Fungal exposome, human health, and unmet needs: A 2022 update with special focus on allergy.

Humans inhale, ingest, and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom, reflected by its complex taxonomy, are in sharp contrast with our scarce knowledge about its distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health, through the lens of fungal allergy and other fungal hypersensitivity reactions. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal-related hypersensitivity diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.

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.

Comparing the concentration levels of allergens and endotoxins in employees' homes and offices.

OBJECTIVE: The aim of the study was to find out whether allergen and endotoxin concentrations in offices differ from those measured at the homes of employees, and identify the parameters that influence exposure. METHODS: Electrostatic dust collectors (EDCs) were placed in five office buildings (68 rooms, 436 EDCs), as well as the homes of the office workers (145 rooms, 405 EDCs) for 14 days, four times a year. In addition, surface samples were collected from the offices four times a year by vacuuming the carpeted floors. Domestic mite (DM), and the major cat and dog allergens (Fel d 1 and Can f 1) were quantified in all samples using fluorescence enzyme immunoassays. Endotoxin was measured in the EDC samples, using the Limulus amoebocyte lysate assay. The allergen and endotoxin concentrations were log transformed and analysed with multilevel models. RESULTS: Endotoxin concentrations were significantly higher in personal homes compared to levels measured in the offices, and depended on the number of persons living in each household, as well as the presence of a dog. DM allergens were significantly higher in households than in offices, and were significantly higher in bedrooms compared to living rooms. Offices occupied by cat owners had significantly higher Fel d 1 concentrations than offices or homes without. Additionally, Can f 1 concentrations were significantly higher in offices occupied by dog owners compared to those without. CONCLUSIONS: Pet owners appear to transfer cat and dog allergens to their offices. Therefore, in case of allergy complaints at the office, employers and physicians might consider possible contamination by cat and dog allergens.

No inflammatory effects after acute inhalation of barium sulfate particles in human volunteers.

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 volunteers were exposed to filtered air and BaSO4 particles (4.0 mg/m3) for two hours including one hour of ergometric cycling at moderate workload. Effect parameters were clinical signs, body temperature, and inflammatory markers in blood and induced sputum. In addition, particle-induced in vitro-chemotaxis of BaSO4 was investigated with regard to mode of action and differences between in vivo and in vitro effects. RESULTS: No local or systemic clinical signs were observed after acute BaSO4 inhalation and, in contrast to our previous human exposure studies with ZnO, no elevated values of biomarkers of inflammation were measured after the challenge. The in vitro chemotaxis induced by BaSO4 particles was minimal and 15-fold lower compared to ZnO. CONCLUSION: The results of this study indicate that BaSO4 as a representative of granular biopersistent particles without specific toxicity does not induce inflammatory effects in humans after acute inhalation. Moreover, the in vitro data fit in with these in vivo results. Despite the careful and complex investigations, limitations must be admitted because the number of local effect parameters were limited and chronic toxicity could not be studied.

Skin symptoms in veterinary assistant staff and veterinarians: A cross-sectional study.

BACKGROUND: Veterinary assistants and veterinarians are at an increased risk of developing an occupational skin disease, for example, irritant/allergic contact dermatitis, contact urticaria and hand eczema (HE). OBJECTIVES: We aimed to investigate the prevalence of skin problems and the influence of predisposing factors especially among veterinary assistants. METHODS: We conducted a cross-sectional study among veterinary assistant staff (n = 103) and veterinarians (n = 19). A questionnaire, specific IgE determination and photographs of hands were evaluated for skin symptoms. Logistic regression models assessed predisposing factors. RESULTS: Over 50% (n = 62/122) of our study population reported hand eczema (HE) in the last 12 months (1-year prevalence). Twenty-seven subjects reported redness and contact urticaria directly after animal contact, 35 had a positive history of allergic contact dermatitis. HE was associated with (i) increased frequency of hand washing (11-15 times per day; OR 4.15, confidence interval [CI] 95% 1.18-14.6, p = 0.027, univariate model) and (ii) unprotected contact to fluids and tensides >5 times per day (OR 4.56, CI 95% 1.53-13.6, multivariate model). CONCLUSIONS: We observed a high prevalence of self-reported HE among staff in veterinary practices. Excessive hand washing, unprotected contact with irritants and long-term glove use should be avoided.

Health effects after inhalation of micro- and nano-sized zinc oxide particles in human volunteers.

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 sputum. Induced sputum was obtained at baseline examination, 22 h after exposure and at the end of the final test. The effects were assessed before, immediately after, about 22 h after, as well as two and three days after each exposure. Neutrophils, monocytes and acute-phase proteins in blood increased 22 h after micro- and nano-sized ZnO exposure. Effects were generally stronger with micro-sized ZnO particles. Parameters in induced sputum showed partial increases on the next day, but the effect strengths were not clearly attributable to particle sizes. The hypothesis that nano-sized ZnO particles induce stronger health effects than micro-sized ZnO particles was not supported by our data. The stronger systemic inflammatory responses after inhalation of micro-sized ZnO particles can be explained by the higher deposition efficiency of micro-sized ZnO particles in the respiratory tract and a substance-specific mode of action, most likely caused by the formation of zinc ions.

Naphthalene: irritative and inflammatory effects on the airways.

OBJECTIVE: This cross-sectional study determined whether acute sensory irritative or (sub)chronic inflammatory effects of the eyes, nose or respiratory tract are observed in employees who are exposed to naphthalene at the workplace. METHODS: Thirtynine healthy and non-smoking male employees with either moderate (n = 22) or high (n = 17) exposure to naphthalene were compared to 22 male employees from the same plants with no or only rare exposure to naphthalene. (Sub)clinical endpoint measures included nasal endoscopy, smell sensitivity, self-reported work-related complaints and the intensity of naphthalene odor and irritation. In addition, cellular and soluble mediators in blood, nasal lavage fluid (NALF) and induced sputum (IS) were analysed. All measurements were carried out pre-shift on Monday and post-shift on Thursday. Personal air monitoring revealed naphthalene shift concentrations up to 11.6 mg/m3 with short-term peak concentrations up to 145.8 mg/m3 and 1- and 2-naphthol levels (sum) in post-shift urine up to 10.1 mg/L. RESULTS: Acute sensory irritating effects at the eyes and upper airways were reported to occur when directly handling naphthalene (e.g., sieving pure naphthalene). Generally, naphthalene odor was described as intense and unpleasant. Habituation effects or olfactory fatigue were not observed. Endoscopic examination revealed mild inflammatory effects at the nasal mucosa of exposed employees in terms of reddening and swelling and abnormal mucus production. No consistent pattern of cellular and soluble mediators in blood, NALF or IS was observed which would indicate a chronic or acute inflammatory effect of naphthalene in exposed workers. CONCLUSIONS: The results suggest that exposure to naphthalene induces acute sensory irritative effects in exposed workers. No (sub)chronic inflammatory effects on the nasal epithelium or the respiratory tract could be observed under the study conditions described here.

Gender and occupational allergy: Report from the task force of the EAACI Environmental and Occupational Allergy Interest Group.

Women's work has traditionally been considered less hazardous to health in comparison with men's work. The increased women's participation in the workforce has led to an increased attention to women's working conditions. Women and men are unequally represented in individual professions or sectors (horizontal segregation), with women also under-represented in leadership positions (vertical segregation). The selection of specific occupations can result in differences between types and levels of occupational exposures among women and men and can affect prevalence of occupational allergy. Gender distribution of work-related asthma appears to vary across countries without clear global difference. Occupational rhinitis tends to be higher in women, although is not clear if this is related to a sex/gender effect or to differences in work exposure. Women are more likely to have occupational contact dermatitis, mainly due to wet work. No clear effects of gender on rates of hypersensitivity pneumonitis have been shown. Besides variation in exposures, physical and physiological characteristics, different behaviours and health consciousness have an impact on the occupational health hazards of women and men. Occupational allergy health promotion strategies need to consider approaches for women and men adjusted by gender, and legislative actions similarly could be implemented in a more gender-sensitive way.

Exposure to welding fumes suppresses the activity of T-helper cells.

Welders have an increased susceptibility to airway infections with non-typeable Haemophilus influenzae (NTHi), which implicates immune defects and might promote pneumonia and chronic obstructive pulmonary disease (COPD). We hypothesized that welding-fume exposure suppresses Th1-lymphocyte activity. Non-effector CD4+ T-cells from blood of 45 welders (n = 23 gas metal arc welders, GMAW; n = 16 tungsten inert gas welders, TIG; n = 6 others) and 25 non-welders were ex vivo activated towards Th1 via polyclonal T-cell receptor stimulation and IL-12 (first activation step) and then stimulated with NTHi extract or lipopolysaccharide (LPS) (second activation step). IFNγ and IL-2 were measured by ELISA. In the first activation step, IFNγ was reduced in welders compared to non-welders and in the GMAW welders with higher concentrations of respirable particles compared to the lower exposed TIG welders. IFNγ was not influenced by tobacco smoking and correlated negatively with welding-fume exposure, respirable manganese, and iron. In the second activation step, NTHi and LPS induced additional IFNγ, which was reduced in current smokers compared to never smokers in welders as well as in non-welders. Analyzing both activation steps together, IFNγ production was lowest in smoking welders and highest in never smoking non-welders. IL-2 was not associated with any of these parameters. Welding-fume exposure might suppress Th1-based immune responses due to effects of particulate matter, which mainly consists of iron and manganese. For responses to NTHi this is strongest in smoking welders because welding fume suppresses T-cell activation towards Th1 and cigarette smoke suppresses the subsequent Th1-response to NTHi via LPS. Both effects are independent from IL-2-regulated T-cell proliferation. This might explain the increased susceptibility to infections and might promote COPD development.

Self-Reported Survey on Allergy Symptoms Among First-Year Students in Veterinary Medicine: A Preamble to the AllergoVet Cohort Study.

Practical work in veterinary medicine provides exposure to various allergens which could increase the risk of sensitization. With the ongoing prospective "AllergoVet" study, we are investigating patterns of allergic symptoms and sensitization among veterinary students. Here, we report the results of the introductory self-reported survey on the presence of allergies in the first-year students of veterinary medicine, who had begun their studies in the years 2013-2016. The survey included 553 students who answered a questionnaire (63% response rate, 83% female ratio). The median age was 20 years (IQR: 19-22 years). About half of the responders indicated an interest in participating in the prospective study ("candidates"). Those who were uninterested in participating were termed "noncandidates". A doctor's diagnosis of any kind of atopic disease was reported by every fourth student. Hay fever was reported by 71 (13%) and allergic asthma by 38 (6.9%) students. The prevalence of hay fever in "candidates" (n = 294) and "noncandidates" (n = 259) was 13.5% and 12.2%, respectively. Allergic asthma was reported by 9.9% of "candidates" and 3.5% of "noncandidates", the difference being significant (p = 0.003). We conclude that the prevalence of self-reported allergic symptoms in the first-year students of veterinary medicine is similar to that in the general population. Pre-existing allergic asthma may have increased the motivation for the enrolment into the longitudinal "AllergoVet-study".

Whole Blood Assay as a Tool to Describe the Effects of Zinc Oxide Exposure on Innate Immunity.

Inhalation of high concentrations of zinc oxide (ZnO) particles may cause metal fume fever. A useful tool to characterize the reactivity of innate immune cells of an individual, e.g., after in vivo exposure, is the whole blood assay (WBA). The measurable outcome of WBA is the release of cytokines, especially pro-inflammatory and pyrogenic cytokines induced by stimulation in vitro. The aim of the study was to evaluate whether inhalation of nano-sized zinc oxide particles modifies the results of WBA from healthy blood donors. Sixteen healthy subjects were exposed to filtered air and ZnO particles (0.5, 1.0, and 2.0 mg/m3) for 4 h on four different days. Blood was collected before and 24 h after exposure, and ex vivo stimulation of the whole blood was performed using different endotoxin concentrations. The release of interleukin (IL)-1ß and IL-8 after 22-h incubation was quantified with specific immunoassays. The dose-response relationship of ex vivo stimulation with different endotoxin concentrations was not affected by previous ZnO exposure. However, based on the previously established calculation models, changes due to ZnO exposure could be described. The range of cytokine release in WBA was calculated for the whole group of blood donors, for the subgroups of low and high responders (each n = 8), and on the individual level. Most changes were observed after 0.5 mg/m3 ZnO exposure. Higher ZnO exposure did not yield higher effects. We conclude that the effects of inhalation of nano-sized ZnO particles in blood of healthy donors using the WBA could be determined. However, it should be noted that cytokine release as outcome of WBA is not a marker of disease.

Occupational allergy to phytase: case series of eight production workers exposed to animal feed additives.

BACKGROUND: In agricultural meat production, adding enzymes such as phytase to animal feed is widespread, but there is little awareness of the allergenic potential and health risks of these fungal enzymes. PATIENTS AND METHODS: We report on eight patients working in a plant producing phytase granulates. All patients complained about work-related rhinitis occurring within six months of the onset of exposure to phytase dust. Asthmatic symptoms and contact urticaria also occurred. To detect sensitizations to phytase, skin prick-, patch-, and basophil activation test were carried out with the factory product. Levels of IgE and IgG against phytase were also measured. RESULTS: There was a positive reaction to phytase with skin prick testing in seven of the eight patients. IgE specific to phytase was detectable in four of the eight patients, and IgG specific to phytase was detectable in six of the eight patients. The basophil activation test was positive in four out of seven patients tested, but the patch test was negative in all patients tested. Transfer to a different workplace with no exposure to phytase completely eliminated the symptoms. CONCLUSIONS: Mold enzymes such as phytase are highly potent occupational allergens. Occupational safety measures must be strictly implemented in order to protect the health of workers.

Food processing and occupational respiratory allergy- An EAACI position paper.

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 of impairment, and worker's compensation. Further studies are needed to identify and characterize major food allergens and define occupational exposure limits, evaluate the relative contribution of respiratory versus cutaneous sensitization to food antigens, evaluate the role of raw versus cooked food in influencing risk, and define the absolute or relative contraindication of patients with ingestion-related food allergy, pollinosis, or oral allergy syndrome continuing to work with exposure to aerosolized food allergens.

Ethyl acrylate: influence of sex or atopy on perceptual ratings and eye blink frequency.

Occupational exposure limits (OELs) are derived for protection from health hazards, assuming that exposed subjects are healthy adult workers. Whether differences in susceptibility to sensory irritation effects from airborne chemicals have to be taken into account is currently under discussion. Thus, we chose atopics as a healthy but possibly susceptible subpopulation that can be identified with a clinical test. To investigate the influence of sex or atopy on sensitivity to airborne chemicals, 22 subjects were exposed for 4 h to ethyl acrylate at three concentrations: 0.05 ppm (odor threshold; sham), 5 ppm (constant), and varying exposure between 0 and 10 ppm. Odor intensity decreased and eye irritation ratings increased in a dose-dependent manner, reflecting the time course of the exposure scenarios. The reports of moderate-to-strong eye irritation were verified by significant increases in eye blink frequency. Our results show that women reported subjective eye irritation to an increasing degree. However, these sex-related differences in ratings could not be verified by objective assessment of eye blink frequency. Atopic subjects reported higher odor intensity than non-atopic subjects, but only during the sham (odorous but not irritating) exposure condition. Differences in ratings on annoyance, and eye or nose irritation were not found. Furthermore, the study revealed that atopic subjects might belong to a group of subjects with frequent eye blink activity. Although the relative increase in blink rates was more pronounced in non-atopic subjects, atopic subjects had significant higher blink rates at the end of the exposure to varying ethyl acrylate concentrations. Our results do not support that atopy enhances chemosensory effects if only the increase of blink rates and not the absolute height are considered as adverse effect. Nevertheless, the results indicate that individuals with frequent eye blink activity should be distinguished from those with normal eye blink activity while investigating blink rates as objective parameter of eye irritation.

Non-invasive tools beyond lung function before and after specific inhalation challenges for diagnosing occupational asthma.

PURPOSE: Increases of fractional exhaled nitric oxide (FeNO), sputum eosinophils, and methacholine responsiveness have been described after specific inhalation challenges (SIC) with occupational allergens, but limited information is available about their comparative performance. It was the aim of the study to assess the diagnostic accuracy of these non-invasive tests before and after SIC for the diagnosis of occupational asthma (OA). METHODS: A total of 122 subjects with work-related shortness of breath were included. The 'gold standard' was defined as airway obstruction (pulmonary responders) and/or an increase of FeNO of at least 13 ppb after SIC. The results were compared with those obtained using the pulmonary responder status alone as 'gold standard'. RESULTS: If the pulmonary responder status and/or an increase of FeNO was used as 'gold standard' for SIC, 28 out of 39 positives (72%), but also 20 out of 83 negatives (24%) showed an increase of sputum eosinophils and/or bronchial hyperresponsiveness after SIC. If the pulmonary responder status alone was used as 'gold standard', an increase of FeNO with a sensitivity of 0.57 and a specificity of 0.82 showed a higher accuracy than increases of sputum eosinophils (0.52/0.75) or bronchial hyperresponsiveness (0.43/0.87). Individual case analyses suggest that a few cases of OA may be detected by increases of sputum eosinophils or bronchial hyperresponsiveness alone, but probably false-positive tests dominate. CONCLUSION: It is recommended to use both lung function and increase of FeNO as primary effect parameters of SIC. Changes of sputum eosinophils and bronchial hyperresponsiveness after SIC have a low additional diagnostic value, but may be useful in individual cases.

Airway inflammation after inhalation of nano-sized zinc oxide particles in human volunteers.

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 significant increases of neutrophils and interleukin-8 (IL-8), interleukin-6 (IL-6), matrix metalloproteinase (MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1) in sputum starting at the lowest ZnO concentration of 0.5 mg/m3. However, a concentration-response relationship was absent. Effects were reversible. Strong correlations were found between neutrophil numbers and concentrations of total protein, IL-8, MMP-9, and TIMP-1. CONCLUSIONS: Controlled exposures of healthy subjects to ZnO nanoparticles induce reversible airway inflammation which was observed at a concentration of 0.5 mg/m3 and higher. The lack of a concentration-response relationship warrants further studies.

Addressing Molecular Diagnosis of Occupational Allergies.

PURPOSE OF REVIEW: Numerous clinically relevant allergenic molecules enhance the performance of specific (s) IgE tests and improve the specificity of allergy diagnosis. This review aimed to summarize our current knowledge of the high-molecular-weight allergens involved in the development of occupational asthma and rhinitis and to critically analyze the contribution of component-resolved diagnosis in the management of these conditions. RECENT FINDINGS: There is a lack of standardization and validation for most available extracts of occupational agents, and assessment of sIgE reactivity to occupational allergen components has been poorly investigated, with the notable exception of natural rubber latex (NRL) and wheat flour. In the case of NRL, the application of recombinant single allergens and amplification of natural extracts with stable recombinant allergens improved the test sensitivity. IgE-sensitization profile in patients with baker's asthma showed great interindividual variation, and extract-based diagnostic is still recommended. For other occupational allergens, it remains necessary to evaluate the relevance of single allergen molecules for the sensitization induced by occupational exposure. Progress has been made to characterize occupational allergens especially NRL and wheat, although there is still an unmet need to increase the knowledge of occupational allergens, to include standardized tools into routine diagnostic, and to evaluate their usefulness in clinical practice.

Concentration-dependent systemic response after inhalation of nano-sized zinc oxide particles in human volunteers.

BACKGROUND: Inhalation of high concentrations of zinc oxide particles (ZnO) may cause metal fume fever. In an earlier human inhalation study, no effects were observed after exposure to ZnO concentrations of 0.5 mg/m3. Further data from experimental studies with pure ZnO in the concentration range between 0.5 and 2.5 mg/m3 are not available. It was the aim of this experimental study to establish the concentration-response relationship of pure nano-sized ZnO particles. METHODS: Sixteen healthy subjects were exposed to filtered air and ZnO particles (0.5, 1.0 and 2.0 mg/m3) for 4 h on 4 different days, including 2 h of cycling with a low workload. The effects were assessed before, immediately after, and about 24 h after each exposure. Effect parameters were symptoms, body temperature, inflammatory markers and clotting factors in blood, and lung function. RESULTS: Concentration-dependent increases in symptoms, body temperature, acute phase proteins and neutrophils in blood were detected after ZnO inhalation. Significant effects were detected with ZnO concentrations of 1.0 mg/m3 or higher, with the most sensitive parameters being inflammatory markers in blood. CONCLUSION: A concentration-response relationship with nano-sized ZnO particles in a low concentration range was demonstrated. Systemic inflammatory effects of inhaled nano-sized ZnO particles were observed at concentrations well below the occpational exposure limit for ZnO in many countries. It is recommended to reassess the exposure limit for ZnO at workplaces.

An increase of fractional exhaled nitric oxide after specific inhalation challenge is highly predictive of occupational asthma.

PURPOSE: An increase of fractional exhaled nitric oxide (FeNO) has been described after specific inhalation challenges (SICs) with occupational allergens, but the clinical role of FeNO measurements before and after SIC is unknown. It was the aim of this study to assess the diagnostic accuracy of FeNO measurements before and after SIC in subjects with suspected occupational asthma (OA). METHODS: One hundred forty-eight patients with suspected OA were examined by SIC with various occupational allergens. Subjects were assigned to pulmonary responders, nonresponders or doubtful by standard lung function criteria. FeNO was measured before SIC (baseline) and 24 h afterwards. Subjects with negative or doubtful SIC but increase of FeNO were evaluated individually by an overall expert rating. Effect modifiers of FeNO increases were assessed by regression analyses. RESULTS: Thirty-one patients (21%) were classified as pulmonary responders, 105 (71%) as nonresponders and 12 (8%) as doubtful. With the pulmonary responder status as gold standard an increase of FeNO ≥ 13 ppb showed a specificity of 0.9 and a sensitivity of 0.5. Seventeen subjects with negative or doubtful responder status showed such an increase of FeNO, among them 13 subjects with definitive or probable OA after expert rating. Regression analyses revealed no significant modifiers for the FeNO increase. CONCLUSION: An increase of FeNO after SIC is highly predictive of OA and should be regarded as an additional criterion for the interpretation of SIC with occupational agents.

Occupational generalized urticaria and anaphylaxis after inhalation of cefuroxime in a nurse.

We present the case of a 53 years old nonatopic female nurse who experienced repeated anaphylactic reactions at work without involvement in drug-specific tasks such as crushing of tablets or preparation of injections. The causal allergen was not identified until a further severe anaphylactic reaction occurred after oral use of cefuroxime during a respiratory infection. Sensitization to cefuroxime was demonstrated by specific IgE, basophil activation test and skin prick test. An inhalation challenge with a dosimeter induced generalized urticaria after a cumulative dose of about 10 µg of the drug, but no asthmatic reaction. Complete exposure cessation was initiated and a 1-year follow-up was without further allergic reactions. We conclude that work-related systemic allergic reactions to ß-lactam antibiotics may occur in nurses after inhalation of low doses and without perceived association with drug-specific tasks like handling of antibiotics.