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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.

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.

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.

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.

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.

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.

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.

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: 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.

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.