Sputum Inflammatory Patterns Are Associated With Distinct Clinical Characteristics in Patients with Occupational Asthma Independently of the Causal Agent

Background: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. Objectives: To further characterize interactions between induced sputum inflammatory patterns, asthma-related outcomes, and the high- or low-molecular-weight category of causal agents in a large cohort of patients with OA. Methods: We conducted a multicenter, retrospective, cross-sectional study of 296 patients with OA confirmed by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. Results: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (OR [95%CI], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting ß2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild, 2.48 [1.21-5.08]; moderate/severe, 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male sex (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), use of short-acting ß2-agonists once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the previous 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the specific inhalation challenge (4.45 [1.85-11.59]). Conclusion: The findings indicate that sputum inflammatory patterns in patients with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with findings reported in nonoccupational asthma and are not related to the type of causal agent. (AU)

Antecedentes: La heterogeneidad clínica en el asma ocupacional (AO) inducida por agentes sensibilizantes y su relación con los perfiles inflamatorios de las vías respiratorias siguen siendo muy poco conocidas. Objetivos: Profundizar en la caracterización de las interrelaciones entre los patrones inflamatorios en esputo inducido, diversas variables relacionadas con el asma y la categoría de agentes causales de alto o bajo peso molecular, en una gran cohorte de sujetos con AO Métodos: Este estudio multicéntrico, retrospectivo y transversal se llevó a cabo en 296 sujetos con OA confirmada mediante una provocación bronquial específica (SIC) positiva, en los que se obtuvieron muestras de esputo inducido antes y 24 horas después de la SIC. Resultados: El análisis de regresión logística multivariable reveló que la presencia de eosinofilia en esputo ≥3 % se asoció significativamente con una dosis alta de corticosteroides inhalados (odds ratio [intervalo de confianza del 95 %], 1,31 [1,11-1,55] por cada incremento de 250 µg en la dosis diaria), el uso de agonistas ß2 de acción corta menos de una vez al día (3,54 [1,82-7,00]), y un nivel de hiperreactividad bronquial inespecífica inicial (leve: 2,48 [1,21-5,08]); moderado/grave: 3,40 [1,44-8,29]). La neutrofilia en esputo ≥76%, se asoció con la edad (1,06 [1,01-1,11]), el sexo masculino (3,34 [1,29-9,99]), la ausencia de uso de corticosteroides (5,47 [2,09-15,16]), el uso de agonistas ß2 de acción corta una vez o más al día (4,09 [1,71-10,01]), la presencia de ≥ 2 exacerbaciones graves en los últimos 12 meses en el trabajo (4,22 [1,14-14,99]) y reacciones inmediatas aisladas durante la SIC (4,45 [1,85-11,59])... (AU)

Serial fractional exhaled nitric oxide measurements at and off work may help to identify immunologic occupational asthma in cases with complex exposures.

Serial measurements of fractional exhaled nitric oxide (FeNO) at home and at work have been described to provide complementary information for the diagnosis of occupational asthma (OA) when specific inhalation challenge (SIC) is missing or doubtful. We describe two cases in which serial FeNO measurements enabled the detection of probable OA after complex exposures. A 25-year-old industrial painter with exposure to a variety of paints suffered from work-related airway symptoms for five years. Lung function was normal, and she was not atopic. SIC with hexamethylene diisocyanate was negative. A 47-year-old sign maker (screen printing, foils) suffering from work-related dyspnoea for seven years. Moderate airway obstruction, but no atopy was detectable. Due to the complex exposures SIC was not performed. Both patients performed FeNO measurements once daily during a 2-week-holiday and a subsequent 2-week-work period. In both cases elevated baseline FeNO decreased to normal (25 ppb) during holidays and increased after resuming work (case 1: 125 ppb, case 2: 45 ppb).

Sputum Inflammatory Patterns are Associated with Distinct Clinical Characteristics in Subjects with Occupational Asthma Independently from the Causal Agent.

BACKGROUND AND OBJECTIVES: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA. METHODS: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. RESULTS: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting b2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting b2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]). CONCLUSIONS: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.

Human Inhalation Study with Zinc Oxide: Analysis of Zinc Levels and Biomarkers in Exhaled Breath Condensate.

Workers in the zinc processing, for example, welding or hot-dip galvanizing, are exposed to aerosols consisting of particles and gases, including zinc oxide (ZnO), which can affect human health. In this study, we addressed the effects of short-term controlled exposure to nano-sized ZnO on the airway inflammatory markers in healthy volunteers. To this end, we determined the influence of ZnO inhalation on the content of zinc and biomarkers (leukotriene B4 (LTB4), peptide leukotrienes (LTC4/D4/E4), 8-iso-PGF2α, pH, and prostaglandin E2 (PGE2)) in exhaled breath condensate (EBC). Sixteen non-smoking subjects (8 females, 8 men) were exposed to filtered air (sham) or ZnO nanoparticles (0.5, 1.0, and 2.0 mg/m3) for 4 h. EBC samples were collected according to specific study design. We found that the peptide leukotrienes were below the limit of quantification (LOQ) in all the EBC samples. ZnO exposure showed no detectable effect on any other parameters investigated when comparing the two groups. The content of Zn in EBC was unaffected by ZnO inhalation at any concentration used. Therefore, we conclude that the evaluation of Zn and biomarker content in EBC would not be a suitable way to assess the exposure to inhaled ZnO.

Baker's Asthma: Is the Ratio of Rye Flour-Specific IgE to Total IgE More Suitable to Predict the Outcome of Challenge Test Than Specific IgE Alone.

Usually the diagnosis of baker's asthma is based on specific inhalation challenge with flours. To a certain extent the concentration of specific IgE to flour predicts the outcome of challenge test in bakers. The aim of this study was to evaluate whether the ratio of specific IgE (sIgE) to total IgE (tIgE) improves challenge test prediction in comparison to sIgE alone. Ninety-five bakers with work-related respiratory symptoms were challenged with rye flour. Total IgE, sIgE, and the sIgE/tIgE ratio were determined. Receiver operator characteristic (ROC) plots including the area under the curve (AUC) were calculated using the challenge test as gold-standard. Total IgE and sIgE concentrations, and their ratio were significantly higher in bakers with a positive challenge test than in those with a negative one (p < 0.0001, p < 0.0001, and p = 0.023, respectively). In ROC analysis, AUC was 0.83 for sIgE alone, 0.79 for tIgE, and 0.64 for the ratio. At optimal cut-offs, tIgE, sIgE, and the ratio reached a positive predicted value (PPV) of 95%, 84% and 77%, respectively. In conclusion, calculating the ratio of rye flour-sIgE to tIgE failed to improve the challenge test prediction in our study group.

[Occupational Allergies to Trypsin and Chymotrypsin]. / Berufliche Allergien gegen Trypsin und Chymotrypsin.

Trypsin and chymotrypsin are proteolytic pancreatic enzymes that are secreted as the inactive precursors trypsinogen and chymotrypsinogen, respectively. They have several pharmacological as well as laboratory applications, especially in protein chemistry. Exposure to enzyme dusts has long been known to cause immediate occupational hypersensitivities of the airways. Also trypsin and chymotrypsin are potential inhalable sensitizers, and clear cases of specific airway sensitization caused by trypsin- and chymotrypsin-containing products have been reported by several studies. Positive skin prick and challenge tests as well as specific IgE antibodies have been described. These results and the clinical symptoms usually matched well, suggesting an immunological mechanism of action. Immediate urticarial reactions of the skin due to contact with these enzymes are possible, but there is no clear evidence of allergic cell-mediated delayed eczematous skin reactions.

How to diagnose mould allergy? Comparison of skin prick tests with specific IgE results.

BACKGROUND: Diagnosis of mould allergy is complicated due to the heterogeneity of the test material and the decrease in the number of commercial mould skin test solutions that are currently available. OBJECTIVES: The aim of this study was to compare skin prick tests (SPT) from different manufacturers to one another and concurrently with sIgE tests for Aspergillus fumigatus (Asp f), Cladosporium herbarum (Cla h), Penicillium chrysogenum (Pen ch), Alternaria alternata (Alt a) and Aspergillus versicolor (Asp v) to ascertain a feasible diagnostic procedure for mould sensitization. METHODS: In this multi-centre study, 168 patients with mould exposure and/or mould-induced respiratory symptoms were included. Mould SPT solutions were analysed biochemically and tested in duplicate on patients' arms. Specific IgE (sIgE) concentrations to corresponding mould species and mould mix (mx1) were measured by ImmunoCAP. SPTs in accordance with one another and with sIgE were further considered. The test efficiency was calculated using receiver-operating characteristic (ROC) analysis. RESULTS: Mould sensitization was more frequently detected by the SPT (90 of 168) than by the sIgE tests (56 of 168). Concordances of double SPT positives were only sufficient (≥ 80%) for environmental allergens, two Asp f and three Alt a SPT solutions, whereas all other mould solutions revealed concordances < 80%. The antigen content of SPT solutions was positively associated with concordant SPT double values as well as with sIgE. Taking sIgE as the 'positive standard', all mould SPT solutions revealed test efficiencies > 80%, but varied up to 20% in sensitivity and positive predictive value with the exception of Alt a. CONCLUSIONS: SPT solutions are sensitive and essential diagnostic tools for the detection of mould sensitization. Our recommendation for diagnosis would be to test at least Alt a, Asp f and Pen ch using SPT and additional sIgE test to mx1.

Spirometry or Body Plethysmography for the Assessment of Bronchial Hyperresponsiveness?

Methacholine testing is one of the standard tools for the diagnosis of mild asthma, but there is little information about optimal outcome measures. In this study a total of 395 college students were tested by the ATS dosimeter protocol for methacholine testing, with minor modification. Body plethysmography and spirometry were measured after each inhalation step. The end-of-test-criteria were (i) decrease in forced expiratory volume in 1 s (FEV1) of ≥ 20 % and (ii) doubling of specific airway resistance and its increase to ≥ 2.0 kPa∙s. The results were expressed by receiver operating characteristic (ROC) plots using questionnaire answers as a reference. The areas under the ROC curves were iteratively calculated for a wide range of thresholds for both measures. We found that ROC plots showed maximal sensitivities of about 0.5-0.6 for FEV1 and about 0.7 for specific airway conductance (sGt), with similar specificities of about 0.7-0.8 taking questions with the known high specificity as references. Accordingly, larger maximal areas under the ROC curve were observed for body plethysmography, but the differences were small. A decrease in FEV1 of about 15 % and a decrease of sGt of about 60 % showed the largest areas under the ROC curves. In conclusion, body plethysmography yielded better sensitivity than spirometry, with similar specificity. However, replacing the common spirometric criterium for a positive test (20 % decrease in FEV1 from baseline) by the optimal body plethysmographic criterium would result in an increase of false positive tests from about 4 to 8 % in healthy young adults.

Specific Inhalation Challenge in Persulfate Asthma.

Specific inhalation challenge (SIC) may be considered the 'gold standard' for the diagnosis of occupational asthma due to persulfate salts. The aim of the study was to develop a safe SIC protocol. Between 2003 and 2014, eight patients with suspected occupational asthma due to persulfate salts were examined (7 females, all hair-dressers). SIC was done with a dosimeter and a nebulizer using ammonium persulfate dissolved in phosphate buffer. Until 2009, a four-step-protocol (doses: 0.0004, 0.0045, 0.045, 0.45 mg; cumulative: 0.5 mg) was used, afterwards a six-step-protocol (doses: 0.0004, 0.0018, 0.007, 0.028, 0.113, 0.45 mg; cumulative: 0.6 mg). With each SIC protocol, four subjects were tested. Skin prick tests with ammonium persulfate (20 mg/mL) were performed in all and patch tests in four subjects. In total, four subjects showed a positive SIC, two with each protocol. All subjects showed an isolated late reaction. The greatest decrease of volume in 1 s was 35 % about 3.5 h after the last inhalation (four-step-protocol). Skin prick test with ammonium persulfate was positive in one SIC positive (2 mm wheal) and in two SIC negative patients (3 and 4 mm wheal). All four subjects tested with patch tests showed a positive reaction; three of them were SICpos. We recommend to include patch-testing in the diagnosis of suspected occupational asthma due to persulfate salts. Isolated late asthmatic reactions may occur after SIC. The proposed six-step SIC protocol was safe in this limited number of subjects.

[Standardization of spirometry: 2015 update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine]. / Leitlinie zur Spirometrie. Leitlinie der Deutschen Atemwegsliga, der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin zur Spirometrie.

Spirometry is a simple test and considered the gold standard in lung function. An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to the maximal volume that can be displaced from the lung. It implies airway narrowing and is defined by a reduced FEV1/FVC ratio below the 5th percentile of the predicted value (lower limit of normal, LLN). A restrictive disorder may be suspected when vital capacity (FVC) is reduced and FEV1/FVC is normal. It is definitely proven, however, only by a decrease in TLC below the 5th percentile of predicted value (LLN). The measurement of TLC by body plethysmography is necessary to confirm or exclude a restrictive defect or hyperinflation of the lung when FVC is below the LLN. 2012 a task force of the ERS published new reference values based on 74,187 records from healthy non-smoking males and females from 26 countries. The new reference equations for the 3-95 age range are now available that include appropriate age-dependent mean values and lower limits of normal (LLN). This presentation aims at providing the reader with recommendations dealing with standardization and interpretation of spirometry.

Effects of Exposure to Welding Fume on Lung Function: Results from the German WELDOX Study.

The association between exposure to welding fume and chronic obstructive pulmonary disease (COPD) has been insufficiently clarified. In this study we assessed the influence of exposure to welding fume on lung function parameters. We investigated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and expiratory flow rates in 219 welders. We measured current exposure to respirable particles and estimated a worker's lifetime exposure considering welding techniques, working conditions and protective measures at current and former workplaces. Multiple regression models were applied to estimate the influence of exposure to welding fume, age, and smoking on lung function. We additionally investigated the duration of working as a welder and the predominant welding technique. The findings were that age- and smoking-adjusted lung function parameters showed no decline with increasing duration, current exposure level, and lifetime exposure to welding fume. However, 15% of the welders had FEV1/FVC below the lower limit of normal, but we could not substantiate the presence of an association with the measures of exposure. Adverse effects of cigarette smoking were confirmed. In conclusion, the study did not support the notion of a possible detrimental effect of exposure to welding fume on lung function in welders.

Exhaled nitric oxide in specific inhalation challenge.

Exhaled nitric oxide (eNO) is a biological mediator in human lungs and can be measured easily in exhaled air. Increasing eNO concentrations after specific inhalation testing (SIT) have been described for subjects with occupational asthma. Nevertheless, interpreting eNO concentrations after SIT is still a challenge because eNO concentrations depend on various confounding factors. In this study, 24 women and 43 men with suspected occupational asthma were examined by a questionnaire, physical examination, routine laboratory testing, skin prick testing (atopy: at least one wheal reaction >3 mm), lung function including methacholine testing, and SIT with various occupational allergens. Exhaled NO was measured before SIT (t0), 2 h (t1) and 20-22 h (t2) afterwards (NIOX Flex, Aerocrine, Sweden). At baseline we observed significantly lower eNO concentrations in smokers than in non-smokers and in non-atopics than in atopics (significant only in SIT non-responders). In the SIT non-responders (n = 45), eNO concentrations showed no change after SIT (t0: 16.0, t1: 12.3, t2: 16.0 ppb). In the SIT responders (n = 22), eNO was elevated significantly at t2 (t0: 22.9, t1: 19.9, t2: 42.0 ppb). In addition to positive responder status and measuring time, missing atopy and exposure to isocyanates were the essential factors leading to increased eNO concentrations. We conclude that the measurements of eNO after SIT may provide valuable information concerning the allergenic status of a patient.

Implementation of non-invasive methods in the diagnosis of diisocyanate-induced asthma.

Diisocyanate-induced asthma is difficult to diagnose since the immunopathological mechanisms and exposure determinants at the workplace are not well defined. The aim of this study was to evaluate the non-invasive methods of nasal lavage fluid (NALF) and induced sputum (IS) to enhance the diagnostic efficiency. Sixty-three diisocyanate-exposed workers with work-related shortness of breath underwent a standardized 4-steps-1-day-whole body exposure test with diisocyanates used at work up to 30 ppb. NALF and IS were collected before, 0.5, and 19 h after the end of exposure. Cellular composition and soluble inflammatory biomarkers were studied in the samples. In addition, ten controls with bronchial hyperresponsiveness, but without prior occupational diisocyanate exposure, were also examined. Twelve out of the 63 subjects (19 %) showed a significant asthmatic reaction (pulmonary responders) after challenge (FEV1 decrease >20 %). NALF samples did not demonstrate significant effects either on cellular composition or on mediator concentrations in the responders, non-responders, or controls at any time point. In contrast, in the IS samples of the pulmonary responders collected 19 h after challenge, the percentage of eosinophils was higher (p = 0.001) compared with baseline before challenge. Eosinophils were also increased 30 min and 19 h after challenge in IS samples of the responders compared with the non-responders or controls. In addition, 19 h after challenge the eosinophilic cationic protein (ECP) concentration was significantly higher in the responders than non-responders (p < 0.04) or controls (p < 0.002). In conclusion, positive asthmatic reactions to diisocyanates are accompanied by an influx of eosinophils into lower airways. Analysis of induced sputum should be implemented in the diagnostic procedure of diisocyanate-related airway diseases.

Evaluation of a 4-steps-1-day whole body challenge protocol for the diagnosis of occupational asthma due to diisocyanates.

Inhalative challenges are important in the diagnosis of occupational asthma due to diisocyanates. As existing protocols are time-consuming and costly, it was the aim of this study to develop a short duration whole body exposure protocol. Ninety three subjects with suspected occupational diisocyanate-induced asthma and verified current or previous occupational exposure to diisocyanates and ten control subjects without diisocyanate exposure but with bronchial hyperresponsiveness were investigated. After baseline examination on the first day, subjects underwent a standardized whole body multiple-steps-1-day challenge with exposures of up to four times 30 min to concentrations of 5, 10, 20, and 30 ppb of the dominant diisocyanate used at work on the second day. Common spirometric and body plethysmographic parameters were used as positivity criteria. Overall, 14 subjects demonstrated a positive diisocyanate challenge, 19 were considered doubtful, and 60 were negative. All controls had negative challenges. Positive reactions occurred during the challenge (n = 10) or during follow-up (n = 4). Eight subjects showed >40 % fall of FEV1. These severe reactions occurred after 5 ppb (n = 2) or 10 ppb (n = 3), while isolated late reactions after 2 h of follow-up were not observed. Multivariate analysis showed an association between a positive challenge and both the degree of previous occupational exposure and the presence of baseline bronchial hyperresponsiveness. In summary, the proposed 4-steps-1-day diisocyanate challenge protocol induced pronounced bronchial reactions in a small number of subjects. As these reactions were more likely to occur after low concentrations, it is recommended to shift the initial concentration/dose step to lower exposures.

Occupational allergic respiratory diseases in garbage workers: relevance of molds and actinomycetes.

Exposures to molds and bacteria (especially actinomycetes) at workplaces are common in garbage workers, but allergic respiratory diseases due to these microorganisms have been described rarely. The aim of our study was a detailed analysis of mold or bacteria-associated occupational respiratory diseases in garbage workers. From 2002 to 2011 four cases of occupational respiratory diseases related to garbage handling were identified in our institute (IPA). Hypersensitivity pneumonitis (HP) was diagnosed in three subjects (cases 1-3, one smoker, two non-smokers), occupational asthma (OA) was diagnosed in one subject (case 4, smoker), but could not be excluded completely in case 2. Cases 1 and 2 worked in composting sites, while cases 3 and 4 worked in packaging recycling plants. Exposure periods were 2-4 years. Molds and actinomycetes were identified as allergens in all cases. Specific IgE antibodies to Aspergillus fumigatus were detected exclusively in case 4. Diagnoses of HP were essentially based on symptoms and the detection of specific IgG serum antibodies to molds and actinomycetes. OA was confirmed by bronchial provocation test with Aspergillus fumigatus in case 4. In conclusion, occupational HP and OA due to molds occur rarely in garbage workers. Technical prevention measures are insufficient and the diagnosis of HP is often inconclusive. Therefore, it is recommended to implement the full repertoire of diagnostic tools including bronchoalveolar lavage and high resolution computed tomography in the baseline examination.

Hypersensitivity pneumonitis due to metalworking fluids: how to find the antigens.

Most surveys of outbreaks of hypersensitivity pneumonitis (HP) in subjects with occupational exposure to water-based metalworking fluids (MWFs) were unable to detect a clear link between symptoms and the precise causative agents. We studied the case of a male 41-year-old industrial knife grinder with exposure to water-based MWFs since 12 years. The diagnosis of HP was made by typical work-related symptoms, the demonstration of high lymphocyte numbers in bronchoalveolar lavage and elevated IgG antibody concentrations to various molds in the patient's serum, and complete recovery after early exposure cessation. Whereas an environmental survey showed only low numbers of mold contamination in one sump sample, high antigenic activity was demonstrated in the same sample by antigen-specific IgG inhibition tests. We conclude that the detection of antigenic molds in water-based MWFs by culture methods may be limited. The link between occupational exposure to specific molds in MWFs and hypersensitivity pneumonitis can be established by the demonstration of antigenic activity by antigen-specific IgG inhibition tests.

[Occupational allergies against pepsin, chymosin and microbial rennet]. / Berufliche Allergien gegen Pepsin, Chymosin und mikrobielle Labersatzstoffe.

Rennet is a mixture of the proteolytic enzymes pepsin and chymosin (rennin), which is usually obtained from the fourth stomach of young ruminants. While pepsin is also used in the pharmaceutical industry, both enzymes (pepsin and chymosin) are used for the coagulation of milk protein in the manufacture of cheese. Additionally, microbial rennet, which is naturally produced by certain microorganisms, has been used as a substitute for natural rennet in the cheese production for decades. Exposure to enzyme dusts has long been known to cause occupational immediate hypersensitivities. The present paper reviews the results of an evaluation of the literature data concerning occupational airway sensitisation due to natural and microbial rennet. Cases of specific airway sensitisation caused by rennet could be shown clearly by several studies. Positive skin prick and challenge tests as well as specific IgE antibodies have been described, thus suggesting an immunological mechanism.

Evaluation of commercial skin prick test solutions for selected occupational allergens.

BACKGROUND: Skin prick testing (SPT) is an important step in the diagnosis of IgE-mediated occupational allergic diseases. The outcome of SPT is related to the quality of allergen extracts. Thus, the aim of the study was to assess different commercially available SPT solutions for selected occupational allergens. METHODS: SPT was performed in 116 bakers, 47 farmers and 33 subjects exposed to natural rubber latex (NRL), all with work-related allergic symptoms. The SPT solutions from different manufacturers (n = 3-5) for wheat flour, rye flour, soy, cow hair/dander, storage mites (Tyrophagus putrescentiae, Lepidoglyphus destructor, Acarus siro) and NRL were analysed with respect to their protein and antigen contents. SPT was carried out in 16 allergy centres in six European countries using standardized procedures. Specific IgE values were used as the gold standard to calculate the sensitivity and specificity of SPT solutions. The optimal cut-point for each SPT solution was determined by Youden Index. RESULTS: Protein and antigen contents and patterns of the SPT solutions varied remarkably depending on the manufacturer. While SPT solutions for wheat flour and soy reached overall low sensitivities, sensitivities of other tested SPT solutions depended on the manufacturer. As a rule, solutions with higher protein and antigen content showed higher sensitivities and test efficiencies. CONCLUSIONS: There is a wide variability of SPT solutions for occupational allergens, and the sensitivity of several solutions is low. Thus, improvement and standardization of SPT solutions for occupational allergens is essential.