Particular characteristics of allergic symptoms in tropical environments: follow up to 24 months in the FRAAT birth cohort study
© Acevedo et al; licensee BioMed Central Ltd. 2012
Received: 6 July 2011
Accepted: 22 March 2012
Published: 22 March 2012
Early wheezing and asthma are relevant health problems in the tropics. Mite sensitization is an important risk factor, but the roles of others, inherent in poverty, are unknown. We designed a birth-cohort study in Cartagena (Colombia) to investigate genetic and environmental risk factors for asthma and atopy, considering as particular features perennial exposure to mites, parasite infections and poor living conditions.
Pregnant women representative of the low-income suburbs of the city were randomly screened for eligibility at delivery; 326 mother-infant pairs were included at baseline and biological samples were collected from birth to 24 months for immunological testing, molecular genetics and gene expression analysis. Pre and post-natal information was collected using questionnaires.
94% of families were from the poorest communes of the city, 40% lacked sewage and 11% tap-water. Intestinal parasites were found as early as 3 months; by the second year, 37.9% of children have had parasites and 5.22% detectable eggs of Ascaris lumbricoides in stools (Median 3458 epg, IQR 975-9256). The prevalence of "wheezing ever" was 17.5% at 6 months, 31.1% at 12 months and 38.3% at 24 months; and recurrent wheezing (3 or more episodes) 7.1% at 12 months and 14.2% at 24 months. Maternal rhinitis [aOR 3.03 (95%CI 1.60-5.74), p = 0.001] and male gender [aOR 2.09 (95%CI 1.09 - 4.01), p = 0.026], increased risk for wheezing at 6 months. At 24 months, maternal asthma was the main predisposing factor for wheezing [aOR 3.65 (95%CI 1.23-10.8), p = 0.01]. Clinical symptoms of milk/egg allergy or other food-induced allergies were scarce (1.8%) and no case of atopic eczema was observed.
Wheezing is the most frequent phenotype during the first 24 months of life and is strongly associated with maternal asthma. At 24 months, the natural history of allergic symptoms is different to the "atopic march" described in some industrialized countries. This cohort is representative of socially deprived urban areas of underdeveloped tropical countries. The collection of biological samples, data on exposure and defined phenotypes, will contribute to understand the gene/environment interactions leading to allergy inception and evolution.
KeywordsBirth cohort study Wheezing Allergy Asthma Rhinitis Eczema Atopic march The tropics Parasite Poverty Cartagena Latin America
There are few Latin American birth-cohort focused on allergic diseases [18–20] and they have explored several phenotypes and risk factors using different study designs. For example, Lopez et al. detected sensitization to D. pteronyssinus in 30% of wheezing and 11% of asymptomatic infants at 12 months of age in a prospective study (n = 102) in Brazil. They also found a weak association between wheezing and specific IgE to mites at 12 months. Environmental exposures and socioeconomic status were not evaluated . Rullo et al. studied the role of respiratory infections, exposure to mouse allergens and breastfeeding on wheezing in 104 children living in a socially deprived community of Brazil. Analysis at 30 months showed strong association of wheezing with "respiratory infections requiring antibiotics". No association was found with endotoxin exposure or mite sensitization . Cooper et al. in a study protocol presented the strategies for investigating the impact of early life exposure to geohelminth infections on the development of vaccine immunity, allergic sensitization and allergic inflammatory diseases in 2,403 neonates followed up to 8 years of age . Our study population is an urban low-income community of admixed genetic background [21, 22], living in the tropics under limited sanitary conditions and exposed to mites and helminth allergens. We hypothesize that, for children growing up under these particular genetic and environmental conditions, the prevalence of some allergic phenotypes, as well as the nature and effects of risk factors are different to those found in cohorts from industrialized countries.
The aims of this study were: 1. To create a community-based birth cohort study for analyzing the effects of allergen exposure, early parasite infections and poor living conditions on the inception of allergic diseases, specially asthma; 2. To evaluate the effects of prenatal and other risk factors on the prevalence of wheezing and eczema and 3. To prospectively collect biological samples of children living in poor neighborhoods of a tropical city for further immunological testing, molecular genetics and molecular microbiology screenings. Here we describe the study protocol, baseline characteristics, demographical observations and risk factors for wheezing up to 24 months, of the "Risk Factors for Asthma and Allergy in the Tropics" (FRAAT) study.
Design, location and study population
The Ethic Committee of the "Fundación Santa Fe de Bogotá", Bogotá-Colombia, approved this study (CCEI-282-206). We created a community based birth cohort for a prospective follow up and collection of epidemiological data and biological samples. Cartagena is a tropical city in the Caribbean North Coast of Colombia (10° 23' 59″ North, 75° 30' 52″ West) with an average annual temperature of 28°C and 80% of relative humidity. Most inhabitants are poor according to governmental indexes that assess type of housing, overcrowding (three or more people per bedroom), access to basic services, income and school attendance. This socioeconomic stratification ranges from 1 to 6 and 90% of the population is grouped in the lowest strata, 1 to 3 . The majority of study participants belonged to the poorest communes and shared environmental conditions. The genetic background of this population resulted from racial admixture between Native Americans, Spaniards, and an important proportion (37.9%) of African ancestry .
Eligibility criteria and enrollment procedures
To ensure adequate representation of the city population, pregnant women attending two public medical centers during parturition (Clínica Maternidad Rafael Calvo and Centro de Atención Permanente La Candelaria) were screened for eligibility by physicians of the research staff between August 2007 and May 2008. These centers serve the majority of the lowest social strata in the city. Mothers were interrogated during admission to the delivery room, examined and followed during labor. Only those fulfilling the following criteria were included: healthy women natives from Cartagena or residents in the city for at least 5 years prior to pregnancy, with singleton pregnancy, without obstetric complications and/or chronic diseases. The exclusion criteria were: high-risk pregnancy, pre-eclampsia, dystocia, autoimmune diseases, tumors, or current use of oral steroids, although asthma was not an exclusion criterion. Informed consent for participating in the study and collecting a cord blood sample was obtained from each mother before delivery. After birth, newborns were examined and those fulfilling the following criteria were included: product of low-risk pregnancy, born by vaginal delivery with a gestational age between 37 and 42 weeks according to Lubchenco method , without labor complications, weight > 2500 grams and APGAR score of at least 7 at five minutes after birth. Children born prematurely, requiring reanimation, pulmonary maturation with steroids, management in intensive care unit after delivery or having congenital deformities were excluded. Three hundred and twenty six mothers agreed to participate with their child and enrolled the study at baseline. After delivery, all families received an explanation about the investigation and signed a written informed consent to participate.
Collection of baseline data and follow-up
A cord blood sample was obtained from the maternal portion immediately after delivery. To avoid contamination with maternal blood, the distal portion of the umbilical cord was closed, the cord was thoroughly cleaned with ethanol and the umbilical vein punctured with disposable syringe. The blood was collected in sterile 15 mL tubes and transported to the laboratory, where serum was separated and frozen for future serological tests. Blood samples from mothers were taken by venipuncture within 12 hours after delivery using the appropriate tubes to obtain sera for antibody determinations and buffy coat as a source of maternal DNA. In children, blood samples were obtained between 6 and 24 months (Figure 3) by venipuncture using disposable syringe. Sera were stored at -20°C for antibody determinations and the clot as a source of DNA. Among the serological test are total IgE and specific IgE to: Dermatophagoides pteronyssinus, Blomia tropicalis, Ascaris spp., purified Ascaris allergens ABA-1 and Asc l 3, cockroach, egg, cat epithelia, mouse, cow's milk and Staphylococcus aureus endotoxin (SEB). Also, other parameters of potential value as risk factors, such as vitamin D, will be evaluated. For RNA collection, 3 mL of cord blood and infant blood were immediately added to PAXgene Blood tubes (PreAnalytix Cat. 762165). RNA was extracted using the PAXgene Blood RNA kit (QIAGEN, Cat. 762134) and kept frozen at -80°C.
Stool samples and parasitological examination
When possible, a meconium sample was collected after delivery in sterile 1.5 mL tubes and kept at -20°C. Mothers were provided with sterile containers and instructed to collect stool samples from their children at different time points between 3 and 24 months. Parasitological analyses were done using 0.85% saline solution and Lugol staining. Ascaris lumbricoides egg counts were done by the Kato Katz method using a commercial kit (Copro Kit, C&M Medical, Brazil) and the results expressed as egg per gram of feces (epg). The presence of eggs from geohelminths or parasite visualization were considered diagnostics of active infection. In order to analyze the gut microbiota using molecular tools, DNA was extracted from meconium and stool samples (QIAamp DNA stool Mini kit, QIAGEN, Cat. 515004) following the manufacturer instructions and stored at -80°C.
Collection of dust samples
For measuring allergen and endotoxin levels, house-dust samples were collected from children homes at 6 months, using a vacuum cleaner (Cyking V-CA241HT, LG Electronics, Korea) adapted to 25 μM cellulose filters. Children mattress and bedroom floor were aspirated two minutes over 1 m2 area as described . Dust samples were placed in sterile recipients, weighted and extracted in 2 mL of pyrogen-free water-0.05% Tween 20 per 100 grams of fine dust, mixed during 1 hour at room temperature and centrifuged (3000 g, 4°C, 10 minutes). An aliquot of supernatant (1/10 of the total volume) was kept at -20°C for endotoxin quantification. The substracted volume was replaced with PBS 10 × -0.05% Tween 20 10 mM PMSF and mixed overnight for protein extraction. After centrifugation aliquots for allergen quantification were obtained and kept at -20°C.
Assessment and validation of clinical outcomes
Wheezing was defined as expiratory stridor with shortness of breath or whistling on children chest. Mothers were interrogated on the question "Have your child ever had wheezing or whistling in the chest at any time in the past?" For each affirmative response additional validation questions were done to obtain further information about the episode, medications and medical management. Only cases with documented medical diagnosis during visits to health centers and/or wheeze detected during physical examination by the research staff, were considered as wheezing episodes. Based on the number of wheezing between 0 and 24 months, children were classified as: Never wheezers (no wheezing at any time point), occasional wheezers (1-2 episodes) or recurrent wheezers (3 or more episodes in 12 months). Eczema was diagnosed when all the following criteria were present: (1) evidence of itchy skin/pruritus, (2) visible flexural dermatitis, (3) typical morphology and distribution including facial, neck and extensor involvement and (4) dry skin, based on Williams [27–29] after Hanifin . We have used these modified criteria considering that in this community other causes of "itchy skin" are common (scabies, insect stings, helminth induced rashes etc); for the same reason the diagnosis always included medical examination. All children whose mothers referred having itching for more than 2 weeks were re-examined every 3 months during 12 months.
The diagnosis of asthma and other allergic diseases among mothers was done using a questionnaire,  and physical examination by a physician from the research staff. Atopy was defined as a positive immediate response to one or more allergens in the skin prick tests, performed between 6 and 12 months, during children follow up. The test was considered positive if the mean diameter of the wheal at 15 minutes was > 3 mm than the negative control. Mothers were tested with a set of aeroallergens, including mites (D. pteronyssinus, B. tropicalis, Aleuroglyphus ovatus, Chortoglyphus arcuatus, Lepidoglyphus destructor, Suidasia medanensis), cockroach (Periplaneta Americana), pollen/grass (Betula alba, Phleum pretense, Artemisia), pets (dog and cat), and molds (Alternaria alternata, Penicillium crysogenum, Aspergillus fumigatus), kindly supplied by Leti, Spain. Histamine phosphate [10 mg/mL] was used as positive control and glycerol as negative control. Children will be skin tested after the second year of age.
Information from interviews was recorded on paper forms, reviewed for accuracy and completeness, and then entered into the database. Statistical analyses were done using SPSS v.13.0 (Chicago, IL, USA). Frequencies and descriptive statistics were calculated at baseline, 6, 12 and 24 months. Chi-square was used to analyze the differences between proportions. For contingency tables with less than 10 cases in any cell, the Fisher's exact test was used. To analyze which parental and/or prenatal factors were related to the development of wheezing, multivariate analyses were performed with children having complete exposures data at 6, 12 and 24 months. Crude odds ratios (OR) and 95% confidence interval were calculated. For risk factors having a significance level p ≤ 0.05, adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were obtained using binary logistic and multinomial logistic regression. Covariates were introduced in the final model if their inclusion changed the estimate of the crude OR by more than 10%. The outcome (dependent) variables were wheezing ever and recurrent wheezing at 6, 12 and 24 months. Variables were analyzed as categorical (e.g. maternal asthma, yes/no) or continuous (e.g. maternal age, number of siblings, birth weight).
We aimed to have at least 100 wheezers with prospective sampling for immunological and molecular screenings up to 24 months. Based on the national prevalence rates [9, 14], we estimated that a minimum sample of 400 children will give us the possibility to recruit that number of cases. For association studies, power was calculated assuming an independent case-control design and expressing the alternative hypothesis as Odds Ratio (ψ). For a given risk factor the calculation is done by setting type I error probability at α = 0.05, number of wheezing cases (n), probability of exposure among non-wheezers (ρ0), and the ratio of controls/cases (m) .
Demographic characteristics of the population
Demographic characteristics of mothers and prevalence of prenatal exposures
24 months (n = 274)
(n = 326)
(n = 169)
(n = 105)
Maternal age at child birth [n (%)]
Maternal age (Mean ± SD)
23.2 ± 5.83
23.6 ± 6.15
22.5 ± 5.37
Primary school only
High school incomplete
High school complete
No. of other children (Mean ± SD)
1.17 ± 1.35
1.14 ± 1.32
1.19 ± 1.31
Type of house
Type of house floor
Exposure to pests at home*
Rodents (mice, rats)
Smoking and contaminants during pregnancy
Maternal smoking (ever)
Maternal smoking during pregnancy
Intradomiciliary passive exposure
Type of domestic cooking fuel
Trash burning at home during pregnancy
Passive exposure to trash fume at neighborhood
Exposure to pets and to other domestic animals
Living with pet during pregnancy
Dog during pregnancy
Cat during pregnancy
Living with dog/cat during the whole pregnancy
Intradomiciliary contact poultry/pigs during pregnancy
Antibiotics during pregnancy
Maternal antecedents of allergic diseases (n = 326)
Duration of asthma (Mean, SD)
14.0 ± 9.01 years
Family history of asthma*
Allergic sensitization (n = 265)**
Any allergy symptom (%)***
Atopy (at least 1 positive test)
Molds (Pen, Asp, Alt)
Pollens (Art, Phl, Bet, Acacia)
Living conditions of children and particular environmental exposures
Prevalence of parasitic infection as determined by stool examination
(n = 200)
(n = 258)
(n = 153)
Prevalence of wheezing and atopic eczema
Frequency of wheezing among children from 0 to 24 months
(n = 286)
(n = 280)
(n = 274)
(n = 280)
(n = 274)
Prevalence of wheeze (%)
Occasional wheezers (1 or 2 episodes)
Recurrent wheezers (3 or more episodes)
Children that only wheeze at time interval (n)
Number of children that wheeze for the first time at each time interval
Risk factors for wheezing during the first two years
Unadjusted associations between maternal factors and prenatal exposures on the risk of wheezing
7 - 12 months
0 - 24 months
(n = 50/236)
(n = 59/221)
(n = 105/169)
(n = 39/235)
Type of house
Type of floor
Prenatal exposure to cigarette smoke
Exposure to fume wood/coal
Exposure to fume trash burning:
Pets during pregnancy
Intradomicilliary (9 mo)
Dog at home
Cat at home
Poultry/pigs at home
Rodents at home
Cockroaches at home
There was no association between natural or propane gas and wheezing. In addition, no association was found between wheezing and conditions considered protective, such as poverty and coexistence with pets and poultries. Furthermore, we found no association with well known risk factors, such as cigarette smoking or passive exposure during pregnancy.
Bronchiolitis during the first 6 months was an important risk factor for wheezing at 6 months (aOR 18.3 (95%CI 7.6-44.0), p < 0.0001) and 24 months (aOR 20.6 (95%CI 6.08-70.1), p < 0.0001). Also for recurrent wheezing at 24 months (aOR 6.8 (95%CI 3.0-15.5), p < 0.0001), after adjustment for maternal asthma, maternal age, number of siblings and children gender.
Birth cohort studies in different environments and populations are useful to understand the natural history of allergic diseases. Nowadays there are a number of such studies, most of them multicentric, with some common objectives and including a wide range of participants [33–36]. The results, mainly from Europe and US, have shown the importance of particular and common risk factors and their differential influences on allergic diseases, supporting the relevance of doing this type of investigations worldwide, to evaluate the great diversity of settings associated, not only with the climate, geographical location and genetic background, but also with low socio-economic conditions that generate particular risk factors and limit the access to health services. The prevalence of allergic diseases varies among regions and in Latin America, figures of asthma and other allergies in children are very high [37–42]. However, as mentioned, prospective birth cohorts in the region are still scarce, although a growing number are being reported [18–20].
A remarkable finding in our study is the high prevalence of wheezing ever and recurrent wheezing, higher than reported in some European cohorts [43–46], similar to data from the USA [47, 48] and lower than those found in some Latin American surveys [19, 41]. Considering that 12% of children of this cohort attended a hospital with bronchiolitis, one explanation of our findings is the effect of viral diseases, as has been shown in other studies from Latin America . In fact, bronchiolitis was a high risk factor for wheezing in our cohort, with odds ratio similar to that found when laboratory diagnosis of viral infection was done . Lower respiratory tract infections by Respiratory Syncytial Virus (RSV) are common in tropical developing countries causing 27 to 96% of all acute wheezing hospitalizations in children under 6 month of age . In our children an important proportion of wheezing during this period might be caused by viruses and this related to the finding that only half of children wheezing before 6 months continued wheezing until 24 months. However, the existence of a group with recurrent wheezing (14.2%) suggests that other factors, including atopy, may be influencing this phenotype . RSV infections can induce a change of the Th1/Th2 balance, expressed by an increase of the IL-4/IFN-gamma ratio and a persistent IgE response over the years [51, 52], and human rhinovirus-induced bronchiolitis carries a markedly risk of persistent wheezing and childhood asthma . Besides, in the tropics, co-exposure to perennial high concentrations of mite allergens and helminth infections may induce an early allergic response with respiratory effects . Also, living in socially deprived urban areas of underdeveloped countries lead to an early exposure to high levels of endotoxin, in turn associated with increased risk of wheezing during the first year of life [55, 56]. Allergy diagnosis by in vitro assays and skin prick tests will help to improve phenotype definition in our cohort and obtain data about risk factors for atopy associated-wheezing .
In this study, maternal asthma was consistently associated with wheezing and recurrent wheezing in the offspring, a finding already observed in different populations and considered an important risk factor for asthma in children before 5 years [58–61]. The mechanisms of this "maternal effect" and why it is more evident during early childhood are unknown. It has been reported that maternal asthma, as well as the child HLA-G genotype contribute to the presence of bronchial hyperreactivity ; in addition, several factors may act in combination with maternal cytokines, antibodies and other mediators that act in utero or during the perinatal period [63, 64]. Furthermore, recent works in animals suggest that epigenetic mechanisms may play a role [65, 66], although the transmission of the maternal susceptibility via epigenetic changes or parental imprinting remains to be demonstrated. Remarkably, this association was detected at 12, from 13 to 24 and 0 to 24 months, suggesting that the maternal effect is on children that start wheezing after 6 months. Moreover, it was also evident with recurrent wheezing, a more severe phenotype and always held up after adjustments for covariates. These results are in agreement with a study in Brazil, were parental asthma was associated with atopic and non-atopic wheezing  but in contrast with other where maternal atopy was a risk factor for wheezing in poor-environments  because we found no association between maternal sensitization alone and wheezing.
Additionally, and in concordance with other surveys [69–71], we found that male gender was associated with wheezing in cases between 0 and 6 months, but the effect disappeared with increasing age. As it has also been reported, the prevalence and severity of asthma are higher in boys than in girls in the first 10 years of life, but this pattern is reversed after puberty . Although the reasons of this observation remain unknown, there are interesting analysis and hypothesis [73, 74].
Contrary to expected, our data show no association of wheezing with active or passive maternal smoking, and the low prevalence of self-reported maternal smoking during pregnancy precluded further association analysis. Therefore, we investigated association between passive intra-domiciliary exposure and wheezing at 6, 12 and 24 months but the results were the same. The prevalence of wheezers was always higher in the group of children with prenatal passive exposure: 6 months (41.1% vs. 50.0%), 12 months (40.4% vs. 47.1%), and 24 months (40.0% vs. 45.2%) but this was not statistically significant. In addition to the type of housing and cultural patterns, another explanation for these results may be a Type II error because the sample is underpowered to detect the effects of smoking. Increasing the sample size and using biological markers of tobacco exposure could help to obtain a more accurate analysis.
The mechanisms of atopic dermatitis are not clear but hereditary factors and environmental exposures are supposed to play important roles [75, 76]. A main finding of this study is that in a socially deprived population of the tropics, the natural history of atopic conditions seems to be different to expected according to the "atopic march", where eczema appears before the first two years followed by allergic respiratory symptoms [77, 78]. In fact, we found no cases of atopic eczema during the first two years of age, while wheezing was a frequent phenotype. Although we do not know yet if atopy is playing a role in the origin of wheezing in these children, it is clear that early respiratory symptoms predominate over cutaneous, atopy-associated, symptoms. In addition, asthma and allergic rhinitis were the most common allergic manifestations in mothers but there was no eczema among them. In a previous study we found a low frequency of atopic dermatitis in the general population of Colombia . In developed countries, the prevalence of this disease is around 10 to 20% in children under 5 years [79, 80], but the ISAAC Phase III study in Latin America reports that, with some exceptions, the prevalence is less than 5% . Under these rates we expected around 15 cases of eczema in our cohort.
Increasing evidence suggest that the "atopic march" includes only a subgroup of patients [82–84]. However, the reasons we found no cases of atopic eczema should be further analyzed. We hypothesized that the genetic background, with an important component of African ancestry and a different distribution of susceptibility alleles for eczema could be protective. Also, particular exposures of these children, with early infections as a hallmark, may confer protection, as has been suggested [56, 85]. The diagnostic criteria we used  are very important when aiming to study this disease in the tropics because infections and other medical conditions producing "itchy skin" are very frequent. Although cases of eczema may appear in our cohort after 2 years, it has been suggested that a great number begin within the first 12 months, disappearing around 3 years in a significant proportion of children . Therefore, monitoring symptoms of this disorder, as well as other allergic diseases in this cohort is mandatory.
There are reports of associations between low income and asthma . We found no relationship of allergy symptoms with socioeconomic strata, possibly because the study population is homogeneously poor and differences between strata are small. Potential risk factors related to poverty, such as housing conditions, access to tap water and sewage system, exposure to fume from firewood and trash burning, intradomiciliary contact with poultry and pigs and large family size were not associated with wheezing. For most of them the prevalence of exposure among non-affected was high enough to detect an effect. Since the study population is not representative of all the social strata of the city the generalization of these results is limited. Further research is needed to evaluate the potential interactions that lead to allergy phenotypes in socially deprived environments.
Since our study was based in a prospective cohort design that included physician assessment of a broad range of factors, we think that accurate information was obtained. This strategy may reduce the number of participants and requires more resources but it is necessary to increase accuracy avoiding the bias from poorly defined phenotypes, as may occur when the information is obtained only from self-administered questionnaires, especially in populations with low education level. This is especially important for atopic eczema and wheezing because they may not be easily evaluated by parents. Two sources of ascertainment bias should be mentioned: one from the type of housing and living conditions that make it difficult to identify some exposures (e.g. pet ownership, smoke exposure) and other from the detection of phenotypes. The diagnosis of wheezing was made only when patients were evaluated by a physician or had documented history of medications and hospital admissions, as has been recommended  and this might bias our attention to the most severe cases, lowering the sensitivity of the survey. However, considering that the biologic samples are intended for serologic and molecular screenings we chose for well-defined phenotypes to reduce heterogeneity. Among the limitations of this study, one is the small number of children recruited, if compared to multicenter surveys. Although, according to the formerly reported prevalence of wheezing in this population our analyses have good power to detect some associations, increasing the number of participants could provide better information. However, many obstacles must be overcome to organize a prospective cohort in countries with high degree of poverty. Low education precludes the use of self-reported questionnaires, limiting the number of enrolled families. Another problem affecting the response rate and the follow-up is the lack of well urbanized neighborhoods, which greatly increase the difficulty of the visits.
As in other birth-cohorts, a valuable selection of biological material has been done in this study . Laboratory tests will help to assess genetic and environmental factors linked to asthma development, providing novel information about disease mechanisms in the tropics. An open question when studying allergies in this zone is the influence of A. lumbricoides infection on the process of IgE sensitization to common allergens, especially house dust mites . Thus, IgE serology to Ascaris spp. and allergen extracts will be serially performed to explore primary sensitizers and how the infection status influences the frequency and strength of specific IgE response. Another aspect to be evaluated is the relationship between the immunological profile at birth and further wheezing in children. Immune- responsiveness gene expression will be monitored at different time-points. As differences in microbiota composition may influence immune response [90–92], stool samples has been collected from birth to 24 months, to identify gut microbiota composition and explore their potential relationship with the IgE responses and allergies.
Here we describe the demographic characteristics of the FRAAT birth cohort study, representative of socially deprived urban areas of underdeveloped tropical countries. At 24 months, the history of allergic symptoms is different to the "atopic march" described in some populations of industrialized countries. Although the rates of wheezing were higher than those reported in these countries, cases of eczema were not found. Wheezing is the most frequent phenotype during the first 24 months of life and is strongly associated with maternal asthma. The availability of cord blood serum and other biological samples, will allow to further study risk factors for asthma and atopy during early childhood, including the effects of particular factors related to poverty, such as early microbial and parasite exposure.
We thank all families that voluntarily participated in this study and the staff of the E.S.E. Cartagena de Indias and Clínica Maternidad Rafael Calvo, by their administrative support. We are also very grateful to Leti, Spain that kindly provided the allergens for skin testing. This study was funded by the Colombian Government (Departamento Administrativo de Ciencia y Tecnología e Innovación, Colciencias), Grant 325-2006 and Fundemeb. NA and JS received a grant from Colciencias (Young Research Program, Call 2007). NA, JS, DM, and AB received financial support from Fundemeb.
- von Mutius E: Gene-environment interactions in asthma. J Allergy Clin Immunol. 2009, 123 (1): 3-11. 10.1016/j.jaci.2008.10.046. quiz 12-13View ArticlePubMedGoogle Scholar
- Pearce N, Ait-Khaled N, Beasley R, Mallol J, Keil U, Mitchell E, Robertson C: Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax. 2007, 62 (9): 758-766. 10.1136/thx.2006.070169.View ArticlePubMedPubMed CentralGoogle Scholar
- Mallol J, Sole D, Asher I, Clayton T, Stein R, Soto-Quiroz M: Prevalence of asthma symptoms in Latin America: the International Study of Asthma and Allergies in Childhood (ISAAC). Pediatr Pulmonol. 2000, 30 (6): 439-444. 10.1002/1099-0496(200012)30:6<439::AID-PPUL1>3.0.CO;2-E.View ArticlePubMedGoogle Scholar
- Pitrez PM, Stein RT: Asthma in Latin America: the dawn of a new epidemic. Curr Opin Allergy Clin Immunol. 2008, 8 (5): 378-383. 10.1097/ACI.0b013e32830fb911.View ArticlePubMedGoogle Scholar
- Sole D, Melo KC, Camelo-Nunes IC, Freitas LS, Britto M, Rosario NA, Jones M, Fischer GB, Naspitz CK: Changes in the prevalence of asthma and allergic diseases among Brazilian schoolchildren (13-14 years old): comparison between ISAAC Phases One and Three. J Trop Pediatr. 2007, 53 (1): 13-21.View ArticlePubMedGoogle Scholar
- Mallol J: Asthma in Latin America: where the asthma causative/protective hypotheses fail. Allergol Immunopathol (Madr). 2008, 36 (3): 150-153.View ArticleGoogle Scholar
- Cooper PJ, Rodrigues LC, Cruz AA, Barreto ML: Asthma in Latin America: a public heath challenge and research opportunity. Allergy. 2009, 64 (1): 5-17. 10.1111/j.1398-9995.2008.01902.x.View ArticlePubMedGoogle Scholar
- Weiss ST: Asthma in early life: is the hygiene hypothesis correct?. J Pediatr (Rio J). 2008, 84 (6): 475-476. 10.1590/S0021-75572008000700002.View ArticleGoogle Scholar
- Dennis R, Caraballo L, Garcia E, Caballero A, Aristizabal G, Cordoba H, Rodriguez MN, Rojas MX, Orduz C, Cardona R, et al: Asthma and other allergic conditions in Colombia: a study in 6 cities. Ann Allergy Asthma Immunol. 2004, 93 (6): 568-574. 10.1016/S1081-1206(10)61265-3.View ArticlePubMedGoogle Scholar
- Rodriguez Martinez C, Sossa M, Goss CH: Factors associated with severe disease in a population of asthmatic children of Bogota, Colombia. J Asthma. 2008, 45 (2): 141-147. 10.1080/02770900701840253.View ArticlePubMedGoogle Scholar
- Caraballo L, Puerta L, Fernandez-Caldas E, Lockey RF, Martinez B: Sensitization to mite allergens and acute asthma in a tropical environment. J Investig Allergol Clin Immunol. 1998, 8 (5): 281-284.PubMedGoogle Scholar
- Puerta L, Fernandez-Caldas E, Lockey RF, Caraballo LR: Mite allergy in the tropics: sensitization to six domestic mite species in Cartagena, Colombia. J Investig Allergol Clin Immunol. 1993, 3 (4): 198-204.PubMedGoogle Scholar
- Garcia E, Aristizabal G, Vasquez C, Rodriguez-Martinez CE, Sarmiento OL, Satizabal CL: Prevalence of and factors associated with current asthma symptoms in school children aged 6-7 and 13-14 yr old in Bogota, Colombia. Pediatr Allergy Immunol. 2008, 19 (4): 307-314. 10.1111/j.1399-3038.2007.00650.x.View ArticlePubMedGoogle Scholar
- Caraballo L, Cadavid A, Mendoza J: Prevalence of asthma in a tropical city of Colombia. Ann Allergy. 1992, 68 (6): 525-529.PubMedGoogle Scholar
- Fernandez-Caldas E, Puerta L, Caraballo L, Mercado D, Lockey RF: Sequential determinations of Dermatophagoides spp. allergens in a tropical city. J Investig Allergol Clin Immunol. 1996, 6 (2): 98-102.PubMedGoogle Scholar
- Fernandez-Caldas E, Puerta L, Mercado D, Lockey RF, Caraballo LR: Mite fauna, Der p I, Der f I and Blomia tropicalis allergen levels in a tropical environment. Clin Exp Allergy. 1993, 23 (4): 292-297. 10.1111/j.1365-2222.1993.tb00325.x.View ArticlePubMedGoogle Scholar
- Puerta L, Fernandez-Caldas E, Mercado D, Lockey RF, Caraballo LR: Sequential determinations of Blomia tropicalis allergens in mattress and floor dust samples in a tropical city. J Allergy Clin Immunol. 1996, 97 (2): 689-691. 10.1016/S0091-6749(96)70315-9.View ArticlePubMedGoogle Scholar
- Lopez N, de Barros-Mazon S, Vilela MM, Condino Neto A, Ribeiro JD: Are immunoglobulin E levels associated with early wheezing? A prospective study in Brazilian infants. Eur Respir J. 2002, 20 (3): 640-645. 10.1183/09031936.02.00219302.View ArticlePubMedGoogle Scholar
- Rullo VE, Arruda LK, Cardoso MR, Valente V, Zampolo AS, Nobrega F, Naspitz CK, Sole D: Respiratory infection, exposure to mouse allergen and breastfeeding: role in recurrent wheezing in early life. Int Arch Allergy Immunol. 2009, 150 (2): 172-178. 10.1159/000218120.View ArticlePubMedGoogle Scholar
- Cooper PJ, Chico ME, Guadalupe I, Sandoval CA, Mitre E, Platts-Mills TA, Barreto ML, Rodrigues LC, Strachan DP, Griffin GE: Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study. BMC Infect Dis. 2011, 11 (1): 184-10.1186/1471-2334-11-184.View ArticlePubMedPubMed CentralGoogle Scholar
- Acevedo N, Mercado D, Vergara C, Sanchez J, Kennedy MW, Jimenez S, Fernandez AM, Gutierrez M, Puerta L, Caraballo L: Association between total immunoglobulin E and antibody responses to naturally acquired Ascaris lumbricoides infection and polymorphisms of immune system-related LIG4, TNFSF13B and IRS2 genes. Clin Exp Immunol. 2009, 157 (2): 282-290. 10.1111/j.1365-2249.2009.03948.x.View ArticlePubMedPubMed CentralGoogle Scholar
- Vergara C, Caraballo L, Mercado D, Jimenez S, Rojas W, Rafaels N, Hand T, Campbell M, Tsai YJ, Gao L, et al: African ancestry is associated with risk of asthma and high total serum IgE in a population from the Caribbean Coast of Colombia. Hum Genet. 2009, 125 (5-6): 565-579. 10.1007/s00439-009-0649-2.View ArticlePubMedGoogle Scholar
- EA Rueda: Will Today's Poor be Tomorrow's Poor? Determinants of the Poverty and Magnitude of the Vulnerability in Cartagena De Indias, Colombia. 2009, Available at SSRN, [http://ssrncom/abstract=1411775]Google Scholar
- Lubchenco LO, Hansman C, Dressler M, Boyd E: Intrauterine growth as estimated from liveborn birth-weight data at 24 to 42 weeks of gestation. Pediatrics. 1963, 32: 793-800.PubMedGoogle Scholar
- Mata Fernandez C, Fernandez-Benitez M, Perez Miranda M, Guillen Grima F: Validation of the Spanish version of the Phase III ISAAC questionnaire on asthma. J Investig Allergol Clin Immunol. 2005, 15 (3): 201-210.PubMedGoogle Scholar
- Heinrich J, Holscher B, Douwes J, Richter K, Koch A, Bischof W, Fahlbusch B, Kinne RW, Wichmann HE: Reproducibility of allergen, endotoxin and fungi measurements in the indoor environment. J Expo Anal Environ Epidemiol. 2003, 13 (2): 152-160. 10.1038/sj.jea.7500267.View ArticlePubMedGoogle Scholar
- Williams HC, Burney PG, Pembroke AC, Hay RJ: Validation of the U.K. diagnostic criteria for atopic dermatitis in a population setting. U.K. Diagnostic Criteria for Atopic Dermatitis Working Party. Br J Dermatol. 1996, 135 (1): 12-17. 10.1111/j.1365-2133.1996.tb03599.x.View ArticlePubMedGoogle Scholar
- Johnke H, Vach W, Norberg LA, Bindslev-Jensen C, Host A, Andersen KE: A comparison between criteria for diagnosing atopic eczema in infants. Br J Dermatol. 2005, 153 (2): 352-358. 10.1111/j.1365-2133.2005.06491.x.View ArticlePubMedGoogle Scholar
- Williams HC: Clinical practice. Atopic dermatitis. N Engl J Med. 2005, 352 (22): 2314-2324. 10.1056/NEJMcp042803.View ArticlePubMedGoogle Scholar
- Hanifin JRG: Diagnostic features of atopic dermatitis. Acta Derm Venereol (Stockh). 1980, 44-47. suppl 92Google Scholar
- Dupont WD, Plummer WD: Power and sample size calculations for studies involving linear regression. Control Clin Trials. 1998, 19 (6): 589-601. 10.1016/S0197-2456(98)00037-3.View ArticlePubMedGoogle Scholar
- WHO: Monitoring helminth control programmes: guidelines for monitoring the impact of control programs aimed at reducing morbidity. WHO/CDS/CPC/SIP/993. 1999Google Scholar
- Keil T, Kulig M, Simpson A, Custovic A, Wickman M, Kull I, Lodrup Carlsen KC, Carlsen KH, Smit HA, Wijga AH, et al: European birth cohort studies on asthma and atopic diseases: II. Comparison of outcomes and exposures--a GA2LEN initiative. Allergy. 2006, 61 (9): 1104-1111. 10.1111/j.1398-9995.2006.01167.x.View ArticlePubMedGoogle Scholar
- Peters JL, Suglia SF, Platts-Mills TA, Hosen J, Gold DR, Wright RJ: Relationships among prenatal aeroallergen exposure and maternal and cord blood IgE: project ACCESS. J Allergy Clin Immunol. 2009, 123 (5): 1041-1046. 10.1016/j.jaci.2009.02.027.View ArticlePubMedPubMed CentralGoogle Scholar
- Gern JE, Visness CM, Gergen PJ, Wood RA, Bloomberg GR, O'Connor GT, Kattan M, Sampson HA, Witter FR, Sandel MT, et al: The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population. BMC Pulm Med. 2009, 9: 17-10.1186/1471-2466-9-17.View ArticlePubMedPubMed CentralGoogle Scholar
- Bisgaard H: The Copenhagen Prospective Study on Asthma in Childhood (COPSAC): design, rationale, and baseline data from a longitudinal birth cohort study. Ann Allergy Asthma Immunol. 2004, 93 (4): 381-389. 10.1016/S1081-1206(10)61398-1.View ArticlePubMedGoogle Scholar
- Rosa AM, Ignotti E, Hacon Sde S, Castro HA: Prevalence of asthma in children and adolescents in a city in the Brazilian Amazon region. J Bras Pneumol. 2009, 35 (1): 7-13.View ArticlePubMedGoogle Scholar
- Chatkin MN, Menezes AM, Victora CG, Barros FC: High prevalence of asthma in preschool children in Southern Brazil: a population-based study. Pediatr Pulmonol. 2003, 35 (4): 296-301. 10.1002/ppul.10229.View ArticlePubMedGoogle Scholar
- Penny ME, Murad S, Madrid SS, Herrera TS, Pineiro A, Caceres DE, Lanata CF: Respiratory symptoms, asthma, exercise test spirometry, and atopy in schoolchildren from a Lima shanty town. Thorax. 2001, 56 (8): 607-612. 10.1136/thorax.56.8.607.View ArticlePubMedPubMed CentralGoogle Scholar
- de Farias MR, Rosa AM, Hacon Sde S, de Castro HA, Ignotti E: Prevalence of asthma in schoolchildren in Alta Floresta- a municipality in the southeast of the Brazilian Amazon. Rev Bras Epidemiol. 2010, 13 (1): 49-57. 10.1590/S1415-790X2010000100005.View ArticlePubMedGoogle Scholar
- Mallol J, Garcia-Marcos L, Sole D, Brand P: International prevalence of recurrent wheezing during the first year of life: variability, treatment patterns and use of health resources. Thorax. 2010, 65 (11): 1004-1009. 10.1136/thx.2009.115188.View ArticlePubMedGoogle Scholar
- Ait-Khaled N, Pearce N, Anderson HR, Ellwood P, Montefort S, Shah J: Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three. Allergy. 2009, 64 (1): 123-148. 10.1111/j.1398-9995.2008.01884.x.View ArticlePubMedGoogle Scholar
- Host A, Halken S, Jacobsen HP, Christensen AE, Herskind AM, Plesner K: Clinical course of cow's milk protein allergy/intolerance and atopic diseases in childhood. Pediatr Allergy Immunol. 2002, 13 (Suppl 15): 23-28.View ArticlePubMedGoogle Scholar
- Halmerbauer G, Gartner C, Schier M, Arshad H, Dean T, Koller DY, Karmaus W, Kuehr J, Forster J, Urbanek R, et al: Study on the prevention of allergy in Children in Europe (SPACE): allergic sensitization in children at 1 year of age in a controlled trial of allergen avoidance from birth. Pediatr Allergy Immunol. 2002, 13 (Suppl 15): 47-54.View ArticlePubMedGoogle Scholar
- Hallberg J, Anderson M, Wickman M, Svartengren M: Factors in infancy and childhood related to reduced lung function in asthmatic children: a birth cohort study (BAMSE). Pediatr Pulmonol. 2010, 45 (4): 341-348.PubMedGoogle Scholar
- Caudri D, Wijga AH, Smit HA, Koppelman GH, Kerkhof M, Hoekstra MO, Brunekreef B, de Jongste JC: Asthma symptoms and medication in the PIAMA birth cohort: Evidence for under and overtreatment. Pediatr Allergy Immunol. 2011, 22 (7): 652-659. 10.1111/j.1399-3038.2011.01193.x.View ArticlePubMedGoogle Scholar
- Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez FD: A clinical index to define risk of asthma in young children with recurrent wheezing. Am J Respir Crit Care Med. 2000, 162 (4 Pt 1): 1403-1406.View ArticlePubMedGoogle Scholar
- Wood RA, Bloomberg GR, Kattan M, Conroy K, Sandel MT, Dresen A, Gergen PJ, Gold DR, Schwarz JC, Visness CM, et al: Relationships among environmental exposures, cord blood cytokine responses, allergy, and wheeze at 1 year of age in an inner-city birth cohort (Urban Environment and Childhood Asthma study). J Allergy Clin Immunol. 2011, 127 (4): 913-919. 10.1016/j.jaci.2010.12.1122. e911-916View ArticlePubMedPubMed CentralGoogle Scholar
- Camara AA, Silva JM, Ferriani VP, Tobias KR, Macedo IS, Padovani MA, Harsi CM, Cardoso MR, Chapman MD, Arruda E, et al: Risk factors for wheezing in a subtropical environment: role of respiratory viruses and allergen sensitization. J Allergy Clin Immunol. 2004, 113 (3): 551-557. 10.1016/j.jaci.2003.11.027.View ArticlePubMedGoogle Scholar
- Weber MW, Mulholland EK, Greenwood BM: Respiratory syncytial virus infection in tropical and developing countries. Trop Med Int Health. 1998, 3 (4): 268-280. 10.1046/j.1365-3156.1998.00213.x.View ArticlePubMedGoogle Scholar
- Roman M, Calhoun WJ, Hinton KL, Avendano LF, Simon V, Escobar AM, Gaggero A, Diaz PV: Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response. Am J Respir Crit Care Med. 1997, 156 (1): 190-195.View ArticlePubMedGoogle Scholar
- Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B: Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med. 2000, 161 (5): 1501-1507.View ArticlePubMedGoogle Scholar
- Jartti T, Korppi M: Rhinovirus-induced bronchiolitis and asthma development. Pediatr Allergy Immunol. 2011, 22 (4): 350-355. 10.1111/j.1399-3038.2011.01170.x.View ArticlePubMedGoogle Scholar
- Acevedo N, Caraballo L: IgE cross-reactivity between Ascaris lumbricoides and mite allergens: possible influences on allergic sensitization and asthma. Parasite Immunol. 2011, 33 (6): 309-321. 10.1111/j.1365-3024.2011.01288.x.View ArticlePubMedGoogle Scholar
- Park JH, Gold DR, Spiegelman DL, Burge HA, Milton DK: House dust endotoxin and wheeze in the first year of life. Am J Respir Crit Care Med. 2001, 163 (2): 322-328.View ArticlePubMedGoogle Scholar
- Gehring U, Bolte G, Borte M, Bischof W, Fahlbusch B, Wichmann HE, Heinrich J: Exposure to endotoxin decreases the risk of atopic eczema in infancy: a cohort study. J Allergy Clin Immunol. 2001, 108 (5): 847-854. 10.1067/mai.2001.119026.View ArticlePubMedGoogle Scholar
- Spycher BD, Silverman M, Kuehni CE: Phenotypes of childhood asthma: are they real?. Clin Exp Allergy. 2010, 40 (8): 1130-1141. 10.1111/j.1365-2222.2010.03541.x.View ArticlePubMedGoogle Scholar
- Abdulrazzaq YM, Bener A, DeBuse P: Association of allergic symptoms in children with those in their parents. Allergy. 1994, 49 (9): 737-743. 10.1111/j.1398-9995.1994.tb02096.x.View ArticlePubMedGoogle Scholar
- Litonjua AA, Carey VJ, Burge HA, Weiss ST, Gold DR: Parental history and the risk for childhood asthma. Does mother confer more risk than father?. Am J Respir Crit Care Med. 1998, 158 (1): 176-181.View ArticlePubMedGoogle Scholar
- Lim RH, Kobzik L, Dahl M: Risk for asthma in offspring of asthmatic mothers versus fathers: a meta-analysis. PLoS One. 2010, 5 (4): e10134-10.1371/journal.pone.0010134.View ArticlePubMedPubMed CentralGoogle Scholar
- Nicolaou NC, Simpson A, Lowe LA, Murray CS, Woodcock A, Custovic A: Day-care attendance, position in sibship, and early childhood wheezing: a population-based birth cohort study. J Allergy Clin Immunol. 2008, e505 (3): 500-506. e505View ArticleGoogle Scholar
- Nicolae D, Cox NJ, Lester LA, Schneider D, Tan Z, Billstrand C, Kuldanek S, Donfack J, Kogut P, Patel NM, et al: Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21. Am J Hum Genet. 2005, 76 (2): 349-357. 10.1086/427763.View ArticlePubMedGoogle Scholar
- Hamada K, Suzaki Y, Goldman A, Ning YY, Goldsmith C, Palecanda A, Coull B, Hubeau C, Kobzik L: Allergen-independent maternal transmission of asthma susceptibility. J Immunol. 2003, 170 (4): 1683-1689.View ArticlePubMedGoogle Scholar
- Matson AP, Zhu L, Lingenheld EG, Schramm CM, Clark RB, Selander DM, Thrall RS, Breen E, Puddington L: Maternal transmission of resistance to development of allergic airway disease. J Immunol. 2007, 179 (2): 1282-1291.View ArticlePubMedPubMed CentralGoogle Scholar
- Lim RH, Kobzik L: Maternal transmission of asthma risk. Am J Reprod Immunol. 2009, 61 (1): 1-10.View ArticlePubMedGoogle Scholar
- Fedulov AV, Kobzik L: Allergy risk is mediated by dendritic cells with congenital epigenetic changes. Am J Respir Cell Mol Biol. 2011, 44 (3): 285-292. 10.1165/rcmb.2009-0400OC.View ArticlePubMedGoogle Scholar
- Barreto ML, Cunha SS, Fiaccone R, Esquivel R, Amorim LD, Alvim S, Prado M, Cruz AA, Cooper PJ, Santos DN, et al: Poverty, dirt, infections and non-atopic wheezing in children from a Brazilian urban center. Respir Res. 2010, 11: 167-10.1186/1465-9921-11-167.View ArticlePubMedPubMed CentralGoogle Scholar
- Belyhun Y, Amberbir A, Medhin G, Erko B, Hanlon C, Venn A, Britton J, Davey G: Prevalence and risk factors of wheeze and eczema in 1-year-old children: the Butajira birth cohort, Ethiopia. Clin Exp Allergy. 2010, 40 (4): 619-626. 10.1111/j.1365-2222.2010.03479.x.View ArticlePubMedGoogle Scholar
- Lima JA, Fischer GB, Sarria EE, Mattiello R, Sole D: Prevalence of and risk factors for wheezing in the first year of life. J Bras Pneumol. 2010, 36 (5): 525-531.View ArticlePubMedGoogle Scholar
- Melen E, Kere J, Pershagen G, Svartengren M, Wickman M: Influence of male sex and parental allergic disease on childhood wheezing: role of interactions. Clin Exp Allergy. 2004, 34 (6): 839-844. 10.1111/j.1365-2222.2004.01957.x.View ArticlePubMedGoogle Scholar
- Wright AL, Stern DA, Kauffmann F, Martinez FD: Factors influencing gender differences in the diagnosis and treatment of asthma in childhood: the Tucson Children's Respiratory Study. Pediatr Pulmonol. 2006, 41 (4): 318-325. 10.1002/ppul.20373.View ArticlePubMedGoogle Scholar
- Almqvist C, Worm M, Leynaert B: Impact of gender on asthma in childhood and adolescence: a GA2LEN review. Allergy. 2008, 63 (1): 47-57.PubMedGoogle Scholar
- Becklake MR, Kauffmann F: Gender differences in airway behaviour over the human life span. Thorax. 1999, 54 (12): 1119-1138. 10.1136/thx.54.12.1119.View ArticlePubMedPubMed CentralGoogle Scholar
- Ober C, Loisel DA, Gilad Y: Sex-specific genetic architecture of human disease. Nat Rev Genet. 2008, 9 (12): 911-922. 10.1038/nrg2415.View ArticlePubMedPubMed CentralGoogle Scholar
- Novak N, Bieber T: Allergic and nonallergic forms of atopic diseases. J Allergy Clin Immunol. 2003, 112 (2): 252-262. 10.1067/mai.2003.1595.View ArticlePubMedGoogle Scholar
- Bieber T: Atopic dermatitis. N Engl J Med. 2008, 358 (14): 1483-1494. 10.1056/NEJMra074081.View ArticlePubMedGoogle Scholar
- Spergel JM: From atopic dermatitis to asthma: the atopic march. Ann Allergy Asthma Immunol. 2010, 105 (2): 99-106. 10.1016/j.anai.2009.10.002. quiz 107-109, 117View ArticlePubMedGoogle Scholar
- Zheng T, Yu J, Oh MH, Zhu Z: The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. Allergy Asthma Immunol Res. 2011, 3 (2): 67-73. 10.4168/aair.2011.3.2.67.View ArticlePubMedPubMed CentralGoogle Scholar
- Simpson EL, Hanifin JM: Atopic dermatitis. Med Clin North Am. 2006, 90 (1): 149-167. 10.1016/j.mcna.2005.09.002. ixView ArticlePubMedGoogle Scholar
- Purvis DJ, Thompson JM, Clark PM, Robinson E, Black PN, Wild CJ, Mitchell EA: Risk factors for atopic dermatitis in New Zealand children at 3.5 years of age. Br J Dermatol. 2005, 152 (4): 742-749. 10.1111/j.1365-2133.2005.06540.x.View ArticlePubMedGoogle Scholar
- Sole D, Mallol J, Wandalsen GF, Aguirre V: Prevalence of symptoms of eczema in Latin America: results of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3. J Investig Allergol Clin Immunol. 2010, 20 (4): 311-323.PubMedGoogle Scholar
- Ker J, Hartert TV: The atopic march: what's the evidence?. Ann Allergy Asthma Immunol. 2009, 103 (4): 282-289. 10.1016/S1081-1206(10)60526-1.View ArticlePubMedPubMed CentralGoogle Scholar
- Kapoor R, Menon C, Hoffstad O, Bilker W, Leclerc P, Margolis DJ: The prevalence of atopic triad in children with physician-confirmed atopic dermatitis. J Am Acad Dermatol. 2008, 58 (1): 68-73. 10.1016/j.jaad.2007.06.041.View ArticlePubMedGoogle Scholar
- Gustafsson D, Sjoberg O, Foucard T: Development of allergies and asthma in infants and young children with atopic dermatitis-a prospective follow-up to 7 years of age. Allergy. 2000, 55 (3): 240-245. 10.1034/j.1398-9995.2000.00391.x.View ArticlePubMedGoogle Scholar
- Simon D, Braathen LR, Simon HU: Increased lipopolysaccharide-induced tumour necrosis factor-alpha, interferon-gamma and interleukin-10 production in atopic dermatitis. Br J Dermatol. 2007, 157 (3): 583-586. 10.1111/j.1365-2133.2007.08050.x.View ArticlePubMedGoogle Scholar
- Illi S, von Mutius E, Lau S, Nickel R, Gruber C, Niggemann B, Wahn U: The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. Allergy Clin Immunol. 2004, 113 (5): 925-931. 10.1016/j.jaci.2004.01.778.View ArticleGoogle Scholar
- Kozyrskyj AL, Kendall GE, Jacoby P, Sly PD, Zubrick SR: Association between socioeconomic status and the development of asthma: analyses of income trajectories. Am J Public Health. 2010, 100 (3): 540-546. 10.2105/AJPH.2008.150771.View ArticlePubMedPubMed CentralGoogle Scholar
- Mohangoo AD, de Koning HJ, Hafkamp-de Groen E, van der Wouden JC, Jaddoe VW, Moll HA, Hofman A, Mackenbach JP, de Jongste JC, Raat H: A comparison of parent-reported wheezing or shortness of breath among infants as assessed by questionnaire and physician-interview: the Generation R study. Pediatr Pulmonol. 2010, 45 (5): 500-507.PubMedGoogle Scholar
- Caraballo L, Acevedo N: New allergens of relevance in tropical regions: the impact of Ascaris lumbricoides infections. WAO Journal. 2011, 4: 77-84.PubMedPubMed CentralGoogle Scholar
- Wang M, Karlsson C, Olsson C, Adlerberth I, Wold AE, Strachan DP, Martricardi PM, Aberg N, Perkin MR, Tripodi S, et al: Reduced diversity in the early fecal microbiota of infants with atopic eczema. J Allergy Clin Immunol. 2008, 121 (1): 129-134. 10.1016/j.jaci.2007.09.011.View ArticlePubMedGoogle Scholar
- Lee YK, Mazmanian SK: Has the microbiota played a critical role in the evolution of the adaptive immune system?. Science. 2010, 330 (6012): 1768-1773. 10.1126/science.1195568.View ArticlePubMedPubMed CentralGoogle Scholar
- Maslowski KM, Mackay CR: Diet, gut microbiota and immune responses. Nat Immunol. 2011, 12 (1): 5-9.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2466/12/13/prepub
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