Upper and lower respiratory airway complaints among female veterinary staff.

OBJECTIVE: Working with animals is characterized by exposure to particulate, biological or chemical matter, and respiratory complaints are common. The aim of our cross-sectional study was to assess the prevalence of respiratory symptoms and diagnoses among veterinary staff. METHODS: Participants working in veterinary practices were examined and a detailed questionnaire was used to collect data. IgE tests to common and animal allergens were performed to specify sensitization. Associations with respiratory outcomes were analysed using logistic regression models while controlling for potential confounders. RESULTS: Atopy was seen in 31% of the 109 female participants. Symptoms of rhinoconjunctivitis were the most frequent complaints (n = 92; 84%). In 18% the diagnosis was confirmed by physicians. Symptoms of upper and lower airways were highly correlated and an asthma diagnosis was confirmed in 11% of participants. Modelling revealed that sensitization against cats/dogs was a significant risk factor for respiratory symptoms of upper [odds ratio (OR) 4.61; 95% confidence interval (CI) 1.13-18.81] and lower airways (OR 5.14; 95% CI 1.25-21.13), physician-confirmed rhinoconjunctivitis (OR 13.43; 95% CI 1.69-106.5) and asthma (OR 9.02; 95% CI 1.16-70.39) in assistant staff of small-animal practices. CONCLUSIONS: In several cases, rhinoconjunctivitis worsened after entering the profession. Atopy and specific sensitization to cats/dogs were risk factors for health impairments. Thus, to implement preventive measures, veterinary practice staff should be educated that upper respiratory tract symptoms are not harmless and should be diagnosed and treated early.

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.

Adaptation to Occupational Exposure to Moderate Endotoxin Concentrations: A Study in Sewage Treatment Plants in Germany.

Acute or chronic inhalation of endotoxin may lead to changes of lung function and inflammatory markers in the airways. Adaptation to workplace exposure may be possible. In this study, we investigated the possible difference in inflammatory markers assessed in nasal lavage fluid (NALF) in chronical exposure compared to voluntary subjects exposed acutely to endotoxin. We sought to define the variability of inflammatory markers in NALF and the dose-related changes after moderate exposure in naïve subjects. Endotoxin exposure (4-1039 EU/m3) resulted from routine work during one shift in sewage treatment plants. Subjects were matched to pairs (8 workers escorted by 10 students). Inflammatory markers were investigated before, directly after, and 16 h after the shift end. Additional NALF samples were collected in students without any specific exposure after 3 days. In NALF, total cell count, and interleukin (IL)-8 and IL-1ß concentrations were significantly higher in workers than in students at all times pointing to workplace-related long-lasting exposure resulting in adaptation. However, concentration of inflammatory markers without specific exposure in students showed a great variability, covering the whole range of values recorded in the workers. The findings of this study make us to recommend a repeated assessment of inflammatory markers in healthy volunteers before the investigation of exposure-related changes and a sample size adequate for statistical analysis.

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.

Impact of Internal and External Factors on EBC-pH and FeNO Changes in Humans Following Challenge with Ethyl Acrylate.

Acute effects of ethyl acrylate exposure at 5 ppm for 4 h include changes of pH in exhaled breath condensate (EBC-pH) and exhaled nitric oxide (FeNO). So far, few data have been reported for atopic persons or the impact of the exposure conditions on biomarkers, e.g., constant versus variable application of irritants. Nine atopic and eighteen healthy volunteers without bronchial hyperresponsiveness were exposed for 4 h to ethyl acrylate concentrations of 0.05 ppm (sham), 5 ppm (constant concentration), and 0-10 ppm (variable, mean concentration of 5 ppm) in an exposure laboratory. A positive atopic status was defined according to specific IgE concentrations to common inhalant allergens (sx1 ≥ 0.35 kU/L). Biomarker levels were assessed before and after challenge and adjusted for levels after sham exposure (net response). Ethyl acrylate at constant, but not at variable concentrations induced a significant change in the net responses of EBC-pH and FeNO. Concerning FeNO, this could be observed only for atopic persons. The changes of biomarker levels were related to their baseline values. Biomarker responses to challenge with ethyl acrylate may be influenced by the patterns of application as well as baseline airway inflammation and atopic status of the volunteers.

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.

Clinical Effects, Exhaled Breath Condensate pH and Exhaled Nitric Oxide in Humans After Ethyl Acrylate Exposure.

Ethyl acrylate is an irritant known to affect the upper airways and eyes. An increase of the eye blink frequency in humans was observed during exposure to 5 ppm. Studies on the lower airways are scant and our study objective was the evaluation of pH in exhaled breath condensate (EBC-pH) and nitric oxide in exhaled breath (FeNO) as markers of inflammation. Sixteen healthy volunteers were exposed for 4 h to ethyl acrylate at a concentration of 5 ppm and to sham (0.05 ppm) in an exposure laboratory. Clinical irritation symptoms, EBC-pH (at a pCO2 of 5.33 kPa) and FeNO were assessed before and after exposure. Differences after ethyl acrylate exposure were adjusted for those after sham exposure. 5 ppm ethyl acrylate induced clinical signs of local irritation in the nose and eyes, but not in lower airways. Exposure produced a subtle, but statistically significant, decrease in breathing frequency (1 breath/min; p = 0.017) and a lower EBC-pH (by 0.045 units; p = 0.037). Concerning FeNO, we did not observe significant changes compared to sham exposure. We conclude that local effects induced by 5 ppm ethyl acrylate consist of sensory irritation of eyes and nose. In addition, acute ethyl acrylate exposure to 5 ppm resulted in a net decrease of EBC-pH. Whether that can be interpreted in terms of additional lower airway irritation or already inflammatory alterations set in needs further investigations.

Methodological implications in pH standardization of exhaled breath condensate.

The variable amount of dissolved carbon dioxide is one of the main confounding factors of exhaled breath condensate (EBC) pH measurements. There have been many attempts at identifying the optimal approach to displace CO2 as a way to gain reproducible and valid pH values in EBC samples. The aim of the present study was to assess the correlation of pH and pCO2 in untreated, neat EBC samples and, after deaeration, to reevaluate the standardization of CO2 as a means to obtain valid pH values. A further aim was to evaluate the impact of deaeration on the acid-base balance in EBC samples. EBC was collected from seven female and 31 male subjects. The pH and pCO2 values immediately determined in untreated, neat EBC samples were strongly correlated (rp = -0.723, p < 0.0001). This correlation was not observed after deaeration with argon (rs = 0.264, p = 0.109). Based on a regression function for the pH/pCO2 relationship, the calculated pH at a pCO2 of 5.33 kPa was 6.07 (IQR 5.99, 6.20). No significant difference was observed between the pH measured in neat EBC samples and those calculated after deaeration with regression function and measured neat pCO2. Our data suggest that pCO2 is the most important confounder of pH measurement in EBC samples and, when adjusting for pCO2, the acid-base balance of EBC samples is not significantly influenced by the process of deaeration. Furthermore, measurement with a blood-gas analyzer and standardization of pH for pCO2 allows sensitive assaying of EBC samples. Therefore, this method provides a basis for detection of even small changes in airway pH due to inhalative exposure or respiratory disease.

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.

Different Patterns in Changes of Exhaled Breath Condensate pH and Exhaled Nitric Oxide After Ozone Exposure.

Study objective was the evaluation of pH in exhaled breath condensate (EBC-pH) and nitric oxide in exhaled breath (FeNO) as biomarkers of ozone induced inflammation. We recently demonstrated that an ozone exposure of 240 ppb is sufficient to reduce lung function indices. We enrolled ten healthy subjects exposed in an intermittent exercise protocol to ozone concentrations of 240 ppb and 40 ppb (sham exposure). EBC-pH and FeNO were assessed before (pre), immediately post (post), and 16 h after exposure (16 h). Findings are that compared to baseline, EBC-pH was significantly higher immediately after sham and ozone exposures, but not 16 h later. There was a negative net change in EBC-pH after adjusting for effects after sham exposure (net-ΔpHpost -0.38%, net-ΔpH16h -0.23%). Concerning FeNO, we observed no changes of values after sham exposure compared to baseline, but measured a significant lower net response at the end of exposure (net-ΔFeNOpost -17.5%) which was transient within 16 h (net-ΔFeNO16h -9.4%). We conclude that exercise known to enhance EBC-pH may compensate for EBC acidification associated with inflammation resulting in diminished change of this biomarker. Ozone imposes an oxidative burden and reactions between reactive oxygen species and NO might be an explanation for reduced FeNO levels.

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.

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.

[EBC: a new matrix for assessment of airway and lung inflammation. Current aspects of environmental and occupational medicine]. / Atemkondensat: Eine neue Matrix zur Erfassung entzündlicher Veränderungen der Atemwege/Lunge. Aktuelle Aspekte aus der Umwelt- und Arbeitsmedizin.

For many environmental and occupational pollutants the respiratory system represents the route of entry. Inflammation is a fundamental process in the pathophysiological cascade leading to respiratory diseases such as asthma or chronic obstructive pulmonary disease. Non-invasive inflammatory monitoring may assist in the diagnosis as well as assessments of severity and response to treatment. Of these, exhaled nitric oxide is the best validated constituent and is used for assessing airway inflammation in clinical practice, particularly in patients with asthma. Exhaled breath condensate (EBC) is the liquid phase of the exhaled breath sampled by cooling. EBC, like blood or urine, is not a marker itself but a matrix in which a wide variety of substances have already been detected. EBC biomarkers reflect acid stress, oxidative stress, or inflammation. There are still many methodological limitations and the interpretation of findings is hampered by the fact that the most widely used devices differ significantly in their collection efficiency for markers of interest and the analytical technology employed is often near the limit of detection. In spite of promising data, standardisation of the already existing procedures is required for the implementation of EBC in clinical practice. EBC might be of particular interest in preventive medicine since adverse inflammatory processes often precede changes in lung function. Concerning the adverse effects of air pollution, there is a special focus on markers reflecting oxidative stress since air pollutants have the ability to drive free radical reactions. This overview focuses on recent data on EBC obtained from articles concerning applications of exhaled breath analysis in environmental and occupational medical research.

[DNA repair: from the mechanisms to the impact on occupational research]. / DNA-Reparatur: Von den Mechanismen zur Bedeutung in der arbeitsmedizinischen Forschung.

The human genome comprises more than three billion base pairs and a part of this information is responsible for the control of cell proliferation. Different internal and external factors are able to affect DNA and could influence the proliferation process. As a consequence critical diseases may occur. To prevent such harmful occurrences, the human body contains multiple repair enzymes that allow for the immediate elimination of DNA damage. Since each individual exhibits a set of gene variants with different properties, each person possesses his/her individual spectrum of DNA repair gene variants. For this reason, the first step of current studies is to obtain more information about the impact of DNA variants in repair enzymes in connection with certain occupational exposures with the aim to use this information in epidemiological models to calculate in which manner such variants are able to modulate DNA adducts or biomonitoring parameters.