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.

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.

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.

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.

Diagnosis and management of hypertension by physicians in the Federal Republic of Germany.

Diagnosis and management of hypertension by physicians in two large cities in the northwest of Germany were studied in 1988. Three hundred and fifteen out-of-hospital physicians (71%) responded to a mailed questionnaire. Sixty-eight per cent reported measuring blood pressure at almost each patient visit and 36% involved allied health professionals in the measurement process. Only 63% used disappearance of sound for the diastolic reading (phase V). A comparison with US data from 1987 showed that German physicians started drug therapy at higher levels of diastolic blood pressure than their American colleagues. Only 43% of the German physicians initiated antihypertensive medication at diastolic blood pressure values below 100 mmHg; this compares with 92% for US physicians. In Germany, beta-blockers were clearly preferred as step-one therapy for young patients, while diuretics were prescribed for the majority of the older patients. Forty per cent reported reducing or stopping antihypertensive medication when the blood pressure was controlled.

Chronic illness and mental health problems in pediatric practice: results from a survey of primary care providers.

The prevalence of chronic physical illnesses and their association with mental disorders was assessed using data collected by primary care pediatricians. A chronic illness was diagnosed in 1573 (15.6%) of 10,058 children aged 4 to 16 years, 945 (9.4%) of whom had a "serious" disorder, 535 (5.3%) had a minor disorder (hay fever or dermatitis), and 121 (1.2%) had a speech or language disorder. Behavioral problems were identified more often among patients with "serious" disorders than among those without chronic illnesses (2.4% vs 1.7%), as were emotional problems (5.0% vs 3.1%). Among those with "serious" conditions involving the central nervous system, the prevalence of behavioral (5.2%) and emotional (10.4%) disorders was still higher. Although children with "serious" disorders not involving the central nervous system also showed elevated prevalence rates of behavioral (2.1%) and emotional (4.5%) disturbances, this increase did not reach statistical significance. No association with "minor" chronic disorders was found. The negative impact of these mental health problems on the child was more severe when a chronic illness was also present, but referrals for mental health services did not reflect his association.

Self-reported wheezing and allergic rhinitis in children and traffic density on street of residence.

A survey of 2050 seventh- and eighth-grade schoolchildren was conducted in Bochum, Germany, in 1991. The prevalence of wheezing and allergic rhinitis was assessed by self-completed written questionnaires and video questionnaires. To estimate the traffic density on the street of residence, children were asked about the frequency of heavy truck traffic on weekdays and to describe the street either as a main road or as a side street. There was a positive correlation between the prevalence of wheezing as well as allergic rhinitis and the indicators of traffic density, controlling for age, sex, nationality, passive smoking, active smoking, parental history of asthma, and so on. The adjusted prevalence odds ratio (ORs) and 95% confidence intervals (CIs) contrasting the "frequent" and "constant" categories for truck traffic with the "never" category were as follows: for wheezing (written questionnaire), OR = 1.53 (CI: 1.06 to 2.20) and OR = 1.67 (CI: 1.05 to 2.66); for wheezing (video questionnaire), OR = 1.58 (CI: 1.13 to 2.20) and OR = 1.94 (CI: 1.26 to 2.99); and for allergic rhinitis, OR = 1.67 (CI: 1.17 to 2.38) and OR = 1.54 (CI: 0.97 to 2.44). In conclusion, a possible role of factors associated with automobile exhausts causing or exacerbating asthma symptoms and allergic rhinitis in children is supported.

Occupational risk factors for mortality from stomach and lung cancer among rubber workers: an analysis using internal controls and refined exposure assessment.

OBJECTIVES: To determine occupational risk factors for stomach and lung cancer among workers in the German rubber industry. METHODS: A cohort of all male German rubber workers (n = 11,633) who had been employed for at least one year in one of five study plants and who were alive and actively employed or retired on 1 January 1981 was followed for mortality from 1 January 1981 through December 1991. A subcohort of n = 8,933 workers who were hired after 1 January 1950 was defined to focus on working conditions in the more recent rubber industry. Work histories were reconstructed using routinely documented 'cost centre codes' and classified into six work areas as well as subgroups of some work areas. The work areas are: 1. preparation of materials, 2. production of technical rubber goods, 3. production of tyres, 4. storage and dispatch, 5. maintenance, 6. others. Standardized mortality ratios (SMR) and Cox proportional hazards models were calculated for each of the work areas (>1 year of employment in the respective work area). Hazard rate ratios were adjusted for age (time marker) and stratified for year of hire (1950-1959, > or =1960) and years of employment in the respective work area (1-9 years, > or =10 years); years of employment were lagged 10 years to account for latency. RESULTS: Compared to the national reference population mortality from cancer of stomach (observed 44, SMR = 117; 95% CI: 85-157) and lung (observed 154, SMR = 123; 95% CI: 104-144) was slightly increased. Using internal controls we observed excess deaths from stomach cancer in work area 1 (relative risk [RR] = 2.3; 95% CI: 1.2-4.2) and from lung cancer in work areas 1 (RR = 1.7; 95% CI: 1.2-2.3), 2 (RR = 1.5; 95% CI: 1.1-2.1), and 3 (RR = 1.3; 95% CI: 0.9-1.8). On the basis of cumulative years of employment an exposure response relationship was observed for mortality from both cancer sites among a subcategory of work area 1: weighing and mixing. Increased risks were also seen for lung cancer among workers employed in production of technical rubber goods. CONCLUSION: Our results support an association between an excess mortality from stomach and lung cancer and employment in early production stages of rubber manufacturing, especially weighing and mixing. This may point to an aetiologic role of asbestos or carbon black. For stomach cancer additional risk factors, e.g. exposure to dust and talc, deserve further investigation. The results of the present study do not support a causal role of nitrosamines for stomach or lung cancer.

The relationship of per capita gross national product to the prevalence of symptoms of asthma and other atopic diseases in children (ISAAC).

BACKGROUND: Increasing prevalence and worldwide variation in asthma and other atopic diseases suggest the influence of environmental factors, at least one possibly related to socioeconomic wellbeing. This paper examines the relationship of symptoms of asthma, rhinitis and eczema with gross national product per capita (GNP per capita). METHODS: The prevalences of atopic symptoms in 6-7- and 13-14-year-old children were assessed in 91 centres (from 38 countries) and 155 centres (from 56 countries), respectively, in the International Study of Asthma and Allergy in Childhood (ISAAC). These symptoms were related to 1993 GNP per capita for each country as reported by the World Bank. The relationships between symptoms of atopic diseases and infant mortality, the human development index and 1982 GNP per capita were also considered. RESULTS: The countries in the lowest quartile of GNP per capita have the lowest median positive responses to all the questions on symptoms of asthma, rhinitis and eczema. There was a statistically significant positive association between wheeze in the last 12 months and GNP per capita in the 13-14-year age group, but not in the 6-7-year age group. There was also a positive association between GNP per capita and eczema in both age groups. CONCLUSIONS: The positive associations between GNP per capita and atopic symptoms being of only moderate strength suggests that the environmental factors are not just related to the wealth of the country.

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 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.

Climate and the prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in children.

AIMS: To investigate the association between climate and atopic diseases using worldwide data from 146 centres of the International Study of Asthma and Allergies in Childhood (ISAAC). METHODS: Between 1992 and 1996, each centre studied random samples of children aged 13-14 and 6-7 years (approx. 3000 per age group and centre) using standardised written and video questionnaires on symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema during the past 12 months. Data on long term climatic conditions in the centres were abstracted from one standardised source, and mixed linear regression models calculated to take the clustering of centres within countries into account. RESULTS: In Western Europe (57 centres in 12 countries), the prevalence of asthma symptoms, assessed by written questionnaire, increased by 2.7% (95% CI 1.0% to 4.5%) with an increase in the estimated annual mean of indoor relative humidity of 10%. Similar associations were seen for the video questionnaire and the younger age group. Altitude and the annual variation of temperature and relative humidity outdoors were negatively associated with asthma symptoms. The prevalence of eczema symptoms correlated with latitude (positively) and mean annual outdoor temperature (negatively). CONCLUSIONS: Results suggest that climate may affect the prevalence of asthma and atopic eczema in children.

An occupational cohort mortality study of women in the German rubber industry: 1976 to 1991.

Few previous studies of workers in the rubber industry have focused on women. We examined patterns of mortality among 2871 women employed in one of five German rubber plants for at least 1 year on or after January 1, 1976, and observed through December 31, 1991. All-causes mortality was near that expected (standardized mortality ratio [lsqbSMR], 101; 95% confidence interval [CI], 87 to 118), but cancer mortality was decreased (SMR, 90; 95% CI, 70 to 115). Nevertheless, excesses were observed for mortality from stomach cancer (SMR, 156; 95% CI, 63 to 322), lung cancer (SMR, 140; 95% CI, 56 to 289), and lymphatic system cancers (SMR, 175; 95% CI, 48 to 448). Stronger associations were observed among sub-cohorts defined by time period hired. Despite limited numbers of deaths, modest excesses of mortality due to specific cancers were observed and are consistent with previous studies.

[Smoking among children and adolescents: a challenge for primary prevention]. / Die Rauchgewohnheiten von Kindern und Jugendlichen: Eine Herausforderung für die primäre Prävention.

The best way to prevent the deleterious health effects of cigarette smoking is helping children to refrain from starting the habit. As a part of a survey of the prevalence of asthma symptoms in children and adolescents, we investigated the smoking habits of grade seven and eight school children in Bochum, a city of approximately 400,000 people in northwestern Germany. A random sample of 2050 children (93%) answered a confidential questionnaire. Fifty-three percent of the children responded that they had ever smoked cigarettes and 26% indicated that they had smoked during the previous month. 10% of the teenagers smoked daily, and 5% smoked more than 10 cigarettes per day. The prevalence of active smoking during the previous month was more frequent among girls (28%) than among boys (23%), but slightly more boys (5%) than girls (4%) smoked more than 10 cigarettes per day. The prevalence of active smoking was increased among children living in families of lower socio-economic status or in households with smokers. The high prevalence of cigarette smoking among the school children in Bochum, Germany, emphasizes the need to develop and implement effective intervention programs for children and adolescents and to contribute to a social environment which is conductive to refraining from smoking.

Knowledge and attitudes towards hypertension and hypercholesterolemia in a population of southern Germany: results from a population survey in the Augsburg area.

The survey was conducted to assess knowledge and attitudes of a population in Southern Germany towards hypertension and hypercholesterolemia. A questionnaire, mailed to a random sample of 2000 citizens of the Augsburg area between 25 and 74 years of age, was responded by 67%. Knowledge about determinants and complications of hypertension or hypercholesterolemia was considerably high. Major deficiencies were found in knowledge about personal values and recommended definitions of the two risk factors. Fifty eight percent claimed to know their personal blood pressure value, but merely 14% reported to know their personal blood cholesterol value. Just 21% were able to give the correct definition of hypertension and 10% defined hypercholesterolemia correctly. People had more trust in the effect of lowering high blood pressure (54%) to prevent heart disease than in the effect of lowering high blood cholesterol (43%). Sixty percent claimed to take some kind of actions to control their blood pressure and blood cholesterol.

[Epidemiology of risks in the workplace]. / Epidemiologie der Risiken am Arbeitsplatz.

Epidemiologic studies of occupationally exposed subjects allow to detect diseases caused by the work environment and to identify hazardous exposures. They provide the basis for preventive measures and workers compensation. Occupational epidemiology traditionally emphasized the study of work related cancer. Long latency periods for the development of most cancers and limited information about the exposure history of the study subjects are problems for all study types. The specific advantages and limitations of different study designs are discussed. Research strategies in occupational epidemiology are demonstrated using as an example two studies from the American tire and rubber industry. The specific contributions of a historical cohort study and a nested case-control study, concerning the association between lymphosarcoma and exposure to solvents, are discussed. Experiences and first results from a historical cohort study in the German rubber industry are reported. Future research in occupational epidemiology should concentrate more on the study of work related morbidity such as musculoskeletal disorders, hearing loss, accidents and the influence of the work environment on the mental and physical well being. Modern research methods such as prospective cohort studies or workforce monitoring should be used more often. Prospective cohort studies provide quantitatively and qualitatively more precise information about exposures and potential confounders, e.g. cigarette smoking or alcohol consumption, than traditional study methods. The promising perspectives of biological markers warrant further research. The situation of occupational epidemiology in Germany can only be improved if all concerned parties and institutions realize the importance of occupational epidemiology. Laws concerning data confidentiality which seriously hamper epidemiologic research must be modified.

[Historical cohort study in the German rubber industry: goals, study design and data collection]. / Historische Kohortenstudie in der deutschen Kautschukindustrie: Zielsetzung, Studiendesign und Erhebungsverfahren.

A historical cohort study is carried out to investigate occupational hazards in the German rubber industry since 1991. We present and discuss the study objectives and study design features such as cohort definition, assessment of occupational exposure and selection of the reference population. Cohort enumeration, assessment of vital status and cause of death ascertainment are described. With approximately 2,800 deaths throughout the observation period 1981 to 1991 it will be possible also to study the occupational etiology of rare diseases.

Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison.

OBJECTIVES: To compare the prevalence of asthma and allergic disorders among children in Munich, western Germany, and Leipzig, eastern Germany, where environmental exposure, particularly air concentrations of sulphur dioxide and particulate matter, and living conditions have differed over the past 45 years. DESIGN: Prevalence surveys among school-children aged 9-11 years in Leipzig and Munich. Self completion of written questionnaire by the children's parents and lung function measurements. SUBJECTS: 1051 children in Leipzig and 5030 in Munich. SETTING: Primary schools. MAIN OUTCOME MEASURES: Reported lifetime prevalence of asthma and allergic disorders, and bronchial hyperresponsiveness assessed by cold air inhalation challenge. RESULTS: The lifetime prevalence of asthma diagnosed by a doctor was 7.3% (72) in Leipzig and 9.3% (435) in Munich; prevalence of wheezing were 20% (191) and 17% (786) respectively. The prevalence of diagnosed bronchitis was higher in Leipzig than Munich (30.9% (303) v 15.9% (739); p < 0.01). A significant drop in forced expiratory volume (> 9%) after cold air challenge was measured in 6.4% (57) of children in Leipzig and in 7.7% (345) of those in Munich. Hay fever (2.4% (24) v 8.6% (410); p < 0.01) and typical symptoms of rhinitis (16.6% (171) v 19.7% (961); p < 0.05) were reported less often in Leipzig than in Munich. CONCLUSIONS: No significant differences were seen in the lifetime prevalence of asthma, wheezing, and bronchial hyperresponsiveness between children in Leipzig and Munich. The lifetime prevalence of bronchitis was higher in Leipzig than in Munich. The lower prevalence rates of allergic disorders in Leipzig could point toward aetiological factors that are associated with Western lifestyle and living conditions.