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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.

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.

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 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.

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: 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.

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.

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. 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.

Summary 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.

SummaryBackground Little is known about the use of prick tests with chemicals in diagnosing occupational diseases. Objective To evaluate the use of prick tests in the diagnosis of occupational contact urticaria, asthma and rhinitis caused by chemicals (undertaken at the Finnish Institute of Occupational Health). Material and methods We retrospectively reviewed the patient and test files for the period 1 January 1991 to 31 May 2011. Prick tests were performed with chemical solutions and human serum albumin (HSA)–chemical conjugates. Results Positive prick test reactions to isocyanate–HSA conjugates were associated with isocyanate-specific IgE in all 20 patients, and 17 patients had a relevant occupational disease. Positive reactions to chloramine-T–HSA conjugates in 10 patients also indicated the presence of specific IgE, although occupational diseases were not always diagnosed. Eleven of 17 patients with positive reactions to persulfate solutions were diagnosed with an occupational disease. Methacrylates, colophonium-related substances, amine hardeners, ethanolamines, glutaraldehyde, glyoxal, pyrocatechol and ammonium thioglycolate did not elicit any relevant prick test reactions. No generalized reactions were detected. Conclusion Prick tests can be safely used for diagnosing contact urticaria, asthma and rhinitis caused by isocyanates, chloramine-T, persulfates, and chlorhexidine, but the results should be carefully interpreted and related to clinical symptoms and other diagnostic tests.

Background Oxidative hair dyes commonly contain paraphenylene diamine (PPD) and its derivatives, a well-known cause of delayed hypersensitivity among both consumers and hairdressers. They are also considered possible causes of occupational respiratory diseases. Despite the widespread use of hair dyes, there are only a few reports of asthma, rhinitis, and contact urticaria caused by PPD and related compounds. Objective To characterize patients with occupational asthma, rhinitis, or contact urticaria associated with oxidative hair dyes and to evaluate the diagnostic methods. Methods We reviewed the patient files of the Finnish Institute of Occupational Health for the period January 1, 2001, through May 31, 2011, to identify patients diagnosed as having asthma, rhinitis, or contact urticaria associated with oxidative hair dyes. The diagnoses of asthma and rhinitis were based on specific inhalation challenges with hair dye products. Skin prick tests were performed with hair dye ingredients as hapten conjugates of human serum albumin and with hair dye products and ingredients as is. Open skin tests confirmed the diagnosis of contact urticaria. Results We describe 11 hairdressers with occupational asthma (5 cases), rhinitis (5 cases), and contact urticaria (3 cases) due to hair dyes. Of the 52 specific inhalation challenges performed, 9 (17%) had positive results. One patient who experienced an anaphylactic reaction when having her own hair dyed had positive skin prick test results to PPD and toluene-2,5-diamine sulfate. Conclusion Hairdressers are at risk for occupational asthma, rhinitis, and contact urticaria due to oxidative hair dyes. Skin prick testing may be insensitive for detecting immediate hypersensitivity to PPD and related compounds.

pecific inhalation challenge is considered a reference standard in the diagnosis of occupational asthma. An updated handbook of challenge techniques for a large number of sensitising agents from 11 European centres is now available. http://bit.ly/2XVpW1P

Background: Rhinitis and asthma commonly coexist and are oen regarded as "unified airways disease." Evidence exists that microRNAs are important in controlling inflam- matory processes, but lile is known about their role in air- way inflammation. The present study evaluated the inflam- matory profiles of patients with allergic rhinitis (AR), with and without concomitant asthma, and of patients with non- allergic rhinitis (NAR). Methods: We analyzed inflammatory cells, cytokines, and microRNAs from nasal biopsies and measured nasal nitric oxide (nNO) levels in 159 young adult subjects subdivided into 4 groups: (1) AR; (2) AR+asthma; (3) NAR; and (4) controls. Results: We observed the upregulation of T-helper 2 (Th2) cytokines and the trend of elevation of nNO levels in AR patients compared to controls. Subjects with current AR symptoms had increased levels of miR-155, miR-205, and miR-498, but reduced levels of let-7e. In addition, patients with positive skin prick test (SPT) reactions exhibited in- creased miR-155 and miR-205 expression and a decreased level of let-7e, compared to subjects with negative SPT find- ings. Concomitant asthma had lile effect on the inflamma- tory profile of AR. No significant changes in inflammatory markers were found in NAR patients compared to healthy controls. Conclusion: Our results suggest that microRNAs miR-155, miR-205, miR-498, and let-7e may be important in the aller- gic inflammation present in nasal mucosa. Regarding NAR, our findings support the view that mechanisms other than inflammation are pivotal. C � 2013 ARS-AAOA, LLC.

Background Eyelash extensions are applied on top of customers' lashes using instant glue containing cyano acrylate, known to cause occupational rhinitis (OR) and occupational asthma (OA). The number of beauty professionals applying these extensions is increasing due to their popularity. Aims To report on a case of OA with OR and a case of OR attributable to lash extension glue and to evaluate respiratory exposure in lash extension work. Methods Two beauty professionals with suspected OA and/or OR underwent inhalation challenge, including both control challenge and work-mimicking challenges using the lash extension glue, each with a 24-h follow-up. Volatile organic compounds (VOCs) present were assessed during the lash extension glue challenge. The glues were analysed for their (meth)acrylate content. Results Both beauty professionals (case 1 and case 2) applied lash extensions regularly for several hours per day as part of their work and had work-related rhinitis. Case 1 had a longer history of lash extension work and also had asthmatic symptoms. The first lash extension glue challenge was negative in both cases, but positive OR reactions were detected in the second test. Case 1 also had a late asthmatic reaction. During the lash extension glue challenge, VOC were present in total concentrations below the irritant threshold and ethylcyanoacrylate (ECA) was detected in a concentration of 0.4mg/m(3). Chemical analysis of the glues revealed ECA was the major component. Conclusions Application of eyelash extensions using small amounts of cyanoacrylate-based glues can cause OA and OR.

Background: The inconsistency of commercial bovine dander extracts hampers the diagnostics of IgE-mediated occupational allergies. Aim: Aim was to investigate whether the in-house extract improves the diagnostics of occupational immediate allergies and reveals new information regarding bovine allergens. Methods: Altogether 102 patients with a suspected bovine-related occupational rhinitis, asthma and/or contact urticaria underwent skin-prick tests (SPTs) with in-house and available commercial bovine dander extracts. The nasal provocation test (NPT) was performed on 31 of the patients to confirm possible occupational rhinitis. The score changes of ≥ 4 point in the bilateral nasal secretion and blockage seen in anterior rhinoscopy were considered positive. Specific IgE- protein reactions from the serums of patients with positive NPTs were studied and allergens were identified from the strongest immunoblot bands using tandem mass spectrometry. Results: The in-house SPT extract yielded more positive reactions (≥ 3mm wheal) than the two commercial agents (44% vs 34% and 11%, p=0.006 and 0.001 respectively). Of the 21 patients who underwent NPTs to both in-house and commercial extract, 13 (62%) reacted only to the in-house extract, whereas five (24%) reacted to both extracts (p Conclusions: The rich allergen content of allergen extracts improves the diagnostic accuracy of immediate allergies to bovine dander. In-house bovine dander extracts are needed in the diagnostics of occupational allergies.

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.

3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)- Benzoic acid powder has been produced periodically in a Finnish chemical factory since 2010. It is an intermediate product of a plant protective agent. We describe two cases with occupational respiratory diseases and urticaria related to that benzoic acid derivate; skin prick test results are presented in the table. To our knowledge, IgE-mediated sensitization or respiratory diseases related to this agent have not been reported earlier. Patient 1, a process manager, had rhinitis, sneezing, cough and dyspnea during the process periods since 2011. He also had urticaria in uncovered skin area after washing the reactor used in the process. Specific inhalation challenge (SIC) showed positive immediate bronchial reaction, FEV1 -17% combined with increase in exhaled nitric oxide and positive nasal reaction. In addition, open skin test was positive. He was diagnosed with occupational asthma, rhinitis and urticaria. Patient 2, a mechanic, had rhinitis, sneezing and urticaria related to the same process since 2013. Open skin test was positive, SIC was not performed. He was diagnosed with occupational urticaria and rhinitis. Conclusions: This benzoic acid derivate seems cause occupational asthma, rhinitis and urticaria via IgE-mediated mechanisms. An evaluation of the respiratory and skin symptoms of the exposed workers in the factory is ongoing.

Introduction Indoor air problems may induce respiratory irritation and inflammation. In occupational settings, long-lasting non-specific building-related symptomatology, not fully medically explained, is encountered. The symptomatology may lead to illness, avoidance behavior and decreased work ability. In Finland, investigations of workers suspected of occupational asthma have revealed excess disability. There are no well-established clinical practices for the condition. Objective The aim was to develop a clinical intervention for patients with non-specific indoor air-related symptoms and decreased work ability. Methods A randomized controlled trial including psychoeducation and promotion of health behavior was carried out in 55 patients investigated for causal relationship between work-related respiratory symptoms and moisture damaged workplaces. Inclusion criteria for disability was the work ability score (WAS) ≤ 7 (scale 0–10) and indoor air-related sick leave ≥14 days the preceding year. After medical evaluation and the 3-session counseling intervention, follow-up at 6-months was assessed using self-evaluated work-ability, sick leave days, quality of life, and illness worries as outcome measures. Results The mean symptom history was 55.5 months. 82% (45 out of 55) had asthma with normal lung function tests in most cases, although reporting abundant asthma symptoms. 81% of patients (39/48) had symptomatology from multiple organ systems without biomedical explanation, despite environmental improvements at work place. At the psychological counseling sessions, 15 (60%) patients of the intervention (INT, n = 25) group showed concerns of a serious disease and in 5 (20%), concerns and fears had led to avoidance and restricted personal life. In the 6-month follow-up, the outcomes in the INT group did not differ from the treatment as usual group. Conclusion No intervention effects were found. Patients shared features with medically unexplained symptoms and sick building syndrome or idiopathic environmental intolerance. Long environment-attributed non-specific symptom history and disability may require more intensive interventions. There is a need for improved recognition and early measures to prevent indoor-associated disability. Trial registration number: Single-center randomized controlled trial (ISRCTN33165676)

Irritant-induced asthma is a rare disease, usually being caused by an accidental or other exceptionally strong exposure to substances irritating the respiratory passages. High-dose inhaled corticosteroid medication is immediately started at the emergency call service. If severe exposure is suspected, it is important to monitor the patient at least for a couple of days in hospital. Immediately after the acute stage diagnostic investigations are carried out, including a metacholine or histamine challenge test, since demonstration of airway hyperreactivity is of diagnostic and prognostic significance. The asthma may remain permanent.

Background The inflammatory processes in the upper and lower airways in allergic rhinitis and asthma are similar. Induced sputum and nasal lavage fluid provide a non-invasive way to examine proteins involved in airway inflammation in these conditions. Objectives We conducted proteomic analyses of sputum and nasal lavage fluid samples to reveal differences in protein abundances and compositions between the asthma and rhinitis patients and to investigate potential underlying mechanisms. Methods Induced sputum and nasal lavage fluid samples were collected from 172 subjects with 1) allergic rhinitis, 2) asthma combined with allergic rhinitis, 3) nonallergic rhinitis and 4) healthy controls. Proteome changes in 21 sputum samples were analysed with two-dimensional difference gel electrophoresis (2D-DIGE), and the found differentially regulated proteins identified with mass spectrometry. Immunological validation of identified proteins in the sputum and nasal lavage fluid samples was performed with Western blot and ELISA. Results Altogether 31 different proteins were identified in the sputum proteome analysis, most of these were found also in the nasal lavage fluid. Fatty acid binding protein 5 (FABP5) was up-regulated in the sputum of asthmatics. Immunological validation in the whole study population confirmed the higher abundance levels of FABP5 in asthmatic subjects in both the sputum and nasal lavage fluid samples. In addition, the vascular endothelial growth factor (VEGF) level was increased in the nasal lavage fluid of asthmatics and there were positive correlations between FABP5 and VEGF levels (r=0.660, p

From the authors: On behalf of our Task Force, I would apologise for “inappropriately” referencing the quoted article co-authored by Jean-Luc Malo, which was published in his highly renowned textbook Asthma In the Workplace [1]. Actually, we referred …

To the Editor: Asthma is described as “occupational” if it has been induced by an agent encountered in the workplace. The avoidance of further exposure to the causative agent often results in resolution of the asthma, especially if it can be achieved soon after the onset of symptoms [1]. Consequently, occupational asthma is one of the very few types of asthma that are potentially curable. The implications of this include the importance of early recognition of occupational asthma and of accurate identification of the causative agent. A variety of methods are available to make a diagnosis [2], among which specific inhalation challenge (SIC) testing is generally considered to be the reference standard [3–5]. In this context, SIC testing is the controlled exposure of a patient, under laboratory conditions, to an agent encountered in their workplace. The technique is complex, specialised and practised only in a limited number of centres. If performed carefully it is an effective, efficient and low-risk strategy for making (or in some cases refuting) a diagnosis of occupational asthma and for identifying a specific causal exposure. In 2011, we established a Task Force on occupational SIC testing, comprising 15 specialist physicians from 10 European countries; funding was granted by the European Respiratory Society (ERS). Our principle aim was to issue guidance on the indications, methodology and interpretation of SIC tests for those who already provide the service and for those who wish to do so in the future. The work programme included a survey of European centres where SIC testing is currently offered; here we present a summary of the responses to this survey. Members of the Task Force devised a 40-item questionnaire designed to enquire about the experience and practice of occupational SIC over the previous 3 years. …

This consensus statement provides practical recommendations for specific inhalation challenge (SIC) in the diagnosis of occupational asthma. They are derived from a systematic literature search, a census of active European centres, a Delphi conference and expert consensus. This article details each step of a SIC, including safety requirements, techniques for delivering agents, and methods for assessing and interpreting bronchial responses. The limitations of the procedure are also discussed. Testing should only be carried out in hospitals where physicians and healthcare professionals have appropriate expertise. Tests should always include a control challenge, a gradual increase of exposure to the suspected agent, and close monitoring of the patient during the challenge and for at least 6 h afterwards. In expert centres, excessive reactions provoked by SIC are rare. A positive response is defined by a fall in forced expiratory volume in 1 s ≥ 15% from baseline. Equivocal reactions can sometimes be clarified by finding changes in nonspecific bronchial responsiveness, sputum eosinophils or exhaled nitric oxide. The sensitivity and specificity of SIC are high but not easily quantified, as the method is usually used as the reference standard for the diagnosis of occupational asthma.

To evaluate current occupational exposure and its associations with asthma control, exacerbations, and severity in middle-aged men with asthma from youth.We used the Finnish Defence Force registers, 1986 to 1990, to select conscripts with asthma to represent mild or moderate asthmatic group (asthma group 1; N = 505), men who were exempted from military service to represent relatively severe asthmatic group (asthma group 2; N = 393), and a control group without asthma (N = 1500). A questionnaire was sent out in 2009.The current self-reported or expert-evaluated exposure to asthma-aggravating factors differed only slightly between the asthmatic groups and the controls. In asthma group 2, being a manual worker or self-employed (odds ratio, 4.5; 95% confidence interval, 1.2 to 16.3) significantly associated with asthma exacerbations.Current work may associate with the asthma outcome of middle-aged men with relatively severe asthma in their youth.

Background: Asthma and allergic rhinitis (AR) commonly coexist and can be taken as manifestations of one syndrome. Evidence exists that microRNAs (miRNAs) are important in controlling inflammatory processes and they are considered promising biomarkers. However, little is known about the differences in miRNA expression in patients with chronic allergic airway disease. This study evaluated the inflammatory and miRNA profiles of the nasal mucosa of patients with long-term asthma with and without AR. Methods: We analyzed inflammatory cells, cytokines, and miRNAs in nasal biopsies and measured exhaled and nasal nitric oxide levels during the nonpollen season in 117 middle-aged men who had suffered mainly from allergic asthma for approximately 20 years and also in 33 healthy controls. Results: The differences in the number of nasal eosinophils and cytokine expression levels were modest in nasal biopsies taken from asthmatics. Downregulation of miR-18a, miR-126, let-7e, miR-155, and miR-224 and upregulation of miR-498, miR-187, miR-874, miR-143, and miR-886-3p were observed in asthmatic patients in comparison to controls. The differences in miRNA expression were mainly similar in asthmatics with and without AR. With regard to asthma severity, a trend of increased miRNA expression in persistent asthma was seen, whereas the downregulation of certain miRNAs was most distinct in nonpersistent-asthma patients. Conclusions: Differences in miRNA expression in the nasal mucosa of subjects with long-term asthma and AR can be seen also when no markers of Th2-type inflammation are detected. Asthma severity had only a minor impact on miRNA expression.

Rhinitis and asthma commonly coexist and are often regarded as "unified airways disease." Evidence exists that microRNAs are important in controlling inflammatory processes, but little is known about their role in airway inflammation. The present study evaluated the inflammatory profiles of patients with allergic rhinitis (AR), with and without concomitant asthma, and of patients with nonallergic rhinitis (NAR).We analyzed inflammatory cells, cytokines, and microRNAs from nasal biopsies and measured nasal nitric oxide (nNO) levels in 159 young adult subjects subdivided into 4 groups: (1) AR; (2) AR+asthma; (3) NAR; and (4) controls.We observed the upregulation of T-helper 2 (Th2) cytokines and the trend of elevation of nNO levels in AR patients compared to controls. Subjects with current AR symptoms had increased levels of miR-155, miR-205, and miR-498, but reduced levels of let-7e. In addition, patients with positive skin prick test (SPT) reactions exhibited increased miR-155 and miR-205 expression and a decreased level of let-7e, compared to subjects with negative SPT findings. Concomitant asthma had little effect on the inflammatory profile of AR. No significant changes in inflammatory markers were found in NAR patients compared to healthy controls.Our results suggest that microRNAs miR-155, miR-205, miR-498, and let-7e may be important in the allergic inflammation present in nasal mucosa. Regarding NAR, our findings support the view that mechanisms other than inflammation are pivotal.

Asthma often begins in childhood or early adulthood and is a common disease among conscripts. The identification of long-term predictive factors for persistent asthma may lead to improved treatment opportunities and better disease control.Our aim was to study the prognostic factors of the severity of asthma among 40-year-old male conscripts whose asthma began in youth.We studied 119 conscripts who were referred to the Central Military Hospital during 1987-1990 due to asthma and who attended a follow-up visit approximately 20 years later. Asthma severity was evaluated during military service according to the medical records, and 20 years later during a follow-up visit using Global Initiative for Asthma guidelines. We used the results of lung function and allergy tests at baseline as predictors of current persistent asthma.Compared with baseline, asthma was less severe at follow-up: 11.8% of subjects were in remission, 42.0% had intermittent asthma, 10.9% had mild persistent asthma, and 35.3% had moderate/severe persistent asthma (p.001). In multivariate models, a positive exercise test at baseline yielded an odds ratio (OR) of 3.2 (95% CI 1.0-9.8, p = .046), a decreased FEV1/FVC % predicted an OR of 4.0 (95% CI 1.7-9.3, p = .002), and a decreased FEF50% % predicted an OR of 2.8 (95% CI 1.3-6.4, p = .012) for current persistent asthma.About half of the men had persistent asthma at the 20-year follow-up. Positive exercise tests and obstructive spirometry results were related to the persistence of asthma and may be useful long-term prognostic factors for asthma severity.

In a specific inhalation challenge (SIC) test the patient inhales an occupational agent in controlled environment and the subsequent asthmatic reaction is monitored. SIC is considered as the reference standard when confirming the diagnosis of sensitizer-induced occupational asthma. However, SIC is not always needed for the diagnosis; in many cases the causal relationship between an occupational agent and asthma can be shown also with serial peak flow measurements and specific immunologic testing. SIC is invaluable in identifying new occupational airway sensitizers. This is essential for preventing occupational asthma in the future.

Occupational exposures can cause adult-onset asthma. Early diagnosis and early avoidance of further exposure to causative agent improves the prognosis of occupational asthma. Occupational and primary care health services have an important role in the identification of new cases of occupational asthma. For the diagnosis of occupational asthma, serial peak expiratory flow (PEF) measurements should be performed in an early stage. Although it requires an effort from the patient, high quality recordings offer the best approach to assess the relationship between workplace exposure and respiratory symptoms. Good guidance and performance of serial PEF measurements in primary care is recommended and is worth the effort.

SummaryWe studied, whether asthma diagnosed in childhood or early adulthood affects work ability 20 years later. We used Finnish Defence Force registers, 1986–1990, to select: (1) conscripts with asthma to represent a mild/moderate asthma group (n = 485), (2) asthmatics who were exempted from military service to represent a relatively severe asthma group (n = 393) and (3) a control group (n = 1500) without asthma. A questionnaire consisting of validated questions on asthma and work ability was sent out in 2009. A total of 54% of the men in the first study group, 44% of those in the second study group and 44% of the controls answered. The mean age of the participants was 41 (range 37–51). Self-assessed current work ability compared with lifetime best had decreased in 28.9% of the first asthma group, in 31.1% of the second asthma group, and in 19.7% of the controls (p = 0.0007). Current smoking (OR 2.5), only basic education (OR 2.6), being a manual worker (OR 2.7) and current severe asthma (OR 3.8) associated most strongly with decreased work ability among the asthmatics. Both mild and more severe asthma at the age of around 20 seems to be associated with reduced work ability in 40-year-old males.