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.

Discrimination Between Atopic, Allergic, and Asthmatic Volunteers for Human Exposure Studies on Sensory Irritation.

Atopic, allergic, and especially asthmatic subjects might be particularly susceptible to sensory irritation induced by airborne chemicals compared to healthy individuals. Therefore, a good characterization of subjects is essential in inhalation exposure studies on sensory irritants. A total of 105 volunteers, 87% of whom reported to be non-allergic, participated in a medical examination that included skin prick test (SPT), measurements of total IgE, specific IgE (sIgE) to an ubiquitous allergen mix (sx1), and fractionated exhaled nitric oxide (FeNO), as well as pulmonary function and methacholine test. The median value of sIgE to sx1 was 0.20 kU/L (0.07-91.3 kU/L) and correlated significantly with total IgE (28.8 kU/L (2-756 kU/L)) and FeNO (14 ppb (5-100 ppb)). Forty-three subjects (41%) had sIgE to sx1 ≥ 0.35 kU/L and were classified as atopic. Thirty-five subjects, all also sx1-positive, were positive in SPT. Obstruction, small airway disease, and/or bronchial hyperreactivity were diagnosed in 18 subjects. Receiver operating characteristics (ROC) were performed to check whether signs of sensitization are useful to discriminate subjects with and without airway diseases. However, sx1, total IgE, FeNO, and SPT reached only low areas under the curve (AUC: 0.57-0.66). Although predominantly young and, according to their own statements, mostly non-allergic subjects participated in the study, almost half of them were atopic, and 10% had airway disease or bronchial hyperreactivity. This indicates that the validity of self-reported data might be inaccurate. In summary, diversified investigations of the allergy-related health status appear necessary for a thorough characterization of subjects for exposure studies on sensory irritants.

The Pattern of Sensitization Influences Exhaled and Nasal Nitric Oxide Levels in Young Adults.

Nitric oxide (NO) from upper (nasal NO, nNO) or lower airways (fractional exhaled NO, FeNO) is considered a surrogate marker for Th2-type inflammation, which is influenced by atopy. The aim of this study was to analyze nNO and FeNO in regard to qualitative and quantitative aspects of sensitization. We evaluated 244 non-smoking young adults. All of them were first-year students recruited for a longitudinal study. An inhalation allergy screening tool was used for atopy definition (specific immunoglobulin E (sIgE) to sx1 ≥ 0.35 kU/L), and also sIgE response to three inhalant perennial allergens, house dust mite (HDM, d1), cat (e1), and dog (e5), was determined in the non-pollen season. With respect to sx1, 100 subjects could be classified as atopic. Sensitization to one, two, or three perennial allergens could be demonstrated in 46, 10, and 16 students, respectively. The subjects with positive IgE response to sx1, but not sensitized to HDM, cat, and/or dog, had FeNO levels comparable to those of non-atopic subjects (13.5 vs. 13.0 ppb, respectively; p = 0.485). These levels were significantly lower compared to atopic subjects being sensitized to any perennial allergen (19.0 ppb; p = 0.0003). After grouping the atopic subjects for perennial sensitization patterns, significantly higher FeNO could be detected in subjects with poly-sensitization (n = 26; 26.0 ppb) compared to the mono-sensitized ones (n = 46; 18.0 ppb; p = 0.023). Regarding nNO, no differences could be observed. Applying a two-way ANOVA, we could reveal a significant correlation of specific HDM-IgE CAP-class with FeNO (p < 0.0001) and nNO levels (p = 0.007). Finally, a significant relationship was found between nNO and FeNO for the whole cohort (p < 0.0001). In summary, our findings support the argument that atopy and perennial sensitization should be considered for the interpretation of NO.

How Healthy Is Healthy? Comparison Between Self-Reported Symptoms and Clinical Outcomes in Connection with the Enrollment of Volunteers for Human Exposure Studies on Sensory Irritation Effects.

Controlled human exposure studies on sensory irritation effects are usually performed with healthy volunteers. Therefore, in most studies pre-screening by a health questionnaire and a detailed medical examination are combined. The aim of this report is to investigate whether self-reported information about smoking and health status is sufficient or whether additional clinical tests are necessary for a successful and safe enrollment of healthy volunteers. There were 409 volunteers (55% female; 17-57 years; 79% non-smokers) who declared interest in participation in the study. However, 87 subjects failed to meet specific inclusion criteria, and further 138 had to be excluded due to the presence of chronic health problems. In effect, 184 subjects passed the initial questionnaire screening and proceed to further examination. Medical examination included electrocardiogram, blood and urine screening, and an olfactory function test. Atopy status was assessed by skin prick or specific IgE testing. Lung function and a methacholine challenge test were performed to assess respiratory health and bronchial hyperresponsiveness. Overall, only 107 non-smoking subjects (58% female; 19-40 years) who had no respiratory diseases, allergies, or chronic illnesses could be finally selected. Out of the 107 subjects, 8 were excluded due to positive cotinine tests, laboratory test results outside the reference range, or atypical ECGs. In another 12 subjects, obstruction or a bronchial hyperreactivity was diagnosed. Among the remaining 87 healthy subjects, 26 were classified as atopic and further two as hyposmic. In conclusion, although young and non-smoking volunteers considered themselves healthy by questionnaire, 20% showed signs of a heart, liver, or airway disease, and additional 24% were classified as atopics. This suggests that more detailed clinical testing may be necessary to safely exclude those who may adversely react to controlled exposure with sensory irritants.

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.

Airway and Blood Inflammatory Markers in Waste Collectors.

Waste collectors are exposed to a heterogeneous mixture of bioaerosols able to induce health effects. The study aim was to evaluate inflammatory processes in blood and in the respiratory tract via analysis of atopy and club cell secretory protein 16 (CC16) in serum, exhaled nitric oxide (FeNO), and cellular and soluble mediators in nasal lavage fluid (NALF) and induced sputum (IS). Sixty nine current waste collectors (48% smokers) and 28 former waste collectors (25% smokers) were included in the cross-sectional study. In both groups, 63 and 64% of workers reported complaints of the eyes, nose and/or upper airways. Thirty two percent of the current and 25% of the former workers were classified as atopics. More atopics suffered from rhinitis and conjunctivitis than non-atopics (64% vs. 40% in current workers; 71% vs. 40% in former workers). CC16 values of present non-smokers were significantly higher compared to smokers. In total, FeNO values of 31 participants were lower than 10 ppb, 94% of them were smokers and 85% had respiratory symptoms of lower airways. Most of the IS biomarkers were significantly higher in smokers than in non-smokers. Non-smoking workers with respiratory symptoms of lower airways had slightly elevated mediator IS concentrations compared to asymptomatic non-smokers. We conclude that inflammatory changes in waste collectors are detectable in the content of IS biomarkers, exhaled NO, and serum CC16, which all are influenced by the smoking habit. No significant differences in biomarkers are detectable between current and former waste collectors.

Rare and new occupational inhalant allergens.

Occupational airway diseases induced by the inhalation of allergens at workplaces have become common, but the inducing substances are diverse and their pathomechanisms are not always clear. Only few allergens were studied in detail (like wheat flour dust and natural rubber latex) and most of the occupational airway sensitizers were documented only as case reports. In this review rare and exotic occupational Type I-aeroallergens according to their workplace application area (e.g., production of dough and bakery products, handling with decorative and economic plants, wood processing, fish-, shellfish-processing and fish breeding) are described.

Effects of bioaerosol exposure on respiratory health in compost workers: a 13-year follow-up study.

OBJECTIVES: To determine the risk of German compost workers developing chronic respiratory effects from long-term exposure to bioaerosols. METHODS: Respiratory health was determined in 74 currently exposed compost workers and 37 non-exposed controls after 13 years of follow-up. In addition, 42 former compost workers (drop-outs) who left their work during the follow-up period were also examined. Respiratory symptoms and working conditions were assessed using identical questionnaires as at baseline. In addition, lung function was measured using the same spirometer as in the initial study. Sera from both surveys were tested for specific IgE and IgG antibodies to moulds and the risk of work-related symptoms was evaluated using regression approaches for prospective studies with binary data. RESULTS: In the follow-up period, the number of participants reporting cough significantly increased in compost workers and drop-outs compared to the controls. Working as a compost worker for at least 5 years increased the relative risk for cough (RR 1.28; 95% CI 1.2 to 1.4) and for cough with phlegm (RR 1.32; 95% CI 1.2 to 1.5). Current and former compost workers had slightly lower predicted percentage of forced expiratory volume in 1 s and predicted percentage of forced vital capacity than controls, but decrease in lung function during follow-up was not different among the 3 groups. In addition, no significant changes could be detected in antibody concentrations. CONCLUSIONS: Our results suggest that chronic exposure to bioaerosols in composting plants is related to a significantly higher risk for cough with phlegm, indicating chronic bronchitis. However, compost workers showed no higher incidence of deterioration of pulmonary function over the study.

[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.

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.

Evaluation of Airway Inflammation in Compost Workers Exposed to Bioaerosols Using Exhaled Breath Condensate and Fractional Exhaled Nitric Oxide.

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 considered highly exposed to bioaerosols than in low exposed workers (86.6 (66.1; 128.8) pg/mL vs. 74.4 (56.3; 96.7) pg/mL, p=0.047). No associations could be observed between exposures and biomarkers concerning compost workers in total, but there were some in atopic workers (duration of employment and FeNO: r=0.376, p=0.041; filtered air supply and FeNO: r=-0.335, p=0.071). Smokers had significantly lower pH values compared to NS (non-atopic, p=0.041; atopic p=0.050). In conclusion, EBC and FeNO might be useful tools for monitoring of inflammation due to bioaerosol exposures, especially in atopic subjects. Besides smoking also atopy should be considered when investigating airway inflammation.

Cellular and Soluble Inflammatory Markers in Induced Sputum of Composting Plant Workers.

Inflammatory processes, including respiratory symptoms, can be induced among workers in composting plants exposed to bioaerosols containing microorganisms and their compounds. We evaluated inflammatory processes in the lower respiratory tract via cellular and soluble mediator profiles in induced sputum (IS). IS samples of 140 current (35% smokers) and 49 former compost workers (29% smokers) as well as 29 white-collar workers (17% smokers) were collected and analyzed for the cell count and composition, and for soluble biomarkers. Significant differences between current and former compost workers and white-collar workers were detected for total cell count (p=0.0004), neutrophils (p=0.0045), sCD14 (p=0.008), and 8-isoprostane (p<0.0001). IS of non-smoking former compost workers showed lower concentrations of IL-8, total protein, immunoreactive MMP-9 and sCD14, compared with non-smoking current compost workers. 10.1% of the study population was suffering from chronic bronchitis with significant differences (p=0.018) between former compost workers (24.5%), current workers (5%), and white-collar workers (10.3%). Significantly lower IL-8 (p=0.0002), neutrophils (p=0.001), and MMP-9 (p=0.0023) values were measured in healthy subjects compared with subjects with chronic bronchitis. In conclusion, changes in lower airways were detected by analysis of biomarkers in IS of current exposed and, to a lesser extent, in IS of former compost workers. These effects are especially pronounced in subjects with chronic bronchitis.

Prevalence of work-related rhino-conjunctivitis and respiratory symptoms among domestic waste collectors.

Waste collectors may suffer from acute and chronic health effects caused by organic dust (bioaerosols). Pathophysiological symptoms may originate either from allergic or irritative pathomechanisms, but an explicit distinction of the etiology is often complicated although crucial for proper risk assessment and workplace prevention. In this cross-sectional study, a total of 69 male waste collectors from the Ruhr area in Germany underwent a customized testing protocol including a modified questionnaire, basic clinical examination, spirometry, and immunologic parameters. Subjects were classified according to their work tasks into loaders (n=27), floaters (n=29), and drivers (n=13). We found that a high percentage of the workers had complaints (eyes 29.0%, nose 39.1%, and cough 34.8%) which were strongly work-related. Multiple logistic regression analyses indicated that duration of employment in waste collection (per 10 years) was associated with an increased prevalence of cough (OR=1.64, 95% CI 0.81; 3.35) and chronic bronchitis (OR=2.18, 95% CI 0.80; 5.92). An association between rhinitis and cough (OR=2.62, 95% CI 0.94; 7.27) was found, which supports the association between the prevalence of upper and lower airway disease. Furthermore, when adjusting for smoking status, atopic subjects suffered more frequently from irritation of the lower airways as indicated by cough (OR=2.71, 95% CI 0.91; 8.08). In conclusion, the study demonstrates associations between the prevalence of upper and lower airway disease in waste collectors. Notably, an underlying allergic disease in waste collectors could be suspected more commonly than previously reported.

EAACI position paper: irritant-induced asthma.

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-onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA.

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.