[Update rheumatism focusing on rheumatoid arthritis]. / Update Rheuma am Beispiel der rheumatoiden Arthritis.

Rheumatic diseases do not only represent a challenge in day to day clinical medicine but also during underwriting and claims handling in insurance medicine. New diagnostic laboratory tests and therapeutic options constantly improve diagnostic quality and treatment outcomes. Using rheumatoid arthritis (RA) as an example this article explains how this new aspects found their way into international diagnostic criteria and treatment guidelines. The introduction of diagnostic ACPAs (Anti-Citrullinated Protein Antibodies) and the therapeutic use of currently still relatively expensive biologicals have to be highlighted in this respect. Backed by modern therapeutic options recent RA morbidity figures of employed persons indicate a shift to less severe morbidity spectra. For individual case evaluation it is of importance to understand the most relevant aspects of such innovations for adequate and sound case assessment in underwriting and claims.

Urban traffic and pollutant exposure related to respiratory outcomes and atopy in a large sample of children.

Conflicting results have been reported for the relationship between traffic exposure and inception of atopy. The effect of traffic on the prevalence of asthma and atopy at school age was investigated in a representative population. Random samples of schoolchildren (n=7,509, response rate 83.7%) were studied using the International Study of Asthma and Allergies in Childhood phase-II protocol with skin-prick tests, measurements of specific immunoglobulin E and lung function. Traffic exposure was assessed via traffic counts and by an emission model which predicted soot, benzene and nitrogen dioxide (NO2). Traffic counts were associated with current asthma, wheeze and cough. In children with tobacco-smoke exposure, traffic volume was additionally associated with a positive skin-prick test. Cough was associated with soot, benzene and NO2, current asthma with soot and benzene, and current wheeze with benzene and NO2. No pollutant was associated with allergic sensitisation. High vehicle traffic was associated with asthma, cough and wheeze, and in children additionally exposed to environmental tobacco smoke, with allergic sensitisation. However, effects of socioeconomic factors associated with living close to busy roads cannot be ruled out.

Are asthma and allergies in children and adolescents increasing? Results from ISAAC phase I and phase III surveys in Münster, Germany.

OBJECTIVE: To assess time trends in symptoms of asthma, allergic rhinitis, and atopic eczema among children in Münster, Germany. METHODS: Two cross-sectional surveys 5-years apart (1994/1995, 1999/2000) using ISAAC core written and video questionnaires and applying the ISAAC protocol. Two main age groups (6-7 and 13-14 year olds) were designated with information collected by parental and self-report for both age groups, respectively. A school-based sample of 7744 participants in the 1994/1995 survey and 7962 participants in the 1999/2000 survey was recruited. In the first and second surveys, response rates for the 6-7 year olds were 81 and 82%, respectively, while for the 13-14 year olds response rates were 94% in both. Analyses focus on the change in 12-month prevalence of symptoms of asthma, rhinitis, and eczema. RESULTS: There is a tendency towards an increase in current symptoms for all three conditions and in both age groups, but more so among girls. Indices of diagnosis either remained the same or increased in parallel to the increase in symptoms. Indices of severity also showed a homogenous increase in the 5-year study period. CONCLUSIONS: Our study shows that symptoms of asthma, rhinitis, and eczema are increasing, reflecting a change in the morbidity of these conditions in our population.

[Application of geographical information systems in epidemiological studies exemplified by the ISAAC study in Munich]. / Der Einsatz von Geoinformationssystemen (GIS) in epidemiologischen Studien dargestellt am Beispiel der ISAAC-Studie München.

Geographical Information Systems (GIS) are increasingly applied as modern tools for analysis and visualization of health-related spatial data, especially in epidemiological research. GIS are used by medical researchers and executives in the public health service. A community-based survey was conducted according to the phase II protocol of the International Study of Asthma and Allergies in Childhood (ISAAC) in Munich. The spatial patterns of disease incidence were analysed and related to exposure data by GIS. The prevalence study on fourth-grade pupils (n = 3354) and school beginners (n = 2890) was conducted during the school term 1995/96 in Munich. Parental questionnaires and measurements of lung function and immunological parameters were used. The questionnaire data were integrated in a GIS database. In this paper we discuss methodological aspects of GIS-based spatial analysis related to epidemiological data. In addition, we investigate whether there were spatial clusters of children with wheeze in the last 12 months of a magnitude unlikely to occur by chance and which could indicate local health risks. The study was based on permutation tests where global and local methods were applied. No spatial clusters of children with asthma symptoms were identified in the city of Munich.

Traffic exposure and allergic sensitization against latex in children.

BACKGROUND: Latex antigens have been found in urban air samples and in debris deposited near freeways. OBJECTIVE: We investigated whether exposure to road traffic in a large city is associated with allergic sensitization against latex in children. METHODS: A population-based sample of 2505 children aged 5 to 11 years was examined in a cross-sectional study in the city of Dresden, Germany. Specific IgE levels against latex and a panel of common aeroallergens (timothy grass, rye, birch, mugwort, Cladosporium herbarum, Dermatophagoides pteronyssinus, cat dander, and dog dander) was determined by using a fluorescence immunoassay (CAP Pharmacia). Traffic exposure was assessed by (1) parental self-report on traffic frequency and truck traffic in the street of residence, (2) traffic counts, and (3) measurements of benzene at 182 points on a 1-km(2) grid for 1 year, which were used to estimate the children's individual exposure at the home address. RESULTS: Eight hundred fifty-four (34.1%) of the children were sensitized against any of the allergens, and 150 (6.0%) had specific IgE (>0.35 kU/L) against latex. The prevalence of latex sensitization was not positively associated with self-reported traffic exposure, traffic counts in the street of residence (adjusted prevalence odds ratio for >5000 vs < or =5000 cars/d, 0.7; 95% confidence interval, 0.4-1.3), or benzene exposure (adjusted prevalence odds ratio for an increase of 1 microg/m(3) air, 0.8; 95% confidence interval, 0.7-1.05). CONCLUSION: The data suggest that exposure to road traffic is not associated with allergic sensitization to latex in children.

Prevalence of respiratory and atopic disorders among children in the East and West of Germany five years after unification.

Living conditions in eastern Germany have changed rapidly since unification in 1990 and little is known about how these changes affect the prevalence of atopic diseases. This study describes methods and prevalences of a large epidemiological project investigating determinants of childhood asthma and allergies in eastern (Dresden and Leipzig) and western (Munich) Germany in 1995/1996. Community based random samples of 9-11 yr old children in Dresden (n=3,017) and Munich (n=2,612), and of 5-7 yr old children in Dresden (n=3,300), Leipzig (n=3,167) and Munich (n=2,165) were studied by parental questionnaires, bronchial challenges with hypertonic saline, skin examination, skin-prick tests, and measurements of specific and total serum immunoglobulin (Ig)E using Phase II modules of the International Study of Asthma and Allergies in Childhood (ISAAC). In 9-11 yr old children, the prevalence of physician diagnosed asthma (7.9% versus 10.3%; p<0.01) and bronchial hyperresponsiveness (15.7% versus 19.9%; p<0.05) was lower in Dresden than in Munich. No difference between Munich and Dresden was observed in the prevalence of diagnosed hay fever, skin test reactivity to > or = 1 allergen, and increased levels (>0.35 kU x L(-1)) of specific IgE against inhalant and food allergens. Symptoms and visible signs of atopic eczema tended to be more prevalent in Dresden. Similar East-West differences between the three study areas were seen in the younger age group. These findings are in line with recently observed increases in the prevalence of hay fever and atopic sensitization, but not of asthma and bronchial hyperresponsiveness, among 9-11 yr old children in Leipzig.

Inner city air pollution and respiratory health and atopy in children.

The impact of inner city air pollution on the development of respiratory and atopic diseases in childhood is still unclear. In a cross sectional study in Dresden, Germany, 5,421 children in two age groups (5-7 yrs and 9-11 yrs) were studied according to the International Study of Asthma and Allergies in Childhood (ISAAC) phase II protocol. The prevalences of wheezing and cough as well as doctor diagnosed asthma and bronchitis were assessed by parental questionnaires. Children also underwent skin-prick testing, venipuncture for the measurement of serum immunoglobulin (Ig)E, lung function testing and a bronchial challenge test (4.5% saline) to assess airway hyperresponsiveness. Exposure was assessed on an individual basis by relating mean annual air pollution levels (SO2, NO2, CO, benzene, and O3) which had been measured on a 1 km2 grid, to the home and school address of each study subject. After adjusting for potential confounding factors an increase in the exposure to benzene of 1 microg x m3 air was associated with an increased prevalence of morning cough (adjusted odds ratio (aOR)): 1.15; 1.04-1.27) and bronchitis (aOR: 1.11; 1.03-1.19). Similar associations were observed for NO2 and CO. In turn, the prevalences of atopic sensitization, symptoms of atopic diseases and bronchial hyperresponsiveness were not positively associated with exposure to any of these pollutants. It is concluded that in this study a moderate increase in exposure to traffic-related air pollution was associated with an increased prevalence of cough and bronchitis, but not with atopic conditions in children.

Asthma and allergies among children in West and East Germany: a comparison between Münster and Greifswald using the ISAAC phase I protocol. International Study of Asthma and Allergies in Childhood.

The study aim was to compare the prevalence of asthma, rhinitis and eczema in children living in Münster, western Germany, and Greifswald, eastern Germany, and to investigate associations of several characteristics and exposures with atopic disease symptoms. In 1994 and 1995, questionnaire information was gathered on 5-8 yr old children (n=3,741 in Münster and n=2,857 in Greifswald) and 12-15 yr olds (n=4,003 and n= 3,153, respectively) using the phase I protocol of the International Study of Asthma and Allergies in Childhood (ISAAC). The 12 month period prevalences of reported atopic disease symptoms in 5-8 yr olds were generally higher in Münster than in Greifswald, whereas only a few prevalence differences were observed in 12-15 yr olds. In both age groups the reported lifetime prevalences of asthma, hay fever and eczema were lower in Greifswald. Indoor exposures such as wood or coal heating and feather bedding were negatively associated with symptoms, whereas exposures such as truck traffic in a residential street or active smoking were positively associated with symptoms. Wood or coal heating could partly explain the prevalence difference of allergic rhinitis symptoms among 5-8 yr olds between Münster and Greifswald. The findings provide additional evidence for a role of several characteristics and exposures as potential determinants of asthma and allergies in children.

Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany.

BACKGROUND: Several surveys in children and adults have shown significantly lower prevalences of asthma and allergic diseases in eastern Europe than in western countries. In the former East Germany tremendous changes towards western lifestyle have occurred since unification. The aim of this survey was to investigate time trends in the prevalence of asthma and allergic diseases among children living in the eastern part of Germany. METHODS: In 1995-96, 2334 (87.5%) schoolchildren in Leipzig participated in a cross-sectional study that used the same methods as a previous survey done shortly after the fall of communism in 1991-92. A self-administered questionnaire was distributed to the parents. Children underwent cold-air challenge and allergy skinprick tests to six common aeroallergens. FINDINGS: The prevalence of hay fever (2.3% [34/1454] vs 5.1% [115/2252], p<0.0001) and atopic sensitisation (19.3% [252/1303] vs 26.7% [434/1624], p<0.0001) increased significantly between 1991-92 and 1995-96. However, there was no significant change in the prevalence of asthma, asthma-related symptoms, or bronchial hyper-responsiveness. INTERPRETATION: These findings suggest important differences in the development of atopic disorders. The children were born about 3 years before unification and were therefore exposed to western living conditions only after the third birthday. Thus, factors operating very early in life may be particularly important for the acquisition of childhood asthma, whereas the development of atopic sensitisation and hay fever may also be affected by environmental factors occurring beyond infancy.

Epidemiological analyses of the relationship between environmental pollution and asthma.

Epidemiological studies performed on children and young adults indicate that the prevalence of asthma has increased over the past decades in a number of countries. Since genetic determinants alone are unlikely to explain these findings, environmental factors are expected to have an important impact on the prevalence of this disease. Environmental pollution, among many other factors, may play a role in the initiation and manifestation of asthma. However, there is little epidemiological evidence for a causal association between the classical major outdoor air pollutants, such as SO2 or particulate matter, and asthma. Evidence for an association between air pollution from motor vehicles and asthma is still controversial. Thus the indoor environment and other environmental determinants--including lifestyle factors--are likely to be more important as causes of asthma. Epidemiological studies are able to evaluate the effects of environmental factors on the health of human populations in their usual environments. In addition, they can measure associations between long-term environmental exposures and health outcomes. By using refined techniques for exposure and disease assessment, as well as time and cost-effective study designs, environmental epidemiology will increase the knowledge about the role of pollution as a possible cause of asthma.

The association between self-reported symptoms of asthma and allergic rhinitis and self-reported traffic density on street of residence in adolescents.

We examined the association between self-reported symptoms of asthma and allergic rhinitis and self-reported exposure to motor vehicle traffic in adolescents in Münster, Germany. A total of 3,703 German students age 12-15 years completed a written and video questionnaire in 1994-1995. We found positive associations between both wheezing and symptoms of allergic rhinitis during the past 12 months and self-reported frequency of truck traffic. The sex- and age-adjusted prevalence odds ratios and 95% confidence intervals (CI) for truck traffic, contrasting the categories "frequent" and "constant" against "never," were, for wheezing obtained by written questionnaire: 1.53 (95% CI = 1.15-2.05) and 2.15 (95% CI = 1.44-3.21); for wheezing obtained by video questionnaire: 1.61 (95% CI = 1.26-2.07) and 2.47 (95% CI = 1.74-3.52); and for symptoms of allergic rhinitis: 1.71 (95% CI = 1.36-2.15) and 1.96 (95% CI = 1.40-2.76), respectively. We found a similar positive association with self-reports on traffic noise. Putative confounding variables, including indicators of socio-economic status, smoking, etc, did not alter these associations substantially. The results correspond closely with findings of a survey carried out in 1991 in Bochum, Germany. Our results support the hypothesis that exposure to motor vehicle traffic is related to symptoms of asthma and allergic rhinitis in children, but we cannot rule out misclassification due to self-reports of traffic exposure.

The International Study of Asthma and Allergies in Childhood (ISAAC): objectives and methods; results from German ISAAC centres concerning traffic density and wheezing and allergic rhinitis.

The International Study of Asthma and Allergies in Childhood (ISAAC) was founded to maximize the value of epidemiological research into asthma and allergic disease by establishing a standardized methodology and facilitating international collaboration and comparison of data. The ISAAC design comprises three phases: Phase I uses validated core questionnaires designed to assess the prevalence and severity of asthma and allergic disease in defined populations; Phase II will investigate possible aetiological factors suggested by findings of Phase I and apply lung, blood and skin tests; Phase III will be a repetition of Phase I after 5 years to assess time trends in the prevalence and severity of wheezing, rhinitis and eczema in each ISAAC centre. In 1991 a survey on wheezing and allergic rhinitis in 2050 12-15 year old adolescents in Bochum showed a positive correlation between the prevalence of wheezing as well as allergic rhinitis and indicators of traffic density, controlling for putative confounders such as age, sex, passive smoking, active smoking, etc. In 1994-1995 an ISAAC Phase I survey conducted on adolescents in Münster, applying methodology similar to that in Bochum, found positive associations between surrogate measures of traffic density and 12 months prevalence of wheezing and lifetime prevalence of allergic rhinitis of a magnitude very close to that found in Bochum. The results from the two German cities provide support to the hypothesis that exposure to automobile emissions is related to wheezing and allergic rhinitis in children.

In vitro studies on enzymatic cleavage of steroid esters in the female organism.

The decreasing water-solubility of steroid esters concomitant with increasing chain lenth of monocarboxylic acids provides a prolonged therapeutic effect of the steroid. Whether a slow release of the steroid from an oily depot in the muscle or a secondary storage of the enter in the body fat ("deep compartment") are responsible for this prolonged action, is open to discussion. The aim of this study was to investigate the steriod ester cleaving enzyme activity of human subcutaneous fatty tissue. The followeing steroid esters were investigated: Testosterone acetate and oenanthate, metenolone acetate and oenanthate, norethisterone acetate and oenanthate, dehydroepiandrosterone acetate and oenanthate, fluocortolone acetate and caproate. In the 10000 X g supernatant phase of the female subcutaneous fatty tissue the rate of enzymatic cleavage of the long-chain oenanthates was considerably greater than that of the corresponding short-chain steroid esters. The nature and position of the ester group in the steroid molecule exhibited a marked effect on the rate of enzymatic cleavage of steroid esters. The cleavage rate of long- and short-chain steroid esters in human myometrium and endometrium resembled that in the fatty tissue. On the other hand, the gastric mucosa, recuts musculature, placenta and vaginal mucosa split the short-chain steroid esters more rapidly than the long-chain esters. The marked differences in the relation of the cleavage rate of long- and short-chain steoid esters in the various tissues allow the assumption that long- and short-chain steroid esters are cleaved by different enzymes.