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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.

Introduction: Prognosis of occupational asthma patients is not fully known. Aims and objectives: We evaluated the work status, exposure to the asthma-causing occupational agent and asthma control about half a year after the occupational asthma diagnosis. Methods: We retrospectively reviewed the patient files of the occupational asthma cases verified with specific inhalation challenge in the Finnish Institute of Occupational Health during 2011-2015. The patients who attended a control visit six months after the diagnosis were included. Asthma symptoms and results of histamine challenge and fractional exhaled nitric oxide (FeNO) were evaluated during the diagnosis and at the control visit. Results: Altogether 102 patients attended a control visit: 2% continued working without change in occupational exposure, 21% with reduced exposure and 15% worked unexposed, 35% participated a retraining program, 15% were on sick leave, 10% were unemployed and 3% were retired. Compared to the time of the diagnosis, a decrease in hyperresponsiveness (p=0.005) and FeNO (p=0.004) and an increase in inhaled corticosteroid dose (p Conclusions: Our results suggest that occupational asthma patients need more support to remain in work life after the diagnosis, because 1/4 of them were not working or attending retraining program half a year after the diagnosis. In a short follow-up we did not find differences in asthma control between unexposed patients and those with continuing exposure.

Widespread belief from developing countries is the implementation of Specific Inhalation Challenge Tests (SICTs)are not quite feasible and can be risky in lower healthcare facilities. The work of setting up a SICTs-Lab started with scientific support of EgeTPAG-Advisory Board Members from FIOH in 2014.A multidisciplinary structure was constituted by Pulmonary/Allergy-immunology/PublicHealth/ Chemisty/Biology to implement of methodology. With Turkey’s first Occupational Fellowship Program, SICTs were officially started in spring 2016. Now, in spring 2017 we are presenting our first year’s very recent data. Among 41 patients who were referred to us, five patients (%12.19) diagnosed as OA with support of SICTs. Two painters, two bakers, one carpenter had work-related dyspnea and history of wheezing during worktimes and common shared features of them were having inconsistent asthma findings. Following negative placebo challenge tests, patients were exposed to their culprit agent in a specifically manufactured challenge cabin in Izmir, as faithful the original one in Helsinki. Ambient levels of particulate matter concentrations in the cabin were continuously monitored and kept under permitted exposure limits.FEV 1 &PEF monitoring kept continue for 8-hours after SICT and the data recorded to OASYS computer program. In the first year of their establishment SICTs have been very helpful either exclude or confirmation of diagnosis of OA. Unlike the common belief of those who hesitate to apply them, they were very safe and economically reasonable. The implementation to a developing country was not easy, but possible with right team and scientific support.

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: Medical surveillance including spirometry is periodically performed among workers who are exposed to agents causing occupational asthma in Finland. Surveillance has been shown to detect occupational asthma at an earlier stage, however only a few studies have assessed its benefits. Aims: Our aim of was to assess the role of surveillance and spirometry in intiating occupational asthma examinations. We also evaluated the quality of the spirometry. Methods: We retrospectively reviewed the medical files of 60 patients diagnosed with sensitizer induced occupational asthma at the Finnish Institute of Occupational Health in 2012-2014 and participated surveillance program. Information about work exposure, respiratory symptoms, the occupational or primary health care visit initiating examinations, first spirometry and the details of the diagnosis were collected. Results: Altogether 11 (18%) cases were detected in medical surveillance and 49 (82%) at non-surveillance doctor9s practice. The median delay from the onset of asthma symptoms to the diagnosis was 2.2 years, it did not differ between these groups. No case was detected based on abnormal spirometry without respiratory symptoms. However, 5 (8%) of the patients reported solely work related rhinitis symptoms. The spirometry was normal in half of the cases, the quality criteria were fulfilled in 86% of the tests. Conclusions: Our results support the view that spirometry for non-symptomatic workers is not beneficial in occupational asthma surveillance and highlight the importance of work related nasal symptoms in detecting occupational asthma.

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.

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

Orthopedic plaster casts contain methylene diphenyl diisocyanate (MDI). A few case reports have suggested occupational asthma to MDI in casting work. However, the knowledge of the exposure levels related to the occupational asthma cases is lacking. We report on two occupational asthma cases due to MDI in nurses irregularly applying orthopedic plaster casts, verified with placebo controlled specific inhalation challenge. The levels of MDI in the air were measured in the exposure chamber during the specific inhalation challenges with a quantitative method including filter collection and subsequent liquid chromatography-mass spectrometry (LC-MS) analysis of the isocyanate groups. In order to estimate the level of airborne MDI in casting work, measurements were conducted also in two hospitals during the application and removal of synthetic plaster casts using the same method. The concentrations were well below the occupational exposure limit in both specific inhalation challenge and hospital measurements. Based on our findings, even minor exposure to airborne MDI in casting work can cause an asthmatic reaction in some patients. Am. J. Ind. Med. 54:906–910, 2011. 2011 Wiley Periodicals, Inc.

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

One out of five working persons with asthma has work-related respiratory symptoms. When exploring the symptoms of a working-age patient it is essential to survey the job description and working conditions. Early intervention in the factors aggravating the respiratory symptoms will decrease morbidity, maintain working capacity and improve the quality of life. Occupational health service and the employer play a central role in identifying and decreasing the exposure factors in the working environment as well as in patient guidance for asthma therapy and protecting from the stimuli. The working capacity of an asthmatic person can be improved by applying vocational rehabilitation.

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 …

OBJECTIVES/HYPOTHESIS The aim of this study was to evaluate the associations between nasal nitric oxide and nasal symptoms, sinus opacification, and markers of allergic inflammation in allergic and in nonallergic rhinitis while taking into account the effect of sinus obstruction. STUDY DESIGN We studied 175 young adult subjects divided into three groups: 1) allergic rhinitis, 2) nonallergic rhinitis, and 3) controls. METHODS We measured nasal nitric oxide using the breath-holding method and exhaled nitric oxide and scored semiquantitatively nasal computed tomography scans for opacification and obstruction. We also assessed the visual analogue scores of nasal symptoms, eosinophil count, and interleukin-13 mRNA levels in nasal biopsies. RESULTS The level of nasal nitric oxide correlated with exhaled nitric oxide (r = 0.377, P

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.