The nature of chronic rejection after lung transplantation: a murine orthotopic lung transplant study.

Introduction: Chronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation. Methods: 40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT. For timing and location of rejection, extra grafts were sacrificed at day 7, 35, 56 and investigated by ex vivo µCT or single cell RNA (scRNA) profiling. Results: Chronic rejection originated as innate inflammation around small arteries evolving toward adaptive organization with subsequent end-arterial fibrosis and obliterans. Subsequently, venous and pleural infiltration appeared, followed by airway related bronchiolar folding and rarely bronchiolitis obliterans was observed. Ex vivo µCT and scRNA profiling validated the time, location and sequence of events with endothelial destruction and activation as primary onset. Conclusion: Against the current belief, chronic rejection in lung transplantation may start as an arterial response, followed by responses in venules, pleura, and, only in the late stage, bronchioles, as may be seen in some but not all patients with CLAD.

Level of BPA contamination in resin composites determines BPA release.

OBJECTIVES: Resin composites may release bisphenol A (BPA) due to impurities present in the monomers. However, there is a lack of knowledge regarding the leaching characteristics of BPA from resin composites. Therefore, experimental resin composites were prepared with known amounts of BPA. The objective of this study was (1) to determine which amount of BPA initially present in the material leaches out in the short term and, (2) how this release is influenced by the resin composition. METHODS: BPA (0, 0.001, 0.01, or 0.1 wt%) was added to experimental resin composites containing 60 mol% BisGMA, BisEMA(3), or UDMA, respectively, as base monomer and 40 mol% TEGDMA as diluent monomer. Polymerized samples (n = 5) were immersed at 37 °C for 7 days in 1 mL of water, which was collected and refreshed daily. BPA release was quantified with UPLC-MS/MS after derivatization with pyridine-3-sulfonyl chloride. RESULTS: Between 0.47 to 0.67 mol% of the originally added BPA eluted from the resin composites after 7 days. Similar elution trends were observed irrespective of the base monomer. Two-way ANOVA showed a significant effect of the base monomer on BPA release, but the differences were small and not consistent. SIGNIFICANCE: The released amount of BPA was directly proportional to the quantity of BPA present in the resin composite as an impurity. BPA release was mainly diffusion-based, while polymer composition seemed to play a minor role. Our results underscore the importance for manufacturers only to use monomers of the highest purity in dental resin composites to avoid unnecessary BPA exposure in patients.

Elution from direct composites for provisional restorations.

Purpose To assess elution from direct composite materials for provisional restorations and compare them with elution from direct restorative composites for permanent restorations.Methods Two dual-cure (Integrity Multi-Cure and Tempsmart DC) and two self-curing composites (Protemp 4 and Structur 3) were used, with Essentia serving as a reference. Cylindrical specimens (n=20) were cured according to the manufacturer's instructions; the dual-cure materials were prepared in both self- and dual-curing modes. Elution experiments were performed using water and absolute ethanol. The samples were incubated at 37 °C for either 24 h or four weeks; the extraction solvents were refreshed weekly. The eluted BisEMA (-3 / -6 / -10), BisGMA, CQ, UDMA, and TEGDMA were quantified using UHPLC-MS/MS.Results Monomer elution was detected in all provisional composites at 24 h and four weeks, but the amounts released did not exceed those released by the reference composite. When prepared in self-curing mode, Integrity Multi-Cure exhibited significantly higher elution of BisEMA-3, -6, and -10 in ethanol both after 24 h and cumulatively after four weeks. Self-cured Tempsmart DC released significantly more CQ, TEGDMA, and UDMA in both water and ethanol after immersion for 24 h and four weeks, along with significantly more BisGMA in ethanol both after 24 h and four weeks comparison to dual-cured Tempsmart DC (two-way ANOVA, post-hoc Tukey, P < 0.05).Conclusions Provisional composite materials did not elute higher amounts of monomers than a restorative composite. Dual-cured materials, prepared in the self-curing mode, show a trend towards higher monomer elution.

Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles.

BACKGROUND: Inhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory and systemic health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of occupational-level silica and ambient-level DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization. RESULTS: The findings highlight the distinct effects of silica and diesel exhaust particles (DEP) on lung injury, inflammation, and autoantibody formation in C57BL/6J and NOD/ShiLtJ mice. Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside mild fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Moreover, antinuclear antibodies correlated with extent of lung inflammation in NOD/ShiLTJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. However, aside from contributing to airway hyperreactivity specifically in NOD/ShiLtJ mice, the ambient-level DEP did not significantly amplify the effects induced by silica. There was no evidence of synergistic or additive interaction between these specific doses of silica and DEP in inducing lung damage or inflammation in either of the mouse strains. CONCLUSION: Mouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of ambient-level DEP on these silica-induced effects was minimal.

Towards a more effective REACH legislation in protecting human health.

There is growing evidence indicating the substantial contribution of man-made products to an increase in the risk of diseases of civilization. In this article, the Belgian Scientific Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) Committee gives a critical view on the working of REACH. The current regulatory framework needs to further evolve taking into account data generated using modern science and technology. There is a need for improved assessment process not only before but also after entering the market. Objectivity, transparency, and the follow-up after market access can be optimized. Additionally, no guidance documents exist for regulation of mixture effects. Further, the lengthiness before regulatory action is a big concern. Decision-making often takes several years leading to uncertainties for both producers and end users. A first proposed improvement is the implementation of independent toxicity testing, to assure objectivity, transparency, and check and improve compliance. A "no data, no market" principle could prevent access of hazardous chemicals to the market. Additionally, the introduction of novel testing could improve information on endpoints such as endocrine disrupting abilities, neurotoxicity, and immunotoxicity. An adapted regulatory framework that integrates data from different sources and comparing the outputs with estimates of exposure is required. Fast toxicology battery testing and toxicokinetic testing could improve speed of decision-making. Hereby, several improvements have been proposed that could improve the current REACH legislation.

Single cell RNA sequencing reveals endothelial cell killing and resolution pathways in experimental malaria-associated acute respiratory distress syndrome.

Plasmodium parasites cause malaria, a global health disease that is responsible for more than 200 million clinical cases and 600 000 deaths each year. Most deaths are caused by various complications, including malaria-associated acute respiratory distress syndrome (MA-ARDS). Despite the very rapid and efficient killing of parasites with antimalarial drugs, 15% of patients with complicated malaria succumb. This stresses the importance of investigating resolution mechanisms that are involved in the recovery from these complications once the parasite is killed. To study the resolution of MA-ARDS, P. berghei NK65-infected C57BL/6 mice were treated with antimalarial drugs after onset of symptoms, resulting in 80% survival. Micro-computed tomography revealed alterations of the lungs upon infection, with an increase in total and non-aerated lung volume due to edema. Whole body plethysmography confirmed a drastically altered lung ventilation, which was restored during resolution. Single-cell RNA sequencing indicated an increased inflammatory state in the lungs upon infection, which was accompanied by a drastic decrease in endothelial cells, consistent with CD8+ T cell-mediated killing. During resolution, anti-inflammatory pathways were upregulated and proliferation of endothelial cells was observed. MultiNicheNet interactome analysis identified important changes in the ligand-receptor interactions during disease resolution that warrant further exploration in order to develop new therapeutic strategies. In conclusion, our study provides insights in pro-resolving pathways that limit inflammation and promote endothelial cell proliferation in experimental MA-ARDS. This information may be useful for the design of adjunctive treatments to enhance resolution after Plasmodium parasite killing by antimalarial drugs.

Household air pollution and risk of pulmonary tuberculosis in HIV-Infected adults.

BACKGROUND: In low- and middle-income countries countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection. METHODS: We conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 - March 2019). Cases had current or recent (<5y) PTB (positive sputum smear or Xpert MTB/RIF), controls had no PTB. Daily and lifetime HAP exposure were assessed by questionnaire and, in a random sub-sample (n=270), by 24-hour measurements of personal carbon monoxide (CO) at home. We used multivariable logistic regression to examine the associations between HAP and PTB. RESULTS: We recruited 435 cases and 842 controls (median age 41 years, [IQR] 33-50; 76% female). Cases were more likely to be female than male (63% vs 37%). Participants reporting cooking for >3h/day and ≥2 times/day and ≥5 days/week were more likely to have PTB (aOR 1·36; 95%CI 1·06-1·75) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 4·64 (95%CI 1·1-20·7) for the highest quintile [12·3-76·2 ppm] compared to the lowest quintile [0·1-1·9 ppm]. CONCLUSION: Time spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women.

Impact of a Polymer-Based Nanoparticle with Formoterol Drug as Nanocarrier System In Vitro and in an Experimental Asthmatic Model.

The implementation of nanotechnology in pulmonary delivery systems might result in better and more specific therapy. Therefore, a nano-sized drug carrier should be toxicologically inert and not induce adverse effects. We aimed to investigate the responses of a polymer nano drug carrier, a lysine poly-hydroxyethyl methacrylate nanoparticle (NP) [Lys-p(HEMA)], loaded with formoterol, both in vitro and in vivo in an ovalbumin (OVA) asthma model. The successfully synthesized nanodrug formulation showed an expectedly steady in vitro release profile. There was no sign of in vitro toxicity, and the 16HBE and THP-1 cell lines remained vital after exposure to the nanocarrier, both loaded and unloaded. In an experimental asthma model (Balb/c mice) of ovalbumin sensitization and challenge, the nanocarrier loaded and unloaded with formoterol was tested in a preventive strategy and compared to treatment with the drug in a normal formulation. The airway hyperresponsiveness (AHR) and pulmonary inflammation in the bronchoalveolar lavage (BAL), both cellular and biochemical, were assessed. The application of formoterol as a regular drug and the unloaded and formoterol-loaded NP in OVA-sensitized mice followed by a saline challenge was not different from the control group. Yet, both the NP formulation and the normal drug application led to a more deteriorated lung function and increased lung inflammation in the OVA-sensitized and -challenged mice, showing that the use of the p(HEMA) nanocarrier loaded with formoterol needs more extensive testing before it can be applied in clinical settings.

Differential Pulmonary Toxicity and Autoantibody Formation in Genetically Distinct Mouse Strains Following Combined Exposure to Silica and Diesel Exhaust Particles.

Background: Inhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of silica and DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization. Results: Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside limited fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. Conclusion: Mouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of diesel exhaust particles on these silica-induced effects was minimal.

Household Air Pollution and Risk of Pulmonary Tuberculosis in HIV-Infected Adults.

Background: In developing countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection. Methods: We conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 - March 2019). Cases had current or recent (<5y) PTB (positive sputum smear or Xpert MTB/RIF), controls had no PTB. Daily and lifetime HAP exposure were assessed by questionnaire and, in a random sub-sample (n=270), by 24-hour measurements of personal carbon monoxide (CO) at home. We used multivariable logistic regression to examine the associations between HAP and PTB. Results: We recruited 435 cases and 842 controls (median age 41 years, [IQR] 33-50; 76% female). Cases were more likely to be female than male (63% vs 37%). Participants reporting cooking for >3h/day and ≥2 times/day and ≥5 days/weekwere more likely to have PTB (aOR 1·36; 95%CI 1·06-1·75) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 4·64 (95%CI 1·1-20·7) for the highest quintile [12·3-76·2 ppm] compared to the lowest quintile [0·1-1·9 ppm]. Conclusion: Time spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women.

Frequent Allergic Sensitization to Farmed Edible Insects in Exposed Employees.

BACKGROUND: Exposure to insects used in pet food, scientific research, or live fish bait can cause an occupational allergy. The recent shift toward enhanced insect production for human consumption and animal feed will likely expose more employees. OBJECTIVE: To investigate sensitization and symptoms in employees exposed to edible insects in Flanders. METHODS: Fifteen insect-exposed employees were recruited and sensitization was explored by skin prick test, basophil activation test, and immunoblotting. Lung function, FeNO, histamine provocation, and sputum induction were studied. Airborne dust sampling was performed and proteins were studied by silver stain and immunoblotting. RESULTS: Sixty percent of employees self-reported upper respiratory tract symptoms related to insect exposure. Ten employees (71.4%) had a positive histamine provocation test concentration causing a 20% drop in FEV1 less than 8 mg/mL and four (26.7%) had FeNO levels above 25 ppb. Four employees (30.7%) had a positive skin prick test for at least one insect, and seven (58.3%) had a positive basophil activation test. In eight participants with insect sensitization, four (50%) had co-occurring house dust mite sensitization. Two participants had strong IgE binding to a 50-kDa migratory locust allergen, one to a 25-kDa mealworm allergen, and one to mealworm α-amylase. In one center, facility adjustment resulted in a substantial decrease in the inhalable dust fraction. CONCLUSIONS: Insect exposure leads to high levels of sensitization among employees. Most employees reported symptoms of the upper respiratory system, and two-thirds of employees had bronchial hyperreactivity. Prevention and health surveillance will be important in the developing insect-rearing industry.

A Multimodal Imaging-Supported Down Syndrome Mouse Model of RSV Infection.

Individuals with Down syndrome (DS) are more prone to develop severe respiratory tract infections. Although a RSV infection has a high clinical impact and severe outcome in individuals with DS, no vaccine nor effective therapeutics are available. Any research into infection pathophysiology or prophylactic and therapeutic antiviral strategies in the specific context of DS would greatly benefit this patient population, but currently such relevant animal models are lacking. This study aimed to develop and characterize the first mouse model of RSV infection in a DS-specific context. Ts65Dn mice and wild type littermates were inoculated with a bioluminescence imaging-enabled recombinant human RSV to longitudinally track viral replication in host cells throughout infection progression. This resulted in an active infection in the upper airways and lungs with similar viral load in Ts65Dn mice and euploid mice. Flow cytometric analysis of leukocytes in lungs and spleen demonstrated immune alterations with lower CD8+ T cells and B-cells in Ts65Dn mice. Overall, our study presents a novel DS-specific mouse model of hRSV infection and shows that potential in using the Ts65Dn preclinical model to study immune-specific responses of RSV in the context of DS and supports the need for models representing the pathological development.

Lung function measurements in preclinical research: What has been done and where is it headed?

Due to the close interaction of lung morphology and functions, repeatable measurements of pulmonary function during longitudinal studies on lung pathophysiology and treatment efficacy have been a great area of interest for lung researchers. Spirometry, as a simple and quick procedure that depends on the maximal inspiration of the patient, is the most common lung function test in clinics that measures lung volumes against time. Similarly, in the preclinical area, plethysmography techniques offer lung functional parameters related to lung volumes. In the past few decades, many innovative techniques have been introduced for in vivo lung function measurements, while each one of these techniques has their own advantages and disadvantages. Before each experiment, depending on the sensitivity of the required pulmonary functional parameters, it should be decided whether an invasive or non-invasive approach is desired. On one hand, invasive techniques offer sensitive and specific readouts related to lung mechanics in anesthetized and tracheotomized animals at endpoints. On the other hand, non-invasive techniques allow repeatable lung function measurements in conscious, free-breathing animals with readouts related to the lung volumes. The biggest disadvantage of these standard techniques for lung function measurements is considering the lung as a single unit and providing only global readouts. However, recent advances in lung imaging modalities such as x-ray computed tomography and magnetic resonance imaging opened new doors toward obtaining both anatomical and functional information from the same scan session, without the requirement for any extra pulmonary functional measurements, in more regional and non-invasive manners. Consequently, a new field of study called pulmonary functional imaging was born which focuses on introducing new techniques for regional quantification of lung function non-invasively using imaging-based techniques. This narrative review provides first an overview of both invasive and non-invasive conventional methods for lung function measurements, mostly focused on small animals for preclinical research, including discussions about their advantages and disadvantages. Then, we focus on those newly developed, non-invasive, imaging-based techniques that can provide either global or regional lung functional readouts at multiple time-points.

Sampling strategies and analytical techniques for assessment of airborne micro and nano plastics.

The atmosphere is pervasively polluted by microplastics and nano plastics (M/NPs) released into indoor and outdoor areas. However, various methodologies and their limitations along with non-standardization make the comparison of information concerning their prevalence difficult. Such diversity in techniques greatly limits the interpretation of results. Herein, We extracted data from publications on PubMed and Embase database up to the year 2022 regarding sampling strategies, identification methods, and reporting data for M/NPs quantification. In this review, 5 major areas for measuring airborne M/NPs have been identified including pre-sampling/ sampling/ post-sampling/ analysis/ and contamination avoidance. There are many challenges specific to each of those sections that need to be resolved through further method development and harmonization. This review mainly focuses on the different methods for collecting atmospheric M/NPs and also the analytical tools which have been used for their identification. While passive sampling is the most user-friendly method, the most precise and reproducible approach for collecting plastic particles is an active method which is directly followed by visual counting as the most common physical analysis technique. Polymers collected using visual sorting are most frequently identified by spectroscopy (FTIR; Raman). However, destructive analytical techniques (thermal degradation) also provide precise chemical information. In all cases, the methods were screened for advantages, limitations, and fieldwork abilities. This review outlines and critiques knowledge gaps, and recommendations to support standardized and comparable future research.

Corrigendum: Innate lymphoid cells are required to induce airway hyperreactivity in a murine neutrophilic asthma model.

[This corrects the article DOI: 10.3389/fimmu.2022.849155.].

Peribronchial Inflammation Resulting from Regulatory T Cell Deficiency Damages the Respiratory Epithelium and Disturbs Barrier Function.

Regulatory T cells (Tregs) that express the transcription factor Foxp3 have a critical role in limiting inflammatory processes and tissue damage. Whether Tregs are functional in maintaining epithelial barriers and in control of tight junction expression has not yet been explored. In this study, we investigated the effect of Treg deficiency on the airway epithelial barrier in an experimental murine model in which diphtheria toxin was repeatedly injected in Foxp3-diphtheria toxin receptor (DTR) mice to deplete Tregs. This resulted in spontaneous peribronchial inflammation and led to a systemic and local increase of IL-4, IL-5, CCL3, IFN-γ, and IL-10 and a local (lung) increase of IL-6 and IL-33 and decreased amphiregulin levels. Moreover, Treg depletion increased airway permeability and decreased epithelial tight junction (protein and mRNA) expression. CTLA4-Ig treatment of Treg-depleted mice almost completely prevented barrier dysfunction together with suppression of lung inflammation and cytokine secretion. Treatment with anti-IL-4 partly reversed the effects of Treg depletion on tight junction expression, whereas neutralization of IL-6 of IFN-γ had either no effect or only a limited effect. We conclude that Tregs are essential to protect the epithelial barrier at the level of tight junctions by restricting spontaneous T cell activation and uncontrolled secretion of cytokines, in particular IL-4, in the bronchi.

Chlorine exposure and intensive exercise induces airway hyperreactivity in a 3-week murine exercise model.

RATIONALE: Exercise-induced bronchoconstriction (EIB) is defined as acute narrowing of the airways during or immediately after exercise. EIB has a high prevalence in elite swimmers probably due to the high ventilation rate and exposure to the chlorine by-products. It is still puzzling which pathophysiological mechanisms drive EIB. OBJECTIVE: In this study, we evaluated airway hyperreactivity, permeability, integrity and inflammation in a murine swimmers EIB model with and without chlorine exposure. METHODS: Mice performed a 3-week swimming protocol in a swimming pool with counter current. Three hours after the last swimming session, airway hyperreactivity to methacholine was assessed. Cytokine levels and cellular differential analysis was performed in BAL fluid. Airway permeability and tight junction expression was measured in serum and lung tissue. T-, B-, dendritic and innate lymphoid cells were determined in lung tissue via flow cytometry. RESULTS: A significant higher airway resistance (Rn; P < 0.0001) was observed in mice swimming in chlorinated water (mean Rn = 1.26 cmH2O.s/ml) compared to mice swimming in tap water (mean Rn = 0.76 cmH2O.s/ml) and both inhalation groups in the absence of cellular inflammation. No significant differences were found in lung immune cell populations or in lung tight junction mRNA expression. Experiments in SCID, Rag2-/-γc-/- or Cpa3cre/+ mice showed a limited involvement of the innate, adaptive immune system or the mast cells. CONCLUSION: Our 3-week swimming murine model mimics intensive swimming in chlorinated water with the presence of airway hyperreactivity in mice swimming in chlorinated water in the absence of airway inflammation and airway epithelial damage.

Occupational Asthma Caused by Low-Molecular-Weight Chemicals Associated With Contact Dermatitis: A Retrospective Study.

BACKGROUND: Occupational asthma (OA) may have different etiologies, but it is not clear whether the etiologic agents influence the clinical presentation, especially the co-occurrence of skin lesions. OBJECTIVE: To determine the impact of different asthmagens on the characteristics of OA, with a focus on the occurrence of prior or concomitant skin disorders. METHODS: In a retrospective analysis of patients who visited the Occupational and Environmental Disease Clinic of a tertiary referral hospital from 2009 to 2019, we classified patients into definite, probable, or possible OA according to prespecified diagnostic guidelines. In multivariate logistic regression with sensitivity analysis, we examined the relation of high- and low-molecular-weight (HMW and LMW) agents with the clinical presentation. RESULTS: Of 209 cases of OA, 66 were caused by HMW agents and 143 by LMW agents. Patients with OA exposed to LMW agents had higher odds of having (had) allergic contact dermatitis (odds ratio, 5.45 [1.80-23.70]; P < .01), compared with patients exposed to HMW agents. Conversely, HMW agents were associated with higher odds of rhinitis symptoms (odds ratio of LMW/HMW, 0.33 [0.17-0.63]; P < .001) and high total IgE (odds ratio of LMW/HMW, 0.35 [0.17-0.70]; P < .01). Risk factors for having coexisting contact dermatitis included construction work, hairdressing, and exposure to metals or epoxy resins. CONCLUSIONS: Among patients with OA, exposure to specific LMW agents was associated with a high frequency of contact dermatitis. Different types of asthmagens within HMW or LMW agents appear to determine the phenotype and comorbidity of OA.

Quantification of three antineoplastic agents in urine using the UniSpray ionisation source.

BACKGROUND: Many guidelines and safety measures led to a decrease in exposure to antineoplastic agents. Since healthcare workers are often exposed to lower concentrations than patients, a sensitive method is needed to quantify occupational exposure. OBJECTIVE: The aim of this study was to develop and validate a sensitive method for simultaneous detection and quantification of cyclophosphamide, ifosfamide and paclitaxel in urine by use of UPLC-MS/MS with a UniSpray ionisation source. METHODS: Compounds were extracted from urine using Novum simplified liquid extraction cartridges, separated on a C18 column, ionised by a UniSpray ionisation source and detected with MS/MS. In the second part of the study, a field study was performed to assess occupational exposure to antineoplastic agents. RESULTS: Eighty-three samples from healthcare workers were analysed and resulted in seventeen samples containing quantifiable concentrations of at least one compound. In conclusion, a sensitive method for simultaneous detection and quantification of cyclophosphamide (LLOQ 0.05 ng/mL), ifosfamide (LLOQ 0.3 ng/mL) and paclitaxel (LLOQ 0.7 ng/mL) was developed and validated.