Secular changes of anthropometric measures for the past 30 years in South-West Germany.

We investigated long-term changes in weight and skinfold thicknesses in German schoolchildren. In 2006, anthropometric measures were collected after a standardized protocol among 1079 children within the Ulm Research on Metabolism, Exercise and Lifestyle in children (URMEL-ICE) study. Data were compared with historical data (1975-1976). In URMEL-ICE, prevalence of overweight (IOTF criteria) was 16.5% (boys) and 17.3% (girls) and of obesity 3.5 and 3.6%, respectively. Compared with historical data the number of children above the 90th percentile(1975/76) increased statistically significantly for weight (approximately 150% both sexes), for subscapular (boys 288%, girls 206%) and triceps skinfold thickness (boys 460%, girls 413%). Statistically significant increases above the 50th percentile(1975/76) were found: weight 36 and 26%, subscapular 43 and 60% and triceps skinfold thickness 63 and 69% for boys and girls, respectively. Body fat among 6- to 9-year-old children increased dramatically within 30 years. Moreover, our data suggest substantial changes in body composition among normal-weight children towards an increased body fat mass.

How well do questionnaires perform compared with physical examination in detecting flexural eczema? Findings from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two.

BACKGROUND: Questionnaires are widely used in epidemiological studies to measure eczema symptom prevalence, but there are concerns regarding their accuracy if used as a diagnostic tool. OBJECTIVES: To compare the performance of a validated eczema symptom questionnaire and a standardized skin examination protocol employed in the second phase of the International Study of Asthma and Allergies in Childhood (ISAAC). METHODS: A total of 30,358 schoolchildren aged 8-12 years from 18 countries were examined for flexural eczema. Parents also completed an eczema symptom questionnaire. We compared prevalence estimates at the population level based on the questionnaire vs. physical examination. We also compared the skin examination and the ISAAC questionnaire in making a diagnosis of flexural eczema. RESULTS: The point prevalences for flexural eczema at centre level based on a single examination were lower than the questionnaire-based 12-month period prevalences (mean centre prevalence 3.9% vs. 9.4%). Correlation between prevalences of both outcome measures was high (r = 0.77, P < 0.001). At the individual level, questionnaire-derived symptoms of 'persistent flexural eczema in the past 12 months' missed < 10% of cases of flexural eczema detected on physical examination. However, between 33% and 100% of questionnaire-based symptoms of 'persistent flexural eczema in the past 12 months' were not confirmed on examination. CONCLUSIONS: ISAAC questionnaire-derived symptom prevalences are sufficiently precise for comparisons between populations. Where diagnostic precision at the individual level is important, questionnaires should be validated and potentially modified in those populations beforehand, or a standardized skin examination protocol should be used.

Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in ISAAC Phase II.

The association between breastfeeding and wheezing, lung function and atopy was evaluated in the International Study of Asthma and Allergy in Childhood (ISAAC) Phase II. Cross-sectional studies were performed in 27 centres in 20 countries. Information on disease and exposure factors was collected by parental questionnaires. Data from 54,000 randomly selected school children (aged 8-12 yrs, 31,759 with skin prick testing) and a stratified subsample (n = 4,888) were used for testing the correlation of breastfeeding with bronchial hyperreactivity and lung function. Random effect models for meta-analysis were applied to calculate combined odds ratios (ORs). Any breastfeeding was associated with less wheeze both in affluent (adjusted OR (OR(adj)) 0.87, 95% confidence interval (CI) 0.78-0.97) and nonaffluent countries (OR(adj) 0.80, 95% CI 0.68-0.94). Further analyses revealed that this was true only for nonatopic wheeze in nonaffluent countries (OR(adj) 0.69, 95% CI 0.53-0.90). Breastfeeding was not associated with atopic wheeze and objective measures of allergy in both affluent and nonaffluent countries. In contrast, breastfeeding was associated with higher predicted forced expiratory volume in one second in affluent countries only (mean ratio 1.11, 95% CI 1.02-1.20). Breastfeeding is associated with protection against nonatopic wheeze, which becomes particularly evident in nonaffluent countries. Overall, breastfeeding was not related to any measure of allergy. These findings may explain some of the controversy regarding breastfeeding, since the direction of the association with breastfeeding depends on the predominating wheeze phenotype (e.g. atopic, nonatopic).

A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2.

BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. RESULTS: Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. CONCLUSIONS: Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.

International variation in prevalence of rhinitis and its relationship with sensitisation to perennial and seasonal allergens.

The relative importance of atopy in the aetiology of rhinitis is largely unknown. The present study investigated the geographical variations in rhinitis in relation to atopy. The cross-sectional study involved 54,178 children (aged 8-12 yrs) from 30 study centres in 22 countries worldwide. Symptoms of rhinoconjunctivitis and rhinitis without conjunctivitis in the last 12 months were reported in parental questionnaires and children were skin-prick tested. The prevalence of rhinoconjunctivitis and rhinitis without conjunctivitis varied widely (1.5-24.5% and 1.4-45.2%, respectively). For rhinoconjunctivitis, the population attributable fraction (PAF) varied 0-71% for a positive skin-prick test to one or more seasonal allergens and 0-41% for perennial allergens. The PAF for sensitisation to seasonal and perennial allergens was higher in affluent countries (36 and 25%, respectively) than nonaffluent countries (1.3 and 12.6%, respectively). For rhinitis without conjunctivitis, the PAF for perennial allergens was 8 and 4% for affluent and nonaffluent countries, respectively. No significant PAF was found for seasonal allergens. Overall, atopy explained only a limited proportion of rhinitis symptoms, suggesting that the importance of other environmental factors has been under emphasised, particularly in less affluent countries. Atopy seems to be only marginally relevant for rhinitis without conjunctivitis, which seems mainly to reflect nonatopic rhinitis.

STAT1 gene variations, IgE regulation and atopy.

BACKGROUND: Signal transducer and activator of transcription 1 (STAT1), an intracellular signal transducer and activator of transcription centrally involved in many inflammatory pathways, was recently suggested to play an important role in allergy related immune responses. AIM: Thus, we investigated the effect of polymorphisms in the STAT1 gene on the development of atopic sensitization and allergic diseases. METHODS: Haplotype tagging single nucleotide polymorphisms (SNPs) previously described in the STAT1 gene were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology in a cross-sectional study population of 3099 German children recruited and phenotyped by the International Study of Asthma and Allergy in Childhood, phase II (ISAAC II). Effects of single SNPs and haplotypes were studied using SAS/Genetics and Haploview. RESULTS: The polymorphism C39134A (rs3771300), located in a potentially cis acting regulatory element in STAT1 intron 24, was inversely related to atopy measured by skin prick test, total and specific serum IgE levels while no effect on atopic disease risk was observed. CONCLUSION: Our results indicate that STAT1 SNP C39134A may protect from atopic sensitization. Because of its location in a highly conserved noncoding sequence near a putative GATA3 binding site, this polymorphism represents an interesting target for further studies.

Leisure time activity and new onset of wheezing during adolescence.

Asthma prevalence is increasing in adult and paediatric patients. In the present study, the association between different leisure time activities and new onset of wheezing was analysed in adolescents aged 16-18 yrs taking part in a questionnaire-based follow-up of the International Study on Asthma and Allergies in Childhood in Munich and Dresden, Germany. Of the 3,785 adolescents who took part in the follow-up (76% response), 2,910 adolescents without earlier episodes of wheezing in childhood were included in the analyses. Of these, 330 (11.3%) reported new onset of wheeze during the previous 12 months. In the bivariate analyses, exercising more than once per week or performing computer work >1 h.day(-1) were inversely related to new onset of wheeze. In contrast, visiting discotheques on a regular basis increased the risk of new onset of wheeze (12.9 versus 9.9%). The observed inverse relationship between physical activity and new onset of wheeze was not an independent effect but mediated by differences in active smoking. The association between physical activity and new onset of wheeze disappeared when active smoking was taken into account. However, the present data do not allow for determining whether smoking operated as a confounder or as an intermediate factor, i.e. whether physical activities prevented active smoking.

Nonatopic asthma is associated with helminth infections and bronchiolitis in poor children.

Asthma is common in urban centres in Latin America, but atopic asthma may not be the main phenotype among children. Helminth infections are highly prevalent in poor populations, and it was hypothesised that they attenuate allergic asthma, whereas other factors are related to the expression of a nonatopic wheeze/asthma phenotype. A total of 1,982 children from Southern Brazil with a mean+/-sd age of 10.1+/-0.76 yrs completed asthma questionnaires, and 1,011 were evaluated for intestinal parasites and atopy using skin-prick tests (SPTs). Wheeze in the previous 12 months was reported by 25.6%, and 9.3% showed current asthma; 13% were SPT-positive and 19.1% were positive for any helminths. Most children with either wheeze or asthma were SPT-negative; however, severe wheeze was more prevalent among the atopic minority. Helminth infections were inversely associated with positive SPT results. Bronchiolitis before the age of 2 yrs was the major independent risk factor for asthma at age 10 yrs; high-load Ascaris infection, a family history of asthma and positive SPT results were also asthma risk factors. Most asthma and wheeze are of the nonatopic phenotype, suggesting that some helminths may exert an attenuating effect on the expression of the atopic portion of the disease, whereas viral bronchiolitis predisposes more specifically to recurrent airway symptoms.

Polymorphisms in eosinophil pathway genes, asthma and atopy.

BACKGROUND: Eosinophilic inflammation is considered to play an important role in the development as well as in the perpetuation of asthma. As eosinophil production and survival is under genetic control we investigated whether polymorphisms in eosinophil regulation pathway genes (IL-3, IL-5, GM-CSF and their respective enhancers and receptors) may influence the development of atopic diseases. METHODS: In two large study populations of children, the German part of the International Study of Asthma and Allergy in Childhood (ISAAC II) and the German Multicentre Atopy Study (MAS), 3099 and 824 children, seven polymorphisms previously associated with the development of atopic diseases were genotyped: two in and around the GM-CSF gene (Ile117Thr and T3085G), one in IL-3 (Pro27Ser), in IL-5 (C-746T), and in the IL-5 high affinity receptor chain IL-5R (G-80A) and two in the common receptor chain CSFR2b for IL-3, IL-5, and GM-CSF (Asp312Asn and Glu249Gln). Statistical analyses were performed using chi-squared tests and variance analyses. Gene by gene interactions were evaluated in logistic regression models. RESULTS: The T allele at position -746 in the IL-5 gene was significantly protective for atopy in the ISAAC II population (P = 0.006). Furthermore, the risk for atopic asthma was decreased in carriers of the T allele (P = 0.036) and evidence for interaction with the enhancer polymorphism 3085 bp 3' of GM-CSF was detected. CONCLUSIONS: IL-5 C-746T influenced atopic outcomes and showed evidence for gene by gene interaction. No significant associations were found with all other tested polymorphisms in the eosinophil regulation pathway after correction for multiple testing.

Smoking and the incidence of asthma during adolescence: results of a large cohort study in Germany.

BACKGROUND: The association between smoking and asthma or wheeze has been extensively studied in cross sectional studies, but evidence from large prospective cohort studies on the incidence of asthma during adolescence is scarce. METHODS: We report data from a cohort study in two German cities, Dresden and Munich. The study population (n = 2936) was first studied in 1995/6 at age 9-11 years as part of phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II) and followed up in 2002/3. At baseline the parents completed a questionnaire and children underwent clinical examination and blood sampling. At follow up the young adults completed questionnaires on respiratory health, living, and exposure conditions. Incidence risk ratios (IRR) were calculated and adjusted for potential confounders using a modified Poisson regression approach. RESULTS: The adjusted IRR for incident wheeze for active smokers compared with non-smokers was 2.30 (95% confidence interval (CI) 1.88 to 2.82). The adjusted IRR was slightly higher for incident wheeze without a cold (2.76, 95% CI 1.99 to 3.84) and the incidence of diagnosed asthma (2.56, 95% CI 1.55 to 4.21). Analysis of duration and intensity of active smoking indicated dose dependent associations. Stratified analyses showed that the risk of incident wheeze without a cold in atopic smokers increased with decreasing plasma alpha(1)-antitrypsin levels at baseline (1.64, 95% CI 1.22 to 2.20 per interquartile range). CONCLUSIONS: Active smoking is an important risk factor for the incidence of asthma during adolescence. Relatively lower plasma levels of alpha(1)-antitrypsin, although well above currently accepted thresholds, may increase susceptibility to respiratory disease among atopic smokers.

Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria.

AIMS/HYPOTHESIS: We investigated relations between fasting blood glucose and the incidence of cancer. METHODS: A population-based cohort of more than 140,000 Austrian adults (63,585 men, 77,228 women) was followed over an average of 8.4 years. Incident cancer (other than non-melanoma skin cancers) was ascertained by a population-based cancer registry (n=5,212). Cox proportional-hazards models were used to estimate hazard rate ratios (HR) stratified for age and adjusted for smoking, occupational group and body mass index. RESULTS: The highest fasting blood glucose category (> or =7.0 mmol/l) was weakly associated with all cancers combined (HR 1.20; 95% CI, 1.03-1.39 in men and 1.28; 95% CI, 1.08-1.53 in women) relative to the reference level (4.2-5.2 mmol/l). The strongest association was found for liver cancer in men (HR 4.58; 95% CI, 1.81-11.62). Positive associations between fasting hyperglycaemia (6.1-6.9 or > or =7.0 mmol/l) and cancer incidence were also observed for non-Hodgkin's lymphoma in men, and for colorectal and bladder cancer in women. Breast cancer in women diagnosed at or after age 65 was also associated with fasting blood glucose > or =7.0 mmol/l. Positive associations with glucose values >5.3 mmol/l were noted for thyroid cancer, gallbladder/bile duct cancer and multiple myeloma in men and women combined. CONCLUSIONS/INTERPRETATION: These findings provide further evidence that elevated blood glucose is associated with the incidence of several types of cancer in men and women.

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.

Cancer mortality in German carbon black workers 1976-98.

BACKGROUND: Few studies have investigated cancer risks in carbon black workers and the findings were inconclusive. METHODS: The current study explores the mortality of a cohort of 1535 male German blue-collar workers employed at a carbon black manufacturing plant for at least one year between 1960 and 1998. Vital status and causes of death were assessed for the period 1976-98. Occupational histories and information on smoking were abstracted from company records. Standardised mortality ratios (SMR) and Poisson regression models were calculated. RESULTS: The SMRs for all cause mortality (observed deaths (obs) 332, SMR 120, 95% CI 108 to 134), and mortality from lung cancer (obs 50, SMR 218, 95% CI 161 to 287) were increased using national rates as reference. Comparisons to regional rates from the federal state gave SMRs of 120 (95% CI 107 to 133) and 183 (95% CI 136 to 241), respectively. However, there was no apparent dose response relationship between lung cancer mortality and several indicators of occupational exposure, including years of employment and carbon black exposure. CONCLUSIONS: The mortality from lung cancer among German carbon black workers was increased. The high lung cancer SMR can not fully be explained by selection, smoking, or other occupational risk factors, but the results also provide little evidence for an effect of carbon black exposure.

Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria.

We investigated the relation of overweight and obesity with cancer in a population-based cohort of more than 145 000 Austrian adults over an average of 9.9 years. Incident cancers (n=6241) were identified through the state cancer registry. Using Cox proportional-hazards models adjusted for smoking and occupation, increases in relative body weight in men were associated with colon cancer (hazard rate (HR) ratio 2.48; 95% confidence interval (CI): 1.15, 5.39 for body mass index (BMI) > or =35 kg m(-2)) and pancreatic cancer (HR 2.34, 95% CI: 1.17, 4.66 for BMI>30 kg m(-2)) compared to participants with normal weight (BMI 18.5-24.9 kg m(-2)). In women, there was a weak positive association between increasing BMI and all cancers combined, and strong associations with non-Hodgkin's lymphomas (HR 2.86, 95% CI: 1.49, 5.49 for BMI> or =30 kg m(-2)) and cancers of the uterine corpus (HR 3.93, 95% CI: 2.35, 6.56 for BMI> or =35 kg m(-2)). Incidence of breast cancer was positively associated with high BMI only after age 65 years. These findings provide further evidence that overweight is associated with the incidence of several types of cancer.

Type of kindergarten and other potential determinants of overweight in pre-school children.

OBJECTIVE: The study aimed to assess the relationship of various types of kindergarten differing in length of care and food availability with the development of overweight in pre-school children. DESIGN, SETTING AND SUBJECTS: A cross-sectional study was carried out in 2002 in Stuttgart, Germany, as part of the school entrance examination. Height and weight of 2140 children (participation 70.2%) were measured and information on type of kindergarten and other potential determinants of overweight was collected by a parental questionnaire. Change in relative body mass index (BMI) position between the ages of 4 and 6 years was assessed using medical records. RESULTS: The prevalence of overweight or change in relative BMI position did not differ according to the type of kindergarten. For the prevalence of overweight in German children, adjusted odds ratios (OR) comparing institutions that open only in the morning with those opening in the morning and afternoon or for the full day were 0.86 (95% confidence interval (CI) 0.40, 1.83) and 0.63 (95% CI 0.25, 1.58), respectively. Parental BMI and duration of television watching were positively associated, and maternal educational status and duration of breast-feeding were negatively associated, with overweight and/or change in relative BMI position. The prevalence of overweight was substantially higher among non-German than among German children (adjusted OR 2.17 (95% CI 1.53, 3.07)). CONCLUSIONS: These data show no association between different types of kindergarten and the development of overweight in early childhood. Duration of television watching and breast-feeding, as well as the relatively high prevalence of overweight in ethnic minorities, deserve further attention.

No increase in the prevalence of asthma, allergies, and atopic sensitisation among children in Germany: 1992-2001.

BACKGROUND: From 1970 to 1990 increasing rates of asthma and allergic sensitisation were observed in several countries. The aim of this study was to investigate time trends in the prevalence of asthma and allergic sensitisation among school children in Germany between 1992 and 2001. METHODS: Parental reports of asthma, hay fever, and wheezing and measurements of specific serum IgE antibodies were investigated in six serial cross sectional surveys of 9-11 year old school children in three study areas in south west Germany. RESULTS: A total of 6762 school children of mean age 10 years (mean participation rate 77.9%) took part in the investigation in the three study areas. Over the 9 year study period no increase in the prevalence of current wheezing and asthma was observed. In addition, the prevalence of atopic sensitisation remained unchanged during the observation period. CONCLUSIONS: These data, using parental reports and objective measures of allergy, suggest that there has been no further increase in the prevalence of asthma and atopy since 1992. The epidemic may thus have reached a plateau.

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.

Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods.

International comparative studies, investigating whether disease incidence or prevalence rates differ between populations and, if so, which factors explain the observed differences, have made important contributions to the understanding of disease aetiology in many areas. In Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence rates of symptoms of asthma, allergic rhinitis and atopic eczema in 13-14-yr-olds, assessed by standardised questionnaires, were found to differ >20-fold between the 155 study centres around the world. Phase II of ISAAC aims to identify determinants of these differences by studying informative populations. A detailed study protocol was developed for use in community-based random samples of children aged 9-11 yrs. The study modules include standardised questionnaires with detailed questions on the occurrence and severity of symptoms of asthma, allergic rhinitis and atopic eczema, their clinical management, and a broad range of previous and current exposure conditions. In addition, standardised protocols were applied for examination of flexural dermatitis, skin-prick testing, bronchial challenge with hypertonic saline, blood sampling for immunoglobulin E analyses and genotyping, and dust sampling for assessment of indoor exposures to allergens and endotoxin. To date, ISAAC II field work had been completed or started in 30 study centres in 22 countries. The majority of centres are in countries that participated in International Study of Asthma and Allergies in Childhood Phase I and reflect almost the full range of the observed variability in Phase I prevalence rates.