Julian Crane

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.

PRESCRIBED FENOTEROL AND DEATH FROM ASTHMA IN NEW ZEALAND, 1981-83; CASE-CONTROL STUDY

A case-control study was conducted to examine the hypothesis that fenoterol by metered dose inhaler (MDI) increases the risk of death in patients with asthma. The case group comprised 117 patients aged 5-45 who died of asthma between August, 1981, and July, 1983. For each case, 4 controls, matched for age and ethnic group, were selected from asthma admissions to hospitals to which the cases themselves would have been admitted, had they survived. The relative risk of asthma death in patients prescribed fenoterol by MDI was 1.55 (95% CI 1.04-2.33, p = 0.03). The possibility of confounding or effect modification by severity was assessed by consideration of subgroups defined by markers of asthma severity. The fenoterol MDI relative risk was 2.21 (95% CI 1.26-3.88, p = 0.01) in patients prescribed three or more categories of asthma drugs, 2.16 (95% CI 1.14-4.11, p = 0.02) in patients with a hospital admission for asthma during the previous 12 months, and 6.45 (95% CI 2.72-15.3, p less than 0.01) in patients prescribed oral corticosteroids at time of death or admission. In the group of patients with the most severe asthma (defined by a hospital admission during the previous year and prescription of oral corticosteroids) the fenoterol MDI relative risk was 13.29 (95% CI 3.45-51.2, p less than 0.01). After adjustment for severity, no other asthma treatment commonly used in New Zealand seemed to be associated with an increased risk of asthma death. Not all sources of bias can be definitely excluded; however, when considered together with other epidemiological and experimental evidence, these findings are consistent with the hypothesis that use of fenoterol by MDI increases the risk of death in severe asthma.

Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in Childhood (ISAAC).

Background: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global prevalence and severity of asthma symptoms in children. Methods: A cross-sectional questionnaire survey of 798 685 children aged 13–14 years from 233 centres in 97 countries, and 388 811 children aged 6–7 years from 144 centres in 61 countries, was conducted between 2000 and 2003 in >90% of the centres. Results: The prevalence of wheeze in the past 12 months (current wheeze) ranged from 0.8% in Tibet (China) to 32.6% in Wellington (New Zealand) in the 13–14 year olds, and from 2.4% in Jodhpur (India) to 37.6% in Costa Rica in the 6–7 year olds. The prevalence of symptoms of severe asthma, defined as ⩾4 attacks of wheeze or ⩾1 night per week sleep disturbance from wheeze or wheeze affecting speech in the past 12 months, ranged from 0.1% in Pune (India) to 16% in Costa Rica in the 13–14 year olds and from 0% to 20.3% in the same two centres, respectively, in the 6–7 year olds. Ecological economic analyses revealed a significant trend towards a higher prevalence of current wheeze in centres in higher income countries in both age groups, but this trend was reversed for the prevalence of severe symptoms among current wheezers, especially in the older age group. Conclusion: Wide variations exist in the symptom prevalence of childhood asthma worldwide. Although asthma symptoms tend to be more prevalent in more affluent countries, they appear to be more severe in less affluent countries.

Cord-Blood 25-Hydroxyvitamin D Levels and Risk of Respiratory Infection, Wheezing, and Asthma

OBJECTIVE: Higher maternal intake of vitamin D during pregnancy is associated with a lower risk of wheezing in offspring. The relationship between cord-blood levels of 25-hydroxyvitamin D (25[OH]D) and childhood wheezing is unknown. We hypothesized that cord-blood levels would be inversely associated with risk of respiratory infection, wheezing, and asthma. PATIENTS AND METHODS: Cord blood from 922 newborns was tested for 25(OH)D. Parents were asked if their child had a history of respiratory infection at 3 months of age or a history of wheezing at 15 months of age and then annually thereafter. Incident asthma was defined as doctor-diagnosed asthma by the time the child was 5 years old and reported inhaler use or wheezing since the age of 4 years. RESULTS: The median cord-blood level of 25(OH)D was 44 nmol/L (interquartile range: 29–78). Follow-up was 89% at the age of 5 years. Adjusting for the season of birth, 25(OH)D had an inverse association with risk of respiratory infection by 3 months of age (odds ratio: 1.00 [reference] for ≥75 nmol/L, 1.39 for 25–74 nmol/L, and 2.16 [95% confidence interval: 1.35–3.46] for <25 nmol/L). Likewise, cord-blood 25(OH)D levels were inversely associated with risk of wheezing by 15 months, 3 years, and 5 years of age (all P < .05). Additional adjustment for more than 12 potential confounders did not materially change these results. In contrast, we found no association between 25(OH)D levels and incident asthma by the age of 5 years. CONCLUSIONS: Cord-blood levels of 25(OH)D had inverse associations with risk of respiratory infection and childhood wheezing but no association with incident asthma.

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.

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 childs 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.

Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study.

The association between inhaled fenoterol and death from asthma has been investigated further by studying 112 asthma deaths (cases) during 1981-7 in patients aged 5-45 years who had been admitted to a major hospital for asthma during the 12 months before death. Two age matched control groups were chosen. Control group A comprised 427 patients who had been admitted to hospital for asthma during the calendar year that the corresponding death occurred and who had also had a previous admission for asthma in the previous 12 months. Control group B comprised 448 patients admitted to hospital for asthma during the calendar year in which the admission of the corresponding case occurred. The inhaled fenoterol odds ratio was 2.11 (95% confidence interval (CI) 1.37-3.23, p less than 0.01) when group A was used as the control (the approach used in previous studies), and 2.66 (95% CI 1.74-4.06, p less than 0.01) with group B as the control (the approach recommended by critics of previous studies). Markers of chronic asthma severity were associated with asthma death when control group B was used, but not when control group A was used (which indicates that these markers were indirectly matched for when control group A was used). Information was also collected on various markers of acute asthma severity and prescription of psychotropic drugs, but it was found that these were not important confounders. These findings address the major criticisms of previous case-control studies of this issue, and add support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma.

Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81.

A previous New Zealand case-control study of asthma deaths in the 5-45 year age group during 1981-3 found that prescription of fenoterol (by metered dose inhaler) was associated with an increased risk of death in patients with severe asthma. One major criticism of this study was that drug data for the cases and controls came from different sources. A new case-control design has been used to evaluate the same hypothesis, with a different set of asthma deaths, the same source for drug information being used for both cases and controls. This depended on identifying deaths from asthma during 1977-81 from national mortality records, and ascertaining which patients from those who died had been admitted to a major hospital for asthma during the 12 months before death. The study was confined to this subgroup, which accounted for about 20% of all asthma deaths in the areas served by a major hospital. For each of the eligible patients who died four age matched controls were selected from patients admitted to hospital for asthma during the year that the death occurred who had also had an admission for asthma in the previous 12 months. For the 58 cases and 227 control subjects information on prescribed drugs was collected from the hospital records relating to the previous admission. The odds ratio of asthma death in patients prescribed inhaled fenoterol was 1.99 (95% confidence interval 1.12-3.55, p = 0.02). As in the previous study, subgroups defined by markers of chronic asthma severity were also considered. The inhaled fenoterol odds ratio was 2.98 (95% CI 1.15-7.70, p = 0.02) in patients prescribed three or more categories of asthma drugs, 3.91 (95% CI 1.79-8.54, p less than 0.01) in patients with a previous admission for asthma in the past 12 months, and 5.83 (95% CI 1.62-21.0, p = 0.01) in patients prescribed oral corticosteroids at the time of admission. In patients with the most severe asthma (defined by a previous admission for asthma during the past 12 months and prescribed oral corticosteroids at time of admission) the inhaled fenoterol odds ratio was 9.82 (95% CI 2.23-43.4, p less than 0.01). These findings add further support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma.

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

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