Fatty acid composition abnormalities in atopic disease: evidence explored and role in the disease process examined

There is a hypothesis causally linking excess intake of n-6 polyunsaturated fatty acids (PUFAs) to atopic disease. Under most dietary conditions, the main precursor of eicosanoids is the n-6 PUFA arachidonic acid (AA). AA-derived eicosanoids play many roles in sensitization to allergens and in allergic inflammation. Long chain n-3 PUFAs inhibit AA incorporation into cell membranes and inhibit AA metabolism to eicosanoids. It is hypothesized that atopy is associated with a higher n-6 PUFA status and with a low n-3 PUFA status. However, measurements of fatty acid composition do not provide a clear picture that such fatty acid abnormalities exist in atopy with no really clear pattern of altered status of a particular fatty acid or a particular fatty acid family. There are few reports of elevated linoleic acid in atopy. Some studies report lower amounts of the n-6 PUFAs, including AA, and of long chain n-3 PUFAs in atopy, although observations on this are not consistent. Taken together these data clearly do not support the hypothesis that atopy is somehow associated with a high exposure to, and status of, n-6 PUFAs. Intervention studies with n-3 PUFAs in pregnant women, infants and children suggest some clinical benefits, although how long lasting these are remains to be determined. The observation that there may be low AA status in atopy suggests that fish oil intervention, which targets AA status and metabolism, may not be ideal and that a combination of fish oil with some longer chain n-6 PUFAs may be more efficacious.     

Atopic disease and its determinants – a focus on the potential role of childhood infection

BACKGROUND: Atopic diseases develop on a genetic background and are modulated by environmental factors among which some infectious diseases are thought to have a protective influence. OBJECTIVE: The aim of this study was to determine the influence of infectious diseases in younger ages, bacterial and viral, on atopic diseases and sensitization to aero- and food-allergens in adults. METHODS: A population-based sample of 4262 subjects aged 25-74 years were interviewed concerning their history of infectious disease within the first 18 years of life. Information about allergic disease, including atopic eczema, allergic rhinitis (AR), and asthma was obtained. A blood sample was drawn and analysed for allergen-specific IgE antibodies against food- and aero-allergens. RESULTS: Multiple logistic regression analyses identified viral infection to be associated with AR (adjusted odds ratio (OR) = 1.39; 95% confidence interval (95% CI): 1.13-1.72) and sensitization to aeroallergens (OR = 1.21; 95% CI: 1.05-1.41). Bacterial disease was a negative predictor for atopy development in the subgroup of patients sensitized to nutritional allergens with concomitant atopic eczema (OR = 0.34; 95% CI: 0.11-0.99), AR (OR = 0.67; 95% CI: 0.42-1.07), or asthma (OR = 0.41; 95% CI: 0.19-0.87). Influences of viral and bacterial infection on AR differed with regard to family history of atopic disease. CONCLUSION: In our study population, history of viral infection was consistently positively associated with AR. Our data suggests that bacterial infections might be preventive for specific subgroups of atopy.     

Polyunsaturated fatty acids in maternal diet, breast milk, and serum lipid fatty acids of infants in relation to atopy

Background: The increased consumption of n-6 polyunsaturated fatty acids (PUFA) has been shown to coincide with the increased prevalence of atopic diseases. We aimed to investigate whether maternal diet and atopic status influence the PUFA composition of breast milk and the serum lipid fatty acids of infants.
Methods: Maternal diet was assessed by a food questionnaire. The PUFA composition of breast milk obtained at 3 months from 20 allergic and 20 healthy mothers and of their infants' (10 atopic and 10 nonatopic/group of mothers) serum lipids was analyzed.
Results: Although no differences in maternal PUFA intake were observed, the breast milk of allergic mothers contained less γ-linolenic acid (18:3 n-6) than that of healthy mothers. Similarly, atopic infants had less γ-linolenic acid in phospholipids than healthy infants, although n-6 PUFA were elevated in other serum lipid fractions in atopic infants. The serum lipid fatty acids in atopic infants did not correlate with those in maternal breast milk.
Conclusions: Our results suggest that dietary n-6 PUFA are not as readily transferred into breast milk or incorporated into serum phospholipids, but may be utilized for other purposes, such as eicosanoid precursors, in allergic/atopic individuals. Subsequently, high dietary proportions of n-6 PUFA, or reduced proportions of regulatory PUFA, such as γ-linolenic acid and n-3 PUFA, may be a risk factor for the development of atopic disease.     

Comparative prevalence of sensitization to common animal, plant and mould allergens in subjects with asthma, or atopic dermatitis and/or allergic rhinitis living in a tropical environment

BACKGROUND AND OBJECTIVES: Current information suggests that the expression of allergic diseases is determined by the exposure and nature of the allergen. The objectives of the present study were to determine if the nature of allergenic exposition to animal, plant or fungal allergens influenced the clinical manifestations of atopic dermatitis (AD), allergic rhinitis (AR) or asthma (AS) in patients living in a tropical environment. The prevalence and degree of sensitization to these allergens were analysed by age and gender. SUBJECTS AND METHODS: A total of 1496 atopic cases, grouped according to the primary diagnosis of AD or AR or AS, were skin tested using a standardized allergen panel. Participants were categorized by age groups. The atopic index (AI) and mean weal diameter (MWD) as well as the prevalence of positive skin tests were determined for each of the patient groups and compared by age groups. RESULTS: The prevalence of atopy as well as the AI and the MWD peaked at 6-15 years of age and declined thereafter. In all the patients tested, the prevalence of sensitization was, in decreasing order; dust mites 94.3%, cockroach 41.5%, pets 31.5%, plant allergens 31.1% and fungal 19.4%. Eight hundred and ninety-three atopic patients were exclusively sensitized only to animal allergens. Of these, 38.4% had AD, 31.3% had AR and 30.5% with AS. CONCLUSION: These data demonstrate that for patients with AD, AR and AS living in a tropical environment, the prevalence of positive skin reactions to animal allergens is highest followed by plant and fungal allergens. We did not observe any association between the type of allergen and clinical manifestations. The index of atopy was similar for both sexes. The prevalence and degree of sensitization were shown to peak in young adults independent of the allergen in AD and AR patients.     

Atopy Risk in Infants and Children in Relation to Early Exposure to Fish,Oily Fish,or Long-Chain Omega-3 Fatty Acids: A Systematic Review

There are two main families of polyunsaturated fatty acids (PUFAs), the n−6 and the n−3 families. It has been suggested that there is a causal relationship between n−6 PUFA intake and allergic disease, and there are biologically plausible mechanisms, involving eicosanoid mediators of the n−6 PUFA arachidonic acid, that could explain this. Fish and fish oils are sources of long-chain n−3 PUFAs and these fatty acids act to oppose the actions of n−6 PUFAs. Thus, it is considered that n−3 PUFAs will protect against atopic sensitization and against the clinical manifestations of atopy. Evidence to examine this has been acquired from epidemiologic studies investigating associations between fish intake in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children and from intervention studies with fish oil supplements in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. One study investigating the effects of maternal fish intake during lactation did not observe any significant associations. The evidence from epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children is inconsistent, although the majority of the studies (nine of 14) showed a protective effect of fish intake during infancy or childhood on atopic outcomes in those infants/children. Fish oil supplementation during pregnancy and lactation or during infancy or childhood results in a higher n−3 PUFA status in the infants or children. Fish oil provision to pregnant women is associated with immunologic changes in cord blood and such changes may persist. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitization to common food allergens and reduce prevalence and severity of atopic dermatitis in the first year of life, with a possible persistence until adolescence with a reduction in eczema, hay fever, and asthma. Fish oil provision to infants or children may be associated with immunologic changes in the blood but it is not clear if these are of clinical significance and whether they persist. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but this benefit may not persist as other factors come into play. It is not clear whether fish oil can be used to treat children with asthma as the two studies conducted to date give divergent results. Further studies of increased long-chain n−3 PUFA provision in during pregnancy, lactation, and infancy are needed to more clearly identify the immunologic and clinical effects in infants and children and to identify protective and therapeutic effects and their persistence.     

Fatty acids in colostrum from mothers of children at high risk of atopy in relation to clinical and laboratory signs of allergy in the first year of life

BACKGROUND: It remains controversial whether fatty acid (FA) composition of breast milk relates to development of atopy in the infant. This study evaluates FA in colostrum from mothers of children at high risk of atopy in association with atopy at the age of 1 year. METHODS: The FA of colostrum were analyzed for 218 children (60 with low birth weight between 1500 and 2500 g, 84 with a history of maternal atopy, and 74 with an elevated cord blood immunoglobulin (Ig)E of >0.9 IU/ml). Total lipids were extracted, methylated and separated by gas-liquid chromatography. Laboratory screening for allergic sensitization and clinical examination took place within the Leipzig Allergy Risk Children's Study (LARS). RESULTS: Low birth weight was correlated with low percentage levels of 20:2n-6, 22:2n-6, and 22:3n-3 (r = 0.14, P < 0.05; r = 0.14, P < 0.05 and r = 0.20, P < 0.01, respectively) and low gestational age at birth was correlated with low 22:3n-3 (r = 0.15, P < 0.05). There was no association between FA and atopic eczema at the age of 1 year. However, high linoleic acid (LA, 18:2n-6) was linked to high specific IgE against cow's milk protein (P < 0.05), and low docosapentaenoic acid (DPA, 22:5n-3) was associated with elevated total serum IgE (P < 0.05) at the age of 1 year, respectively. CONCLUSIONS: The polyunsaturated fatty acid composition of colostrum in a high risk newborn population shows associations with atopic sensitization at the age of 1 year and may be predictive for later atopic disease.     

A dual long-term effect of breastfeeding on atopy in relation to heredity in children at 4 years of age

BACKGROUND: The long-term effect of early feeding on atopic sensitization is still unsolved. The aim of this study was to evaluate the long-term effect of breastfeeding on atopy in groups of 4-year-old children stratified by atopic heredity. METHODS: We collected four groups of 4-year-old children from a birth cohort: two groups with differing backgrounds of atopic heredity, all exclusively breast-fed for at least 3 months; and two groups with differing atopic heredity, but all fed with cow's milk-based formula during their first weeks. The data were collected with a questionnaire, skin prick testing, and measurement of serum total and allergen-specific IgE levels. RESULTS: Breastfeeding significantly decreased the risk of allergic rhino-conjunctivitis [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.18-0.95] and sensitization to furred pets, as measured by skin prick results, in children with atopic heredity, whereas in children without atopic heredity, breastfeeding was related to an increased risk of symptomatic atopy (OR 2.57, 95% CI 1.16-5.70), and high serum IgE values. A significant interaction was found between heredity and breastfeeding. CONCLUSIONS: The long-term effect of breastfeeding was dual: in children with atopic heredity, breastfeeding protected against atopy, whereas in children without atopic heredity, it increased the risk of atopy.     

Increased levels of serum-specific immunoglobulin e to staphylococcal enterotoxin a and B in patients with allergic rhinitis and bronchial asthma

BACKGROUND: The association between staphylococcal enterotoxins and atopic dermatitis (AD) is well characterized. We aim to evaluate the association between sensitization to staphylococcal enterotoxin A (SEA) and/or B (SEB) and the development of allergic airway disease. METHODS: Two hundred and seventy-four patients were grouped into allergic rhinitis (AR) and/or bronchial asthma (BA) only, AD only and AR/BA+AD. The AR/BA only group was further divided into AR only, AR and airway hyperresponsiveness (AR+AHR) and BA. The allergen-specific and total immunoglobulin E (IgE) antibodies were determined by the CAP system. The associations of sensitization to SEA/SEB with allergic airway disease were analyzed by logistic regression analysis. RESULTS: The overall rate of sensitization to SEA/SEB was 25.7%, whereas the rate of the AD only group (45.5%) was significantly higher than that of the AR/BA only group (24.5%, chi2=8.1). After sensitization to SEA/SEB, the geometric mean total IgE levels were significantly elevated in patients with AR+AHR and BA, but not in those with AR only. BA patients had higher geometric mean values of SEA- and SEB-specific IgE than AR only and AR+AHR patients. Logistic regression revealed that AR/BA only was more associated with sensitization to SEA/SEB (odds ratio 6.57) than AD only and AR/BA+AD (odds ratio 2.44 and 1.72). CONCLUSIONS: Atopic status after sensitization to SEA/SEB was more closely associated with BA than with other airway allergy, implying that SEA/SEB may play a role in exacerbating airway allergy and increasing the risk of allergic airway disease. Our study suggests that staphylococcal enterotoxins play a prominent role in the pathogenesis of allergic airway disease as well as AD.     

Early endotoxin exposure and atopy development in infants: results of a birth cohort study

BACKGROUND: Exposure to endotoxin in childhood is currently discussed to protect from the development of allergic diseases. OBJECTIVE: To study the effect of early endotoxin exposure on incidence of atopic sensitization, atopic dermatitis and wheezing until the age of 2 years in infants with different risk status in terms of parental atopy. METHODS: Data of 1942 infants of an ongoing birth cohort study were analysed by logistic regression. Endotoxin was measured in settled dust of the mothers' mattresses at infants' age of 3 months. Data on allergic symptoms and physicians' diagnoses were gathered by questionnaire. Sensitization to common food and inhalant allergens was assessed by specific serum IgE. RESULTS: High endotoxin levels increased the risk of repeated wheeze [adjusted odds ratio (OR) for 4th exposure quartile (Q4) 1.52, 95% confidence interval (CI) 1.08-2.14], but were associated with neither sensitization to food allergens nor atopic dermatitis. Stratification by parental atopy showed that there was an association of endotoxin exposure with incidence of repeated wheeze as well as with sensitization to inhalant allergens (P for trend = 0.008 and 0.044, respectively) only in infants with parental atopy, with the highest risk in the 4th exposure quartile (repeated wheeze: ORQ4 1.77, 95% CI 1.14-2.73; sensitization to inhalant allergens: ORQ4 1.69, 95% CI 0.70-4.11). CONCLUSION: Early endotoxin exposure in terms of mattress dust endotoxin levels seemed to increase the risk of atopic reactions to inhalant allergens at the age of 2 years, especially in infants at risk due to parental atopy. Our data disagree with an early protective effect of endotoxin on atopy development until the age of 2 years.     

Antioxidants and allergic disease: a case of too little or too much?

Speculation persists as to the possible role, if any, of dietary antioxidants in allergic disease. While it has been hypothesized that the recent increase in allergic disease is a consequence of declining dietary antioxidant intake, an alternative hypothesis proposes that the increase in allergic disease is due to increasing antioxidant intake. Dietary trends are conflicting; the intake of some antioxidants has declined, for others intakes are likely to have increased. Animal model studies demonstrate that antioxidant supplementation at the time of primary and subsequent allergen exposure attenuates allergic inflammatory responses. The data from human studies are less clear. Observational epidemiological studies of humans are beset by several methodological limitations associated with the assessment of diet and predominantly focus on asthma. Most observational studies report potentially beneficial associations between dietary antioxidants and allergic outcomes, but a small minority report potentially adverse associations. Human intervention studies suggest that single antioxidant supplements confer minimal, if any clinical benefit in adults with asthma, however, there is still scope for studies in children, atopic dermatitis, allergic rhinitis (AR) and of antioxidant combinations. More recently, it has been suggested that dietary antioxidants in the developmental context of fetal and infant development influence the development childhood asthma and atopic sensitization possibly by affecting the first interactions between the neonatal immune system and allergens. While a small number of birth cohort studies have reported potentially beneficial associations between maternal intake of some antioxidants during pregnancy and childhood asthma, there is very limited data suggesting associations between maternal antioxidant intake and childhood atopic dermatitis and AR. The available epidemiological, animal, molecular and immunological data suggest that there are associations between antioxidants and asthma and to a much lesser extent, atopic dermatitis and AR. However, the exact nature of the relationships and the potential for therapeutic intervention remain unclear. Cite this as: K. Allan, F. J. Kelly and G. Devereux, Clinical & Experimental Allergy, 2010 (40) 370–380.     

Prevalence and risk factors for allergic rhinitis and atopic eczema among schoolchildren in Israel: results from a national study.

BACKGROUND: There is growing evidence that the prevalence rates of asthma and allergic diseases are increasing, especially among children. Several risk factors are under investigation. OBJECTIVE: To evaluate the prevalence and risk factors for allergic diseases, including allergic rhinitis (AR) and atopic eczema (AE), among 13- to 14-year-old schoolchildren in Israel. METHODS: A modified version of the International Study of Asthma and Allergies in Childhood written questionnaire was administered to a national sample of schoolchildren 13 to 14 years old in Israel. The questionnaire was completed by the schoolchildren themselves. RESULTS: There were 10,057 complete questionnaires available for analysis. The prevalence of AR symptoms ever and current AR were 41.6% and 9.4%, respectively. Allergic rhinoconjunctivitis symptoms ever were reported by 15.8% of the children. The prevalence rates of 6 months of itchy rash ever and AE were 5.9% and 7.8%, respectively. After adjustment for demographic and environmental factors, current asthma, parental history of asthma, and population group were the most significant risk factors for current AR (odds ratio [OR], 4.47; 95% confidence interval [CI], 3.70-5.40; OR, 1.30; 95% CI, 1.02-1.66; and OR, 1.75; 95% CI 1.45-2.13; respectively) and AE (OR, 2.30; 95% CI, 1.80-2.90; OR, 1.80; 95% CI, 1.40-2.30; and OR, 1.70; 95% CI, 1.40-2.00; respectively). CONCLUSIONS: Israeli children have a low prevalence rate of current AR and a midrange rate of AE. Arabs have lower prevalence rates of allergic diseases than Jews, and the prominent risk factors for those diseases are current asthma and parental history of asthma.     

Serum cholesterol level in infancy is inversely associated with subsequent allergy in children and adolescents. A 20-year follow-up study

Background Previous studies suggest an association between an altered lipoprotein profile and atopy. The association has been hypothesized to be due to alterations in the dietary fat intake, a factor possibly contributing to the increase of allergic diseases in industrialized countries. Objective We aimed at assessing whether there is an association between the serum lipid levels in infancy and subsequent development of allergic symptoms in childhood and adolescence. Methods A cohort of 200 unselected newborns was prospectively followed up from birth to age 20 years (from 1981 to 2002) with repeated measurements of total cholesterol from birth and throughout the first year of life. The subjects were re‐examined at the ages of 5, 11 and 20 years, with assessment of the occurrence of allergic symptoms, skin prick testing (SPT) and measurement of total IgE and of the total, high‐ and low‐density lipoprotein cholesterol. Results Children and adolescents with allergic symptoms, SPT positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the non‐atopic subjects. The difference was not detectable in cord blood, but became significant from age 2 months onward. Conclusion The inverse association between the cholesterol level in infancy and subsequent manifestations of atopy seems not to be due to atopy‐related dietary alterations, because it was already present in early infancy, when virtually all the infants were on a similar diet, i.e. on exclusive breastfeeding.     

Antenatal determinants of neonatal immune responses to allergens

BACKGROUND: The environmental factors responsible for recent increases in the prevalence of asthma and atopic disease have been assumed to act after birth. Their possible effects on fetal immune development in utero have not been investigated systematically, although sensitization to allergens may occur before birth. OBJECTIVE: This prospective study determined whether the risk factors for asthma and atopic disease, namely family history of atopic disease, maternal smoking, birth order, or maternal dietary intake of antioxidant vitamins, exert antenatal effects on the fetal immune system that may predispose to childhood atopy. METHODS: The T helper (Th) cell proliferative responses of cord blood mononuclear cells (CBMC) from a sample of 223 neonates, representative of children born to a cohort of 2000 pregnant women, were measured and related to family, maternal and environmental factors associated with the pregnancy. RESULTS: The magnitude of CBMC-proliferative responses to allergens increased significantly in association with a family history of atopic disease or maternal smoking, and decreased significantly with increasing birth order and high maternal dietary intake of vitamin E. The epidemiological association between birth order and atopy may therefore be a consequence of antenatal influences rather than of protective effects of childhood infections. The association between maternal intake of vitamin E and CBMC responsiveness suggests that diet during pregnancy may influence the fetal immune system in such a way as to modulate the risk of childhood atopy. CONCLUSION: These results provide a new insight into the aetiology of atopic disease by demonstrating that the maternal environmental risk factors for atopy, diet, birth order and smoking, influence the development of the fetal immune system. This raises the prospect of preventative public health interventions during pregnancy.     

Atopy and house dust mite sensitization as risk factors for asthma in children

BACKGROUND: Recent evidence suggests that asthma is not invariably related to atopy. The aim of this study was to evaluate the frequency of atopy, asthma and sensitization to eight common allergens in a large group of children with allergic symptoms. METHODS: 1426 children referred to our Paediatric Asthma and Allergy Center because of allergic symptoms were examined. Bronchial asthma, allergic rhino-conjunctivitis, food allergy and atopic dermatitis were diagnosed with standardized methods. Atopy was diagnosed if at least one skin test was positive. RESULTS: Of the 1426 children examined, 629 (44%) were atopic and 769 (56%) were non-atopic. Asthma was diagnosed in the same proportion (i.e., 64%) of atopic and non-atopic children. However, after division into age groups, non-atopic asthma was significantly more prevalent (chi2 = 8.46) in children between 0 and 3 years old (group 1). On the other hand, atopy was significantly associated with asthma only in group 3 (odds ratio 1.85). Furthermore, a significant association with asthma symptoms was found for house dust mite (HDM) in group 3 (odds ratio 4.8). CONCLUSIONS: Asthma is related to atopy in pre-selected children only from the age of 7 years. House dust mite sensitization seems to be an important determinant of asthma in these "older" children.     

Early-onset atopy is associated with enhanced lymphocyte cytokine responses in 11-year-old children

BACKGROUND: Early age at onset of atopy is associated with more severe asthma and increased airway responsiveness (AR); the underlying mechanism is unclear but may involve T cell responses. OBJECTIVE: To test the hypothesis that enhanced T cell responses may be associated with early-onset atopy. METHODS: In a longitudinal study, atopy was determined in infancy and at 6 and 11 years of age. Individuals were categorized as persistent infant-onset atopy (PIOA), early childhood-onset atopy (ECOA) and later childhood-onset atopy (LCOA). At 11 years of age, peripheral blood T cell cytokine responses, AR, exhaled nitric oxide (FE(NO)) and forced expiratory volume in 1 s were determined. RESULTS: The age at onset of atopy was determined for 60 children, of whom 15 had PIOA, 24 had ECOA and 21 had LCOA. An additional 76 children who were never atopic were also included. T cell responses to house dust mite, including interleukin-5, -9, -10 and tumour necrosis factor alpha, were higher among children with PIA and ECOA, and lower in children with LCOA, P<0.05. In contrast, those children with LCOA or who were not atopic had the highest IL-10 response to PHA (P=0.014). Children with PIOA and ECOA, but not LCOA, had higher AR and FE(NO) compared with non-atopic children (P<0.05). The group with PIOA were more likely among the atopic children to be admitted to hospital for asthma (P<0.05) and also had lower %FEV(1) compared with non-atopic children (P=0.023). CONCLUSIONS: Early age at sensitization is associated with enhanced T cell cytokine responses and indices of adverse asthma outcome. T cell cytokine responses might be programmed at the time of initial atopic sensitization.     

Defining childhood atopic phenotypes to investigate the association of atopic sensitization with allergic disease

AIMS: Although atopic sensitization is common in childhood, its relationship to clinical allergic disease remains incompletely understood. We therefore sought to explore this relationship by defining sensitization based atopic phenotypes. METHODS: Children were recruited at birth (n = 1456) and reviewed at 1, 2, 4 and 10 years. Skin prick testing (SPT) to common allergens was done at 4 (n = 980) and 10 years (n = 1036) with lung function (n = 981), bronchial challenge (n = 784) and serum IgE (n = 953) testing at 10. Atopic phenotypes were defined, by sensitization pattern, for children with SPT at both 4 and 10 years (n = 823). RESULTS: Of phenotyped children, 68.0% were never atopic, 4.3% early childhood atopic (only atopic at age 4), 16.5% chronic childhood atopics (at 4 and 10 years) and 11.2% delayed childhood atopics (only at 10). Never atopics showed small but identifiable prevalence of allergic diseases such as asthma, eczema and rhinitis. Amongst allergen-sensitized subjects, aeroallergen predominated over food sensitization throughout childhood. Chronic childhood atopics showed highest prevalence of lifetime plus persistent wheeze, eczema and rhinitis, increased prevalence of aeroallergen sensitization, some evidence of persistent food sensitization, significantly greater cord IgE than never atopics (P = 0.006), plus higher total IgE (P < 0.001) and bronchial hyper-responsiveness (P < 0.001) at 10 years than other phenotypes. CONCLUSION: A proportion of childhood eczema, rhinitis and asthma is nonatopic. The commonest childhood pattern of atopy is chronic sensitization, associated with early, persisting and clinically significant allergic disease. The currently accepted childhood 'Allergic March' may oversimplify the natural history of childhood atopy and allergic disease.     

Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy.

BACKGROUND AND OBJECTIVES: The epidemiological association between higher dietary n-3 polyunsaturated fatty acids (PUFA) and lower prevalence of asthma, has led to interest in the role of early dietary modification in allergic disease prevention. In this study we examined the effects of maternal n-3 (PUFA)-rich fish oil supplementation on cord blood (CB) IgE and cytokine levels in neonates at risk of developing allergic disease. METHODS: In a randomized double-blind, placebo-controlled trial, 83 atopic pregnant women received either fish oil capsules (n = 40) containing 3.7 g n-3 PUFA/day or placebo capsules (n = 43) from 20 weeks gestation until delivery. CB cytokine levels (IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, TNF-alpha and IFN-gamma) and total IgE levels were measured and compared between the two groups. Fatty acid composition of red cell membranes was analysed by gas chromatography and the relationships among PUFA, cytokine and IgE levels were examined. RESULTS: Maternal fish oil supplementation resulted in a significant increase in n-3 PUFA levels (P < 0.001) in neonatal erythrocyte membranes. Neonates whose mothers had fish oil supplementation had significantly lower plasma IL-13 (P < 0.05) compared to the control group. There was also a significant inverse relationship between levels of n-3 PUFA in neonatal cell membranes and plasma IL-13. There was no difference in levels of IgE and the other cytokines measured. CONCLUSIONS: This study provides preliminary evidence that increasing neonatal n-3 PUFA levels with maternal dietary supplementation can achieve subtle modification of neonatal cytokine levels. Further assessment of immune function and clinical follow-up of these infants will help determine if there are any significant effects on postnatal immune development and expression of allergic disease.     

FADS gene variants modulate the effect of dietary fatty acid intake on allergic diseases in children

Background The association between dietary fatty acid intake and the development of atopic diseases has been inconsistent. This could be due to inter‐individual genetic differences in fatty acid metabolism. Objective The aim of the current study was to assess the influence of FADS1 FADS2 gene cluster polymorphisms on the association between dietary fatty acid intake and atopic diseases and allergic sensitization in 10‐year‐old children. Methods The analysis was based on data from two German prospective birth cohort studies. Data on margarine and fatty acid intake were collected using a food frequency questionnaire. Information on atopic diseases was collected using a questionnaire completed by the parents. Specific IgE against common food and inhalant allergens were measured. Six variants of the FADS1 FADS2 gene cluster (rs174545, rs174546, rs174556, rs174561, rs174575 and rs3834458) were tested. Logistic regression modelling, adjusted for gender, age, maternal education level and study centre, was used to analyse the association between fatty acid intake and atopic diseases stratified by genotype. Results No significant association was found between the six FADS single nucleotide polymorphisms (SNPs) and allergic diseases or atopic sensitization. The total n‐3/total n‐6 ratio was positive associated with an increased risk of hayfever in homozygous major allele carriers ranging from an adjusted odds ratios of 1.25 (95%‐CI: 1.00–1.57) to 1.31 (95%‐CI: 1.01–1.69) across the six tested SNPs although this association was not significant anymore after correcting for multiple testing. Daily margarine intake was significantly associated with asthma [1.17 (1.03–1.34) to 1.22 (1.06–1.40)] in individuals carrying the homozygous major allele. This association was also significant after correcting for multiple testing. Conclusions & Clinical Relevance The association between dietary intake of fatty acids and allergic diseases might be modulated by FADS gene variants in children. Cite this as: M. Standl, S. Sausenthaler, E. Lattka, S. Koletzko, C.‐P. Bauer, H.‐E. Wichmann, A. von Berg, D. Berdel, U. Krämer, B. Schaaf, S. Röder, O. Herbarth, N. Klopp, B. Koletzko and J. Heinrich for the GINIplus and LISAplus Study Group, Clinical & Experimental Allergy, 2011 (41) 1757–1766.     

Mothers of very low birth weight infants have less atopy than mothers of full-term infants

BACKGROUND: Studies on the pregnancy outcome of asthmatic mothers have suggested an increased rate of preterm deliveries. In contrast, our earlier study suggests that mothers of very low birth weight (VLBW) (<1500 g) infants less frequently had atopy than did mothers of full-term infants. METHODS: We inquired about symptoms of atopy and doctor-diagnosed atopy in parents of 370 infants of VLBW (<1500 g) and 544 parents of full-term infants. Odds ratios for atopic symptoms and diagnosed atopy were calculated, and groups were compared with a trend test. RESULTS: Mothers of preterm infants of birth weight (BW) <1000 g significantly less often had physician-diagnosed allergic rhinitis (AR) (P=0.02). Among all the mothers, a trend test showed that maternal AR was significantly (P=0.03) higher in parallel with a higher infant BW. Fathers of infants with different BWs showed no differences in prevalence of atopic symptoms. CONCLUSION: We thus infer that maternal balance between T-helper type 1 (Th1) and Th2 cells, shifted towards Th2 in those with AR, may have a favourable effect on maintenance of pregnancy before gestational week 30.