Primary sensitisation to inhalant allergens during infancy

The early postnatal period has been identified as a time of increased risk lor primary sensitisation to aeroallergens. The expression of the allergic phenotype is predominantly genetically determined but is influenced by a myriad of environmental factors. The underlying mechanisms for allergic sensitisation to inhalant allergens have been investigated in both humans and experimental animal models. Data from the literature in both these areas are in agreement that the nature of the initial response of the T-cell arm of the immune system to first encounters with an aero-allergen can potentially determine whether allergic sensitisation will occur and be manifest in later life as allergic respiratory disease. The combination of exposure to environmental "risk factors" along with the immaturity of the mucosal component of the infant's immune system may provide a basis for the increased risk of allergic sensitisation in early childhood.     

Immunological basis and management of food allergy

One of the most common allergies in children involves cow's milk, which contains approximately 20 different proteins that can cause allergic reactions. It is well known that children exhibiting signs of cow's milk allergy early in life often go on to develop allergy-related respiratory diseases; thus, management of early sensitisations and symptoms of food allergies is crucial to preventing subsequent allergic complications. Constant allergen exposure and other environmental factors determine whether a sensitised individual will become chronically allergic and experience persistent symptoms. Management of food allergies in children focuses on minimising sensitisation and encouraging immune system maturation through the exposure of children to exogenous stimuli known to prime the immune system. Hypoallergenic molecules or allergen avoidance can also be used to induce tolerance in allergy-prone children. Available evidence suggests that the onset of the sensitisation phase and the degree of inflammation can be modulated by external factors such as nutrition, and guidelines outlining the most effective dietary regimen for the prevention of allergic disease have been published. The underlying mechanisms of tolerance induction and the potential benefits of prophylactic treatment for food allergies remain to be determined.     

What's new in respiratory allergy?

The past 10 years have seen important advances in our understanding of allergic respiratory disease and the targets for potential therapies. Sensitisation and triggering of allergic reactions now appear to be better understood at a clinical and molecular level. Environmental intervention studies are underway attempting to reduce the sensitisation and the triggering of symptoms. Therapeutic intervention studies targeting key pathways in the allergic cascade are also taking place. This paper will assess both of these aspects of respiratory allergy, updating readers on the new evidence in our quest to understand how and when sensitisation occurs and also how we might be able to control triggered reactions using targeted therapeutics against specific elements of the allergic cascade.     

Asthma phenotypes in childhood: lessons from an epidemiological approach

Asthma is a heterogenous disease with variable signs and symptoms among patients. It also presents significant individual variability over time. Recently, some important population-based studies that followed children from birth or from early childhood into adulthood have shed new light on how we understand this syndrome. Three phenotypes have been identified in children with asthma: transient wheezing, non-atopic wheezing of the toddler and pre-school-aged child and IgE-mediated wheezing. Transient wheezing is associated with symptoms that are limited to the first 3-5 years of life, decreased lung function, maternal smoking during pregnancy and exposure to other siblings or children at daycare centres. There is no association between transient wheezing and family history of asthma or allergic sensitisation. Children wheezing with respiratory syncytial virus in the first years of life are more likely to be wheezing up to 13 years of age; this is independent of atopy (non-atopic wheezers) and is not related to atopic sensitisation. Wheezing associated with evidence of allergic sensitisation has been identified as the 'classic' asthma phenotype. Early allergic sensitisation is a major risk factor for persistent asthma.     

Prevention of atopic disorders

Prevention of sensitization, onset of disease and disease exacerbations is a very important aspect of holistic approach towards allergic disorders. The prevalence of allergic or atopic disorders has increased significantly in children over the last three decades. There are significant variations in prevalence between countries and also within many countries. Environmental factors obviously play a major role. Environmental allergens are responsible for sensitisation, disease and exacerbations of disease symptoms. Preventive strategies at each level are important : Primary prevention is to stop the process of sensitisation and secondary prevention to prevent re-exposures or prolonged exposure in those who have become sensitized while tertiary prevention is to reduce or minimise morbidity. Various allergen avoidance measures are discussed, with reference to India so that physicians can incorporate these in the management not only of atopic patients but also as preventive strategy in high risk families.     

Early sensitisation and development of allergic airway disease - risk factors and predictors

The development and phenotypic expression of allergic airway disease depends on a complex interaction between genetic and several environmental factors, such as exposure to food, inhalant allergens and non-specific adjuvant factors (e.g. tobacco smoke, air pollution and infections). The first months of life seem to be a particularly vulnerable period and there is evidence that sensitisation is related to the level of allergen exposure during early life. At present, the combination of atopic heredity and elevated cord-blood IgE seems to result in the best predictive discrimination as regards development of allergic disease at birth. Early sensitisation, cow's milk allergy and atopic eczema are predictors for later development of allergic airway disease.Exposure to indoor allergens, especially house dust mite allergens, is a risk factor for sensitisation and development of asthma later in childhood in high-risk infants and infants with early atopic manifestations.     

Cord blood lymphocyte responses to food antigens for the prediction of allergic disorders.

Proliferative responses of cord blood lymphocytes (CBLs) to food antigens and cord blood IgE concentrations were measured in 37 full term newborn infants for the prediction of allergic disorders. In these 37 infants who were followed up for two years, allergic history of the family was found in four (sensitivity 57.1%) and cord blood IgE concentrations were greater than 0.5 IU/ml in three (sensitivity 42.9%) of seven infants who developed allergic disorders. When CBLs were stimulated twice by ovalbumin or bovine serum albumin, the value of the stimulation index in proliferative responses of CBLs to ovalbumin or bovine serum albumin was greater than 1.5 in six (sensitivity 85.7%) of seven infants who developed allergic disorders. The specificity of the responses of CBLs in the prediction of the development of allergic disorders was 93.3%. The proliferative responses of CBLs to food antigens were useful in the prediction of not only development of allergic disorders but also offending allergens. These observations provide further evidence that sensitisation is occurring in utero. This would appear to be increasingly important in the genesis of early atopic problems. As our follow up is only two years, in utero sensitisation is a prediction for the early development of atopic disease but only longer follow up will show whether this holds good for allergic disorders at any age.     

Practical aspects of allergy-testing

Allergy-testing is a prerequisite for specific allergy treatment, including specific allergen avoidance measures, relevant pharmacotherapy and specific allergy vaccination. All children with persisting, recurrent or severe possible "allergic symptoms" or those with a need for continuous treatment should be tested, irrespective of the child's age. Allergy-testing includes a careful case history and a determination of IgE sensitisation by skin prick test or the measurement of allergen-specific IgE in serum by standardised and validated methods. The diagnosis of food allergy cannot usually be based solely on the case history and IgE sensitisation; the diagnosis has to be confirmed by controlled food elimination and food challenge procedures. The diagnosis of inhalant allergic disease requires only confirmatory nasal, conjunctival or bronchial challenges in equivocal cases or before specific allergy treatment such as extensive allergen avoidance measures or allergy vaccination.     

Season of birth as predictor of atopic manifestations

The relation between month of birth, sensitisation, and manifestations of atopy was assessed in 209 children who were followed from birth to 12-15 years. Children born during the tree pollen season were less likely to develop allergic rhinoconjunctivitis, IgE antibodies to pollen, or a positive screening test for IgE antibodies (odds ratio 0.28, 0.41, 0.35, respectively) than children born during the rest of the year. The prevalence of IgE antibodies to food and animal dander at 9 months and to atopic disease was higher in children born in the autumn and winter, that is, September to February, compared to the spring and summer (egg 20% v 6%; milk 10% v 2%). Thus sensitisation to pollen and allergic rhinoconjunctivitis is least common in children born in the spring, while birth in September to February is associated with an increased incidence of sensitisation to food and of atopic disease.     

Understanding allergy

The prevalence rates of allergic conditions have risen at an alarming rate throughout the world in the past 50 years. The UK has the highest prevalence of asthma in the world and the rate of sensitisation to food allergen has trebled in a mere 6 years. The burden of allergic disease and service provision within the UK is such that large numbers of children are suffering a very poor quality of life. A phenomenon known as the ‘allergic march’ has also been described where children tend to progress from infantile eczema to developing food allergies, asthma and rhinitis.This review outlines the immunopathogenic origins of allergic disease and the clinical implications underlying the hygiene hypothesis as well as the influence of maternal and early infant nutrition on allergy prevalence. Factors associated with its primary prevention are also considered as a strategy to stem the current global epidemic of allergy.     

Phenotype of acute respiratory syncytial virus induced lower respiratory tract illness in infancy and subsequent morbidity

The objective of this study was to investigate the association hypothesis that outcome following respiratory syncytial virus (RSV) induced bronchiolitis (RSVB) and RSV induced wheeze (RSVW) are different. At 3 years respiratory symptoms were more common in those with RSV infection than the control group but there was no increase in allergic sensitisation (11% vs 10%). Those with RSVW were more likely to have evidence of allergic sensitisation when compared with RSVB subjects (22% vs 7%), and have increased symptoms and increased use of inhaled steroids. Conclusion: The data argue that RSV infection during infancy does not induce allergic asthma and that host factors rather than the virus determine long-term outcomes.     

Food allergy as seen by an allergist

The clinical expression of allergic disease is the consequence of a series of complex gene-environment interactions that occur at the materno-fetal interface and throughout infancy, leading to persistence of the Th2 immune response. It has been proposed that atopic eczema is the cutaneous manifestation of a systemic disorder that also gives rise to asthma, food allergy, and allergic rhinitis. The recent emergence of genes regulating epidermal barrier function has raised the question of whether the skin barrier in atopic eczema is defective from the outset, rendering the epidermis "leaky," thereby increasing the risk of allergen penetration and the succeeding inflammatory reaction that contributes to atopic eczema. Food allergic sensitisation and eczema frequently coexist during the first 2 years of life, and food allergy is more prevalent in infants and children with moderate to severe eczematous inflammation. The majority of food allergic reactions are caused by 8 foods, with milk, egg, and peanut occurring with greatest frequency. The acquisition of food-specific tolerance occurs predominantly with foods in which the epitopes are grouped together in a conformational structure (milk, egg, wheat, soy), whilst it rarely occurs in patients allergic to foods in which the epitopes are arranged in a linear fashion (nuts, seeds, fish). Better tests and novel therapies, such as immunotherapy and oral tolerance induction, are required for the management of food allergy.     

Birth anthropometric measures, body mass index and allergic diseases in a birth cohort study (BAMSE).

OBJECTIVE: We aimed to assess increased birth weight or birth length in relation to allergic diseases at 4 years of age, taking body mass index (BMI) at age 4 as a covariate in the adjustment. METHODS: The parents of a large prospective birth cohort answered questionnaires on environmental factors and allergic symptoms when their children were 2 months and 1, 2 and 4 years old. Perinatal data on weight and length at birth were received from the child care health centres. The children were clinically examined at 4 years of age and height and weight recorded. Blood was drawn for analysis of specific IgE antibodies to common inhalant allergens. Risk associations between birth anthropometric measures and wheeze, allergic diseases or sensitisation were estimated in multivariate logistic regression analyses (n = 2869). RESULTS: There were no clear overall associations between birth weight and allergic diseases at 4 years of age. Birth length > or =90th percentile was inversely associated with any wheeze at age 4 (adjusted OR 0.64, 95% CI 0.44 to 0.92) but was significantly associated only with late-onset wheeze (adjusted OR 0.40, 95% CI 0.21 to 0.77). No such associations were seen for persistent or transient wheeze, eczema, rhinitis or allergic sensitisation. Transient wheeze during the first 2 years of age tended to be associated with increased BMI at age 4. CONCLUSION: Increased birth weight was not associated with wheeze or allergic disease. Increased birth length may play a protective role in late-onset wheeze in early childhood.     

Allergic disease in the first year of life is associated with differences in subsequent neurodevelopment and behaviour

Background

Recent trials suggest a link between neuropsychological function, atopy and allergic disease particularly in early childhood; however the nature of this association remains unclear.

Aims

To investigate the relationship between early allergic disease and sensitisation at 12 months of age and neurodevelopmental outcomes at 18 months.

Study design

Linear or binary logistic regression analysis was used to determine whether allergic diseases or sensitization at 12 months of age was a significant predictor of neurodevelopmental test scores at the 18 months.

Subjects

Infants with a maternal history of allergic disease (n = 324).

Outcome measures

Allergic outcomes at 12 months of age included allergen sensitisation, eczema, IgE-mediated and food allergy, and neurodevelopmental outcomes at 18 included the Bayley Scales of Infant Toddler Development III Edition, the Achenbach Child Behaviour Checklist and the Macarthur Scales of Infant Toddler Development.

Results

Children with any diagnosed allergic disease at 12 months had evidence of reduced motor scores (p = .016), and this was most apparent for a diagnosis of eczema (p = .007). Non-IgE mediated food allergy was significantly positively associated with problem Internalising Behaviours (p = .010), along with a trend for effects on the Social–Emotional composite score for IgE-Mediated food allergies (p = .052). Allergic sensitisation was not independently associated with any effects on neurodevelopmental outcomes.

Conclusion

This study provides evidence that an allergic phenotype in infancy is associated with effects on neurodevelopment. Further research is required to investigate the nature of this relationship.     

Understanding primary oral tolerance induction: the end of the beginning

Clinical non-responsiveness to food antigens is the mucosal default mechanism in the majority of the population. Good clinical and experimental evidence suggests that oral tolerance exists in humans. The timing of antigen (food) administration is an important factor in the development of food allergic sensitisation and disease. Induction of tolerance is often seen as a Th2 skewed response, which on the one hand may prevent harmful mucosal immune reactions but on the other may contribute to adverse responses in the susceptible individual. The primary mechanisms by which tolerance may be mediated include T-cell deletion, anergy, suppression, "ignorance" and apoptosis. Cell-mediated delayed hypersensitivity reactions (Th1), which are implicated as a pathogenetic principle in the development of autoimmune and gastrointestinal inflammation, are particularly well suppressed.Regulatory events during the induction of tolerance (or sensitisation) are not well understood at the molecular level. The balance between tolerance (suppression) and sensitisation (priming) is dependent on several factors such as genetic background, nature and dose of antigen, frequency of administration, age at first antigen exposure, immunological status of the host (e.g. virus infection), dietary exposure of the mother, antigen transmission via breast milk, bacterial colonization and other factors.     

Airway infections in infancy and the presence of allergy and asthma in school age children.

AIM: To investigate the association between a history of otitis media and respiratory tract infections in infancy and allergic sensitisation and asthma in school age children of atopic and non-atopic parents. METHODS: Based on a survey of 4585 schoolchildren, three groups of children aged 6-16 years were selected, of whom 502 were eligible with complete data: (1) diagnosed asthma (n = 166); (2) wheeze within past 12 months (n = 155); and (3) no asthma/no wheeze (n = 181). This study population was further analyzed by subgroups of children with or without parental atopy. Main outcome measures were allergic sensitisation verified by skin prick test and asthma. RESULTS: Children of atopic parents had a reduced risk of developing allergic sensitisation in school age if they had a combined history of both otitis media and lower respiratory tract infections during infancy (adjusted odds ratio (aOR) 0.13, 95% CI 0.03 to 0.50) or a history of otitis media (aOR 0.31, 95% CI 0.12 to 0.83). A history of lower respiratory tract infections in infancy increased the risk of asthma in children of non-atopic parents (aOR 4.21, 95% CI 1.68 to 10.57). CONCLUSION: In the present study population, a history of otitis media in infancy seems to be negatively associated with allergic sensitisation in school age children of atopic parents, whereas a history of lower respiratory tract infections was positively associated with asthma in children of non-atopic parents.     

Airway infections in infancy and the presence of allergy and asthma in school age children

Aim: To investigate the association between a history of otitis media and respiratory tract infections in infancy and allergic sensitisation and asthma in school age children of atopic and non-atopic parents. Methods: Based on a survey of 4585 schoolchildren, three groups of children aged 6–16 years were selected, of whom 502 were eligible with complete data: (1) diagnosed asthma (n = 166); (2) wheeze within past 12 months (n = 155); and (3) no asthma/no wheeze (n = 181). This study population was further analyzed by subgroups of children with or without parental atopy. Main outcome measures were allergic sensitisation verified by skin prick test and asthma. Results: Children of atopic parents had a reduced risk of developing allergic sensitisation in school age if they had a combined history of both otitis media and lower respiratory tract infections during infancy (adjusted odds ratio (aOR) 0.13, 95% CI 0.03 to 0.50) or a history of otitis media (aOR 0.31, 95% CI 0.12 to 0.83). A history of lower respiratory tract infections in infancy increased the risk of asthma in children of non-atopic parents (aOR 4.21, 95% CI 1.68 to 10.57). Conclusion: In the present study population, a history of otitis media in infancy seems to be negatively associated with allergic sensitisation in school age children of atopic parents, whereas a history of lower respiratory tract infections was positively associated with asthma in children of non-atopic parents.     

Latex allergy: Two educational cases

Natural rubber latex (NRL) allergy is a significant problem both for health care workers and for children with complex medical and surgical conditions that require multiple surgical interventions. Primary and secondary prophylaxis are effective measures in identified high risk groups, such as spina bifida (SB). It is therefore likely that with proper attention to prevention and secondary prophylaxis in the highest risk groups that the numbers of paediatric SB patients with NRL allergy will continue to decrease. In contrast medical awareness of established latex allergy needs to be maintained. The issue of latex sensitisation via fruit and food allergy will also remain, so some of the attention that SB patients have received in the past may need to be refocussed onto other emerging high risk groups. Innovative immunomodulatory approaches may soon translate to the clinic for latex sensitised or allergic subjects.     

Could whey be responsible for the development of cow's milk allergy in newborns and infants?

Cow's milk allergy is the most common type of food allergy in infants. Most infants develop symptoms one week after initiating the feeding of cow's milk based formulas though sensitisation in utero and via mother's milk are also possible. We report on three newborns who received whey baths after birth and developed allergic skin reactions. Cow's milk allergy was diagnosed. In our opinion the whey baths could be responsible for the sensitisation via skin and the allergic skin reactions. The risks and benefits of whey baths for newborns and infants should therefore be carefully considered.     

Birth anthropometric measures, body mass index and allergic diseases in a birth cohort study (BAMSE)

Objective

We aimed to assess increased birth weight or birth length in relation to allergic diseases at 4 years of age, taking body mass index (BMI) at age 4 as a covariate in the adjustment.

Methods

The parents of a large prospective birth cohort answered questionnaires on environmental factors and allergic symptoms when their children were 2 months and 1, 2 and 4 years old. Perinatal data on weight and length at birth were received from the child care health centres. The children were clinically examined at 4 years of age and height and weight recorded. Blood was drawn for analysis of specific IgE antibodies to common inhalant allergens. Risk associations between birth anthropometric measures and wheeze, allergic diseases or sensitisation were estimated in multivariate logistic regression analyses (n = 2869).

Results

There were no clear overall associations between birth weight and allergic diseases at 4 years of age. Birth length ⩾90th percentile was inversely associated with any wheeze at age 4 (adjusted OR 0.64, 95% CI 0.44 to 0.92) but was significantly associated only with late‐onset wheeze (adjusted OR 0.40, 95% CI 0.21 to 0.77). No such associations were seen for persistent or transient wheeze, eczema, rhinitis or allergic sensitisation. Transient wheeze during the first 2 years of age tended to be associated with increased BMI at age 4.

Conclusion

Increased birth weight was not associated with wheeze or allergic disease. Increased birth length may play a protective role in late‐onset wheeze in early childhood.