a tertiary centre.

Pyromellitic dianhydride (PMDA) may cause occupational asthma.

INTRODUCTION: Anhydrides are widely used as cross-linking agents in epoxy resins and alkyd production, for example, as coatings and adhesives in plastic products. Sensitisation to several anhydrides is known to cause occupational asthma. There are indications that the lesser known pyromellitic dianhydride (PMDA) can cause irritative respiratory symptoms and possibly asthma. We report three cases of workers from a plastic foil manufacturing plant, who developed asthma when exposed to PMDA during specific inhalation challenge (SIC). METHODS: SIC was performed over 2 days according to recommendations of European Respiratory Society. Lactose powder was used in control challenges and a mixture of 10% PMDA and 90% lactose powder in active challenges. RESULTS: All cases experienced a delayed decrease in forced expiratory flow in 1 s (FEV1) 4-12 hours after active challenge. FEV1 decreased by 19%, 15% and 16%, respectively. After 21 hours, FEV1 decreased by 24% in one worker. DISCUSSION: Respiratory symptoms after working hours may represent delayed work-related asthma. During SIC, the three patients developed lower respiratory symptoms and a delayed decrease in FEV1 which suggest sensitisation. The mechanism of anhydride-related asthma is not well understood. Anhydrides are known irritants and hence an irritative response cannot be excluded. The company improved ventilation and enforced the use of respiratory protection equipment, and finally phased out PMDA. Occupational workplace risk identification may help to identify exposures. SIC can contribute to improving working conditions, by identifying and confirming asthmogens in the environment.

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.