Birthweight and the risk of atopic diseases: the ISAAC Phase III study.

BACKGROUND: The association between birthweight and asthma, eczema and rhinoconjunctivitisis conflicting. AIMS: To examine the association between birthweight and symptoms of asthma, eczema and rhinoconjunctivitis. METHODS: Parents or guardians of children aged 6­7 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(<2.5 kg) was associated with an increased risk of symptoms of asthma (current wheeze odds ratio = 1.20; 95% confidence interval = 1.12­1.30). Low birthweight was associated with a lower risk of eczema ever. Low birthweight was not associated with rhinoconjunctivitis. Large babies (birthweight ≥4.5 kg) were not associated with any of these outcomes. CONCLUSIONS: This study has confirmed that low birthweight is a risk factor for symptoms of asthma, but not for rhinoconjunctivitis. The findings for eczema are equivocal.

Time trends, ethnicity and risk factors for eczema in New Zealand children: ISAAC Phase Three.

BACKGROUND: Eczema is a common chronic disease which has significant morbidity and costs for children and their families. Phase One (1993) of the International Study of Asthma and Allergies in Childhood (ISAAC) found a high prevalence of symptoms of eczema in New Zealand. OBJECTIVE: In Phase Three (2001-3) we aimed to answer these three questions: Is the prevalence of eczema changing over time?; Are there ethnic differences in prevalence?; and What are the risk factors for eczema? METHODS: Five New Zealand centres participated in ISAAC Phases One and Three using the same methodology. Questionnaires about ethnicity, symptoms of eczema and environmental factors were completed by parents of 6-7 year olds (children) and self-completed by 13-14 year olds (adolescents). Prevalence and change per year were calculated by centre, ethnicity and gender. Prevalence differences between centres and associations with environmental factors were examined using logistic regression. RESULTS: There was little change in prevalence over time for the children, and a decrease in prevalence for the adolescents. Prevalence was higher among Maori and even higher among Pacific participants than among European children. Positive associations with current eczema symptoms were found for both age groups for truck traffic in the street of residence, and current paracetamol consumption, and for children only, antibiotics or paracetamol in the 1st year of life. Inverse associations were found with residence in New Zealand less than 5 years, consumption of milk, seafood, and eggs, and presence of a dog in the home. CONCLUSION: Eczema remains a significant problem, particularly for young Maori and Pacific New Zealanders in whom less recognition of eczema and poorer access to effective, sustained eczema management may be contributing factors. Reverse causation may explain all the environmental findings apart from truck traffic which is increasing in New Zealand.

Time trends and risk factors for rhinoconjunctivitis in New Zealand children: an International Study of Asthma and Allergies in Childhood (ISAAC) survey.

AIM: To investigate prevalence, time trends and factors associated with rhinitis and rhinoconjunctivitis not related to acute infections in New Zealand. METHODS: The International Study of Asthma and Allergies in Childhood (ISAAC) surveyed children aged 6-7 and 13-14 years for symptoms of these conditions. Five New Zealand centres were surveyed on two occasions (Phase One and Phase Three) 8-10 years apart. In Phase Three, questions were included on environmental factors, which might be associated with rhinoconjunctivitis. We report findings related to symptoms of rhinoconjunctivitis among 24 190 New Zealand children. RESULTS: Symptoms of rhinoconjunctivitis in the past year were reported in 11.4% of 6- to 7-year-old children and 18% of 13- to 14-year-old adolescents in Phase Three compared with 9.5 and 19.1%, respectively, in Phase One. Severe symptoms of rhinoconjunctivitis were reported in 0.5% of children and 0.8% of adolescents. Current symptoms were more common in males at 6-7 years and in females of 13-14 years, and Maori and Pacific Island ethnic groups had higher prevalence compared with those of European descent, especially in the older age group. For immigrant children, there was a very strong positive relationship between symptoms and length of time resident in New Zealand, supporting the probable importance of environmental factors. A positive association was found between symptoms and use of paracetamol in infancy or in the last year, and weaker associations were noted for antibiotic use, exercise, and regular pasta ingestion. CONCLUSIONS: Further study of environmental factors is recommended.

Satellite-based estimates of ambient air pollution and global variations in childhood asthma prevalence.

BACKGROUND: The effect of ambient air pollution on global variations and trends in asthma prevalence is unclear. OBJECTIVES: Our goal was to investigate community-level associations between asthma prevalence data from the International Study of Asthma and Allergies in Childhood (ISAAC) and satellite-based estimates of particulate matter with aerodynamic diameter < 2.5 µm (PM2.5) and nitrogen dioxide (NO2), and modelled estimates of ozone. METHODS: We assigned satellite-based estimates of PM2.5 and NO2 at a spatial resolution of 0.1° × 0.1° and modeled estimates of ozone at a resolution of 1° × 1° to 183 ISAAC centers. We used center-level prevalence of severe asthma as the outcome and multilevel models to adjust for gross national income (GNI) and center- and country-level sex, climate, and population density. We examined associations (adjusting for GNI) between air pollution and asthma prevalence over time in centers with data from ISAAC Phase One (mid-1900s) and Phase Three (2001-2003). RESULTS: For the 13- to 14-year age group (128 centers in 28 countries), the estimated average within-country change in center-level asthma prevalence per 100 children per 10% increase in center-level PM2.5 and NO2 was -0.043 [95% confidence interval (CI): -0.139, 0.053] and 0.017 (95% CI: -0.030, 0.064) respectively. For ozone the estimated change in prevalence per parts per billion by volume was -0.116 (95% CI: -0.234, 0.001). Equivalent results for the 6- to 7-year age group (83 centers in 20 countries), though slightly different, were not significantly positive. For the 13- to 14-year age group, change in center-level asthma prevalence over time per 100 children per 10% increase in PM2.5 from Phase One to Phase Three was -0.139 (95% CI: -0.347, 0.068). The corresponding association with ozone (per ppbV) was -0.171 (95% CI: -0.275, -0.067). CONCLUSION: In contrast to reports from within-community studies of individuals exposed to traffic pollution, we did not find evidence of a positive association between ambient air pollution and asthma prevalence as measured at the community level.

Early life exposure to farm animals and symptoms of asthma, rhinoconjunctivitis and eczema: an ISAAC Phase Three Study.

BACKGROUND: Associations between early life exposure to farm animals and respiratory symptoms and allergy in children have been reported in developed countries, but little is known about such associations in developing countries. OBJECTIVE: To study the association between early life exposure to farm animals and symptoms of asthma, rhinoconjunctivitis and eczema in a worldwide study. METHODS: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) was carried out in 6- to 7-year-old children in urban populations across the world. Questions about early life exposure to farm animals (at least once/week) were included in an additional questionnaire. The association between such exposures and symptoms of asthma, rhinoconjunctivitis and eczema was investigated with logistic regression. Adjustments were made for gender, region of the world, language, gross national income and 10 other subject-specific covariates. RESULTS: A positive association was found between early exposure to farm animals and the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, especially in non-affluent countries. In these countries, odds ratios (ORs) for 'current wheeze', 'farm animal exposure in the first year of life' and 'farm animal exposure in pregnancy' were 1.27 [95% confidence interval (CI) 1.12-1.44] and 1.38 (95% CI 1.21-1.58), respectively. The corresponding ORs for affluent countries were 0.96 (95% CI 0.86-1.08) and 0.95 (95% CI 0.84-1.08), respectively. CONCLUSION: Exposure to farm animals during pregnancy and in the first year of life was associated with increased symptoms of asthma, rhinoconjunctivitis and eczema in 6- to 7-year-old children living in non-affluent but not in affluent countries.

Acetaminophen use and risk of asthma, rhinoconjunctivitis, and eczema in adolescents: International Study of Asthma and Allergies in Childhood Phase Three.

RATIONALE: There is epidemiological evidence that the use of acetaminophen may increase the risk of developing asthma. OBJECTIVES: To investigate the risk of asthma and other allergic disorders associated with the current use of acetaminophen in 13- to 14-year-old children in different populations worldwide. METHODS: As part of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three, 13- to 14-year-old children completed written and video questionnaires obtaining data on current symptoms of asthma, rhinoconjunctivitis, and eczema, and a written environmental questionnaire obtaining data on putative risk factors, including acetaminophen use in the past 12 months. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the odds ratio (OR) of current asthma symptoms associated with acetaminophen use calculated by logistic regression. A total of 322,959 adolescent children from 113 centers in 50 countries participated. In the multivariate analyses the recent use of acetaminophen was associated with an exposure-dependent increased risk of current asthma symptoms (OR, 1.43 [95% confidence interval, 1.33-1.53] and 2.51 [95% confidence interval, 2.33-2.70] for medium and high versus no use, respectively). Acetaminophen use was also associated with an exposure-dependent increased risk of current symptoms of rhinoconjunctivitis and eczema. CONCLUSIONS: Acetaminophen use may represent an important risk factor for the development and/or maintenance of asthma, rhinoconjunctivitis, and eczema in adolescent children.

Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three.

BACKGROUND: In 1999, The International Study of Asthma and Allergies in Childhood (ISAAC) Phase One reported the prevalence of eczema symptoms in 715,033 children from 154 centers in 56 countries by using standardized epidemiologic tools. OBJECTIVE: To update the world map of eczema prevalence after 5 to 10 years (ISAAC Phase Three) and include additional data from over 100 new centers. METHODS: Cross-sectional surveys using the ISAAC questionnaire on eczema symptoms were completed by adolescents 13 to 14 years old and by parents of children 6 to 7 years old. Current eczema was defined as an itchy flexural rash in the past 12 months and was considered severe eczema if associated with 1 or more nights per week of sleep disturbance. RESULTS: For the age group 6 to 7 years, data on 385,853 participants from 143 centers in 60 countries showed that the prevalence of current eczema ranged from 0.9% in India to 22.5% in Ecuador, with new data showing high values in Asia and Latin America. For the age group 13 to 14 years, data on 663,256 participants from 230 centers in 96 countries showed prevalence values ranging from 0.2% in China to 24.6% in Columbia with the highest values in Africa and Latin America. Current eczema was lower for boys than girls (odds ratio, 0.94 and 0.72 at ages 6 to 7 years and 13 to 14 years, respectively). CONCLUSION: ISAAC Phase Three provides comprehensive global data on the prevalence of eczema symptoms that is essential for public health planning. New data reveal that eczema is a disease of developing as well as developed countries.

Cross-sectional survey of risk factors for asthma in 6-7-year-old children in New Zealand: International Study of Asthma and Allergy in Childhood Phase Three.

AIM: To identify risk factors for asthma in primary school-aged children in New Zealand. METHODS: A cross-sectional survey of 10,873 6-7-year-old children in Auckland, Bay of Plenty, Nelson and Christchurch (a response rate of 85.2%). A questionnaire was completed by the parent or care giver. RESULTS: 22.2% of children wheezed in the last 12 months (current wheeze). Maori children were at greater risk of current wheeze compared with European children (adjusted odds ratio (adjOR) = 1.37; 95% confidence interval = 1.18-1.59). Antibiotics and paracetamol used in the first year of life were associated with an increased risk of current wheeze (adjOR = 1.78 (1.56-2.04) and adjOR = 1.31 (1.06-1.61), respectively). Watching television for 5 or more hours per day was associated with an increased risk of current wheeze (adjOR = 1.44 (1.13-1.83)). Milk and egg consumption in the last 12 months was associated with a reduced risk of current wheeze. CONCLUSIONS: This study has identified risk factors for asthma in children aged 6-7 years, although causal pathways cannot be established. These associations have important public health implications if causal.

The prevalence of atopic symptoms in children with otitis media with effusion.

OBJECTIVE: To determine the prevalence of allergic symptoms in children with otitis media with effusion (OME). STUDY DESIGN: A validated questionnaire from the International Study of Asthma and Allergies in Childhood was used to determine the prevalence of allergic symptoms in children. The questionnaire was completed by the parents of children with OME undergoing ventilation tube insertion, and the results were compared with a large reference group of school children of the same age. SUBJECTS AND METHODS: Children aged 6 or 7 years old with OME confirmed intraoperatively during ventilation tube insertion between 2001 and 2005 (n=89). The prevalence of allergic symptoms and nasal symptoms in children with OME was compared with an age-matched reference group. RESULTS: There was no difference in the prevalence of allergic symptoms suggesting rhinoconjunctivitis, asthma, or eczema between the OME and reference group. The prevalence of nasal symptoms, however, was greater in the children with OME than in the reference group 38.2 percent versus 23.5 percent (odds ratio=2.01; 95% confidence interval, 1.30-3.10; P<0.001). CONCLUSION: The prevalence of allergic symptoms was similar in 6- to 7-year-old children with OME and the reference group, suggesting a limited effect of allergy in the pathogenesis of OME in this age group. Nasal symptoms were more common in the OME group, which may reflect a higher prevalence of adenoidal hyperplasia.

Has the prevalence and severity of symptoms of asthma changed among children in New Zealand? ISAAC Phase Three.

AIM: To investigate time trends in prevalence of symptoms of asthma by repeating, during 2001-3 (Phase Three), the International Study of Asthma and Allergies in Childhood (ISAAC) Phase One study that was conducted in New Zealand in 1992-3. METHODS: ISAAC Phase Three involved repeating the cross-sectional questionnaire survey of two age groups of school children (6-7 years and 13-14 years, children and adolescents respectively) using the same methodology as Phase One. In New Zealand it was conducted in Auckland, Bay of Plenty, Christchurch, Nelson, and Wellington. RESULTS: After 9 years, reported asthma ever increased from 24.6% to 30.2% in children and from 24.1% to 32.4% in adolescents (p<0.001). Current wheeze (written questionnaire) significantly decreased in children from 23.6% to 22.2% (p=0.002) and in adolescents from 29.7% to 26.7% (p=0.047), and for the video questionnaire from 18.1% to 11.1% (p<0.001). There was a significant reduction in wheezing limiting speech from 5.0% to 3.7% in children, and 7.9% to 6.2% in adolescents. Little regional variation was found. A higher proportion of children with asthma symptoms now report having ever had asthma. CONCLUSIONS: The decrease in prevalence and severity of symptoms of asthma is encouraging, but the reasons for these trends are currently unclear. Increases in asthma labelling are likely to be due to greater awareness of asthma. A trend of decreasing prevalence of asthma symptoms, if maintained, has positive implications for lessened burden of disease among asthmatics and lowered cost of treatment.

Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme.

BACKGROUND: Exposure to paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma. We studied 6-7-year-old children from Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) programme to investigate the association between paracetamol consumption and asthma. METHODS: As part of Phase Three of ISAAC, parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis, and eczema, and several risk factors, including the use of paracetamol for fever in the child's first year of life and the frequency of paracetamol use in the past 12 months. The primary outcome variable was the odds ratio (OR) of asthma symptoms in these children associated with the use of paracetamol for fever in the first year of life, as calculated by logistic regression. FINDINGS: 205 487 children aged 6-7 years from 73 centres in 31 countries were included in the analysis. In the multivariate analyses, use of paracetamol for fever in the first year of life was associated with an increased risk of asthma symptoms when aged 6-7 years (OR 1.46 [95% CI 1.36-1.56]). Current use of paracetamol was associated with a dose-dependent increased risk of asthma symptoms (1.61 [1.46-1.77] and 3.23 [2.91-3.60] for medium and high use vs no use, respectively). Use of paracetamol was similarly associated with the risk of severe asthma symptoms, with population-attributable risks between 22% and 38%. Paracetamol use, both in the first year of life and in children aged 6-7 years, was also associated with an increased risk of symptoms of rhinoconjunctivitis and eczema. INTERPRETATION: Use of paracetamol in the first year of life and in later childhood, is associated with risk of asthma, rhinoconjunctivitis, and eczema at age 6 to 7 years. We suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood.

Worldwide time trends for symptoms of rhinitis and conjunctivitis: Phase III of the International Study of Asthma and Allergies in Childhood.

In Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC) time trends in the prevalence of rhinoconjunctivitis symptoms were analysed. Cross-sectional questionnaire surveys with identical protocols and questionnaires were completed a mean of 7 yr apart in two age groups comprising 498,083 children. In the 13- to 14-yr age group 106 centres in 56 countries participated, and in the 6- to 7-yr age group 66 centres in 37 countries participated. A slight worldwide increase in rhinoconjunctivitis prevalence was observed, but the variations were large among the centres and there was no consistent regional pattern. Prevalence increases in the older children exceeding 1% per year were recorded in 13 centres, including 3 of 9 centres in Africa, 2 of 15 in Asia-Pacific, 1 of 8 in India, 3 of 15 in Latin America, 3 of 9 in Eastern Europe and 1 of 34 in Western and Northern Europe. Decreasing rhinoconjunctivititis prevalence of similar magnitude was only seen in four centres. The changes were less pronounced in the 6- to 7-yr-old children and only in one centre did any change exceed 1% per year. The decrease in highest prevalence rates in ISAAC Phase I suggests that the prevalence has peaked in those regions. An increase was recorded in several centres, mostly in low and mid-income countries. The increases were more pronounced in the older age group, suggesting that environmental influences on the development of allergy may not be limited to early childhood.

Asthma prevalence in European, Maori, and Pacific children in New Zealand: ISAAC study.

The International Study of Asthma and Allergies in Childhood (ISAAC) demonstrated that the highest prevalence of asthma in the world is in English-speaking countries, including New Zealand. In this paper, we compare asthma symptom prevalence in the three major ethnic groups (Maori, Pacific, and European) in the six participating centers in New Zealand. Hospital admission rates for asthma are higher among Maori and Pacific children compared to European children. The working hypothesis was that there were important differences in prevalence of asthma symptoms or diagnosis between ethnic groups which might explain these observed differences in asthma morbidity. In each center in 1992-1993, we sampled approximately 3000 children at each of the age brackets 6-7 years and 13-14 years. There were 37592 participants. Maori children had higher rates of diagnosed asthma and reported asthma symptoms than Pacific children in both age groups (diagnosed asthma in 6-7-year-olds: Maori, 31.7%; Pacific, 21.2%; 95% confidence interval on difference (CID), 7.2, 13.8; P < 0.001; 13-14-year-olds: Maori, 24.7%; Pacific, 19.2%; CID 2.5, 8.5; P < 0.001; recent wheeze in 6-7-year-olds: Maori, 27.6%; Pacific, 22.0%; CID, 2.6, 8.6; P < 0.001; 13-14-year-olds: Maori, 30.8%; Pacific, 21.1%; CID, 4.8, 14.5; P < 0.001;). European children had rates intermediate between those of Maori and Pacific children (6-7-year-olds) or similar to those of Maori children (13-14-year-olds), but had the lowest prevalence of night waking with wheeze in both age groups (e.g., 6-7-year-olds: European, 2.6%; Maori, 5.8%; Pacific, 5.7%; European-Maori CID: -4.2, -2.2, P < 0.001; European-Pacific CID: -4.7, -1.7, P < 0.001; Maori-Pacific CID: -1.7, 1.8, P = 1.0). The pattern of differences closely resembled that in a 1985 Auckland study, despite a 1.5-1.7-fold overall increase in prevalence. In conclusion, there are important differences in asthma prevalence among Maori, Pacific, and European children. These differences are small compared to worldwide variation, but their pattern is stable over time. The higher rate of severe asthma symptoms that Maori and Pacific children report may be one reason for the increased asthma morbidity in these groups. Further studies are needed to determine the reasons for these apparent differences in asthma severity.