Perinatal influences on the development of asthma and atopy in childhood

BackgroundIn most children with asthma and atopy, onset of disease occurs early in life, indicating a crucial role of in utero and early childhood environment. However, only a small part of this burden of disease established early in life has been explained.ObjectiveTo examine the effects of early environmental exposures on the development of asthma and atopy within the setting of an affluent urban population.MethodsThe authors followed 526 German children from birth to 5 years of age. Parental interviews in pregnancy and then yearly assessed the health of the child and environmental characteristics. Endotoxin and allergens in house dust were measured at 3 months. Atopic sensitization was assessed at 1 and 5 years.ResultsIn atopic mothers, acute atopic symptoms during pregnancy were associated with increased risk of early atopic dermatitis (adjusted odds ratio [aOR] 1.74, 95% confidence interval [CI] 1.00–3.02) and allergic rhinitis at 5 years (aOR 2.11, 95% CI 1.01–4.41). Further, maternal illnesses during pregnancy (ie, repeated common colds) increased the risk of asthma at 5 years (aOR 2.31, 95% CI 1.12–4.78). Endotoxin in the child's mattress was inversely associated with atopic sensitization (aOR 0.79, 95% CI 0.64–0.97) and asthma (aOR 0.71, 95% CI 0.55–0.93). A contrasting effect of early endotoxin and mite exposure was observed for mite sensitization: mite exposure increased the risk of mite sensitization at 5 years (aOR 1.30, 95% CI 1.11–1.53), whereas endotoxin exposure was inversely associated with mite sensitization (aOR 0.73, 95% CI 0.57–0.95).ConclusionFactors affecting the in utero environment, such as maternal atopy and infections, and bacterial exposure in pregnancy or early life may act as immunomodulators enhancing or inhibiting the development of asthma and atopy in childhood.     

Urinary eosinophilic protein X, atopy, and symptoms suggestive of allergic disease at 3 years of age

BACKGROUND: Urinary eosinophilic protein X (U-EPX) measurement is easy to perform in children. However, its use for prediction, diagnosis, and monitoring of asthma and atopy is unclear. OBJECTIVE: We sought to investigate the relationship between U-EPX and clinical phenotypes suggestive of allergic diseases. METHODS: U-EPX measurement (RIA), respiratory questionnaires, and skin testing were completed at age 3 years in 903 children followed prospectively from birth. Specific airway resistance was measured in 503 currently asymptomatic children by using whole-body plethysmography during tidal breathing. RESULTS: Nonatopic children with wheezing or eczema had slightly increased U-EPX levels compared with nonatopic asymptomatic children. U-EPX levels (geometric mean EPX/creatinine ratio) were as follows: nonatopic asymptomatic children (n = 313), 61.3 microg/mmol (95% CI, 56.4-66.6 microg/mmol); nonatopic children with wheezing (n = 148), 71.2 microg/mmol (95% CI, 63.2-80.1 microg/mmol); nonatopic children with eczema (n = 90), 65.7 microg/mmol (95% CI, 56.7-76.2 microg/mmol); and nonatopic children with wheezing and eczema (n= 86), 79.7 microg/mmol (95% CI, 67.4-94.3 microg/mmol). Children who had persistent atopy early in life had significantly higher U-EPX levels at age 3 years (nonatopic at 1 and 3 years [n = 263], 63.4 microg/mmol [95% CI, 58.4-69.0 microg/mmol]; atopic at 1 but not 3 years [n = 24], 65.1 microg/mmol [95% CI, 43.8-96.7 microg/mmol]; nonatopic at 1 year and atopic at 3 years [n = 62], 90.0 microg/mmol [95% CI, 74.6-108.4 microg/mmol]; atopic at 1 and 3 years [n = 35], 111.5 microg/mmol [95% CI, 89.2-139.3 microg/mmol]; P <.002). Atopy alone and with wheezing, eczema, or both was associated with significantly increased U-EPX levels (P <.0001). Wheezing appeared to be associated with higher U-EPX levels compared with eczema in both atopic and nonatopic children. The highest U-EPX level was found in atopic children with a history of wheezing and eczema (P <.0001). There was no relationship between U-EPX level and lung function. CONCLUSION: U-EPX level reflects the presence of atopy and associated symptoms and might be useful for monitoring the progression of allergic disease.     

Not all farming environments protect against the development of asthma and wheeze in children

BACKGROUND: In recent years, studies have shown a protective effect of being raised in a farm environment on the development of hay fever and atopic sensitization. Inconsistent data on the relation of farming to asthma and wheeze have raised some doubt about a true protective effect. OBJECTIVE: We sought to study the differential effects of farm-associated exposures on specific asthma-related health outcomes. METHODS: The cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle study included 8263 school-age children from rural areas in 5 European countries. Information on farm-related exposures and health outcomes was obtained by using questionnaires. In subsamples allergen-specific IgE and RNA expression of CD14 and Toll-like receptor genes were measured, and dust from children's mattresses was evaluated for microbial components. RESULTS: Inverse relations with a diagnosis of asthma were found for pig keeping (odds ratio [OR], 0.57; 95% CI, 0.38-0.86), farm milk consumption (OR, 0.77; 95% CI, 0.60-0.99), frequent stay in animal sheds (OR, 0.71; 95% CI, 0.54-0.95), child's involvement in haying (OR, 0.56; 95% CI, 0.38-0.81), and use of silage (OR, 0.55; 95% CI, 0.31-0.98; for nonatopic asthma) and in Germany for agriculture (OR, 0.34; 95% CI, 0.22-0.53). Protective factors were related with higher expression levels of genes of the innate immunity. Potential risk factors for asthma and wheeze were also identified in the farm milieu. Levels of endotoxin and extracellular polysaccharides were related to the health outcomes independently of the farm exposures. CONCLUSIONS: The protective effect of being raised in a farm environment was ascribed to distinct exposures. CLINICAL IMPLICATIONS: The development of atopic sensitization and atopic and nonatopic asthma is most likely determined by different environmental factors, possibly reflecting distinct pathomechanisms.     

The -159 C-->T polymorphism of CD14 is associated with nonatopic asthma and food allergy

BACKGROUND: CD14, the receptor for LPS, plays an important role in innate immunity. A polymorphism in the promotor for CD14, -159 C-->T, has been implicated in atopy. OBJECTIVE: We explored the relationship of this polymorphism with both atopic and nonatopic asthma, as well as with food allergy. METHODS: Patients with asthma and food allergy were recruited along with nonatopic, nonasthmatic control subjects. The -159 C-->T polymorphism was genotyped by using the PCR-based RFLP assay. RESULTS: The -159 T allele was more common among patients with nonatopic asthma and food allergy than among control subjects (chi(2) = 6.03, P =.01 and chi(2) = 4.94; P =.03, respectively). Patients with food allergy had a 4-fold increased odds of having the TT genotype versus carriers of the C allele compared with control subjects (odds ratio [OR] = 3.9, 95% CI = 1.5-10.3), whereas patients with nonatopic asthma had a 3-fold increased odds of having the TT genotype (OR = 3.1 [95% CI = 1.1-9.1]). Controlling for sex differences between groups did not alter this relationship, which remained significant for patients with food allergy (OR = 3.7 [95% CI = 1.4-10.1]) or nonatopic asthma (OR = 2.7 [95% CI = 0.9-8.0]). We performed a stratified analysis, limited to white patients, to reduce population stratification. The relationship with the TT genotype was stronger in white patients with nonatopic asthma (OR = 4.4 [95% CI = 1.3-14.8]) and patients with food allergy (OR = 5.1 [95% CI = 1.6-16.2]), even adjusting for sex differences (OR = 3.9 [95% CI = 1.1-13.5] and OR = 4.6 [95% CI = 1.4-14.8], respectively). CONCLUSIONS: The TT genotype of -159 C-->T CD14 is associated with nonatopic asthma and food allergy, particularly in white subjects. Thus CD14 is a candidate gene specifically for nonatopic asthma and not for asthma in general. This indicates that atopic and nonatopic asthma might be distinct conditions in their genetic predisposition, despite the fact that they are very similar once they have been established.     

Reduced risk of hay fever and asthma among children of farmers

BACKGROUND: The prevalence of atopic diseases is on the rise. Traditional lifestyles may be associated with a reduced risk of atopy. OBJECTIVES: To test the hypothesis that children living on a farm have lower prevalences of atopic diseases. To identify differences in living conditions between farmers and other families which are associated with the development of atopic conditions. DESIGN: Cross-sectional survey among children entering school (aged 5-7 years). A written questionnaire including the ISAAC core questions and asking for exposures on a farm and elsewhere was administered to the parents. Setting: School health entry examination in two Bavarian districts with extensive farming activity. Subjects: 10 163 children. MAIN OUTCOME MEASURES: The prevalence of doctor's diagnoses and symptoms of hay fever, asthma and eczema as assessed by parental report. RESULTS: Farmers' children had lower prevalences of hay fever (adjusted odds ratio = 0. 52, 95% CI 0.28-0.99), asthma (0.65, 0.39-1.09), and wheeze (0.55, 0. 36-0.86) than their peers not living in an agricultural environment. The reduction in risk was stronger for children whose families were running the farm on a full-time basis as compared with families with part-time farming activity. Among farmers' children increasing exposure to livestock was related to a decreasing prevalence of atopic diseases (aOR = 0.41, 95% CI 0.23-0.74). CONCLUSIONS: Factors related to environmental influences on a farm such as increased exposure to bacterial compounds in stables where livestock is kept prevent the development of allergic disorders in children.     

Long-term exposure to background air pollution related to respiratory and allergic health in schoolchildren

BACKGROUND: The impact of air pollution on asthma and allergies still remains a debate. OBJECTIVE: Our cross-sectional study was intended to analyse the associations between long-term exposure to background air pollution and atopic and respiratory outcomes in a large population-based sample of schoolchildren. METHODS: Six thousand six hundred and seventy-two children aged 9-11 years recruited from 108 randomly schools in six French cities underwent a clinical examination including a skin prick test (SPT) to common allergens, exercise-induced bronchial reactivity (EIB) and skin examination for flexural dermatitis. The prevalence of asthma, allergic rhinitis (AR) and atopic dermatitis was assessed by a standardized health questionnaire completed by the parents. Three-year-averaged concentrations of air pollutants (NO2, SO2, PM10 and O3) were calculated at children' schools using measurements of background monitoring stations. RESULTS: After adjusting for confounders, EIB, lifetime asthma and lifetime AR were found to be positively related to an increase in the exposure to SO2, PM10 and O3. The adjusted odds ratios (aOR) per increase of 5 microg/m3 of SO2 was 1.39 (95% confidence interval (CI)=1.15-1.66) for EIB and 1.19 (1.00-1.41) for lifetime asthma. The aOR for lifetime AR per increase of 10 microg/m3 of PM10 was 1.32 (CI=1.04-1.68). Moreover, SPT positivity was associated with O3 (aOR=1.34; CI=1.24-1.46). Associations with past year symptoms were consistent, even if not always statistically significant. Results persisted in long-term resident (current address for at least 8 years) children. However, no consistent positive association was found with NO2. CONCLUSIONS: A moderate increase in long-term exposure to background ambient air pollution was associated with an increased prevalence of respiratory and atopic indicators in children.     

IL-5 and thromboxane A2 receptor gene polymorphisms are associated with decreased pulmonary function in Korean children with atopic asthma

BACKGROUND: Asthmatic airways undergo chronic inflammatory cell infiltration by T cells and eosinophils, which results in sustained airway hyperresponsiveness. IL-5 is important for eosinophil-induced airway inflammation and airway hyperresponsiveness. Thromboxane A2 and its receptor, TBXA2R, are involved in constriction of respiratory smooth muscles and may play a role in thickening and remodeling of airways, which contributes to the severity of asthma. The relationship between IL-5 and TBXA2R gene polymorphisms and pulmonary function in children with asthma has rarely been examined. OBJECTIVE: To determine whether IL-5 (T-746C) and TBXA2R (T924C) gene polymorphisms are associated with asthma phenotype and pulmonary function in Korean children with atopic and nonatopic asthma. METHODS: We conducted an association study between known polymorphisms of IL-5 (T-746C) and TBXA2R (T924C) and asthma phenotype and the parameters of atopy and pulmonary function in atopic and nonatopic Korean children with asthma. The subjects were 240 atopic children with asthma, 70 nonatopic children with asthma, and 106 nonatopic healthy children. Asthma phenotypes and bronchial responsiveness to methacholine were determined by a physician. IL-5 and TBXA2R gene polymorphisms were determined by genotyping by using PCR-RFLP assays. RESULTS: The genotype frequencies of IL-5 and TBXA2R polymorphisms did not differ between healthy controls and atopic or nonatopic children with asthma. A significant association was observed between the IL-5 polymorphism and forced expiratory flow at 25% to 75% of forced vital capacity (FEF 25-75% ; %; P = .002), and between the TBXA2R polymorphism and FEV 1 (%; P = .035) and FEF 25-75% (%; P = .042) in children with atopic asthma, whereas no such association between the polymorphisms and lung function was observed in nonatopic or control children. In atopic children with asthma, we identified a significant gene-gene interaction in that the combination of the IL-5 (T-746C) and TBXA2R (T924C) mutant alleles was shown to be associated with reduced pulmonary function as determined by FEF 25-75% (%) measurement. CONCLUSION: The current study indicates that IL-5 (T-746C) and TBXA2R (T924C) polymorphisms alone are associated with spirometric markers of asthma severity, whereas they are not associated with presence of asthma per se. In addition, the data suggest that an interaction between IL-5 and TBXA2R genes may contribute to the severity of asthma, especially atopic asthma. These results suggest that IL-5 and TBXA2R genes may be disease-modifying genes in Korean children with atopic asthma.     

Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure

Background:  Filaggrin gene ( FLG ) mutations contribute to the development of eczema and asthma, but their contribution to sensitization and hay fever remains unclear.
Methods:  FLG mutations R501X, 2282del4 and R2447X were genotyped in the Prevention and Incidence of Asthma and Mite Allergy birth cohort ( n  = 934) to evaluate longitudinally, for up to 8 years, their association with eczema, sensitization, asthma, hay fever and their interaction with cat exposure.
Results:  The combined FLG mutations were significantly associated with eczema at all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4–2.8). Combined FLG mutations were associated with both atopic and nonatopic eczema, as well as asthma (OR = 3.7; 95% CI: 1.8–7.5). When the FLG 2282del4 mutation was analysed separately, it was significantly associated with the development of eczema during the first year, having eczema up to 8 years and sensitization at the age of 8 years, which was enhanced by early-life cat exposure (ORs being 8.2; 95% CI: 2.6–25.9, 6.0; 95% CI: 3.2–11.3 and 5.4; 95% CI: 1.2–23.6 respectively). FLG 2282del4 was significantly associated with hay fever from the age 5 years onwards (OR = 3.9; 95% CI: 1.5–10.5).
Conclusions:  FLG mutations are associated both with atopic and nonatopic eczema starting in the first year of life. FLG mutations combined with eczema in the first year of life are associated with a later development of asthma and hay fever, a clear example of the atopic march. We confirm that cat exposure enhances the effect of a FLG mutation on the development of eczema and sensitization.     

Allergen-specific sensitization in asthma and allergic diseases in children: the study on farmers'' and non-farmers'' children

BACKGROUND: Farmers' children are less frequently sensitized to common allergens than the non-farmers' children, but less is known about their sensitization to other allergens and its association with clinical diseases. OBJECTIVE: To examine the association of farm environment with atopic sensitization, allergic diseases, expression of allergen-induced symptoms, and the importance of specific sensitization against 'common' (timothy, dog, cat, birch, Dermatophagoides pteronyssimus, mugwort) and 'other' (cockroach, horse, Lepidoglyphus destructor, cow) allergens for asthma and allergic diseases in children. METHODS: A cross-sectional study including 344 farmers' and 366 non-farmers' children aged 6-13 years in eastern Finland, using a self-administered written questionnaire and skin prick tests against the above-mentioned allergens. RESULTS: Farmers' children had less asthma and allergic diseases and were less often sensitized against common allergens than the non-farmers' children. However, little difference was observed in sensitization against the other allergens between the farmers' (17.2%) and non-farmers (14.5%) children [adjusted odds ratios (aOR) 1.11 (0.71-1.72)]. Being sensitized against only other allergens, without sensitization against common allergens, was unrelated to asthma or allergic diseases. Among the single allergens, sensitization against pets or pollen, or against horse or cow, had the strongest association with asthma, hayfever, and atopic eczema; no such association was seen in D. pteronyssimus, mugwort, cockroach, or L. destructor. Farmers' children had significantly less often symptoms of allergic rhinitis in contact with dog (aOR 0.32%, 95% confidence interval (CI) 0.15-0.67), cat (aOR 0.45, 0.22-0.88), or pollen (aOR 0.58%, 95% CI 0.37-0.90) than the non-farmers' children. CONCLUSION: Farm environment reduces the occurrence of asthma, allergic diseases, and atopic sensitization in children, and also the occurrence of allergen-induced rhinitis. Remarkable differences were observed between single allergens in their association with allergic disease, stressing the importance of allergen selection when defining atopy in epidemiological studies.     

Determinants of increased exhaled nitric oxide in patients with suspected asthma

Exhaled nitric oxide (FENO) has been proposed as a marker of asthmatic inflammation, but it is unclear whether FENO in clinical use selects patients primarily according to their atopic or asthmatic status. The aim of this study was to investigate the determinants of increased FENO in patients with suspected asthma, by means of multinomial logistic regression analysis. The FENO of 132 patients referred because of symptoms suggestive of asthma were studied, and the explanatory factors tested included atopy according to prick skin tests, clinical asthma according to lung function tests, sputum eosinophilia and bronchial hyperresponsiveness (BHR). Slightly elevated FE(NO) levels were significantly explained only by sputum eosinophilia (OR: 3.7; 95% CI: 1.1-13.1; P=0.04), but for high levels of FE(NO) (> or =3 SD of predicted), clinical asthma (OR: 16.3; 95% CI: 5.4-49.7; P <0.0001) and sputum eosinophilia (OR: 12.0; 95% CI: 4.1-35.0; P >0.0001) were the characteristics with the highest prediction, followed by atopy and BHR. A significant interaction between asthma and atopy was observed relating to the effect on high FENO, but further analyses stratified by atopy showed significant associations between asthma and high FENO both in atopic and nonatopic patients. We conclude that in patients with symptoms suggesting asthma, slightly elevated and high levels of FENO are associated with sputum eosinophilia, whereas asthma is significantly associated only with high levels of FENO, irrespective of atopy. The results suggest that FENO is primarily a marker of airway eosinophilia, and that only high values of FENO may be useful to identify patients with atopic or nonatopic asthma.     

Allergic disease and sensitization in Steiner school children

BACKGROUND: The anthroposophic lifestyle has several features of interest in relation to allergy: for example, a restrictive use of antibiotics and certain vaccinations. In a previous Swedish study, Steiner school children (who often have an anthroposophic lifestyle) showed a reduced risk of atopy, but specific protective factors could not be identified. OBJECTIVE: To investigate factors that may contribute to the lower risk of allergy among Steiner school children. METHODS: Cross-sectional multicenter study including 6630 children age 5 to 13 years (4606 from Steiner schools and 2024 from reference schools) in 5 European countries. RESULTS: The prevalence of several studied outcomes was lower in Steiner school children than in the reference group. Overall, there were statistically significant reduced risks for rhinoconjunctivitis, atopic eczema, and atopic sensitization (allergen-specific IgE > or =0.35 kU/L), with some heterogeneity between the countries. Focusing on doctor-diagnosed disease, use of antibiotics during first year of life was associated with increased risks of rhinoconjunctivitis (odds ratio [OR], 1.97; 95% CI, 1.26-3.08), asthma (OR, 2.79; 95% CI, 2.03-3.83), and atopic eczema (OR, 1.63; 95% CI, 1.22-2.17). Early use of antipyretics was related to an increased risk of asthma (OR, 1.54; 95% CI, 1.11-2.13) and atopic eczema (OR, 1.32; 95% CI, 1.02-1.71). Children having received measles, mumps, and rubella vaccination showed an increased risk of rhinoconjunctivitis, whereas measles infection was associated with a lower risk of IgE-mediated eczema. CONCLUSION: Certain features of the anthroposophic lifestyle, such as restrictive use of antibiotics and antipyretics, are associated with a reduced risk of allergic disease in children.     

Central obesity is associated with nonatopic but not atopic asthma in a representative population sample

BACKGROUND: Epidemiologic studies have consistently demonstrated the association between high body mass index (BMI) and asthma, yet the relationship between asthma and the alternative central obesity phenotypes, waist circumference (WC) and waist-to-hip ratio (WHR), has not been assessed in a representative population sample. OBJECTIVE: To determine the strength of the association of WC and WHR with current asthma and whether the association is modified by atopic status in a representative population sample. METHODS: The North West Adelaide Health Study, a biomedical population study of n = 4060, assessed current asthma, respiratory symptoms, and participant demographics by self-completed questionnaire. Clinic assessment included measures of WC and WHR, spirometry, and skin prick tests to a panel of allergens. RESULTS: Logistic regression analysis showed a significant, marginal increased adjusted risk of asthma associated with obese levels of WC and WHR and BMI > or =35.0 kg/m2 in female subjects only. When the association was considered stratified according to atopic status, the relationship between obese levels of WC and WHR with asthma held only for the nonatopic population in both males (WC: odds ratio [OR] 5.7, 95% confidence interval [CI] 1.1-28.8; WHR: OR 6.2, 95% CI, 1.1-32.9) and females (WC: OR 2.3, 95% CI, 1.2-4.4; WHR: OR 3.0, 95% CI, 1.5-5.9). BMI > or =35.0 kg/m2 showed an inconsistent pattern in the association with asthma. CONCLUSION: Central obesity was significantly associated with an increased risk of nonatopic asthma only. The causal pathway is unknown, but this study suggests the involvement of different pathophysiological mechanisms requiring further investigation. CLINICAL IMPLICATIONS: Asthma should be considered in older, nonatopic, centrally obese, symptomatic individuals.     

T cell and eosinophil activation in mild and moderate atopic and nonatopic children's asthma in remission

BACKGROUND: Inflammation in the pathogenesis of asthma is associated with products of activated T cells and eosinophils. The aim of this study was to determine whether ongoing inflammation persists in children with different phenotypes of asthma despite the disease in remission. METHODS: Serum samples were collected from 68 children with atopic or nonatopic asthma in remission and from 15 healthy children. Soluble interleukin-2 receptor (sIL-2R), IL-2 and IL-4 were examined by using an enzyme-linked immunosorbent assay. Total and specific immunoglobulin E, and eosinophil cationic protein (ECP) were analysed by fluoroimmunoassay (Pharmacia CAP System). RESULTS: In patients with moderate persistent atopic asthma, sIL-2R was increased significantly when compared with mild persistent atopic asthma (P < 0.05). No changes of sIL-2R were seen in nonatopic asthmatics compared with atopics and controls. The level of IL-2 was elevated in moderate persistent atopic and nonatopic asthmatic children compared with controls (P < 0.05 and P < 0.05 respectively) and compared with mild persistent atopic asthmatics and mild persistent nonatopic asthmatics (P < 0.05 in both cases). The levels of IL-4 in most patients and controls remained below the sensitivity of the assay. Eosinophil cationic protein levels in moderate persistent atopic and nonatopic asthmatics were significantly higher than in mild persistent asthma severity cases (P < 0.001 and P < 0.01 respectively) and in healthy children (P < 0.01 in both cases). CONCLUSION: Changes in the concentration of sIL-2R, IL-2 and ECP reflect increased T cell and eosinophil activity in relation to the level of severity of asthma in atopic and nonatopic children, thereby proving the presence of persistent inflammation despite the absence of disease symptoms.     

Prevalence,risk factors,and clinical outcomes of atopic and nonatopic asthma among rural children

Background

Because of time and cost constraints, objective classification of atopic and nonatopic asthma has been limited in large epidemiologic studies. However, as we try to better understand exposure-outcome associations and ensure appropriate treatment of asthma, it is important to focus on phenotype-defined asthma classification.

Day-care attendance and increased risk for respiratory and allergic symptoms in preschool age

BACKGROUND: The reported impact of day-care attendance on respiratory and atopic symptoms has varied between studies from different countries. Regarding to the 'hygiene-hypothesis', day-care attendance may lead to less sensitization later in life, but the question still is whether day-care attendance and subsequent exposure to more frequent early infections is a risk or a protection against future allergic disease or asthma (atopic and nonatopic). METHODS: A cross-sectional postal questionnaire was replied by parents of 10,851 children, aged 1-6 years, in the year 2000 in a Swedish region (DBH-phase 1). The questionnaire focused on respiratory and atopic symptoms, the home environment and information on day care of the children. RESULTS: Children in day care were reported to have more symptoms than children in home care: adjusted odds ratio (AOR) for wheezing last 12 months, AOR 1.33 (CI 95%: 1.12-1.58), cough at night apart from colds last 12 months AOR 1.56 (CI: 1.17-2.07), doctor diagnosed asthma AOR 1.23 (CI: 0.88-1.71), rhinitis last 12 months AOR 1.15 (CI: 0.92-1.44), doctor diagnosed hay fever AOR 1.75 (CI: 0.94-3.23), eczema last 12 months, AOR 1.49 (CI: 1.24-1.79), allergic reactions to foods, AOR 1.27 (CI: 1.07-1.52), >6 colds last 12 months of 2.57 (CI: 2.12-3.12) and ear infection ever AOR 2.14 (CI: 1.87-2.45). The increased risks were mainly seen and reached significance in the youngest group of children, aged 1-4 years. Adjusting and stratification for the number of airway infections last year did not change the risk associated with day-care attendance for allergic diseases. CONCLUSIONS: Attending day care was associated with an increased risk of symptoms related to airways infections as well with eczema and allergic reactions to food. No sign of protection from day-care attendance for allergic diseases was found up to 6 years of age. Multiple airway infections and day-care attendance were found to be independently associated with asthma and allergic symptoms.     

Risk of childhood asthma and allergic rhinitis in relation to pregnancy complications

BACKGROUND: Events occurring during fetal life may affect the development of the immune and respiratory systems and increase the risk of asthma and allergic diseases. OBJECTIVES: We sought to elaborate the relations between the occurrence of pregnancy complications and other pregnancy-related conditions and the risk of bronchial obstruction during the first 2 years of life and the occurrence of asthma and allergic rhinitis by the age of 4 years. Pregnancy complications were considered both as predictors of the health outcomes and as possible effects caused by other prenatal factors. METHODS: A population-based, 4-year, cohort study was carried out involving 2531 children born in Oslo, Norway. We collected information on maternally related (hyperemesis, hypertension, and preeclampsia) and uterus-related complications in pregnancy (antepartum hemorrhage, preterm contractions, insufficient placenta, and restricted growth of the uterus) and the child's health and environmental exposures at birth and at 6, 12, 18, and 24 months and 4 years of age. The outcomes of interest were bronchial obstruction during the first 2 years and asthma and allergic rhinitis at the age of 4 years. RESULTS: In a logistic regression analysis adjusting for potential confounders, uterus-related, but not other pregnancy-related, complications increased the risk of bronchial obstruction (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3-3.4), asthma (OR, 3.0; 95% CI, 1.8-5.4), and allergic rhinitis (OR, 2.9; 95% CI, 1.6-5.2). These relations were similar in children of atopic and nonatopic parents. CONCLUSIONS: Uterus-related complications in pregnancy increase the risk of having asthma and allergic rhinitis in childhood.     

Breastfeeding Might Have Protective Effects on Atopy in Children With the CD14C-159T CT/CC Genotype

Breastfeeding is widely recommended to reduce risk of sensitization, eczema and asthma. However, the role of breastfeeding in prevention of allergic diseases is uncertain. We aimed to investigate whether the relationship between breastfeeding and sensitization to aeroallergens is modified by cluster of differentiation 14 (CD14) genotype. This study included 1,828 school children aged 9-12. We administered a detailed questionnaire and genotyped the CD14C-159T polymorphism. Skin prick tests for 12 aeroallergens were performed. School children who had been breastfed were less likely sensitized to aeroallergens (adjusted odds ratio [aOR] 0.712, 95% confidence interval [CI]: 0.555-0.914). There was no significant association between CD14C-159T genotype and atopy. Breastfeeding was associated with a decreased risk of atopic sensitization in children with CT/CC genotype (aOR 0.667, 95% CI: 0.463-0.960). Our data might identify the gene-environment interaction between the CD14C-159T polymorphism and breastfeeding in relation to aeroallergen sensitization.     

Environmental determinants of atopic eczema phenotypes in relation to asthma and atopic sensitization

BACKGROUND: There is still uncertainty about the determinants of atopic eczema (AE). To explain the heterogeneity of the disease, different phenotypes of AE have been suggested. METHODS: The cross-sectional PARSIFAL study included 14 893 school-age children of farmers or children attending Steiner schools and their respective reference groups. A detailed questionnaire was completed, and house dust was collected for the measurement of endotoxin and glucans. Atopic sensitization was defined by allergen-specific IgE levels in the serum. RESULTS: In multivariate analyses, helping with haying was the only variable related to a farming environment having a consistent inverse association with both current symptoms and a doctor's diagnosis of AE [aOR = 0.65 (95% CI: 0.46-0.93) and 0.73 (0.51-1.05)], respectively. Severe lower respiratory tract infections (LRTI) in the first 2 years of life and usage of antibiotics ever were found to be positively related only to asthma-associated AE, whereas the effect of LRTI on AE without asthma had an opposite effect. Levels of beta(1-->3)-glucans in mattress dust were inversely related to a doctor's diagnosis of asthma-associated AE [aOR = 0.75 (0.57-0.98)], and endotoxin levels to current symptoms of asthma-associated AE [aOR = 0.73 (0.57-0.94)]. CONCLUSIONS: The analyses of the PARSIFAL study revealed two different phenotypes of AE, depending on the association with asthma and wheezing ever. With regard to the hygiene hypothesis, help with haying, exposure to beta(1-->3)-glucans and endotoxin were found to be inversely associated with the AE phenotype associated with asthma and wheezing.     

Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study

BACKGROUND: Two factors thought to influence the risk of asthma are the promoting effect of sensitization to house dust mites and the preventive effect of increased omega-3 fatty acids. Although house dust mite allergen avoidance has been used as a preventive strategy in several trials, the effect of omega-3 fatty acid supplementation in the primary prevention of asthma and allergic disease is not known. OBJECTIVE: To measure the effects of dietary supplementation with omega-3 fatty acids and house dust mite allergen avoidance in children with a family history of asthma. METHODS: A total of 616 children at high risk of asthma were enrolled antenatally in a randomized controlled trial, and 526 children remained in the trial at age 3 years. The outcomes were symptoms of allergic disease and allergen sensitization. RESULTS: There was a significant 10.0% (95% CI, 3.7-16.4) reduction in the prevalence of cough in atopic children in the active diet group ( P=.003; number needed to treat, 10) but a negligible 1.1% (95% CI, -7.1 to 9.5) reduction cough among nonatopic children. There was a 7.2% (95% CI, 10.11-14.3) reduction in sensitization to house dust mite in the active allergen avoidance group ( P=.05; number needed to treat, 14). No significant differences in wheeze were found with either intervention. CONCLUSION: These results suggest that our interventions, designed to be used in simple public health campaigns, may have a role in preventing the development of allergic sensitization and airways disease in early childhood. This offers the prospect of reducing allergic disease in later life.     

Childhood asthma and continuous exposure to cats since the first year of life with cats allowed in the child's bedroom

Background: There are controversial data as to interdependencies of exposure to furred pets in infancy and the prevalence of asthma and hay fever in children. Does the timing, intensity and type of pet exposure matter? Methods: Cross‐sectional questionnaire data on 8216 German schoolchildren aged 5–7 years not living on a farm in ten rural districts in Bavaria in 1997 were analysed. The diagnosis of asthma and hay fever was ascertained with the International Study of Asthma and Allergies in Childhood (ISAAC) core questions. Wheeze and asthma were classified as ‘atopic’ in children who also had hay fever or atopic dermatitis. Prevalence and intensity of exposure to pets in the first year of life and at present were assessed via questionnaire. Results: Although the study was of considerable size we found no convincing association between atopic disease and pet exposure in general. Exposure to cats from the first year of life to school entry, however, was associated with a reduced prevalence of atopic asthma, if cats were allowed to be in the child's bedroom: no case of atopic asthma in 296 children exposed and an aOR 0.11 (95% CI:0.01–0.52) for atopic wheeze in the last 12 months. Conclusions: Allowing cats to be in the child's bedroom from the first year of life onwards may be an indicator of intensive exposure to cats and appears to prevent the development of childhood asthma.