Prevention Of Atopy Research Articles

Immunoglobulin A (IgA) Is a Natural Ligand of Hepatitis A Virus Cellular Receptor 1 (HAVCR1), and the Association of IgA with HAVCR1 Enhances Virus-Receptor Interactions

The hepatitis A virus cellular receptor 1 (HAVCR1/TIM1), a member of the T-cell immunoglobulin mucin (TIM) family, is an important atopy susceptibility gene in humans. The exact natural function of HAVCR1/TIM1 and the inverse association between HAV infection and prevention of atopy are not well understood. To identify natural ligands of human HAVCR1/TIM1, we used an expression cloning strategy based on the binding of dog cells transfected with a human lymph node cDNA library to a HAVCR1/TIM1 Fc fusion protein. The transfected cells that bound to the human HAVCR1/TIM1 Fc contained cDNA of human immunoglobulin alpha 1 heavy (Igalpha1) and lambda light (Iglambda) chain and secreted human IgA1lambda antibody that bound to the cell surface. Cotransfection of the isolated Igalpha1 and Iglambda cDNAs to naïve dog cells resulted in the secretion of IgA1lambda that bound to HAVCR1/TIM1 Fc but not to a poliovirus receptor Fc fusion protein in a capture enzyme-linked immunosorbent assay. The interaction of HAVCR1/TIM1 with IgA was inhibited by monoclonal antibodies (MAbs) against Igalpha1 and Iglambda, excess IgA1lambda, or anti-HAVCR1/TIM1 MAb. IgA did not inhibit HAV infection of African green monkey cells, suggesting that the IgA and the virus binding sites are in different epitopes on HAVCR1/TIM1. IgA enhanced significantly the neutralization of HAV by HAVCR1/TIM1 Fc. Our results indicate that IgA1lambda is a specific ligand of HAVCR1/TIM1 and that their association has a synergistic effect in virus-receptor interactions.

Effect of Partially Hydrolyzed Formula in Atopy Prevention of High Risk Infants Identified by Atopic Risk Score

Effect of Partially Hydrolyzed Formula in Atopy Prevention of High Risk Infants Identified by Atopic Risk Score

Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe

Dietary interventions as a means for atopy prevention attract great interest. Some studies in rural environments claimed an inverse association between consumption of farm-produced dairy products and the prevalence of allergic diseases, but current evidence is controversial. To investigate whether consumption of farm-produced products is associated with a lower prevalence of asthma and allergy when compared with shop-purchased products. Cross sectional multi-centre study (PARSIFAL) including 14,893 children aged 5-13 years from five European countries (2823 from farm families and 4606 attending Steiner Schools as well as 5440 farm reference and 2024 Steiner reference children). A detailed questionnaire including a dietary component was completed and allergen-specific IgE was measured in serum. Farm milk consumption ever in life showed a statistically significant inverse association with asthma: covariate adjusted odds ratio (aOR) 0.74 [95% confidence interval (CI) 0.61-0.88], rhinoconjunctivitis: aOR 0.56 (0.43-0.73) and sensitization to pollen and the food mix fx5 (cut-off level of >or=3.5 kU/L): aOR 0.67 (0.47-0.96) and aOR 0.42 (0.19-0.92), respectively, and sensitization to horse dander: aOR 0.50 (95% CI 0.28-0.87). The associations were observed in all four subpopulations and independent of farm-related co-exposures. Other farm-produced products were not independently related to any allergy-related health outcome. Our results indicate that consumption of farm milk may offer protection against asthma and allergy. A deepened understanding of the relevant protective components of farm milk and a better insight into the biological mechanisms underlying this association are warranted as a basis for the development of a safe product for prevention.

Probiotics in the atopic march: highlights and new insights

The frequent development of allergic respiratory diseases in patients with histories of atopic dermatitis (AD) in early childhood has been known for a long time. At school age, AD has been associated with an increased risk of asthma, and was thus regarded as one of the first steps in a successive “atopic march” leading from AD to asthma. Probiotics are cultures of potentially beneficial bacteria that positively affect the host by enhancing the microbial balance and therefore restore the normal intestinal permeability and gut microecology. They also improve the intestine's immunological barrier function and reduce the generation of proinflammatory cytokines characteristic of allergic inflammation. In clinical trials probiotics appear to be useful for the treatment of various clinical conditions such as food allergy, AD and allergic rhinitis, and in primary prevention of atopy. We can hypothesize that it may be possible, in the future, to use probiotics in primary prevention of asthma.

Risk Factors for Atopic Dermatitis in New Zealand Children at 3.5 Years of Age

Purpose of the Study. To examine factors associated with a diagnosis of atopic dermatitis (AD) at 3.5 years of age, especially factors implicated by the hygiene hypothesis. Study Population. There were 871 children enrolled at birth for the Auckland Birthweight Collaborative study, 744 (85.4%) participated at 1 year, and 550 (63.2%) at 3.5 years. AD was diagnosed in 87 (15.8%) children at 3.5 years. Methods. The Auckland Birthweight Collaborative study is a case-control study of risk factors for small-for-gestational-age infants. Case subjects were born at term with birth weight at ≤10th percentile; controls were appropriate for gestational age, with birth weight >10th percentile. AD was defined as the presence of an itchy rash in the past 12 months with ≥3 of the following by history: flexural involvement, generally dry skin, atopic disease in parents or siblings, or visible flexural dermatitis by photographic protocol. Results. The prevalence of AD did not differ by birth weight. AD at 3.5 years was associated with raised serum immunoglobulin E, wheezing, asthma, rash, or eczema at 1 year. In multivariate analysis adjusting for parental atopy and breastfeeding, AD at 3.5 years was associated with atopic disease in the parents (maternal atopy only [adjusted odds ratio (aOR): 3.83; 95% confidence interval (CI): 1.2–12.2]; paternal atopy only [aOR: 3.6; 95% CI: 1.09–11.75]; both parents atopic [aOR: 6.12; 95% CI: 2.0–18.5]). There was a higher risk of AD with longer duration of breastfeeding (<6 months [aOR: 6.13; 95% CI: 1.5–25.9]; >6 months [aOR: 9.70; 95% CI: 2.5–38.2]) compared with never breastfeeding. AD at 3.5 years had a negative association with cat ownership (aOR: 0.5; 95% CI: 0.2–0.97) but was not associated with owning a dog at 3.5 years, having pets at 1 year, or with older siblings. AD at 3.5 years was not associated with gender, socioeconomic status, maternal smoking, parity, mold exposure, immunizations, BMI, or antibiotic use in the first year of life. Conclusions. A personal and a parental history of atopic disease are risk factors for AD at 3.5 years. Duration of breastfeeding was associated with an increased risk of AD. No association was found with factors implicated by the hygiene hypothesis. Reviewer Comments. This is one of many studies to look at various risk factors for atopy, here focusing on AD. Similar to other studies, the authors show that family history of atopy is a risk factor for AD. However, compared with other studies, the authors did not find any association with gender, socioeconomic status, environmental risks, or BMI. This discrepancy is probably attributable to differences in populations and different environmental factors. The data on atopy prevention by breastfeeding remain unclear and may be affected by reverse causation (breastfeeding longer in response to observing AD); although this is one of several negative studies, meta-analyses of multiple studies typically show a prevention effect.

Prolonged exclusive breastfeeding is associated with increased atopic dermatitis: a prospective follow‐up study of unselected healthy newborns from birth to age 20 years

Exclusive breastfeeding for the first 6 months is recommended by the World Health Organization and considered allergy preventive. However, it is not known whether prolonging exclusive breastfeeding for over 6 months provides further benefit in allergy prevention. The aim of this prospective 20-year follow-up study was to find out whether the allergy protective effect can be enhanced by prolonging strictly exclusive breastfeeding for > or =9 months of age. A total of 200 unselected healthy newborns were enrolled in the study. Their mothers were encouraged to maintain exclusive breastfeeding for as long as possible. The number of infants on strictly exclusive breastfeeding was 167 at 2, 116 at 6, 36 at 9 and 7 at 12 months of age. Of the 200 infants, 42% had a family history of allergy. The children were re-assessed at ages 5 (n=163), 11 (n=150) and 20 years (n=164) with clinical examination, skin prick testing, and parental and personal structured interviews. Exclusive breastfeeding prolonged for > or =9 months was associated with atopic dermatitis (P=0.002) and symptoms of food hypersensitivity (P=0.02) at age 5 years, and with symptoms of food hypersensitivity at age 11 years (P=0.01), in children with a family history of allergy. Prolonging strictly exclusive breastfeeding for > or =9 months was not helpful in atopy prevention, instead, it was associated with increased atopic dermatitis and food hypersensitivity symptoms in childhood.

Primary Prevention by Nutrition Intervention in Infancy and Childhood

Foreword Contributors Introduction Infant Nutrition and Primary Prevention: Current and Future Perspectives: Lucas, A. Sampson, H.A. Reduction in Risk of Cardiovascular Diseases Nutritional Interventions in Infancy and Childhood for Prevention of Atherosclerosis and the Metabolic Syndrome: Singhal, A. Childhood Obesity: Potential Mechanisms for the Development of an Epidemic: Maffeis, C. Prenatal and Postnatal Development of Obesity: Primary Prevention Trials and Observational Studies: Kroke, A. Childhood Diabetes Mellitus with Emphasis on Perinatal Factors: Laron, Z. Prevention of Atopy, Allergy and Infectious Diseases The Gut Microbiota and Potential Health Effects of Intervention: Bjorksten, B. The Relationship of Breastfeeding to the Development of Atopic Disorders: Zeiger, R.S. Friedman, N.J. Prevention of Atopy and Allergic Disease: Type of Infant Formula: Sampson, H.A. Introduction of Solid Foods: von Berg, A. Other Potentially Preventable Diseases Osteoporosis: Is Primary Prevention Possible? Fewtrell, M.S. Nutrition and Cancer Prevention: Targets, Strategies, and the Importance of Early Life Interventions: Hursting, S.D. Cantwell, M.M. Sansbury, L.B. Forman, M.R. LC-PUFAs: Influence on Multiple Health Outcome Long-Chain Polyunsaturated Fatty Acids in Early Life: Effects on Multiple Health Outcomes. A Critical Review of Current Status, Gaps and Knowledge: Fewtrell, M.S. Perinatal PUFA Intake Affects Leptin and Oral Tolerance in Neonatal Rats and Possibly Immunoreactivity in Intrauterine Growth Retardation in Man: Hanson, L.A. Korotkova, M. Hahn-Zoric, M. Zaman, S. Malik, A. Ashraf, R. Amu, S. Padyukov, L. Telemo, E. Strandvik, B. The Crucial Role of Dietary n-6 Polyunsaturated Fatty Acids in Excessive Adipose Tissue Development: Relationship to Childhood Obesity: Massiera, F. Guesnet, P. Ailhaud, G. Impact of Nutrition on Health Mechanism Aspects -Omics for Prevention: Gene, Protein and Metabolite Profiling to Better Understand Individual Disposition to Disease: Affolter, M. Bergonzelli, G.E. Blaser, K. Blum-Sperisen, S. Corthesy, B. Fay, L.B. Garcia-Rodenas, C. Lopes, L.V. Marvin-Guy, L. Mercenier, A. Mutch, D.M. Panchaud, A. Raymond, F. Schmidt-Weber, C. Schumann, A. Spertini, F. Williamson, G. Kussmann, M. Concluding Remarks.

Intestinal microbiota and its effect on the immune system — A nested case-cohort study on prevention of atopy among small children in Trondheim: The IMPACT study

Background In the past 20–30 years, the prevalence of atopic diseases, particularly among children in the Western world, has increased. It has been suggested that Western lifestyle may have reduced the overall exposure to microbial stimulation early in life. The role of the gut flora in this connection has been studied, but prospective studies are in demand. Within the frame of a comprehensive controlled prospective primary prevention study of atopy and allergic diseases with the aim to reduce the incidence of atopy and allergic diseases among children from birth to six years, a nested case-cohort study is established, “The IMPACT study”. Aim The aim of “The IMPACT study” is to study the impact of gut microbiota composition on cytokine profile development, and on development of atopic disease. Design Information on risk factors and on disease, together with biological specimens, will be collected prospectively, and analysed in a nested case-cohort design. Method 720 pregnant women are recruited from the control-cohort in the PACT study. The composition of the infant gut microbiota is analysed in stool samples from all children with atopic disease, and randomly selected children sensitized and not sensitized at age 2, at 4, 7, 10 days after birth, and at age 4, 12 and 24 months. 16S rDNA hybridisation technique will be used to specify and quantify the microbial composition in faeces. Cord blood from the same children and venous blood at age 10 days, 4, 12 and 24 months are collected to study the cytokine profile at different ages, in relation to microbial stimulation. Peripheral blood mononuclear cells (PBMC) are stored in liquid nitrogen, and faeces are stored at − 80 °C. Atopic children will be identified by questionnaire, and the diagnosis confirmed by paediatric examination at age 2 years.

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Hydrolysed milk in preterm infants: An open problem

To review knowledge about the role, indications and nutritional adequacy of protein hydrolysate formulas (HF) in the preterm newborn. A review of the available literature was carried out. No data support the use of HF for atopy prevention. HF could have a positive role in the early feeding of very-low-birthweight infants, but several concerns exist about their nutritional adequacy. Further investigations addressing protein and mineral metabolism as well as long-term effects, including neurodevelopment, are needed.

Atopy and Asthma Prevention: New Paradigms?

Atopy and Asthma Prevention: New Paradigms?

The role of probiotics in the clinical management of food allergy and atopic dermatitis.

The probiotics are cultures of potentially beneficial bacteria that positively affects host by enhancing the microbial balance and therefore restore the normal intestinal permeability and gut microecology, improve the intestine's immunologic barrier function and reduce the generation of proinflammatory cycochines characteristics of allergic inflammation. The authors made a survey of the most relevant studies concerning the use of probiotics in the food allergy, atopic dermatitis, and in primary prevention of atopy. On the basis of these trials probiotic therapy alleviates allergic inflammation as demonstrated by the control of clinical symptoms and the reduction of local and systemic inflammatory markers.

Allergen avoidance and prevention of atopy.

Recent increases in the prevalence of atopic disease argue strongly that environmental factors operating primarily in early life play a significant role. Exposure to food and inhalant allergens early in life may constitute a risk factor amenable to manipulation. Recent observational and interventional studies have produced conflicting data regarding the effectiveness of allergen avoidance in primary and secondary prevention of atopic diseases. Exclusive breast feeding for 4-6 months may protect against the development of allergic diseases in early childhood and remains good advice. Convincing proof for the preventive effects of the delayed introduction of solid foods and hydrolyzed formula in formula-fed infants is lacking. There is some evidence to support a preventive effect of house dust mite allergen avoidance before sensitization occurs. The effect of exposure to animal allergen is uncertain, with some studies showing an increase in sensitization while others suggest a protective effect. Therefore, no evidence-based advice can be given at this stage regarding allergen avoidance measures to be adopted by families with infants at high risk of atopy, except perhaps to breast feed exclusively for at least 4 months. Data regarding the secondary prevention of allergic disease by allergen avoidance were more secure until the publication this year of two randomized controlled trials which suggest that mattress impermeable covers, the main dust mite allergen avoidance measure, may not work. Allergen avoidance, however, should remain an essential part of the management of allergic diseases, even if the benefit of mattress covers is in doubt.

The genetics of CD14 in allergic disease.

The 'hygiene hypothesis' implies that infections in early childhood prevent the development of atopy. Atopy is caused by the interaction of the environment with genetic factors. Therefore, both contacts with microbial products such as endotoxin as well as CD14, a gene involved in the immunological response to endotoxin, are discussed in this review. CD14 is a multifunctional receptor for endotoxin and other bacterial wall components. Membrane-bound CD14 is expressed on monocytes and macrophages. It forms a complex with Toll-like receptor 4. Genetic studies have shown an association of variants in the CD14 gene with the prevention of (and severity of) atopy. However, phenotype definitions and the allele that showed association differed between studies. In addition, the presence of endotoxin in house dust appears to be inversely related to atopy in different studies. It can be hypothesized that different levels of endotoxin exposure could interact with specific CD14 variants in the prevention of atopy. If confirmed in prospective cohort studies, this might represent an important gene by environmental interaction in the development of atopy. This could possibly open ways for the primary prevention of atopy.

Risk factors for atopic dermatitis in infancy: are we closer to effective primary atopy prevention?

Risk factors for atopic dermatitis in infancy: are we closer to effective primary atopy prevention?

Dietary prevention of allergy, atopy, and allergic diseases

Dietary prevention of allergy, atopy, and allergic diseases

Probiotics in the Management and Prevention of Atopy

Probiotics in the Management and Prevention of Atopy

Probiotics in the management and prevention of atopy.

Probiotics in the management and prevention of atopy.

Hyper immunoglobulin E response in mice with monoclonal populations of B and T lymphocytes.

A key event in the pathogenesis of allergies is the production of antibodies of the immunoglobulin (Ig)E class. In normal individuals the levels of IgE are tightly regulated, as illustrated by the low serum IgE concentration. In addition, multiple immunizations are usually required to generate detectable IgE responses in normal experimental animals. To define the parameters that regulate IgE production in vivo, we generated mice bearing monoclonal populations of B and T lymphocytes specific for influenza virus hemagglutinin (HA) and chicken ovalbumin (OVA), respectively. A single immunization of the monoclonal mice with the cross-linked OVA-HA antigen led to serum IgE levels that reached 30-200 microg/ml. This unusually high IgE response was prevented by the infusion of regulatory alpha/beta CD4(+) T cells belonging to both CD25(+) and CD25(-) subpopulations. The regulation by the infused T cells impeded the development of fully competent OVA-specific effector/memory Th2 lymphocytes without inhibiting the initial proliferative response of T cells or promoting activation-induced cell death. Our results indicate that hyper IgE responses do not occur in normal individuals due to the presence of regulatory T cells, and imply that the induction of regulatory CD4(+) T cells could be used for the prevention of atopy.

The Childhood Asthma Prevention Study (CAPS): Design and Research Protocol of a Randomized Trial for the Primary Prevention of Asthma

The Childhood Asthma Prevention Study is a randomized controlled trial to measure whether the incidence of atopy and asthma can be reduced by house dust mite allergen reduction, a diet supplemented with omega-3 fatty acids, or a combination of both interventions. Six hundred and sixteen pregnant women whose unborn children were at high risk of developing asthma because of a family history were randomized prenatally. Study groups are as follows: Group A (placebo diet intervention, no house dust mite reduction), Group B (placebo diet intervention, active house dust mite reduction), Group C (active diet intervention, no house dust mite reduction), and Group D (active diet intervention, active house dust mite reduction). The house dust mite reduction intervention comprises use of physical and chemical methods to reduce allergen contact. The dietary intervention comprises use of a daily oil supplement from 6 months or at onset of bottle-feeding, and use of margarine and cooking oils based on sunflower or canola oils to increase omega-3 dietary intake. Data is collected quarterly until the infant is 1 year old and then half yearly until age 5 years. Questionnaires are used to collect respiratory illness history and information about diet and home environment. Dust is collected from the child's bed and bedroom and playroom floors. Blinded assessments are conducted at 18 months, 3 years, and 5 years. Skin prick tests to common allergens, blood tests, and detailed illness, medication use, and vaccination histories are collected. Primary outcomes will be the development of allergic sensitization and the presence and severity of asthma. This study is designed to measure the effectiveness of allergen reduction and dietary supplementation, both separately and in combination, for the primary prevention of atopy and asthma. The results of this study may have important implications for public health policies to reduce the incidence of childhood asthma. Control Clin Trials 2001;22:333–354