Potential links between the emerging risk factors for food allergy and vitamin D status.

A variety of hypotheses have been proposed to explain the recently described increase in food allergy among children living in developed countries. In this study, we summarize the emerging risk factors for IgE-mediated food allergy in early life, and then review the evidence for and against an association between low vitamin status (VDS) and food allergy. We consider whether each of the epidemiological variables that have been associated with food allergy may also be associated with VDS; and argue that future studies must adequately account for the potential relationships between risk factors for food allergy and VDS, and must also discriminate between vitamin D derived by sun exposure, diet and oral supplementation.

The role of self-injury in the organisation of behaviour.

BACKGROUND: Self-injuring acts are among the most dramatic behaviours exhibited by human beings. There is no known single cause and there is no universally agreed upon treatment. Sophisticated sequential and temporal analysis of behaviour has provided alternative descriptions of self-injury that provide new insights into its initiation and maintenance. METHOD: Forty hours of observations for each of 32 participants were collected in a contiguous 2-week period. Twenty categories of behavioural and environmental events were recorded electronically that captured the precise time each observation occurred. Temporal behavioural/environmental patterns associated with self-injurious events were revealed with a method (t-patterns; THEME) for detecting non-linear, real-time patterns. RESULTS: Results indicated that acts of self-injury contributed both to more patterns and to more complex patterns. Moreover, self-injury left its imprint on the organisation of behaviour even when counts of self-injury were expelled from the continuous record. CONCLUSIONS: Behaviour of participants was organised in a more diverse array of patterns when self-injurious behaviour was present. Self-injuring acts may function as singular points, increasing coherence within self-organising patterns of behaviour.

Psychometric comparison of standard and computerized administration of the Alzheimer's Disease Assessment Scale: Cognitive Subscale (ADASCog).

BACKGROUND: The Alzheimer's Disease Assessment Scale ­ Cognitive Subscale (ADAS-Cog) has become the de facto gold standard for assessing the efficacy of anti-dementia treatments. However, manual administration of the ADAS-Cog is subject to procedural inconsistencies, including scoring and transcription errors, which can introduce unwanted variance and compromise data quality within and across sites and trials. To address such concerns, a computerized version was developed that integrates, rather than replaces, the examiner, standardizes administration, and uses electronic data capture at the point of patient contact. The examiner can control administration and pacing, pause or repeat digitized instructions, score verbal report and overt behavioral performance, and freely interact with the subject. PURPOSE: To conduct psychometric comparisons of traditional, paper-based administration of the standard ADAS-Cog (sADAS) with examiner- assisted administration of the computerized ADAS-Cog (cADAS). METHODS: Eighty-eight patients (39M; 49F) with mild to moderate Alzheimer's disease were tested on three occasions with each version over a period of one year with one month between paired visits. RESULTS: Intraclass Correlation Coefficients (ICC) comparisons between sADAS and cADAS were significant for total score (ICC=0.96) and all subscores (ICCs ranged 0.78-0.93), with no significant differences on paired t-tests. The mean ICCs across cADAS scores for test-retest reliability for short-term (mean ICC=0.96) and long-term (mean ICC=0.91) comparisons were significantly higher than across sADAS scores (mean ICCs were 0.87 and 0.84, respectively). CONCLUSIONS: These results indicate that examiner-assisted, computerized administration is equivalent to traditional, paper-based administration, and shows significantly greater test-retest reliability.

Maternal antenatal peanut consumption and peanut and rye sensitization in the offspring at adolescence.

BACKGROUND: There is considerable controversy whether maternal peanut ingestion during pregnancy might influence sensitization in later life. Objective To examine whether maternal peanut ingestion during pregnancy might increase sensitization in the offspring. METHODS: A population-based longitudinal cohort study with 16 years follow-up was conducted (N=373). Subjects were recruited at birth as part of an infant health study. Maternal antenatal peanut consumption was documented at birth and peanut and rye sensitization were determined by measurement of serum-specific IgE at age 16. RESULTS: Peanut sensitization was common (14%). In the entire cohort (n=310), there was no association between antenatal peanut ingestion and peanut sensitization (P=0.17). However, there was a strong association between antenatal peanut ingestion and decreased risk of rye sensitization and peanut sensitization in those (n=201) without a family history (FH) of asthma (Rye OR 0.30, 95% CI 0.14-0.63, P=0.001 and Peanut OR 0.18, 95% CI 0.04-0.78, P=0.02). There was an increased risk of rye sensitization in those (n=108) with a FH of asthma and antenatal peanut ingestion (Rye OR 2.69, 95% CI 1.11-6.51 P=0.03). It was considered that these sensitizations were likely to be related to the presence of IgE antibodies to cross-reacting carbohydrate epitopes common to rye and peanut allergens. CONCLUSIONS AND CLINICAL RELEVANCE: Antenatal peanut ingestion may influence the development of IgE antibody to cross-reacting carbohydrate epitopes in later life. Genetic factors may modify this association.

Food allergy: is strict avoidance the only answer?

It is an immunological paradigm that avoidance of food allergen may reduce the risk or prevent immunological reactions and conversely that a greater exposure increases the magnitude of the immune response. Consequently, food allergen avoidance has been recommended to reduce the risk of sensitization in infants and to prevent clinical reactions in children with positive skin prick tests (SPT). In the latter setting, it is hoped that avoidance may either promote or at least not retard the development of tolerance. Animal studies, however, have demonstrated that tolerance to food allergens may be induced by either large (high zone tolerance) or small (low zone tolerance) doses, whereas doses in between may actually stimulate immune responses. In this review, we discuss whether strict allergen avoidance is always the most appropriate strategy for preventing or managing IgE-mediated food allergy.

Rice: a common and severe cause of food protein-induced enterocolitis syndrome.

OBJECTIVE: To examine and compare the characteristics of food protein-induced enterocolitis syndrome (FPIES) caused by rice and cow's milk/soy. DESIGN: Retrospective study of children presenting with FPIES to the Children's Hospital at Westmead, NSW, Australia, over a 16-year period. RESULTS: There were 14 children with 26 episodes of rice FPIES compared with 17 children with 30 episodes of cow's milk (n = 10) or soy (n = 7) FPIES. Children with rice FPIES were more likely to have FPIES caused by other foods (36%) than children with FPIES caused by cow's milk/soy (0%). Rice caused more episodes of FPIES before a correct diagnosis was made (median 4 (range 1-4) vs median 2 (range 1-4)) and triggered more severe reactions with higher rates of intravenous fluid resuscitation (42% vs 17%) than reactions caused by cow's milk/soy. CONCLUSIONS: This study highlights the emerging importance of rice, a food commonly thought to be "hypoallergenic", as a significant trigger of FPIES. Paediatricians should be aware that rice not only has the potential to cause FPIES, but that such reactions tend be more severe than those caused by cow's milk/soy.

Adherence to allergy prevention recommendations in children with a family history of asthma.

Allergen avoidance has been a major component of most programs for primary prevention of asthma and allergic diseases in childhood. As a part of the Childhood Asthma Prevention Study, families were provided with written and oral information on measures considered to be helpful in the primary prevention of allergic disease in high-risk infants. Dietary measures included advice to breastfeed for 6 months or longer, to delay the introduction of solid foods until after the infant turned 6 months of age, and to delay giving allergenic foods (egg and peanut butter) until after 12 months of age. In the active group of the randomized controlled trial aimed at reducing house dust mite (HDM) allergen levels, parents were advised to use an HDM-impermeable study mattress cover and an acaricide, to avoid sheep skins, and not to use a pillow before 12 months of age. Families received regular visits from the research nurses at 1, 3, 6, 9 and 12 months and phone calls every 6 wk. Only 43.4% of mothers were breastfeeding by 6 months and less than 20% by 12 months. The introduction of solid foods before 6 months was common, 26% by 3 months and 96% by 6 months. Adherence to infant-feeding recommendations was significantly greater in women over 30 yr of age, women who did not smoke during pregnancy, and women who had a tertiary education. Adherence to HDM reduction measures was greater than to those for infant feeding. The presence of symptoms in the form of an itchy rash by 4 wk did not significantly increase adherence. Complete adherence to infant-feeding recommendations in this intervention study of high-risk infants was low despite the provision of written information and reinforcement at home visits. In considering allergy prevention advice offered during clinical care, the likelihood of adherence is a factor which needs to be evaluated in assessing any potential benefits of allergy prevention regimens.

Early predictors for developing allergic disease and asthma: examining separate steps in the 'allergic march'.

BACKGROUND: Sensitization and symptoms of allergic disease are strongly correlated, but little is known about the early clinical precursors of the development of allergen sensitization in childhood. The aim of this study was to identify these predictors, and to examine separately the effect of early sensitization on subsequent wheeze, asthma, rhinitis and eczema. METHODS: In the Childhood Asthma Prevention Study, children with a family history of asthma were assessed for allergen sensitization, total serum IgE, wheeze, asthma, eczema and rhinitis at ages 18 months and 5 years. To examine predictors, at 18 months, for subsequent sensitization, children who were non-sensitized at 18 months and had data on sensitization at 5 years were investigated, n=375. To examine the predictors, at age 18 months, of subsequent onset of symptoms, children who did not have wheeze, asthma, eczema or rhinitis at 18 months were followed-up at 5 years, n=177. RESULTS: Among children who were non-sensitized at age 18 months, the presence of eczema [adjusted relative risk (aRR), 1.67, 95% confidence interval (CI) 1.20-2.33], but not wheeze, asthma or rhinitis, was an independent predictor of the onset of sensitization by age 5 years. Among children who were asymptomatic at age 18 months, sensitization to any allergen at 18 months was an independent predictor for the presence of wheeze (aRR 2.41, 95% CI 1.28-4.55), asthma (aRR 4.66, 95% CI 1.88-11.54) and rhinitis (aRR 1.77, 95% CI 1.08-2.90), but not for the development of eczema (aRR 0.78, 95% CI 0.23-2.64) at 5 years. CONCLUSION: In non-sensitized children, eczema, but not wheeze, asthma or rhinitis is a predictor for subsequent development of sensitization. This suggests that early childhood eczema, rather than wheeze and rhinitis, may promote subsequent allergen sensitization and raises the possibility that early management of eczema may reduce the prevalence of sensitization in children.

Do immune responses to inhaled skin flakes modulate the expression of allergic disease?

We examine the nature of the immune responses to inhaled skin particles and query whether early exposure could play a role in providing protection against the development of allergic disease. Currently, the main hypothesis used to explain environmental modulation of allergic diseases, the 'hygiene hypothesis', is linked exclusively to microbial exposures acting upon the innate immune system. However, many of the exposures sustaining this hypothesis also involve co-exposure to skin flakes from humans or animals. Such skin flakes contain a complex mixture of antigens, glycolipids and small peptides that may induce immune responses. Should these responses prove relevant to the modulation of allergic diseases, it provides new opportunities to better understand the epidemic of allergic disease and to develop new interventions for its prevention.

The association between infant feeding practices and subsequent atopy among children with a family history of asthma.

BACKGROUND: Although longer duration of breastfeeding and later introduction of solid foods are both recommended for the prevention of asthma and allergic disease, evidence to support these recommendations is controversial. OBJECTIVE: To examine the relation between infant feeding practices and the risk of asthma and allergic disease at age 5 years. METHODS: A cohort of children with a family history of asthma in Sydney, Australia, was followed from birth to age 5 years. Data on infant feeding practices and on early manifestations of eczema were collected prospectively. The presence of eczema, asthma and atopy (positive allergen skin prick tests) were determined at age 5 years. RESULTS: In 516 children evaluated at age 5 years, there was no significant association between the duration of breastfeeding or timing of introduction of solid foods and protection against asthma or other allergic disease, after adjustment for confounding factors. However, breastfeeding for 6 months or more and introduction of solid foods after 3 months were both associated with an increased risk of atopy at age 5 years (P=0.02 and 0.01, respectively). There was no significant association between the presence of eczema at 4 weeks and at 3 months and continued breastfeeding beyond those times. CONCLUSION: Longer duration of breastfeeding and later introduction of solid foods did not prevent the onset of asthma, eczema or atopy by age 5 years.

EpiPen epidemic: suggestions for rational prescribing in childhood food allergy.

There has been a marked increase in community concerns of the risk of food induced anaphylaxis in children and a consequent increase in the provision of the self or carer injectable epinephrine (EpiPen) (CSL Ltd, Parkville, Victoria, Australia)). The Australian use of EpiPens in children under 10 years has increased by 300% over 5 years with a crude rate of EpiPen provision of 1 per 544 Australian children aged under 10 years. However, the risk of a fatal reaction to food, particularly in preschool children, is remote (in Australia, an estimated one fatality in 30 years in the under 5-year-old population and two deaths in 10 years in the entire child population). It is therefore important to provide a perspective on the risk of death from food induced anaphylactic to parents and carers in view of the anxiety generated on this issue. The indications for provision of an EpiPen to children are not well defined. Six risk factors, which can be considered in evaluating the risk of a life-threatening reaction (age over 5 years; a history of respiratory tract involvement with the initial or subsequent reactions; a history of asthma requiring preventer medication; peanut or tree nut sensitivity; reactions induced by traces or small amounts of allergen; a strongly positive skin prick test) are proposed. It is suggested that the greater the number that are positive, the lower the threshold for provision of an EpiPen. In addition, instruction in EpiPen administration and the provision of both a clear and simple anaphylaxis action plan and a rational perspective on the remote risk of death is just as important as the provision of the device itself.

Age-related T cell responses to allergens in childhood.

BACKGROUND: T cell priming, as determined by allergen-induced proliferative responses, is believed to occur principally in early childhood in both atopic and non-atopic infants under the influence of multiple factors including environmental allergen exposure. It is considered that T cell priming with expansion of Th2 cells is a crucial factor in the development of atopic disease. OBJECTIVE: To examine T cell priming to commonly encountered allergens in childhood in relation to age. METHODS: In a cross-sectional study T cell proliferation in relation to age was examined for three common allergens, ovalbumin (OVA), house dust mite (HDM) and rye grass pollen (RYE), in atopic and non-atopic children. The effect of age on Th1 (IFN-gamma) and Th2 (IL-5 and IL-13) cytokine production in response to these allergens was investigated to examine the possibility of immune deviation with time. RESULTS: A significant increase in T cell proliferation with age was observed with RYE among atopic children only. However, the same was not observed with the two other allergens studied (i.e. OVA and HDM). In addition, RYE-induced (but not HDM or OVA) cytokine production showed an increased Th2 deviation with age as reflected in the increasing IL-5/IFN-gamma and IL-13/IFN-gamma ratios only among the atopic subjects with rye grass pollen sensitivity. CONCLUSION: These findings suggest that grass pollen sensitivity in childhood is accompanied by a progressive accumulation of allergen-primed T cells and progressive deviation of the allergen-induced cytokine response towards a Th2 response in atopic subjects throughout childhood.

Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease.

BACKGROUND: Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen-induced T cell responses can provide information on cytokine production by allergen-reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non-specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN-gamma responses to allergens in atopic subjects. OBJECTIVE: To examine childhood polyclonal and allergen-induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease. METHODS: PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non-atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic). RESULTS: Atopic children had significantly reduced IFN-gamma and increased IL-4 and IL-5 but not IL13 production to SEB superantigen stimulation when compared with non-atopic children. HDM and RYE allergens stimulated significantly increased IFN-gamma, IL-5 and IL-13, while OVA stimulated significantly increased IFN-gamma production in atopic children. CONCLUSION: We show that a polyclonal stimulus induces a reduced Th1 (IFN-gamma) and increased Th2 (IL-4 and IL-5) cytokine pattern. In contrast, the allergen-induced cytokine responses in atopic children were associated with both increased Th1 (INF-gamma) and Th2 (IL-5 and IL-13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to allergens exists concomitantly with a decreased Th1 response to a polyclonal stimulus in atopic children.

Polyclonal and allergen-induced cytokine responses in children with elevated immunoglobulin E but no atopic disease.

BACKGROUND: Reduced Th1 and elevated Th2 cytokine responses are considered to be a principal mechanism in the generation of the inflammation leading to the manifestations of atopic disease in the skin of atopic dermatitis and in the airways of asthma. If reduced Th1 and elevated Th2 responses are principal determinants of the manifestation of atopic disease it might be expected that subjects with established disease would exhibit differences in their cytokine profiles as compared with atopic patients without clinical disease. OBJECTIVE: To determine whether asymptomatic atopic children exhibit a cytokine imbalance similar to that seen in patients with established atopic disease or if they behave like non-atopic controls. Cytokine responses in a group of children with elevated IgE but no clinical manifestations of disease, atopic children with established disease and non-atopic controls were compared. METHODS: We examined allergen-induced (house dust mite, HDM, rye grass pollen and RYE) cytokine responses in parallel with polyclonal (staphylococcal enterotoxin B, SEB) cytokine responses in a group of children with elevated serum IgE levels without current or past evidence of atopic disease (median age 6.6 years) and compared these with a non-atopic control group (median age 6.5 years) and a group of children with atopic disease (median age 6.7 years). RESULTS: Symptomatic atopic children had reduced SEB-induced IFN-gamma and increased SEB-induced IL-4 and IL-5 as compared with non-atopic controls. In contrast, SEB-induced IFN-gamma, IL-4 and IL-5 production in asymptomatic atopics was not significantly different from the non-atopic control subjects. Allergen-induced Th1 (IFN-gamma) and Th2 (IL-5 and IL-13) cytokine production was increased in both symptomatic atopics and asymptomatic atopics when compared with non-atopic controls. CONCLUSION: The defect in polyclonally induced IFN-gamma production was associated with the clinical manifestation of atopic disease but not the atopic stateper se. This suggests that the global reduction in IFN-gamma is the key determinant of the development of overt atopic disease. In contrast, elevated allergen-induced Th2 cytokine responses in children related to the atopic state per se irrespective of the presence of clinical atopic disease.

Ontogeny of T-helper 1 and T-helper 2 cytokine production in childhood.

Compared to adults, infants and young children demonstrate differences in their immune response, indicating that there is maturation or change over time and it is probable that this may be reflected in cytokine production. Cytokine responses have been demonstrated to be different in atopic and non-atopic individuals. In this study, we examined T-helper 1 (Th1) (interferon-gamma [IFN-gamma]) and T-helper 2 (Th2) (interleukin [IL]-4, IL-5, and IL-13) cytokine release from atopic and non-atopic children in response to the staphylococcal superantigen, staphylococcal enterotoxin B (SEB). In non-atopic and atopic children, IFN-gamma, IL-4, and IL-5 release was significantly related to age. Non-atopic children younger than 2 years of age were found to have significantly reduced Th2 (IL-4, IL-5, and IL-13) responses when compared with older, non-atopic children. Atopic children had a reduced IFN-gamma response when compared with non-atopics in early childhood; however, the decreased IFN-gamma response seen in early childhood did not persist after 10 years. These age-related changes in cytokine production provide further support for the concept that cytokine deviations may determine the natural history of atopic disease during early childhood. In addition, the present study indicates the necessity of age-matched controls when examining children for both Th1 (IFN-gamma) and Th2 (IL-4) cytokine release.

Clinical correlates of response to pneumococcal immunization.

OBJECTIVE: The inability to form antibodies to polysaccharide antigens may occur as a part of a more significant immunodeficiency or as an isolated defect. The latter has been reported in some children with recurrent upper and lower respiratory tract infections and evaluation of the responsiveness of such patients to polysaccharide antigens is indicated as part of their assessment. The present study evaluated the pattern of antibody responses of patients immunized with pneumococcal vaccine as part of the investigation of recurrent upper and lower respiratory tract infections to determine if any correlation exists between these responses and clinical presentation. METHODOLOGY: An analysis was performed of antibody responses to pneumococcal serotypes 3, 4 and 6 following immunization with a 23-valent vaccine in 42 children with normal IgG levels who were evaluated for recurrent infections. Antibody responses were assessed in relation to clinical features and the results of other immunological investigations. RESULTS: Of the 42 patients evaluated, 25 (59%) were responders to all serotypes tested. Failure to respond to serotype 3 alone was the least common pattern of non-response. Recurrent pneumonia, but not otitis media with discharge or chronic productive cough, was significantly associated with a lack of response to two or three serotypes. Failure to respond to serotype 3 alone or in combination with other serotypes was associated with more significant immune abnormalities. CONCLUSION: In a selected population of children with recurrent bacterial infections, pneumococcal serotype 3 is a strong immunogen. In this clinical group recurrent pneumonia is associated with a defect in response to multiple pneumococcal serotypes.