Body mass index change and atopic diseases are not always associated in children and adolescents.

BACKGROUND: Several studies have suggested an association between the increasing prevalence of allergic diseases and dietary factors. OBJECTIVE: To prospectively explore the association between changes in body mass index (BMI) and symptoms of asthma, rhinitis, rhinoconjunctivitis, and atopic dermatitis to find out whether an increase in BMI increases the risk of developing atopic diseases in adolescence. METHODS: Comprehensive questionnaires and anthropometric measurements were applied in a random subsample of the International Study of Asthma and Allergies in Childhood phase II (1995-1996, 9 to 11 years of age) in Germany. Of these participants, 1,794 could be followed up in 2002 to 2003 in the Study on Occupational Allergy Risks (16 to 18 years of age). The associations between changes of BMI from baseline to follow-up and incident and persistent respiratory diseases and atopic dermatitis were assessed. RESULTS: In logistic regression analyses, weight change in either direction was not statistically significantly associated with the incidence or persistence of any of the diseases of interest except for rhinitis. An increase in BMI was linked to an increased risk of incident rhinitis (odds ratio 1.9, 95% confidence interval 1.2-2.9). CONCLUSION: These results indicate a nonsignificant trend between increased body weight and risk of atopic diseases. Aside from limitations owing to a small subgroup of obese participants and questionnaire-based asthma diagnosis, reasons might be related to an interaction between BMI and hormonal influences, age, and duration and severity of overweight. The results underline that BMI does not necessarily play a decisive role in the course of atopic diseases in all populations.

Short-term effects of PM10 and NO2 on respiratory health among children with asthma or asthma-like symptoms: a systematic review and meta-analysis.

OBJECTIVE: Our goal was to quantify the short-term effects of particulate matter with aerodynamic diameter < or = 10 microm (PM10) and nitrogen dioxide (NO2) on respiratory health of asthmatic children from published panel studies, and to investigate the influence of study and population characteristics as effect modifiers. DATA EXTRACTION: After a systematic literature review, we extracted quantitative estimates of the association of PM10 and/or NO2 with respiratory symptoms and peak expiratory flow (PEF). Combined effect estimates for an increase of 10 microg/m3 were calculated by random effects meta-analysis for all studies and for different strata defined by study characteristics. The effect of publication bias was investigated with Egger's and Begg's tests and "trim-and-fill" analyses. DATA SYNTHESIS: We identified 36 studies; 14 were part of the European Pollution Effects on Asthmatic Children in Europe (PEACE) study. Adverse associations of PM10 with asthma symptoms were statistically significant [odds ratio (OR) = 1.028; 95% confidence interval (CI), 1.006-1.051]. There were also associations, although not statistically significant, of PM10 with cough (OR = 1.012; 95% CI, 0.997-1.026) and on PEF (decrease of -0.082 L/min; 95% CI, -0.214 to 0.050). NO2 had statistically significant associations with asthma symptoms in the overall analysis considering all possible lags (OR = 1.031; 95% CI, 1.001-1.062), but not when we evaluated only the 0-1 lag. We found no publication bias, although it appeared when excluding the PEACE studies. When we applied the trim-and-fill method to the data set without the PEACE studies, the results were similar to the overall estimates from all studies. There was an indication for stronger PM10 associations for studies conducted in summer, outside of Europe, with longer lags, and in locations with higher NO2 concentrations. CONCLUSIONS: We found clear evidence of effects of PM10 on the occurrence of asthma symptom episodes, and to a lesser extent on cough and PEF. The results for NO2 are more difficult to interpret because they depend on the lag times examined. There was an indication of effect modification by several study conditions.

Ambient particulate pollution and the world-wide prevalence of asthma, rhinoconjunctivitis and eczema in children: Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC).

OBJECTIVES: To investigate the effect of ambient particulate matter on variation in childhood prevalence of asthma, rhinoconjunctivitis and eczema. METHODS: Prevalences of asthma, rhinoconjunctivitis and eczema obtained in Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) were matched with city-level estimates of residential PM(10) obtained from a World Bank model. Associations were investigated using binomial regression adjusting for GNP per capita and for clustering within country. For countries with more than one centre, a two stage meta-analysis was carried out. The results were compared with a meta-analysis of published multi-centre studies. RESULTS: Annual concentrations of PM(10) at city level were obtained for 105 ISAAC centres in 51 countries. After controlling for GNP per capita, there was a weak negative association between PM(10) and various outcomes. For severe wheeze in 13-14-year-olds, the OR for a 10 microg/m(3) increase in PM(10) was 0.92 (95% CI 0.84 to 1.00). In 24 countries with more than one centre, most summary estimates for within-country associations were weakly positive. For severe wheeze in 13-14-year-olds, the summary OR for a 10 microg/m(3) increase in PM(10) was 1.01 (0.92 to 1.10). This result was close to a summary OR of 0.99 (0.91 to 1.06) obtained from published multi-centre studies. CONCLUSIONS: Modelled estimates of particulate matter at city level are imprecise and incomplete estimates of personal exposure to ambient air pollutants. Nevertheless, our results together with those of previous multi-centre studies, suggest that urban background PM(10) has little or no association with the prevalence of childhood asthma, rhinoconjunctivitis or eczema either within or between countries.

Determinants of obesity in the Ulm Research on Metabolism, Exercise and Lifestyle in Children (URMEL-ICE).

We investigated the prevalence of overweight and obesity in German schoolchildren and analyzed determinants of overweight. In the context of a randomized intervention study, a baseline cross-sectional assessment was carried out in 2006. During a physical examination, height, weight, skin fold thickness, and upper arm and waist circumferences were measured according to a standardized protocol among 1.079 children aged 6-9 years. Overweight and obesity were classified according to the definitions of the International Obesity Task Force. Parents completed a questionnaire on potential determinants of overweight. Logistic regression models were calculated for determinants of overweight and obesity. The prevalence of overweight was 16.5% in boys and 17.3% in girls and of obesity 3.5% and 3.6%, respectively. Migration (29.4 %) was correlated with overweight and obesity. In particular, among boys with migration background, overweight (24.0%) and obesity (6.6%) were highly prevalent. Higher obesity prevalence was associated with maternal smoking during pregnancy, parental overweight, and low parental education. Indicators for physical inactivity such as watching television more than 1 h per weekday, participation in club sports less than once a week, consumption of sweetened drinks (>or=3 times per week), and skipping breakfast before school were associated with childhood obesity. Our results provide further evidence that parental factors such as migration background and education are strongly associated with body mass of the offspring. Physically inactive children with regular consumption of sweetened drinks and no breakfast were prone to be overweight or obese. Changes of these lifestyle factors as targets of interventions are promising to prevent childhood obesity.

Association of apolipoproteins with symptoms of asthma and atopy among schoolchildren.

BACKGROUND: There is evidence for an association between serum cholesterol concentrations and asthma, but little is known about the underlying mechanisms. We explored the associations between serum apolipoprotein concentrations and symptoms of asthma and atopy. METHODS: In a population-based cross-sectional study among 10-year-old schoolchildren (n = 462), plasma concentrations of apolipoprotein AI (apoAI) and apolipoprotein B (apoB) were measured. Information on disease symptoms and diagnoses was collected by parental questionnaire. Multivariate logistic regression models were used to analyse the data. RESULTS: High plasma apoAI concentrations (>or=1.74 g/l) were associated with high prevalence of wheeze (OR 3.65; 95% CI 1.43-9.33), and a trend was seen with asthma (OR 3.35; 95% CI 0.94-11.93). In linear analyses, plasma apoAI concentrations were positively related to wheeze (beta-coefficient = 3.20; p = 0.045) and non-atopic wheeze (beta-coefficient = 4.47; p = 0.036), and a trend was found for asthma (beta-coefficient = 3.29; p = 0.099). Overall, plasma apoB concentrations were not associated with either symptoms of asthma or allergy. CONCLUSION: Our results support the hypothesis that high apoAI is associated with the manifestation of asthma and atopy. The underlying pathomechanism still remains to be fully elucidated, but suggests that immune mechanisms may play a central role. However, our results are based on a small study sample and larger studies are warranted to confirm these observations.

Associations of adipokines with asthma, rhinoconjunctivitis, and eczema in German schoolchildren.

There is growing evidence for an association between obesity and asthma, but little is known about the underlying mechanisms. We hypothesized that high plasma leptin and low plasma adiponectin concentrations might be related to asthma and allergies in children. Plasma leptin and adiponectin concentrations were measured in a cross-sectional study involving 462 children aged 10 years. Information on disease symptoms and diagnosis was collected by parental questioning. Multivariate linear and logistic regression models were used to assess the association between biomarkers and disease. High leptin levels were associated with increased lifetime prevalence of asthma [odds ratio (OR): 3.76; 95% confidence interval (CI): 1.42-9.92]. The relationship was particularly strong for non-atopic asthma (OR: 5.51; 95% CI: 1.99-17.51). No associations were observed between plasma leptin levels and hay fever, and rhinoconjunctivitis. Low adiponectin levels were associated with increased prevalence of both symptoms of atopic dermatitis (OR: 3.23; 95% CI: 1.28-7.76) and ever-diagnosed eczema (OR: 2.35; 95% CI: 1.13-4.89). In girls and non-atopic children, stronger associations for both leptin and adiponectin levels with asthma than in boys and atopic children were observed. These results suggest that adipokines may contribute to increased asthma and allergy risk in obese subjects. Stronger associations among girls with non-atopic asthma may indicate diverse pathological mechanisms.

Toll-like receptor heterodimer variants protect from childhood asthma.

BACKGROUND: Early exposure to microbes reduces the risk for asthma. Toll-like receptors (TLRs) represent a major group of receptors for the specific recognition of pathogen-associated molecular patterns of microbes capable of activating innate and adaptive immunity. OBJECTIVE: Because TLRs can influence key events in the induction and perpetuation of asthma and atopy, we sought to determine whether genetic alterations in TLR genes affect asthma risk. METHODS: We systematically evaluated putatively functional genetic variants in all 10 human TLR genes for their association with different asthma phenotypes in a case-control study (n = 1872) by using matrix-assisted laser desorption/ionization time-of-flight genotyping. For polymorphisms showing association with atopic asthma, effects on gene and protein expression were studied by means of RT-PCR and flow cytometry ex vivo. T-cell cytokine production was evaluated by means of ELISA after stimulation of the respective TLRs with specific ligands. RESULTS: Protective effects on atopic asthma were identified for single nucleotide polymorphisms in TLR1 (odds ratio [OR], 0.54; 95% CI, 0.37-0.81; P = .002), TLR6 (OR, 0.54; 95% CI, 0.37-0.79; P = .003), and TLR10 (OR, 0.58; 95% CI, 0.39-0.86; P = .006), all capable of forming heterodimers with TLR2. Effects remained significant after correction for multiple comparisons. PBMCs of minor allele carriers showed increased levels of the respective TLR mRNA and proteins, augmented inflammatory responses, increased T(H)1 cytokine expression, and reduced T(H)2-associated IL-4 production after specific stimulation. CONCLUSION: These results suggest that functional relevant TLR1 and TLR6 variants are directly involved in asthma development.

Endotoxin levels in cow's milk samples from farming and non-farming families - the PASTURE study.

BACKGROUND: Children from farming families have less allergies than their peers. Consumption of farm milk or unpasteurized milk has been shown to explain (part of) the farming effect or protect against allergies independent of farming status. OBJECTIVES: We investigated whether the protective effect of farm milk consumption can be explained by higher levels of bacterial endotoxin in milk. METHODS: We measured endotoxin in approximately 400 farm milk and shop milk samples from farming and non-farming families, respectively, with the kinetic chromogenic Limulus Amebocyte Lysate test and compared endotoxin levels between groups defined by farming status and type of milk (farm milk/shop milk). RESULTS: Endotoxin levels were significantly higher in milk samples from non-farming families compared to farming families [adjusted geometric means ratio (95% confidence interval)=2.61 (1.53-4.43)]. No significant difference in endotoxin levels was found between shop milk and farm milk samples [adjusted geometric means ratio (95% confidence interval)=1.56 (0.94-2.58)]. The difference between farming and non-farming families could be explained completely for farm milk and partially for shop milk by storage conditions and temperature during transportation to the fieldworker's home. CONCLUSION: The farming effect and the effect of farm milk consumption cannot be explained by higher levels of endotoxin in milk from farmers and farm milk, respectively.

Filaggrin mutations, atopic eczema, hay fever, and asthma in children.

BACKGROUND: Mutations in the filaggrin gene (FLG) have been shown to play a significant role in ichthyosis vulgaris and eczema, 2 common chronic skin diseases. However, their role in the development of other atopic diseases such as asthma and rhinitis has not yet been clarified in large population-based studies. OBJECTIVES: To study the effect of FLG mutations at the population level and their effect on other atopic phenotypes. METHODS: Association analysis of the 2 common FLG-null mutations R501X and 2282del4 and 3 recently identified rare FLG variants (R2447X, S3247X, 3702delG) was performed on our cross-sectional population of German children (n = 3099) recruited as part of the International Study of Asthma and Allergies in Childhood II in Munich (n = 1159) and Dresden (n = 1940). RESULTS: FLG variants increased the risk for eczema more than 3-fold (odds ratio [OR], 3.12; 95% CI, 2.33-4.173; P = 2.5 x 10(-14); population-attributable risk, 13.5%). Independent of eczema, FLG mutations conferred a substantial risk for allergic rhinitis (OR, 2.64; 95% CI, 1.76-4.00; P = 2.5 x 10(-6); population-attributable risk, 10.8%). Nasal biopsies demonstrated strong filaggrin expression in the cornified epithelium of the nasal vestibular lining, but not the transitional and respiratory nasal epithelia. In contrast, the association with asthma (OR, 1.79; 95% CI, 1.19-2.68; P = .0048) was restricted to asthma occurring in the context of eczema, and there was a strong association with the complex phenotype eczema plus asthma (OR, 3.49; 95% CI, 2.00-6.08; P = 1.0 x 10(-5)). CONCLUSION: Our results suggest that FLG mutations are key organ specific factors predominantly affecting the development of eczema and confer significant risks of allergic sensitization and allergic rhinitis as well as asthma in the context of eczema.

Prevalence and cluster of cardiometabolic biomarkers in overweight and obese schoolchildren: results from a large survey in southwest Germany.

BACKGROUND: Obesity is associated with substantial metabolic changes and subclinical inflammation. We explored associations between body mass index (BMI) and cardiometabolic biomarkers and their clustering in overweight and obese schoolchildren. METHODS: In this population-based, cross-sectional study among 450 children 10 years old, we measured adiponectin, leptin, inflammatory markers, apolipoprotein (apo) AI and B, and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)). Except for adiponectin and apoAI (10th percentile) the 90th percentile was used as cutoff point. Body weight was categorized in age- and sex-specific BMI percentiles and overweight and obesity according to International Obesity Task Force definitions. RESULTS: In linear regression models, all cardiometabolic markers except apoB were statistically significantly associated with overweight. In logistic regression models, compared with the reference category (25th-75th percentile of BMI), overweight was associated with increased concentrations of leptin [odds ratio (OR) 59.80; 95% CI 16.68-214.39], C-reactive protein (6.30; 2.95-13.45), fibrinogen (2.82; 1.33-6.01), and low apoAI (2.62; 1.19-5.75). Overweight was positively associated with interleukin-6, Lp-PLA(2), and apoB concentrations and inversely with adiponectin concentrations. Most importantly, in obese children 35% showed one, 20% two, 10% three, and 15% four or more abnormal cardiometabolic biomarkers. The number of abnormal cardiometabolic markers increased in overweight (p(trend) <0.001) and obese (p(trend) <0.001) children. CONCLUSIONS: Overweight and obesity in children are associated with complex metabolic changes and a low-grade inflammatory response, and thus might not only accelerate cardiovascular disease later on, but may also be associated with the initiation of atherosclerosis in early life.

IRF-1 gene variations influence IgE regulation and atopy.

RATIONALE: The development of atopic diseases is characterized by skewed immune responses to common allergens. Only recently, interferons have been identified to play a crucial role in these mechanisms. OBJECTIVES: Because interferon regulatory factor (IRF)-1 is critical for interferon expression, we tested the hypotheses that genetic changes in this essential transcription factor may have consequences for the development of atopy. METHODS: The IRF-1 gene locus was resequenced in 80 human chromosomes. Association and haplotype analyses were performed in a cross-sectional study population of German children from Dresden (n = 1,940), and results were replicated in a second population sample from Munich (n = 1,159), both part of the ISAAC (International Study of Asthma and Allergy in Childhood) phase II. Promoter polymorphism effects were studied using electrophoretic mobility shift assay and colorimetric binding assays. Allele-specific IRF-1 gene expression was studied in vitro using luciferase reporter assays, whereas we assessed ex vivo expression of IRF-1 by real-time polymerase chain reaction and IFN-gamma protein by Luminex technology (Bio-Rad, Hercules, CA). Statistical analyses were performed using SAS/Genetics (SAS 9.1.3; SAS Institute, Cary, NC). MEASUREMENTS AND MAIN RESULTS: By resequencing, 49 polymorphisms were identified within the IRF-1 gene. Four blocks containing 11 polymorphisms were significantly associated with atopy, total IgE levels, or specific IgE levels in both populations (P < 0.05). Two polymorphisms changed transcription factor binding of nuclear factor (NF)-kappaB and EGR1 (early growth response 1) to the IRF-1 promoter, altered gene expression in vitro (P = 0.0004), and altered IRF-1 mRNA and IFN-gamma protein expression ex vivo. CONCLUSIONS: Our results suggest that functionally relevant IRF-1 polymorphisms influence atopy risk, potentially by altering transcription factor binding, IRF-1 gene expression, and IFN-gamma regulation.

The role of atopic sensitization in flexural eczema: findings from the International Study of Asthma and Allergies in Childhood Phase Two.

BACKGROUND: The association between allergic sensitization and eczema has been debated for years. OBJECTIVE: We sought to determine and compare the strength of the association between allergen skin sensitization and eczema in both developing and industrialized countries. METHODS: Twenty-eight thousand five hundred ninety-one randomly selected 8- to 12-year-old schoolchildren in 20 countries were physically examined for flexural eczema and received skin prick testing to Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat hair, Alternaria tenuis, mixed tree and grass pollen, and allergens of local relevance. RESULTS: The age- and sex-adjusted odds ratios (ORs) for a positive association between flexural eczema and atopy ranged between 0.74 (95% CI, 0.31-1.81) and 4.53 (95% CI, 1.72-11.93), with a significantly stronger association in affluent compared with nonaffluent countries (combined age- and sex-adjusted OR(affluent) = 2.69 [95% CI, 2.31-3.13] and OR(nonaffluent) = 1.17 [95% CI, 0.81-1.70]). The combined population attributable fraction for atopy in flexural eczema was 27.9% for affluent and 1.2% for nonaffluent-country centers. Correlating gross national per-capita income with either ORs or population attributable fractions for atopy in flexural eczema confirmed a highly significant positive association (P = .006 and P < .001, respectively). CONCLUSIONS: The association between atopy and flexural eczema is weak and more variable than previously suggested, and the strength of this association is positively linked to gross national income.

Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma.

Asthma is caused by a combination of poorly understood genetic and environmental factors. We have systematically mapped the effects of single nucleotide polymorphisms (SNPs) on the presence of childhood onset asthma by genome-wide association. We characterized more than 317,000 SNPs in DNA from 994 patients with childhood onset asthma and 1,243 non-asthmatics, using family and case-referent panels. Here we show multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P value of P < 10(-12). In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P < 10(-22)) in cis with transcript levels of ORMDL3, a member of a gene family that encodes transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.

Atopic sensitization and the international variation of asthma symptom prevalence in children.

RATIONALE: Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further. OBJECTIVES: To investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma. METHODS: Cross-sectional studies of random samples of 8- to 12-year-old children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 31,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI). MEASUREMENTS AND MAIN RESULTS: The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient rho = 0.50, P = 0.006, and rho = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (rho = 0.47, P = 0.01). CONCLUSIONS: The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.

CX3CR1 polymorphisms are associated with atopy but not asthma in German children.

Chemokines and their receptors are involved in many aspects of immunity. Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration and macrophage differentiation as well as T cell-dependent inflammation. Two common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk for asthma. Using matrix-assisted laser desorption/ionization time-of-flight technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross-sectional population of German children from Munich (n = 1,159) and Dresden (n = 1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63-0.96; p = 0.017) and for 280Met an odds ratio of 0.71 (95% confidence interval 0.56-0.89; p = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. Potentially, other factors such as environmental effects may modify the role of CX3CR1 polymorphisms.

Analyses of case-control data for additional outcomes.

Consider a case-control study in which prevalent cases of a given disease define the index series and members of the base population without the disease are sampled to provide the referent series. Information on a set of explanatory variables (eg, genotypes) is collected at great cost for cases and controls. The objective of the study is to evaluate the relationship between case status and the explanatory variables. Subsequently, an investigator notes that the prevalence of a second disease was measured for the members of the index and referent series. The investigator wishes to make efficient use of the available data by assessing the relationship between this second disease and the set of explanatory variables. In this paper, we discuss 2 analytic approaches that might be used to assess associations between the explanatory variables and an outcome other than the original disease. One is through the inclusion of a design variable for original disease status as a covariate; and, the second is through weighted logistic regression using the inverse of the sampling fractions as the weights. The latter approach allows the investigator to derive an estimate of association between the explanatory variables and the second disease without adjustment for the first disease. Weighted logistic regression methods are readily implemented using available statistical packages.

Increasing life expectancy in Germany: quantitative contributions from changes in age- and disease-specific mortality.

BACKGROUND: Between 1962 and 2002 the average life expectancy in Germany has increased from 67.1 years to 75.6 years in men and from 72.7 years to 81.3 in women. METHODS: The cumulative and annual contributions of different age- and disease-groups on life expectancy were calculated using Pollard's actuarial method of decomposing mortality rates. Mortality data were provided by the German Statistical Office. RESULTS: Considering the cumulative contribution over the period of 40 years, the largest contributions came from persons with at least 65 years of age (2.9 years in men and 4.0 years in women). Reductions in cardiovascular disease mortality had the greatest cumulative impact on life expectancy (2.7 years in men and 3.0 years in women). The contribution from reduced cancer mortality on life expectancy was substantially lower (0.6 and 0.9 years, respectively). The annual contributions of several disease-groups varied considerably over time. The positive contribution from cardiovascular diseases started only after 1970, and in men it became solid only after 1980. Regarding malignant neoplasms, the largest cumulative contribution came from stomach cancer (0.4 in both sexes). The annual analyses showed increasing contributions from reduced cancer mortality after 1990. These were strongly influenced by lung, stomach, prostate and colorectal cancer in men, and by breast, colorectal and stomach cancer in women. CONCLUSIONS: While life expectancy has increased by about 2.2 years per decade the observed variations in the age- and disease-specific contributions over time have implications for future health care planning and prevention strategies.

Sleep duration and smoking cessation in student nurses.

STUDY OBJECTIVES: To assess predictors of smoking cessation in young adults. DESIGN: Prospective study of smoking cessation. SETTING: 32 Schools of Nursing in Southwest Germany. PARTICIPANTS: 500 student nurses, 82% female, median age 19.9 years, who smoked at baseline. MEASUREMENTS AND RESULTS: Smoking status and potential predictors of smoking cessation were assessed by two questionnaires within a median time interval of 13.1 months. At follow-up, 10.6% of the participants had stopped smoking. Sleep duration was positively associated with smoking cessation. One hour additional sleep per night at baseline increased the relative probability to stop smoking by 1.48 (95% CI 1.14-1.93). The number of cigarettes per day and the 'self-assessment of smoking behaviour in 5 years' were additional factors predicting smoking cessation. CONCLUSIONS: Sleep duration may influence smoking cessation and may have relevance for advising people who want to quit smoking.

Assessing bronchial responsiveness to hypertonic saline using the stepwise protocol of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC II).

Measurement of bronchial responsiveness to hypertonic saline was applied in 22 study centers worldwide as part of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two). Because the amount of inhaled saline was difficult to standardize during the stepwise protocol with inhalation periods of increasing duration, we evaluated different statistical procedures based on inhalation time in relation to wheeze and current asthma. Data on random samples on 9 to 11-year-old children (n = 1,418) from two German centers were analyzed. The following statistical approaches were evaluated: (1) bronchial hyperreactivity (BHR) defined dichotomously as a fall in FEV1 (forced expiratory volume in 1 s) >or=15%; (2) PT15: the provocation time causing BHR using survival-analyses methods; (3) time-response-slope (continuous) of the individual FEV1-courses calculated by a linear model after comparing different mathematical models. The sensitivity and specificity of BHR versus current asthma were 47% and 87%, respectively. Analyses of the provocation time indicated an increased risk (adjusted hazard-ratio: 4.3; 95% CI: 2.8-6.5) for a fall in FEV1 >or= 15% among children with current asthma in comparison to those without. The time-response-slope differed markedly between children with and without wheeze and current asthma (P < 0.0001). BHR is meaningful and relatively easy to use, but has low sensitivity. Time-response-slopes utilize the available information from the stepwise protocol better than BHR and survival-analysis based on PT15. Response parameters based on inhalation time discriminate well between children with and without asthma and will be compared in the analyses of ISAAC Phase Two data.

Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys.

BACKGROUND: Data for trends in prevalence of asthma, allergic rhinoconjunctivitis, and eczema over time are scarce. We repeated the International Study of Asthma and Allergies in Childhood (ISAAC) at least 5 years after Phase One, to examine changes in the prevalence of symptoms of these disorders. METHODS: For the ISAAC Phase Three study, between 2002 and 2003, we did a cross-sectional questionnaire survey of 193,404 children aged 6-7 years from 66 centres in 37 countries, and 304,679 children aged 13-14 years from 106 centres in 56 countries, chosen from a random sample of schools in a defined geographical area. FINDINGS: Phase Three was completed a mean of 7 years after Phase One. Most centres showed a change in prevalence of 1 or more SE for at least one disorder, with increases being twice as common as decreases, and increases being more common in the 6-7 year age-group than in the 13-14 year age-group, and at most levels of mean prevalence. An exception was asthma symptoms in the older age-group, in which decreases were more common at high prevalence. For both age-groups, more centres showed increases in all three disorders more often than showing decreases, but most centres had mixed changes. INTERPRETATION: The rise in prevalence of symptoms in many centres is concerning, but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring. The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders.