[Guideline for the Diagnosis and Treatment of COPD Patients - Issued by the German Respiratory Society and the German Atemwegsliga in Cooperation with the Austrian Society of Pneumology]. / Leitlinie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD).

This document is a revision of the guideline for diagnosis and treatment of COPD that replaces the version from 2007. A multitude of recent reports regarding risk factors, diagnosis, assessment, prevention and pharmacological as well as non-pharmacological treatment options made a major revision mandatory. The new guideline is based on the GOLD document taking into account specifics in Germany and Austria.

Occupational exposure to ultrafine particles in police officers: no evidence for adverse respiratory effects.

BACKGROUND: Inhalation exposure to fine and ultrafine particles (UFPs) has been associated with respiratory diseases. However, little is known on the quality, threshold levels and concentration of these particles causing adverse health effects. METHODS: The impact of occupational exposure to submicrometer and UFPs was assessed in 30 healthy police shooting instructors by clinical investigation, self-assessment questionnaire, sputum and spirometry and compared to a control group. General laboratory chemistry parameters, circulating cytokines (interleukin [IL]-2, IL-4, IL-5, IL-6, IL-8, interferon-gamma [IFN-γ]), and granulocyte macrophage colony-stimulating factor (GM-CSF) in serum were measured. UFP exposure was recorded by Scanning Mobility Particle Sizer. RESULTS: Concentrations of submicrometer sized airborne particles (< 700 nm) measured between 3.34 × 105/cm3 and 7.58 × 105/cm3 at shooting sites, with highest concentrations found in the UFP range (< 100 nm). The size of the monodispersed particles ranged from 54.74 ± 16.25 nm to 98.19 ± 22.83 nm. Short term exposure (4 h) to high levels of UFPs caused an increase of IFN-γ in exposed subjects (p = 0.022). 24 h after exposure a significant decrease of IgG, albumin fibrinogen and factor VII was found. Neither directly after 4 h of high levels UFPs exposure nor 24 h after exposure subjective complaints or objective measurements indicating adverse respiratory effects in exposed subjects were found. CONCLUSIONS: No consistent indications for adverse respiratory or inflammatory effects directly following exposure and 24 h after exposure to high levels of UFPs in our study group were detected. However we showed the assessment of short-term exposure effects at a genuine occupational setting, which might is relevant when a risk assessment of high level occupational exposures to UFPs is considered.

A case-control study of the relation between plasma selenium and asthma in European populations: a GAL2EN project.

BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

The relation between paracetamol use and asthma: a GA2LEN European case-control study.

Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking. As part of a multicentric case-control study organised by the Global Allergy and Asthma European Network (GA(2)LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (20-45 yrs) and place of residence. In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma. These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations.

Cloning and molecular characterization of the Hevea brasiliensis allergen Hev b 11, a class I chitinase.

BACKGROUND: In the last 10 years type-I allergy against proteins from Hevea brasiliensis latex has become an acknowledged medical issue. Fruit-allergic patients represent one risk group for developing latex allergy. Class I chitinases have been identified from chestnut, avocado and banana as relevant allergens. The chitin binding (hevein) domain from these class I chitinases has been postulated to bear the important IgE binding epitopes. OBJECTIVE: To clone the cDNA of an allergenic latex class I chitinase, to express the recombinant protein and to determine its IgE cross-reactivity with hevein (Hev b 6.02). METHODS: A full-length cDNA coding for a class I chitinase has been isolated from Hevea latex RNA by reverse transcription followed by PCR. The chitinase encoding sequence has been subcloned into the pMAL expression vector and expressed in E. coli as a fusion protein to maltose binding protein. The highly enriched recombinant protein fraction has been tested for its IgE binding capacity in immunoblots and ELISA. Furthermore, the pathogenesis-related function of the recombinant protein was tested in a fungal growth inhibition assay. RESULTS: The Hevea brasiliensis latex chitinase, designated Hev b 11, displays 70% identity to the endochitinase from avocado and its hevein-domain 58% to hevein (Hev b 6.02). The recombinant Hev b 11-maltose binding protein is recognized by latex- and fruit-allergic patients with IgE binding in both, ELISA and immunoblots. Pre-incubation of sera with rHev b 11-maltose binding protein showed an overall 16% inhibition of subsequent binding to rHev b 6.02-maltose binding protein on solid phase. The growth of F. oxysporum was inhibited in a dose dependent manner by addition of rHev b 11-maltose binding protein to the culture. CONCLUSIONS: Hev b 11, a class I chitinase, is another allergen from Hevea latex with a chitin binding domain and displays a different IgE binding capacity compared with hevein.

Lack of correlation between nonspecific nasal and bronchial reactivity in allergic rhinitis subjects.

A link between allergic rhinitis and asthma has long been suspected, allergic rhinitis being considered a precursor of asthma. The hypothesis is that if such a link exists, then nonspecific nasal and bronchial reactivity are already correlated in acute rhinitis patients. To test for this correlation, we compared nonspecific nasal and bronchial reactivity in two groups of rhinitis subjects: 37 rhinitis pollinosis patients tested during the pollen season and 35 rhinitis pollinosis patients tested outside the pollen season. We also assessed how smoking affects this link. In each subject, allergy, nonspecific nasal, and nonspecific bronchial reactivity were tested, and smoking was categorized. We found no correlation between nonspecific nasal and bronchial reactivity in the two nonasthmatic rhinitis groups. During active allergic inflammation (pollinosis season) no shift toward a stronger link between upper and lower airways can be found compared with the latent period (out of pollinosis season). Unexpectedly, among smokers we found a significant relationship between nonspecific nasal and bronchial reactivity. Thus, there is not yet sufficient evidence for a straightforward link between nasal and bronchial hyperreactivity in nonasthmatic pollinosis rhinitis subjects. The development of asthma seems to be crucial for this link.

Nasal challenge with histamine decreases nonspecific bronchial reactivity in workers exposed to respiratory irritants.

BACKGROUND: A link ("naso-bronchial reflex") between nasal and bronchial reactivity seems to exist. The effect of nonspecific nasal challenge (standing for the exposure to irritative stimuli at the workplace) on lung function indices and nonspecific bronchial reactivity is not known. METHODS: In 80 healthy workers (age: 36.0 +/- 8.6 years) continuously exposed to acceptable levels of different respiratory irritants (for more than 2 years) nasal challenge was performed by spraying doubling concentrations of histamine (0.0625-16.0 mg/mL, doses of histamine: 7.8 micrograms-2.08 mg) into each nostril. Before and immediately after nasal challenge spirometry and the bronchoprovocation test with histamine (0.5-128 mg/mL) was performed. RESULTS: Although nasal challenge with histamine had not reduced airway caliber (before nasal challenge vs. following nasal challenge: FEV1 3.8 +/- 0.8 vs. 3.7 +/- 0.8 L, and MEF50 4.3 +/- 1.4 vs. 4.3 +/- 1.4 L/s, mean +/- SD, respectively), it had significantly reduced nonspecific bronchial reactivity in 30.2% of the irritant-exposed subjects. CONCLUSIONS: Nasal challenge with histamine decreases nonspecific bronchial reactivity in workers occupationally exposed to respiratory irritants. Thus, a methodological implication would be that these two tests should not be performed consecutively in less than 2 hr in the same subjects.

Non-specific nasal and bronchial reactivity are not correlated in non-asthmatic subjects occupationally exposed to irritants and in healthy subjects.

BACKGROUND: Non-specific nasal and bronchial reactivity are frequently correlated in disease (rhinitis and asthma). It is not known whether such a correlation exists in subjects exposed to irritants and in healthy subjects. In order to test the hypothesis that a correlation between non-specific nasal and bronchial reactivity exists in non-asthmatic subjects, two groups of subjects were studied: 110 workers occupationally exposed to respiratory irritants, and 86 non-exposed healthy controls. METHODS: Allergy, non-specific nasal, and non-specific bronchial reactivity were tested, and smoking habits were categorized in each subject. RESULTS: Respiratory irritants cause a substantial increase in nasal and bronchial reactivity when compared with the group of healthy, non-exposed subjects (33.6% nasal hyperreactors and 20.0% bronchial hyperreactors vs. 4.7% nasal hyperreactors and 2.3% bronchial hyperreactors, respectively). But, occupational exposure to respiratory irritants does not induce a correlation between non-specific nasal and bronchial reactivity frequently found in asthmatic and rhinitic subjects. CONCLUSIONS: We found no correlation between non-specific nasal and bronchial reactivity either in subjects occupationally exposed to respiratory irritants or in the group of healthy subjects. This lack of correlation in both studied groups seems to be a feature of non-diseased airways. Smoking as an additional factor does not increase nasal and bronchial reactivity either in workers exposed to irritants or in healthy subjects. Smoking also does not strengthen the correlation between upper and lower airways' reactivity in both groups.

Respiratory and immunological findings in brewery workers.

BACKGROUND: Occupational exposure of brewery workers to organic dusts such as hops, barley, and brewery yeast has the potential to change respiratory function and immunological status. METHODS: Ninety-seven male workers employed in a brewery plant were studied. The mean age of the workers in this plant was 40 years, the mean duration of their employment was 16 years. In addition, a group of 76 unexposed workers was studied as a control. Respiratory symptoms were recorded. Lung function was measured by recording maximum expiratory flow-volume (MEFV) curves. Immunological testing was performed on all brewery workers and some control volunteers using skin prick testing with hops, barley, and yeast antigens as well as other nonoccupational allergens, and by determining total serum IgE levels. RESULTS: There was a significantly higher prevalence of most of the chronic respiratory symptoms in brewery workers compared to controls (P < 0.01). Occupational asthma, however, was recorded in only 2 (2.1%) of the brewery workers. Logistic regression analysis showed that smoking was the major studied factor responsible for the high prevalence of chronic respiratory symptoms in workers. A large number of brewery workers complained of acute symptoms that developed during the work shift. Lung function tests were decreased compared to predicted. Multivariate analysis of these respiratory function parameters suggested the importance of workplace exposure in explaining lung function abnormalities. Significantly higher prevalences of positive skin prick tests were recorded in 37 brewery workers for molds, hops, and barley than in controls. Increased serum levels of total IgE were documented in 34/97 (45.1%) brewery workers and in 1/76 (2.7%) of the control workers (P < 0.01). However, workers with positive skin prick tests had prevalences of chronic respiratory symptoms and lung function changes similar to those of workers with negative skin prick tests. CONCLUSION: Our data suggest that both smoking and dust exposure in the brewery industry may be responsible for the development of respiratory impairment and immunological reactions.

Respiratory findings in workers employed in the brick-manufacturing industry.

We studied 233 male workers employed in two brick-manufacturing plants and 149 matched control workers. The mean age of the brick workers was 35 years, with a mean duration of employment in this industry of 16 years. The prevalence of chronic respiratory symptoms as well as acute symptoms during the work shift were recorded. Lung function was measured on Monday during the work shift by recording maximum expiratory flow-volume (MEFV) curves, from which the forced vital capacity (FVC), the one-second forced expiratory volume (FEV1) and flow rates at 50% and the last 75% of the FVC (FEF50, FEF75) were measured. The results of periodic chest roentgenograms were reviewed. There was a significantly higher prevalence of chronic cough (31.8%), chronic phlegm (26.2%), and chest tightness (24.0%) in exposed workers, compared with control workers (20.1%; 18.1%; 0%) (P < 0.05). This increased symptom frequency was also documented among nonsmokers studied by age and by length of employment, suggesting a work-related effect. Among work shift-related symptoms, high prevalences were noted for upper respiratory tract symptoms (e.g., dry throat, eye irritation, throat irritation). The measured FVC and FEV1 were significantly lower than predicted for brick workers and suggested a restrictive pattern. The mean FVC (as a percent of predicted) was 78.1% and FEV1 was 88.1%. The FEF50 and FEF25 were not significantly decreased. A multiple regression analysis with age, exposure, and smoking as predictors and lung function parameters as response variables showed a significant effect between exposure and FVC. Significant chest roentgenographic abnormalities were not documented. These findings of a restrictive lung function pattern in brick workers with normal chest roentgenograms may suggest early interstitial disease. Additionally, a bronchitic component, as suggested by the respiratory symptoms, may also be present.

Respiratory findings in synthetic textile workers.

We studied 308 female and 92 male textile workers employed in a factory that produced synthetic fiber hosiery. The mean age of the women was 38 years, their mean duration of employment 16 years. The mean age of the men was 39 years with a mean duration of employment of 16 years. A control group of 160 female and 78 male nonexposed workers was also studied. Chronic and acute work related symptoms were recorded for all workers. Ventilatory capacity was measured by recording maximum expiratory flow-volume (MEFV) curves from which the forced vital capacity (FVC), the 1-sec forced expiratory volume (FEV1) and maximum expiratory flow rates at 50% and the last 25% (FEF50, FEF75) were read. There was a higher prevalence of all chronic respiratory symptoms in exposed than in control workers, although the differences were statistically significant only for dyspnea, sinusitis, and nasal catarrh (P < 0.01) in female synthetic textile workers, and for nasal catarrh (P < 0.01) in male synthetic textile workers. Occupational asthma was recorded in 3 (0.9%) of the women textile workers, and in 1 (1.1%) of male textile workers. There was a high prevalence of acute symptoms during the work shift, which was greatest for cough (female: 46%; male: 59%), dryness of the throat (female: 49%; male: 40%), dryness of the nose (female: 53%; male: 43%) and eye irritation (female: 46%; male: 36%). Ventilatory capacity data among the synthetic textile workers demonstrated significantly decreased FEF75 compared to predicted (P < 0.05). Our data suggest that inhalation of dust in synthetic textile plants causes the respiratory impairment.

Respiratory function and immunological status in cocoa and flour processing workers.

Respiratory function and immunological status were studied in 40 cocoa and 53 flour processing workers employed as packers in a confectionery industry and in 65 unexposed control workers in the same industry. A high prevalence of chronic respiratory symptoms was recorded in exposed workers, varying from 5.0% to 30.0% in cocoa workers and from 5.7% to 28.3% in flour workers. Occupational asthma was diagnosed in 2 (5%) of the cocoa workers and in 3 (5.7%) of the flour workers. None of the control workers suffered from occupational asthma. The prevalence of almost all chronic respiratory symptoms was significantly greater in cocoa and flour workers than in control workers. There was also a high prevalence of acute symptoms that developed during the work shift, being highest for cough (cocoa: 57.5%; flour: 50.9%) and eye irritation (cocoa: 50.0%; flour: 54.7%). Significant across-shift reductions of ventilatory capacity were recorded in exposed workers, being largest for flow rates at 50% and the last 25% of the vital capacity on maximum expiratory flow-volume (MEFV) curves (FEF50, FEF75). The prevalence of positive skin tests for cocoa (60.2%) was significantly higher than the prevalence of positive skin tests for flour (25.8%) among the 93 exposed workers (p < 0.05). Control workers had significantly lower prevalences of positive skin tests to cocoa (4.6%) and flour (12.3%) than exposed workers (p < 0.01). Increased total serum IgE levels were found in 17.5% of cocoa and in 18.7% of flour workers; none of the control workers had increased IgE levels. Bronchoprovocation testing demonstrated significant decreases in lung function following inhalation of cocoa dust extract and flour dust in workers with respiratory symptoms and large across-shift reductions in lung function. Dust concentrations in the working environment were higher than those recommended by Croatian standards. These data suggest that workers employed in the processing of cocoa and flour may be at a high risk for the development of allergic sensitization and respiratory impairment.

Recombinant Bet v 1, the major birch pollen allergen, induces hypersensitivity reactions equal to those induced by natural Bet v 1 in the airways of patients allergic to tree pollen.

BACKGROUND: Atopic allergens produced by recombinant DNA methods are promising tools for diagnosis and therapy of Type I allergy. To evaluate the immunologic properties of these molecules, it is necessary to compare them with natural allergens in vitro and in vivo. OBJECTIVE: The study was carried out to determine whether the potency of recombinant Bet v 1 (rBet v 1) is comparable to that of natural Bet v 1 (nBet v 1) in inducing allergic reactions in the nose and bronchi. METHODS: Thirteen patients allergic to birch pollen with bronchial asthma and/or rhinitis were investigated. Skin prick tests and nasal and bronchial challenges were performed with rBet v 1 and nBet v 1. RESULTS: In patients allergic to birch pollen, both allergens induced comparable skin reactions. In subjects with rhinitis rBet v 1 was equally potent in inducing nasal reactions (mean PD(+60)NR +/- SD, 10.48 +/- 17.42 microg vs 7.98 +/- 8.9 microg, p > 0.05). In patients with asthma, rBet v 1 was equally potent in inducing bronchial reactions (PD20 FEV1, 0.81 +/- 1.74 microg vs 0.62 +/- 1.44 microg, p > 0.05) as nBet v 1. CONCLUSION: No significant differences were observed between natural and recombinant allergen. We conclude that allergens produced by recombinant techniques can induce typical allergic reactions in important target organs of Type I allergy: the nose and bronchi.

[Respiratory symptoms and ventilatory function of the lungs in wool textile industry workers]. / Respiracijski simptomi i ventilacijska funkcija pluca radnica u tekstilnoj industriji na preradi vune.

Subjects in the study were 158 female wool textile workers and 87 control non-exposed workers. Respiratory symptoms were assessed by means of a questionnaire. Ventilatory capacity was measured in wool workers by recording maximum expiratory flow-volume (MEFV) curves on Monday before and after the work shift. Forced vital capacity (FVC), one-second forced expiratory volume (FEV1) and flow rates at 50% and the last 25% of the vital capacity (FEF50, FEF25) were measured on MEFV curves. Significantly higher prevalences of all chronic respiratory symptoms were recorded in exposed than in control workers (P < 0.01). Exposure to wool dust caused significant across shift reductions of ventilatory capacity varying from 2.0 to 9.1%. Those reductions were similar in textile workers exposed to wool for more than 10 years showed similar across shift reductions of ventilatory capacity tests as those with shorter exposure. Smokers and non-smokers had similar acute and chronic lung function changes. In a larger number of wool workers FEF50 and FEF25 were below 70% of predicted normal values. Bronchoprovocation testing with wool dust extract did not demonstrate correlation with respiratory impairment. Our data suggest that dust exposure in wool textile mills may be associated with the development of chronic respiratory symptoms and impaired lung function.

Immunological reactions and respiratory function in wool textile workers.

Immunological status and respiratory function were studied in a group of 64 wool textile workers (52 women and 12 men). A group of 46 workers not exposed to wool dust served as a control for the respiratory symptoms and immunologic testing. Skin testing was performed with different wool allergens (domestic and Australian) as well as with common allergens. Ventilatory capacity was measured in wool workers on Mondays before and after the work shift. The prevalence of positive skin tests to all allergens was higher in wool than in control workers, although the difference was statistically significant only for washed domestic wool (wool workers: 42.2%; control workers: 19.6%; p < 0.05). Increased serum IgE levels were more frequent in wool (26.6%) than in control workers (3.1%) (p < 0.01). In wool textile workers there was a high prevalence of acute and chronic respiratory symptoms. Significant across-shift reductions in ventilatory capacity tests, as well as abnormal baseline lung function, were recorded in wool textile workers. Individual data demonstrated that many of the wool workers had FEF25 lower than 70% of predicted. In general, the prevalence of symptoms and the lung function abnormalities did not correlate with the results of specific (wool) skin tests. Our data indicate that exposure to wool dust in some workers may be associated with the development of acute and chronic respiratory symptoms and impairment of lung function. Immunologic abnormalities, although frequent in this group, do not appear to be associated with the severity of these changes.

Respiratory symptoms and lung function in wool textile workers.

Our study investigated a group of 216 wool textile workers (158 women and 58 men). Respiratory symptoms were assessed by questionnaire in wool textile workers and in 130 not exposed (control) workers. Ventilatory capacity was measured in wool workers by recording maximum expiratory flow-volume (MEFV) curves on Monday before and after the work shift. Forced vital capacity (FVC), 1-second forced expiratory volume (FEV1), and flow rates at 50% and the last 25% of the vital capacity (FEF50, FEF25) were measured on the MEFV curves. Analysis of the data demonstrated a significantly higher prevalence of all chronic respiratory symptoms in wool workers than in controls, being the highest in wool workers for nasal catarrh (M: 63.8%; F: 44.9%) and for sinusitis (M: 62.1%; F: 43.0%). A high prevalence of acute symptoms, associated with the work shift, was also noted in wool workers. Exposure to wool dust caused significant across-shift reductions of ventilatory capacity varying from 1.4% for FEV1 to 9.1% for FEF50. Textile workers exposed to wool for > 10 years in the workplace had similar across-shift reductions of ventilatory capacity tests as those with shorter exposures. In a large number of these wool workers, FEF50 and FEF25 were below 70% of predicted normal values. Smokers had acute and chronic lung function changes similar to those of nonsmokers, indicating that smoking did not account for all the respiratory effects seen in wool processing workers. Our data suggest that dust exposures in wool textile mills may be associated with the development of chronic respiratory symptoms and impaired lung function.