Human Keratinocyte Response to 4,4'-Methylene Diphenyl Diisocyanate-Glutathione Conjugate Exposure.

Workplace exposure to diisocyanates like 4,4'-methylene diphenyl diisocyanate can cause occupational asthma (MDI-OA), and the underlying biological pathways are still being researched.Although uncertainty remains, evidence supports the hypothesis that dermal exposure to MDI plays an important role in the development of MDI-OA.Gene expression, proteomics, and informatics tools were utilized to characterize changes in expression of RNA and protein in cultured human HEKa keratinocyte cells following exposure to conjugates of MDI with glutathione (MDI-GSH).RT-qPCR analysis using a panel of 39 candidate primers demonstrated 9 candidate genes upregulated and 30 unchanged.HPLC-MS/MS analysis of HEKa cell lysate identified 18,540 proteins across all samples Sixty proteins demonstrate statistically significant differential expression in exposed cells, some of which suggest activation of immune and inflammatory pathways.The results support the hypothesis that dermal exposures have the potential to play an important role in the development of MDI-OA. Furthermore, proteomic and gene expression data suggest multiple immune (adaptive and innate) and inflammatory pathways may be involved in the development of MDI-OA.

Chemical respiratory sensitization-Current status of mechanistic understanding, knowledge gaps and possible identification methods of sensitizers.

Respiratory sensitization is a complex immunological process eventually leading to hypersensitivity following re-exposure to the chemical. A frequent consequence is occupational asthma, which may occur after long latency periods. Although chemical-induced respiratory hypersensitivity has been known for decades, there are currently no comprehensive and validated approaches available for the prospective identification of chemicals that induce respiratory sensitization, while the expectations of new approach methodologies (NAMs) are high. A great hope is that due to a better understanding of the molecular key events, new methods can be developed now. However, this is a big challenge due to the different chemical classes to which respiratory sensitizers belong, as well as because of the complexity of the response and the late manifestation of symptoms. In this review article, the current information on respiratory sensitization related processes is summarized by introducing it in the available adverse outcome pathway (AOP) concept. Potentially useful models for prediction are discussed. Knowledge gaps and gaps of regulatory concern are identified.

Impact of Ongoing Treatment With Inhaled Corticosteroids During Specific Inhalation Challenges for Diagnosing Occupational Asthma.

BACKGROUND: Specific inhalation challenge (SIC) tests are still the reference test for diagnosing sensitizer-induced occupational asthma (SIOA). The European Respiratory Society recommends the cessation of inhaled corticosteroids (ICS) 72 hours before SIC. OBJECTIVE: To assess the effect of an ongoing ICS treatment during SIC on the maximum fall in forced expiratory volume in 1 second (FEV1), the change in methacholine provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20), and sputum eosinophil counts after exposure to the suspected agent. METHODS: We performed a retrospective analysis using a database of cases referred to our center for suspected SIOA from 1999 to 2022. The results of the SIC were compared between subjects treated with ICS during SIC and steroid-naïve subjects. RESULTS: Six hundred and seventy-one individuals underwent SIC in the laboratory. Three hundred and eighteen were treated with ICS, whereas 353 were steroid naïve. The proportion of subjects with a positive SIC was greater among ICS-treated subjects (39. 6%) compared with steroid-naïve subjects (27.5%, P < .001). A treatment with ICS did not influence the outcome of the SIC. There was no difference in the change in PC20 or the percentage of sputum eosinophils after SIC between steroid-treated and steroid-naïve subjects. CONCLUSIONS: An ongoing ICS treatment during an SIC did not affect the occurrence of an asthmatic reaction, the change in airway responsiveness, or eosinophilic inflammation after exposure to the suspected agent in subjects who have been treated with ICS for a long period of time.

Occupational agents-mediated asthma: From the perspective of autophagy.

Occupational asthma (OA) is a common occupational pulmonary disease that is frequently underdiagnosed and underreported. The complexity of diagnosing and treating OA creates a significant social and economic burden, making it an important public health issue. In addition to avoiding allergens, patients with OA require pharmacotherapy; however, new therapeutic targets and strategies need further investigation. Autophagy may be a promising intervention target, but there is a lack of relevant studies summarizing the role of autophagy in OA. In this review consolidates the current understanding of OA, detailing principal and novel agents responsible for its onset. Additionally, we summarize the mechanisms of autophagy in HMW and LMW agents induced OA, revealing that occupational allergens can induce autophagy disorders in lung epithelial cells, smooth muscle cells, and dendritic cells, ultimately leading to OA through involving inflammatory responses, oxidative stress, and cell death. Finally, we discuss the prospects of targeting autophagy as an effective strategy for managing OA and even steroid-resistant asthma, encompassing autophagy interventions focused on organoids, organ-on-a-chip systems, nanomaterials vehicle, and nanobubbles; developing combined exposure models, and the role of non-classical autophagy in occupational asthma. In briefly, this review summarizes the role of autophagy in occupational asthma, offers a theoretical foundation for OA interventions based on autophagy, and identifies directions and challenges for future research.

[Occupational diseases related to otorhinolaryngology]. / Berufskrankheiten mit Bezug zur HNO-Heilkunde.

In the German Ordinance on Occupational Diseases (BKV), there are currently 82 occupational diseases listed, of which 18 partially or completely fall within the field of ENT medicine due to the associated health disorders. Noise-induced hearing loss is usually the focus of attention for the ENT specialist, but it has long since ceased to be the only occupational disease. In order to help uncover possible causalities between occupational noxious substances and diseases, it is important that physicians report their own observations and new scientific findings regarding suspected cases to the German Social Accident Insurance, especially in situations where cancer may be linked to occupational influences.

The impact of years of training and possible technical, procedural, and individual risk factors for the development of atopic symptoms among bakery and confectionery trainees.

PURPOSE: Occupational asthma is commonly observed in bakers and confectioners. Endogenous and exogenous risk factors contribute to bakers' asthma. A heightened awareness of this and early diagnosis can be helpful in terms of prevention. The aim of the study was to identify a temporal relationship between the years of training, as well as possible technical, procedural, and individual risk factors for the development of flour-exposure related atopic symptoms such as rhinitis, cough, and rash in young professionals. METHODS: 127 bakers and confectioner trainees were observed over a one-year period. Two questionnaires served as test instruments. It was investigated whether the rates of atopic symptoms change over the course of a school year and which conditions in the workplace could be responsible for this. Descriptive statistics were used to answer the research questions concerning flour exposure and symptom rates. The Pearson-Chi-Square test was used for testing statistical differences between different groups (e.g. year of training, working conditions). RESULTS: An increase in rates of self-reported rhinitis, coughing, and rashes throughout the duration of traineeship was shown (e.g. rhinitis of bakers at work: 0% in the first year of training, 20% in the second and 33% in the third year of training). The installation of vapour extraction systems and low-dust transfer of baking agents led to fewer symptoms in the workplace (30% of participants with rhinitis symptoms worked with no installed vapour extraction systems). A medical history of atopy was positively correlated with the occurrence of symptoms. CONCLUSION: To prevent the development of asthma in bakers, methods to improve occupational health and safety should be developed. Creating low dust working conditions e.g., due to the use of vapour extraction systems should be considered.

Diagnostic Accuracy of Specific IgE Against Wheat and Rye in Flour-Induced Occupational Asthma.

BACKGROUND: Assessment of IgE-mediated sensitization to flour allergens is widely used to investigate flour-induced occupational asthma. The diagnostic efficiency of detecting specific IgE antibodies (sIgEs) against wheat and rye flour, however, has not been thoroughly compared with other diagnostic procedures. OBJECTIVE: We sought to evaluate the diagnostic accuracy of sIgE against wheat and rye compared with specific inhalation challenge (SIC) with flour as the reference standard. METHODS: This retrospective multicenter study included 264 subjects who completed an SIC with flour in eight tertiary centers, of whom 205 subjects showed a positive SIC result. RESULTS: Compared with SIC, sIgE levels of 0.35 kUA/L or greater against wheat and rye provided similar sensitivities (84% to 85%, respectively), specificities (71% to 78%), positive predictive values (91% to 93%), and negative predictive values (56% to 61%). Increasing the threshold sIgE value to 5.10 kUA/L for wheat and to 6.20 kUA/L for rye provided a specificity of 95% or greater and further enhanced the positive predictive value to 98%. Among subjects with a positive SIC, those who failed to demonstrate sIgE against wheat and rye (n = 26) had significantly lower total serum IgE level and blood and sputum eosinophil counts and a lesser increase in postchallenge FeNO compared with subjects with a detectable sIgE. CONCLUSION: High levels of sIgE against wheat and/or rye flour strongly support a diagnosis of flour-induced occupational asthma without the need to perform an SIC. The absence of detectable sIgE against wheat and rye in subjects with a positive SIC seems to be associated with lower levels of TH2 biomarkers.

How Allergists Can Perform an Occupational History in Every Patient.

The occupational history is often neglected in the routine evaluation of new patients with asthma, chronic rhinitis, or dermatologic complaints. Such omissions are inadvertent because work-related conditions are often not prioritized. There also may be lack of awareness of the scope of respiratory or cutaneous allergens capable of inducing occupational asthma (OA) or work-related contact dermatitis. Evidence exists suggesting that the occupational history is often neglected among primary care physicians and specialists. Failure to diagnose OA in a timely fashion by identifying occupational sources of exposure, for example, may result in unnecessary morbidity in workers whose exposure is not modified. In this commentary, we propose a brief intake survey to be administered to all patients coming to an allergy practice to quickly screen for possible work-related respiratory symptoms and another for occupational dermatitis. This would require minimal physician time and could be self-administered at the initial encounter and incorporated into the medical record. A positive response to either survey should trigger a more detailed evaluation by the allergy specialist. More detailed approaches for stepwise clinical evaluation of the worker suspected of OA and contact dermatitis are discussed.

[Asthma]. / Asma.

Asthma is a chronic inflammatory disease that affects about 5% of the world's population and generates high health and social costs. Proper management of the disease requires a correct diagnosis, based on objective measures of functional impairment, as well as symptom control and assessment of the future risk of exacerbations.It has been estimated that 18% of asthma patients in Western Europe have severe asthma and approximately 50% of them have poor control. The severity of asthma is established based on the minimum maintenance treatment needs to achieve control. Asthma clinical practice guidelines recommend classifying severe patients into allergic asthma (T2); eosinophilic asthma (T2) and non-T2 asthma in order to establish the most appropriate treatment.In recent decades, new biological therapies have been developed that can be applied according to the phenotype and endotype of asthma, allowing for selective and personalized treatment. These phenotypes and endotypes can change over time and therefore, the identification of biomarkers capable of predicting the severity, the course of the disease and the response to a given treatment seems essential. A large number of biomarkers have been studied in asthma, but so far only a few can be readily used in routine clinical practice. The application of omics technologies (epigenomics, genomics, transcriptomics, proteomics, metabolomics, lipidomics, etc.) for this purpose is still in the research phase.

MicroRNA-mediated Krüppel-like factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4'-methylene diphenyl diisocyanate exposed macrophages.

1. Occupational exposure to 4,4'-methylene diphenyl diisocyanate (MDI) is associated with occupational asthma (OA) development. Alveolar macrophage-induced recruitment of immune cells to the lung microenvironment plays an important role during asthma pathogenesis. Previous studies identified that MDI/MDI-glutathione (GSH)-exposure downregulates endogenous hsa-miR-206-3p/hsa-miR-381-3p. Our prior report shows that alternatively activated (M2) macrophage-associated markers/chemokines are induced by MDI/MDI-GSH-mediated Krüppel-Like Factor 4 (KLF4) upregulation in macrophages and stimulates immune cell chemotaxis. However, the underlying molecular mechanism(s) by which MDI/MDI-GSH upregulates KLF4 remain unclear.2. Following MDI-GSH exposure, microRNA(miR)-inhibitors/mimics or plasmid transfection, endogenous hsa-miR-206-3p/hsa-miR-381-3p, KLF4, or M2 macrophage-associated markers (CD206, TGM2), and chemokines (CCL17, CCL22, CCL24) were measured by either RT-qPCR, western blot, or luciferase assay.3. MDI-GSH exposure downregulates hsa-miR-206-3p/hsa-miR-381-3p by 1.46- to 9.75-fold whereas upregulates KLF4 by 1.68- to 1.99-fold, respectively. In silico analysis predicts binding between hsa-miR-206-3p/hsa-miR-381-3p and KLF4. Gain- and loss-of-function, luciferase reporter assays and RNA-induced silencing complex-immunoprecipitation (RISC-IP) studies confirm the posttranscriptional regulatory roles of hsa-miR-206-3p/hsa-miR-381-3p and KLF4 in macrophages. Furthermore, hsa-miR-206-3p/hsa-miR-381-3p regulate the expression of M2 macrophage-associated markers and chemokines via KLF4.4. In conclusion, hsa-miR-206-3p/hsa-miR-381-3p play a major role in regulation of MDI/MDI-GSH-induced M2 macrophage-associated markers and chemokines by targeting the KLF4 transcript, and KLF4-mediated regulation in macrophages.

Asma ocupacional: a propósito de un caso / Work-related Asthma: a case report / Asma ocupacional: relato de caso

Se presenta el caso de un trabajador de 31 años que desempeña tareas en un molino de granos desde hace 12 años y que ha desarrollado asma ocupacional. El objetivo del artículo es presentar los fundamentos utilizados para sostener el origen profesional del asma adquirido. Se describen las tareas laborales que desarrolla, materiales y medios de trabajo que utiliza. Se analiza en particular la exposición laboral a polvo orgánico y su vinculación temporal con la sintomatología respiratoria. Esta información permite comprender la importancia de las condiciones en las que realiza el trabajo y la exposición a un factor de riesgo, el polvo orgánico, para el desarrollo de la patología respiratoria laboral. Se realizaron mediciones de volumen máximo espiratorio pulmonar, con técnica de pico flujo, durante la jornada laboral y fuera de ésta. Se observaron variaciones del flujo espiratorio mayores a 20%, tanto durante la jornada laboral como fuera de ella, con similar patrón sintomático, según relata el trabajador. Se concluyó que existe evidencia del nexo causal entre el asma y el trabajo, por lo que se plantea el diagnóstico de asma ocupacional. Se destaca la importancia de evaluar los riesgos laborales en cada actividad para implementar planes de vigilancia de la salud, tanto del operario como del ambiente de trabajo, para prevenir la aparición como la evolución de esta u otras patologías que en muchos casos generan incapacidad para la tarea y deterioro de la calidad de vida de los trabajadores.

We present the case of a 31-year-old worker who has been working in a grain mill for 12 years and has developed work-related asthma. The objective of this article is to present the foundations used to support the occupational origin of the acquired asthma. The study describe the work tasks performed, the materials used, and the working methods. The work-related exposure to organic dust and its temporal relationship with respiratory symptoms is particularly analyzed. This information allows us to understand the importance of working conditions and exposure to organic dust, a risk factor, for the development of this work-related respiratory pathology. Measurements of maximum expiratory lung volume were made using the peak flow technique during and outside of the workday. Expiratory flow variations greater than 20% were observed, both during and outside of the workday, which followed a similar symptomatic pattern as reported by the worker. The study concluded that there is evidence of a causal link between asthma and work, thus suggesting the diagnosis of work-related asthma. The importance of assessing occupational risks in each activity to implement health surveillance plans for both workers and the work environment is highlighted, aiming to prevent the onset and progression of this and other pathologies that often result in work incapacity and deterioration of workers' quality of life.

Apresentamos o caso de um paciente de 31 anos de idade que trabalha em um moinho de grãos há 12 anos e desenvolveu asma ocupacional. O objetivo do artigo é apresentar a justificativa da origem ocupacional da asma adquirida. Descrevemos as tarefas realizadas, os materiais e os meios de trabalho utilizados. Analisamos especialmente a exposição ocupacional à poeira orgânica e sua conexão temporal com a sintomatologia respiratória. Essas informações nos permitem entender a importância das condições em que o trabalho é realizado e a exposição a um fator de risco, a poeira orgânica, para o desenvolvimento da patologia respiratória ocupacional. As medições do volume pulmonar expiratório máximo foram realizadas com a técnica de pico de fluxo durante e fora da jornada de trabalho. Observamos variações no fluxo expiratório superiores a 20%, tanto durante quanto fora do horário de trabalho, com um padrão sintomático semelhante ao relatado pelo trabalhador. Concluímos que há evidências de um nexo causal entre asma e trabalho e, portanto, propomos o diagnóstico de asma ocupacional. Destacamos a importância de avaliar os riscos ocupacionais em cada atividade para implementar planos de vigilância da saúde tanto do trabalhador quanto do ambiente de trabalho, a fim de evitar o surgimento e a evolução dessa ou de outras patologias que, em muitos casos, geram incapacidade para a tarefa e deterioração da qualidade de vida dos trabalhadores.

Identification of toxicity-induced biomarkers in human non-immune airway cells exposed to respiratory sensitizers: A mechanistic approach.

Occupational asthma covers a group of work-related diseases whose clinical manifestations include airway hyperresponsiveness and airflow limitation. Although the chemical respiratory allergy (CRA) induced by Low Molecular Weight (LMW) sensitizers is a major concern, especially in terms of the regulatory framework, to date there are no methods available for preclinically addressing this toxicological outcome, as its mechanistic background is not fully understood at molecular or cellular levels. This paper proposes a mechanistic study applying New Approach Methodologies (NAM) of the pro-inflammatory and functional effects triggered by LMW respiratory allergens in different respiratory tract cell lines, including bronchial epithelial (BEAS-2B), lung fibroblast (MRC-5), and endothelial cells (EA.hy926), and an analysis of the capacity of such chemicals to interact with the mucin protein, to address certain toxicodynamic aspects of such compounds. The results showed that some of the sensitizers evaluated interact with mucin, the main protein mucus component, but the toxicant-mucin complex formation does not seem to be a common feature of different chemical classes of allergens. At a cellular level, sensitizers promoted an increase in IL-8, IL-6, and IL-1ß production in the evaluated cell types. It also impaired the MUC1 expression by bronchial cells and activated endothelial cells, thereby increasing the ICAM-I surface expression. Taken together, our results showed that these aforementioned cell types participate in the CRA Adverse Outcome Pathway and must be considered when developing preclinical testing strategies, particularly investigating danger signal production after exposure to LMW sensitizers in different tissue compartments.

Comparison of high- and low-molecular-weight sensitizing agents causing occupational asthma: an evidence-based insight.

INTRODUCTION: The many substances used at the workplace that can cause sensitizer-induced occupational asthma are conventionally categorized into high-molecular-weight (HMW) agents and low-molecular-weight (LMW) agents, implying implicitly that these two categories of agents are associated with distinct phenotypic profiles and pathophysiological mechanisms. AREAS COVERED: The authors conducted an evidence-based review of available data in order to identify the similarities and differences between HMW and LMW sensitizing agents. EXPERT OPINION: Compared with LMW agents, HMW agents are associated with a few distinct clinical features (i.e. concomitant work-related rhinitis, incidence of immediate asthmatic reactions and increase in fractional exhaled nitric oxide upon exposure) and risk factors (i.e. atopy and smoking). However, some LMW agents may exhibit 'HMW-like' phenotypic characteristics, indicating that LMW agents are a heterogeneous group of agents and that pooling them into a single group may be misleading. Regardless of the presence of detectable specific IgE antibodies, both HMW and LMW agents are associated with a mixed Th1/Th2 immune response and a predominantly eosinophilic pattern of airway inflammation. Large-scale multicenter studies are needed that use objective diagnostic criteria and assessment of airway inflammatory biomarkers to identify the pathobiological pathways involved in OA caused by the various non-protein agents.

Identification of true chemical respiratory allergens: Current status, limitations and recommendations.

Asthma in the workplace is an important occupational health issue. It comprises various subtypes: occupational asthma (OA; both allergic asthma and irritant-induced asthma) and work-exacerbated asthma (WEA). Current regulatory paradigms for the management of OA are not fit for purpose. There is therefore an important unmet need, for the purposes of both effective human health protection and appropriate and proportionate regulation, that sub-types of work-related asthma can be accurately identified and classified, and that chemical respiratory allergens that drive allergic asthma can be differentiated according to potency. In this article presently available strategies for the diagnosis and characterisation of asthma in the workplace are described and critically evaluated. These include human health studies, clinical investigations and experimental approaches (structure-activity relationships, assessments of chemical reactivity, experimental animal studies and in vitro methods). Each of these approaches has limitations with respect to providing a clear discrimination between OA and WEA, and between allergen-induced and irritant-induced asthma. Against this background the needs for improved characterisation of work-related asthma, in the context of more appropriate regulation is discussed.

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)

4,4'-Methylene diphenyl diisocyanate exposure induces expression of alternatively activated macrophage-associated markers and chemokines partially through Krüppel-like factor 4 mediated signaling in macrophages.

Occupational exposure to the most widely used monomeric diisocyanate (dNCO), 4,4'-methylene diphenyl diisocyanate (MDI), may lead to the development of occupational asthma (OA). Alveolar macrophages with alternatively activated (M2) phenotype have been implicated in allergic airway responses and the pathogenesis of asthma. Recent in vivo studies demonstrate that M2 macrophage-associated markers and chemokines are induced by MDI-exposure, however, the underlying molecular mechanism(s) by which this proceeds is unclear.Following MDI exposure (in vivo and in vitro) M2 macrophage-associated transcription factors (TFs), markers, and chemokines were determined by RT-qPCR, western blots, and ELISA.Expression of M2 macrophage-associated TFs and markers including Klf4/KLF4, Cd206/CD206, Tgm2/TGM2, Ccl17/CCL17, Ccl22/CCL22, and CCL24 were induced by MDI/MDI-GSH exposure in bronchoalveolar lavage cells (BALCs)/THP-1 macrophages. The expression of CD206, TGM2, CCL17, CCL22, and CCL24 are upregulated by 3.83-, 7.69-, 6.22-, 6.08-, and 1.90-fold in KLF4-overexpressed macrophages, respectively. Endogenous CD206 and TGM2 were downregulated by 1.65-5.17-fold, and 1.15-1.78-fold, whereas CCL17, CCL22, and CCL24 remain unchanged in KLF4-knockdown macrophages. Finally, MDI-glutathione (GSH) conjugate-treated macrophages show increased chemotactic ability to T-cells and eosinophils, which may be attenuated by KLF4 knockdown.Our data suggest that MDI exposure may induce M2 macrophage-associated markers partially through induction of KLF4.

[Level of knowledge on occupational asthma and asthmagens: Assessment among healthcare workers by a validated questionnaire]. / Niveau de connaissance sur l'asthme professionnel et les agents asthmogènes : évaluation auprès du personnel de santé par un questionnaire validé.

INTRODUCTION: The health system is one of the professional sectors perhaps most at risk of occupational asthma. The aims of this study were to evaluate the level of knowledge of health care workers (HCWs) on occupational asthma and asthmogenic agents and to pave the way to effective educational action on the subject. METHODS: A multicenter transversal study including 180 HCWs was carried out between July and December 2020. A validated questionnaire addressed four dimensions: knowledge of asthmatic disease, knowledge of occupational asthma, knowledge of prognosis of occupational asthma and knowledge on the prevention of occupational asthma. RESULTS: The average total score was 13.71/18 (76.17%). There was no correlation between average total score and age, educational level, seniority or status of paramedical staff. Mean total scores were significantly higher for participants with no fixed work schedule and those practicing in non-university structures. The difficulty indexes for the four aforementioned dimensions were 82.22%, 77.56%, 53.52% and 66.67% respectively. CONCLUSIONS: Knowledge gaps affect all professional categories but to different degrees. A review of the level of knowledge of persons in each category would be the first step on the road to planned educational action.

Baker's rhinitis and asthma with concomitant wheat anaphylaxis: a rare overlap of clinical entities / Rinite e asma do padeiro com anafilaxia após ingestão de trigo: um caso raro de sobreposição de entidades clínicas

Wheat is one of the fundamental sources of food worldwide. Baker's asthma and occupational rhinitis are both frequent and can be attributable to work exposure in bakers. However, the association between baker's asthma and wheat allergy is very rare. The authors report the case of a bakery worker who developed baker's asthma and occupational rhinitis after years of working in a bakery and later developed anaphylactic reactions after wheat ingestion.

O trigo é uma das fontes alimentares mais importantes em todo o mundo. A asma do padeiro e a rinite ocupacional são frequentes e podem ser atribuídas à exposição a farinhas em padeiros. No entanto, a associação entre asma do padeiro e alergia alimentar ao trigo é muito rara. Os autores descrevem um caso em que um trabalhador de panificação desenvolveu asma do padeiro e rinite ocupacional após anos trabalhando em uma padaria, e posteriormente desenvolveu reações anafiláticas após a ingestão de trigo.

Occupational asthma related to indoor air pollution in a worker at an indoor air gun shooting range: a case report.

Background: Indoor air pollution can cause and exacerbate asthma. We report a previously undescribed case of occupational asthma related to indoor air pollution in a worker at an indoor air gun shooting range and highlight the potential risk of developing occupational asthma in this environment. Case presentation: A 31-year-old man presented with dyspnea, cough, and sputum and was diagnosed with asthma complicated by pneumonia. Objective evidence of asthma was obtained by performing a methacholine bronchial provocation test. It was suspected that the patient had occupational asthma, which began one month after changing jobs to work within the indoor air gun shooting range. The highest peak expiratory flow (PEF) diurnal variability on working days was 15%, but the highest variation was 24%, with 4 days out of 4 weeks having a variation of over 20% related to workplace exposure. Conversely, the diurnal variability on the rest days was 7%, and no day showed a variation exceeding 20%. The difference in the average PEF between working and rest days was 52 L/min. PEF deterioration during working days and improvement on rest days were noted. Conclusions: The results obtained from the in-depth analysis of the PEF were adequate to diagnose the patient with occupational asthma. Exposure to indoor air pollution and lead and the patient's atopy and allergic rhinitis may have contributed to the development of occupational asthma.