Edwin A. Mitchell

International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods.

The aetiology of asthma and allergic disease remains poorly understood, despite considerable research. The International Study of Asthma and Allergies in Childhood (ISAAC), was founded to maximize the value of epidemiological research into asthma and allergic disease, by establishing a standardized methodology and facilitating international collaboration. Its specific aims are: 1) to describe the prevalence and severity of asthma, rhinitis and eczema in children living in different centres, and to make comparisons within and between countries; 2) to obtain baseline measures for assessment of future trends in the prevalence and severity of these diseases; and 3) to provide a framework for further aetiological research into genetic, lifestyle, environmental, and medical care factors affecting these diseases. The ISAAC design comprises three phases. Phase 1 uses core questionnaires designed to assess the prevalence and severity of asthma and allergic disease in defined populations. Phase 2 will investigate possible aetiological factors, particularly those suggested by the findings of Phase 1. Phase 3 will be a repetition of Phase 1 to assess trends in prevalence.

Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC)

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.

Worldwide variations in the prevalence of symptoms of atopic eczema in the international study of asthma and allergies in childhood

BACKGROUND Little is known about the prevalence of atopic eczema outside Northern Europe. OBJECTIVES We sought to describe the magnitude and variation in the prevalence of atopic eczema symptoms throughout the world. METHODS A cross-sectional questionnaire survey was conducted on random samples of schoolchildren aged 6 to 7 years and 13 to 14 years from centers in 56 countries throughout the world. Those children with a positive response to being questioned about the presence of an itchy relapsing skin rash in the last 12 months that had affected their skin creases were considered to have atopic eczema. Children whose atopic eczema symptoms resulted in sleep disturbance for 1 or more nights per week were considered to have severe atopic eczema. RESULTS Complete data was available for 256,410 children aged 6 to 7 years in 90 centers and 458,623 children aged 13 to 14 years in 153 centers. The prevalence range for symptoms of atopic eczema was from less than 2% in Iran to over 16% in Japan and Sweden in the 6 to 7 year age range and less than 1% in Albania to over 17% in Nigeria for the 13 to 14 year age range. Higher prevalences of atopic eczema symptoms were reported in Australasia and Northern Europe, and lower prevalences were reported in Eastern and Central Europe and Asia. Similar patterns were seen for symptoms of severe atopic eczema. CONCLUSIONS Atopic eczema is a common health problem for children and adolescents throughout the world. Symptoms of atopic eczema exhibit wide variations in prevalence both within and between countries inhabited by similar ethnic groups, suggesting that environmental factors may be critical in determining disease expression. Studies that include objective skin examinations are required to confirm these findings.

Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC).

Background: As part of the International Study of Asthma and Allergies in Childhood (ISAAC), prevalence surveys were conducted among representative samples of school children from locations in Europe, Asia, Africa, Australasia, North and South America.

A differential effect of 2 probiotics in the prevention of eczema and atopy: A double-blind, randomized, placebo-controlled trial

BACKGROUND The role of probiotics in prevention of allergic disease is still not clearly established, although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years. OBJECTIVE To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years. METHODS Double-blind, randomized placebo-controlled trial of infants at risk of allergic disease. Pregnant women were randomized to take Lactobacillus rhamnosus HN001 (L rhamnosus), Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding, and their infants were randomized to receive the same treatment from birth to 2 years (n = 474). The infants cumulative prevalence of eczema and point prevalence of atopy, using skin prick tests to common allergens, was assessed at 2 years. RESULTS Infants receiving L rhamnosus had a significantly (P = .01) reduced risk of eczema (hazard ratio [HR], 0.51; 95% CI, 0.30-0.85) compared with placebo, but this was not the case for B animalis subsp lactis (HR, 0.90; 95% CI, 0.58-1.41). There was no significant effect of L rhamnosus (HR, 0.74; 95% CI, 0.46-1.18) or B animalis subsp lactis (HR, 0.82; 95% CI, 0.52-1.28) on atopy. L rhamnosus (71.5%) was more likely than B animalis subsp lactis (22.6%) to be present in the feces at 3 months, although detection rates were similar by 24 months. CONCLUSION We found that supplementation with L rhamnosus, but not B animalis subsp lactis, substantially reduced the cumulative prevalence of eczema, but not atopy, by 2 years. Understanding how Lactobacilli act to prevent eczema requires further investigation.

Clinical Characteristics and Serum Essential Fatty Acid Levels in Hyperactive Children

This study compared 48 hyperactive children with 49 age-and-sex-matched controls. Significantly more hyperactive children had auditory, visual, language, reading, and learning difficulties, and the birth weight of hyperactive children was significantly lower than that of controls (3,058 and 3,410 g, respectively; p < 0.01). In addition, significantly more hyperactive children had frequent coughs and colds, polydypsia, polyuria, and a serious illness or accident in the past year than controls, but there was no increase in asthma, eczema, or other allergies. Serum essential fatty acid (EFA) levels were measured in 44 hyperactive subjects and 45 controls. The levels of docasahexaenoic, dihomogammalinolenic, and arachidonic acids were significantly lower in hyperactive children than controls (docosahexaenoic: 41.6 and 49.5 μg/ml serum respectively, p = 0.045; dihomogammolinolenic: 34.9 and 41.3 μg/ml serum, p = 0.007; arachidonic : 127.1 and 147.0 μg/ml serum, p = 0.027). These findings have possible therapeutic and diagnostic implications, but further research is needed to attempt to replicate these differences.

The effects of essential fatty acid supplementation by efamol in hyperactive children

Thirty-one children, selected for marked inattention and overactivity, were studied in a double-blind, placebo-controlled crossover study of essential fatty acid (EFA) supplementation. Subjects received the active treatment and placebo conditions for 4 weeks each and were assessed on a variety of cognitive, motor, and standardized rating scale measures. EFA supplementation (evening primrose oil; Efamol®) resulted in significantly lower levels of palmitoleic acid (a nonessential fatty acid) and higher concentrations of dihomogammalinolenic acid, an EFA previously found to be deficient in some hyperactive children. Supplementation was also associated with significant changes on two performance tasks and with significant improvement to parent ratings on the subscales designated as Attention Problem and Motor Excess of the Revised Behavior Problem Checklist. However, a variety of eight other psychomotor performance tests and two standardized teacher rating scales failed to indicate treatment effects. When the experimentwise probability level was set at.05, only 2 of 42 variables showed treatment effects. Baseline EFA concentrations appeared to be unrelated to treatment response. It was concluded that EFA supplementation, as employed here, produces minimal or no improvements in hyperactive children selected without regard to baseline EFA concentrations.

Bed sharing when parents do not smoke: is there a risk of SIDS? An individual level analysis of five major case–control studies

Objective To resolve uncertainty as to the risk of Sudden Infant Death Syndrome (SIDS) associated with sleeping in bed with your baby if neither parent smokes and the baby is breastfed. Design Bed sharing was defined as sleeping with a baby in the parents’ bed; room sharing as baby sleeping in the parents’ room. Frequency of bed sharing during last sleep was compared between babies who died of SIDS and living control infants. Five large SIDS case–control datasets were combined. Missing data were imputed. Random effects logistic regression controlled for confounding factors. Setting Home sleeping arrangements of infants in 19 studies across the UK, Europe and Australasia. Participants 1472 SIDS cases, and 4679 controls. Each study effectively included all cases, by standard criteria. Controls were randomly selected normal infants of similar age, time and place. Results In the combined dataset, 22.2% of cases and 9.6% of controls were bed sharing, adjusted OR (AOR) for all ages 2.7; 95% CI (1.4 to 5.3). Bed sharing risk decreased with increasing infant age. When neither parent smoked, and the baby was less than 3 months, breastfed and had no other risk factors, the AOR for bed sharing versus room sharing was 5.1 (2.3 to 11.4) and estimated absolute risk for these room sharing infants was very low (0.08 (0.05 to 0.14)/1000 live-births). This increased to 0.23 (0.11 to 0.43)/1000 when bed sharing. Smoking and alcohol use greatly increased bed sharing risk. Conclusions Bed sharing for sleep when the parents do not smoke or take alcohol or drugs increases the risk of SIDS. Risks associated with bed sharing are greatly increased when combined with parental smoking, maternal alcohol consumption and/or drug use. A substantial reduction of SIDS rates could be achieved if parents avoided bed sharing.

Side sleeping position and bed sharing in the sudden infant death syndrome

In the last decade there have been major reductions in the sudden infant death syndrome (SIDS) rate following prevention programmes in Australasia, Europe and North America, mainly due to changing infants from the prone sleeping position onto their sides or backs. This report reviews previous SIDS observational studies with data on side sleeping position and bed sharing. The relative risk for SIDS calculated from previous studies for side vs back sleeping position is 2.02 (95% CI = 1.68, 2.43). This result suggests that further substantial decreases in SIDS could be expected if infants were placed to sleep on their backs. With regard to bed sharing, the summary SIDS relative risk is 2.06 (1.70, 2.50) for infants of smoking mothers and 1.42 (1.12, 1.79) for infants of nonsmoking mothers. Public health policy should be directed against bed sharing by infants whose mothers smoke as they carry an increased risk of SIDS from bed sharing in addition to their already increased risk from maternal smoking. For infants of nonsmoking mothers, who have a low absolute risk of SIDS, the 40-50% increase in risk needs to be balanced against other perceived benefits from bed sharing, such as increased breastfeeding.

Risk factors for asthma: is prevention possible?

Asthma is one of the most common diseases in the world, resulting in a substantial burden of disease. Although rates of deaths due to asthma worldwide have reduced greatly over the past 25 years, no available therapeutic regimens can cure asthma, and the burden of asthma will continue to be driven by increasing prevalence. The reasons for the increase in asthma prevalence have not been defined, which limits the opportunities to develop targeted primary prevention measures. Although associations are reported between a wide range of risk factors and childhood asthma, substantiation of causality is inherently difficult from observational studies, and few risk factors have been assessed in primary prevention studies. Furthermore, none of the primary prevention intervention strategies that have undergone scrutiny in randomised controlled trials has provided sufficient evidence to lead to widespread implementation in clinical practice. A better understanding of the factors that cause asthma is urgently needed, and this knowledge could be used to develop public health and pharmacological primary prevention measures that are effective in reducing the prevalence of asthma worldwide. To achieve this it will be necessary to think outside the box, not only in terms of risk factors for the causation of asthma, but also the types of novel primary prevention strategies that are developed, and the research methods used to provide the evidence base for their implementation. In the interim, public health efforts should remain focused on measures with the potential to improve lung and general health, such as: reducing tobacco smoking and environmental tobacco smoke exposure; reducing indoor and outdoor air pollution and occupational exposures; reducing childhood obesity and encouraging a diet high in vegetables and fruit; improving feto-maternal health; encouraging breastfeeding; promoting childhood vaccinations; and reducing social inequalities.