Polymorphisms in the bradykinin B2 receptor gene and childhood asthma

Bradykinin has been suggested as one of the key mediators of bronchial asthma. Polymorphisms with a potential functional relevance have been described in the B2 bradykinin receptor gene. Study of these polymorphisms in 77 children with asthma and 73 controls revealed no association. However, when comparing the asthmatics according to their age at onset (before and after age 4), the exon 1 allele BE1-2G was significantly associated with late-onset asthma (p <0.05). Since BE1-2G has previously been shown to lead to a higher transcription rate of the B2 receptor, this result warrants further investigation of the role of bradykinin in conferring susceptibility to pediatric asthma

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. Copyright (c) 2007 S. Karger AG, Basel

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

This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhinoconjunctivitis and eczema was 11.7%, 8.5% and 7.9%, respectively. The study shows a wide variability in the prevalence and severity of asthma, rhinoconjunctivitis and eczema which occurs not just between regions and countries but between centres in the same country and centres in the same city. This study definitively establishes that the prevalence of those diseases can be very high in non-affluent centres with low socioeconomic conditions. The large variability also suggests a crucial role of local environment characteristics to determine the differences in prevalence between one place and another. Thus, ISAAC Phase Three has provided a large body of epidemiological information on asthma, rhinoconjunctivitis and eczema in childhood from contrasting environments which is expected to yield new clues about the aetiology of those conditions and reasons for their marked global variability. © 2012 SEICAP

Novel statistical approaches for non-normal censored immunological data: analysis of cytokine and gene expression data

Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects. Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding. Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping. Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression. Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets

Asthma Prevalence, Knowledge, and Perceptions among Secondary School Pupils in Rural and Urban Costal Districts in Tanzania.

Asthma is a common chronic disease of childhood that is associated with significant morbidity and mortality. We aimed to estimate the prevalence of asthma among secondary school pupils in urban and rural areas of coast districts of Tanzania. The study also aimed to describe pupils' perception towards asthma, and to assess their knowledge on symptoms, triggers, and treatment of asthma. A total of 610 pupils from Ilala district and 619 pupils from Bagamoyo district formed the urban and rural groups, respectively. Using a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, a history of "diagnosed" asthma or the presence of a wheeze in the previous 12 months was obtained from all the studied pupils, along with documentation of their perceptions regarding asthma. Pupils without asthma or wheeze in the prior 12 months were subsequently selected and underwent a free running exercise testing. A >= 20% decrease in the post-exercise Peak Expiratory Flow Rate (PEFR) values was the criterion for diagnosing exercise-induced asthma. The mean age of participants was 16.8 (+/-1.8) years. The prevalence of wheeze in the past 12 months was 12.1% in Bagamoyo district and 23.1% in Ilala district (p < 0.001). Self-reported asthma was found in 17.6% and 6.4% of pupils in Ilala and Bagamoyo districts, respectively (p < 0.001). The prevalence of exercise-induced asthma was 2.4% in Bagamoyo, and 26.3% in Ilala (P < 0.002). In both districts, most information on asthma came from parents, and there was variation in symptoms and triggers of asthma reported by the pupils. Non-asthmatic pupils feared sleeping, playing, and eating with their asthmatic peers. The prevalence rates of self-reported asthma, wheezing in the past 12 months, and exercise-induced asthma were significantly higher among urban than rural pupils. Although bronchial asthma is a common disease, pupils' perceptions about asthma were associated with fear of contact with their asthmatic peers in both rural and urban schools

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 PM10 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 PM₁₀ 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 PM₁₀ and various outcomes. For severe wheeze in 13-14-year-olds, the OR for a 10 μg/m³ increase in PM₁₀ 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 μg/m³ increase in PM₁₀ 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 PM₁₀ has little or no association with the prevalence of childhood asthma, rhinoconjunctivitis or eczema either within or between countries

Spirometry reference equations for central European populations from school age to old age.

Spirometry reference values are important for the interpretation of spirometry results. Reference values should be updated regularly, derived from a population as similar to the population for which they are to be used and span across all ages. Such spirometry reference equations are currently lacking for central European populations. To develop spirometry reference equations for central European populations between 8 and 90 years of age. We used data collected between January 1993 and December 2010 from a central European population. The data was modelled using "Generalized Additive Models for Location, Scale and Shape" (GAMLSS). The spirometry reference equations were derived from 118'891 individuals consisting of 60'624 (51%) females and 58'267 (49%) males. Altogether, there were 18'211 (15.3%) children under the age of 18 years. We developed spirometry reference equations for a central European population between 8 and 90 years of age that can be implemented in a wide range of clinical settings

Early age exposure to moisture damage and systemic inflammation at the age of 6 years

Cross-sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life. At age 6 years, subclinical systemic inflammation was measured by serum C-reactive protein(CRP) and blood leucocytes and immune responsiveness by ex vivo production of interleukin 1-beta(IL-1beta), IL-6 and tumor necrosis factor-alpha(TNF-alpha) in whole blood cultures without stimulation or after 24h stimulation with phorbol 12-myristate 13-acetate and ionomycin(PI), lipopolysaccharide(LPS) or peptidoglycan(PPG) in 251 to 270 children. Moisture damage in child's main living areas in infancy was not significantly associated with elevated levels of CRP or leucocytes at 6 years. In contrast, there was some suggestion for an effect on immune responsiveness, as moisture damage with visible mold was positively associated with LPS-stimulated production of TNF-alpha and minor moisture damage was inversely associated with PI-stimulated IL-1beta. While early life exposure to mold damage may have some influence on later immune responsiveness, it does not seem to increase subclinical systemic inflammation in later life. This article is protected by copyright. All rights reserved

Exposure to animals and risk of oligoarticular juvenile idiopathic arthritis: a multicenter case-control study

<p>Abstract</p> <p>Background</p> <p>An inverse association between early contact with microbial compounds and respiratory allergies is well established. The protective effect of infant contact with animals was also shown for inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE). We aimed to test the association between animal contact in infancy and oligoarticular juvenile idiopathic arthritis (OA JIA).</p> <p>Methods</p> <p>Parents of children with OA JIA registered at the Hospital for Pediatric Rheumatology in Garmisch-Partenkirchen were asked to complete a questionnaire. Children who underwent strabismus surgery at six referral centers for ophthalmology served as controls. Children age 6 to 18 years born in Germany without malformations were included (238 cases; response 89% and 832 controls; response 86%). Data were analyzed using logistic regression models after adjusting for potential confounders.</p> <p>Results</p> <p>Neither place of living (urban vs. rural area), living on a farm, nor regular farm animal (adjusted odds ratio 0.79; 95% confidence interval 0.42-1.47) or pet contact (0.79; 0.55-1.14) during infancy were clearly related to case status. Allergic rhinitis was inversely related to OA JIA (0.57; 0.34-0.95).</p> <p>Neither place of living (urban vs. rural area), living on a farm, nor regular farm animal (adjusted odds ratio 0.79; 95% confidence interval 0.42-1.47) or pet contact (0.79; 0.55-1.14) during infancy were related to case status. Allergic rhinitis was inversely related to OA JIA (0.57; 0.34-0.95).</p> <p>Conclusions</p> <p>Contact with farm environments in infancy might not be associated with OA JIA. This finding is consistent with previous findings for diabetes mellitus type 1 but contradicts results for IBD and SLE.</p

Sensitization to Aeroallergens in Korean Children: A Population-based Study in 2010

We performed this study to assess the prevalence of sensitization to aeroallergens and to analyze the difference between prevalence rates according to children's ages and residential areas. In this nationwide cross-sectional study, first grade students of 45 elementary schools and 40 middle schools were randomly selected, and skin prick tests were performed for 18 inhalant allergens between October and November 2010. Of 7,829 analyzed subjects, 3,753 (47.9%) were sensitized to at least one aeroallergen. Sensitization to Dermatophagoides farinae was found to be the most prevalent in elementary schoolchildren (32.4%), followed by Dermatophagoides pteronyssinus, Tyrophagus putrescentiae, Japanese hop, and oak. In middle schoolchildren, D. pteronyssinus yielded the highest prevalence (42.7%), followed by D. farinae, T. putrescentiae, Japanese hop, and cat. In middle schoolchildren, the sensitization rate to aeroallergens in metropolitan, urban, and rural areas was 57.2%, 54.3%, and 49.8%, respectively (P = 0.019). In this age group, the sensitization rate in low, middle, high, and very high income groups was 53.8%, 51.8%, 59.0%, and 59.6%, respectively (P = 0.002). In conclusion, the sensitization rate is 47.9% and house dust mite is the most prevalent allergen in the pediatric population in Korea. The rate is higher in metropolitan areas and the highest income group than in rural areas and low income groups