Can environment or allergy explain international variation in prevalence of wheeze in childhood?

Asthma prevalence in children varies substantially around the world, but the contribution of known risk factors to this international variation is uncertain. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two studied 8-12 year old children in 30 centres worldwide with parent-completed symptom and risk factor questionnaires and aeroallergen skin prick testing. We used multilevel logistic regression modelling to investigate the effect of adjustment for individual and ecological risk factors on the between-centre variation in the prevalence of recent wheeze. Adjustment for single individual-level risk factors changed the centre-level variation from a reduction of up to 8.4% (and 8.5% for atopy) to an increase of up to 6.8%. Modeling the 11 most influential environmental factors among all children simultaneously, the centre-level variation changed little overall (2.4% increase). Modelling only factors that decreased the variance, the 6 most influential factors (synthetic and feather quilt, mother's smoking, heating stoves, dampness and foam pillows) in combination resulted in a 21% reduction in variance. Ecological (centre-level) risk factors generally explained higher proportions of the variation than did individual risk factors. Single environmental factors and aeroallergen sensitisation measured at the individual (child) level did not explain much of the between-center variation in wheeze prevalence

Lack of evidence for a protective effect of prolonged breastfeeding on childhood eczema: lessons from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two

Background: Exclusive breastfeeding for at least 4 months is recommended by many governments and allergy organizations to prevent allergic disease. Objectives: To investigate whether exclusive breastfeeding protects against childhood eczema. Methods: Study subjects comprised 51,119 randomly selected 8- to 12-year-old schoolchildren in 21 countries. Information on eczema and breastfeeding was gathered by parental questionnaire. Children were also examined for flexural eczema and underwent skin prick testing. Odds ratios (ORs) were calculated for each study centre and then pooled across populations. Results: There was a small increase in the risk of reported 'eczema ever' in association with 'breastfeeding ever' and breastfeeding 6 months (pooled adjusted OR 1·09, 95% CI 0·94-1·26). Risk estimates were very similar for exclusive breastfeeding 4 months and for eczema symptoms in the past 12 months and eczema on skin examination. As for more severe eczema, breastfeeding per se conveyed a risk reduction on sleep disturbed eczema (pooled adjusted OR 0·71, 95% CI 0·53-0·96), but this effect was lost where children had been exclusively breastfed for > 4 months (pooled adjusted OR 1·02, 95% CI 0·67-1·54). Allergic sensitization and a history of maternal allergic disease did not modify any of these findings. Conclusions: Although there was a protective effect of ever having been breastfed on more severe disease, we found no evidence that exclusive breastfeeding for 4 months or longer protects against eczema. Our results are consistent with findings from a recent systematic review of prospective studies. The U.K. breastfeeding guidelines with regard to eczema should be reviewed. Intervention studies are now required to explore how and when solids should be introduced alongside breastfeeding to aid protection against eczema and other allergic diseases

Effect of diet on asthma and allergic sensitisation in the International Study on Allergies and Asthma in Childhood (ISAAC) Phase Two

Background: The increasing prevalence of asthma and allergy might be related to diet, particularly in Western countries. A study was undertaken to assess the association between dietary factors, asthma and allergy in a large international study including objective measurements of atopy. Methods: Between 1995 and 2005, cross-sectional studies were performed in 29 centres in 20 countries. Parental questionnaires were used to collect information on allergic diseases and exposure factors and data from 50 004 randomly selected schoolchildren (8-12 years, 29 579 with skin prick testing) were analysed. Random effect models for meta-analysis were applied to calculate combined ORs. Results: Fruit intake was associated with a low prevalence of current wheeze in affluent (OR(adj) 0.86, 95% CI 0.73 to 1.02) and non-affluent countries (OR(adj) 0.71, 95% CI 0.57 to 0.88). Consumption of fish in affluent countries (OR(adj) 0.85, 95% CI 0.74 to 0.97) and of cooked green vegetables in non-affluent countries (OR(adj) 0.78, 95% CI 0.65 to 0.95) was associated with a lower prevalence of current wheeze. Overall, more frequent consumption of fruit, vegetables and fish was associated with a lower lifetime prevalence of asthma, whereas high burger consumption was associated with higher lifetime asthma prevalence. None of the food items was associated with allergic sensitisation. Except for fruit juice and fruit consumption, no associations were found with atopic wheeze. Food selection according to the 'Mediterranean diet' was associated with a lower prevalence of current wheeze and asthma ever (p(trend)=0.03). Conclusion: Diet is associated with wheeze and asthma but not with allergic sensitisation in children. These results provide further evidence that adherence to the 'Mediterranean diet' may provide some protection against wheeze and asthma in childhood

Association of pertussis and measles infections and immunizations with asthma and allergic sensitization in ISAAC Phase Two

Background: Many studies report that damp housing conditions are associated with respiratory symptoms. Less is known about mechanisms and possible effect modifiers. Studies of dampness in relation to allergic sensitization and eczema are scarce. Objective: We study the influence of damp housing conditions world-wide on symptoms and objective outcomes. Methods: Cross-sectional studies of 8-12-year-old children in 20 countries used standardized methodology from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC). Symptoms of asthma, rhinitis and eczema, plus residential exposure to dampness and moulds, were ascertained by parental questionnaires (n = 46 051). Skin examination, skin prick tests (n = 26 967) and hypertonic saline bronchial challenge (n = 5713) were performed. In subsamples stratified by wheeze (n = 1175), dust was sampled and analysed for house dust mite (HDM) allergens and endotoxin. Results: Current exposure to dampness was more common for wheezy children (pooled odds ratio 1.58, 95% CI 1.40-1.79) and was associated with greater symptom severity among wheezers, irrespective of atopy. A significant (P < 0.01) adverse effect of dampness was also seen for cough and phlegm, rhinitis and reported eczema, but not for examined eczema, nor bronchial hyperresponsiveness. HDM sensitization was more common in damp homes (OR 1.16, 1.03-1.32). HDM-allergen levels were higher in damp homes and were positively associated with HDM-sensitization, but not wheeze. Conclusion: A consistent association of dampness with respiratory and other symptoms was found in both affluent and non-affluent countries, among both atopic and non-atopic children. HDM exposure and sensitization may contribute, but the link seems to be related principally to non-atopic mechanisms

Overweight/Obesity and Respiratory and Allergic Disease in Children: International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two

Background: Childhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated. Methods: Cross-sectional studies of stratified random samples of 8-12-year-old children (n = 10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated. Results: Overweight (odds ratio = 1.14, 95%-confidence interval: 0.98; 1.33) and obesity (odds ratio = 1.67, 95%-confidence interval: 1.25; 2.21) were related to wheeze. The relationship was stronger in affluent than in non-affluent centres. Similar results were found for cough and phlegm, rhinitis and eczema but the associations were mostly driven by children with wheeze. There was a clear association of overweight and obesity with airways obstruction (change in FEV1/FVC, -0.90, 95%-confidence interval: -1.33%; -0.47%, for overweight and -2.46%, 95%-confidence interval: -3.84%; -1.07%, for obesity) whereas the results for the other objective markers, including atopy, were null. Conclusions: Our data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries. Moreover, body mass index is associated with an objective marker of airways obstruction (FEV1/FVC) but no other objective markers of respiratory and allergic disorders

Tuberculosis, bacillus Calmette–Guérin vaccination, and allergic disease: Findings from the International Study of Asthma and Allergies in Childhood Phase Two

Some have suggested a protective effect of tuberculosis (TB) infection on allergic disease risk, but few studies have examined the association between the two. We therefore investigated whether TB disease and bacillus Calmette-Guérin (BCG) vaccination in early life protect against allergic disease. Information on allergic disease symptoms, past TB disease, and BCG vaccination as well as potential confounding factors was gathered by parental questionnaire from a randomly selected subset of 23,901 8- to 12-yr-old schoolchildren in 20 centers in both developed and developing countries. Children were also physically examined for flexural eczema and underwent skin prick testing. Pooled odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) across study centers were calculated, using random effects meta-analysis models. There were 245 (1.0%) reported cases of TB disease, and 66.3% (15,857) of all children received the BCG vaccine. Asthma, hay fever, and flexural eczema symptoms in the past year as well as flexural eczema on skin examination were all positively linked to a history of TB (adjusted pooled OR 'wheeze in the past year' = 2.27, 95% CI 1.52-3.41; adjusted pooled OR 'hay fever symptoms in the past year' = 2.23, 1.22-4.09; adjusted pooled OR 'flexural eczema symptoms in the past year' = 3.21, 2.01-5.12; adjusted pooled OR 'flexural eczema on skin examination' = 4.04, 1.71-9.56). Even higher risk estimates were seen for severe asthma and eczema symptoms [adjusted OR = 4.02 (2.17-7.47) and adjusted OR = 6.31 (2.19-18.17), respectively]. There was no significant association between past TB and skin prick test positivity (adjusted pooled OR = 1.32, 0.87-2.02). BCG vaccination during the first year of life was also not associated with any of the allergy outcomes. We found a uniform positive association between TB and all allergic disease outcomes, including eczema on skin examination. As this was a cross-sectional study, it is unclear whether this positive association is attributable to a causal relationship, and further longitudinal studies are required

Dampness and moulds in relation to respiratory and allergic symptoms in children: results from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two)

Background: Many studies report that damp housing conditions are associated with respiratory symptoms. Less is known about mechanisms and possible effect modifiers. Studies of dampness in relation to allergic sensitization and eczema are scarce. Objective: We study the influence of damp housing conditions world-wide on symptoms and objective outcomes. Methods: Cross-sectional studies of 8-12-year-old children in 20 countries used standardized methodology from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC). Symptoms of asthma, rhinitis and eczema, plus residential exposure to dampness and moulds, were ascertained by parental questionnaires (n = 46 051). Skin examination, skin prick tests (n = 26 967) and hypertonic saline bronchial challenge (n = 5713) were performed. In subsamples stratified by wheeze (n = 1175), dust was sampled and analysed for house dust mite (HDM) allergens and endotoxin. Results: Current exposure to dampness was more common for wheezy children (pooled odds ratio 1.58, 95% CI 1.40-1.79) and was associated with greater symptom severity among wheezers, irrespective of atopy. A significant (P < 0.01) adverse effect of dampness was also seen for cough and phlegm, rhinitis and reported eczema, but not for examined eczema, nor bronchial hyperresponsiveness. HDM sensitization was more common in damp homes (OR 1.16, 1.03-1.32). HDM-allergen levels were higher in damp homes and were positively associated with HDM-sensitization, but not wheeze. Conclusion: A consistent association of dampness with respiratory and other symptoms was found in both affluent and non-affluent countries, among both atopic and non-atopic children. HDM exposure and sensitization may contribute, but the link seems to be related principally to non-atopic mechanisms

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

Asthma and allergic symptoms in relation to house dust endotoxin: Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II)

Background: Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent. Objectives: To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries. Methods: Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi-centre cross-sectional study of 840 children aged 9-12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end-points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen-specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure. Results: Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29-0.96) for endotoxin levels per m(2) of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64-0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever. Conclusion: These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children