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    Monika Raulf-heimsoth

    Background Most threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates... more
    Background Most threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates whether the results on the inflammatory effects of particles that have been demonstrated in animal models can be confirmed in acute inhalation studies in humans. Such studies have not been conducted so far for barium sulfate particles (BaSO4), a substance with very low solubility and without known substance-specific toxicity. Previous inhalation studies with zinc oxide (ZnO), which has a substance-specific toxicity, have shown local and systemic inflammatory respones. The design of these human ZnO inhalation studies was adopted for BaSO4 to compare the effects of particles with known inflammatory activity and supposedly inert particles. For further comparison, in vitro investigations on inflammatory processes were carried out. Methods Sixteen healthy v...
    ObjectiveStandardised quantitative analysis of the humoral immune response to SARS‐CoV‐2 antigens may be useful for estimating the extent and duration of immunity. The aim was to develop enzyme‐linked immunosorbent assays (ELISAs) for the... more
    ObjectiveStandardised quantitative analysis of the humoral immune response to SARS‐CoV‐2 antigens may be useful for estimating the extent and duration of immunity. The aim was to develop enzyme‐linked immunosorbent assays (ELISAs) for the quantification of human IgG antibodies against SARS‐CoV‐2 antigens.MethodsEnzyme‐linked immunosorbent assays were developed based on monoclonal antibodies against human IgG and recombinant SARS‐CoV‐2 antigens (Spike‐S1 and Nucleocapsid). The WHO 67/086 immunoglobulin and WHO 20/136 SARS‐CoV‐2 references were used for standardisation. Sera of a study group of COVID‐19‐positive subjects (n = 144), pre‐pandemic controls (n = 135) and individuals vaccinated with BioNTech–Pfizer BNT162b2 vaccine (n = 48) were analysed. The study group sera were also tested using EuroImmun SARS‐CoV‐2‐ELISAs and a quantitative S1‐specific fluorescence enzyme immunoassay (FEIA) from Thermo Fisher.ResultsThe ELISA results were repeatable and traceable to international units...
    Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized... more
    Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized particles compared to microparticles. No effects at all were observed after inhalation of micro- and nano-sized zinc oxide (ZnO) particle concentrations of 0.5 mg/m3. Studies with different particle sizes of ZnO at higher exposures are not available. Accordingly, we hypothesized that inhalation of nano-sized ZnO particles induces stronger health effects than the inhalation of the same airborne mass concentration of micro-sized ZnO particles. 16 healthy volunteers (eight men, eight women) were exposed to filtered air and ZnO particles (2.0 mg/m3) for 2 h (one session with nano- and one with micro-sized ZnO) including 1 h of cycling at moderate workload. Effect parameters were symptoms, body temperature, inflammatory markers in blood and in induced sp...
    A small population of T-cells does not express the conventional T-cell receptor (TCR), characterized by the alpha and beta polypeptide chains (alpha/beta TCR) but two polypeptides termed gamma and delta (gamma/delta TCR). Changes in... more
    A small population of T-cells does not express the conventional T-cell receptor (TCR), characterized by the alpha and beta polypeptide chains (alpha/beta TCR) but two polypeptides termed gamma and delta (gamma/delta TCR). Changes in gamma/delta TCR expression may be relevant as the cause or consequence of several diseases. Our study was undertaken to determine and compare the distribution of T-cells expressing gamma/delta TCR in blood and bronchoalveolar lavage (BAL) of patients with sarcoidosis, hypersensitivity pneumonitis (HP), idiopathic pulmonary fibrosis (IPF), and of healthy controls. In addition, the association between gamma/delta TCR of blood T-lymphocytes and accessory molecules was analysed. Using direct immunofluorescence with the anti-gamma/delta TCR and anti-CD3 monoclonal antibodies (MoAbs) followed by flow cytometric analysis, the blood of patients with pulmonary sarcoidosis, HP, IPF and of healthy controls was analysed. To reveal the association between gamma/delta...
    SummaryBackground: Exposure to airborne wheat allergens in the bakery trade is associated with a high risk of occupational allergy and asthma. Control and reduction of allergen exposure require relatively simple but reliable monitoring... more
    SummaryBackground: Exposure to airborne wheat allergens in the bakery trade is associated with a high risk of occupational allergy and asthma. Control and reduction of allergen exposure require relatively simple but reliable monitoring techniques. We developed new rabbit IgG‐based enzyme immunoassays (EIA) for wheat allergens, which might be a convenient alternative for the thus far used human IgG4 inhibition assay.Methods: The reactivity and specificity of rabbit antibodies were assessed by EIA and immunoblotting, and compared with those of IgE from wheat‐sensitized bakers, and with the antibodies used in the IgG4 inhibition EIA. An IgG inhibition and a sandwich EIA were developed for analysis of airborne dust samples.Results: Human IgG4 and rabbit IgG inhibition EIAs had comparable sensitivities, with limits of detection (LOD) between 18 and 88 ng/mL, while the sandwich EIA was much more sensitive (LOD<0.2 ng/mL). Human IgG4 and rabbit IgG reacted in immunoblotting with most of...
    Sulphur dioxide (SO(2)) is an important environmental and workplace air pollutant. Some studies demonstrate that subjects without adaptation respond to SO(2) up to 10 ppm with irritative effects on the airways. The aim of our study was to... more
    Sulphur dioxide (SO(2)) is an important environmental and workplace air pollutant. Some studies demonstrate that subjects without adaptation respond to SO(2) up to 10 ppm with irritative effects on the airways. The aim of our study was to assess irritative effects of SO(2) up to 2 ppm on the airways using non-invasive methods like exhaled breath condensate (EBC), nasal lavage fluid (NALF) and exhaled nitric oxide (FeNO). Sixteen healthy volunteers were exposed for 4 h to SO(2) in concentrations of 0 (clean air), 0.5, 1.0 and 2.0 ppm in a repeated measures cross-over design. Before and after exposure, FeNO and biomarkers of airway inflammation in NALF and EBC were measured. All EBC pH values, collected after exposure, were more alkaline than before, significant only for clean air (7.05 + or - 0.4 vs. 7.27 + or - 0.3, P = 0.0031) and 0.5 ppm SO(2) exposure (6.85 + or - 0.53 vs. 7.08 + or - 0.42, P = 0.0251). No dose-dependent differences before and after exposure were measured for LTB(4), PGE(2) and 8-isoPGF(2alpha). Substance P in NALF collected after exposure tended to result in higher concentrations compared to pre-samples, without clear dose effect. Further cellular and soluble parameters measured were not significantly affected. Our results show that 4 h SO(2) exposure up to 2.0 ppm did not induce significant changes in the biomarker composition of the EBC and NALF when compared with clean air or with pre-samples of the same subject. Therefore our data suggest that acute low dose SO(2) exposure in not adapted subjects did not induce airway irritation or/and inflammation measured under these conditions.
    It was the aim of this study to evaluate the effect of different devices on the metal concentration in exhaled breath condensate (EBC) and to prove whether working conditions in different welding companies result in diverse composition of... more
    It was the aim of this study to evaluate the effect of different devices on the metal concentration in exhaled breath condensate (EBC) and to prove whether working conditions in different welding companies result in diverse composition of metallic elements. The influence of two collection devices (ECoScreen, ECoScreen2) on detection of metallic elements in EBC was evaluated in 24 control subjects. Properties of ECoScreen and a frequent use can alter EBC metal content due to contamination from metallic components. ECoScreen2 turned out to be favourable for metal assessment. Concentrations of iron, nickel and chromium in EBC sampled with ECoScreen2 were compared between non-exposed controls and industrial welders. Metal concentrations in EBC were higher in 36 welders recruited from three companies. Exposure to welding fumes could be demonstrated predominantly for increased iron concentrations. Concentrations of iron and nickel differed by working conditions, but chromium could not be detected in EBC.
    Background Workers in the zinc production and processing of galvanized sheet steel are exposed to a complex mixture of particles and gases, including zinc oxide (ZnO) that can affect human health. We aimed to study the effects of... more
    Background Workers in the zinc production and processing of galvanized sheet steel are exposed to a complex mixture of particles and gases, including zinc oxide (ZnO) that can affect human health. We aimed to study the effects of short-term controlled exposure to nano-sized ZnO on airway inflammatory markers in healthy volunteers. Methods Sixteen subjects (8 females, 8 men; age 19–42, non-smokers) were exposed to filtered air and ZnO nanoparticles (0.5, 1.0 and 2.0 mg/m3) for 4 h, including 2 h of cycling with a low workload. Induced sputum samples were collected during a medical baseline and a final examination and also about 24 h after each exposure. A number of inflammatory cellular and soluble markers were analyzed. Results Frequency and intensity of symptoms of airway irritation (throat irritation and cough) were increased in some subjects 24 h after ZnO exposures when compared to filtered air. The group comparison between filtered air and ZnO exposures showed statistically sig...
    Occupational exposure to foods is responsible for up to 25% of cases of occupational asthma and rhinitis. Animal and vegetable high‐molecular‐weight proteins present in aerosolized foods during food processing, additives, preservatives,... more
    Occupational exposure to foods is responsible for up to 25% of cases of occupational asthma and rhinitis. Animal and vegetable high‐molecular‐weight proteins present in aerosolized foods during food processing, additives, preservatives, antioxidants, and food contaminants are the main inhalant allergen sources. Most agents typically cause IgE‐mediated allergic reactions, causing a distinct form of food allergy (Class 3 food allergy). The allergenicity of a food protein, allergen exposure levels, and atopy are important risk factors. Diagnosis relies on a thorough medical and occupational history, functional assessment, assessment of sensitization, including component‐resolved diagnostics where appropriate, and in selected cases specific inhalation tests. Exposure assessment, including allergen determination, is a cornerstone for establishing preventive measures. Management includes allergen exposure avoidance or reduction (second best option), pharmacological treatment, assessment o...
    The availability of allergen molecules (‘components’) from several protein families has advanced our understanding of immunoglobulin E (IgE)‐mediated responses and enabled ‘component‐resolved diagnosis’ (CRD). The European Academy of... more
    The availability of allergen molecules (‘components’) from several protein families has advanced our understanding of immunoglobulin E (IgE)‐mediated responses and enabled ‘component‐resolved diagnosis’ (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low‐abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross‐reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE‐mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, m...
    The aim of this document is to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition.... more
    The aim of this document is to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli and surrounding interstitial tissue which develops as the result of a non-IgE mediated allergic reaction to a variety of organic materials or low-molecular-weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low-molecular-weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests in order to ascertain the work-relatedness of the disease. Both the clinical and the occupa...
    In vitro allergy diagnostics is rapidly advancing. This is primarily due to the development of component-based diagnostic tools. The availability of allergen components now allows a more precise and patient-tailored diagnostics, which has... more
    In vitro allergy diagnostics is rapidly advancing. This is primarily due to the development of component-based diagnostic tools. The availability of allergen components now allows a more precise and patient-tailored diagnostics, which has implications for therapeutic strategies including decision about specific immunotherapy. Furthermore, differential diagnostics of food intolerances and food allergies is also advancing because of this novel test. Another area of advancement is cellular diagnostics, which is primarily based on basophile activation tests. These recent developments will be discussed in this article.
    Cattle are well-known sources of respiratory allergens in agricultural environments. Breed-specific differences in Bos d 2 (a major bovine allergen) levels in cattle hair have been previously suggested but not fully characterized.... more
    Cattle are well-known sources of respiratory allergens in agricultural environments. Breed-specific differences in Bos d 2 (a major bovine allergen) levels in cattle hair have been previously suggested but not fully characterized. Therefore, the aim of the current study was to determine whether hair from common cattle breeds differs in protein and allergen content. In total, 80 hair samples from 16 different cattle breeds were analyzed. The protein concentration was determined using the Bradford assay. The allergen content was measured using a sandwich ELISA based on polyclonal antibodies against a bovine hair protein extract and a commercial immunoassay based on monoclonal antibodies against Bos d 2. Results are given in micrograms per gram of hair. Statistical analysis was performed using the Kruskal-Wallis test and Spearman's rank correlation. A wide variability in all 3 tested parameters was observed between the individual samples. The protein content differed by about 35-fo...
    Occupational bioaerosol exposures are capable to cause respiratory diseases. We studied the relationship between exposure to bioaerosols and biomarkers' concentration in exhaled breath condensate (EBC) and fractional exhaled nitric... more
    Occupational bioaerosol exposures are capable to cause respiratory diseases. We studied the relationship between exposure to bioaerosols and biomarkers' concentration in exhaled breath condensate (EBC) and fractional exhaled nitric oxide (FeNO) in 119 bioaerosol-exposed compost workers taking into account atopy and smoking habits. Atopy was classified according to specific IgE concentrations to common inhalant allergens (sx1). Bioaerosol exposure was estimated according to job title, duration of employment, results of ambient monitoring at the workplaces, and shift time worked under protection of filtered air supply. Concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α), prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and acid-base balance (pH) in EBC and FeNO were assessed in 59 never-smoking (NS) and 60 smoking (S) compost workers. We found that atopic subjects were equally distributed among NS and S (n = 16 each). Levels of 8-iso-PGF2α were significantly higher in workers c...
    The term irritant-induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be... more
    The term irritant-induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high-level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant-related asthma: (i) definite IIA, that is acute-onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA, that is asthma that develops in workers with multiple symptomatic high-level exposures to irritants; and (iii) possible IIA, that is asthma occurring with a delayed...
    Component-resolved diagnosis using microarray technology has recently been introduced in clinical allergology, but its applicability in patients with natural rubber latex (NRL) allergy has not been investigated. To evaluate the utility of... more
    Component-resolved diagnosis using microarray technology has recently been introduced in clinical allergology, but its applicability in patients with natural rubber latex (NRL) allergy has not been investigated. To evaluate the utility of microarray-based immunoglobulin (Ig) E detection in the diagnostic workup of NRL allergy and to compare this new diagnostic tool with established methods of NRL-specific IgE detection. We investigated 52 adults with immediate-type NRL allergy and 50 control patients. Determination of specific serum IgE against 8 recombinant Hevea brasiliensis allergen components was performed using a customized allergen microarray and a conventional fluorescence enzyme immunoassay (FEIA). The panel of microarrayed allergen components was shown to represent a comprehensive repertoire of clinically relevant NRL proteins. NRL-specific IgE recognition patterns and sensitization rates determined by microarray analysis were similar to those obtained by conventional FEIA....
    Introduction: Welding fumes are known to contain chromium (Cr) compounds. Particulate matter, Cr and other constituents of welding fume may induce inflammatory reactions. Aims and objectives: We studied irritative effects of welding fume... more
    Introduction: Welding fumes are known to contain chromium (Cr) compounds. Particulate matter, Cr and other constituents of welding fume may induce inflammatory reactions. Aims and objectives: We studied irritative effects of welding fume and Cr in non-smoking welders using spirometry and fractional exhaled nitric oxide (FeNO). Methods: Shift exposure to respirable particles in the welding fume was measured with personal samplers in the breathing zone of 119 non-smoking welders. The Cr concentration in these fume samples was determined by inductively coupled plasma mass spectrometry. Post-shift spirometry was performed with pneumotachography. FeNO was determined with a handheld device (NIOX Mino®). A potential irritative effect of Cr and welding fume was evaluated with multiple regression models. Results: Lung function measurements revealed normal average values standardized to European Community of Coal and Steel. (median of forced vital capacity (FVC): 111.2%; forced expiratory volume in on second (FEV1):104.7%; Tiffeneau index (FEV1/FVC): 77%). Median of FeNO was 17.5 ppb. Cr, respirable welding fume and use of dust masks together explained less than 10% of the variance of the variables under study. We found no effect of any of these potential predictors measured during a single working shift on FeNO or Tiffeneau index. Conclusion: Our data analysis did not reveal an acute irritative effect of Cr and welding fumes in non-smoking welders assessed with spirometry and FeNO. Nevertheless, further investigations with the implementation of non-invasive methods to assess inflammatory processes in the upper airways are necessary to make final conclusions.

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