The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: A global synthesis

This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13–14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6–7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability(AU)

The association between BMI, vigorous physical activity and television viewing and the risk of symptoms of asthma, rhinoconjunctivitis and eczema in children and adolescents: ISAAC Phase Three.

BACKGROUND: Several studies have observed an association between obesity and asthma, but whether or not there is an association with rhinoconjunctivitis or eczema is unclear. AIMS: To examine the relationship between body mass index categories (underweight, overweight and obesity), vigorous physical activity and television viewing and the risk of symptoms of asthma, rhinoconjunctivitis and eczema. METHODS: As part of International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three, parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis and eczema, and several potential risk factors, such as vigorous physical activity and television viewing, and other information such as the child's height and weight. Adolescents aged 13-14 years self-completed the questionnaires on these symptoms and potential risk factors and reported their own height and weight. For 28% of children and 24% of adolescents, the height and weight was objectively measured. RESULTS: A total of 76 164 children aged 6-7 years (from 29 centres and 17 countries) and 201 370 adolescents aged 13-14 years (from 73 centres and 35 countries) provided data meeting the inclusion criteria. There were associations between overweight and obesity, but not underweight, and symptoms of asthma and eczema but not rhinoconjunctivitis. Vigorous physical activity was positively associated with symptoms of asthma, rhinoconjunctivitis and eczema in adolescents, but not children. Viewing television for five or more hours/day was associated with an increased risk of symptoms of asthma, rhinoconjunctivitis and eczema in adolescents and symptoms of asthma in children. CONCLUSIONS AND CLINICAL RELEVANCE: This study has confirmed the association between overweight and obesity and symptoms of asthma. It has extended these observations to include significant associations with symptoms of eczema, but not rhinoconjunctivitis. There are complex relationships between obesity, vigorous physical activity and sedentary behaviour and the symptoms of asthma, rhinoconjunctivitis and eczema in children.

The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis.

This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability.

Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: the MONICA/KORA Augsburg cohort study.

BACKGROUND AND AIM: It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. METHODS AND RESULTS: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n=833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n=36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n=21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). CONCLUSIONS: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes.

HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk.

OBJECTIVE: We aimed to clarify some previous inconsistencies regarding the role of high density lipoprotein cholesterol (HDL-C) as a CVD protective factor. METHODS: The SCORE dataset contained data on HDL-C for 104,961 individuals (45% women) without pre-existing coronary heart disease (CHD). These were from 7 pooled European prospective studies. The effect of HDL-C, both in quintiles and as a continuous variable, on risk of CVD and CHD mortality was examined, using Cox proportional hazards model, adjusted for age, total cholesterol, systolic blood pressure, smoking, diabetes and body mass index and stratified by gender, age group, country and category of SCORE CVD risk. RESULTS: A strong, graded, independent, inverse relationship between HDL-C and both CVD and CHD mortality was demonstrated. Adjusted hazard ratios per 0.5mmol/l increase in HDL-C were 0.60 (0.51, 0.69) and 0.76 (0.70, 0.83) in women and men, respectively for the CVD mortality endpoint. The corresponding hazard ratios were 0.53 (0.42, 0.68) and 0.79 (0.64, 0.98) in elderly women and men, respectively. The relationship was significant in all SCORE CVD risk strata and age groups. CONCLUSIONS: This multivariable analysis, the largest of its kind to date, has confirmed the inverse, independent, strong and graded relationship between HDL-C and both CVD and CHD mortality. We have clarified previous suggestions that the relationship is stronger in women and that it applies in all age groups. This is the first prospective study to demonstrate the independent relationship specifically in healthy elderly women and to show that the relationship holds at all levels of total CVD risk.

Fatty acids in serum cholesteryl esters in relation to asthma and lung function in children.

BACKGROUND: Dietary fatty acid intake has been proposed to contribute to asthma development with n-6 polyunsaturated fatty acids (PUFA) having a detrimental and n-3 PUFA a protective effect. OBJECTIVE: The aim of our analysis was to explore the relationship between fatty acid composition of serum cholesteryl esters as marker of dietary intake and prevalence of asthma, impaired lung function and bronchial hyper-responsiveness in children. METHODS: The study population consisted of 242 girls and 284 boys aged 8-11 years, living in Munich, Germany. Data were collected by parental questionnaire, lung function measurement and skin prick test according to the International Study of Asthma and Allergies in Childhood phase II protocol. Confounder-adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated for the association between quartiles of fatty acid concentration and health outcomes with the first quartile as reference. RESULTS: n-3 PUFA: levels of eicosapentaenoic acid were not related to asthma and impaired lung function. Linolenic acid levels were positively associated with current asthma (OR for fourth quartile 3.35, 95% CI 1.29-8.66). Forced expiratory volume in 1 s (FEV(1)) values decreased with increasing levels of linolenic acid (p for trend=0.057). n-6 PUFA: there was a strong positive association between arachidonic acid levels and current asthma (OR(4th quartile) 4.54, 1.77-11.62) and a negative association with FEV(1) (P=0.036). In contrast, linoleic acid was negatively related to current asthma (OR(4th quartile) 0.34, 0.14-0.87) and FEV(1) values increased with increasing levels of linoleic acid (P=0.022). The ratio of measured n-6 to n-3 PUFA as well as levels of palmitic and oleic acid were not consistently related to asthma or lung function. CONCLUSION: Our data do not support the hypothesis of a protective role of n-3 PUFA. Elevated arachidonic acid levels in children with asthma may be because of a disturbed balance in the metabolism of n-6 PUFA or may be secondary to inflammation in these patients.

Atopic dermatitis, extrinsic atopic dermatitis and the hygiene hypothesis: results from a cross-sectional study.

BACKGROUND: Atopic Dermatitis (AD), hayfever and asthma are commonly summarized as atopic diseases. The spatial distribution of AD differs from that of asthma and hayfever, suggesting that AD might follow a different risk pattern than these diseases. AD can be differentiated into an allergic extrinsic form (EAD) and a non-allergic intrinsic form (IAD). Only EAD might follow the distribution and risk pattern that have been ascribed to asthma and hayfever. OBJECTIVE: To investigate the distribution and risk factor profile of AD and EAD focusing on environmental factors relating to the hygiene hypothesis. METHODS: Population-based cross-sectional study on 12,601 children aged 5-7 and 9-11 years from Dresden (Eastern Germany) and Munich (Western Germany). Information was obtained by International Study of Asthma and Allergic Childhood questionnaires, dermatological examinations and skin prick testing. AD-diagnosis ever, current AD-symptoms and visible eczema were investigated with their respective extrinsic forms. RESULTS: Maternal and paternal history of AD were equally strong determinants of the child's AD status. Factors related to the hygiene hypothesis like day-care attendance and number of older siblings were not associated with a decreased risk of AD. The proportion of EAD within AD was higher in Eastern than in Western Germany. The determinants of the diseases appeared to be similar for both EAD and IAD. CONCLUSIONS: There was no evidence of the hygiene hypothesis holding true for AD or EAD. AD might be a separate entity than respiratory atopic diseases. Little is known about the risk factors of AD and factors different from those of respiratory allergic diseases should be considered in future research.

[The Worldwide WHO MONICA Project: results and perspectives]. / Das weltweite WHO-MONICA-Projekt: Ergebnisse und Ausblick.

After World War II coronary heart disease (CHD) assumed epidemic proportions in western countries. In many countries the peak of the epidemic occurred in 1968. In 1978 the National Heart, Lung and Blood Institute of the NIH organized the Bethesda conference on the decline in CHD mortality. The aim of the conference was to find out whether measures of prevention or improvements in acute coronary care were responsible for the decline in age-specific CHD mortality rates. Because of lack of appropriate data in 1978 these questions remained unanswered. To answer these questions the WHO MONICA (Monitoring trends and determinants in cardiovascular disease) project was organized as a monitoring system to assess trends and determinants of cardiovascular mortality, incidence and case fatality from the mid 1980 s to the mid 1990 s in 38 populations in 21 countries worldwide. Altogether some 13 million people were monitored over a 10 year period. 166,000 myocardial infarction patients were registered and more than 300,000 men and women were sampled and examined for their cardiovascular risk factors and many other health data. In Western countries, where the CHD mortality decline was on average 2-3 % annually, two thirds of this decline could be explained by a decline in CHD incidence and one third by a decline in CHD case fatality. When relating risk factor changes to changes in CHD event rates in men over a time period of 10 years in all MONICA populations it turned out that the greatest contribution to the CHD decline came from a decrease in smoking. On a worldwide scale the Seven Countries Study, the Framingham Heart Study and the WHO MONICA Project have contributed most to the development of epidemiology and prevention of cardiovascular diseases.

Symptoms of asthma and the home environment. The ISAAC I and III cross-sectional surveys in Münster, Germany.

BACKGROUND: The indoor home environment has been shown to be associated with the presence of respiratory symptoms and atopic disease. METHODS: Two cross-sectional surveys (1995-2000) were conducted, using data from the ISAAC phase I and III surveys, collected in Münster, Germany (n = 6,996, response 81.8%). We analyzed the prevalence ratio (PR) for several indoor exposures and asthma-related outcomes in 6- to 7-year-old children, adjusting for potential confounders. RESULTS: Positive associations were observed regarding exposure to molds, environmental tobacco smoke, cooking with gas and space heating with fossil fuels, but most associations were not statistically significant. Surprisingly, presence of a carpet was negatively associated with most respiratory conditions. When restricting the analysis to participants without avoidance of a carpet due to a history of atopic disease, the protective associations disappeared. Mostly, present pet ownership did not show positive associations with respiratory symptoms. However, ownership at different times in life revealed positive associations, particularly in regard to birds owned in the first year of life (PR 1.51, 95% CI 1.11-2.06, for sleep disturbance due to wheeze and PR 1.28, 95% CI 1.01-1.63, for wheeze during the last 12 months, respectively). CONCLUSIONS: Only few indoor factors were positively associated with the studied outcomes. The change of associations in participants that reported allergy-related avoidance of carpets suggests that the observed effects are a result of asthmatics' changed behavior. The effect of allergy-related change in behavior and the results observed concerning the ownership of pets at different ages underline the need of establishing a precise temporal relationship between disease and exposure.

Elevated nitric oxide production mediates beta-amyloid-induced mitochondria failure.

Mitochondrial dysfunction has been identified in a large proportion of neurodegenerative disorders including Alzheimer's disease (AD). In addition, the involvement of nitric oxide (NO) has been implicated in the pathogenesis of AD. Thus, we investigated the effects of the Swedish double mutation (K670M/N671L) in the beta-amyloid precursor protein (APPsw) on NO levels and mitochondrial function in PC12 cells. Interestingly, APPsw PC12 cells showed increased NO levels, decreased cytochrome C oxidase activity and reduced ATP levels compared to wild-type APP bearing cells and empty vector transfected cells. On the basis of our data, we propose a hypothetical sequence of events linking amyloid beta-peptide and NO production with mitochondria failure.

[Recommendations for statin therapy in the elderly]. / Empfehlungen zur Statintherapie im AlterDaten und Konsensus.

Elderly patients are significantly less likely to receive statins than younger patients possibly because of doubts regarding compliance or concerns regarding the increased likelihood of adverse events and drug interactions. Poor compliance can be expected especially in patients suffering from dementia or depression as well as those whose stage of cardiovascular disease exhibits few symptoms. On the other hand, the clinical significance of CHD events is high in the elderly, and 80% of coronary deaths occur in patients aged over 65 years. The average statistical life expectancy of elderly and old patients is often underestimated. The HPS and PROSPER studies showed that statins reduce mortality and morbidity even in very elderly individuals with a high global cardiovascular risk and/or CAD. Patients up to the age of 79 years should be treated according to the same guidelines as younger patients. Statin therapy should only be considered for patients aged 80 years and older who are at a very high risk for cardiovascular events.

Risk factor management in diabetic and non-diabetic patients with coronary heart disease. Findings from the EUROASPIRE I AND II surveys.

AIMS/HYPOTHESIS: We examined risk factor management in diabetic and non-diabetic patients with CHD based on data from EUROASPIRE surveys. METHODS: Consecutive CHD patients aged 70 years or younger were interviewed and examined at least 6 months after hospitalisation for a revascularisation procedure or acute myocardial infarction or ischaemia. Of these patients, 3569 were from the EUROASPIRE I study, undertaken from 1995 to 1996 in nine countries, and 5556 were from the EUROASPIRE II study, conducted between 1999 and 2000 in 15 countries. RESULTS: In EUROASPIRE I and II 18% and 20% of CHD patients respectively had been previously diagnosed with diabetes. Fasting glucose screening raised the prevalence of diabetes in EUROASPIRE II to 28%. In EUROSPIRE II the prevalence of risk factors (known diabetic/non-diabetic) was: current smoking 17%/22 % ( p=0.25); obesity (BMI >/=30 kg/m(2)) 43%/29% ( p<0.001); raised blood pressure (>/=140/90 mm Hg) 57%/49% ( p<0.001); and elevated total cholesterol (>/=5.0 mmol/l) 55%/59% ( p<0.001). The proportion of users of cardiovascular medication was: antiplatelet drugs 83%/86% (NS); beta-blockers 62%/63% (NS); ACE inhibitors 49%/35% ( p<0.001); and lipid-lowering drugs 62%/61% (NS). A comparison of both studies showed that for diabetic and non-diabetic patients the prevalence of smoking had increased somewhat and that the prevalence of obesity had increased clearly. There was no improvement in blood pressure control, but cholesterol control had improved, mainly explained by the increased use of lipid-lowering drugs. CONCLUSIONS/INTERPRETATION: These European surveys show a high prevalence of adverse lifestyles and modifiable risk factors among diabetic and non-diabetic patients with CHD. The risk factor status was more adverse in diabetic patients.

Adapting smoking cessation interventions for developing countries: a model for the Middle East.

OBJECTIVE: To describe the rationale and methods for the development of culturally-sensitive smoking cessation interventions for primary care settings in developing countries. RATIONALE: Smokers in the Middle East have great difficulty quitting. Effective smoking cessation programs are currently lacking in the Middle East, and the development of culturally sensitive programs is hindered by the dearth of standardized information regarding tobacco use and dependence in this region. METHODS: Epidemiological and clinical laboratory methods are needed to determine the prevalence and patterns of tobacco use and nicotine dependence. One strategy is to adapt smoking cessation methods widely used in industrialized countries to the Syrian and Middle Eastern environment. In a recently initiated project, the Syrian Center for Tobacco Studies has been established to address these issues. Initial work is focusing on collecting formative data including key informant interviews, focus groups, and epidemiological surveys to assess smokers' use patterns, needs, and resources. Clinical laboratory techniques are also being applied to assess the physiological, behavioral, and subjective effects of local tobacco use methods, such as narghile (water pipe) smoking. These data will be used to help adapt existing smoking cessation interventions from industrialized countries to be evaluated in a randomized controlled trial. CONCLUSION: There is a great need to develop and disseminate effective cessation interventions in low-income countries. Successful interventions will contribute to a culturally sensitive and sustainable regional tobacco control infrastructure. This paper describes one approach to the development of such an infrastructure that is currently underway in the Middle East.

The relation of markers of fetal growth with asthma, allergies and serum immunoglobulin E levels in children at age 5-7 years.

BACKGROUND: It has been suggested that fetal growth and maturation have an impact on the development of allergic diseases later in life. OBJECTIVE: To examine the association between measures of fetal growth and allergic disease in children at age 5-7 years. METHODS: As part of the German International Study of Asthma and Allergies in Childhood phase II surveys, a random sample of school beginners (n=1138) was examined in 1995. Data on anthropometric measures at birth and gestational age were obtained from maternal copies of birth records. Data on symptoms and doctor-diagnosed asthma, atopic dermatitis and hayfever were gathered by parental questionnaires. Atopic sensitization was assessed by serum IgE and skin prick tests to common aeroallergens. Children (741) had complete data for the explanatory variables of interest and were thus eligible for this analysis. Confounder-adjusted prevalence odds ratios (PORs) and means ratios with 95% confidence intervals (CI) were calculated using multiple logistic and linear regression. RESULTS: Birth weight and gestational age were positively associated with atopic sensitization (Ptrend=0.025 and 0.035, respectively). Children with a low birth weight relative to head circumference had a decreased risk of sensitization (POR 0.44, 95% CI 0.21-0.91; Ptrend=0.020). Moreover, total serum IgE increased with increasing birth weight (Ptrend=0.042). No consistent relationship was observed between markers of fetal growth and wheezing, doctor-diagnosed asthma, atopic dermatitis and hayfever. CONCLUSION: These data suggest that fetal growth and maturity are associated with atopic sensitization and total serum IgE levels in childhood.

Different methods to calculate effect estimates in cross-sectional studies. A comparison between prevalence odds ratio and prevalence ratio.

OBJECTIVES: According to results from the epidemiological literature, it can be expected that the prevalence odds ratio (POR) and the prevalence ratio (PR) differ with increasing disease prevalence. We illustrate different concepts to calculate these effect measures in cross-sectional studies and discuss their advantages and weaknesses, using actual data from the ISAAC Phase III cross-sectional survey in Münster, Germany. METHODS: We analyzed data on the association between self-reported traffic density and wheeze and asthma by means of the POR, obtained from a logistic regression, and the PR, which was estimated from a log-linear binomial model and from different variants of a Poisson regression. RESULTS: The analysis based on the less frequent disease, i.e. asthma with an overall prevalence of 7.8%, yielded similar results for all estimates. When wheezing with a prevalence of 17.5% was analyzed, the POR produced the highest estimates with the widest confidence intervals. While the point estimates were similar in the log-binomial model and Poisson regression, the latter showed wider confidence intervals. When we calculated the Poisson regression with robust variances, confidence intervals narrowed. CONCLUSIONS: Since cross-sectional studies often deal with frequent diseases, we encourage analyzing cross-sectional data based on log-linear binomial models, which is the 'natural method' for estimating prevalence ratios. If algorithms fail to converge, a useful alternative is to define appropriate starting values or, if models still do not converge, to calculate a Poisson regression with robust estimates to control for overestimation of errors in the binomial data.

Effects of EGb 761 Ginkgo biloba extract on mitochondrial function and oxidative stress.

As major sources of reactive oxygen species (ROS), mitochondrial structures are exposed to high concentrations of ROS and may therefore be particularly susceptible to oxidative damage. Mitochondrial damage could play a pivotal role in the cell death decision. A decrease in mitochondrial energy charge and redox state, loss of transmembrane potential (depolarization), mitochondrial respiratory chain impairment, and release of substances such as calcium and cytochrome c all contribute to apoptosis. These mitochondrial abnormalities may constitute a part of the spectrum of chronic oxidative stress in Alzheimer's disease. Accumulation of amyloid beta (Abeta) in form of senile plaques is also thought to play a central role in the pathogenesis of Alzheimer's disease mediated by oxidative stress. In addition, increasing evidence shows that Abeta generates free radicals in vitro, which mediate the toxicity of this peptide. In our study, PC12 cells were used to examine the protective features of EGb 761(definition see editorial) on mitochondria stressed with hydrogen peroxide and antimycin, an inhibitor of complex III. In addition, we investigated the efficacy of EGb 761 in Abeta-induced MTT reduction in PC12 cells. Moreover, we examined the effects of EGb 761 on ROS levels and ROS-induced apoptosis in lymphocytes from aged mice after in vivo administration. Here, we will report that EGb 761 was able to protect mitochondria from the attack of hydrogen peroxide, antimycin and Abeta. Furthermore, EGb 761 reduced ROS levels and ROS-induced apoptosis in lymphocytes from aged mice treated orally with EGb 761 for 2 weeks. Our data further emphasize neuroprotective properties of EGb 761, such as protection against Abeta-toxicity, and antiapoptotic properties, which are probably due to its preventive effects on mitochondria.