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1.  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
2.  Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study 
Nutrition Journal  2012;11:19.
Background
Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan.
Methods
Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index.
Results
The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis.
Conclusions
The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.
doi:10.1186/1475-2891-11-19
PMCID: PMC3342884  PMID: 22449171
3.  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
4.  Developmental Profiles of Eczema, Wheeze, and Rhinitis: Two Population-Based Birth Cohort Studies 
PLoS Medicine  2014;11(10):e1001748.
Using data from two population-based birth cohorts, Danielle Belgrave and colleagues examine the evidence for atopic march in developmental profiles for allergic disorders.
Please see later in the article for the Editors' Summary
Background
The term “atopic march” has been used to imply a natural progression of a cascade of symptoms from eczema to asthma and rhinitis through childhood. We hypothesize that this expression does not adequately describe the natural history of eczema, wheeze, and rhinitis during childhood. We propose that this paradigm arose from cross-sectional analyses of longitudinal studies, and may reflect a population pattern that may not predominate at the individual level.
Methods and Findings
Data from 9,801 children in two population-based birth cohorts were used to determine individual profiles of eczema, wheeze, and rhinitis and whether the manifestations of these symptoms followed an atopic march pattern. Children were assessed at ages 1, 3, 5, 8, and 11 y. We used Bayesian machine learning methods to identify distinct latent classes based on individual profiles of eczema, wheeze, and rhinitis. This approach allowed us to identify groups of children with similar patterns of eczema, wheeze, and rhinitis over time.
Using a latent disease profile model, the data were best described by eight latent classes: no disease (51.3%), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%). When latent variable modelling was carried out separately for the two cohorts, similar results were obtained. Highly concordant patterns of sensitisation were associated with different profiles of eczema, rhinitis, and wheeze. The main limitation of this study was the difference in wording of the questions used to ascertain the presence of eczema, wheeze, and rhinitis in the two cohorts.
Conclusions
The developmental profiles of eczema, wheeze, and rhinitis are heterogeneous; only a small proportion of children (∼7% of those with symptoms) follow trajectory profiles resembling the atopic march.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Our immune system protects us from viruses, bacteria, and other pathogens by recognizing specific molecules on the invader's surface and initiating a sequence of events that culminates in the death of the pathogen. Sometimes, however, our immune system responds to harmless materials (allergens such as pollen) and triggers allergic, or atopic, symptoms. Common atopic symptoms include eczema (transient dry itchy patches on the skin), wheeze (high pitched whistling in the chest, a symptom of asthma), and rhinitis (sneezing or a runny nose in the absence of a cold or influenza). All these symptoms are very common during childhood, but recent epidemiological studies (examinations of the patterns and causes of diseases in a population) have revealed age-related changes in the proportions of children affected by each symptom. So, for example, eczema is more common in infants than in school-age children. These findings have led to the idea of “atopic march,” a natural progression of symptoms within individual children that starts with eczema, then progresses to wheeze and finally rhinitis.
Why Was This Study Done?
The concept of atopic march has led to the initiation of studies that aim to prevent the development of asthma in children who are thought to be at risk of asthma because they have eczema. Moreover, some guidelines recommend that clinicians tell parents that children with eczema may later develop asthma or rhinitis. However, because of the design of the epidemiological studies that support the concept of atopic march, children with eczema who later develop wheeze and rhinitis may actually belong to a distinct subgroup of children, rather than representing the typical progression of atopic diseases. It is important to know whether atopic march adequately describes the natural history of atopic diseases during childhood to avoid the imposition of unnecessary strategies on children with eczema to prevent asthma. Here, the researchers use machine learning techniques to model the developmental profiles of eczema, wheeze, and rhinitis during childhood in two large population-based birth cohorts by taking into account time-related (longitudinal) changes in symptoms within individuals. Machine learning is a data-driven approach that identifies structure within the data (for example, a typical progression of symptoms) using unsupervised learning of latent variables (variables that are not directly measured but are inferred from other observable characteristics).
What Did the Researchers Do and Find?
The researchers used data from two UK birth cohorts—the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Manchester Asthma and Allergy Study (MAAS)—for their study (9,801 children in total). Both studies enrolled children at birth and monitored their subsequent health at regular review clinics. At each review clinic, information about eczema, wheeze, and rhinitis was collected from the parents using validated questionnaires. The researchers then used these data and machine learning methods to identify groups of children with similar patterns of onset of eczema, wheeze, and rhinitis over the first 11 years of life. Using a type of statistical model called a latent disease profile model, the researchers found that the data were best described by eight latent classes—no disease (51.3% of the children), atopic march (3.1%), persistent eczema and wheeze (2.7%), persistent eczema with later-onset rhinitis (4.7%), persistent wheeze with later-onset rhinitis (5.7%), transient wheeze (7.7%), eczema only (15.3%), and rhinitis only (9.6%).
What Do These Findings Mean?
These findings show that, in two large UK birth cohorts, the developmental profiles of eczema, wheeze, and rhinitis were heterogeneous. Most notably, the progression of symptoms fitted the profile of atopic march in fewer than 7% of children with symptoms. The researchers acknowledge that their study has some limitations. For example, small differences in the wording of the questions used to gather information from parents about their children's symptoms in the two cohorts may have slightly affected the findings. However, based on their findings, the researchers propose that, because eczema, wheeze, and rhinitis are common, these symptoms often coexist in individuals, but as independent entities rather than as a linked progression of symptoms. Thus, using eczema as an indicator of subsequent asthma risk and assigning “preventative” measures to children with eczema is flawed. Importantly, clinicians need to understand the heterogeneity of patterns of atopic diseases in children and to communicate this variability to parents when advising them about the development and resolution of atopic symptoms in their children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001748.
The UK National Health Service Choices website provides information about eczema (including personal stories), asthma (including personal stories), and rhinitis
The US National Institute of Allergy and Infectious Diseases provides information about atopic diseases
The UK not-for-profit organization Allergy UK provides information about atopic diseases and a description of the atopic march
MedlinePlus encyclopedia has pages on eczema, wheezing, and rhinitis (in English and Spanish)
MedlinePlus provides links to further resources about allergies, eczema, and asthma (in English and Spanish)
Information about ALSPAC and MAAS is available
Wikipedia has pages on machine learning and latent disease profile models (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001748
PMCID: PMC4204810  PMID: 25335105
5.  Active or Passive Exposure to Tobacco Smoking and Allergic Rhinitis, Allergic Dermatitis, and Food Allergy in Adults and Children: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(3):e1001611.
In a systematic review and meta-analysis, Bahi Takkouche and colleagues examine the associations between exposure to tobacco smoke and allergic disorders in children and adults.
Please see later in the article for the Editors' Summary
Background
Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases, especially among children, and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. The objective of this study was to examine the evidence for an association between active smoking (AS) or passive exposure to secondhand smoke and allergic conditions.
Methods and Findings
We retrieved studies published in any language up to June 30th, 2013 by systematically searching Medline, Embase, the five regional bibliographic databases of the World Health Organization, and ISI-Proceedings databases, by manually examining the references of the original articles and reviews retrieved, and by establishing personal contact with clinical researchers. We included cohort, case-control, and cross-sectional studies reporting odds ratio (OR) or relative risk (RR) estimates and confidence intervals of smoking and allergic conditions, first among the general population and then among children.
We retrieved 97 studies on allergic rhinitis, 91 on allergic dermatitis, and eight on food allergy published in 139 different articles. When all studies were analyzed together (showing random effects model results and pooled ORs expressed as RR), allergic rhinitis was not associated with active smoking (pooled RR, 1.02 [95% CI 0.92–1.15]), but was associated with passive smoking (pooled RR 1.10 [95% CI 1.06–1.15]). Allergic dermatitis was associated with both active (pooled RR, 1.21 [95% CI 1.14–1.29]) and passive smoking (pooled RR, 1.07 [95% CI 1.03–1.12]). In children and adolescent, allergic rhinitis was associated with active (pooled RR, 1.40 (95% CI 1.24–1.59) and passive smoking (pooled RR, 1.09 [95% CI 1.04–1.14]). Allergic dermatitis was associated with active (pooled RR, 1.36 [95% CI 1.17–1.46]) and passive smoking (pooled RR, 1.06 [95% CI 1.01–1.11]). Food allergy was associated with SHS (1.43 [1.12–1.83]) when cohort studies only were examined, but not when all studies were combined.
The findings are limited by the potential for confounding and bias given that most of the individual studies used a cross-sectional design. Furthermore, the studies showed a high degree of heterogeneity and the exposure and outcome measures were assessed by self-report, which may increase the potential for misclassification.
Conclusions
We observed very modest associations between smoking and some allergic diseases among adults. Among children and adolescents, both active and passive exposure to SHS were associated with a modest increased risk for allergic diseases, and passive smoking was associated with an increased risk for food allergy. Additional studies with detailed measurement of exposure and better case definition are needed to further explore the role of smoking in allergic diseases.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The immune system protects the human body from viruses, bacteria, and other pathogens. Whenever a pathogen enters the body, immune system cells called T lymphocytes recognize specific molecules on its surface and release chemical messengers that recruit and activate other types of immune cells, which then attack the pathogen. Sometimes, however, the immune system responds to harmless materials (for example, pollen; scientists call these materials allergens) and triggers an allergic disease such as allergic rhinitis (inflammation of the inside of the nose; hay fever is a type of allergic rhinitis), allergic dermatitis (also known as eczema, a disease characterized by dry, itchy patches on the skin), and food allergy. Recent studies suggest that all these allergic (atopic) diseases are part of a continuous state called the “atopic march” in which individuals develop allergic diseases in a specific sequence that starts with allergic dermatitis during infancy, and progresses to food allergy, allergic rhinitis, and finally asthma (inflammation of the airways).
Why Was This Study Done?
Allergic diseases are extremely common, particularly in children. Allergic rhinitis alone affects 10%–30% of the world's population and up to 40% of children in some countries. Moreover, allergic diseases are becoming increasingly common. Allergic diseases affect the quality of life of patients and are financially costly to both patients and health systems. It is important, therefore, to identify the factors that cause or potentiate their development. One potential risk factor for allergic diseases is active or passive exposure to tobacco smoke. In some countries up to 80% of children are exposed to second-hand smoke so, from a public health point of view, it would be useful to know whether exposure to tobacco smoke is associated with the development of allergic diseases. Here, the researchers undertake a systematic review (a study that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical approach for combining the results of several studies) to investigate this issue.
What Did the Researchers Do and Find?
The researchers identified 196 observational studies (investigations that observe outcomes in populations without trying to affect these outcomes in any way) that examined the association between smoke exposure and allergic rhinitis, allergic dermatitis, or food allergy. When all studies were analyzed together, allergic rhinitis was not associated with active smoking but was slightly associated with exposure to second-hand smoke. Specifically, compared to people not exposed to second-hand smoke, the pooled relative risk (RR) of allergic rhinitis among people exposed to second-hand smoke was 1.10 (an RR of greater than 1 indicates an increased risk of disease development in an exposed population compared to an unexposed population). Allergic dermatitis was associated with both active smoking (RR = 1.21) and exposure to second-hand smoke (RR = 1.07). In the populations of children and adolescents included in the studies, allergic rhinitis was associated with both active smoking and exposure to second-hand smoke (RRs of 1.40 and 1.09, respectively), as was allergic dermatitis (RRs of 1.36 and 1.06, respectively). Finally food allergy was associated with exposure to second-hand smoke (RR = 1.43) when cohort studies (a specific type of observational study) only were examined but not when all the studies were combined.
What Do These Findings Mean?
These findings provide limited evidence for a weak association between smoke exposure and allergic disease in adults but suggest that both active and passive smoking are associated with a modestly increased risk of allergic diseases in children and adolescents. The accuracy of these findings may be affected by the use of questionnaires to assess smoke exposure and allergic disease development in most of the studies in the meta-analysis and by the possibility that individuals exposed to smoke may have shared other characteristics that were actually responsible for their increased risk of allergic diseases. To shed more light on the role of smoking in allergic diseases, additional studies are needed that accurately measure exposure and outcomes. However, the present findings suggest that, in countries where many people smoke, 14% and 13% of allergic rhinitis and allergic dermatitis, respectively, among children may be attributable to active smoking. Thus, the elimination of active smoking among children and adolescents could prevent one in seven cases of allergic rhinitis and one in eight cases of allergic dermatitis in such countries.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001611.
The UK National Health Service Choices website provides information about allergic rhinitis, hay fever (including personal stories), allergic dermatitis (including personal stories), and food allergy (including personal stories)
The US National Institute of Allergy and Infectious Disease provides information about allergic diseases
The UK not-for-profit organization Allergy UK provides information about all aspects of allergic diseases and a description of the atopic march
MedlinePlus encyclopedia has pages on allergic rhinitis and allergic dermatitis (in English and Spanish)
MedlinePlus provides links to further resources about allergies, eczema, and food allergy (in English and Spanish)
doi:10.1371/journal.pmed.1001611
PMCID: PMC3949681  PMID: 24618794
6.  Case-control study of IL13 polymorphisms, smoking, and rhinoconjunctivitis in Japanese women: the Kyushu Okinawa Maternal and Child Health Study 
BMC Medical Genetics  2011;12:143.
Background
Six previous studies have examined the relationships between single nucleotide polymorphisms (SNPs) in the IL13 gene and allergic rhinitis, but the results have been inconsistent. However, a recent meta-analysis using data from these 6 studies has shown that the A allele of IL13 SNP rs20541 was associated with an increased risk of allergic rhinitis, whereas no such relationship existed between IL13 SNP rs1800925 and allergic rhinitis. We investigated the associations between IL13 SNPs rs1800925 and rs20541 and the risk of rhinoconjunctivitis in Japanese women.
Methods
Included were 393 cases who met the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC) for rhinoconjunctivitis. Control subjects were 767 women without rhinoconjunctivitis according to the ISAAC criteria, who had also not been diagnosed with allergic rhinitis by a doctor. Adjustment was made for age, region of residence, presence of older siblings, smoking, family history of allergic rhinitis, and education.
Results
Compared with the GG genotype of IL13 SNP rs20541, the AA genotype, occurring in 7.1% of control subjects, was significantly positively related to the risk of rhinoconjunctivitis: the adjusted odds ratio was 1.65 (95% confidence interval: 1.05 - 2.60). SNP rs1800925 was not associated with rhinoconjunctivitis. The haplotype comprising the rs1800925 C allele and the rs20541 A allele was significantly positively related to rhinoconjunctivitis. The multiplicative interactions between the two SNPs under study and smoking on the risk of rhinoconjunctivitis were not statistically significant. Based on the recessive model, however, the additive interaction between SNP rs1800925, but not rs20541, and smoking was significant.
Conclusions
This study suggests that the minor genotype of IL13 SNP rs20541 and the CA haplotype are significantly positively associated with the risk of rhinoconjunctivitis. In addition, a new pattern of biological interaction that affects the risk of rhinoconjunctivitis is described between SNP rs1800925 and smoking.
doi:10.1186/1471-2350-12-143
PMCID: PMC3214177  PMID: 22023794
7.  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
8.  Severe Eczema in Infancy Can Predict Asthma Development. A Prospective Study to the Age of 10 Years 
PLoS ONE  2014;9(6):e99609.
Background
Children with atopic eczema in infancy often develop allergic rhinoconjunctivitis and asthma, but the term “atopic march” has been questioned as the relations between atopic disorders seem more complicated than one condition progressing into another.
Objective
In this prospective multicenter study we followed children with eczema from infancy to the age of 10 years focusing on sensitization to allergens, severity of eczema and development of allergic airway symptoms at 4.5 and 10 years of age.
Methods
On inclusion, 123 children were examined. Hanifin-Rajka criteria and SCORAD index were used to describe the eczema. Episodes of wheezing were registered, skin prick tests and IgE tests were conducted and questionnaires were filled out. Procedures were repeated at 4.5 and 10 years of age with additional examinations for ARC and asthma.
Results
94 out of 123 completed the entire study. High SCORAD points on inclusion were correlated with the risk of developing ARC, (B = 9.86, P = 0.01) and asthma, (B = 10.17, P = 0.01). For infants with eczema and wheezing at the first visit, the OR for developing asthma was 4.05(P = 0.01). ARC at 4.5 years of age resulted in an OR of 11.28(P = 0.00) for asthma development at 10 years.
Conclusion
This study indicates that infant eczema with high SCORAD points is associated with an increased risk of asthma at 10 years of age. Children with eczema and wheezing episodes during infancy are more likely to develop asthma than are infants with eczema alone. Eczema in infancy combined with early onset of ARC seems to indicate a more severe allergic disease, which often leads to asthma development. The progression from eczema in infancy to ARC at an early age and asthma later in childhood shown in this study supports the relevance of the term “atopic march”, at least in more severe allergic disease.
doi:10.1371/journal.pone.0099609
PMCID: PMC4051764  PMID: 24914552
9.  Association between environmental factors and current asthma, rhinoconjunctivitis and eczema symptoms in school-aged children from Oropeza Province – Bolivia: a cross-sectional study 
Environmental Health  2013;12:95.
Background
In recent years, the prevalence of asthma, rhinoconjunctivitis and eczema symptoms in childhood has considerably increased in developing countries including Bolivia, possibly due to changes in lifestyle, environmental and domestic factors. This study aimed to assess the association between environmental factors and asthma, rhinoconjuctivitis and eczema symptoms in school-aged children from Oropeza Province in Chuquisaca, Bolivia.
Methods
A cross-sectional study was performed in 2340 children attending the fifth grade in 36 randomly selected elementary schools in Oropeza province. The prevalence of symptoms was determined using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Environmental factors were assessed by the ISAAC environmental questionnaire including questions related to exposure to pets, farm animals, indoor and outdoor pollution, presence of disease vectors at home and precarious household conditions. Generalized linear mixed-effects models were adjusted for age, sex and place of living.
Results
Thirty seven percent of children reported that at least one of their parents smoked at home. Wood or coal was used as cooking fuel in 19% of the homes and 29% reported intense truck traffic on the street where they lived. With respect to hygiene conditions, 86% reported exposure to dogs, 59% exposure to cats and 36% regular contact to farm animals. More than one precarious household condition was reported by 8% of children. In the adjusted model exposure to dog (adjusted OR 1.4; CI 95% 1.0-1.9), cat (1.2; 1.0-1.5), farm animals (1.5; 1.2-1.8); intense truck traffic (1.3; 1.0-1.6), parents smoking at home (1.2; 1.0-1.5), presence of disease vectors at home (fourth quartile vs. first quartile: 1.6; 1.2-2.3) and two or more precarious household conditions (1.5; 1.0-2.2) were significantly associated with rhinoconjunctivitis symptoms. The associations were similar for asthma and eczema symptoms; however it did not reach the level of statistical significance for all items.
Conclusion
Our results support previous findings reported for poor communities especially in Latin America, showing that lower hygiene conditions did not have protective effect against asthma and rhinoconjunctivitis and eczema symptoms.
doi:10.1186/1476-069X-12-95
PMCID: PMC4228317  PMID: 24192069
Asthma; Rhinoconjunctivitis; Eczema; Children; Environmental factors
10.  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
11.  The Role of Acetaminophen and Geohelminth Infection on the Incidence of Wheeze and Eczema 
Rationale: Acetaminophen has been hypothesized to increase the risk of asthma and allergic disease, and geohelminth infection to reduce the risk, but evidence from longitudinal cohort studies is lacking.
Objectives: To investigate the independent effects of these exposures on the incidence of wheeze and eczema in a birth cohort.
Methods: In 2005–2006 a population-based cohort of 1,065 pregnant women from Butajira, Ethiopia, was established, to whom 1,006 live singleton babies were born. At ages 1 and 3, questionnaire data were collected on wheeze, eczema, child's use of acetaminophen, and various potential confounders, along with a stool sample for geohelminth analysis. Those without wheeze (n = 756) or eczema (n = 780) at age 1 were analyzed to determine the independent effects of geohelminth infection and acetaminophen use in the first year of life on the incidence of wheeze and eczema by age 3.
Measurements and Main Results: Wheeze and eczema incidence between the ages of 1 and 3 were reported in 7.7% (58 of 756) and 7.3% (57 of 780) of children, respectively. Acetaminophen use was significantly associated with a dose-dependent increased risk of incident wheeze (adjusted odds ratio = 1.88 and 95% confidence interval 1.03–3.44 for one to three tablets and 7.25 and 2.02–25.95 for ≥4 tablets in the past month at age 1 vs. never), but not eczema. Geohelminth infection was insufficiently prevalent (<4%) to compute estimates of effect.
Conclusions: These findings suggest frequent acetaminophen use early in life increases the risk of new-onset wheeze, whereas the role of geohelminth infection on allergic disease incidence remains to be seen as the cohort matures.
doi:10.1164/rccm.201006-0989OC
PMCID: PMC3040388  PMID: 20935107
acetaminophen; parasite; asthma; wheeze; eczema
12.  408 Prevalence and Risk Factors Associated to Symptoms of Rhinoconjunctivitis in Mexican School Children. A Multicenter Study 
Background
According to ISAAC symptoms of allergic rhinoconjunctivitis (RC), have a worldwide prevalence of 8.5% in school children. Multiple risk factors had been associated with its prevalence, though little is known about the regional variations of these risk factors.
Objective
Identify the prevalence and the main risk factors associated to the presence of symptoms of rhinoconjunctivitis in the last 12 months in Mexican school children.
Methods
Cross-sectional, multicenter, prospective, based in ISAAC methodology of 9 registered sites in 8 cities (north, center and south of the Mexican Republic) with a validated and standardized survey applied to tutors of children aged 6 to 7 years old. Risk analysis was made through multivariate logistical regression, central tendency and dispersion measures were obtained with respective 95% confidence intervals.
Results
24,902 surveys were obtained. The prevalence and 95%CI of symptoms of rhinitis was as follows: Monterrey 23%(21.4-24.5%), Mexicali 28.7% (26.9-30.5%), Ciudad Victoria 21.3%(19.7-22.8%), Villahermosa 39% (37-41%), North Federal District 45.6% (44.1-47.2%), Toluca-18.6% (17.3-20%), Tijuana 24.5% (22.9-26.1%), southeast Federal District 53%(50.7-55.4%) Veracruz 25% (23.1-26.8%) and conjunctivitis: Monterrey 8.8% (7.8-9.9%), Mexicali 13.2%(11.9-14.5%), Ciudad Victoria 7.3%(6.3-8.3%), Villahermosa 18.7% (17-20.3%), North Federal District 20.4%(19.1-21.7%), Toluca 7.3%(6.4-8.2%), Tijuana 8.7%(7.6-9.7%), southeast Federal District 25.1%(23-27.1%) Veracruz 8.7% (7.5-9.9%). The prevalence de rhinoconjunctivitis were 12.8%.
Identified risk factors for the presence of rhinitis in the last 12 months were: asthma symptoms in the last 12 months OR-2.59 (95% CI, 2.25-2.98; P ≤ 0.0001), wheezing ever OR-1.78 (95% CI, 1.61-1.96; P ≤ 0.0001), eczema symptoms in the last 12 months OR-1.61 (95% CI, 1.35-1.93; P ≤ 0.0001), atopic dermatitis ever OR-2.97 (95% CI, 2.52-3.51; P ≤ 0.0001).
Identified risk factors for the presence of conjunctivitis in the last 12 months were: wheezing ever OR-1.88 (95% CI, 1.64-2.16; P ≤ 0.0001), asthma symptoms in the last 12 months OR-2.97 (95% CI, 2.52-3.51; P ≤ 0.0001) eczema symptoms in the last 12 months OR-1.95 (95% CI, 1.58-2.41; P ≤ 0.0001), atopic dermatitis ever OR-2.14 (95% CI, 1.81-2.54; P ≤ 0.0001).
Conclusions
The highest prevalence of rhinoconjunctivitis in Mexican School Children is in the southeast of the Federal District.
The presence of asthma symptoms in the last 12 months, wheezing ever, eczema symptoms in the last 12 months, atopic dermatitis ever, risk factors are present symptoms of rhinoconjunctivitis.
doi:10.1097/01.WOX.0000412171.15972.bf
PMCID: PMC3513007
13.  The Burden of Rhinitis and Rhinoconjunctivitis in Adolescents 
Purpose
Rhinitis and conjunctivitis are common diseases worldwide that are frequently associated. Nevertheless, the risk factors for rhinoconjunctivitis are not well-described and the impact of conjunctivitis on rhinitis and asthma in children remains unknown. This study explored the different risk factors and evaluated the burden of rhinoconjunctivitis among adolescents.
Methods
This was a cross-sectional study conducted on a random sample of schoolchildren, aged 10-17 years, using skin prick tests and a self-administered questionnaire on respiratory health investigating the impact of rhinitis and rhinoconjunctivitis on daily activities.
Results
A complete evaluation was obtained for 2,150 children. The prevalence of rhinitis alone was 18.2% and rhinitis associated with conjunctivitis was 20.5%. Rhinoconjunctivitis was more frequently associated with females, a parental history of atopy, domestic exposure to mold/dampness, passive smoke exposure, and reported truck traffic in residential streets. Moreover, rhinoconjunctivitis was associated with a higher level of allergic sensitization. The prevalence of current asthma was 1.7% in subjects without rhinitis or rhinoconjunctivitis, 5.1% in rhinitis and 10.7% in rhinoconjunctivitis. In a logistic model, rhinoconjunctivitis yielded a 2-fold risk for current asthma with respect to rhinitis. Subjects with rhinoconjunctivitis had poorer quality of life (QoL); there was an impact on daily activities in 4.6% of rhinitis and 10.7% of rhinoconjunctivitis.
Conclusions
Ocular symptoms increase the role of rhinitis as a risk factor for asthma and its impact on daily activities in children.
doi:10.4168/aair.2015.7.1.44
PMCID: PMC4274469  PMID: 25553262
Rhinitis; conjunctivitis; epidemiology; asthma; children
14.  A Randomised Controlled Trial of Ion-Exchange Water Softeners for the Treatment of Eczema in Children 
PLoS Medicine  2011;8(2):e1000395.
In a randomized trial evaluating the effect of installation of ion-exchange water softeners in the households of children with eczema, the researchers found no evidence of improvement in eczema severity as compared to usual care in the study population.
Background
Epidemiological studies and anecdotal reports suggest a possible link between household use of hard water and atopic eczema. We sought to test whether installation of an ion-exchange water softener in the home can improve eczema in children.
Methods and Findings
This was an observer-blind randomised trial involving 336 children (aged 6 months to 16 years) with moderate/severe atopic eczema. All lived in hard water areas (≥200 mg/l calcium carbonate). Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care, or usual eczema care alone. The primary outcome was change in eczema severity (Six Area Six Sign Atopic Dermatitis Score, SASSAD) at 12 weeks, measured by research nurses who were blinded to treatment allocation. Analysis was based on the intent-to-treat population. Eczema severity improved for both groups during the trial. The mean change in SASSAD at 12 weeks was −5.0 (20% improvement) for the water softener group and −5.7 (22% improvement) for the usual care group (mean difference 0.66, 95% confidence interval −1.37 to 2.69, p = 0.53). No between-group differences were noted in the use of topical corticosteroids or calcineurin inhibitors.
Conclusions
Water softeners provided no additional benefit to usual care in this study population. Small but statistically significant differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias, since participants were aware of their treatment allocation. A detailed report for this trial is also available at http://www.hta.ac.uk.
Trial registration
Current Controlled Trials ISRCTN71423189
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Eczema (sometimes referred to as atopic dermatitis) is a chronic, inflammatory skin condition that affects about 20% of school children in developed countries. Eczema is often associated with other conditions, such as asthma, hay-fever and food allergy and can cause intractable itching leading to thickened skin, bleeding, secondary infection, sleep loss, poor concentration, and psychological distress. Current topical treatments for eczema have side effects, for example, topical corticosteroids may cause skin thinning and the long term safety of topical tacrolimus and pimecrolimus has yet to be determined. Therefore, there is a lot of interest in exploring the benefits of non-pharmacological treatments that have no apparent side effects.
Water hardness (≥200 mg/l calcium carbonate) has become a recent focus of attention.
Why Was This Study Done?
In addition to some epidemiological evidence linking increased water hardness with increased eczema prevalence, there have been widespread anecdotal reports of improvement in the skin of children with eczema when the family has moved from a hard to a soft water area. In addition, some patients report how their eczema symptoms have rapidly improved following the installation of a water softener. However, to date there have been no relevant published trials evaluating the potential benefit of water softeners for eczema. Given the lack of evidence, the high public interest in their potential benefit and the low risk of adverse effects, the researcher conducted a study to assess whether the installation of an ion-exchange water softener reduces the severity of eczema in children with moderate to severe eczema.
What Did the Researchers Do and Find?
The researchers did a pilot study that showed that it was not possible to blind participants to their treatment allocation using real and “dummy” water softener units because the softened water produced more soap suds. So the researchers conducted an observer-blind randomised controlled trial in which they used trained research nurses to conduct an objective assessment of every participant's skin. The researchers recruited 336 children who all lived in hard water areas in England. Eligible children were aged 6 months to 16 years who had a diagnosis of eczema (in line with the UK working party's diagnostic criteria) and an eczema severity score of 10 or over. Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care, or usual eczema care alone. Trained research nurses examined each child's skin at baseline and at 6, 12, and 16 weeks to record changes in eczema severity. The researchers also analysed any changes in symptoms over the study period such as, sleep loss and itchiness, the amount of topical corticosteroid/calcineurin inhibitors used, the Dermatitis Family Impact questionnaire and the health related Quality of Life (children's version).
Although both treatment groups improved in disease severity during the course of the trial, the researchers found no difference between the treatment groups in the main outcome—eczema severity. Similar finding were found for night movement (scratching) and the use of topical medications (creams/ointments applied to the skin), both of which were blinded to intervention status. Nevertheless, parents in the trial did report small health benefits, and just over 50% chose to buy the water softener at the end of the trial because of perceived improvements in the eczema and the wider benefits of water softeners. It is unclear how much of this effect can be explained by prior belief in the effectiveness of the water softeners for the treatment of eczema.
What Do These Findings Mean?
The results of this study suggest that water softeners provide no additional clinical benefit to usual care in children with eczema so the use of ion-exchange water softeners for the treatment of moderate to severe eczema in children should not be recommended. However, it is up to each family to decide whether or not the wider benefits of installing a water softener in their home are sufficient to consider buying one.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000395.
The UK's NHS presents information on eczema for patients and families
MedlinePlus gives information for patients, families, and caregivers on eczema and other similar conditions
The National Eczema Society in the UK provides information and a helpline for eczema patients, families, and caregivers
Medinfo provides information for eczema patients
Wikipedia has more information about water softening (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1000395
PMCID: PMC3039684  PMID: 21358807
15.  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
16.  Prevalence of self-reported eczema in relation to living environment, socio-economic status and respiratory symptoms assessed in a questionnaire study 
BMC Dermatology  2003;3:4.
Background
Potential links between eczema and obstructive pulmonary diseases have been postulated. Previously we have reported the prevalence of upper and lower respiratory diseases and the relation to environmental and socio-economic factors in a randomly selected adult population in southern Sweden using a postal questionnaire.
In the present study we wanted to analyse the prevalence of eczema and its relation to socio-economic status, heredity factors and environmental factors in an adult population.
Methods
Self-reported eczema, upper and lower respiratory symptoms, asthma and Chronic Bronchitis Emphysema (CBE) were examined in 12,071 adults, aged 20–59 years, living in southern Sweden by using a postal questionnaire. There were comparable numbers of males and females in all age groups.
Multiple logistic regression analysis (forward conditional) was applied to estimate the association between the proposed risk factors (heredity, self-reported asthma and CBE, nasal symptoms, socio-economic group, environmental factors, age, gender and smoking habits) and self-reported eczema.
Results
The response rate was 70.1%. In all, 1240 subjects (14.6%) stated that they had eczema. In all age cohorts self-reported eczema was more frequently reported by women than by men (p < 0.05). The prevalence of self-reported eczema among the economically active population varied from 17.1% to 8.2% with the highest rates among assistant non-manual employees. However, when controlling for age, gender and risk occupation there was no association between low social position and eczema. Living close to heavy traffic (OR = 1.45, 95% CI 1.25–1.67) and living seaside (OR = 1.17, 95% CI 1.01–1.35) but not urban/suburban living was associated with eczema. Heredity of eczema (OR = 5.77, 95% CI 5.02–6.64), self reported allergic rhinitis (OR = 2.31, 95% CI 2.00–2.68), self reported asthma (OR = 1.98, 95% CI 1.56–2.51) and self reported CBE (OR = 1.42, 95% CI 1.08–1.87) were all associated with eczema.
Conclusions
In this epidemiological study we see that self-reported eczema is a common disease in an adult population especially among women. Eczema seems to be linked to environment factors, obstructive pulmonary diseases and rhinitis.
doi:10.1186/1471-5945-3-4
PMCID: PMC183835  PMID: 12859793
Eczema; environmental factors; genetic factors; socio-economy; postal questionnaire; respiratory symptoms; smoking.
17.  Foetal Exposure to Maternal Passive Smoking Is Associated with Childhood Asthma, Allergic Rhinitis, and Eczema 
The Scientific World Journal  2012;2012:542983.
Objective. We examined the hypothesis that foetal exposure to maternal passive smoking is associated with childhood asthma, allergic rhinitis, and eczema. Methods. The study was a population-based cross-sectional survey of Hong Kong Chinese children aged ≤14 years carried out in 2005 to 2006. Results. Foetal exposure to maternal passive smoking was significantly associated with wheeze ever (OR 2.05; 95% CI 1.58–2.67), current wheeze (OR 2.06; 95% CI 1.48–2.86), allergic rhinitis ever (OR 1.22; 95% CI 1.09–1.37), and eczema ever (OR 1.61; 95% CI 1.38–1.87). Foetal exposure to maternal active smoking was significantly associated with asthma ever (OR 2.10; 95% CI 1.14–3.84), wheeze ever (OR 2.46; 95% CI 1.27–4.78), and current wheeze (OR 2.74; 95% CI 1.24–6.01) but not with allergic rhinitis ever (OR 1.01; 95% CI 0.70–1.46) or eczema ever (OR 1.38; 95% CI 0.87–2.18). The dose response relationship between wheeze ever and current wheeze with increasing exposure, from no exposure to maternal passive smoking and then to maternal active smoking, further supports causality. Conclusion. There is significant association between foetal exposure to maternal passive smoking and maternal active smoking with childhood asthma and related atopic illnesses. Further studies are warranted to explore the potential causal relationship.
doi:10.1100/2012/542983
PMCID: PMC3425811  PMID: 22927783
18.  337 Allergic Disorders Prevented by Helicobacter Pylori Colonization 
The World Allergy Organization Journal  2012;5(Suppl 2):S125-S126.
Background
Previous studies suggest that an association exists between microbiological colonization and allergic disorders. The derived hygiene hypothesis postulates that the increase in atopic diseases may in part be due to diminished exposure to microorganisms. The study should contribute to clear up whether the association exists focused on chronic microbial colonization/infection and which type of infection does render the expected protection.
Methods
As part of a 3 times repeated cross-sectional epidemiological study 4925 children in total have been medical checked up. Gastrointestinal and respiratory types of infection where considered: (1) gastrointestinal colonization (Helicobacter pylori detection using in vivo [13C] urea breath test) and (2) respiratory infections (physician-diagnosed lower (bronchitis) and upper (common cold) respiratory tract infections). Physician diagnosed allergic asthma, atopic eczema, rhinitis allergica and allergic symptoms were selected as allergic target variables.
Results
Descriptive: Whereas respiratory infections lead to higher prevalence of the allergic disorders (not infected/infected: asthma 3/10%, eczema 10/24%, hay fever 6/12%) Helicobacter pylori colonization protects against allergies (not infected/infected: asthma 6/3%, eczema 16/7%, hay fever 8/7%). Analytical: The descriptive results could be confirmed using a logistic regression adjusted for relevant confounders (gender, smoking and passive smoking, parental predisposition, pets (like cats), number of older siblings, duration of breastfeeding, socioeconomic status) except and not significant for rhinitis allergica. Related to asthma/eczema/hay fever the adjusted odds ratios (aOR) for Helicobacter pylori colonization were 0.58 (P = 0.05)/0.48 (P < 0.01)/1.07 (P = 0.75). Contrary respiratory tract infection shows an amplifying effect on asthma/eczema/hay fever of aOR 3.75 (P < 0.01)/1.96 (P < 0.01)/2.07 (P < 0.01).
Conclusions
Helicobacter pylori colonization seems to protect against allergic disorders in comparison with the effect of respiratory tract infections. The hygiene hypothesis may be better explained when this kind of gastrointestinal and respiratory tract infections are subtly differentiated.
doi:10.1097/01.WOX.0000412100.41590.b7
PMCID: PMC3512867
19.  Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure  
PLoS Medicine  2008;5(6):e131.
Background
Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema.
Methods and Findings
We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27–4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79–32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24–1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13–3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35–10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16–2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation.
Conclusions
We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.
In two independent cohorts of children, Hans Bisgaard and colleagues show an association between mutations in the filaggrin gene (FLG) and ownership of cats, but not dogs, with development of eczema.
Editors' Summary
Background.
Eczema is a skin condition characterized by dry, red, and itchy patches on the skin. Eczema is associated with asthma and allergy, though allergy rarely plays a role in development or severity of eczema. Eczema usually begins during infancy, typically on the face, scalp, neck, extensor sides of the forearms, and legs. Up to one in five infants develops eczema, but in more than half of them, the condition improves or disappears completely before they are 15 years old. If eczema persists into adulthood, it usually affects the face and the skin inside the knees and elbows. There is no cure for eczema but it can be controlled by avoiding anything that makes its symptoms worse. These triggers include irritants such as wool, strong soaps, perfumes, and dry environments. A good skin-care routine and frequent moisturizing can also help to keep eczema under control, but in many cases, corticosteroid creams and ointments may be necessary to reduce inflammation.
Why Was This Study Done?
Eczema tends to run in families. This suggests that eczema is caused by genetic factors as well as by environmental factors. Recently, researchers discovered that two common “loss-of-function” variants in the gene encoding filaggrin (FLG) predispose people to eczema. People who inherit one or two defective genes make no filaggrin, a protein that normally forms a physical barrier in the skin that protects the body from potentially harmful substances in the environment. Might the weakening of this barrier in filaggrin-deficient individuals affect their responses to environmental substances to which the skin is exposed? In this study, the researchers test this potential explanation for how genetic and environmental factors (in particular, exposure to pets) might interact to determine an individual's chances of developing eczema.
What Did the Researchers Do and Find?
To test their hypothesis, the researchers studied two independent groups of infants during their first year of life—a high-risk group consisting of infants born in Copenhagen, Denmark to mothers with asthma and a group of infants born to women from the general population in Manchester, United Kingdom. The researchers determined which FLG variants each child had inherited and classified those with either one or two defective copies of FLG as having an FLG mutation. They determined pet exposure in early life by asking whether a dog or a cat was living in the parental home when the child was born (“pet ownership”) and then analyzed how these genetic and environmental factors affected the age of onset of eczema. In both groups, children with FLG mutations were twice as likely to develop eczema during the first year of life as children without FLG mutations. For children without FLG mutations, cat ownership at birth had no effect on eczema risk but for children with FLG mutations, cat ownership at birth (but not dog ownership) further increased the risk of developing eczema.
What Do These Findings Mean?
These findings show that FLG mutations and cat ownership at birth interact to determine the chances of a child developing eczema during the first year of life. They provide support, therefore, for the researchers' suggestion that the weakening of the skin's protective barrier that is caused by filaggrin deficiency increases the child's susceptibility to factors associated with cat exposure. Only a small number of children in this study carried FLG mutations and were exposed to cats from birth, so these findings need confirming in independent studies. In addition, it is still not clear how exposure to cats drives the development of eczema. Allergy was not the mechanism as the FLG-deficient children exposed to cat and who developed eczema did not develop cat-specific immunoglobin E antibodies. Nevertheless, these findings suggest that, to reduce their risk of developing eczema, filaggrin-deficient individuals should avoid cats (but not dogs) during the first few months of life.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050131.
The MedlinePlus Encyclopedia has a page on eczema (in English and Spanish); links to further information are provided by MedlinePlus
EczemaNet is a comprehensive online information resource about eczema provided by the American Academy of Dermatologists
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases provides information on eczema
The UK National Health Service Direct health encyclopedia provides information for patients on eczema (in several languages)
The Copenhagen Studies on Asthma in Childhood (COPSAC) and Manchester Asthma and Allergy Study (MAAS) Web sites provide more information about the children involved in this research
doi:10.1371/journal.pmed.0050131
PMCID: PMC2504043  PMID: 18578563
20.  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
21.  Effects of Early Life Paracetamol Use on the Incidence of Allergic Disease and Sensitization: 5 Year Follow-Up of an Ethiopian Birth Cohort 
PLoS ONE  2014;9(4):e93869.
Introduction
The hypothesis that paracetamol, one of the most widely used medicines, may increase the risk of asthma and allergic disease is of obvious importance but prospective cohort data looking at dose and timing of exposure are lacking.
Objective
The aim of the study is to investigate the role of paracetamol use in early life on the prevalence and incidence of wheeze, eczema, rhinitis and allergic sensitization, prospectively over 5 years in an Ethiopian birth cohort.
Methods
In 2005/6 a birth cohort of 1006 newborns was established in Butajira, Ethiopia. Questionnaire data on allergic disease symptoms, paracetamol use and numerous potential confounders were collected at ages 1, 3 and 5, and allergen skin sensitivity measured at ages 3 and 5. Multivariate logistic regression was used to determine independent effects of paracetamol exposure on the incidence of each outcome between ages 3 and 5, and prevalence at age 5.
Findings
Paracetamol use in the first 3 years of life was reported in 60% of children and was associated with increased incidence of wheeze, eczema, rhinitis and allergic sensitisation between ages 3 and 5 which was statistically significant for wheeze and eczema. High exposure (reported use in the past month at age 1 and 3) was associated with a more than 3-fold increased risk of new onset wheeze (adjusted odds ratio (OR) 3.64; 95% confidence interval, 1.34 to 9.90) compared to never users. Use in the past year at age 3 but not age 1 was associated with ORs at least as large as those for use in first year of life only. Significant positive dose-response effects of early life use were seen in relation to the prevalence of all outcomes at age 5.
Conclusions
Use of paracetamol in early life is a strong risk factor for incident allergic disease in childhood.
doi:10.1371/journal.pone.0093869
PMCID: PMC3981735  PMID: 24718577
22.  Endotoxin in inner-city homes: Associations with wheeze and eczema in early childhood 
Background
An inverse association between domestic exposure to endotoxin and atopy in childhood has been observed. The relevance of this aspect of the “hygiene hypothesis” to U.S. inner-city communities that have disproportionately high asthma prevalence has not been determined.
Objectives
To measure endotoxin in the dust from inner-city homes, evaluate associations between endotoxin and housing/lifestyle characteristics, and determine whether endotoxin exposure predicted wheeze, allergic rhinitis and eczema over the first three years of life.
Methods
As part of an ongoing prospective birth cohort study, children of Dominican and African-American mothers living in New York City underwent repeated questionnaire measures. Dust samples collected from bedroom floors at age 12 or 36 months were assayed for endotoxin.
Results
Among the samples collected from 301 participant’s homes, the geometric mean endotoxin concentration [95% C.I.] was 75.9 EU/mg [66–87] and load was 3,892 EU/m2 [3,351–4,522]. Lower endotoxin concentrations were associated with wet mop cleaning and certain neighborhoods. Endotoxin concentration correlated weakly with cockroach (Bla g 2: r=0.22,p<0.001) and mouse (MUP: r=0.28,p<0.001) allergens in the dust. Children in homes with higher endotoxin concentration were less likely to have eczema at age 1 year (O.R. 0.70 [0.53–0.93]) and more likely to wheeze at age 2 years (O.R. 1.34 [1.01–1.78]). These associations were stronger among children with a maternal history of asthma.
Conclusions
Endotoxin levels in this inner-city community are similar to non-farm homes elsewhere. In this community, domestic endotoxin exposure was inversely associated with eczema at age 1, but positively associated with wheeze at age 2.
Clinical Implications
Endotoxin exposure in the inner-city community may be related to wheeze in the early life; however, given the inverse association seen with eczema, the long term development of allergic disease is still in question.
doi:10.1016/j.jaci.2005.12.1348
PMCID: PMC2040050  PMID: 16675336
Endotoxin; asthma; allergy; hygiene hypothesis; wheeze; inner-city; eczema
23.  Mould/dampness exposure at home is associated with respiratory disorders in Italian children and adolescents: the SIDRIA-2 Study 
Aims: To report on the relation between home mould and/or dampness exposure and respiratory disorders in a large sample of children and adolescents in Italy, accounting for age at time of exposure.
Methods: 20 016 children (mean age 7 years) and 13 266 adolescents (mean age 13 years) completed questionnaires on indoor exposures and respiratory symptoms/diseases. Statistical analyses were adjusted for sex, age, questionnaire's compiler, area of residence, season of interview, parental educational status, family history of asthma, rhinitis, eczema, chronic obstructive pulmonary disease, presence of gas water heaters, passive smoking, pets, and active smoking (only for adolescents). Population attributable risk % (PAR) was also computed.
Results: Asthma was more strongly related to only early than to only current exposure, both in children (OR 1.80, 95% CI 1.41 to 2.30) and adolescents (OR 1.89, 95% CI 1.38 to 2.59). The same result was found for rhino-conjunctivitis (OR 1.46, 95% CI 1.17 to 1.82), in children, and for wheeze among adolescents (OR 1.56, 95% CI 1.15 to 2.11). In children, wheeze (OR 1.98, 95% CI 1.47 to 2.66) and eczema (OR 1.44, 95% CI 1.09 to 1.91) were more strongly related to mould/dampness when exposed both early and currently; the same occurred in adolescents for rhino-conjunctivitis (1.78, 95% CI 1.30 to 2.45). Although persistent cough/phlegm was significantly related to mould/dampness exposure in children, regardless of exposure timing, no significant association between mould/dampness exposure and eczema or cough/phlegm was found among adolescents. PAR estimates were higher for only early than only current exposures. Avoiding early only exposure would abate wheeze by 6%, asthma or cough/phlegm by 7%, rhino-conjunctivitis in children by 4%, and in adolescents, asthma by 6%, and wheeze by 4%.
Conclusions: Respiratory disorders such as wheeze and asthma can often be explained by exposure to home mould/dampness, especially early in life. The association seems more evident in children than in adolescents. These findings may suggest the need for environmental prevention strategies.
doi:10.1136/oem.2004.018291
PMCID: PMC1741087  PMID: 16109818
24.  Is allergic rhinitis a trivial disease? 
Clinics  2011;66(9):1573-1577.
BACKGROUND:
Asthma and rhinitis often coexist, which potentially increases the disease severity and can negatively impact a patients' quality of life. However, there are few reports based on data obtained from the International Study of Asthma and Allergies in Childhood examining asthma severity in combination with rhinitis-related symptoms.
OBJECTIVE:
To demonstrate whether current rhinitis and current rhinoconjunctivitis are associated with the development of asthma or its increasing severity in Brazilian adolescents.
METHODS:
The prevalence of current asthma was correlated with the prevalence of current rhinitis and current rhinoconjunctivitis in adolescents (13 to 14 year olds) from 16 Brazilian centers (based on Spearman's rank correlation index). The influence of current rhinitis and current rhinoconjunctivitis on asthma presentation was also evaluated using the chi-squared test and was expressed as odds ratios with 95% confidence intervals (95%CI).
RESULTS:
A significant positive correlation was observed between the prevalence of current asthma and current rhinitis (rs = 0.82; 95%CI: 0.60–0.93, p<0.0001) and between the prevalence of current asthma and current rhinoconjunctivitis (rs = 0.75; 95%CI: 0.47–0.89, p<0.0001). Current rhinitis was associated with a significantly increased risk of current asthma and of more severe asthma. Similar results were observed for current rhinoconjunctivitis.
CONCLUSION:
In this epidemiologic study of Brazilian adolescents, the presence of current rhinitis and current rhinoconjunctivitis was associated with a high risk of developing asthma and increased asthma severity. The mutual evaluation of rhinitis and asthma is necessary to establish an adequate treatment plan.
doi:10.1590/S1807-59322011000900012
PMCID: PMC3164407  PMID: 22179162
Epidemiology; Asthma; Rhinitis; Rhinoconjunctivitis; ISAAC
25.  Asthma and allergies in Jamaican children aged 2–17 years: a cross-sectional prevalence survey 
BMJ Open  2012;2(4):e001132.
Objective
To determine the prevalence and severity of asthma and allergies as well as risk factors for asthma among Jamaican children aged 2–17 years.
Design
A cross-sectional, community-based prevalence survey using the International Study of Asthma and Allergies in Childhood questionnaire. The authors selected a representative sample of 2017 children using stratified, multistage cluster sampling design using enumeration districts as primary sampling units.
Setting
Jamaica, a Caribbean island with a total population of approximately 2.6 million, geographically divided into 14 parishes.
Participants
Children aged 2–17 years, who were resident in private households. Institutionalised children such as those in boarding schools and hospitals were excluded from the survey.
Primary and secondary outcome measures
The prevalence and severity of asthma and allergy symptoms, doctor-diagnosed asthma and risk factors for asthma.
Results
Almost a fifth (19.6%) of Jamaican children aged 2–17 years had current wheeze, while 16.7% had self-reported doctor-diagnosed asthma. Both were more common among males than among females. The prevalence of rhinitis, hay fever and eczema among children was 24.5%, 25% and 17.3%, respectively. Current wheeze was more common among children with rhinitis in the last 12 months (44.3% vs 12.6%, p<0.001), hay fever (36.8% vs 13.8%, p<0.001) and eczema (34.1% vs 16.4%, p<0.001). Independent risk factors for current wheeze (ORs, 95% CI) were chest infections in the first year of life 4.83 (3.00 to 7.77), parental asthma 4.19 (2.8 to 6.08), rhinitis in the last 12 months 6.92 (5.16 to 9.29), hay fever 4.82 (3.62 to 6.41), moulds in the home 2.25 (1.16 to 4.45), cat in the home 2.44 (1.66 to 3.58) and dog in the home 1.81 (1.18 to 2.78).
Conclusions
The prevalence of asthma and allergies in Jamaican children is high. Significant risk factors for asthma include chest infections in the first year of life, a history of asthma in the family, allergies, moulds and pets in the home.
Article summary
Article focus
The prevalence of asthma and allergies in both developed and developing countries is continuing to rise.
In some Caribbean countries, asthma is a public health problem associated with high economic costs.
This study determined the prevalence of asthma, allergy symptoms and associated risk factors.
Key messages
We demonstrated that the prevalence of asthma and allergy symptoms among Jamaican children aged 2–17 years is high.
Both the prevalence and severity of asthma symptoms are comparable to that reported among children in high-income countries.
Current wheeze and doctor-diagnosed asthma were more common in males and in children with allergies.
A history of asthma in the family, chest infections in the first year of life, allergies, exposure to moulds and pets in the home were associated with significant risk for asthma.
Identifying children at high risk for asthma and controlling modifiable risk factors is important in reducing the prevalence and morbidity related to asthma.
Strengths and limitations of this study
This is the first national study on asthma and allergies in Jamaica using a nationally representative sample of children with a response rate of 80%.
We used a modified ISAAC protocol in which sampling was done by household rather than by school. Using a population-based sampling strategy; we sampled one child and one adult per household. This approach enabled us to obtain national prevalence estimates for both adults and children in one survey at a reduced cost.
Limitations of this study include the fact that the prevalence of asthma and allergies was based solely on self-reports, no objective measures were done. Also in younger children, caregivers responded to questionnaires.
doi:10.1136/bmjopen-2012-001132
PMCID: PMC3400072  PMID: 22798254

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