Respiratory Sensitization Research Articles

Assessment of the feed additive consisting of copper chelate of hydroxy analogue of methionine for all animal species for the renewal of its authorisation (Novus Europe S.A./N.V.).

The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the application for renewal of authorisation of copper chelate of hydroxy analogue of methionine (Mintrex®Cu) for all animal species. The FEEDAP Panel has delivered two opinions (in 2008 and 2009) on the safety and efficacy of the additive. The additive was authorised in 2010 as ‘Copper chelate of hydroxy analogue of methionine’ containing 18% copper, 79.5−81% (2‐hydroxy‐4‐methylthio)butanoic acid (DL‐methionine hydroxy analogue, HMTBa) and 1% mineral oil. Following some modifications in the manufacturing process, the additive does not contain mineral oil and the applicant proposes the following specifications: ≥ 16% copper and ≥ 78% HMTBa. The data provided indicate that the additive complies with the new specifications. No new evidence was found that would make the FEEDAP Panel reconsidering its previous conclusions on the safety for target species, consumers and environment. The applicant provided new studies on the effects of the additive on the respiratory tract and on skin and eyes. Data on the characterisation of the additive and the new studies on skin/eyes led the Panel to reconsider the safety for the user. Mintrex®Cu is considered as a skin and eye irritant and a skin sensitiser; the risk of respiratory sensitisation is considered low. The present application did not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive; therefore, there was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

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.

Safety and efficacy of a feed additive consisting of endo‐1,4‐β‐xylanase (ECONASE® XT) produced by Trichoderma reesei CBS 140027 as a feed additive for piglets (weaned), pigs for fattening, chickens for fattening, chickens reared for laying, laying hens, turkeys for fattening, turkeys reared for breeding and minor poultry species (Roal Oy)

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of ECONASE ® XT (endo‐1,4‐β‐xylanase) produced by a genetically modified strain of Trichoderma reesei (CBS 140027) as a zootechnical feed additive for piglets (weaned), pigs for fattening, chickens for fattening, chickens reared for laying, laying hens, turkeys for fattening, turkeys reared for breeding and minor poultry species. The recipient strain and the production strain T. reesei CBS 140027 are considered safe. The additive is safe for chickens for fattening and weaned piglets at the maximum recommended doses (16,000 and 24,000 BXU/kg feed, respectively) with a wide margin of safety (100‐fold and 50‐fold, respectively). These conclusions are extended to chickens reared for laying and to pigs for fattening at 16,000 and 24,000 BXU/kg feed, respectively. The additive is safe for turkeys for fattening or reared for breeding at 16,000 BXU/kg feed. The FEEDAP Panel cannot conclude on the safety of the additive for laying hens and for minor poultry species for laying at the proposed conditions of use. The information provided does not allow to conclude on the safety of the use of ECONASE XT ® P/L produced by T. reesei CBS 140027 in animal nutrition for the consumers. The use of the additive under assessment in animal nutrition does not raise safety concerns for the environment. ECONASE ® XT L is non‐irritant to the skin or to the eyes. In absence of data, the FEEDAP Panel cannot conclude on the potential of the solid product to be irritant to skin and eyes and on the potential of the additive in all forms to be a dermal sensitiser. All forms of the additive should be considered as respiratory sensitisers. All forms of the additive are considered efficacious at the minimum recommended levels for the target species.

Occupational exposure limits for acetaldehyde, 2-bromopropane, glyphosate, manganese and inorganic manganese compounds, and zinc oxide nanoparticle, and the biological exposure indices for cadmium and cadmium compounds and ethylbenzene, and carcinogenicity, occupational sensitizer, and reproductive toxicant classifications.

Occupational exposure limits for acetaldehyde, 2-bromopropane, glyphosate, manganese and inorganic manganese compounds, and zinc oxide nanoparticle, and the biological exposure indices for cadmium and cadmium compounds and ethylbenzene, and carcinogenicity, occupational sensitizer, and reproductive toxicant classifications.

Seasonality of asthma exacerbation in children caused by respiratory virus infection and allergen sensitization

Purpose: Acute asthma exacerbations in children have seasonal variations and occur frequently in fall. Respiratory viral infections and environmental allergens are associated with asthma exacerbation. This study aimed to identify seasonal trends of asthma exac-erbation and the effects of respiratory viral infection and allergen sensitization on the seasonality of asthma exacerbation in children. Methods: Children under the age of 18 years who visited to the Emergency Department or hospitalized for acute asthma exacerba-tions from 2011 to 2019 were included. We reviewed medical records, including demographics, date of asthma exacerbation, results of respiratory virus and allergen sensitization, and they were analyzed to identify the seasonal trends of asthma exacerbation. Results: A total of 320 asthma exacerbations were included, with the highest frequency in fall. Human rhinovirus was positive in 64.7% and 60.0% in fall and spring exacerbations, respectively. House dust mite sensitization was highest in fall at 78.5%, while food sensitization was highest in spring at 76.9%. In patients who were sensitized to house dust mites or food allergens, respiratory viral infections further increased asthma exacerbation in fall and spring, respectively. Conclusion: Respiratory virus may be associated with asthma exacerbation in fall and spring. House dust mite and food sensitiza-tions may be associated with fall and spring asthma exacerbations by worsening the severity of asthma symptoms caused by respi-ratory viral infections. In childhood asthmatic patients with allergen sensitization, avoidance of sensitized allergens, prevention of viral infection, and more active treatment of viral infection may help prevent acute asthma exacerbations. (Allergy Asthma Respir Dis 2021;9:238-244)

Пищевая и ингаляционная сенсибилизация при атопическом дерматите

Aim: to study the association of food and inhalation sensitization with the severity of atopic dermatitis (AtD) in order to improve its treatment and prevention methods. Patients and Methods: the study included 50 patients with AtD from 2 to 44 years old. The study included clinical and laboratory research methods. The survey analyzed the history and anamnesis vitae, estimated the age at the AtD onset, determined the nature of concomitant pathology, the possible causes of cutaneous exacerbation, the allergic severity in the family history, the severity score on the SCORAD (Scoring of Atopic Dermatitis) scale and the efficacy of previous therapy. The immunological examination consisted of the quantitative determination of specific IgE and IgG antibodies in the blood serum to inhaled and food allergens by immunochemiluminescence assay on an IMMULITE 2000 XPi analyzer. Results: according to the detection frequency of IgE to food allergens in patients with AtD: the leading positions were taken by the chicken egg (egg white in 26% of cases, egg yolk in 20%); IgE to banana was detected in 17% of cases; in 12% — to cow’s milk, more common — to the β-lactoglobulin fraction. When studying the activity of inhaled allergens, respiratory sensitization to the cat epithelium was detected in 26% of cases, and to black birch — in 24%. Hypersensitivity to herbs (wormwood, herbal mixture) and house dust allergens (8%, respectively) was found much less common. In severe AtD, IgE to respiratory allergens prevailed: at n=38, the IgE concentration to cat epithelium and black birch was 12.4±1.4 IU/mL each. Besides, there was a significant sensitization to food allergens, namely, the IgE concentration to egg white — 5.4±0.9 IU/mL. Conclusion: the study revealed the sensitization of patients with AtD to food (mainly egg white, egg yolk, banana and cow’s milk) and respiratory (mainly cat epithelium, black birch) allergens. Determination of the IgE concentration in the blood serum of patients showed that there was a significant concentration increase to egg white, cat and black birch in severe AtD. Therefore, it is advisable to test for specific allergens in all patients with moderate to severe AtD. KEYWORDS: food sensitization, inhalation sensitization, atopic dermatitis, allergy, allergens, antibodies, immunochemiluminescence assay, IgE, triggers. FOR CITATION: Vasilyeva E.A., Rusak Yu.E., Efanova E.N., Lebedeva L.N. Food and inhalation sensitization in atopic dermatitis. Russian Medical Inquiry. 2021;5(1):17–20. DOI: 10.32364/2587-6821-2021-5-1-17-20.

Occupational Respiratory Allergy: Risk Factors, Diagnosis, and Management.

Occupational allergies are among the most common recorded occupational diseases. The skin and the upper and lower respiratory tract are the classical manifestation organs. More than 400 occupational agents are currently documented as being potential "respiratory sensitizers" and new reported causative agents are reported each year. These agents may induce occupational rhinitis (OR) or occupational asthma (OA) and can be divided into high-molecular weight (HMW) and low-molecular weight (LMW) agents. The most common occupational HMW agents are (glycol)proteins found in flour and grains, enzymes, laboratory animals, fish and seafood, molds, and Hevea brasiliensis latex. Typical LMW substances are isocyanates, metals, quaternary ammonium persulfate, acid anhydrides, and cleaning products/disinfectants. Diagnosis of occupational respiratory allergy is made by a combination of medical history, physical examination, positive methacholine challenge result or bronchodilator responsiveness, determination of IgE-mediated sensitization, and specific inhalation challenge tests as the gold standard. Accurate diagnosis of asthma is the first step to managing OA as shown above. Removal from the causative agent is of central importance for the management of OA. The best strategy to avoid OA is primary prevention, ideally by avoiding the use of and exposure to the sensitizer or substituting safer substances for these agents.

Behavior of Chemical Respiratory Sensitizers in in Vitro Methods for Skin Sensitization

Behavior of Chemical Respiratory Sensitizers in <i>in Vitro</i> Methods for Skin Sensitization

Size fractionation of bioaerosol emissions from green-waste composting

Particle size is a significant factor in determining the dispersal and inhalation risk from bioaerosols. Green-waste composting is a significant source of bioaerosols (including pathogens), but little is known about the distribution of specific taxa across size fractions. To characterise size fractionated bioaerosol emissions from a compost facility, we used a Spectral Intensity Bioaerosol Sensor (SIBS) to quantify total bioaerosols and qPCR and metabarcoding to quantify microbial bioaerosols. Overall, sub-micron bioaerosols predominated, but molecular analysis showed that most (>75%) of the airborne microorganisms were associated with the larger size fractions (>3.3 µm da). The microbial taxa varied significantly by size, with Bacilli dominating the larger, and Actinobacteria the smaller, size fractions. The human pathogen Aspergillus fumigatus dominated the intermediate size fractions (>50% da 1.1–4.7 µm), indicating that it has the potential to disperse widely and once inhaled may penetrate deep into the respiratory system. The abundance of Actinobacteria (>60% at da < 2.1 µm) and other sub-micron bioaerosols suggest that the main health effects from composting bioaerosols may come from allergenic respiratory sensitisation rather than directly via infection. These results emphasise the need to better understand the size distributions of bioaerosols across all taxa in order to model their dispersal and to inform risk assessments of human health related to composting facilities.

Mapping Chemical Respiratory Sensitization: How Useful Are Our Current Computational Tools?

Chemical respiratory sensitization is an immunological process that manifests clinically mostly as occupational asthma and is responsible for 1 in 6 cases of adult asthma, although this may be an underestimate of the prevalence, as it is under-diagnosed. Occupational asthma results in unemployment for roughly one-third of those affected due to severe health issues. Despite its high prevalence, chemical respiratory sensitization is difficult to predict, as there are currently no validated models and the mechanisms are not entirely understood, creating a significant challenge for regulatory bodies and industry alike. The Adverse Outcome Pathway (AOP) for respiratory sensitization is currently incomplete. However, some key events have been identified, and there is overlap with the comparatively well-characterized AOP for dermal sensitization. Because of this, and the fact that dermal sensitization is often assessed by in vivo, in chemico, or in silico methods, regulatory bodies are defaulting to the dermal sensitization status of chemicals as a proxy for respiratory sensitization status when evaluating chemical safety. We identified a data set of known human respiratory sensitizers, which we used to investigate the accuracy of a structural alert model, Toxtree, designed for skin sensitization and the Centre for Occupational and Environmental Health (COEH)'s model, a model developed specifically for occupational asthma. While both models had a reasonable level of accuracy, the COEH model achieved the highest balanced accuracy at 76%; when the models agreed, the overall accuracy was 87%. There were important differences between the models: Toxtree had superior performance for some structural alerts and some categories of well-characterized skin sensitizers, while the COEH model had high accuracy in identifying sensitizers that lacked identified skin sensitization reactivity domains. Overall, both models achieved respectable accuracy. However, neither model addresses potency, which, along with data quality, remains a hurdle, and the field must prioritize these issues to move forward.

New causes of immunologic occupational asthma 2014-2020.

The purpose of this review was to list all new confirmed cases of immunological occupational asthma (IOA) described between mid-2014 and April 2020. Several new agents, both of high and low molecular weight, have been identified in the last 6 years as potential respiratory sensitizers being able to induce immunological occupational asthma. This review confirms that new causes of IOA are still identified regularly, particularly in subjects exposed to high molecular agents, in the food industry (farming, pest control, food processing), pharmaceutical industry (antibiotics, various drugs) and cosmetic environment (dyes, powders). It stressed the need for clinicians to stay alert and suspect occupational asthma in any adult with new onset asthma or newly uncontrolled asthma.

Allergies aux fruits

Fruit allergies are frequent, representing for Rosaceae fruits 14 % of reported allergies and 5 % for fruits crossing with latex. They can be linked to a primary sensitization to pollens or isolated. The concept of fruit allergy is complex for the practitioner because of the difficulties in defining the fruit, variable according to classifications, the evaluation of the risk of cross-allergy and the particularities of the clinical expressions of a food allergy according to the allergens involved. This review specifies the botanical, culinary and allergological definitions of fruit, the main families of allergens responsible for food allergies, and the clinical, diagnostic and therapeutic particularities of fruit allergy. Sensitization can occur by respiratory sensitization (pollen-fruit cross-reactivity) or by primary sensitization to fruit by the digestive tract or by contact. Plant epitopes may be continuous or discontinuous. The thermal behaviour of allergens, their resistance to digestion and their stability in an acidic environment makes it possible to characterise their risk. Allergenicity often varies with the cultivar, the method of preservation, the food processing technologies used (cooking, canning, fermentation, texturisation, hydrolysis, filtration, etc.). The diagnosis is established on the basis of an algorithm based on anamnesis, prick-tests with native foods, the search for the specific IgE, the reintroduction test. The importance of using native foods for skin testing should be stressed because of the particular sensitivity of plant allergens to denaturation. The treatment is based on the removal of the offending fruit. Immunotherapy trials with fruit allergens are under study. Tolerance protocols using fruits at different cooking times are promising for thermolabile allergens.

The link between delivered aerosol dose and inflammatory responses: Exposing a lung Cell Co-Culture system to selected Allergens and irritants

Traditional in vivo inhalation studies to inform hazard identification and risk assessment are time-intensive and financially expensive. Cell culture models combined with aerosol exposure systems have shown promise as surrogates in screening assays when multiple substances require preliminary information on hazard potential associated with aerosolized materials. This paper presents two different aerosol exposure apparatuses: a settling chamber and a gentle impactor. Both apparatuses have been demonstrated for aerosol delivery capable of exposing cells in culture at the air-liquid interface. The settling chamber was constructed with simple design specifications, but exhibited a low deposition efficiency. The gentle impactor required a more sophisticated design based on aerosol dynamics of target size for the droplet delivery, but ultimately produced 64.25-fold greater deposition efficiency than the settling chamber. This led to a shorter exposure duration for the same dosage. It also enabled consistent exposure to the same sized aerosols. From these results, the gentle impactor shows promise as a high-throughput exposure tool that could be used in conjunction with cell-based co-culture models. Using a triple cell co-culture model of epithelial, dendritic, and macrophage cell-types, the induced inflammatory markers produced a more definitive dose-response for known irritants and positive indication for sensitizers. The materials tested include toluene-2,4-diisocyanate and trimellitic anhydride as known respiratory sensitizers; silica as a known respiratory irritant; and d-limonene as a known dermal sensitizer. Conversely, when using single cell monolayers, no significant different responses in inflammatory biomarkers was observed, suggesting cellular cross-talk is important. Evaluation of the ability to deliver aerosolized substances consistently and measure cytotoxicity and inflammatory endpoints is possible and demonstrates a potential high throughput screening tool.

Influence of Genetic Variance on Biomarker Levels After Occupational Exposure to 1,6-Hexamethylene Diisocyanate Monomer and 1,6-Hexamethylene Diisocyanate Isocyanurate.

We evaluated the impact of genetic variance on biomarker levels in a population of workers in the automotive repair and refinishing industry who were exposed to respiratory sensitizers 1,6-hexamethylene diisocyanate (HDI) monomer and one of its trimers, HDI isocyanurate. The exposures and respective urine and plasma biomarkers 1,6-diaminohexane (HDA) and trisaminohexyl isocyanurate (TAHI) were measured in 33 workers; and genome-wide microarrays (Affymetrix 6.0) were used to genotype the workers’ single-nucleotide polymorphisms (SNPs). Linear mixed model analyses have indicated that interindividual variations in both inhalation and skin exposures influenced these biomarker levels. Using exposure values as covariates and a false discovery rate < 0.10 to assess statistical significance, we observed that seven SNPs were associated with HDA in plasma, five were associated with HDA in urine, none reached significance for TAHI in plasma, and eight were associated with TAHI levels in urine. The different genotypes for the 20 significant SNPs accounted for 4- to 16-fold changes observed in biomarker levels. Associated gene functions include transcription regulation, calcium ion transport, vascular morphogenesis, and transforming growth factor beta signaling pathway, which may impact toxicokinetics indirectly by altering inflammation levels. Additionally, in an expanded analysis using a minor allele cutoff of 0.05 instead of 0.10, there were biomarker-associated SNPs within three genes that have been associated with isocyanate-induced asthma: ALK, DOCK2, and LHPP. We demonstrate that genetic variance impacts the biomarker levels in workers exposed to HDI monomer and HDI isocyanurate and that genetics can be used to refine exposure predictions in small cohorts when quantitative personal exposure and biomarker measurements are included in the models.

RIFM fragrance ingredient safety assessment, furfuryl thioacetate, CAS Registry Number 13678-68-7

Furfuryl thioacetate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that furfuryl thioacetate is not genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the threshold of toxicological concern (TTC) for a Cramer Class III material, and the exposure to furfuryl thioacetate is below the TTC (0.0015 mg/kg/day, 0.0015 mg/kg/day, and 0.47 mg/day, respectively). The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for reactive materials (64 μg/cm2); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; furfuryl thioacetate is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; furfuryl thioacetate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

Skin Exposure to Acrylates in Nail Salons.

The nail salon industry has seen significant growth in recent years. Nail technicians provide manicures, pedicures and apply artificial nails; tasks that expose them to chemicals, including acrylates that are known skin and respiratory sensitizers. This paper reports on potential skin exposure to acrylates among nail technicians in Toronto, Canada. Hand skin wipes were collected after (i) the application of artificial nails, (ii) the application of ultraviolet cured gel nail polish, and (iii) deliberate contact with nail polish. Surface wipes were collected from work areas and surfaces contaminated with known products. Wipe samples were analysed for eight acrylates: methyl acrylate (MA), ethyl acrylate (EA), methyl methacrylate (MMA), ethyl methacrylate (EMA), 2-hydroxyethyl acrylate (HEA), 2-hydroxyethyl methacrylate (HEMA), 2-hydroxypropyl methacrylate (HPMA), and ethylene glycol dimethacrylate (EGDMA) by gas chromatography with mass spectrometry. Thirty-five wipe samples were collected. No acrylates were detected in skin samples (n = 8) or work surfaces (n = 6). However, MMA, EMA, EA, HEMA, and HPMA were detected in the samples of surfaces contaminated with known products. MMA was detected in 28% of products tested. HEMA and HPMA were detected where deliberate contact with nail polish occurred. These results confirm that acrylates are present in nail products. However, no acrylates were detected in skin wipes. MMA, a chemical prohibited for use in cosmetics in Canada, was detected in nail polishes. Nail technicians should continue to employ safe work practices that reduce the probability of skin contact with acrylates and other chemicals.

FABP5 as a possible biomarker in atopic march: FABP5-induced Th17 polarization, both in mouse model and human samples.

BackgroundWhile the incidence of patients with atopic dermatitis (AD) with atopic march (AM) showing respiratory allergy is steadily rising, the pathomechanism is still unknown. There are currently no biomarkers to predict progression of AM.MethodsTo explore the mechanism of AM, patients with AD and AM and healthy controls were recruited and RNA microarray, flow cytometry, quantitative real-time polymerase chain reaction, and immunofluorescence staining were performed. We also co-cultured dendritic cells and CD4+T cells with various Dermatophagoides farinae allergen fractions. Cytokine levels were evaluated using enzyme-linked immunosorbent assay.FindingsBoth fatty-acid-binding protein 5 (FABP5) and Th17-related genes were more highly expressed in AM. FABP5 knockdown significantly decreased Th17-inducing cytokines in keratinocytes and IL-17A in T cells from AM patients. Further confirmation was obtained using an AM mice model compared to mice without AM. Der f 1, a major D. farinae allergen, increased FABP5 and IL-17A expression in T cells from AM patients. Higher serum FABP5 levels from AM patients were positively correlated with serum IL-17A levels.InterpretationFABP5 expression, possibly enhanced by higher epicutaneous and respiratory sensitization to Der f 1, may directly promote Th17 responses in AD patients with AM. Thus, AM progression can be explained by Th17 reaction induced by FABP5. FABP5 was identified as a potential biomarker in AM.FundingThis study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; No. NRF-2017R1A2B4009568), grants of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, and the Republic of Korea (HI13C0010, HI14C1324, HI14C1799).

Safety of 3-phytase FLF1000 and FSF10000 as a feed additive for pigs for fattening and minor growing porcine species.

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety of 3‐phytase FLF1000/FSF10000 as a feed additive for pigs for fattening and minor porcine species for growing. This additive contains 3‐phytase produced by a genetically modified strain of Komagataella phaffii and it is authorised in its liquid FLF1000 and solid form FSF10000 as a feed additive for chickens for fattening, laying hens, chickens reared for laying and for minor poultry species for fattening or reared for laying or for breeding. The FEEDAP Panel has adopted an opinion regarding the use of this product as a feed additive in pigs for fattening and minor porcine species for growing. In that opinion, the FEEDAP Panel concluded that the use of the product as a feed additive would raise no concerns for the consumer safety nor for the environment but that the additive should be regarded as a potential respiratory sensitizer. The Panel also concluded that the additive has a potential to be efficacious in improving the phosphorus utilisation in the target species. However, the Panel could not conclude on the safety for the target species due to the limitations identified in the data provided. The applicant has now complemented the information and made it available to the Panel. The tolerance trial was done in weaned piglets in which the animals received up to 10 times the recommended dose of 1,000 FTU/kg feed. The results showed no adverse effects of the phytase on the performance of the animals or on the haematological and biochemical parameters measured in blood. Therefore, the Panel concluded that the additive (3‐phytase FLF1000 and FSF10000) is safe for pigs for fattening and minor growing porcine species at the recommended dose of 1,000 FTU/kg feed.

Allergic and Respiratory Symptoms in Employees of Indoor Cannabis Grow Facilities.

While little is known about the occupational hazards associated with Cannabis cultivation, both historical research in the hemp industry and preliminary data from modern grow houses, suggest that Cannabis workers may be at increased risk of respiratory and allergic diseases. We sought to investigate the association between workplace exposures and health symptoms in an indoor Cannabis grow facility in Washington State, USA. We performed a cross-sectional study with all consenting employees in an indoor Cannabis grow facility in Seattle, WA using a questionnaire. The questionnaire gathered data on respiratory, ocular, nasal, and dermal symptoms. A subset of employees with work-related symptoms underwent repeated cross-shift and cross-week measurement of spirometry, fractional exhaled nitrogen oxide (FeNO), and skin prick testing for Cannabis sensitization. Exposure to Cannabis dust was classified based on self-described tasks, expert opinion, and exposure monitoring of particulate matter. Multivariable logistic regression was undertaken to examine associations between exposure to Cannabis dust (classified as low, medium, and high) and health symptoms. Linear mixed effects models examined the relationship between cross-shift and cross-week changes in spirometry and FeNO. Ninety-seven percent (97%) of the employees (n = 31) surveyed were recreational cannabis users, with 81% (n = 25) smoking cannabis multiple times per day. Twenty-two (71%) employees reported one or more work-related symptoms: 65% respiratory, 39% ocular, 32% nasal, and 26% dermal symptoms. There was a trend toward increased likelihood of work-related symptoms with increasing exposure to Cannabis dust, although none of these results were statistically significant. Of the 10 employees with work-aggravated symptoms, 5 had borderline-high or high FeNO, 7 had abnormal spirometry, and 5 had evidence of Cannabis sensitization on skin prick testing. FeNO increased by 3.78 ppb (95% confidence interval 0.68-6.88 ppb) across the work-week and there was a trend toward cross-week and cross-shift reduced airflow. We found a high prevalence of work-related allergic- and particularly respiratory symptoms in the employees of one indoor Cannabis grow facility in Washington State. A high proportion of employees with work-aggravated symptoms had findings consistent with probable work-related asthma based on high FeNO, airflow obstruction on spirometry, and Cannabis sensitization on skin prick testing. However, due to the high incidence of recreational cannabis use among these workers, the relative influence of occupational versus recreational exposure to Cannabis dust on the respiratory health and sensitization status of these workers could not be resolved in this study.