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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-gamma were suppressed in all the asthma groups. In transcriptomephenotype correlations, hyperresponsiveness (R similar to vertical bar 0.6 vertical bar) 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.

The short-term asthma outcome of irritant-induced asthma (IIA) is poorer than that of low-molecular-weight (LMW) sensitizer-induced occupational asthma (OA).To evaluate the long-term asthma outcome of IIA and LMW-induced OA and to determine which baseline features are associated with poor long-term outcome.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.The median interval since OA diagnosis was 6.3 years (interquartile range (IQR) 4.4-11.3). 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=0.036, respectively). Among all participants, older age (OR 1.08 per year, 95% CI 1.02-1.15), a fractional exhaled nitric oxide (FeNO) value20 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.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 worse long-term outcome among those with IIA and LMW-induced OA.

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 (HA) 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 beta-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. HA 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). HA 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. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.

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.

CONTEXTE : Bien que l’évaluation de l’inflammation bronchique, par expectoration induite, permette d’identifier différents phénotypes, chez les patients asthmatiques, il n’y a que peu d’informations sur le déterminant du pattern d’inflammation bronchique chez les patients présentant un asthme professionnel par sensibilisation. OBJECTIF : Déterminer si le pattern d’inflammation bronchique, déterminé par expectoration induite, permet de définir des phénotypes cliniques distincts. MÉTHODE : Cette étude multicentrique rétrospective a été réalisée auprès de 372 patients, présentant un asthme professionnel diagnostiqué par test d’exposition spécifique, qui étaient recrutés par le biais de la cohorte du groupe European network for Phenotypique of Ocupational Asthma. Chaque patient a bénéficié d’une expectoration induite avant et après test d’exposition spécifique. L’éosinophilie bronchique était définie par un pourcentage d’éosinophiles supérieur ou égal à 3 % dans l’expectoration induite, après test d’exposition spécifique, alors que la neutrophilie bronchique était définie par un pourcentage de neutrophiles supérieur ou égal à 76 %. RÉSULTATS : Au total, 268 (72 %) et 42 patients (11 %) présentaient respectivement une éosinophilie et une neutrophilie bronchique. Les analyses de régression logistique ont mis en évidence une association entre l’éosinophilie bronchique et l’exposition aux agents de haut poids moléculaire (odds ratio [OR], 1,89 ; IC 95 % 1,18–3,04), l’asthme persistant modéré (OR, 3,17 ; IC 95 %, 1,43–7,0) et l’asthme persistant sévère (OR, 2,39 ; IC 95 %, 1,06–5,43). La neutrophilie bronchique était associée à l’âge (OR pour chaque année supplémentaire, 1,04 ; IC 95 % 1,01–1,08), au genre masculin (OR, 2,83 : IC 95 %, 1,14–6,87), à l’asthme persistant léger (OR, 3,26 ; IC 95 %, 1,24–8,88), et à la dysphonie (OR, 2,83 ; IC95 %, 1,14–6,87). CONCLUSIONS : La majorité des patients avec un asthme professionnel par sensibilisation présentait une éosinophilie bronchique post-test d’exposition spécifique. L’éosinophilie et la neutrophilie, dans les expectorations induites, permettaient de définir des phénotypes cliniques différents, notamment en termes de sévérité et selon l’agent causal. [Phenotypes of occupational asthma defined with induced sputum after specific inhalation challenge] RATIONALE : Although the non-invasive assessment of airway inflammation through the induced sputum (IS) technique identified distinct asthma phenotypes, there is few information on the determinants of airway inflammatory pattern in sensitizer-induced occupational asthma (OA). AIM : To investigate whether the pattern of airway inflammation in IS is associated with distinct clinical phenotypes of OA. METHODS : This retrospective multicentric study was conducted among 372 patients with OA confirmed by a positive specific inhalation challenge (SIC) who were recruited in the European network for the Phenotyping of OCupational Asthma cohort (2006–2018). Each patient underwent an analysis of IS before and 24 hours after the SIC. Sputum eosinophilia and neutrophilia were defined by the presence of ≥ 3% eosinophils and ≥ 76% neutrophils in sputum samples collected after the SIC. RESULTS : In total, 268 (72%) and 42 patients (11%) exhibited sputum eosinophilia and neutrophilia, respectively. Multivariate logistic regression analysis revealed that eosinophilia was associated with exposure to a high molecular weight agent (odds ratio [OR], 1.89; 95% CI, 1.18–3.04), moderate asthma (OR, 3.17; 95% CI, 1,43–7.0) and severe asthma (OR, 2.39; 95% CI, 1.06–5.43). Sputum neutrophilia was associated with age (OR for each additional year, 1.04; 95% CI, 1.01–1.08), male gender (OR, 2.74; 95% CI, 1,21–6.8), mild asthma (OR, 3.26; 95% CI, 1.24–8.88), and dysphonia (OR, 2.83; 95% CI, 1.14–6.87). CONCLUSIONS : Sputum eosinophilia post-SIC was predominant in OA patients. Sputum eosinophilia and neutrophilia were associated with distinct clinical phenotypes of OA, especially in terms of causal agents and asthma severity.

BackgroundExposures leading to irritant-induced asthma (IIA) are poorly documented.MethodsWe 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.ResultsAltogether 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%).ConclusionsAccidents 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.

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. 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.

TO THE EDITOR, In industrialized and developing countries, occupational asthma (OA) is one of the most common chronic occupational respiratory diseases. Worldwide, especially in developing countries, OA remains under-recognized and poorly diagnosed. [...]

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. Keywords: Building-related intolerance, Disability evaluation, Environmental intolerance, Functional somatic syndromes, Indoor air

This Monograph provides the general respiratory physician with a working reference based on the latest literature and expert opinion. The initial chapter provides a contemporaneous global perspective of the epidemiology of occupational and environmental lung diseases in an ever-evolving landscape. The book then goes on to consider specific occupational lung diseases. Each chapter has a clear clinical focus and considers: key questions to ask in the history; appropriate investigations to undertake; differential diagnoses; and management. Controversies or diagnostic conundrums encountered in the clinic are also considered, and further chapters are more broadly centred on the non-workplace environment; specifically, the respiratory symptoms and diseases associated with both the outdoor and indoor environments.

Our aim was to identify occupations at risk for irritant-induced occupational asthma (IIOA) in Finland (population of 5,5 million) in 2000-2018. We searched all cases with the diagnosis number J68 and J45 (ICD-10) with relevant exposure to irritant agent from the patient register of Finnish Institute of Occupational Health and selected the subjects with verified IIOA according to the patients’ records to the study. We coded the occupations using International Standard Classification of Occupations (ISCO- 08) and grouped them based on the three-digit level. The exposure event and causing agents were analyzed in detail. We identified 69 subjects with IIOA (58/84% men, mean age 46,2 years, SD 10,1 years). Machinery mechanics and repairers was the most common occupation (Table 1). The most workers belonging to this group worked in heavy industry doing repairing tasks. Conclusions: IIOA is a rare disease. The preventive actions should be directed to the workers in risky occupations e.g. machinery mechanics and repairers, metal, chemical and food processors and agricultural workers. Table 1 The most common occupations of irritant induced occupational asthma in Finland in 2000-2018.

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 FEV1 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.

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 Fundacion Jimenez Diaz 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.

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.

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.

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.

SummaryBackground 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.

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.

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. (C) 2019 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

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.

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 ).

Background: In a medium-sized company polyvinyl chloride-polyurethane (PVC-PU) –impregnated polyester fabrics are processed to canvas and tents by cutting and jointing with electric charge. Large areas of freshly-impregnated fabrics are handled, and the temperature of them rises up to about 140 degrees Celsius in the jointing process. Building ventilation system functioned insufficiently in 2016, when eight out of seventeen workers contacted their occupational physician due to respiratory or skin symptoms. Aim: To describe the respiratory and skin diseases of the workers and to assess exposure in the processing of PVC-PU fabrics. Methods: We investigated five exposed workers in 2016-2018. Exposure was assessed in 2017 by observations of the work processes and by measuring total dust, volatile organic compounds (VOC), toluene diisocyanate (TDI) and hydrochlorid acid in the air. Results: The work-related symptoms of all 5 workers had started in 2016. We diagnosed asthma in 4 workers. Rhinitis and skin symptoms occurred in 4 workers. Total VOC varied between 2200-4200 µg/m3, and they consisted mainly of solvents used in the production. Small traces of methyl methacrylate were identified. The concentrations of all other air impurities were very low. TDI concentrations were 0.01% and 0.04% of the occupational exposure limit (OEL) for isocyanates (35 ug/m3). The results indicated that the concentrations had not been near OEL during ventilation problems in 2016, either. Conclusions: Processing of PVC-PU fabrics is a potential health hazard for lungs. The rapid onset of symptoms refers to irritants at the workplace. Further investigations are ongoing to find out the causative agent.

Background: Changes in airway proteome during specific inhalation challenge are poorly known. Nasal sample could represent the protein profile of entire airways in accordance with the “united airway” concept. Aim: To investigate changes in protein abundances in the upper airways during specific inhalation challenge to different types of occupational agents in subjects with work-related asthma. Methods: Nasal brush samples were collected from 24 non-smoking work-related asthma patients exposed to 1) protein allergens, 2) isocyanates, or 3) welding fumes before specific inhalation challenge. The second sample was collected the day after a specific inhalation challenge to an agent they were exposed at work. Proteome changes were analyzed by two-dimensional difference gel electrophoresis (2D-DIGE), and the found differentially regulated proteins were identified by mass spectrometry. Unsupervised classification analyses (hierarchical clustering and principal component analysis) were applied to data to gain an overview of protein expression patterns. Results: We found clear clustering of the protein allergen, isocyanate and welding fume groups. In all exposure groups, the differences in nasal proteome before and after challenge were small. Conclusions: Minor changes in nasal proteomes were detected during specific inhalation challenge in work-related asthma patients. Our results suggest that proteomic profiles in the airways of work-related asthma patients exposed to different occupational agents are persistent.

Introduction Exposure to chemicals occurs in a wide range of professional fields. Chemicals typically induce delayed, cell-mediated sensitisation, but some chemical agents are able to induce immediate-type allergy. The mechanisms of immediate sensitisation to chemicals are still mainly unknown, but specific IgE seems to play a role, at least for some chemical groups. The aim of our study was to evaluate the diagnostic procedures of occupational immediate allergic diseases caused by chemicals and assess the feasibility of skin testing in the diagnostics. Methods We retrospectively reviewed the patient files of the Finnish Institute of Occupational Health for the period of 1991–2011 to find patients diagnosed with immediate sensitisation to chemicals. We collected data on occupation, exposure, work-related symptoms, clinical and immunological test results, and occupational allergic diseases. Results Positive skin prick tests (SPT) were noted for organic acid anhydrides, diisocyanates, persulfates, epoxy resin, chlorhexidine and aziridine. Amine hardeners and formaldehyde induced multiple small indifferent reactions. For several other groups of chemicals sporadic or no positive SPTs were noted. Occupational contact urticaria (CU) caused by chemicals was diagnosed in 41 patients during the study period, 21 of them caused by acid anhydrides. More than half of the CU patients (54%) had a concomitant allergic airway disease. Discussion SPTs provide a fast and safe complementary tool for diagnosing immediate allergic diseases to some chemical groups, but the results should be interpreted cautiously and related to symptoms and other clinical tests. Occupational CU caused by chemicals is often accompanied by occupational airway diseases caused by the same agent.