Search

Objective Identify associated factors for recurrent wheezing (RW) in male and female infants. Methods Cross-sectional multicentric study using the standardized questionnaire from the Estudio Internacional sobre Sibilancias en Lactantes (EISL). The questionnaire was applied to parents of 9345 infants aged 12–15 months at the time of immunization/routine visits. Results One thousand two hundred and sixty-one (13.5%) males and nine hundred sixty-three (10.3%) females have had RW (≥3 episodes), respectively (p10 colds episodes (OR = 3.46; IC 95% 2.35–5.07), air pollution (OR = 1.33; IC 95% 1.12–1.59), molds at home (OR = 1.23; IC 95% 1.03–1.47), Afro-descendants (OR = 1.42; IC 95% 1.20–1.69), bronchopneumonia (OR = 1.41; IC; 1.11–1.78), severe episodes of wheezing in the first year (OR = 1.56; IC 95% 1.29–1.89), treatment with bronchodilators (OR = 1.60; IC 95% 1.22–2,1) and treatment with oral corticosteroids (OR = 1,23; IC 95% 0.99–1,52). Associated factors for RW for females were passive smoking (OR = 1.24; IC 95% 1.01−1,51), parents diagnosed with asthma (OR = 1.32; IC 95% 1,08−1,62), parents with allergic rhinitis (OR = 1.26; IC 95% 1.04–1.53), daycare attendance (OR = 1.48; IC 95% 1.17−1,88), colds in the first 6 months of life (OR = 2.19; IC 95% 1.69–2.82), personal diagnosis of asthma (OR = 1.84; IC 95% 1.39–2.44), emergency room visits (OR = 1.78; IC 95% 1.44–2.21), nighttime symptoms (OR = 2.89; IC 95% 2.34–3.53) and updated immunization (OR = 0.62; IC 95% 0.41−0.96). Conclusion There are differences in associated factors for RW between genders. Identification of these differences could be useful to the approach and management of RW between boys and girls.

Background: Contrary to what happens in children and adults, the prevalence and the factors related to hospitalisation for asthma/wheezing in infants with recurrent asthma-like symptoms are poorly known.Methods: This study is part of the International Study of Wheezing in infants Phase 3; 2,079 infants (aged 12–18 months) with recurrent asthma-like symptoms, from 11 South American centres, were studied to determine the prevalence and the associated factors for wheezing exacerbation admission. Descriptive statistics and multivariate logistic regression were employed for analysis.Results: The prevalence of admission for wheezing was 29.7% (95% CI 27.7–31.6) and was significantly associated to severe wheezing episodes (OR: 3.89; 95% CI: 2.93–5.18, p < 0.001), physician-diagnosed asthma (OR: 1.79; 95% CI: 1.33–2.41, p < 0.0001), use of inhaled corticosteroids (OR: 1.78; 95%CI: 1.38–2.29, p < 0.0001), maternal tobacco smoking during pregnancy (OR:1.69; 95% CI: 1.19–2.39, p = 0.003) and onset of wheezing in the first trimester of life (OR: 1.30; 95% CI: 1.02–1.66, p = 0.038). Breast feeding ≥4 months (OR: 0.72; 95% CI: 0.54–0.96, p = 0.004), maternal high educational level (>12 years) (OR: 0.66; 95% CI: 0.51–0.85, p = 0.001) and total monthly household income ≥US$ 3,000 (OR: 0.34; 95% CI: 0.18–0.67, p = 0.002), were protective factors.Conclusions: Infants with recurrent asthma-like symptoms have a high rate of admissions. Tobacco smoking in pregnancy, viral respiratory illness in the first trimester of life and severe progression were risks for admissions. Improving medical management to prevent severe exacerbations, prolonging the postnatal period at home longer than 3 months, favouring breastfeeding and avoiding smoking during pregnancy may have a preventive role for admissions in infants with recurrent asthma-like symptoms.

Background: Tobacco-smoking in children is one of the most crucial public health concerns, which could be highly prevalent in underprivileged populations. Methods: A cross sectional, random sampling survey was conducted to determine the prevalence of current tobacco-smoking and related risk factors among adolescents living in a low-income area of Santiago de Chile. Results: Of the 2,747 adolescents participating in the study, 24.0% [95% confidence interval (CI) 22.3–25.5] were current smokers, with no significant difference between girls and boys. Factors associated with current smoking were as follows: positive attitude to smoking cigarettes offered by peers [odds ratio (OR) 8.0; 95% CI 5.7–11.3, P

Functional and inflammatory measures have been recommended to corroborate asthma diagnosis in schoolchildren, but the evidence in this regard is conflicting. We aimed to determine, in real-life clinical situation, the value of spirometry, spirometric bronchial reversibility to salbutamol (BDR), bronchial responsiveness to methacholine (MCT) and fractional exhaled nitric oxide (FENO), to corroborate the diagnosis of asthma in children on regular inhaled corticosteroids (ICS) referred from primary care.One hundred and seventy-seven schoolchildren with mild-moderate persistent asthma, on treatment with regular ICS, participated in the study. Abnormal tests were defined as FENO ≥ 27 ppb, BDR (FEV1 ≥ 12%) and methacholine PC20 ≤ 4 mg/mL.The proportions of positive BDR, FENO and MCT, were 16.4%, 33.3%, and 87.0%, respectively. MCT was associated with FENO (p 0.03) and BDR (p = 0.001); FENO was associated with BDR (p = 0.045), family history of asthma (p = 0.003) and use of asthma medication in the first two years of life (p = 0.004). BDR was significantly related with passive tobacco exposure (p = 0.003).Spirometry, BDR and BDR had a poor performance for corroborating diagnosis in our asthmatic children on ICS treatment; on the contrary, MCT was positive in most of them, which agrees with previous reports. Although asthma tests are useful to corroborate asthma when positive, clinical diagnosis remains the best current approach for asthma diagnosis, at least while better objective and feasible measurements at the daily practice are available. At present, these tests may have a better role for assessing the management and progression of the condition.

Background Recurrent wheezing during the first year of life is a major cause of respiratory morbidity worldwide, yet there are no studies on its prevalence in Portugal. Objective Determine the prevalence and severity of recurrent wheezing, treatments employed and other related aspects, in infants during their first year of life in Setubal, Portugal. Methods This is a cross-sectional study of a random sample of infants aged 12–15 months living in Setubal district. It uses a validated questionnaire answered by parents/caregivers at local healthcare facilities where infants attend for growth/development monitoring and/or vaccine administration. Results Among the 202 infants surveyed, 44.6% (95% CI 37.7–51.4) had at least one episode of wheezing; and 18.3% (95% CI 12.9–23.6) had recurrent wheezing. There was significant morbidity associated to recurrent wheezing in terms of severe episodes (17.3%–95% CI 12–22.5), visits to the emergency department (26.2%–95% CI 20.1–32.2) and hospital admissions (5.4%–95% CI 2.2–8.5); 10.4% (95% CI 6.1–14.6) used inhaled corticosteroids and 7.9% (95% CI 4.1–11.6) used a leukotriene receptor antagonist. Conclusions The prevalence of recurrent wheezing in infants during the first year of life is high and is associated with significant morbidity, presenting as a relevant public health problem. An important proportion of infants’ progress with a more severe condition, resulting in high use of health resources (visits to emergency department and hospitalisations). The prevalence of recurrent wheezing in this district of Portugal stays between those related in other European and Latin American Centres, suggesting that maybe some of the well-known risk factors are shared with affluent countries.

N/A

Aim To examine the relationship between reported vigorous physical activity (VPA) and body mass index (BMI) in children (6-7 years) and adolescents (13-14 years). Methods In the International Study of Asthma and Allergies in Childhood Phase Three, 75,895 children's parents and 199,502 adolescents answered questions relating to VPA, height and weight. The association between VPA and BMI was analysed using general linear models, adjusting for country gross national index. Results Compared to children who undertook no VPA, those in the infrequent group (once or twice per week) and those in the frequent group (three or more times per week) had mean (95%CI) BMI values 0.07 kg/m2 (0.03 to 0.11) and 0.09 kg/m2 (0.03 to 0.15) greater respectively (P=0.001). Compared to adolescents reporting no VPA, those in the infrequent group had a BMI 0.19 kg/m2 (0.15 to 0.23) greater while those in the frequent group had a BMI 0.01 kg/m2 (-0.03 to 0.05) greater (P

Objective: Despite anti-smoking prevention programs, many adolescents start smoking at school age. The main objectives of this study were to determine the prevalence and risk factors associated with smoking in adolescents living in Uruguaiana, RS, Brazil. Methods: A prospective study was conducted in adolescents (12–19 years), enrolled in municipal schools, who answered a self-administered questionnaire on smoking. Results: 798 adolescents were enrolled in the study, with equal distribution between genders. The tobacco experimentation frequency (ever tried a cigarette, even one or two puffs) was 29.3%; 14.5% started smoking before 12 years of age and 13.0% reported smoking at least one cigarette/day last month. Having a smoking friend (OR: 5.67, 95% CI: 2.06–7.09), having cigarettes offered by friends (OR: 4.21, 95% CI: 2.46–5.76) and having easy access to cigarettes (OR: 3.82, 95% CI: 1.22–5.41) was identified as factors associated with smoking. Having parental guidance on smoking (OR: 0.67, 95% CI: 0.45–0.77), having no contact with cigarettes at home in the last week (OR: 0.51, 95% CI: 0.11–0.79) and knowing about the dangers of electronic cigarettes (OR: 0.88, 95% CI: 0.21–0.92) were identified as protection factors. Conclusion: The prevalence of smoking among adolescents in Uruguaiana is high. The implementation of measures to reduce/stop tobacco use and its new forms of consumption, such as electronic cigarettes and hookah, are urgent and imperative in schools. Resumo: Objetivo: Apesar dos programas de prevenção antitabagista, muitos adolescentes começam a fumar na idade escolar. Foram objetivos do estudo determinar a prevalência e os fatores de risco associados ao consumo de tabaco em adolescentes moradores do município de Uruguaiana RS, Brasil. Métodos: Estudo transversal, realizado em adolescentes de 12 a 19 anos, matriculados em escolas do município, que responderam questionário autoaplicável sobre tabagismo. Resultados: Participaram 798 adolescentes com igual distribuição entre os gêneros. A frequência de experimentação de tabaco (Alguma vez tentou fumar um cigarro, mesmo que uma ou duas tragadas) foi 29,3%, sendo que 14,5% começaram fumar antes dos 12 anos de vida e 13,0% deles afirmaram terem fumado pelo menos um cigarro/dia no último mês. Foram identificados como associados ao tabagismo: ter amigo tabagista (OR:5,67, IC95%:2,06-7,09), ter oferta de cigarro pelo amigo (OR:4,21, IC95%:2,46-5,76) e facilidade de conseguir cigarros (OR:3,82, IC95%:1,22-5,41). Ter orientações dos pais sobre tabagismo (OR:0,67, IC95%:0,45-0,77), não ter contato com cigarro em casa na última semana (OR:0,51, IC95%:0,11-0,79) e saber os malefícios do cigarro eletrônico (OR:0,88, IC95%:0,21-0,92) foram identificados como de proteção. Conclusões: A prevalência de tabagismo entre os adolescentes de Uruguaiana é alta. A implantação de medidas nas escolas para reduzir ou acabar o consumo de tabaco e de suas novas modalidades, como os cigarros eletrônicos e o narguilé é urgente e imperiosa. Keywords: Tobacco, Adolescent, Risk factors, Cigarette, Palavras-chave: Tabaco, Adolescente, Fatores de risco, Cigarro

RESUMO Objetivo: Avaliar a prevalência e a gravidade da sibilância em lactentes no primeiro ano de vida, utilizando o protocolo padronizado do Estudio Internacional de Sibilancias en Lactantes- fase 3, e comparar os valores obtidos com os observados no Estudio Internacional de Sibilancias en Lactantes- fase 1, realizado no mesmo centro. Métodos: Entre 2009 e 2010, pais e responsáveis de lactentes responderam ao questionário escrito do Estudio Internacional de Sibilancias en Lactantes- fase 3, e os resultados obtidos foram comparados aos do Estudio Internacional de Sibilancias en Lactantes- fase 1, realizado entre 2005 e 2006. Oslactentes foram separados em sibilantes e “não sibilantes”. Osprimeiros foram divididos de acordo com a frequência dos episódios: sibilância ocasional, quando apresentaram menos de três, e sibilância recorrente, quando manifestaram três ou mais. Resultados: A prevalência de sibilantes foi similar nas duas fases (44,6 versus46%). Segundo a frequência, houve aumento na prevalência de sibilância ocasional (19,4 versus 23%; p=0,03) e redução na de sibilância recorrente (26,7 versus 21,6%; p=0,005). Observou-se, ainda, aumento expressivo no diagnóstico de asma (7,5 versus 21,8%) e no uso de corticosteroides inalatórios (11,7 versus 35%), como também na hospitalização por sibilância na fase 3 (19,7 versus 32,6%), período da pandemia Influenza A (H1N1), o que pode ter contribuído para este desfecho. Conclusões: A prevalência da sibilância no primeiro ano de vida permanece elevada. Apesar de a avaliação temporal mostrar queda na prevalência da sibilância recorrente, aumento significante de sua morbidade foi identificado pelo maior número de hospitalizações. Além disso, houve indícios de melhora no manejo da sibilância dos lactentes, refletido pelo aumento do diagnóstico de asma e maior indicação de tratamentos preventivos.

Background: The relationship between pneumonia and recurrent wheezing (RW) and the factors associated to pneumonia in wheezing and non-wheezing infants have not been compared between affluent and non-affluent populations. Methods: The International Study of Wheezing in Infants (EISL) is a large population-based cross-sectional study carried out in Latin America (LA) and Europe (EU). We used a validated questionnaire for identifying wheeze in the first year of life. The questionnaire also inquired about pneumonia diagnosis, together with other potentially related factors. Associations between both conditions and between potential risk/protective factors for pneumonia were tested by random-effects logit model and adjusting for all factors found previously associated to RW in this cohort. Results: Pneumonia and RW were strongly associated to each other in LA and EU (aOR 5.42; 95% CI: 4.87-6.04 and aOR 13.99; 95% CI: 9.61-20.36, respectively). Infant eczema was the most consistent risk factor of pneumonia in both continents, in the whole population and also among wheezers and non-wheezers (aOR ranging from 1.30; 95% CI: 1.11-1.52 to 2.65; 95% CI: 1.68-4.18); while breast feeding for at least 3 months was the most consistent protective factor (aOR ranging from 0.60; 95% CI: 0.51-0.71 to 0.76; 95% CI: 0.69-0.84). Factors associated to pneumonia were similar between continents among wheezers, but differed considerably among non-wheezers. Conclusion: Pneumonia and RW are associated conditions sharing many risk/protective factors in EU and LA among wheezing infants, but not among non-wheezing infants. The association between pneumonia and RW could be due to shared pathophysiology or by diagnostic confusion between the two conditions. (C) 2015 Wiley Periodicals, Inc.

OBJETIVO: Determinar a prevalência de sintomas relacionados à asma, à rinite e ao eczema atópico em adolescentes (13-14 anos, AD) residentes em sete cidades brasileiras com o questionário escrito (QE) padronizado do International Study of Asthma and Allergies in Childhood (Isaac) e verificar a tendência temporal passados nove anos da última avaliação do Isaac fase 3 (ISF3). MÉTODOS: O QE Isaac foi respondido por 20.099 AD (13-14 anos) moradores em centros das regiões Norte, Nordeste, Sudeste e Sul. Os índices obtidos foram comparados aos do ISF3 com o teste não paramétrico (qui-quadrado ou Fisher) e foi estabelecida a taxa de incremento/decremento anual para cada um dos centros segundo o sintoma avaliado. RESULTADOS: Em relação ao ISF3, considerando-se os dados nacionais, houve queda da prevalência média de asma ativa (18,5% vs. 17,5%) com elevação da frequência de asma grave (4,5% vs. 4,7%) e de asma diagnosticada por médico (14,3% vs. 17,6%). Aumento da prevalência de rinite e rinoconjuntivite e de eczema flexural também ocorreram. CONCLUSÕES: A prevalência de asma, rinite e eczema atópico no Brasil foi variável. Valores mais altos, sobretudo de asma e eczema, foram observados nos centros localizados mais próximos ao Equador. OBJECTIVE: To determine the prevalence of symptoms of asthma, rhinitis, and atopic eczema in adolescents (AD; 13-14 years) living in seven Brazilian cities, by applying the standardized written questionnaire (WQ) of the International Study of Asthma and Allergies in Childhood (ISAAC), and to evaluate the time trend nine years after the last assessment of ISAAC phase 3 (ISP3). METHODS: The ISAAC-WQ was answered by 20,099 AD from the Northern, Northeastern, Southeastern, and Southern Brazilian regions. Values obtained were compared to those observed in ISP3 using nonparametric (chi-squared or Fisher) tests, and the ratio of annual increment/decrement was established for each of the centers, according to the symptom assessed. RESULTS: Considering the national data and comparing to values of ISP3, there was a decrease in the mean prevalence of active asthma (18.5% vs. 17.5%) and an increase in the frequency of severe asthma (4.5% vs. 4.7%) and physician-diagnosed asthma (14.3% vs. 17.6%). An increase in prevalence of rhinitis, rhinoconjunctivitis, and atopic eczema was also observed. CONCLUSIONS: The prevalence of asthma, rhinitis, and atopic eczema in Brazil was variable; higher prevalence values, especially of asthma and eczema, were observed in regions located closer to the Equator. Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of Pediatrics Universidade Federal do Paraná Universidade Federal de Pernambuco Department of Pediatrics Universidade Estadual do Pará Universidade Federal de Alagoas Department of Pediatrics Universidade Federal de Sergipe Department of Pediatrics Universidade Federal de Minas Gerais Department of Pediatrics Universidade de Santiago UNIFESP, EPM, Department of Pediatrics SciELO

To identify changes in the prevalence and severity of recurrent wheezing (RW) in infants using data obtained from two surveys administered seven years apart.A cross-sectional, international, population-based study in infants aged 12-15 months was conducted. Data were obtained from two surveys (S1 and S2, in 2005 and 2012, respectively) using the same methodology in three large Latin American cities: Curitiba (Brazil), São Paulo (Brazil), and Santiago (Chile).A decrease in the overall prevalence of RW was identified between S1 (23.3%) and S2 (20.4%), p = 0.004, but it was mainly driven by the reduction observed in São Paulo; in Curitiba and Santiago, this change was not significant. The mean prevalence of the following RW severity indicators remained high and stable: severe wheezing episodes (56.9% in S1 and 54.2% in S2, p = 0.32) and emergency department (ED) visits for wheezing (S1 = 68.1%, S2 70.9%, p = 0.21). A significant increase in admissions for wheezing (21.1% to 26.7%, p = 0.004) was observed. In Curitiba and São Paulo, there were significant increases in the prevalence of physician-diagnosed asthma and in the use of inhaled corticosteroids and oral antileukotrienes.The prevalence and severity of RW during the first year of life remained high over time, with remarkably high rates of ED visits, admissions for wheezing and use of asthma medications. This study suggests the need for considering early asthma diagnosis and to establish an appropriate treatment in infants with recurrent and severe asthma-like symptoms.

BACKGROUND: Associations of larger families with lower prevalences of hay fever, eczema and objective markers of allergic sensitization have been found fairly consistently in affluent countries, but little is known about these relationships in less affluent countries. METHODS: Questionnaire data for 210,200 children aged 6-7 years from 31 countries, and 337,226 children aged 13-14 years from 52 countries, were collected by Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations of disease symptoms and labels of asthma, rhinoconjunctivitis and eczema were analysed by numbers of total, older and younger siblings, using mixed (multi-level) logistic regression models to adjust for individual covariates and at the centre level for region, language and national affluence. RESULTS: In both age groups, inverse trends (P < 0.0001) were observed for reported 'hay fever ever' and 'eczema ever' with increasing numbers of total siblings, and more specifically older siblings. These inverse associations were significantly (P < 0.005) stronger in more affluent countries. In contrast, symptoms of severe asthma and severe eczema were positively associated (P < 0.0001) with total sibship size in both age groups. These associations with disease severity were largely independent of position within the sibship and national GNI per capita. CONCLUSIONS: These global findings on sibship size and childhood asthma, rhinoconjunctivitis and eczema suggest at least two distinct trends. Inverse associations with older siblings (observations which prompted the 'hygiene hypothesis' for allergic disease) are mainly a phenomenon of more affluent countries, whereas greater severity of symptoms in larger families is globally more widespread.

Background: The prevalence of atopy in asthmatic children is widely variable around the world as demonstrated by large multicentric international studies. Aim: To determine the prevalence of atopy, defined as a positive reaction to one or more allergens in the skin prick test (SPT), in children with persistent asthma. Material and methods: We studied 1,199 children (54% male), aged between 4 and 16 years of age with confirmed diagnosis of asthma and followed at a Department of Pediatric Respiratory Medicine, between 2006 and 2011. SPT was performed according to international recommendations using standardized aeroallergens, in the forearm. A positive reaction was defined as a wheal ?3 mm to one or more allergens. Results: The overall prevalence of atopy (positive SPT) was 49.4% (95% confidence interval (CI) 46.5-52.2) and there was a significant trend towards a higher prevalence with increasing age (p

Background The association between birthweight and asthma, eczema and rhinoconjunctivitis is conflicting. Aims To examine the association between birthweight and symptoms of asthma, eczema and rhinoconjunctivitis. Methods Parents or guardians of children aged 6–7 yr completed written questionnaires about symptoms of asthma, rhinoconjunctivitis and eczema, and several risk factors, including birthweight. Results There were 162,324 children from 60 centres in 26 countries. Low birthweight (

Objective: to identify possible risk factors associated with wheezing in infants (12-15 months-old) in the state of Mato Grosso, Brazil. Methods: this was a cross-sectional study performed by applying a standardized written questionnaire from the international study on wheezing in infants (Estudio Internacional de Sibilancia en Lactantes - EISL), phase 3. Parents and/or guardians of infants were interviewed at primary health care clinics or at home from August of 2009 to November of 2010. Factors associated to wheezing were studied using bivariate and multivariate analysis (using the Statistical Package for Social Sciences [SPSS] v.18.0), and expressed as odds ratios (OR) and 95% confidence intervals (95% CI). Results: the written questionnaire was answered by 1,060 parents and/or guardians. The risk factors for wheezing were: history of asthma in the family [mother (OR = 1.62; 95% CI = 1.07-2.43); father (OR = 1.98; 95% CI = 1.22-3.23); siblings (OR = 2.13; 95% CI = 1.18-3.87)]; history of previous pneumonia (OR = 10.80; 95% CI = 4.52-25.77); having had more than six upper respiratory tract infections (URTIs) (OR = 2.95; 95% CI = 2.11-4.14); having had first URTI before the third month of life (OR = 1.50; 95% CI = 1.04-2.17); living in a moderately polluted area (OR = 1.59; 95% CI = 1.08-2.33); paracetamol use for URTI (OR = 2.13; 95% CI = 1.54-2.95); and antibiotic use for skin infection (OR = 2.29; 95% CI = 1.18-4.46). Conclusions: the study of risk factors for wheezing in the first year of life is important to help physicians identify young children at high risk of developing asthma and to improve public health prevention strategies in order to reduce the morbidity of wheezing in childhood. Resumo: Objetivo: identificar possíveis fatores de risco associados à sibilância em lactentes (12 a 15 meses) no estado de Mato Grosso, Brasil. Métodos: estudo transversal, utilizando o questionário escrito padronizado do Estudio Internacional de Sibilancia en Lactantes (EISL) – fase 3. Pais e/ou responsáveis pela criança foram entrevistados em Unidades Básicas de Saúde quando as procuravam para imunização de rotina ou durante visitas nos domicílios de crianças matriculadas nos programas de saúde da família, no período de agosto de 2009 a novembro de 2010. Fatores associados à sibilância foram avaliados utilizando análise bivariada e multivariada e expressos como odds ratio (OR) e intervalo de confiança 95% (IC95%). Resultados: ao todo, um mil e sessenta (n = 1.060) pais e/ou responsáveis responderam o questionário escrito. Os fatores de risco para sibilância foram: história familiar de asma [mãe (OR = 1,62; IC95%= 1,07-2,43); pai (OR = 1,98; IC95% = 1,22-3,23); irmãos (OR = 2,13; IC95% = 1,18-3,87)]; história prévia de pneumonia (OR = 10,8; IC 95% = 4,52-25,77); ter mais de seis infecções de vias aéreas superiores (IVAS) (OR = 2,95; IC95% = 2,11-4,14) e a primeira IVAS antes dos três meses de idade (OR = 1,50; IC95% = 1,04-2,17); residir em local com moderada poluição (OR = 1,59; IC95% = 1,08-2,33); uso de paracetamol por IVAS (OR = 2,13; IC95% = 1,54-2,95); e uso de antibiótico por infecção na pele (OR = 2,29; IC 95% = 1,18-4,46). Conclusões: O estudo dos fatores de risco para sibilância no primeiro ano de vida é importante para auxiliar na identificação, entre os lactentes sibilantes, aqueles de alto risco para desenvolver asma, e para o desenvolvimento de estratégias de prevenção por políticas pública de saúde visando minimizar a morbidade da sibilância na infância. Keywords: Infant, Wheezing, Asthma, Risk factors, Palavras-chave: Lactente, Sibilos, Asma, Fatores de risco

Background: Although the association between latitude and asthma prevalence has been studied to a certain extent, its influence on the magnitude of the association of risk/protective factors with recurrent wheeze in infants has never been reported.Methods: The adjusted odd ratios (aOR) of various risk/protective factors for recurrent wheeze from 31 920 infants from 19 centres of the "Estudio Internacional de Sibilacias en Lactantes" (EISL) in very different parts of the world were used to build a meta-regression using the strength of the aOR of each factor as dependent variable and centre latitude as explanatory variable. The meta-regression was further adjusted for continent.Results: There was a positive significant correlation between latitude and the magnitude of the aOR between recurrent wheeze and having cold(s) during the first three months of life (p = 0.004); attending a nursery school (p = 0.011); and having additional siblings (p = 0.003). Furthermore, there was a negative correlation for having been breastfed for at Least three months (p = 0.044). Heterogeneity (as measured by I-2) of the magnitude of aORs between centres was quite high except for breast feeding: 73.1% for colds; 66.9% for nursery school; 52.6% for additional siblings; and 18.1% for breast feeding. Latitude explained a considerable amount of that heterogeneity: 63.8% for colds; 52.8% for nursery school; 86.6% for additional siblings; and 100% for breast feeding, probably as a consequence of its low heterogeneity.Conclusion: The magnitude in which some risk/protective factors are associated to recurrent wheeze during the first year of life varies significantly with latitude. (C) 2013 Elsevier Ltd. All rights reserved.

The objective of this study was to identify risk factors for wheezing disorders in the first year of life in infants living in São Paulo (SP), Brazil, applying the standardized protocol of the Estudio Internacional de sibilancia en lactentes-Phase 1. A total of 1014 parents or caregivers of infants, who attended for routine evaluation and immunization in public health centers were interviewed in Southern SP city. Risk factors significantly associated with recurrent wheezing were: history of previous pneumonia, daycare attendance, consumption of processed food, presence of a cat at home, more than five upper respiratory infection (URI) episodes and the first URI before the age of sixth month. Most of these risk factors for wheezing can be avoided or controlled. Prospective studies on wheezing, especially in children with a severe presentation, are needed to analyze the impact of these risk factors and the effect of preventive actions.

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-Guerin (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.

Summary Background In Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC), we investigated the relationship between breast feeding in infancy and symptoms of asthma, rhinoconjunctivitis and eczema in 6–7 year old children. Methods Parents or guardians of 6–7 year old children completed written questionnaires on current symptoms of asthma, rhinoconjunctivitis and eczema, and on a range of possible asthma risk factors including a history of breast feeding ever. Prevalence odds ratios were estimated using logistic regression, adjusted for gender, region of the world, language, per capita gross national income, and other risk factors. Results In all 206,453 children from 72 centres in 31 countries participated in the study. Reported breast feeding ever was not associated with current wheeze, with an odds ratio (adjusted for gender, region of the world, language, per capita gross national income, and factors encountered in infancy) of 0.99 (95% CI 0.92–1.05), current rhinoconjunctivitis (OR 1.00, 95% CI 0.93–1.08), current eczema (OR 1.05, 95% CI 0.97–1.12), or symptoms of severe asthma (OR 0.95, 95% CI 0.87–1.05). Breast feeding was however associated with a reduced risk of severe rhinoconjunctivitis (OR 0.74, 95% CI 0.59–0.94) and severe eczema (OR 0.79, 95% CI 0.66–0.95). Conclusions There was no consistent association between breast feeding use in the first year of life and either a history or current symptoms of wheezing, rhinoconjunctivitis or eczema in 6–7 year old children, but possibly an effect on severe symptoms of the latter two conditions.

Verificar a prevalência de sibilância no primeiro ano de vida em lactentes da cidade do Recife, Pernambuco, Brasil e identificar fatores de risco a ela associados. Estudo realizado segundo o protocolo do Estudio Internacional de Sibilancia en Lactantes (EISL) em crianças com idades entre 12 e 15 meses. A amostra foi analisada segundo a presença ou não de sibilância. Foram entrevistados 1.071 pais por crianças com idades entre 12 e 15 meses. A prevalência de sibilância no primeiro ano de vida foi de 43%, sem diferenças quanto aos gêneros. O relato de sibilância no primeiro ano de vida foi associado a ter tido pneumonia, ter familiares com asma, mais de nove episódios de infecções de vias aéreas superiores e primeiro episódio de resfriado antes de seis meses de idade (p < 0,001). A prevalência de sibilância no primeiro ano de vida entre lactentes da cidade do Recife é alta. Início precoce e número elevado de resfriados, ter familiares com asma e ter pneumonia foram fatores associados aos quadros de sibilância nessas crianças. The aim of this study was to verify the prevalence of wheezing in infants (< 1 year of age) in Recife, Pernambuco State, Brazil, and to identify associated risk factors. Sample and methods: the study was performed according to the protocol of the International Study of Wheezing in Infants (EISL) in children ranging from 12 to 15 months of age. The sample was analyzed for presence or absence of wheezing. A total of 1,071 parents of children ranging from 12 to 15 months of age were interviewed. Prevalence of wheezing in the first year of life was 43%, with no difference between the sexes. Wheezing in the first year of life was associated with pneumonia, family history of asthma, more than nine episodes of upper airway infection, and the first cold before six months of age (p < 0.001). Prevalence of wheezing in the first year of life was high in Recife. Early onset (and high number) of colds, family history of asthma, and pneumonia were associated with wheezing in these children. Universidade Federal de Pernambuco Universidad de Santiago de Chile Universidade Federal de São Paulo (UNIFESP) Universidade Federal de São Paulo, EPM, São Paulo, Brazil SciELO

Background Recurrent wheezing (RW) during the first year of life is a major cause of respiratory morbidity worldwide, yet there are no studies on its prevalence at an international level. A study was undertaken to determine the prevalence of RW in infants during their first year of life in affluent and non-affluent localities. Methods This international population-based study was performed in random samples of infants aged 12–15 months from 17 centres in Latin America and Europe. It uses a validated questionnaire answered by parents at the primary care health clinics where infants attend for growth/development monitoring and/or vaccine administration. Results Among the 30 093 infants surveyed, 45.2% (95% CI 44.7% to 45.8%) had at least one episode of wheezing and 20.3% (95% CI 19.8% to 20.7%) had RW. The mean prevalence of RW in Latin American and European centres was 21.4% (95% CI 20.9% to 21.9%) and 15.0% (95% CI 14.0% to 15.9%), respectively (p

Objetivo: Avaliar a prevalencia e a gravidade da sibilância, bem como sua relacao com o diagnostico medico de asma, em lactentes no primeiro ano de vida, utilizando o protocolo padronizado do “Estudio Internacional de Sibilancias en Lactantes” (EISL, Estudo Internacional de Sibilâncias em Lactentes). Metodos: Entre marco de 2005 e agosto de 2006, os pais ou responsaveis de lactentes que procuraram unidades basicas de saude na regiao centro-sul de Sao Paulo (SP) para procedimentos de rotina e imunizacao responderam ao questionario escrito do EISL. Resultados: A amostra foi constituida por 1.014 lactentes (media de idade = 5,0 ± 3,0 meses), 467 (46,0%) dos quais apresentaram sibilância no primeiro ano de vida, sendo que 270 (26,6%) tiveram tres ou mais episodios. Entre esses ultimos, o uso de β 2 -agonista inalatorio, corticosteroide inalatorio e antileucotrieno, assim como a presenca de sintomas noturnos, dificuldade para respirar, pneumonia, idas ao pronto socorro e internacao por sibilância grave, foram significantemente mais frequentes (p < 0,05). Os pais de 35 (7,5%) dos 467 lactentes relataram o diagnostico medico de asma, o qual foi associado ao uso de corticosteroide inalatorio, percepcao de falta de ar durante as crises e seis ou mais episodios de sibilância no primeiro ano de vida. Entretanto, menos de 40% desses lactentes recebiam corticosteroide inalatorio ou antileucotrieno como tratamento. Conclusoes: A prevalencia da sibilância no primeiro ano de vida de lactentes no estudo foi alta e teve inicio precoce. A proporcao de lactentes diagnosticados e tratados como asmaticos foi baixa. Descritores: Asma/diagnostico; Asma/epidemiologia; Sons respiratorios.

Background Risk factors for wheezing specifically during the first year of life have been studied in well-developed countries, but the information from developing countries is very scarce. There are no such studies focusing on factors derived from poverty. The aim of the present study was to determine if risk factors related to poverty are associated to wheezing during the first year of life in infants from Honduras and El Salvador. Methods A survey, using a validated questionnaire, was carried out in the metropolitan area of San Pedro Sula (Honduras) and in La Libertad (El Salvador) in centres where infants attended for a scheduled vaccination shot or a healthy child visit at 12 months of age. Fieldworkers offered questionnaires to parents and helped the illiterate when necessary. The main outcome variable was wheezing during the first year of life, as reported by parents. Results A total of 1047 infants in El Salvador and 780 in Honduras were included in the analysis. The prevalence of wheeze in the first year was higher in El Salvador (41.2%) than in Honduras (27.7%), as was recurrent wheezing defined as three or more episodes (18.4% vs. 11.7%). Wheezing and recurrent wheezing was associated to unpaved floor in the household (summary odds ratios for both countries 1.55, p=0.036 and 1.72, p=0.054 for any wheeze and recurrent wheezing, respectively); dust entering from streets (1.30, p=0.052 and 1.67, p=0.008); living in a heavily polluted area (1.33, p=0.037 and 1.52, p=0.033); and having mould stains on the household walls (1.36, p=0.072 and 1.76, p=0.007). Furthermore, marginal associations were found for additional person at home and use of kerosene as cooking fuel. University studies in the mother (0.34, p=0.046 and 0.32, p=0.022) and a professional occupation in the father (0.34, p=0.046 and 0.26, p=0.047) were associated to a lower risk. Conclusions The prevalence of wheezing and recurrent wheezing is notoriously high in El Salvador and Honduras. In those populations factors related to poverty are associated to a higher prevalence of wheezing and recurrent wheezing, whereas higher maternal education and paternal professional occupation behave as protective factors.

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 (ORadj 0.86, 95% CI 0.73 to 1.02) and non-affluent countries (ORadj 0.71, 95% CI 0.57 to 0.88). Consumption of fish in affluent countries (ORadj 0.85, 95% CI 0.74 to 0.97) and of cooked green vegetables in non-affluent countries (ORadj 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 (ptrend=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.

Risk factors for wheezing during the first year of life (a major cause of respiratory morbidity worldwide) are poorly known in non-affluent countries. We studied and compared risk factors in infants living in affluent and non-affluent areas of the world. A population-based study was carried out in random samples of infants from centres in Latin America (LA) and Europe (EU). Parents answered validated questionnaires referring to the first year of their infant's life during routine health visits. Wheezing was stratified into occasional (1-2 episodes, OW) and recurrent (3 + episodes, RW). Among the 28687 infants included, the most important independent risk factors for OW and RW (both in LA and in EU) were having a cold during the first 3 months of life [OR for RW 3.12 (2.60-3.78) and 3.15 (2.51-3.97); population attributable fraction (PAF) 25.0% and 23.7%]; and attending nursery school [OR for RW 2.50 (2.04-3.08) and 3.09 (2.04-4.67); PAF 7.4% and 20.3%]. Other risk factors were as follows: male gender, smoking during pregnancy, family history of asthma/rhinitis, and infant eczema. Breast feeding for >3 months protected from RW [OR 0.8 (0.71-0.89) in LA and 0.77 (0.63-0.93) in EU]. University studies of mother protected only in LA [OR for OW 0.85 (0.76-0.95) and for RW 0.80 (0.70-0.90)]. Although most risk factors for wheezing are common in LA and EU; their public health impact may be quite different. Avoiding nursery schools and smoking in pregnancy, breastfeeding babies >3 months, and improving mother's education would have a substantial impact in lowering its prevalence worldwide.

Objective To test the hypothesis that consuming Mediterranean diet and using olive oil for cooking/dressing salads during pregnancy might be associated with less wheezing during the first year of the offspring's life. Methods A study was conducted in 1,409 infants (mean age, 16.6 ± 2.5 months) attending healthy infant clinics in Spain. Dietary data of mothers' intake during pregnancy was collected by means of a parental food frequency questionnaire. Demographic information and data on wheezing during the first year of the offspring's life were also recorded. Infants were stratified according to any wheezing (42.2%) during the first year of life. Results In the univariate analysis, adherence to a Mediterranean diet and using olive oil for cooking/dressing salads during pregnancy were both significantly associated with less wheezing during the first year of life. However, after multivariate analysis, only olive oil consumption during pregnancy remained associated with less wheezing in the studied period (aOR = 0.57 [95% CI = 0.4–0.9]); whereas male gender (1.8 [1.4–2.3]), day care attendance (2.15 [1.5–3.1]), maternal asthma (2.16 [1.3–3.6]), maternal smoking during pregnancy (1.83 [1.3–2.2]), infant eczema (1.95 [1.3–2.9]), and mould stains on the household walls (1.72 [1.2–2.5]) remained associated with wheezing. Conclusion Our findings suggest a protective effect (primary prevention) of olive oil use during pregnancy on wheezing during the first year of the offspring's life. Pediatr Pulmonol. 2010; 45:395–402. © 2010 Wiley-Liss, Inc.

Background The image findings of post-infectious bronchiolitis obliterans (PIBO) have been described, however, we do not know if such findings can predict lung function (LF) deterioration with increasing patient age. Aim: To assess whether computed tomography (CT) abnormalities detected at an early stage of the disease can anticipate abnormal LF a decade later in children with PIBO. Methods We compared CT scans of 21 children with PIBO, done within their first 3 years of life, and their actual LF. To evaluate CT scans we used a modified Bhalla score and, for LF, FEV1 as percentage of predicted values. We calculated prevalence ratios (PRs) by comparing the proportion of patients with worst CT score and worst LF, with the proportion of those with best CT score and worst LF. Results PR was 1.17 (CI 1.02; 1.34, P = 0.02). Conclusions The CT finding early in the life of children with PIBO, when assessed by the Bhalla, score seem to anticipate future LF status. Pediatr Pulmonol. 2010; 45:315–319. © 2010 Wiley-Liss, Inc.

Background Phase III of the International Study of Asthma and Allergies in Childhood measured the global prevalence of symptoms of asthma, rhinoconjunctivitis, and eczema in children. Objective To investigate the associations between the use of antibiotics in the first year of life and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old. Methods Parents or guardians of children 6 and 7 years old completed written questionnaires on current symptoms and possible risk factors. Prevalence odds ratios (ORs) were estimated by using logistic regression. Results A total of 193,412 children from 71 centers in 29 countries participated. Reported use of antibiotics in the first year of life was associated with an increased risk of current asthma symptoms (wheezing in the previous 12 months) with an OR (adjusted for sex, region of the world, language, and per capita gross national income) of 1.96 (95% CI, 1.85-2.07); this fell to 1.70 (1.60-1.80) when adjusted for other risk factors for asthma. Similar associations were observed for severe asthma symptoms (OR, 1.82; 95% CI, 1.67-1.98), and asthma ever (OR, 1.94; 95% CI, 1.83-2.06). Use of antibiotics in the first year of life was also associated, but less strongly, with increased risks of current symptoms of rhinoconjunctivitis (OR, 1.56; 95% CI, 1.46-1.66) and eczema (OR, 1.58; 95% CI, 1.33-1.51). Conclusion There is an association between antibiotic use in the first year of life and current symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old. Further research is required to determine whether the observed associations are causal or are a result of confounding by indication or reverse causation.

Inhaled corticosteroids are used to treat infants with troublesome asthma-like symptoms but their effect on the lung function of these young patients is controversial.Forty-four infants with recurrent wheezing (more than 3 episodes) and family history of asthma completed this randomised, parallel, double-blind, controlled trial to compare the effect on lung function (main endpoint) of once-daily inhaled fluticasone (375 microg) versus placebo for 3 months. Pulmonary function was measured while infants were asymptomatic, using the raised volume rapid thoracic compression technique (spirometry-like), and values were converted to z-scores.The fluticasone group showed a significant increase in forced flows, (p0.001), a lower number of physician diagnosed wheezing episodes (p0.002), and a significant decrease in the parent-reported number of wheezing episodes per month (p0.03), as compared to placebo. One third of parents in the placebo group reported a clinical improvement in their infants. There was no significant difference in morning plasma cortisol between groups at entry or discharge.We conclude that once-daily treatment with 375 microg fluticasone increased forced flows and controlled symptoms in infants with recurrent wheezing without altering plasma cortisol levels. The spirometry-like technique is a useful tool to objectively assess the efficacy of anti-asthma medications in infants with repeated troublesome asthma-like symptoms.

protection have been the subject of challenges and changes during the last years. Probably the most important are related with the findings of large, well-standardized epidemiological studies undertaken at global scale which have included children from several countries in different stages of development and with diverse ethnic and cultural backgrounds1-3. These studies have provided information on largely ignored aspects related to asthma prevalence in low-resourced countries, and have shown that findings, conclusions and hypotheses based on studies from well-resourced countries are not globally applicable. Furthermore, they are widely insufficient to explain the peculiarities of the distribution pattern of asthma symptoms’ prevalence in the world. The consistent lack of representation of low-resourced and culturally diverse populations in past epidemiologic studies on asthma in children has subtracted global validity to their results and has been probably an important impediment for advancing in the determination of the etiopathogenic bases of the disease. The inadequacy and partiality of this developed-countries’ approach, has been recently shown by worldwide large and inclusive studies which indicate that several “truths” regarding asthma-related epidemiologic issues are not consistent and are probably applicable only to the minority of asthmatic children. The International Study of Asthma and Allergies in Childhood (ISAAC), the largest epidemiological study ever performed at global-scale, has consistently demonstrated a remarkable variability of current asthma symptoms in the different countries and regions of the world, high prevalence in developing countries, lack of universal application of hypotheses on causation (low proportion of asthma attributable to atopy), and protection (high prevalence of asthma in children living in developing localities and low hygienic standards), and an erratic relationship between air pollution (smog) and prevalence of asthma symptoms (low asthma prevalence in centres with heavy air pollution). In Latin America, a developing region where there was no regional comparative information of childhood asthma until the advent of ISAAC (13 years ago), it has been consistently found that several of its centres were among those with the highest prevalence of asthma symptoms in the world2,4,5. The high prevalence of asthma in developing countries has been simplistically explained as that in such localities there is a different type of asthma, mainly determined by infections or viral respiratory diseases and where allergy or atopy plays a very minor role. The concept that asthma is non-atopic in developing countries, and atopic in developed ones, has commanded the notions on asthma causality, at least from a first world perspective for a long time. This would be supported by the theory that the lack of stimulation of the immune system by agents and fac

Background: Although thousands of infants under the age of 12 months die each year from pneumonia in Latin America, little is known regarding the true occurrence of pneumonia, wheezing and other related respiratory illnesses in this age group. Methods and results: In order to describe the prevalence and risk factors for radiologically confirmed pneumonia during the first year of life, a birth-cohort (n = 188) of infants born in a low-income area in Santiago, Chile was followed up monthly. Results: The prevalence of pneumonia during the first year of life was 13.3 % and there were no fatal events. Exclusive breastfeeding during the first 4 months of life was more prevalent in the non pneumonia group; conversely, wheezing episodes during 0-3 and 3-6 months of age, and hospitalization due to lower respiratory infection during 3-6 and 9-12 months of age were more prevalent in the pneumonia group. After a logistic multivariate analysis, the only risk factor that remained related with pneumonia was wheezing during the first 3 months of life (adjusted OR: 7.7, 95 CI: 1.32-44.92, p = 0.024); while breastfeeding during the first 4 months was an independent protective factor for pneumonia (adjusted OR: 0.11, 95 CI: 0.03-0.44, p = 0.002). Conclusion: The significant protective effect of exclusive breast feeding against pneumonia in this cohort and the evident role of recurrent wheezing as risk factor for pneumonia during the first year of life support the implementation or reinforcement of public policies encouraging exclusive breastfeeding and an adequate management of wheezing since the first months of life.

Spanish 'Fondo de Investigacion Sanitaria' 'Secretaria de Estado para la Cooperacion Internacional' Regional Government of Murcia, Spain Foundation to Combat Asthma (Stichting Astmabestrijding), Amsterdam, The Netherlands Male gender, asthmatic heredity, perinatal tobacco smoke exposure and respiratory infections have been associated with wheeze in the first years of life, among other risk factors. However, information about what factors modify the time to the first episode of wheeze in infants is lacking. The present study analyses which factors are associated with shorter time to the first episode of wheeze in infants. Parents of 11- to 24-month-old children were surveyed when attending their health-care centres for a control visit. They answered a questionnaire including the age in months when a first wheeze episode (if any) had occurred (outcome variable). The study was performed in 14 centres in Latin America (LA) and in 8 centres in Europe (EU) (at least 1,000 infants per centre). Factors known to be associated with wheezing in the cohort were included in a survival analysis (Cox proportional hazards model). Summary hazard ratios adjusted for all risk factors (aHR) were calculated using the meta-analysis approach with random effects. A total of 15,067 infants had experienced wheezing at least once, out of 35,049 surveyed. Male gender in LA (aHR 1.05, 95% confidence interval (CI) 1.00-1.10, P = 0.047), parental asthma in LA and EU (aHR 1.05, 95% CI 1.00-1.11, P = 0.037), infant eczema in EU (aHR 1.25, 95% CI 1.12-1.39, P < 0.001) and having a cold during the first 3 months in LA and EU (aHR 1.97, 95% CI 1.90-2.04, P < 0.001), in LA (aHR 1.98, 95% CI 1.90-2.06, P < 0.001) and in EU (aHR 1.91, 95% CI 1.75-2.09, P < 0.001) were associated with a shorter period of time to the first episode. Breast feeding for at least 3 months was associated with a longer period, only in LA (aHR 0.91, 95% CI 0.86-0.96, P < 0.001). Cold symptoms during the first 3 months is the most consistent factor shortening the time to the first episode of wheezing; breast feeding for >= 3 months delays it only in LA, whereas eczema shortens it only in EU. Avoiding a common cold in the first months of life could be a good strategy to delay the first wheeze episode; however, cohort studies will help to elucidate this association. Univ Murcia, Virgen de la Arrixaca Univ Childrens Hosp, Pediat Resp & Allergy Unit, Murcia, Spain Univ Santiago Chile USACH, Dept Pediat Resp Med, Hosp El Pino, Santiago, Chile Fed Univ Sao Paulo UNIFESP, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, Sao Paulo, Brazil Isala Klin, Princess Amalia Childrens Clin, Zwolle, Netherlands Univ Med Ctr Groningen, UMCG Postgrad Sch Med, NL-9713 AV Groningen, Netherlands Univ Murcia, Dept Pediat, Murcia, Spain IMIB Biores Inst, Murcia, Spain Fed Univ Sao Paulo UNIFESP, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, Sao Paulo, Brazil Spanish 'Fondo de Investigacion Sanitaria': PI050480 'Secretaria de Estado para la Cooperacion Internacional': A/3069/05 'Secretaria de Estado para la Cooperacion Internacional': A/5189/06 Web of Science

BACKGROUND: Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC) was designed to allow worldwide comparisons of the prevalence of asthma symptoms. In phase III the phase I survey was repeated in order to assess changes over time. METHODS: The phase I survey was repeated after an interval of 5-10 years in 106 centres in 56 countries in children aged 13-14 years (n = 304,679) and in 66 centres in 37 countries in children aged 6-7 years (n = 193,404). RESULTS: The mean symptom prevalence of current wheeze in the last 12 months changed slightly from 13.2% to 13.7% in the 13-14 year age group (mean increase of 0.06% per year) and from 11.1% to 11.6% in the 6-7 year age group (mean increase of 0.13% per year). There was also little change in the mean symptom prevalence of severe asthma or the symptom prevalence measured with the asthma video questionnaire. However, the time trends in asthma symptom prevalence showed different regional patterns. In Western Europe, current wheeze decreased by 0.07% per year in children aged 13-14 years but increased by 0.20% per year in children aged 6-7 years. The corresponding findings per year for the other regions in children aged 13-14 years and 6-7 years, respectively, were: Oceania (-0.39% and -0.21%); Latin America (+0.32% and +0.07%); Northern and Eastern Europe (+0.26% and +0.05%); Africa (+0.16% and +0.10%); North America (+0.12% and +0.32%); Eastern Mediterranean (-0.10% and +0.79%); Asia-Pacific (+0.07% and -0.06%); and the Indian subcontinent (+0.02% and +0.06%). There was a particularly marked reduction in current asthma symptom prevalence in English language countries (-0.51% and -0.09%). Similar patterns were observed for symptoms of severe asthma. However, the percentage of children reported to have had asthma at some time in their lives increased by 0.28% per year in the 13-14 year age group and by 0.18% per year in the 6-7 year age group. CONCLUSIONS: These findings indicate that international differences in asthma symptom prevalence have reduced, particularly in the 13-14 year age group, with decreases in prevalence in English speaking countries and Western Europe and increases in prevalence in regions where prevalence was previously low. Although there was little change in the overall prevalence of current wheeze, the percentage of children reported to have had asthma increased significantly, possibly reflecting greater awareness of this condition and/or changes in diagnostic practice. The increases in asthma symptom prevalence in Africa, Latin America and parts of Asia indicate that the global burden of asthma is continuing to rise, but the global prevalence differences are lessening.

OBJETIVO: Verificar a prevalência da sibilância recorrente em lactentes na cidade de Curitiba (PR). MÉTODOS: Estudo transversal pela aplicação de questionários aos pais de lactentes, idade entre 12 e 15 meses, que procuraram unidades de saúde para imunização no período entre agosto de 2005 e dezembro de 2006. Este instrumento padronizado e validado consiste de perguntas sobre características demográficas, sibilância, infecções respiratórias e fatores de risco. Durante o período de estudo, a Secretaria Municipal de Saúde possuía 107 unidades de saúde, das quais 35 foram selecionadas por sorteio e distribuídas homogeneamente no território municipal. RESULTADOS: Um total de 1.364 lactentes (45,4%) apresentou um ou mais episódios de sibilância nos primeiros 12 meses de vida, com início aos 5,5±3,1 meses (média ± desvio padrão), e 678 (22,6%) tiveram três ou mais episódios. Utilizaram β2-agonistas, corticóides inalatórios, corticóides orais e antagonistas do receptor de leucotrienos 84,6, 18,5, 24,3 e 5,4% dos sibilantes, respectivamente. Sintomas noturnos, dificuldade intensa para respirar e visitas a emergência estiveram presente em 58,9, 46,2 e 57,6% dos lactentes que sibilaram; destes, 12,7% foram hospitalizados por asma e 10,9% tiveram diagnóstico médico de asma. Sintomas noturnos, visitas à emergência, gravidade dos sintomas, hospitalização por asma e diagnóstico médico de asma foram mais freqüentes entre os que apresentaram três ou mais crises (p < 0,001). CONCLUSÃO: A prevalência de lactentes sibilantes em Curitiba é elevada, com início precoce e alta morbidade. Possivelmente, esses lactentes representam um contingente expressivo de asmáticos. OBJECTIVE: To identify the prevalence of recurrent wheezing in infants in the city of Curitiba, PR, Brazil. METHODS: A cross-sectional study carried out by means of administering questionnaires to the parents of infants aged 12 to 15 months attending health centers for immunization during the period between August 2005 and December 2006. This is a standardized and validated instrument consisting of questions on demographic characteristics, wheezing, respiratory infections and risk factors. At the time of the study the City Health Department had 107 health centers, 35 of which were selected by lots and distributed homogeneously across the municipal territory. RESULTS: A total of 1,364 infants (45.4%) had episodes of wheezing during their first 12 months of life, with onset at 5.5±3.1 months (mean ± standard deviation), and 678 (22.6%) had had three or more episodes. In 84.6% of the wheezing children treatment was with β2-agonists, with inhaled corticosteroids in 18.5%, oral corticosteroids in 24.3% and leukotriene receptor antagonists were used with 5.4%. The wheezing children exhibited nocturnal symptoms, intense difficulty breathing and visits to emergency services in the proportions of 58.9, 46.2 and 57.6%, respectively; 12.7% were admitted to hospital for asthma and 10.9% had had a medical diagnosis of asthma. Nocturnal symptoms, visits to emergency, severity of symptoms, hospital admissions for asthma and medical diagnoses of asthma were all more common among those who had suffered three or more crises (p < 0.001). CONCLUSIONS: There is an elevated prevalence of wheezing among the infants of Curitiba, with early onset and elevated morbidity. It is possible that these infants represent a large contingent of asthmatics.

The aim of this study was to determine the tuberculin skin test (TST) response to three different BCG modalities [0.1 ml Tokyo (n=104), 0.05 ml Pasteur-Merieux (n=137) and 0.1 ml Pasteur-Merieux (n=100)] in a cohort of healthy newborns 5 months after vaccination at birth in Santiago, Chile. Among the 341 infants, 91.2% had a response to TST, and the mean+/-SD TST reaction size was significantly larger in infants receiving the Tokyo strain than in those receiving the 0.05 ml or 0.1 ml Pasteur-Merieux strains (4.4+/-2.0, 3.5+/-1.3 and 3.1+/-1.4 mm, respectively; P

The prevalence of asthma in adolescents markedly varies between different localities as found by the International Study of Asthma and Allergies in Childhood (ISAAC) and this may be due to environmental factors. Although tobacco smoke exposure is related to an increase in the prevalence of asthma, there is lack of information on that respect in children from developing countries, where active tobacco smoking usually starts early in adolescence. This study was undertaken to assess the effect of tobacco smoking on the prevalence of asthma symptoms in a random sample of 4738 adolescents aged 13.4 +/- 1.05 years who responded the ISAAC video questionnaires plus questions on tobacco smoking. The prevalence of tobacco smoking in the last 12 months was 16.2%, with significant female predominance. The persistent smokers had a significantly higher prevalence of asthma-like symptoms ever and in the last 12 months (wheezing, wheezing with exercise, nocturnal wheezing, severe wheezing, and dry nocturnal cough) than ex-smokers and nonsmokers. More than 27% of asthma symptoms in our adolescents are attributable to active tobacco consumption (population attributable risk). This study strongly suggests that potent and more effective campaigns against tobacco smoking should be implemented in developing countries, where active tobacco smoking is dramatically increasing in children.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado Background: There are no internationally validated questionnaires to investigate the prevalence of infant wheezing. This study was undertaken to validate a questionnaire for the International Study on the Prevalence of Wheezing in Infants (Estudio Internacional de Sibilancias en Lactantes, EISL). Material and Methods: Construct and criterion validity were tested for the question 'Has your baby had wheezing or whistling in the chest during his/her first 12 months of life?'. Construct validity (i.e. the ability of parents and doctors to refer to the same symptoms with the same words) was tested in a sample of 50 wheezing and 50 non-wheezy infants 12-15 months of age in each of 10 centres from 6 different Spanish- or Portuguese-speaking countries. Criterion validity (i.e. the ability of parents to correctly detect the symptom in the general population) was evaluated in 2 samples (Santiago, Chile and Cartagena, Spain) of 50 wheezing and 50 non-wheezing infants (according to parents) of the same age, randomly selected from the general population, who were later blindly diagnosed by a paediatric pulmonologist. Results: Construct validity was very high (κ test: 0.98-1) in all centres. According to Youden's index, criterion validity was good both in Cartagena (75.5%) and in Santiago (67.0%). Adding questions about asthma medication did not improve diagnosis accuracy. Conclusions: The EISL questionnaire significantly distinguished wheezy infants from healthy ones. This questionnaire has a strong validity and can be employed in large international multicentre studies on wheezing during infancy. Revisión por pares

Objectives Wheezing is a very common problem in infants in the first months of life. The objective of this study is to identify risk factors that may be acted upon in order to modify the evolution of recurrent wheezing in the first months of life, and to develop a model based on certain factors associated to recurrent wheezing in nursing infants capable of predicting the probability of developing recurrent wheezing in the first year of life. Methods The sample was drawn from a cross-sectional, multicentre, descriptive epidemiological study based on the general population. A total of 1164 children were studied, corresponding to a questionnaire response rate of 71%. The questionnaire of the Estudio Internacional de Sibilancias en Lactantes (EISL) was used. Multiple logistic regression analysis was used to estimate the probability of developing recurrent wheezing and to quantify the contribution of each individual variable in the presence of the rest. Results Infants presenting eczema and attending nursery school, with a mother who has asthma, smoked during the third trimester of pregnancy, and did not consume a Mediterranean diet during pregnancy were found to have a probability of 79.7% of developing recurrent wheezing in the first year of life. In contrast, infants with none of these factors were seen to have a probability of only 4.1% of developing recurrent wheezing in the first year of life. These results in turn varied according to modifications in the risk or protective factors. Conclusions The mathematical model estimated the probability of developing recurrent wheezing in infants under one year of age in the province of Salamanca (Spain), according to the risk or protective factors associated to recurrent wheezing to which the infants are or have been exposed.

Atopic dermatitis (AD) is common in childhood, with peak prevalence in early childhood. However, international comparisons of prevalence have focused on older children. We analysed differences in prevalence rates of AD and the associations with putative risk and protective factors, among infants in two European and two Central American countries.In 1-yr old infants participating in the International Study of Wheezing in Infants (EISL), prevalence of AD and putative risk and protective factors were assessed by a questionnaire applied to parents. For each risk/protective factor summary, odds ratios with 95% confidence intervals were calculated by means of random effects meta-analysis.Data from 9803 infants were analysed. AD prevalence varied from 10.6% (Valencia, Spain) to 28.2% (San Pedro Sula, Honduras). Average AD prevalences were lower in Europe (14.2%) than in Central America (18.2%, p0.01). Consistent with older children, presence of siblings decreased (OR 0.82 [0.72-0.94]), whereas family history of asthma (OR 1.32 [1.10-1.59]), rhinitis (OR 1.33 [1.14-1.54]) and atopic dermatitis (OR 2.40 [1.89-3.05]) increased the risk of infantile AD. However, gender, family size, breastfeeding and socio-economic status were not associated with AD prevalence.This study shows almost threefold differences in the prevalence of AD in infancy between countries. Risk and protective factors involved in the expression of infantile AD differ from those in older children, possibly suggesting a different pathophysiology. There is a need for additional international epidemiological surveys on AD in young children, the peak prevalence age of this condition.

Ciclesonide (CIC) is an effective inhaled corticosteroid for treating asthmatic children. However, its effect on airway inflammation assessed by the fraction of exhaled nitric oxide (FENO) in children with persistent asthma is virtually unknown. We aimed to assess the effect of once-daily generic CIC, 80 or 160 μg, on FENO, lung function, asthma control and bronchial hyperresponsiveness, in atopic children with persistent asthma.This was a 12-week, randomised, double-blind, parallel-group study. Sixty children with mild-to-moderate persistent asthma were recruited. Changes in FENO, asthma control score, lung function (FEV1) and bronchial hyperresponsiveness to methacholine (BHR) were used to assess the effects of both CIC doses. Non-normally distributed variables were log-transformed to approximate normality, and parametric tests were used for comparisons within and between groups at baseline and after 12 weeks of treatment.In the CIC 80 μg group, FENO decreased from 45.0 ppb (95% CI 37.8-53.7) to 32.7 ppb (95% CI 21.0-47.3) at the end of study (P=0.021), whereas in the CIC 160 μg group, FENO decreased from 47.3 ppb (95% CI 40.4-55.3) to 30.5 ppb (95% CI 24.1-38.7) (P0.001). The difference between groups in FENO at the end of study was not significant (P=0.693). There was a significant improvement of asthma control with both CIC doses but there was no significant change in BHR or FEV1 in either group.Once-daily generic ciclesonide (80 μg or 160 μg), for 12 weeks, is effective to improve airway inflammation and asthma control in atopic children with persistent asthma.

Background The fraction of exhaled nitric oxide (FENO) measured using portable devices is increasingly used in the clinical setting to assess asthmatic children. However, there is little and variable information on the reference values obtained using these devices in healthy children from different populations. Methods 190 healthy non-smoker children (8–15 years old) were randomly selected from public schools participating in this study. The objective was to determine FENO reference values for healthy Chilean schoolchildren. Healthy individuals were identified by medical interview and parent questionnaire on the use of asthma medications, and current and past symptoms of asthma, rhinoconjunctivitis and eczema. FENO was measured at schools using a portable device with electrochemical sensor (NIO MINOX). Reference values of FENO were expressed as geometric mean and upper limit of the 95% reference interval (right-sided). The relationship of FENO with gender, age, height, body mass, and other factors was assessed by multiple regression, and the difference between groups was contrasted by ANOVA. Results The FENO geometric mean was 15.4 ppb with a 95% reference interval upper limit (right-sided), of 27.4 ppb (90%CI 25.6–29.2). The 5th and 95th percentiles were 9.0 ppb and 28.0 ppb, respectively. Height was the only factor significantly associated to FENO (p = 0.022). There was no significant difference in mean FENO regarding age, gender, weight, parent reported rhinoconjunctivitis and eczema. Conclusion This study suggests that FENO values higher than 27 ppb are likely to be abnormal and would reflect airway inflammation in children as those in the present study.

Objective: to investigate the prevalence and risk factors associated with wheezing in infants in the first year of life. Methods: this was a cross-sectional study, in which a validated questionnaire (Estudio Internacional de Sibilancias en Lactantes - International Study of Wheezing in Infants - EISL) was applied to parents of infants aged between 12 and 15 months treated in 26 of 85 primary health care units in the period between 2006 and 2007. The dependent variable, wheezing, was defined using the following standards: occasional (up to two episodes of wheezing) and recurrent (three or more episodes of wheezing). The independent variables were shown using frequency distribution to compare the groups. Measures of association were based on odds ratio (OR) with a confidence interval of 95% (95% CI), using bivariate analysis, followed by multivariate analysis (adjusted OR [aOR]). Results: a total of 1,029 (37.7%) infants had wheezing episodes in the first 12 months of life; of these, 16.2% had recurrent wheezing. Risk factors for wheezing were family history of asthma (OR = 2.12; 95% CI: 1.76-2.54) and six or more episodes of colds (OR = 2.38; 95% CI: 1.91-2.97) and pneumonia (OR = 3.02; 95% CI: 2.43-3.76). For recurrent wheezing, risk factors were: familial asthma (aOR = 1.73; 95% CI: 1.22–2.46); early onset wheezing (aOR = 1.83; 95% CI: 1.75-3.75); nocturnal symptoms (aOR = 2.56; 95% CI: 1.75-3.75), and more than six colds (aOR = 2.07; 95% CI 1.43- .00). Conclusion: the main risk factors associated with wheezing in Fortaleza were respiratory infections and family history of asthma. Knowing the risk factors for this disease should be a priority for public health, in order to develop control and treatment strategies. Resumo: Objetivo: verificar a prevalência e fatores de risco associados à sibilância em lactentes no primeiro ano de vida. Métodos: estudo transversal, onde foi aplicado o questionário padronizado e validado (Estudio Internacional de Sibilancias en Lactantes-EISL) aos pais de lactentes com idade entre 12 e 15 meses que procuraram 26 das 85 unidades de atenção básica, no período 2006 a 2007. A variável dependente, sibilância, foi definida utilizando os seguintes padrões: ocasional (até dois episódios de sibilância) e recorrente (três ou mais episódios). As variáveis independentes foram apresentadas usando distribuição de frequências, utilizadas para comparar os grupos. As medidas de associações foram baseadas em razão de chances (odds ratio-OR), com intervalo de confiança de 95% (IC95%), com análise bivariada, seguida de análise multivariada (OR ajustada). Resultados: um total de 1.029 (37,7%) lactentes apresentou sibilância nos primeiros 12 meses de vida e destes, 16,2% tiveram sibilância recorrente. Os principais fatores de risco associados à sibilância foram: história familiar de asma (ORa = 2,12; IC95%: 1,76-2,54); seis ou mais episódios de resfriado (ORa = 2,38; IC95%: 1,91-2,97) e pneumonia (ORa = 3,02; IC95%: 2,43-3,76) e sibilância recorrente foram: asma na família (ORa = 1,73; IC95%: 1,22-2,46); início precoce de sibilância (ORa = 1,83; IC95%: 1,75-3,75); sintomas noturnos (ORa = 2,56; IC95%: 1,75-3,75); mais de 6 resfriados (ORa = 2,07; IC95%: 1,43-3,00). Conclusão: os principais fatores de risco associados à sibilância foram as infecções respiratórias e história de asma na família. Conhecer os fatores de risco dessa enfermidade deve ser uma prioridade para a saúde pública, que poderá desenvolver estratégias de controle e tratamento. Keywords: Prevalence, Risk factors, Cross-sectional studies, Infant, Palavras-chave: Prevalência, Fatores de risco, Estudos transversais, Lactente

The aim of this study was to determine the influence of altering the nebulizer flow rate and volume fill on intrapulmonary deposition of nebulized gentamicin in adolescents with cystic fibrosis (CF). A single group of individuals inhaled randomly from two nebulization systems in a cross-over fashion. For System A, gentamicin 80 mg labeled with 4 mCi Tc 99m DTPA, diluted to 2 ml were placed in a jet nebulizer (JN) driven by an airflow of 5.5 1/min. For System B, the volume fill was 4 ml and the flow 10 1/min. The mass median diameter (MMD) of aerosol in System A and B was 4.4 m and 3.1 m, respectively. The nebulizer in System B released twice the volume (3.47 ± 0.04 ml) of gentamicin solution compared to System A (1.71 ± 0.03 ml) during similar nebulization time. Intrathoracic deposition was 4.0 ± 2.7% for System A and 7.1 ± 2.8% for System B. Lung deposition in patients inhaling from System A and B was 3.2 ± 1.8% and 6.2 ± 2.1%, respectively (p < 0.05). This study demonstrates that operating cond...

Twenty asymptomatic infants with cystic fibrosis (CF) were studied to determine the amount of radiolabeled aerosol [99m technetium diethylenetriamine penta acetic acid (Tc99m DTPA)] deposited in the respiratory system and its distribution. Aerosols were generated by jet nebulization systems that were used in the wards and the laboratory. Subjects were studied in three groups: group A (n = 10) was sedated with chloral hydrate; children inhaled an aerosol of 7.7 μm mass median diameter (MMD): group B (n = 5) was not sedated, using the same nebulization system (same aerosol particle size as group A); and group C (n = 5) was not sedated; these children inhaled an aerosol with an MMD of 3.6 μm. Normal saline plus 4 mCi of Tc99m bound to DTPA was added to each nebulizer. A closed system was used to collect the expired aerosol. Radioactivity in each infant and in the equipment was measured with a gamma camera on completion of nebulization. In groups A and B, the percentages of the total dose deposited in the lung were 0.97 ± 0.35% and 0.76 ± 0.36%, respectively. In group C, 2.0 ± 0.71% was deposited in the lung (P < 0.01). Deposition in the nose, mouth, and pharynx was least in group C (P < 0.01). In groups A and B, the intrathoracic deposition occurred predominantly in the trachea and main bronchi, whereas in group C, significantly more aerosol was deposited in the lung region. There was marked inter-subject variability in the percentage of aerosol deposition within the three groups. There was no correlation between percentage of aerosol deposited in the respiratory system and age, height, or weight. Sedation did not have a significant effect on deposition of aerosol in infants. This study indicates that only a small proportion of nebulized solution is deposited in the lungs of infants and that this proportion is influenced by the particle size of the aerosol. The smaller particle size (3.6 μm MMD) was deposited in the lung better than large particles. Pediatr Pulmonol. 1996; 21:276–281. © 1996 Wiley-Liss, Inc.

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.

Background The International Study of Asthma and Allergies in Childhood (ISAAC) used standardised methods to examine symptom prevalence of asthma, rhinitis and eczema in adolescents and children between Phases I and III. Centres followed essential rules to ensure comparability of methodology, examined by a centralised data centre. Methods Centre reports (CRs) were compared for both phases and age groups. Methodological differences were categorised under major deviations (centres excluded), minor deviations (deviations identified in published tables) and very minor deviations (deviations not identified). Results There were 112 CRs for adolescents and 70 for children. Six centres for adolescents and four for children had major deviations and were excluded. Minor deviations (35 for adolescents and 20 for children) were identified in the publications. Very minor deviations (92 for adolescents and 51 for children) were not identified. The odds ratios for having any differences in methodology between phases with a change in Principal Investigator were 0.80 (95%CI 0.36-1.81) for adolescents and 0.91 (95%CI 0.32-2.62) for children. Conclusion The majority of the centres replicated the ISAAC methodology to a high standard. Careful documentation of methodology using standardised tools with careful checks allows the full potential of studies such as ISAAC to be realised.