Cause Of Occupational Asthma Research Articles

Occupational asthma, rhinitis and contact urticaria from greenhouse work.

The current knowledge about occupational allergic diseases among greenhouse workers is scant. To describe greenhouse workers' occupational allergic diseases. 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). 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. 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.

Laboratory study of the effectiveness of substituting traditional wheat flour with low dust flour and use of different sieve designs as controls to reduce exposure to inhalable flour dust in commercial bakeries.

Exposure to flour dust remains one of the leading causes of occupational asthma in Great Britain (GB). The average annual incidence rate per 100,000 bakers and flour confectioners in GB was 47.8 for the 3 yr period 2017 to 2019 compared with 0.53 for all occupations. There are many processes in commercial bakeries that can cause exposure to flour dust. Exposures are typically controlled by using local exhaust ventilation or respiratory protective equipment. The aim of this study was to evaluate the potential to reduce exposure to inhalable flour dust in commercial bakeries by modification of the process by use of a conical sieve in place of a round sieve; and substitution of traditional wheat flour (TWF) with 'low dust' flours LD1 and LD2 for dusting surfaces. Two simulated commercial bakery tasks were performed in a laboratory whilst dust exposures were measured in the breathing zone of the operator using an Institute of Occupational Medicine (IOM) sampler, button sampler and a real-time direct reading monitor. Analysis of variance tests were used to assess whether differences in mean exposures were statistically significant with the different control approaches. A qualitative visual exposure assessment was also undertaken using Tyndall illumination. Substituting TWF with LD1 and LD2 reduced exposure to inhalable flour dust by 86% and 53% respectively when sieving and by 78% and 67% respectively when filling a hopper. There was no statistically significant difference between dust emissions for all 3 flours when using the conical sieve instead of the round sieve for flour dusting tasks. This laboratory study has shown that substituting TWF with low-dust flour may reduce inhalable dust exposures when dusting surfaces in bakeries.

141 Total Reactive Isocyanate Group (Trig) Measurement – a Commentary

Abstract Exposure to airborne isocyanates has, for decades, been a leading cause of occupational. As respiratory sensitisers, isocyanates can induce allergic respiratory diseases with symptoms persisting even without further exposure. As this cause of occupational asthma is recognised it should be almost entirely preventable. In several countries isocyanates are assigned occupational exposure limits based on the total of reactive isocyanate groups (TRIG). The measurement of TRIG has some significant advantages over the measurement of individual isocyanate compounds. This exposure metric is explicit, simplifying calculations and comparisons across published data. It reduces the risk of underestimating exposure by ‘missing’ important isocyanate compounds that may be present but are not the target analytes. It allows for quantification of exposure to complex mixtures of isocyanates, di-isocyanates monomers, prepolymers, polyisocyanates, oligomers, and/or intermediate forms. This is becoming increasingly important as more complex isocyanate products are being used in the workplace. There are many methods and techniques for measuring air concentrations / potential exposure to isocyanates. Several established methods have been standardised and published as International Organization for Standardization (ISO) methods. While some may be applied directly for determination of TRIG, others (developed for determination of individual isocyanates), require modification. This presentation aims to highlight the relative merits and limitations of those methods capable of determining TRIG and also considers potential future developments.

91 Isocyanates Aerosols Sampling for Occupational Exposures Assessment

Abstract Isocyanate compounds are potent sensitizers, in particular through the development of skin dermatitis and allergies. They are one of the main causes of occupational asthma. None no-adverse-effect level has been establishes for isocyanates, therefore, it is important to measure isocyanates level at workplaces. Most of the time, isocyanates are present in workplaces atmosphere both in gas and particle phase, which makes their quantitative sampling difficult. Actual sampling methods do not fit with individual sampling over 8 hours. The aim of this work was first to characterize the particles size distribution in workplaces, depending on the isocyanate and the process used. Then, we studied the effectiveness of CIP 10-I as a sampling device for four isocyanates, compared to impinger and impregnated filter. Particles size distribution was determined thank to different cascade impactors such as Andersen, DLPI+ and MiniMOUDI-8. The Mass Median Aerodynamic Diameter (MMAD) of 4,4’-MDI (4,4’-diphenylmethane diisocyanate) particles in polyurethane foam projection process was found to be higher than 4 µm. In paint spray process, HDI (hexamethylene diisocyanate) particles MMAD was between 1 and 2 µm. The aerosol generation system was designed to obtain particles sizes closed to those observed in workplaces. The CIP 10-I collection foam was impregnated with the same derivative agent as filters. HDI, 2,4-TDI and 2,6-TDI (Toluene diisocyanate) aerosols were generating at concentrations between 10 and 250 µg/m3 in dry air. Whatever the concentration, CIP 10-I collection efficiency is higher than that of filters. Further investigation are currently performed to investigate CIP 10-I performance for MDI sampling.

A physiologically-based kinetic (PBK) model for work-related diisocyanate exposure: Relevance for the design and reporting of biomonitoring studies

Diisocyanates are highly reactive substances and known causes of occupational asthma. Exposure occurs mainly in the occupational setting and can be assessed through biomonitoring which accounts for inhalation and dermal exposure and potential effects of protective equipment. However the interpretation of biomonitoring data can be challenging for chemicals with complex kinetic behavior and multiple exposure routes, as is the case for diisocyanates. To better understand the relation between external exposure and urinary concentrations of metabolites of diisocyanates, we developed a physiologically based kinetic (PBK) model for methylene bisphenyl isocyanate (MDI) and toluene di-isocyanate (TDI). The PBK model covers both inhalation and dermal exposure, and can be used to estimate biomarker levels after either single or chronic exposures. Key parameters such as absorption and elimination rates of diisocyanates were based on results from human controlled exposure studies. A global sensitivity analysis was performed on model predictions after assigning distributions reflecting a mixture of parameter uncertainty and population variability.Although model-based predictions of urinary concentrations of the degradation products of MDI and TDI for longer-term exposure scenarios compared relatively well to empirical results for a limited set of biomonitoring studies in the peer-reviewed literature, validation of model predictions was difficult because of the many uncertainties regarding the precise exposure scenarios that were used. Sensitivity analyses indicated that parameters with a relatively large impact on model estimates included the fraction of diisocyanates absorbed and the binding rate of diisocyanates to albumin relative to other macro molecules.We additionally investigated the effects of timing of exposure and intermittent urination, and found that both had a considerable impact on estimated urinary biomarker levels. This suggests that these factors should be taken into account when interpreting biomonitoring data and included in the standard reporting of isocyanate biomonitoring studies.

Total Reactive Isocyanate Group (TRIG) Measurement: A Commentary.

Exposure to airborne isocyanates has, for decades, been a leading cause of occupational asthma. As respiratory sensitizers, isocyanates can induce allergic respiratory diseases with symptoms persisting even without further exposure. As this cause of occupational asthma is recognized it should be almost entirely preventable. In several countries isocyanates are assigned occupational exposure limits based on the total of reactive isocyanate groups (TRIG). The measurement of TRIG has some significant advantages over the measurement of individual isocyanate compounds. This exposure metric is explicit, simplifying calculations, and comparisons across published data. It reduces the risk of underestimating exposure by 'missing' important isocyanate compounds that may be present but are not the target analytes. It allows for quantification of exposure to complex mixtures of isocyanates, di-isocyanates monomers, prepolymers, polyisocyanates, oligomers, and/or intermediate forms. This is becoming increasingly important as more complex isocyanate products are being used in the workplace. There are many methods and techniques for measuring air concentrations/potential exposure to isocyanates. Several established methods have been standardized and published as International Organization for Standardization (ISO) methods. While some may be applied directly for determination of TRIG, others (developed for determination of individual isocyanates), require modification. This commentary aims to highlight the relative merits and limitations of those methods capable of determining TRIG and also considers potential future developments.

ERS International Congress 2022: highlights from the Epidemiology and Environment Assembly.

In this article, early career members of the Epidemiology and Environment Assembly of the European Respiratory Society summarise a selection of five sessions from the Society's 2022 International Congress, with a focus on areas of specific interest for the Assembly, i.e. epidemiology and risk factors of respiratory diseases in both children and adults. Topics covered include the characterisation of obstructive respiratory diseases, their comorbidities and their evolution, with novel insight from large cohorts. The importance of early-life factors in respiratory health was also emphasised, including maternal exposures and habits during pregnancy. As smoking behaviours have changed following the introduction of e-cigarettes and heated tobacco products, research remains very active to determine the health consequences and predictors of these novel uses, especially in teenagers. The impact of environmental and occupational exposures on respiratory health remained a major topic of the congress, with a focus on emerging risk factors such as landscape fire smoke, non-exhaust particles and nanoparticles. Regarding workplace exposures, old and novel causes of occupational asthma and rhinitis were discussed.

Shoseiryuto Ameliorated TDI-Induced Allergic Rhinitis by Suppressing IL-33 Release from Nasal Epithelial Cells.

Toluene diisocyanate (TDI) is a major cause of occupational asthma and rhinitis. Shoseiryuto (SST) is one of the traditional herbal medicines (Kampo medicine) and has long been used as a natural medicine for allergic diseases such as allergic rhinitis (AR) and asthma. Recent studies have shown that the expression and release of IL-33, which regulates the TH2 cytokine response in epithelial cells, is an important step in developing the inflammatory response of the nasal mucosa. In this study, we investigated whether SST may ameliorate the TDI-induced AR-related symptoms in rats and inhibit IL-33 release from nasal epithelial cells. An AR rat model was generated by sensitization and induction with TDI. SST was administered during the sensitization period. AR-related symptoms in rats were evaluated, and IL-33 release was measured both in vivo and in vitro. SST suppressed symptoms appearing in TDI-induced AR model rats, such as elevated serum histamine and IL-33 levels in nasal lavage fluid (NLF)/serum, which were suppressed by SST administration. TDI-induced IL-33 release from the nasal epithelial cell nuclei was also observed and suppressed in SST-treated rats and cultured nasal epithelial cells. These results suggest that SST ameliorates the symptoms of TDI-induced AR at least partially by inhibiting IL-33 release from nasal epithelial cells.

Occupational asthma in teachers.

Work-related asthma symptoms are common in teachers and teaching assistants, there are few studies evaluating their causes. To identify causes of occupational asthma in teachers and teaching assistants referred to the Birmingham Occupational Lung Disease clinic 2000-20 using evaluation of serial Peak Expiratory Flow (PEF) records. Teachers and teaching assistants with possible occupational asthma were asked to record PEF 2-hourly at home and work for 4 weeks. Their records were evaluated with the Oasys programme. Those with a positive score for any of the three scores (area between curves (ABC), timepoint and Oasys score from discriminant analysis) were included. Repeat records were made as indicated to help identify the cause and the effects of remedial actions. Thirty-eight teachers or teaching assistants met the inclusion criteria with all three Oasys scores positive in 24, 2/3 scores in nine and 1/3 in five. The building was the likely cause in 17 (in new builds particularly acrylates from carpet adhesives and in old buildings mould and construction dust), bystander exposure to agents in the schools in 12 (cleaning agents, acrylates from photocopiers and chloramines from indoor pools) and materials used in the classroom in 9 (most commonly MDF in design and technology classes). We illustrate how the PEF records helped identify the cause. Oasys analysis of PEF records is a useful method of evaluating occupational asthma in teachers and identified difficult to confirm causes where successful remediation or redeployment was achieved.

Methylenediphenyl diisocyanate lysine conjugates in the urine of workers exposed to methylenediphenyl diisocyanate.

Diisocyanates have long been a leading cause of occupational asthma. As control often relies on personal protective equipment and there is the potential for skin uptake, biological monitoring is often used to assess worker exposure. Current routine biological monitoring methods do not distinguish between a diisocyanate and the corresponding diamine exposure in urine samples; therefore, a specific urinary biomarker is desirable. Urine samples were obtained from a group of workers exposed to methylenediphenyl diisocyanate (MDI) where aerosol generation was unlikely. Lysine conjugates of MDI were extracted from urine by solid phase extraction; analysis was performed by liquid chromatography tandem mass spectrometry. Acetylated MDI-lysine (acMDI-Lys) conjugates were detected in 73% of samples tested from persons with exposure to MDI compared to 93% of samples that were positive for methylene dianiline (MDA) in hydrolysed urine. There was a weak but significant positive correlation between the two biomarkers (r2 = 0.377). This is the first report detecting and quantifying acMDI-Lys in the urine of workers exposed to MDI, and acMDI-Lys may be a useful non-invasive biomarker in discriminating between MDI and MDA exposures.

HBM4EU Diisocyanates Study-Research Protocol for a Collaborative European Human Biological Monitoring Study on Occupational Exposure.

Diisocyanates have long been a leading cause of occupational asthma in Europe, and recently, they have been subjected to a restriction under the REACH regulations. As part of the European Human Biomonitoring project (HBM4EU), we present a study protocol designed to assess occupational exposure to diisocyanates in five European countries. The objectives of the study are to assess exposure in a number of sectors that have not been widely reported on in the past (for example, the manufacturing of large vehicles, such as in aerospace; the construction sector, where there are potentially several sources of exposure (e.g., sprayed insulation, floor screeds); the use of MDI-based glues, and the manufacture of spray adhesives or coatings) to test the usability of different biomarkers in the assessment of exposure to diisocyanates and to provide background data for regulatory purposes. The study will collect urine samples (analysed for diisocyanate-derived diamines and acetyl–MDI–lysine), blood samples (analysed for diisocyanate-specific IgE and IgG antibodies, inflammatory markers, and diisocyanate-specific Hb adducts for MDI), and buccal cells (micronucleus analysis) and measure fractional exhaled nitric oxide. In addition, occupational hygiene measurements (air monitoring and skin wipe samples) and questionnaire data will be collected. The protocol is harmonised across the participating countries to enable pooling of data, leading to better and more robust insights and recommendations.

MicroRNA-mediated calcineurin signaling activation induces CCL2, CCL3, CCL5, IL8, and chemotactic activities in 4,4′-methylene diphenyl diisocyanate exposed macrophages

Occupational exposure to 4,4′-methylene diphenyl diisocyanate (MDI), the most widely used monomeric diisocyanate, is one of the leading causes of occupational asthma (OA). Previously, we identified microRNA (miR)-206-3p/miR-381-3p-mediated PPP3CA/calcineurin signalling regulated iNOS transcription in macrophages and bronchoalveolar lavage cells (BALCs) after acute MDI exposure; however, whether PPP3CA/calcineurin signalling participates in regulation of other asthma-associated mediators secreted by macrophages/BALCs after MDI exposure is unknown. Several asthma-associated, macrophage-secreted mediator mRNAs from MDI exposed murine BALCs and MDI-glutathione (GSH) conjugate treated differentiated THP-1 macrophages were analysed using RT-qPCR. Endogenous IL1B, TNF, CCL2, CCL3, CCL5, and TGFB1 were upregulated in MDI or MDI-GSH conjugate exposed BALCs and macrophages, respectively. Calcineurin inhibitor tacrolimus (FK506) attenuated the MDI-GSH conjugate-mediated induction of CCL2, CCL3, CCL5, and CXCL8/IL8 but not others. Transfection of either miR-inhibitor-206-3p or miR-inhibitor-381-3p in macrophages induced chemokine CCL2, CCL3, CCL5, and CXCL8 transcription, whereas FK506 attenuated the miR-inhibitor-206-3p or miR-inhibitor-381-3p-mediated effects. Finally, MDI-GSH conjugate treated macrophages showed increased chemotactic ability to various immune cells, which may be attenuated by FK506. In conclusion, these results indicate that MDI exposure to macrophages/BALCs may recruit immune cells into the airway via induction of chemokines by miR-206-3p and miR-381-3p-mediated calcineurin signalling activation.

Epigenetic Markers Are Associated With Differences in Isocyanate Biomarker Levels in Exposed Spray-Painters.

Isocyanates are respiratory and skin sensitizers that are one of the main causes of occupational asthma globally. Genetic and epigenetic markers are associated with isocyanate-induced asthma and, before asthma develops, we have shown that genetic polymorphisms are associated with variation in plasma and urine biomarker levels in exposed workers. Inter-individual epigenetic variance may also have a significant role in the observed biomarker variability following isocyanate exposure. Therefore, we determined the percent methylation for CpG islands from DNA extracted from mononuclear blood cells of 24 male spray-painters exposed to 1,6-hexamethylene diisocyanate (HDI) monomer and HDI isocyanurate. Spray-painters’ personal inhalation and skin exposure to these compounds and the respective biomarker levels of 1,6-diaminohexane (HDA) and trisaminohexyl isocyanurate (TAHI) in their plasma and urine were measured during three repeated industrial hygiene monitoring visits. We controlled for inhalation exposure, skin exposure, age, smoking status, and ethnicity as covariates and performed an epigenome-wide association study (EWAS) using likelihood-ratio statistical modeling. We identified 38 CpG markers associated with differences in isocyanate biomarker levels (Bonferroni < 0.05). Annotations for these markers included 18 genes: ALG1, ANKRD11, C16orf89, CHD7, COL27A, FUZ, FZD9, HMGN1, KRT6A, LEPR, MAPK10, MED25, NOSIP, PKD1, SNX19, UNC13A, UROS, and ZFHX3. We explored the functions of the genes that have been published in the literature and used GeneMANIA to investigate gene ontologies and predicted protein-interaction networks. The protein functions of the predicted networks include keratinocyte migration, cell–cell adhesions, calcium transport, neurotransmitter release, nitric oxide production, and apoptosis regulation. Many of the protein pathway functions overlap with previous findings on genetic markers associated with variability both in isocyanate biomarker levels and asthma susceptibility, which suggests there are overlapping protein pathways that contribute to both isocyanate toxicokinetics and toxicodynamics. These predicted protein networks can inform future research on the mechanism of allergic airway sensitization by isocyanates and aid in the development of mitigation strategies to better protect worker health.

Occupational Asthma Caused by Quaternary Ammonium Compounds: A Multicenter Cohort Study

Quaternary ammonium compounds (QACs) are used extensively for cleaning and disinfection and have been documented in scattered reports as a cause of occupational asthma (OA) through bronchoprovocation tests (BPTs). To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low-molecular weight (LMW) agents. The study was conducted in a retrospective multicenter cohort of 871 subjects with OA ascertained by a positive BPT. Subjects with QAC-induced OA (n= 22) were identified based on a positive BPT to QACs after exclusion of those challenged with cleaning products or disinfectants that contained other potential respiratory sensitizers. They were compared with 289 subjects with OA caused by other LMW agents. Most subjects with QAC-induced OA were working in the health care sector (n= 14). A twofold or greater increase in the postchallenge level of nonspecific bronchial hyperresponsiveness was recorded in eight of 11 subjects with QAC-induced OA (72.7%) and in 49.7% of those with OA caused by other LMW agents. Although sputum assessment was available in only eight subjects with QAC-induced OA, they showed a significantly greater median (interquartile) increase in sputum eosinophils (18.1% [range, 12.1% to 21.1%]) compared with those with OA caused by other LMW agents (2.0% [range, 0% to 5.2%]; P < .001). This study indicates that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents.

Occupational Exposure to Diisocyanates in the European Union.

ObjectivesDiisocyanates are a chemical group that are widely used at workplaces in many sectors. They are also potent skin- and respiratory sensitizers. Exposure to diisocyanates is a main cause of occupational asthma in the European Union. To reduce occupational exposure to diisocyanates and consequently the cases of diisocyanate-induced asthma, a restriction on diisocyanates was recently adopted under the REACH Regulation in the European Union.MethodsA comprehensive evaluation of the data on occupational exposure to the most important diisocyanates at workplaces was made and is reported here. The diisocyanates considered are methylene diphenyl diisocyanate (MDI), toluene diisocyanate (TDI), and hexamethylene diisocyanate (HDI), accounting for more than 95% of the market volume in the EU. The exposure assessment is based on data from Chemical Safety Reports (CSRs) of REACH Registration Dossiers, workplace air monitoring data from Germany, from the UK Health and Safety Executive (HSE), and literature data relevant for the EU, and the USA.ResultsOccupational exposure to diisocyanates is particularly relevant in: (i) C.A.S.E. applications (Coatings, Adhesives, Sealants, Elastomers), (ii) production of polyurethanes (PUs) (e.g. slab-stock foam), (iii) handling of partly uncured PU products (e.g. cutting, demoulding, spray application of foam), and (iv) when diisocyanates/PUs are heated (e.g. hot lamination, foundry applications/casting forms). Ranking of the reported data on inhalation to diisocyanate exposure at workplaces (maximum values) leads to following order: (i) HDI and its oligomers in coatings, (ii) MDI in spray foam applications, (iii) TDI in manufacture of foam, (iv) TDI in manufacture of PUs and PU composite materials, (v) TDI in adhesives, (vi) MDI in adhesives, (vii) MDI in manufacture of PUs and PU composite materials, (viii) TDI in coatings, (ix) MDI in manufacture of foam, and (x) HDI in adhesives.

Baker's asthma in bread factory workers.

Background: Baker's asthma (BA) is one of the most common causes of occupational asthma. Prevalence of BA varies from 3 to 24% in various studies; however, in our country, there are not enough data on its prevalence. Objective: The aim of this study was to evaluate wheat flour sensitivity and to determine the rate of BA in workers at a large bread factory in Ankara. Methods: All steps of the study were carried out in the workplace by the research team who made regular visits to the bread factory. A questionnaire was used to determine the presence of respiratory symptoms and its relation with the occupation. Skin-prick tests and specific immunoglobulin E measurements were performed. Pulmonary function tests and specific inhalation challenges (SIC) were performed to confirm the BA diagnosis. Results: A total of 162 workers (women/men, 3/159; mean ±standard error age, 38.25 ± 7.8 years) were included in the study. Of the 99 workers who described symptoms, 88 (88.8%) had nasal and 57 (57.5%) had lower respiratory symptoms. Sensitivity to wheat flour was present in 23 of the workers (14.2%) among all the workers. Among all the workers, seven (4.32%) were diagnosed with BA and SICs were positive in four (2.46%). Conclusion: Wheat sensitivity was high among the bakers who were exposed to wheat flour; however, the prevalence of BA was quite lower than the previous data in the literature.

Toluene diisocyanate-induced inflammation and airway remodeling involves autophagy in human bronchial epithelial cells

Toluene-diisocyanate (TDI) is one of the main causes of occupational asthma. To study the role of autophagy in TDI-induced airway inflammation and airway remodeling in bronchial airway epithelial (16HBE) cells. We treated 16HBE cells with TDI-human serum albumin (TDI-HSA) conjugate to observe reactive oxygen species (ROS) release, autophagy activation, airway inflammation and airway remodeling. 3-Methyladenine (3-MA) and Rapamycin (Rapa) intervention were used to explore the effects of autophagy on inflammatory response and protein expression related to airway remodeling in 16HBE cells treated with TDI-HSA. Experimental results suggested that various concentrations of TDI-HSA (0, 40, 80 and 120 μg/mL) increased the release of ROS and the expression of Nrf2, activated autophagy and increased the expression of AMPK, Beclin-1, LC3 and decreased the expression of p62, promoted the levels of IL-5, IL-6 and IL-8 in 16HBE cells. Results also showed that E-cadherin expression decreased but an increase was observed in α-SMA and MMP-9 in the TDI-HSA group. The treatment of TDI-HSA combined with Rapa aggravated the above reaction whereas the inverse was true for TDI-HSA combined with 3-MA. These results indicated that autophagy is involved in TDI-induced airway inflammation and airway remodeling as a positive regulatory mechanism, inhibiting autophagy can significantly alleviate the TDI-induced inflammatory response and attenuate airway remodeling protein expression in 16HBE cells.

JNK modulates RAGE/β-catenin signaling and is essential for allergic airway inflammation in asthma

As a leading cause of occupational asthma, toluene diisocyanate (TDI)-induced asthma is an inflammatory disease of the airways with one of the most significant characteristics involving inflammation, in which the receptor of advanced glycation end products (RAGE) plays an extremely important role. However, the mechanism underlying the upregulation of RAGE is still unknown. The aim of the present study was to examine whether JNK mediates β-catenin stabilization via activation of RAGE in asthma. Herein from the results by analyzing the blood from healthy donors and patients with asthma, it was found that the expression of RAGE and p-JNK is highly correlated and elevated concomitantly with the severity of bronchial asthma. Additionally, upon sensitizing and challenging the mice with TDI, we found that RAGE inhibitor (FPS-ZM1) and JNK inhibitor (SP600125) significantly reduced the TDI-induced asthma inflammation in vivo. Furthermore, SP600125 also considerably restored RAGE and p-JNK expression. Besides, the in vitro results from TDI-HSA treatment of 16HBE cells reveal that therapeutic inhibition of JNK reduced TDI driving RAGE expression and β-catenin translocation, while treatment with Anisomycin, a JNK agonist, showed the opposite effect. Moreover, genetic knockdown of RAGE does not contribute to JNK phosphorylation, indicating that JNK functions upstream of RAGE. Collectively, these findings highlight a role for JNK signaling in RAGE/β-catenin regulation and have important therapeutic implications for the treatment of TDI induced asthma.

Prevalence of Asthma Symptoms Based on ISAAC Questionnaire and Pulmonary Function Tests in Cotton Ginnery Workers in Gezira State

Background: The prevalence of asthma symptoms in the adult Sudanese population was found to be 10% according to the international study of asthma and allergies in childhood (ISAAC) questionnaire and was more than that in dusty working places. Occupational asthma is caused by breathing chemical fumes, gases, dust or other substances on the job. More than 250 workplace substances have been identified as possible causes of occupational asthma. These include animal substances, chemicals, enzymes, metals, plant substances, and respiratory irritants. Exposure to airborne asthma triggers can cause permanent lung destruction, byssinosis and resulting in disability or death. Objectives: The aim of this study is to evaluate the prevalence of asthma symptoms in cotton gin workers in Gezira state, Sudan. Methods: This is a cross-sectional study conducted in cotton ginnery in Rufaa - al-Gezira State in the middle of Sudan; to evaluate the prevalence of asthma symptoms in cotton gin workers. The aim of the study was explained to all participants after taking their consent and the modified international study of asthma and allergies in childhood (ISAAC) questionnaire was used and had been filled by 60 workers. Pulmonary function test (PFT) also had been done for them and the results were compared with the normal values for each participant. A T-test was used to compare the statistical significance (P-value ?0.05 was considered statistically significant). Results: (43) of the participants were males and (17) were females. Analysis of data revealed that (13.3%) had to wheeze in the last 12 months, and (3.3%) had chest tightness early morning. Also (3.3%) had an episode of chest tightness which awakes them from sleeping. The forced expiratory volume in the first second and the forced vital capacity were significantly lower than the Sudanese normal values. Conclusion: The prevalence of asthma symptoms in cotton gin workers is higher than the general population with lower lung function values. Further big-scale studies are recommended to be done.

Molecular Characterization and Experimental Utility of Monoclonal Antibodies with Specificity for Aliphatic Di- and Polyisocyanates.

Aliphatic di- and polyisocyanates are crucial chemical ingredients in many industrial processes and are a well-recognized cause of occupational asthma. Serologic detection of "chemical epitopes" in biological samples could serve as an exposure surveillance approach toward disease prevention, and thus we sought to generate aliphatic isocyanate-specific monoclonal antibodies (mAbs). Three hybridomas were generated from Balb/c mice immunized with a commercial product containing a combination of uretdione, homopolymer, and monomeric forms of hexamethylene diisocyanate (HDI). Three stable hybridomas were subcloned by limiting dilution, two secreting IgG1κ and one secreting IgMκ mAb that bind aliphatic di- and polyisocyanates (conjugated to albumin), but not aromatic toluene or methylene diphenyl diisocyanate (TDI or MDI). Each mAb demonstrates slight differences in epitope specificity, for example, recognition of hydrogenated MDI (HMDI) or different carrier proteins (transferrin, actin) reacted with vapor phase HDI, and is encoded by unique recombination of different germline antibody genes, with distinct complementary determining regions. By western blot, all three mAbs detect a molecule with characteristics of an albumin adduct uniquely in urine from mice skin exposed to a mixture of aliphatic di- and polyisocyanate. Together, the data define molecular determinants of humoral immune recognition of aliphatic di- and polyisocyanates through new mAbs, which will serve as useful research reagents and may be applicable to future exposure surveillance efforts.