Sputum Inflammatory Patterns Are Associated With Distinct Clinical Characteristics in Patients with Occupational Asthma Independently of the Causal Agent

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

Antecedentes: La heterogeneidad clínica en el asma ocupacional (AO) inducida por agentes sensibilizantes y su relación con los perfiles inflamatorios de las vías respiratorias siguen siendo muy poco conocidas. Objetivos: Profundizar en la caracterización de las interrelaciones entre los patrones inflamatorios en esputo inducido, diversas variables relacionadas con el asma y la categoría de agentes causales de alto o bajo peso molecular, en una gran cohorte de sujetos con AO Métodos: Este estudio multicéntrico, retrospectivo y transversal se llevó a cabo en 296 sujetos con OA confirmada mediante una provocación bronquial específica (SIC) positiva, en los que se obtuvieron muestras de esputo inducido antes y 24 horas después de la SIC. Resultados: El análisis de regresión logística multivariable reveló que la presencia de eosinofilia en esputo ≥3 % se asoció significativamente con una dosis alta de corticosteroides inhalados (odds ratio [intervalo de confianza del 95 %], 1,31 [1,11-1,55] por cada incremento de 250 µg en la dosis diaria), el uso de agonistas ß2 de acción corta menos de una vez al día (3,54 [1,82-7,00]), y un nivel de hiperreactividad bronquial inespecífica inicial (leve: 2,48 [1,21-5,08]); moderado/grave: 3,40 [1,44-8,29]). La neutrofilia en esputo ≥76%, se asoció con la edad (1,06 [1,01-1,11]), el sexo masculino (3,34 [1,29-9,99]), la ausencia de uso de corticosteroides (5,47 [2,09-15,16]), el uso de agonistas ß2 de acción corta una vez o más al día (4,09 [1,71-10,01]), la presencia de ≥ 2 exacerbaciones graves en los últimos 12 meses en el trabajo (4,22 [1,14-14,99]) y reacciones inmediatas aisladas durante la SIC (4,45 [1,85-11,59])... (AU)

Characterization of Relevant Bovine DanderAllergen Components

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

Antecedentes : las pruebas de diagnóstico en enfermedades alérgicas profesionales dependen en gran medida de la calidad de los extractos de alérgenos disponibles y de las pruebas de IgE específicas. Para mejorar las pruebas de diagnóstico en rinitis, asma y urticaria ocupacional relacionadas con el ganado, produjimos un extracto de caspa de vaca internamente, evaluamos su perfil de alérgenos y su desempeño en pruebas clínicas, y lo comparamos con extractos de caspa bovina comerciales. Métodos : Cien pacientes con sospecha de enfermedad profesional relacionada con el ganado se sometieron a pruebas cutáneas (SPT) con extractos de caspa bovina internos y 1 o 2 comerciales. Se realizaron pruebas de provocación con alérgenos nasales a 31 pacientes con sospecha de rinitis ocupacional. Utilizamos Western blot para estudiar las reacciones específicas de la proteína IgE de los sueros de los pacientes con resultados positivos en la prueba de provocación e identificamos alérgenos a partir de bandas de inmunotransferencia mediante espectrometría de masas en tándem.Resultados : La proteína fijadora de olores Bos d OBP, la albúmina sérica bovina (Bos d 6) y la lipocalina (Bos d 2) se identificaron como los principales alérgenos. Encontramos un total de 24 alérgenos de la caspa bovina, de los cuales varios eran desconocidos hasta el momento. La sensibilidad y especificidad del extracto interno en los SPT fueron del 100% y 94%, respectivamente, en 87 pacientes. Los resultados del SPT fueron negativos en 20 controles sanos. Las pruebas de provocación de alérgenos nasales con extracto interno detectaron rinitis ocupacional con una sensibilidad del 100% en 21 pacientes. Los resultados de la provocación siguieron siendo negativos en 5 controles sanos(AU)

Occupational asthma, rhinitis and contact urticaria from greenhouse work.

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

Sputum Inflammatory Patterns are Associated with Distinct Clinical Characteristics in Subjects with Occupational Asthma Independently from the Causal Agent.

BACKGROUND AND OBJECTIVES: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA. METHODS: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. RESULTS: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting b2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting b2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]). CONCLUSIONS: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.

Characterization of relevant bovine dander allergen components.

BACKGROUND: The diagnostics of allergic occupational diseases is highly dependent on the quality of the allergen extracts and specific IgE tests available. To enhance the diagnostics of bovine-related occupational rhinitis, asthma and urticaria, we produced an in-house cow dander extract, assessed its allergen profile and performance in clinical tests, and compared it to commercial bovine dander extracts. METHODS: One hundred patients with a suspected bovine-related occupational disease underwent skin prick tests (SPTs) with in-house and one to two commercial bovine dander extracts. Nasal allergen provocation tests were performed on 31 patients with suspected occupational rhinitis. We used Western blot to study the specific IgE-protein reactions from the serums of the patients with positive provocation tests, and identified allergens from immunoblot bands using tandem mass spectrometry. RESULTS: Odorant-binding protein Bos d OBP, bovine serum albumin Bos d 6, and lipocalin Bos d 2 were identified as the major allergens. We found altogether 24 bovine dander allergens, of which several were formerly unknown. The in-house extract sensitivity and specificity in SPTs were 100% and 94%, in 87 patients respectively and SPTs appeared negative in 20 healthy controls. Nasal allergen provocation tests with inhouse extract detected occupational rhinitis with 100% sensitivity in 21 patients. Five healthy controls remained negative in the provocation tests. CONCLUSIONS: Three major and several minor allergens were found from bovine dander as a cause of occupational rhinitis. A sufficient concentration and variety of tested allergens were essential in the diagnostics of bovine-related occupational diseases.

Nasal mucosa and blood cell transcriptome profiles do not reflect respiratory symptoms associated with moisture damage.

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.

Nasal protein profiles in work-related asthma caused by different exposures.

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.

Diagnosing occupational asthma.

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.

Medical surveillance for occupational asthma-how are cases detected?

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.

Occupational asthma and rhinitis caused by cyanoacrylate-based eyelash extension glues.

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.