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Background: Exposure-related changes in exhaled nitric oxide (FeNO) and sputum eosinophils have not been thoroughly compared in the investigation of occupational asthma., Objective: This study aimed at comparing the accuracies of the changes in FeNO concentrations and sputum eosinophil counts in identifying asthmatic reactions induced by occupational agents during specific inhalation challenges (SICs)., Methods: This retrospective multicenter study included 321 subjects who completed an assessment of FeNO and sputum eosinophils before and 24 h after SICs with various occupational agents, of whom 156 showed a positive result., Results: Post-challenge changes in FeNO and sputum eosinophils showed similar accuracies, with areas under the receiver operating characteristics curve of 0.78 (95% confidence interval [95% CI], 0.72-0.83) and 0.81 (95% CI, 0.76-0.86), respectively. Increases in FeNO level ≥ 13 ppb and sputum eosinophils ≥ 1.25% were identified as the optimal threshold values for differentiating positive from negative SICs. Using these thresholds, the changes in FeNO and sputum eosinophils each achieved a ≥ 95% specificity but a low sensitivity (55% and 62%, respectively). FeNO and sputum eosinophils showed discordant increases in 38% of subjects with a positive SIC. Combining either a rise in FeNO ≥ 13 ppb or an increase in sputum eosinophils ≥ 1.25% increased the sensitivity to 77%., Conclusions: Increases in FeNO concentration and/or sputum eosinophils after exposure to occupational agents strongly support a diagnosis of occupational asthma. The assessment of both markers of airway inflammation should be regarded as a reliable complementary tool to spirometry for identifying bronchial responses to occupational agents., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Occupational exposure to irritants is associated with poor asthma control, but the long-term clinical characteristics of irritant-induced occupational asthma (IIA) are poorly known., Objective: To evaluate whether any distinguishable features contribute to IIA patients' poor outcomes and whether clinical characteristics change over time., Methods: We re-evaluated 28 IIA patients with a median of 6.8 years (IQR 4.6-11.1) after their diagnosis at the Finnish Institute of Occupational Health in 2004-2018. We measured their lung function, non-specific bronchial hyper-responsiveness, inflammation profile and exercise capacity using an ergometric bicycle test. The participants also underwent an Asthma Control Test (ACT) and responded to questionnaires assessing their laryngeal hypersensitivity (LHQ) and dysfunctional breathing (Nijmegen Questionnaires, NQ)., Results: At follow-up, 22 (79%) participants used inhaled corticosteroids, 4 (14%) had asthma exacerbation within 1 year, 11 (39%) had ACT<20 (ie, poor asthma symptom control), 7 (26%) had abnormal spirometry and 8 (36%) had a positive methacholine challenge test result. 17 (61%) participants showed at least one elevated eosinophilic inflammation marker. Six (23%) had an abnormal LHQ score and 7 (26%) had an abnormal NQ score. 15 (58%) participants showed reduced physical capacity that was related to extensive asthma medication, poor asthma symptom control and acute IIA phenotype. A higher ACT score was the only significant change between diagnosis and follow-up (p=0.014)., Conclusion: Most of the IIA patients had normal lung function at follow-up, which had only changed a little over time. Reduced physical capacity was a common finding and appears to be related to poor asthma symptom control., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Assessment of IgE-mediated sensitization to flour allergens is widely used to investigate flour-induced occupational asthma. The diagnostic efficiency of detecting specific IgE antibodies (sIgEs) against wheat and rye flour, however, has not been thoroughly compared with other diagnostic procedures., Objective: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared with specific inhalation challenge (SIC) with flour as the reference standard., Methods: This retrospective multicenter study included 264 subjects who completed an SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result., Results: Compared with SIC, sIgE levels of 0.35 kU A /L or greater against wheat and rye provided similar sensitivities (84% to 85%, respectively), specificities (71% to 78%), positive predictive values (91% to 93%), and negative predictive values (56% to 61%). Increasing the threshold sIgE value to 5.10 kU A /L for wheat and to 6.20 kU A /L for rye provided a specificity of 95% or greater and further enhanced the positive predictive value to 98%. Among subjects with a positive SIC, those who failed to demonstrate sIgE against wheat and rye (n = 26) had significantly lower total serum IgE level and blood and sputum eosinophil counts and a lesser increase in postchallenge FeNO compared with subjects with a detectable sIgE., Conclusion: High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need to perform an SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of T H 2 biomarkers., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study is to assess the long-term physical condition, health-related quality of life, employment, and work ability of irritant-induced asthma (IIA) patients., Methods: Forty-three IIA patients completed a follow-up questionnaire a median of eight (interquartile range 4-11) years after asthma diagnosis. We compared their results with those of 43 low-molecular-weight (LMW) sensitizer-induced occupational asthma (OA) patients and those of 206 adult-onset asthmatics in the general population., Results: Of the IIA patients, 40% reported depressive symptoms. Of the <65-year-olds, 56% were employed, of whom 39% assessed their work ability as limited. IIA patients had more difficulty climbing several flights of stairs than LMW-induced OA patients (70% vs 47%, OR = 4.83 95% CI: 1.51-15.47). Most of the IIA patients' outcomes were inferior to those of the adult-onset asthmatics in the general population., Conclusions: IIA prognosis appeared poor but resembled that of LMW-induced OA., Competing Interests: Conflicts of interest: None declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Background and Objectives: Background: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. Objectives: To further characterize interactions between induced sputum inflammatory patterns, asthma-related outcomes, and the high- or low-molecular-weight category of causal agents in a large cohort of patients with OA., Methods: We conducted a multicenter, retrospective, cross-sectional study of 296 patients with OA confirmed by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure., Results: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (OR [95%CI], 1.31 [1.11 1.55] for each 250-μg increment in daily dose), short-acting ß2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild, 2.48 [1.21-5.08]; moderate/severe, 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male sex (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), use of short-acting ß2-agonists once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the previous 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the specific inhalation challenge (4.45 [1.85-11.59])., Conclusions: The findings indicate that sputum inflammatory patterns in patients with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with findings reported in nonoccupational asthma and are not related to the type of causal agent.

Purpose of Review: This review summarizes the recent literature on the long-term outcome of sensitizer-induced and irritant-induced occupational asthma., Recent Findings: Recent studies of sensitizer-induced occupational asthma show that after the offending exposure has ceased, most patients report at least partial relief of symptoms. However, in the long term, the diagnosis may negatively impact their careers, incomes, and quality of life. The studies also offer new insights into diisocyanate-induced occupational asthma phenotypes and asthma remission rates. One third of these cases were in remission in long-term after reduction or cessation of exposure. The long-term prognosis of irritant-induced occupational asthma was demonstrated to be poorer than sensitizer-induced occupational asthma. Older age, low fractional exhaled nitric oxide levels and uncontrolled asthma at the time of diagnosis predicted uncontrolled asthma in the long term in patients with irritant and low-molecular-weight sensitizer induced occupational asthma., Summary: Recent studies provide further evidence of the long-term outcome of different occupational asthma phenotypes and the factors that affect them. These findings help us identify patients at risk of poor asthma outcomes, who need close monitoring and support. It should also be borne in mind that occupational asthma diagnosis may have wider-ranging negative impacts on patients' lives., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Diagnostic tests in occupational allergic diseases are highly dependent on the quality of available allergen extracts and specific IgE tests. To enhance diagnostic testing in cattle-related occupational rhinitis, asthma, and urticaria, we produced an in- house cow dander extract, assessed its allergen profile and performance in clinical tests, and compared it with commercial bovine dander extracts., Methods: One hundred patients with a suspected cattle-related occupational disease underwent skin prick tests (SPTs) with in-house and 1 or 2 commercial bovine dander extracts. Nasal allergen provocation tests were performed on 31 patients with suspected occupational rhinitis. We used Western blot to study the specific IgE-protein reactions from the sera of the patients with positive provocation test results and identified allergens from immunoblot bands using tandem mass spectrometry., Results: The odorant-binding protein Bos d OBP, bovine serum albumin (Bos d 6), and the lipocalin (Bos d 2) were identified as the major allergens. We found a total of 24 bovine dander allergens, of which several were formerly unknown. The sensitivity and specificity of the in-house extract in SPTs were 100% and 94%, respectively, in 87 patients. The SPT results were negative in 20 healthy controls. Nasal allergen provocation tests with in-house extract detected occupational rhinitis with 100% sensitivity in 21 patients. The provocation results remained negative in 5 healthy controls., Conclusions: Three major and several minor allergens in bovine dander caused occupational rhinitis. Diagnosis of bovine allergen-related occupational diseases requires a sufficient concentration and variety of tested allergens.

Background: The current knowledge about occupational allergic diseases among greenhouse workers is scant., Aims: To describe greenhouse workers' occupational allergic diseases., Methods: We identified 28 greenhouse workers with occupational allergic diseases in 2002-2020 by conducting a systematic search in the patient register of the Finnish Institute of Occupational Health. All the patients worked in tomato- or cucumber-growing greenhouses and showed immunoglobulin-E-mediated sensitization to occupational agents. Specific inhalation challenges or workplace peak expiratory flow monitoring confirmed occupational asthma (OA), nasal allergen challenges confirmed occupational rhinitis (OR) and open skin tests confirmed occupational contact urticaria (OCU)., Results: Most patients had more than one occupational disease and were sensitized to several workplace agents. Tomato plants were the most common cause of occupational diseases and induced 22 allergic diseases in 14 patients. Cucumber plants caused occupational diseases in 10 patients (3 OA, 7 OR and 6 OCU). The pest control mite Amblyseius swirskii and a mixture of parasitic wasps Encarsia formosa and Eretmocerus eremicus both induced two OA cases. Three patients had an occupational disease caused by storage mites and three others had a work-related systemic reaction to a bumblebee sting., Conclusions: The greenhouse workers typically suffered from several occupational allergic diseases and were sensitized to cultivated plants, various pest control organisms and storage mites. All these can cause OA and OR, but in this study, OCU was only induced by cultivation plants. Cucumber plant is a novel cause of OA and OR, and A. swirskii is a novel cause of OA., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Exposure to toxic inhalants in the workplace has the potential to cause (in susceptible individuals) almost any major type of lung disease, such as asthma, COPD and interstitial lung diseases. Patients with occupational lung disease will often present to or will be managed by respiratory specialists without training in occupational respiratory medicine, and patients (or their clinicians) may not identify a link between their disease and their current or a past job. Without an awareness of the range of different occupational lung diseases that exist, their similarity to their non-occupational counterparts, and without directed questioning, these conditions may go unidentified. Patients with occupational lung diseases are often in lower paid work and are disproportionally affected by health inequality. Both clinical and socioeconomic outcomes generally improve if cases are identified early. This allows appropriate advice to be given about the risks of ongoing exposure, clinical management, occupational mobility and, in some cases, eligibility for legal compensation. As respiratory professionals, it is important that these cases are not missed, and if needed, are discussed with a physician with specialised expertise. Here we describe some of the most common occupational lung diseases and outline the diagnostic and treatment approach., Competing Interests: Conflict of interest: R.E. de la Hoz was funded in part by grant U01 OH011697 from the Centers for Disease Control/National Institute for Occupational Safety and Health (CDC/NIOSH), but his contributions reflect his views, and do not necessarily represent the official views of, nor an endorsement by, the NIOSH, the CDC, or the US Government. The other authors have no conflicts of interest to declare., (Copyright ©ERS 2023.)

Background: The short-term asthma outcome of irritant-induced asthma (IIA) is poorer than that of low-molecular-weight (LMW) sensitizer-induced occupational asthma (OA)., Objectives: To evaluate the long-term asthma outcome of IIA and LMW-induced OA and to determine which baseline features are associated with a poor long-term outcome., Methods: This follow-up questionnaire study assessed 43 patients diagnosed with IIA and 43 patients with LMW-induced OA at the Finnish Institute of Occupational Health in 2004-2018. The baseline results were analyzed to detect features associated with uncontrolled asthma (Asthma Control Test [ACT] score of ≤19, or ≥2 exacerbations or ≥1 serious exacerbation within 1 year) at follow-up., Results: The median interval since OA diagnosis was 6.3 years (interquartile range [IQR]: 4.4-11.3 years). Uncontrolled asthma was more frequent with IIA than with LMW-induced OA (58% vs 40%, adjusted odds ratio [OR]: 3.60, 95% confidence interval [CI]: 1.20-10.81). Poor symptom control was the main factor for this difference (median [IQR] ACT score of 18 [15-22] vs 21 [18-23], P = .036, respectively). Among all participants, older age (OR: 1.08 per year, 95% CI: 1.02-1.15), a fractional exhaled nitric oxide (FeNO) value <20 ppb (OR: 5.08, 95% CI: 1.45-17.80), and uncontrolled asthma at baseline (OR: 3.94, 95% CI: 1.31-11.88) were associated with uncontrolled asthma at follow-up., Conclusions: Long-term asthma control of IIA appears to be inferior to that of LMW-induced OA. Older age, a low FeNO value, and uncontrolled asthma at baseline might indicate a worse long-term outcome among those with IIA and LMW-induced OA., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Work is a substantial contributing factor of adult-onset asthma. A subtype of occupational asthma (OA) is caused by irritant agents, but knowledge of the clinical outcomes of irritant-induced asthma (IIA) is incomplete., Objectives: To evaluate whether the clinical picture of IIA differs from that of sensitizer-induced OA., Methods: This retrospective study analyzed acute and subacute IIA patients diagnosed in an occupational medicine clinic during 2004 to 2018. Sixty-nine patients fulfilled the inclusion criteria, and their characteristics were analyzed at the time of the diagnosis and 6 months later. The results were compared with those of 2 subgroups of sensitizer-induced OA: 69 high-molecular-weight (HMW) and 89 low-molecular-weight (LMW) agent-induced OA patients., Results: Six months after the diagnosis, 30% of the patients with IIA needed daily short-acting β-agonists (SABA), 68% were treated with Global Initiative for Asthma, 2020 report (GINA) step 4-5 medication, and 24% of the patients had asthma exacerbation after the first appointment. IIA depicted inferiority to LMW-induced OA in daily need for SABA (odds ratio [OR]: 3.80, 95% confidence interval [CI]: 1.38-10.46), treatment with GINA step 4-5 medication (OR: 2.22, 95% CI: 1.08-4.57), and exacerbation (OR: 3.85, 95% CI: 1.35-11.04). IIA showed poorer results than HMW-induced OA in the latter 2 of these features (OR: 2.49, 95% CI: 1.07-5.79 and OR: 6.29, 95% CI: 1.53-25.83, respectively)., Conclusions: Six months after the OA diagnosis, a significant proportion of the patients with IIA remain symptomatic and the majority of these patients use asthma medications extensively suggesting uncontrolled asthma. The short-term outcomes of IIA appear poorer than that of sensitizer-induced OA., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Exposures leading to irritant-induced asthma (IIA) are poorly documented., Methods: We retrospectively screened the medical records of patients with IIA diagnosed in an occupational medicine clinic during 2000-2018. We classified the cases into acute (onset after single exposure) and subacute (onset after multiple exposures) IIA. We analysed in detail, occupations, causative agents and their air levels in the workplace, exposure events and the root causes of high exposure., Results: Altogether 69 patients were diagnosed with IIA, 30 with acute and 39 with subacute IIA. The most common occupational groups were industrial operators (n=23, 33%), metal and machinery workers (n=16, 11%) and construction workers (n=12, 8%). Among industrial operators significantly more cases had subacute IIA than acute IIA (p=0.002). Forty cases (57%) were attributable to some type of corrosive acidic or alkaline chemical. Acute IIA followed accidents at work in different types of occupation, while subacute IIA was typical among industrial operators performing their normal work tasks under poor work hygiene conditions. The most common root cause was lack of information or false guidance in acute IIA (n=11, 36%) and neglect of workplace hygiene measures in subacute IIA (n=29, 74%)., Conclusions: Accidents are the main causes of acute IIA, whereas subacute IIA can develop in normal work in risk trades with poor work hygiene. Airborne strong acids or bases seem to be the most important causative agents of acute and subacute IIA. The different risk profiles of acute and subacute IIA should be considered in the prevention and identification of the cases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mites and insects are widely used as biologic pest control in greenhouses. A few studies have reported sensitization to mites among greenhouse workers, but the prevalence of sensitization to pest control insects is not known., Objective: We aimed to determine the prevalence of IgE-mediated sensitization to pests and their control organisms in the population of exposed greenhouse workers and the relationship between sensitization and allergic symptoms., Methods: In a cross-sectional study, we interviewed 117 tomato and cucumber greenhouse workers from eight companies that use biologic pest control. Sensitization to nine organisms was assessed by serum-specific IgE measurement. We also measured fractional exhaled nitric oxide., Results: The prevalence of specific sensitization to pests and pest control organisms was 50%; to mites, 29%; and to insects, 46%. Of the individual species, Macrolophus pygmaeus insect sensitization had the highest prevalence (46%). Asthma symptoms were significantly associated with sensitization to pest and pest control organisms (odds ratio [OR] = 3.9; 95% confidence interval [CI], 1.2-12.5) and with a fractional exhaled nitric oxide level of 25 ppb or greater (OR = 4.8; 95% CI, 1.7-13.8), indicating eosinophilic airway inflammation. Southeast Asian origin was significantly associated with sensitization (OR = 5.1; 95% CI, 2.1-12.1) and rhinitis (OR = 2.8; 95% CI, 1.2-6.3)., Conclusions: Tomato and cucumber greenhouse workers were commonly sensitized to predatory insect M pygmaeus and pest control mites. Our findings stress the importance of surveilling and preventing work-related allergic diseases among greenhouse workers., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.

Background: Work exposures play a significant role in adult-onset asthma, but the mechanisms of work-related asthma are not fully elucidated., Objective: We aimed to reveal the molecular mechanisms of work-related asthma associated with exposure to flour (flour asthma), isocyanate (isocyanate asthma), or welding fumes (welding asthma) and identify potential biomarkers that distinguish these groups from each other., Methods: We used a combination of clinical tests, transcriptomic analysis, and associated pathway analyses to investigate the underlying disease mechanisms of the blood immune cells and the airway epithelium of 61 men., Results: Compared with the healthy controls, the welding asthma patients had more differentially expressed genes than the flour asthma and isocyanate asthma patients, both in the airway epithelia and in the blood immune cells. In the airway epithelia, active inflammation was detected only in welding asthma patients. In contrast, many differentially expressed genes were detected in blood cells in all 3 asthma groups. Disease-related immune functions in blood cells, including leukocyte migration and inflammatory responses, and decreased expression of upstream cytokines such as TNF and IFN-γ were suppressed in all the asthma groups. In transcriptome-phenotype correlations, hyperresponsiveness (R ∼ |0.6|) had the highest clinical relevance and was associated with a set of exposure group-specific genes. Finally, biomarker subsets of only 5 genes specifically distinguished each of the asthma exposure groups., Conclusions: This study provides novel data on the molecular mechanisms underlying work-related asthma. We identified a set of 5 promising biomarkers in asthma related to flour, isocyanate, and welding fume exposure to be tested and clinically validated in future studies., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Quaternary ammonium compounds (QACs) are used extensively for cleaning and disinfection and have been documented in scattered reports as a cause of occupational asthma (OA) through bronchoprovocation tests (BPTs)., Objective: To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low-molecular weight (LMW) agents., Methods: The study was conducted in a retrospective multicenter cohort of 871 subjects with OA ascertained by a positive BPT. Subjects with QAC-induced OA (n = 22) were identified based on a positive BPT to QACs after exclusion of those challenged with cleaning products or disinfectants that contained other potential respiratory sensitizers. They were compared with 289 subjects with OA caused by other LMW agents., Results: Most subjects with QAC-induced OA were working in the health care sector (n = 14). A twofold or greater increase in the postchallenge level of nonspecific bronchial hyperresponsiveness was recorded in eight of 11 subjects with QAC-induced OA (72.7%) and in 49.7% of those with OA caused by other LMW agents. Although sputum assessment was available in only eight subjects with QAC-induced OA, they showed a significantly greater median (interquartile) increase in sputum eosinophils (18.1% [range, 12.1% to 21.1%]) compared with those with OA caused by other LMW agents (2.0% [range, 0% to 5.2%]; P < .001)., Conclusions: This study indicates that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports., Objective: We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents., Methods: In this retrospective multicenter study, OEB was defined by (1) a fall in FEV 1 less than 15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness both before and after the SIC and (2) a postchallenge increase of 3% or more in sputum eosinophils. The subjects who fulfilled these criteria were compared with 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline nonspecific bronchial hyperresponsiveness., Results: An isolated increase in postchallenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in fractional exhaled nitric oxide in identifying OEB among subjects with a negative SIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%)., Conclusions: This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Fluorinated hydrocarbons, which can thermally degrade into toxic hydrofluoric acid, are widely used as, for example, cooling agents in refrigerators and air conditioning systems and as medical aerosol propellants. Hydrofluoric acid is a known causative agent of irritant-induced asthma. We report on two patients with asthma initiation shortly after exposure to fluorinated hydrocarbon-based cooling agents while welding or smoking cigarettes in a confined space. Both cases developed respiratory symptoms and headache and later demonstrated nonspecific bronchial hyperresponsiveness. In follow-up, asthma was persistent and responded poorly to asthma medication. Exposure to the fluorinated hydrocarbons themselves is unlikely to have caused asthma due to their low toxicity. Instead, exposure to small amounts of hydrofluoric acid via the thermal degradation of the fluorinated hydrocarbons was considered the most likely cause of asthma onset. This is supported by the typical clinical picture of irritant-induced asthma and acute symptoms resembling hydrofluoric acid poisoning. When fluorinated hydrocarbons are used in the presence of combustion, thermal degradation may lead to the formation of hydrofluoric acid. In confined spaces, this exposure may induce asthma via irritation. Welding, smoking, and other sources of combustion in confined spaces may be a risk in workplaces and other places in which fluorinated hydrocarbons are used., (© 2020 Wiley Periodicals LLC.)

Background: While acrylates are well-known skin sensitizers, they are not classified as respiratory sensitizers although several cases of acrylate-induced occupational asthma (OA) have been reported., Objective: To evaluate the characteristics of acrylate-induced OA in a large series of cases and compare those with OA induced by other low-molecular-weight (LMW) agents., Methods: Jobs and exposures, 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 to acrylates (n = 55) or other LMW agents (n = 418) including isocyanates (n = 125)., Results: Acrylate-containing glues were the most prevalent products, and industrial manufacturing, dental work, and beauty care were typical occupations causing OA. Work-related rhinitis was more common in acrylate-than in isocyanate-induced asthma (P < .001). The increase in postchallenge fractional exhaled nitric oxide was significantly greater in acrylate-induced OA (26.0; 8.2 to 38.0 parts per billion [ppb]) than in OA induced by other LMW agents (3.0; -1.0 to 10.0 ppb; P < .001) or isocyanates (5.0; 2.0 to 16.0 ppb; P = .010). Multivariable models confirmed that OA induced by acrylates was significantly and independently associated with a postchallenge increase in fractional exhaled nitric oxide (≥17.5 ppb)., Conclusions: Acrylate-induced OA shows specific characteristics, concomitant work-related rhinitis, and exposure-related increases in fractional exhaled nitric oxide, suggesting that acrylates may induce asthma through different immunologic mechanisms compared with mechanisms through which other LMW agents may induce asthma. Our findings reinforce the need for a reevaluation of the hazard classification of acrylates, and further investigation of the pathophysiological mechanisms underlying their respiratory sensitizing potential., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Persistent physical symptoms (PPS) associated with indoor air without an adequate pathophysiological- or environmental-related explanation may lead to work disability and decreased health-related quality of life (HRQoL). We attempted to assess the effect of cognitive behavioural therapy (CBT) for PPS and also psychoeducation (PE) on these symptoms involving disability., Method: The intention-to-treat (ITT) sample included 52 employees recruited from an occupational healthcare service randomised as either controls undergoing treatment as usual (TAU) or TAU enhanced with CBT or PE. The primary outcome was HRQoL measuring the severity of symptoms and restrictions in everyday life caused by them. Secondary outcomes included depressive, anxiety and insomnia symptoms, and intolerance to environmental factors, assessed at baseline and at 3-, 6- and 12-month follow-ups., Results: At the 12-month follow-up assessment point, no statistically significant differences between treatments emerged following adjustment for gender, age, and HRQoL before the waiting period in the ITT analysis [F(2,46)=2.89, p=.07]. The secondary analysis revealed a significant improvement in HRQoL in the combined intervention group as compared with controls [F(1,47)=5.06, p=.03, g=0.41]. In total, 15% of participants dropped out during follow-up., Conclusions: The results suggest that CBT for PPS or PE might not have a robust effect on HRQoL in PPS associated with indoor air, but the study did not achieve the planned power. Despite difficulties during the recruitment process, the final dropout rates remained low, and participants positively evaluated CBT, suggesting that it represents an acceptable treatment to them. Trial status This study was registered at the ClinicalTrials.gov registry (NCT02069002)., Competing Interests: Competing interests Data collection was financially supported by the Finnish Work Environment Fund (ref 113076) and the Social Insurance Institution of Finland (Kela; ref. 23/26/2014). KK worked as a part-time medical consultant at Varma Mutual Pension Insurance Company until 30 November 2019. AV works as a part-time medical consultant at OP Insurance Ltd. and worked as a part-time medical consultant at the Social Insurance Institution of Finland (Kela, until 30 November 2018). AV was a substitute member of the medical expert group of the Unemployment Security Appeal Board (TTLK, in accordance with the Unemployment Security Commission Act) until 31 December 2017. MS works as a part-time medical adviser to the Finnish Patient Insurance Centre (in accordance with the Patient Injuries Act). These affiliations (AV, KK and MS) caused no conflicts of interest regarding this manuscript. None of these institutions profits financially or in any other way from this intervention study, from the publication of the methods used, or from the results reported. Neither the authors' institutions nor the funders had any authority over the trial activities or the preparation of the manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Chronic nonspecific symptoms attributed to indoor nonindustrial work environments are common and may cause disability, but the medical nature of this disability is unclear. The aim was to medically characterize the disability manifested by chronic, recurrent symptoms and restrictions to work participation attributed to low-level indoor pollutants at workplace and whether the condition shares features with idiopathic environmental intolerance., Methods: We investigated 12 patients with indoor air-related work disability. The examinations included somatic, psychological, and psychiatric evaluations as well as investigations of the autonomic nervous system, cortisol measurements, lung function, and allergy tests. We evaluated well-being, health, disability, insomnia, pain, anxiety, depression, and burnout via questionnaires., Results: The mean symptom history was 10.5 years; for disabling symptoms, 2.7 years. Eleven patients reported reactions triggered mainly by indoor molds, one by fragrances only. Ten reported sensitivity to odorous chemicals, and three, electric devices. Nearly all had co-occurrent somatic and psychiatric diagnoses and signs of pain, insomnia, burnout, and/or elevated sympathetic responses. Avoiding certain environments had led to restrictions in several life areas. On self-assessment scales, disability showed higher severity and anxiety showed lower severity than in physician assessments., Conclusion: No medical cause was found to explain the disability. Findings support that the condition is a form of idiopathic environmental intolerance and belongs to functional somatic syndromes. Instead of endless avoidance, rehabilitation approaches of functional somatic syndromes are applicable.

Background: Although sensitizer-induced occupational asthma (OA) accounts for an appreciable fraction of adult asthma, the severity of OA has received little attention., Objective: The aim of this study was to characterize the burden and determinants of severe OA in a large multicenter cohort of subjects with OA., Methods: This retrospective study included 997 subjects with OA ascertained by a positive specific inhalation challenge completed in 20 tertiary centers in 11 European countries during the period 2006 to 2015. Severe asthma was defined by a high level of treatment and any 1 of the following criteria: (1) daily need for a reliever medication, (2) 2 or more severe exacerbations in the previous year, or (3) airflow obstruction., Results: Overall, 162 (16.2%; 95% CI, 14.0%-18.7%) subjects were classified as having severe OA. Multivariable logistic regression analysis revealed that severe OA was associated with persistent (vs reduced) exposure to the causal agent at work (odds ratio [OR], 2.78; 95% CI, 1.50-5.60); a longer duration of the disease (OR, 1.04; 95% CI, 1.00-1.07); a low level of education (OR, 2.69; 95% CI, 1.73-4.18); childhood asthma (OR, 2.92; 95% CI, 1.13-7.36); and sputum production (OR, 2.86; 95% CI, 1.87-4.38). In subjects removed from exposure, severe OA was associated only with sputum production (OR, 3.68; 95% CI, 1.87-7.40); a low education level (OR, 3.41; 95% CI, 1.72-6.80); and obesity (OR, 1.98; 95% CI, 0.97-3.97)., Conclusions: This study indicates that a substantial proportion of subjects with OA experience severe asthma and identifies potentially modifiable risk factors for severe OA that should be targeted to reduce the adverse impacts of the disease., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Nonspecific health complaints associated with indoor air are common in work environments. In some individuals, symptoms become persistent without an adequate explanation. The aim was to study factors that associate with the health-related quality of life (HRQoL) of employees with persistent, nonspecific indoor-air-related symptomatology., Methods: We present baseline results of a randomized controlled trial of interventions targeted on the HRQoL of the employees with indoor-air-associated nonspecific symptoms. The main participant-inclusion criterion was the presence of persistent indoor-air-related multiorgan symptoms with no known pathophysiological or environment-related explanation. As a comparison for participants´ HRQoL (n = 52) we used data from the general-population Health 2011 study (BRIF8901) including information on subjects matched to the participants´ working status and age and subjects with asthma, anxiety or depressive disorder, or other chronic conditions with work disability., Results: The participants showed greater and a clinically significant impairment of HRQoL [M = 0.83, SE = 0.013] than individuals from the general population [M = 0.95, SE = 0.001, p < .001, Hedges´ g = 2.33] and those with asthma [M = 0.93, SE = 0.005, p < .001, Hedges´ g = 1.46], anxiety and depressive disorder [M = 0.89, SE = 0.006, p < .001, Hedges´ g = 0.73], or a chronic condition with work disability [M = 0.91, SE = 0.003, p < .001, Hedges´ g = 1.11]. Prevalent symptoms of depression, anxiety, and insomnia and poor recovery from work were associated with a poor HRQoL., Conclusions: Individuals with nonspecific indoor-air-associated symptoms have a poorer HRQoL than individuals in the general population with a globally burdensome disease. Psychological distress associated with a poor HRQoL should be considered in the making of decisions about the treatment of these patients., Trial Registration: ClinicalTrials.gov, NCT02069002., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Two-component epoxy resin systems (ERSs) composed of epoxy resin and polyamine hardeners are extensively used in industrial and construction coating. Triglycidyl isocyanurate (TGIC) is another type of epoxy derivative, mostly encountered in polyester powder paints. Epoxy compounds are well-known skin sensitizers, but their respiratory-sensitizing potential is largely unknown., Objective: To report patients examined for occupational asthma (OA) from epoxy compounds., Methods: We retrospectively reviewed patient files of cases tested with a placebo-controlled specific inhalation challenge (SIC) according to their workplace exposure-either by mixing epoxy resin and the polyamine hardener of a 2-component paint or by dusting or heating TGIC-containing powder paint. The data were collected from the Finnish Institute of Occupational Health, Helsinki, Finland, and at Fundación Jiménez Díaz Hospital, Madrid, Spain, during 1997 to 2018. We also measured airborne polyamine and solvent vapors at the workplace and during SIC with ERSs., Results: Altogether 113 patients with work-related asthma symptoms underwent SIC with ERSs. Fifteen cases (13%) had positive SIC reactions confirming OA; in 12 cases reactions were late-type, in 1 case early, and in 2 cases combined. The median duration of exposure for patients with OA was 10 years; 2 of them (13%) had a diagnosis of allergic contact dermatitis from ERS compounds. In addition, 3 cases had a positive SIC reaction to TGIC. The airborne polyamine levels measured were low., Conclusion: ERSs and TGIC can cause sensitizer-induced OA in some exposed workers. Respiratory exposure to ERSs is difficult to demonstrate using air measurements., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Upper and lower respiratory symptoms and asthma are adverse health effects associated with moisture-damaged buildings. Quantitative measures to detect adverse health effects related to exposure to dampness and mold are needed. Here, we investigate differences in gene expression between occupants of moisture-damaged and reference buildings. Moisture-damaged (N = 11) and control (N = 5) buildings were evaluated for dampness and mold by trained inspectors. The transcriptomics cohort consisted of nasal brushings and peripheral blood mononuclear cells (PBMCs) from 86 teachers, with/without self-perceived respiratory symptoms. Subject categories comprised reference (R) and damaged (D) buildings with (S) or without (NS) symptoms, that is, R-S, R-NS, DS, and D-NS. Component analyses and k-means clustering of transcriptome profiles did not distinguish building status (R/D) or presence of respiratory symptoms (S/NS). Only one nasal mucosa gene (YBX3P1) exhibited a significant change in expression between D-S and D-NS. Nine other nasal mucosa genes were differentially expressed between R-S and D-S teachers. No differentially expressed genes were identified in PBMCs. We conclude that the observed mRNA differences provide very weak biological evidence for adverse health effects associated with subject occupancy of the specified moisture-damaged buildings. This emphasizes the need to evaluate all potential factors (including those not related to toxicity) influencing perceived/self-reported ill health in moisture-damaged buildings., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: 3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)-benzoic acid (BCMBA) has not previously been identified as a respiratory sensitiser. We detected two cases who presented respiratory and urticaria symptoms related to BCMBA and had positive skin prick tests to the agent. Subsequently, we conducted outbreak investigations at the BCMBA-producing factory and performed clinical examinations to confirm occupational diseases., Methods: The outbreak investigations included observations of work processes, assessment of exposure, a medical survey with a questionnaire and skin prick tests with 0.5% BCMBA water solution on 85 exposed workers and 9 unexposed workers. We used specific inhalation or nasal challenge and open skin application test to investigate BCMBA-related occupational asthma, rhinitis and contact urticaria., Results: We identified nine workers with respiratory and/or skin symptoms and positive skin prick tests to BCMBA in a chemical factory. A survey among chemical factory workers indicated a BCMBA-related sensitisation rate of 8% among all exposed workers; the rate was highest (25%) among production workers in the production hall. Sensitisation was detected only in workers with the estimated highest exposure levels. Six cases of occupational asthma, rhinitis and/or contact urticaria caused by BCMBA were confirmed with challenge tests. Asthma-provoking doses in specific inhalation challenges were very low (0.03% or 0.3% BCMBA in lactose)., Conclusions: We identified a new low molecular weight agent causing occupational asthma, rhinitis and contact urticaria. A typical clinical picture of allergic diseases and positive skin prick tests suggest underlying IgE-mediated disease mechanisms. Stringent exposure control measures are needed in order to prevent BCMBA-related diseases., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The mechanisms of work-related asthma (WRA) are incompletely delineated. Nasal cell samples may be informative about processes in the lower airways. Our aim was to determine the nasal protein expression profiles of WRA caused by different kind of exposures., Methods: We collected nasal brush samples from 82 nonsmoking participants, including healthy controls and WRA patients exposed to (i) protein allergens, (ii) isocyanates and (iii) welding fumes the day after relevant exposure. The proteome changes in samples were analysed by two-dimensional difference gel electrophoresis, and the differentially regulated proteins found were identified by mass spectrometry. Immunological comparison was carried out using Western blot., Results: We detected an average of 2500 spots per protein gel. Altogether, 228 protein spots were chosen for identification, yielding 77 different proteins. Compared to the controls, exposure to protein allergens had the largest effects on the proteome. Hierarchical clustering revealed that protein allergen- and isocyanate-related asthma had similar profiles, whereas asthma related to welding fumes differed. The highly overrepresented functional categories in the asthma groups were defence response, protease inhibitor activity, inflammatory and calcium signalling, complement activation and cellular response to oxidative stress. Immunological analysis confirmed the found abundance differences in galectin 10 and protein S100-A9 between the groups., Conclusions: Work-related asthma patients exposed to protein allergens and isocyanates elicit similar nasal proteome responses and the profiles of welders and healthy controls were alike. Revealed biological activities of the protein expression changes are associated with allergic inflammation and asthma., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Contact urticaria (CU) and protein contact dermatitis (PCD) are mainly induced by an immediate, IgE-mediated immunological mechanism. Immediate sensitization is also linked to asthma and/or allergic rhinitis., Objectives: To report causes of work-induced CU and PCD, and to evaluate the occurrence of concomitant airway diseases., Methods: We retrospectively reviewed the patient files of cases diagnosed with CU or PCD at the Finnish Institute of Occupational Health during 1995-2011. We obtained data on occupation, exposures, clinical and immunological test results, and diagnosed occupational skin and respiratory diseases., Results: Altogether, 291 cases of occupational CU or PCD were diagnosed during the study period. The most common causes were flour, cow dander, natural rubber latex and acid anhydrides. Concomitant occupational asthma caused by the same agent as the skin disease was detected in 60 patients (21%), and occupational rhinitis was detected in 111 patients (38%)., Conclusions: Almost half of the patients (46%) with occupational CU and PCD had concomitant occupational airway disease. Patients with CU/PCD should always be asked about respiratory symptoms, and preventive measures at the workplace should include protection of both the skin and the airways., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Seasonal allergic rhinitis (SAR) caused by intermittent exposure to seasonal pollen causes itching, nasal congestion, and repeated sneezing, with profound effects on quality of life, work productivity, and school performance. Although both the genotype and environmental factors can contribute to the immunologic basis of allergic reactions, the molecular underpinnings associated with the pathogenesis of allergic rhinitis are not entirely clear., Methods: To address these questions, nasal epithelial brushings were collected from 29 patients with SAR and 31 control subjects during and after the pollen season. We then implemented an orbitrap-based, bottom-up, label-free quantitative proteomics approach, followed by multivariate analyses to identify differentially abundant (DA) proteins among the 4 sample groups., Results: We identified a total of 133 DA proteins for which the most significantly overrepresented functional category was found to be interferon 1 signaling. Two proteins, cystatin 1 and myeloblastin, the former of which protects against protease activity of allergens and the latter with a role in epithelial barrier function, were DA in patients with SAR and control subjects, irrespective of season. Moreover, interferon-inducible protein with tetratricopeptide repeats 1, cystatin 1, and interferon-inducible protein with tetratricopeptide repeats 3 were found to be differentially regulated between patients with SAR and control subjects, with inverse abundance dynamics during the transition from fall to spring., Conclusion: We identified type 1 interferon-regulated proteins as biomarkers in patients with SAR, potentially playing an important role in its pathogenesis. Moreover, when compared with patients with SAR, healthy subjects exhibit an antagonistic proteomic response across seasons, which might prove to be a therapeutic target for disease prevention., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Occupational exposure is an important, global cause of respiratory disease. Unlike many other non-communicable lung diseases, the proximal causes of many occupational lung diseases are well understood and they should be amenable to control with use of established and effective approaches. Therefore, the risks arising from exposure to silica and asbestos are well known, as are the means of their prevention. Although the incidence of occupational lung disease has decreased in many countries, in parts of the world undergoing rapid economic transition and population growth-often with large informal and unregulated workforces-occupational exposures continue to impose a heavy burden of disease. The incidence of interstitial and malignant lung diseases remains unacceptably high because control measures are not implemented or exposures arise in novel ways. With the advent of innovative technologies, new threats are continually introduced to the workplace (eg, indium compounds and vicinal diketones). In developed countries, work-related asthma is the commonest occupational lung disease of short latency. Although generic control measures to reduce the risk of developing or exacerbating asthma are well recognised, there is still uncertainty, for example, with regards to the management of workers who develop asthma but remain in the same job. In this Review, we provide recommendations for research, surveillance, and other action for reducing the burden of occupational lung diseases., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: In Finland, medical surveillance, including spirometry, is periodically performed for workers who are exposed to agents capable of causing occupational asthma (OA). Although it has been shown that surveillance can detect OA at an early stage, few studies have assessed its benefits or the role of surveillance spirometry., Aims: To assess the role of surveillance and spirometry in detecting OA and to evaluate the quality of spirometry., Methods: We retrospectively reviewed the medical files of patients in health surveillance programmes who were diagnosed with sensitizer-induced OA at the Finnish Institute of Occupational Health in 2012‒14. We collected information on work exposure, respiratory symptoms, healthcare visits that initiated the diagnostic process, first spirometry and other diagnostic tests., Results: Sixty files were reviewed. Medical surveillance detected 11 cases (18%) and 49 cases (82%) were detected at doctors' appointments that were not related to surveillance. The median delay from the onset of asthma symptoms to diagnosis was 2.2 years. Delay did not differ between these groups. No cases were detected on the basis of abnormal spirometry without respiratory symptoms. However, five patients (8%) initially reported solely work-related rhinitis symptoms. Spirometry was normal in half of the cases and quality criteria were fulfilled in 86% of the tests., Conclusions: Fewer than one in five OA cases were detected through medical surveillance. Investigations were initiated by respiratory symptoms. No asymptomatic worker was referred because of abnormal spirometry. Our results highlight the importance of work-related nasal symptoms in detecting OA., (© The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Making an accurate diagnosis of occupational asthma (OA) is, generally, important. The condition has not only significant health consequences for affected workers, but also substantial socio-economic impacts for workers, their employers and wider society. Missing a diagnosis of OA may lead to continued exposure to a causative agent and progressive worsening of disease; conversely, diagnosing OA when it is not present may lead to inappropriate removal from exposure and unnecessary financial and social consequences. While the most accurate investigation is specific inhalation challenge in an experienced centre, this is a scarce resource, and in many cases, reliance is on other tests. This review provides a technical dossier of the diagnostic value of the available methods which include an appropriate clinical history, the use of specific immunology and measurement of inflammatory markers, and various methods of relating functional changes in airway calibre to periods at work. It is recommended that these approaches are used iteratively and in judicious combination, in cognizance of the individual patient's circumstances and requirements. Based on available evidence, a working diagnostic algorithm is proposed that can be adapted to the suspected agent, purpose of diagnosis and available resources. For better or worse, many of the techniques - and their interpretation - are available only in specialized centres and where there is room for doubt, referral to such a centre is probably wise. Accordingly, the implementation or development of such specialized centres with appropriate equipment and expertise should greatly improve the diagnostic evaluation of work-related asthma., (© 2016 John Wiley & Sons Ltd.)

Introduction: Indoor air-related conditions share similarities with other conditions that are characterised by medically unexplained symptoms (MUS)-a combination of non-specific symptoms that cannot be fully explained by structural bodily pathology. In cases of indoor air-related conditions, these symptoms are not fully explained by either medical conditions or the immunological-toxicological effects of environmental factors. The condition may be disabling, including a non-adaptive health behaviour. In this multifaceted phenomenon, psychosocial factors influence the experienced symptoms. Currently, there is no evidence of clinical management of symptoms, which are associated with the indoor environment and cannot be resolved by removing the triggering environmental factors. The aim of this study is to compare the effect of treatment-as-usual (TAU) and two psychosocial interventions on the quality of life, and the work ability of employees with non-specific indoor air-related symptomatology., Methods and Analyses: The aim of this ongoing randomised controlled trial is to recruit 60 participants, in collaboration with 5 occupational health service units. The main inclusion criterion is the presence of indoor air-related recurrent symptoms in ≥2 organ systems, which have no pathophysiological explanation. After baseline clinical investigations, participants are randomised into interventions, which all include TAU: cognitive-behavioural psychotherapy, psychoeducation and TAU (control condition). Health-related quality of life, measured using the 15D-scale, is the primary outcome. Secondary outcomes include somatic and psychiatric symptoms, occupational factors, and related underlying mechanisms (ie, cognitive functioning). Questionnaires are completed at baseline, at 3, 6 and 12-month follow-ups. Data collection will continue until 2017. The study will provide new information on the individual factors related to indoor air-associated symptoms, and on ways in which to support work ability., Ethics and Dissemination: The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa, Finland, has granted approval for the study. The results will be published in peer-reviewed journals., Trial Registration Number: NCT02069002; Pre-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)