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1.  Maternal intestinal flora and wheeze in early childhood 
Background
Increasing evidence links altered intestinal flora in infancy to eczema and asthma. No studies have investigated the influence of maternal intestinal flora on wheezing and eczema in early childhood.
Objective
To investigate the link between maternal intestinal flora during pregnancy and development of wheeze and eczema in infancy.
Methods
Sixty pregnant women from the Boston area gave stool samples during the third trimester of their pregnancy and answered questions during pregnancy about their own health, and about their children’s health when the child was 2 and 6 months of age. Quantitative culture was performed on stool samples and measured in log10colony-forming units(CFU)/gram stool. Primary outcomes included infant wheeze and eczema in the first 6 months of life. Atopic wheeze, defined as wheeze and eczema, was analyzed as a secondary outcome.
Results
In multivariate models adjusted for breastfeeding, daycare attendance and maternal atopy, higher counts of maternal total aerobes (TA) and enterococci (E) were associated with increased risk of infant wheeze (TA: OR 2.32 for 1 log increase in CFU/g stool [95% CI 1.22, 4.42]; E: OR 1.57 [95% CI 1.06, 2.31]). No organisms were associated with either eczema or atopic wheeze.
Conclusions & Clinical Relevance
In our cohort, higher maternal total aerobes and enterococci were related to increased risk of infant wheeze. Maternal intestinal flora may be an important environmental exposure in early immune system development.
doi:10.1111/j.1365-2222.2011.03950.x
PMCID: PMC3428746  PMID: 22909161
infant wheeze; eczema; asthma; microbiota; intestinal flora; maternal flora
2.  Risk factors in childhood eczema. 
The cumulative rate of childhood eczema during the first three years was studied in a birth cohort of 1265 New Zealand infants. A parental history of eczema was the strongest predictor of rates of childhood eczema but parental asthma was also related to childhood eczema. Children exposed to an early diverse solid-food diet also had increased risks of eczema, but there was no evidence to suggest that breast-feeding practices had any effect on rates of eczema. Analysis of the data suggested that the apparent association between exclusive breast-feeding and reduced rates of eczema reported in previous studies may be because exclusively breast-fed infants were not exposed to early solid feeding rather than to any beneficial effect of breast milk itself.
PMCID: PMC1052908  PMID: 6896887
3.  Self-reported prevalence of childhood allergic diseases in three cities of China: a multicenter study 
BMC Public Health  2010;10:551.
Background
Several studies conducted during the 1990s indicated that childhood allergic diseases were increasing worldwide, but more recent investigations in some Western countries have suggested that the trend is stabilizing or may even be reversing. However, few data are available on the current status of allergic disease prevalence in Chinese children. The aim of the present study was to investigate the prevalence rates of asthma, allergic rhinitis, and eczema in children of three major cities of China, to determine the status of allergic diseases among Chinese children generally, and to evaluate the prevalence of allergic diseases in children of different ages.
Methods
We conducted a cross-sectional survey between October 2008 and May 2009 in three major cities of China (Beijing, Chongqing, and Guangzhou) to evaluate the prevalence rates of childhood allergic diseases including asthma, allergic rhinitis, and eczema, using a questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC) group. A total of 24,290 children aged 0-14 years were interviewed, using a multi-stage sampling method. To acquire data on children aged 3-14 years, we visited schools and kindergartens. To access children too young to attend school or kindergarten, we extended our survey to community health service centers. Each questionnaire was completed by a parent or guardian of a child after an informed consent form was signed.
Results
Of the 24,290 children in our study, 12,908 (53.14%) were males and 11,382 (46.86%) females; 10,372 (42.70%) were from Beijing, 9,846 (40.53%) from Chongqing, and 4,072 (16.77%) from Guangzhou. Our survey indicated that in Beijing, Chongqing, and Guangzhou, the prevalence rates of asthma were 3.15%, 7.45%, and 2.09%, respectively; the rates of allergic rhinitis were 14.46%, 20.42%, and 7.83%; and the rates of eczema were 20.64%, 10.02%, and 7.22%. The prevalence of allergic diseases varied with age. Asthma was relatively less common both in children aged under 2 years, and in those aged 9 years or more, in each of the three cities. The prevalence of allergic rhinitis was also lower in children younger than 2 years. The prevalence of eczema fell with age.
Conclusions
A marked increase in the prevalence rates of allergic diseases in China (compared with earlier data) was evident. Further studies exploring the precise causes of this increase are warranted.
doi:10.1186/1471-2458-10-551
PMCID: PMC2944377  PMID: 20836838
4.  338 Early Clinical Differential Diagnosis between Infant Atopic Dermatitis and Seborrheic Eczema 
Background
Clinical differential diagnosis between atopic dermatitis and seborrheic eczema is sometimes difficult. Early differential diagnosis is important, since atopic dermatitis can be more difficult to treat and may be associated with asthma and allergic rhinitis.
Methods
In a cohort study, 96 infants with high risk for atopic dermatitis were followed up from the maternal ward until they completed one year of age. The infants were submitted to complete skin examination, monthly, for a 1 year period. A full skin examination was performed and any sign of eczema was registered. Therapy with hydrocortisone 1% cream was prescribed. Eczema onset time, skin distribution, response to therapy and the presence of pruritus were evaluated.
Results
87 (96%) infants fulfilled the study criteria (physical examination at least 10 months). Fivty four (62%) infants had signs of eczema during one year follow up. Atopic dermatitis was diagnosed in 14 (16%) patients and seborrheic eczema in 30 (34.5%) infants, with 10 (11.5%) classified as: both eczemas. Atopic eczema onset was mainly between 2 and 4 months and seborrheic eczema between 1 week and 3 months, with an important coincident period. Facial eczema had similar onset and semiological aspect for both diseases in its beginning. Head eczema was present in 40 (74%) eczema infants, 33 (82.5%) with a posterior diagnosis of seborrheic eczema and 7 (17.5%) with atopic dermatitis. After 3 to 5 months, axillar and groin folds eczema were the main signs of seborrheic dermatitis diagnosis, while face, neck and limbs were the main eczema sites in atopic dermatitis. The 10 infants with dubious eczema just after 6 months could have a more accurate eczema diagnosis. Hanifin et Rajka diagnostic criteria for infants showed to be useful just after 6 months, since some of its criteria are evolutive. All patients improved with hydrocortisone cream, but seborrheic eczema infants had a better response and prognosis, with complete eczema resolution until 8 months. The presence of pruritus could be securely established just after 6 months of age.
Conclusions
Continuous follow up is indispensable for Infant atopic dermatitis differential diagnosis with seborrheic eczema. Eczema distribution and therapy response are the best predictors for differential diagnosis in infant eczema.
doi:10.1097/01.WOX.0000412101.79708.1d
PMCID: PMC3513086
5.  Smoking and prevalence of allergic disorders in Japanese pregnant women: baseline data from the Kyushu Okinawa Maternal and Child Health Study 
Environmental Health  2012;11:15.
Background
Studies on the associations between smoking and allergic diseases have mostly focused on asthma. Epidemiological studies in adults on the effects of smoking on allergic diseases other than asthma, such as eczema and rhinoconjunctivitis, have been limited, and the information that is available has been inconsistent. The aim of this study was to investigate the association between smoking status and environmental tobacco smoke (ETS) exposure and the prevalence of allergic diseases.
Methods
Study subjects were 1743 pregnant Japanese women. The definitions of wheeze and asthma were based on criteria from the European Community Respiratory Health Survey whereas those of eczema and rhinoconjunctivitis were based on criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for age; region of residence; family history of asthma, atopic eczema, and allergic rhinitis; household income; and education.
Results
Compared with never smoking, current smoking and ≥ 4 pack-years of smoking were independently positively associated with the prevalence of wheeze. There were no associations between smoking status and the prevalence of asthma, eczema, or rhinoconjunctivitis. When subjects who had never smoked were classified into four categories based on the source of ETS exposure (never, only at home, only at work, and both), exposure occurring both at home and at work was independently associated with an increased prevalence of two outcomes: wheeze and rhinoconjunctivitis. No relationships were observed between exposure to ETS and the prevalence of asthma or eczema.
Conclusions
Our results provide evidence that current smoking and ETS exposure may increase the likelihood of wheeze. The possibility of a positive association between ETS exposure and rhinoconjunctivitis was also suggested.
doi:10.1186/1476-069X-11-15
PMCID: PMC3317840  PMID: 22413964
Asthma; Cross-sectional studies; Eczema; Environmental tobacco smoke; Smoking; Wheeze; Rhinoconjunctivitis
6.  Risk factors for asthma and allergic diseases in school children across Lebanon 
Introduction:
Childhood asthma is one of important diseases of childhood. There is no known prevalence of asthma and allergic diseases in Lebanon. This study was conducted with a secondary objective of finding the odds of exposure to asthma, allergic rhinitis and eczema potential risk factors in Lebanese children.
Material and methods:
It is a cross-sectional study on children in public and private schools. A sample of 22 schools participated, where standardized written core questionnaires were distributed. 5–12 year old students completed the questionnaires at home, while 13–14 year old students filled it in class.
Results:
5522 children were evaluated for asthma, allergic rhinitis and atopic eczema prevalence and their associated factors. These diseases seem to be similarly affected by parental respiratory problems, parental smoking, infancy gastroesophageal reflux, recurrent otitis, and previous pertussis. Humidity on the bedroom walls is associated with both asthma and allergic rhinitis, a spongy pillow with both allergic rhinitis and eczema, animal possession with asthma, and noncotton mattress with atopic eczema. The adjusted odds ratios for significant associations varied between 1.25 and 3 (0.0001 < p-value < 0.01).
Conclusion:
These factors are preventable, thus permitting a possible reduction of the prevalence of these diseases.
PMCID: PMC3048605  PMID: 21437138
asthma; eczema; rhinitis; allergic disease; risk factors
7.  Polyunsaturated fatty acid intake and prevalence of eczema and rhinoconjunctivitis in Japanese children: The Ryukyus Child Health Study 
BMC Public Health  2011;11:358.
Background
The recent increase in the prevalence of allergic disorders might be a consequence of increased intake of n-6 polyunsaturated fatty acids (PUFAs) and reduced intake of n-3 PUFAs. The current cross-sectional study examined the association between intake levels and the prevalence of eczema and rhinoconjunctivitis in Japanese children.
Methods
Subjects were 23,388 schoolchildren aged 6-15 years residing in Okinawa. The presence of eczema and/or rhinoconjunctivitis was determined according to the criteria of the International Study of Asthma and Allergies in Childhood. A brief diet history questionnaire for children and adolescents was administered to acquire information on dietary factors. Adjustment was made for age, sex, residential municipality, number of siblings, smoking in the household, body mass index, paternal and maternal history of allergic diseases, and paternal and maternal educational level.
Results
The prevalences of eczema and rhinoconjunctivitis in the previous 12 months were 7.0% and 8.0%, respectively. Consumption of PUFAs, n-3 PUFAs, α-linolenic acid, n-6 PUFAs, and linoleic acid was positively associated with the prevalence of eczema: the adjusted odds ratios (ORs) between extreme quintiles (95% confidence intervals [CIs], P for trend) were 1.26 (1.07-1.48, 0.04), 1.31 (1.11-1.54, 0.009), 1.31 (1.12-1.55, 0.003), 1.26 (1.07-1.48, 0.01), and 1.27 (1.08-1.49, 0.01), respectively. Arachidonic acid intake was independently inversely related to eczema: the adjusted OR between extreme quintiles was 0.81 (0.69-0.95, 0.0008). Eczema was not associated with eicosapentaenoic or docosahexaenoic acid intake, or with the ratio of n-3 to n-6 PUFA intake. Only arachidonic acid intake was statistically significantly related to the prevalence of rhinoconjunctivitis, showing a clear inverse linear trend: the adjusted OR between extreme quintiles was 0.86 (0.74-0.997, 0.03).
Conclusions
Consumption of n-3 and n-6 PUFAs, especially α-linolenic acid and linoleic acid, may be positively associated with eczema. Arachidonic acid intake may be inversely related to eczema and rhinoconjunctivitis.
doi:10.1186/1471-2458-11-358
PMCID: PMC3112140  PMID: 21599987
8.  Swimming Pool Attendance, Asthma, Allergies, and Lung Function in the Avon Longitudinal Study of Parents and Children Cohort 
Rationale: Cross-sectional studies have reported inconsistent findings for the association between recreational swimming pool attendance and asthma and allergic diseases in childhood.
Objectives: To examine whether swimming in infancy and childhood was associated with asthma and allergic symptoms at age 7 and 10 years in a UK longitudinal population-based birth cohort, the Avon Longitudinal Study of Parents and Children.
Methods: Data on swimming were collected by questionnaire at 6, 18, 38, 42, 57, 65, and 81 months. Data on rhinitis, wheezing, asthma, eczema, hay fever, asthma medication, and potential confounders were collected through questionnaires at 7 and 10 years. Spirometry and skin prick testing were performed at 7 to 8 years. Data for analysis were available for 5,738 children.
Measurements and Main Results: At age 7 years, more than 50% of the children swam once per week or more. Swimming frequency did not increase the risk of any evaluated symptom, either overall or in atopic children. Children with a high versus low cumulative swimming pool attendance from birth to 7 years had an odds ratio of 0.88 (95% confidence interval, 0.56–1.38) and 0.50 (0.28–0.87), respectively, for ever and current asthma at 7 years, and a 0.20 (0.02–0.39) standard deviation increase in the forced midexpiratory flow. Children with asthma with a high versus low cumulative swimming had an odds ratio for current asthma at 10 years of 0.34 (0.14–0.80).
Conclusions: This first prospective longitudinal study suggests that swimming did not increase the risk of asthma or allergic symptoms in British children. Swimming was associated with increased lung function and lower risk of asthma symptoms, especially among children with preexisting respiratory conditions.
doi:10.1164/rccm.201005-0761OC
PMCID: PMC3081279  PMID: 20889905
Avon Longitudinal Study of Parents and Children; pediatric; epidemiology, prospective; irritants
9.  Association of variants in innate immune genes with asthma and eczema 
Background
The innate immune pathway is important in the pathogenesis of asthma and eczema. However, only a few variants in these genes have been associated with either disease. We investigate the association between polymorphisms of genes in the innate immune pathway with childhood asthma and eczema. In addition, we compare individual associations with those discovered using a multivariate approach.
Methods
Using a novel method, case control based association testing (C2BAT), 569 single nucleotide polymorphisms (SNPs) in 44 innate immune genes were tested for association with asthma and eczema in children from the Boston Home Allergens and Asthma Study and the Connecticut Childhood Asthma Study. The screening algorithm was used to identify the top SNPs associated with asthma and eczema. We next investigated the interaction of innate immune variants with asthma and eczema risk using Bayesian networks.
Results
After correction for multiple comparisons, 7 SNPs in 6 genes (CARD25, TGFB1, LY96, ACAA1, DEFB1, and IFNG) were associated with asthma (adjusted p-value<0.02), while 5 SNPs in 3 different genes (CD80, STAT4, and IRAKI) were significantly associated with eczema (adjusted p-value < 0.02). None of these SNPs were associated with both asthma and eczema. Bayesian network analysis identified 4 SNPs that were predictive of asthma and 10 SNPs that predicted eczema. Of the genes identified using Bayesian networks, only CD80 was associated with eczema in the single-SNP study. Using novel methodology that allows for screening and replication in the same population, we have identified associations of innate immune genes with asthma and eczema. Bayesian network analysis suggests that additional SNPs influence disease susceptibility via SNP interactions.
Conclusion
Our findings suggest that innate immune genes contribute to the pathogenesis of asthma and eczema, and that these diseases likely have different genetic determinants.
doi:10.1111/j.1399-3038.2011.01243.x
PMCID: PMC3412627  PMID: 22192168
asthma; Bayesian network; genetic association; eczema; innate immunity
10.  CLIMATE CHANGE, AEROALLERGENS AND PEDIATRIC ALLERGIC DISEASE 
The degree to which aeroallergens are contributing to the global increase in pediatric allergic disease is incompletely understood. We review the evidence that links climate change to changes in aeroallergens such as pollen and outdoor mold concentrations and subsequently, aeroallergen association with pediatric allergic disease. We specifically explore the evidence on both the exacerbation and the development of allergic disease in children related to outdoor pollen and mold concentrations. Pediatric allergic diseases include atopic dermatitis or eczema, allergic rhinitis or hay fever, and some types of asthma in children, typically defined as less than 18 years of age. We discuss how the timing of aeroallergen exposure both in utero and in childhood could be associated with allergies. We conclude that the magnitude and type of health impacts due to climate change will depend on improved understanding of the relationship between climatic variables, multiple allergen factors, and allergic disease. Improved public health strategies such as adequate humidity control, optimum air filtration and ventilation, and improved anticipatory public health messaging will be critical to adaptation.
doi:10.1002/msj.20232
PMCID: PMC3075981  PMID: 21259264
aeroallergen; allergic rhinitis; ambient air; atopy; fungal spore; global warming; greenhouse gas; sensitization
11.  Eczema in early childhood is strongly associated with the development of asthma and rhinitis in a prospective cohort 
BMC Dermatology  2012;12:11.
Background
This study aimed to estimate the association between eczema in early childhood and the onset of asthma and rhinitis later in life in children.
Methods
A total of 3,124 children aged 1–2 years were included in the Dampness in Building and Health (DBH) study in the year 2000, and followed up 5 years later by a parental questionnaire based on an International Study of Asthma and Allergies in Childhood protocol. The association between eczema in early childhood and the incidence of asthma and rhinitis later in life was estimated by univariable and multivariable logistic regression modelling.
Results
The prevalence of eczema in children aged 1–2 years was 17.6% at baseline. Children with eczema had a 3-fold increased odds of developing asthma (adjusted odds ratio [aOR], 3.07; 95% confidence interval (CI) 1.79–5.27), and a nearly 3-fold increased odds of developing rhinitis (aOR, 2.63; 1.85–3.73) at follow-up compared with children without eczema, adjusted for age, sex, parental allergic disease, parental smoking, length of breastfeeding, site of living, polyvinylchloride flooring material, and concomitant allergic disease. When eczema was divided into subgroups, moderate to severe eczema (aOR, 3.56; 1.62–7.83 and aOR, 3.87; 2.37–6.33, respectively), early onset of eczema (aOR, 3.44; 1.94–6.09 and aOR, 4.05; 2.82–5.81; respectively), and persistence of eczema (aOR, 5.16; 2.62–10.18 and aOR, 4.00; 2.53–6.22, respectively) further increased the odds of developing asthma and rhinitis. Further independent risk factors increasing the odds of developing asthma were a parental history of allergic disease (aOR, 1.83; 1.29–2.60) and a period of breast feeding shorter than 6 months (aOR, 1.57; 1.03–2.39). The incidence of rhinitis was increased for parental history of allergic disease (aOR, 2.00; 1.59–2.51) and polyvinylchloride flooring (aOR, 1.60; 1.02–2.51).
Conclusion
Eczema in infancy is associated with development of asthma and rhinitis during the following 5-year period, and eczema is one of the strongest risk factors. Early identification is valuable for prediction of the atopic march.
doi:10.1186/1471-5945-12-11
PMCID: PMC3469362  PMID: 22839963
12.  Early prescriptions of antibiotics and the risk of allergic disease in adults: a cohort study 
Thorax  2004;59(1):11-15.
Background: It is frequently asserted that antibiotic prescriptions in childhood are associated with the development of allergic disease, especially asthma. A study was undertaken to establish the direction of this relationship.
Methods: A retrospective cohort study of 746 adults was performed in three general practices. Antibiotic prescriptions in the first 5years of life, collected from contemporary medical records, were related to self-reports of asthma and hay fever and the results of skin prick testing with common aeroallergens.
Results: There was no relationship between early antibiotic prescription and atopy, either for all antibiotic use (OR 1.01) or for antibiotics prescribed at different ages. The significant associations between prescriptions at ages 4 and 5 and hay fever (OR 1.23 and 1.16, respectively) were explained by coexisting asthma. Relationships between antibiotic use and asthma (allergic or otherwise) were statistically significant and strengthened with increasing age of prescription, but were largely confined to antibiotics prescribed for lower respiratory symptoms.
Conclusions: The reported associations between childhood antibiotic use and asthma are most plausibly explained by "reverse causation"—the tendency for prescriptions to be written for the early manifestations of pre-existing asthma.
PMCID: PMC1758860  PMID: 14694239
13.  Genetic variation in small proline rich protein 2B as a predictor for asthma among children with eczema 
Background
Small proline rich protein 2B (SPRR2B) is a skin and lung epithelial protein associated with allergic inflammation in mice that has not been evaluated in human atopic diseases.
Objective
To determine whether single-nucleotide polymorphisms (SNPs) in SPRR2B are associated with childhood eczema and with the phenotype of childhood eczema combined with asthma.
Methods
Genotyping for SPRR2B and filaggrin (FLG) was performed in 2 independent populations: the Cincinnati Childhood Allergy & Air Pollution Study (CCAAPS; N = 762; birth-age, 4 years) and the Greater Cincinnati Pediatric Clinical Repository (GCPCR;N = 1152; ages 5–10 years). Eczema and eczema plus asthma were clinical outcomes based on parental report and clinician’s diagnosis. Genetic analyses were restricted to whites and adjusted for sex in both cohorts and adjusted for environmental covariates in CCAAPS.
Results
Variants in SPRR2B were not significantly associated with eczema in either cohort after Bonferroni adjustment. Children from both cohorts with the CC genotype of the SPRR2B rs6693927 SNP were at 4 times the risk for eczema plus asthma (adjusted odds ratio, 4.1; 95% confidence interval, 1.5– 10.9; P = .005 in CCAAPS; and adjusted odds ratio, 4.0; 95% confidence interval, 1.8 –9.1; P <.001 in the GCPCR), however. SNPs in SPRR2B were not in strong linkage disequilibrium with the R501X and del2282 FLG mutations, and these findings were independent of FLG.
Conclusions
An SNP in SPRR2B was predictive of asthma among white children with eczema from 2 independent populations. SPRR2B polymorphisms may serve as important predictive markers for the combined eczema plus asthma phenotype.
doi:10.1016/j.anai.2012.01.004
PMCID: PMC3759990  PMID: 22374195
14.  Experiences of carers managing childhood eczema and their views on its treatment: a qualitative study 
The British Journal of General Practice  2012;62(597):e261-e267.
Background
Childhood eczema causes significant impact on quality of life for some families, yet non-concordance with treatment is common.
Aim
To explore parents' and carers' views of childhood eczema and its treatment.
Design and setting
Qualitative interview study in primary care in the south of England.
Method
Carers of children aged ≤5 years with a recorded diagnosis of eczema, who reported that eczema was still a problem, were invited to participate. Thirty-one parents were interviewed from 28 families.
Results
Many parents expressed frustration with both medical care and prescribed treatments. They felt their child's suffering was not ‘taken seriously’, and experienced messages about a ‘trial and error’ prescribing approach and assurance that their child would ‘grow out of it’ as a further ‘fobbing off’, or dismissal. Many carers were ambivalent about eczema treatments, mainly topical corticosteroids but also emollients. Dietary exclusions as a potential cure were of interest to most families, although they perceived healthcare professionals as uninterested in this. Families varied in the extent to which they felt able to manage eczema and the length of time taken to gain control. In some instances, this was linked to not understanding advice or receiving conflicting advice from different healthcare providers.
Conclusion
Poor concordance with treatments seems unsurprising in the presence of such dissonance between carers' and healthcare providers' agendas. Acknowledging the impact of the condition, greater attention to how key messages are delivered and addressing carers' treatment beliefs are likely to improve engagement with effective self-care.
doi:10.3399/bjgp12X636083
PMCID: PMC3310032  PMID: 22520913
atopic dermatitis; child; eczema; medication adherence; primary health care; qualitative research
15.  International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis, and eczema 
Thorax  2000;55(6):449-453.
BACKGROUND—An ecological analysis was conducted of the relationship between tuberculosis notification rates and the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema in 85 centres from 23 countries in which standardised data are available. These essentially comprised countries in Europe as well as the USA, Canada, Australia, and New Zealand.
METHODS—Tuberculosis notification rates were obtained from the World Health Organization. Data on the prevalence of symptoms of asthma, rhinitis, and eczema in 235 477 children aged 13-14 years were based on the responses to the written and video questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC). The analysis was adjusted for gross national product (GNP) as an estimate of the level of affluence.
RESULTS—Tuberculosis notification rates were significantly inversely associated with the lifetime prevalence of wheeze and asthma and the 12 month period prevalence of wheeze at rest as assessed by the video questionnaire. An increase in the tuberculosis notification rates of 25 per 100 000 was associated with an absolute decrease in the prevalence of wheeze ever of 4.7%. Symptoms of allergic rhinoconjunctivitis in the past 12 months were inversely associated with tuberculosis notification rates, but there were no other significant associations with other ISAAC questions on allergic rhinoconjunctivitis or atopic eczema.
CONCLUSIONS—These findings are consistent with recent experimental evidence which suggests that exposure to Mycobacterium tuberculosis may reduce the risk of developing asthma.


doi:10.1136/thorax.55.6.449
PMCID: PMC1745787  PMID: 10817790
16.  Time trends, ethnicity and risk factors for eczema in New Zealand children: ISAAC Phase Three 
Asia Pacific Allergy  2013;3(3):161-178.
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 Māori 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 Māori 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.
doi:10.5415/apallergy.2013.3.3.161
PMCID: PMC3736373  PMID: 23956963
Eczema; Children; Adolescents; Ethnicity; New Zealand; Environment
17.  Interactive effect of STAT6 and IL13 gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study 
BMC Medical Genetics  2013;14:67.
Background
Eczema is a prevalent skin disease that is mainly characterized by systemic deviation of immune response and defective epidermal barrier. Th2 cytokines, such as IL-13 and transcription factor STAT6 are key elements in the inflammatory response that characterize allergic disorders, including eczema. Previous genetic association studies showed inconsistent results for the association of single nucleotide polymorphisms (SNPs) with eczema. Our aim was to investigate whether SNPs in IL13 and STAT6 genes, which share a biological pathway, have an interactive effect on eczema risk.
Methods
Data from two independent population-based studies were analyzed, namely the Isle of Wight birth cohort study (IOW; n = 1,456) and for the purpose of replication the Swansea PAPA (Poblogaeth Asthma Prifysgol Abertawe; n = 1,445) cross-sectional study. Log-binomial regressions were applied to (i) account for the interaction between IL13 (rs20541) and STAT6 (rs1059513) polymorphisms and (ii) estimate the combined effect, in terms of risk ratios (RRs), of both risk factors on the risk of eczema.
Results
Under a dominant genetic model, the interaction term [IL13 (rs20541) × STAT6 (rs1059513)] was statistically significant in both studies (IOW: adjusted Pinteraction = 0.046; PAPA: Pinteraction = 0.037). The assessment of the combined effect associated with having risk genotypes in both SNPs yielded a 1.52-fold increased risk of eczema in the IOW study (95% confidence interval (CI): 1.05 – 2.20; P = 0.028) and a 2.01-fold higher risk of eczema (95% CI: 1.29 – 3.12; P = 0.002) in the PAPA study population.
Conclusions
Our study adds to the current knowledge of genetic susceptibility by demonstrating for the first time an interactive effect between SNPs in IL13 (rs20541) and STAT6 (rs1059513) on the occurrence of eczema in two independent samples. Findings of this report further support the emerging evidence that points toward the existence of genetic effects that occur via complex networks involving gene-gene interactions (epistasis).
doi:10.1186/1471-2350-14-67
PMCID: PMC3700873  PMID: 23815671
Eczema; Gene-gene Interaction; Epistasis; STAT6; IL13; Genetic Association Study
18.  Self-Reported Truck Traffic on the Street of Residence and Symptoms of Asthma and Allergic Disease: A Global Relationship in ISAAC Phase 3 
Environmental Health Perspectives  2009;117(11):1791-1798.
Background
Associations between traffic pollution on the street of residence and a range of respiratory and allergic outcomes in children have been reported in developed countries, but little is known about such associations in developing countries.
Methods
The third phase of the International Study of Asthma and Allergies in Childhood (ISAAC) was carried out in 13- to 14-year-old and 6- to 7-year-old children across the world. A question about frequency of truck traffic on the street of residence was included in an additional questionnaire. We investigated the association between self-reported truck traffic on the street of residence and symptoms of asthma, rhinoconjunctivitis, and eczema with logistic regression. Adjustments were made for sex, region of the world, language, gross national income, and 10 other subject-specific covariates.
Results
Frequency of truck traffic on the street of residence was positively associated with the prevalence of symptoms of asthma, rhinoconjunctivitis, and eczema with an exposure–response relationship. Odds ratios (95% confidence intervals) for “current wheeze” and “almost the whole day” versus “never” truck traffic were 1.35 (1.23–1.49) for 13- to 14-year-olds and 1.35 (1.22–1.48) for 6- to 7-year-olds.
Conclusions
Higher exposure to self-reported truck traffic on the street of residence is associated with increased reports of symptoms of asthma, rhinitis, and eczema in many locations in the world. These findings require further investigation in view of increasing exposure of the world’s children to traffic.
doi:10.1289/ehp.0800467
PMCID: PMC2801184  PMID: 20049134
air pollution; asthma; eczema; rhinitis; truck traffic
19.  IL13 genetic polymorphisms, smoking, and eczema in women: a case-control study in Japan 
BMC Medical Genetics  2011;12:142.
Background
Several genetic association studies have examined the relationships between single nucleotide polymorphisms (SNPs) in the IL13 gene and eczema, and have provided contradictory results. We investigated the relationship between the IL13 SNPs rs1800925 and rs20541 and the risk of eczema in Japanese young adult women.
Methods
Included were 188 cases who met the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC) for eczema. Control subjects were 1,082 women without eczema according to the ISAAC criteria, who had not been diagnosed with atopic eczema by a doctor and who had no current asthma as defined by the European Community Respiratory Health Survey criteria. Adjustment was made for age, region of residence, number of children, smoking, and education.
Results
The minor TT genotype of SNP rs1800925 was significantly associated with an increased risk of eczema in the co-dominant model: the adjusted odds ratio was 2.19 (95% confidence interval: 1.03-4.67). SNP rs20541 was not related to eczema. None of the haplotypes were significantly associated with eczema. Compared with women with the CC or CT genotype of SNP rs1800925 who had never smoked, those with the TT genotype who had ever smoked had a 2.85-fold increased risk of eczema, though the adjusted odds ratio was not statistically significant, and neither multiplicative nor additive interaction was statistically significant.
Conclusions
Our findings suggest that the IL13 SNP rs1800925 is significantly associated with eczema in Japanese young adult women. We could not find evidence for an interaction between SNP rs1800925 and smoking with regard to eczema.
doi:10.1186/1471-2350-12-142
PMCID: PMC3206833  PMID: 22013915
20.  Endotoxin Exposure and Eczema in the First Year of Life 
Pediatrics  2004;114(1):13-18.
Objective
Exposure to endotoxin in early life has been proposed as a factor that may protect against the development of allergic diseases such as eczema. The objective of this study was to examine the relation between endotoxin exposure in early life and eczema in the first year of life in children with parental history of asthma or allergies.
Methods
This study used a prospective birth cohort study of 498 children who had a history of allergy or asthma in at least 1 parent and lived in metropolitan Boston. A subset of 401 living rooms had house dust samples adequate for analysis of endotoxin.
Results
In multivariate analyses adjusting for gender, income, and season of birth, endotoxin levels in the living room at 2 to 3 months of age was inversely associated with physician- or nurse-diagnosed eczema in the first year of life (odds ratio [OR] for each quartile increment: 0.76; 95% confidence interval [CI]: 0.61–0.96). Exposure to a dog in the home at age 2 to 3 months was also inversely associated with eczema in the first year of life, but the CI widened when endotoxin was included in the multivariate model (OR: 0.54; 95% CI: 0.27–1.09). Other variables associated with eczema in the first year of life included paternal history of eczema (OR: 1.91; 95% CI: 1.03–3.55) and maternal specific immunoglobulin E positivity to ≥1 allergen (OR: 1.61; 95% CI: 1.01–2.56).
Conclusions
Among children with parental history of asthma or allergies, exposure to high levels of endotoxin in early life may be protective against eczema in the first year of life. In these children, paternal history of eczema and maternal sensitization to at least 1 allergen are associated with an increased risk of eczema in the first year of life.
PMCID: PMC1242194  PMID: 15231902
Ig, immunoglobulin; OR, odds ratio; CI, confidence interval; Th2, T-helper cell type 2
21.  Hygiene levels in a contemporary population cohort are associated with wheezing and atopic eczema in preschool infants 
Background: The hygiene hypothesis states that insufficient exposure to certain infectious agents during childhood increases the risk of developing asthma and atopic diseases. Improvements in hygiene levels may be partly responsible for this decline in exposure.
Aims: To assess whether hygiene levels in infancy are associated with wheeze and/or atopic eczema, independent of a number of possible confounding factors.
Methods: Data were gathered from the Avon Longitudinal Study of Parents and Children (ALSPAC). Parental self completion questionnaires provided symptom data on infant wheeze and atopic eczema at 0–6 months and 30–42 months, respectively. A simple hygiene score was derived using questionnaire responses at 15 months, which ranged from least hygienic to most hygienic. Multivariable logistic regression models analysed the effect of hygiene scores on health outcomes, while adjusting for a number of important confounding variables.
Results: Increasing hygiene scores were independently associated with wheezing (OR = 1.04; 95% CI: 1.00 to 1.08) and atopic eczema (OR = 1.04; 95% CI: 1.01 to 1.07) between 30 and 42 months, but not in the first six months. The odds ratio was higher for atopic eczema if the rash was reported to have become sore and oozy (OR = 1.09; 95% CI: 1.02 to 1.16).
Conclusions: High levels of hygiene at 15 months of age were independently associated with wheeze and atopic eczema reported between 30 and 42 months, and there was an increased risk for children with more severe eczema during this period. The importance of hygiene in public health should not be dismissed; however, the creation of a sterile environment through excessive cleanliness may potentially be harmful to the immune system.
doi:10.1136/adc.87.1.26
PMCID: PMC1751124  PMID: 12089117
22.  Sibling number and prevalence of allergic disorders in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study 
BMC Public Health  2011;11:561.
Background
Although an inverse relationship between number of siblings and likelihood of allergic disorders has been shown in many epidemiological studies, the biological mechanism underlying this phenomenon has not yet been identified. There is no epidemiological research regarding the sibling effect on allergic disorders in Japanese adults. The current cross-sectional study examined the relationship between number of siblings and prevalence of allergic disorders among adult women in Japan.
Methods
Subjects were 1745 pregnant women. This study was based on questionnaire data. The definitions of wheeze and asthma were based on criteria from the European Community Respiratory Health Survey whereas those of eczema and rhinoconjunctivitis were based on criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for age, region of residence, pack-years of smoking, secondhand smoke exposure at home and at work, family history of asthma, atopic eczema, and allergic rhinitis, household income, and education.
Results
The prevalence values of wheeze, asthma, eczema, and rhinoconjunctivitis in the past 12 months were 10.4%, 5.5%, 13.0%, and 25.9%, respectively. A significant inverse exposure-response relationship was observed between the number of older siblings and rhinoconjunctivitis, but not wheeze, asthma, or eczema (P for trend = 0.03); however, the adjusted odds ratio (OR) for having 2 or more older siblings was not significant although the adjusted OR for having 1 older sibling was statistically significant (adjusted OR = 0.71 [95% CI: 0.56-0.91]). Number of total siblings and number of younger siblings were not related to wheeze, asthma, eczema, or rhinoconjunctivitis.
Conclusions
This study found a significant inverse relationship between the number of older siblings and the prevalence of rhinoconjunctivitis among pregnant Japanese women. Our findings are likely to support the intrauterine programming hypothesis; however, we could not rule out the hygiene hypothesis.
doi:10.1186/1471-2458-11-561
PMCID: PMC3142516  PMID: 21752304
23.  Association of parental eczema, hayfever, and asthma with atopic dermatitis in infancy: birth cohort study 
Archives of Disease in Childhood  2004;89(10):917-921.
Objective: To evaluate the association of parental history of atopic disease with childhood atopic dermatitis, and to examine the relative strength of associations with maternal and paternal disease.
Design: Mothers were recruited to the Avon longitudinal study of parents and children (ALSPAC) from the eighth week of pregnancy. Before parturition, both parents were asked, separately, to report their lifetime history of eczema, asthma, and hayfever. Parents reported symptoms of atopic dermatitis in their children at ages 6, 18, 30, and 42 months.
Results: Of 8530 children with complete information on rash at ages 6, 18, 30, and 42 months, 7969 had complete information on maternal atopic disease and 5658 on maternal and paternal atopic disease. There was a strong association between parental eczema and childhood atopic dermatitis: odds ratio 1.69 (95% confidence interval, 1.47 to 1.95) for maternal eczema only, 1.74 (1.44 to 2.09) for paternal eczema only, and 2.72 (2.09 to 3.53) for eczema in both parents. Associations with parental asthma or hayfever were attenuated after controlling for parental eczema. There was no evidence that associations with maternal atopy were stronger than with paternal.
Conclusions: Associations between parents' atopic disease and the risk of atopic dermatitis in offspring vary according to the type of atopic disease in the parents, but not according to parental sex. These results are at variance with previous studies reporting stronger associations with maternal than paternal atopy, and suggest that there is no "parent-of-origin" effect in atopic dermatitis. Parental eczema may be a better marker than parental asthma/hayfever in predisposing to childhood eczema.
doi:10.1136/adc.2003.034033
PMCID: PMC1719677  PMID: 15383434
24.  Biosocial factors in the epidemiology of childhood asthma in a British national sample. 
The relation between biosocial factors and childhood asthma in a British national sample (n = greater than 14 000) is examined. The presence of asthma was found to associate with sex of the child, parental age and occupation, housing type, and overcrowding as well as eczema and some infectious diseases. Discriminant analysis showed that it was possible to differentiate between asthmatics and non-asthmatics due mainly to allergy related factors.
PMCID: PMC1052424  PMID: 4009098
25.  Invited Commentary: Childhood Acute Lymphoblastic Leukemia and Allergies: Biology or Bias? 
American Journal of Epidemiology  2012;176(11):979-983.
Previous epidemiologic studies have shown an inverse association between a personal history of atopy/allergies, both overall and among asthma, eczema, and hay fever investigated separately, and childhood acute lymphoblastic leukemia (ALL) with some consistency; however, in most of these studies, exposure data were collected by maternal interview. Now, in a population-based and records-based study in this issue of the Journal (Am J Epidemiol. 2012;176(11):970–978), Chang et al. report an increased risk for allergic conditions across different etiologic time periods, calling the former paradigm into doubt. A review of the basic biology literature shows that proposed mechanisms support either a positive or an inverse association. In light of this ambiguity, it is epidemiology's turn to determine the direction of association.
doi:10.1093/aje/kws265
PMCID: PMC3571240  PMID: 23171875
child; hypersensitivity; leukemia

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