Advances in pediatric asthma and atopic dermatitis

PURPOSE OF REVIEW: Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. RECENT FINDINGS: With increasing options for the treatment of allergic diseases, much work is now focused on methods for individualizing treatments to a patient's phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regimens for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extends to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. SUMMARY: Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patient-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review.     

Asthma und Allergie Genetische Prädisposition und Umweltfaktoren

Genetic disposition and environmental factors determine the development of asthma and other allergic diseases. Genetic disposition can be viewed as a complex combination of changes in a number of genes involved in various diseases causing mechanisms. Using a number of different approaches candidate genes for the development of asthma and allergy have been identified and polymorphisms in those genes have been detected. While numerous studies reported associations between polymorphisms and asthma and allergy related phenotypes the functional background of those associations are not jet clear. Variations in the signaling pathway of IL-4 and IL-13 highlight the complexity of gene-gene interactions. Furthermore, it can be speculated that gene-environment interactions might determine the development of asthma and allergy as effects of exposure to bacterial lipopolysaccharide (LPS) are influenced by genetic variants of the LPS-receptor CD14. In addition, successful therapy of asthma symptoms is also dependant on the genetic background of the patient. Discussion. While the role of genetic factors in the development, expression and therapy of asthma and other allergic diseases starts to unfold in the context of recent studies numerous questions still remain.     

EAACI guidelines on allergen immunotherapy: Prevention of allergy

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease‐modifying treatment for IgE‐mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence‐based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer‐review of draft recommendations. Our key recommendation is that a 3‐year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate‐to‐severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post‐AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2 years post‐AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease‐modifying treatment exists but there is an urgent need for more high‐quality clinical trials.     

Epicutaneous sensitization to food allergens in atopic dermatitis: What do we know?

Atopic dermatitis (AD) is a chronic inflammatory skin disease mainly affecting children, which has no definitive curative therapy apart from natural outgrowing. AD is persistent in 30%-40% of children. Epithelial barrier dysfunction in AD is a significant risk factor for the development of epicutaneous food sensitization, food allergy, and other allergic disorders. There is evidence that prophylactic emollient applications from birth may be useful for primary prevention of AD, but biomarkers are needed to guide cost-effective targeted therapy for high-risk individuals. In established early-onset AD, secondary preventive strategies are needed to attenuate progression to other allergic disorders such as food allergy, asthma, and allergic rhinitis (the atopic march). This review aims to describe the mechanisms underpinning the development of epicutaneous sensitization to food allergens and progression to clinical food allergy; summarize current evidence for interventions to halt the progression from AD to food sensitization and clinical food allergy; and highlight unmet needs and directions for future research.     

Probiotics for allergic diseases: Realities and myths

Yao T‐C, Chang C‐J, Hsu Y‐H, Huang J‐L. Probiotics for allergic diseases: Realities and myths.
Pediatr Allergy Immunol 2010: 21: 900–919.
© 2009 John Wiley & Sons A/S The prevalence of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis has increased sharply over the past two to three decades in many countries, and allergies are now the most common chronic disease among children throughout the world. In the past few years, probiotics have been advocated for the management of allergic diseases in many parts of the world. Physicians have a responsibility to ensure the efficacy and safety of any products they prescribe or recommend. This article provides a comprehensive overview and a critical interpretation of currently available evidence regarding the role of probiotics in the prevention and treatment of allergic diseases in humans and also discusses several major myths and potential risks associated with the use of probiotics. In the current era of evidence‐based medicine, there is still insufficient evidence to recommend probiotics for the prevention of allergic diseases or as part of standard management for any allergic conditions in children.     

Clinical practice

The increase in allergic disease prevalence has led to heightened interest in the factors determining allergy risk, fuelled by the hope that by influencing these factors one could reduce the prevalence of allergic conditions. The most important modifiable risk factors for allergy are maternal smoking behaviour and the type of feeding. A smoke-free environment for the child (to be), exclusive breastfeeding for 4–6 months and the postponement of supplementary feeding (solids) until 4 months of age are the main measures considered effective. There is no place for restricted diets during pregnancy or lactation. Although meta-analyses suggest that hypoallergenic formula after weaning from breastfeeding grants protection against the development of allergic disease, the evidence is limited and weak. Moreover, all current feeding measures aiming at allergy prevention fail to show effects on allergic manifestations later in life, such as asthma. In conclusion, the allergy preventive effect of dietary interventions in infancy is limited. Counselling of future parents on allergy prevention should pay attention to these limitations.     

New visions for basic research and primary prevention of pediatric allergy: An iPAC summary and future trends

Hydrolyzed formula feeding, delayed introduction of solid food, indoor allergen avoidance, smoke and pollutants avoidance have been applied for several decades as primary preventive measures for allergic diseases. Unfortunately, some of these strategies have had no or modest success. Therefore, resources need to be focused on better understanding of the early allergic events and on interventional studies to investigate new strategies of primary and secondary prevention. Accordingly, this review summarizes the state-of-the-art of genetic, immunological and clinical aspects of primary prevention of allergic diseases. Studies investigating gene-by-gene and gene-by-environment interactions suggest that prevention of allergic diseases must be tailored to the individual genetic susceptibilities ('gene profiling') and environmental exposures. The expanding knowledge on new T cell populations (Th17, TSLP (thymic stromal derived lymphopoietin)-dependent 'inflammatory Th2 cells') is also inspiring new concepts on the origins of allergic diseases. The old concept of 'blocking immunoglobulin G antibodies' has been re-appraised and it is likely to generate novel preventive and therapeutic strategies. The major task for future clinical research is to clearly define the timing of optimal exposure to potential allergens. In addition, the role of microbial products such as certain bacteria, or their components, and of helminths or their larvae at different times in early life, alone or with potential allergens, definitely need to be further investigated. The benefit of efficient allergy prevention, based on focusing resources on novel and promising research lines, will be of prime importance to both affluent countries and other parts of the world where allergy is only currently emerging.     

Early life nutrition and allergy

The gene/environment interactions that influence the development of allergic sensitisation and disease commence early in foetal life. The health, nutrition and environmental exposures of the mother during pregnancy have a profound effect not only on immune ontogeny but also on airway form and function. However, the influences on susceptibility to allergy may be different to those that affect manifestations of allergic disease such as asthma. A number of macro- and micro-nutrients have effects on either the risk of allergic sensitisation or allergic disease or both. Understanding the interactions will facilitate the identification of nutritional supplements which might lead to interventions which will prevent disease.     

Asthma and allergic rhinitis in childhood: what's new

Novel approaches are currently offered for the diagnostic workup and therapeutic management of allergic rhinitis and asthma. New predictive biomarkers of allergy and asthma are available. Primary and secondary prevention, earlier intervention, and modification of the natural history of allergic rhinitis and asthma are being intensively investigated. This review highlights advances in the understanding of the etiology, diagnosis, and management of atopic airway diseases in childhood, as well as prenatal and early‐life risk factors and strategies for prevention.     

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??There is strong evidence implicating the intestinal flora disturbance in developing allergicdisease including allergic rhinoconjunctivitis??asthma??eczema and food allergy. Experimental studies with animal model of allergy have shown that probiotics can improve allergic manifestations by induceing immune regulation Treg cell??inhibiting the secretion of allergen-induced IgE and Th2 cytokines??attenuating eosinophils infiltration and allergic inflammation in target organs. Probiotics have been proved effective in treatment of IgE-mediated eczema;however??because of the conflicting results??probiotics are recommended for prevention of allergy only in populations at high risk of allergy.     

Advances in pediatric allergy

PURPOSE OF REVIEW: The purpose of this review is to highlight several important findings related to the broad topic of pediatric allergic diseases reported over the past year, focusing primarily on asthma, urticaria, food allergy, and vaccine reactions. RECENT FINDINGS: Progress continues to be made in identifying environmental exposures during the first years of life that are important for the development of atopic diseases, including asthma. Interventions are being sought based on these findings, to prevent the development of atopic diseases. Chronic urticaria in children is difficult to manage and there is little data related specifically to children to guide treatment and education. Two reports of large populations of children with chronic urticaria were reported in the past year; one dealing with chronic idiopathic, urticaria and one with acquired cold urticaria. Food allergy continues to increase in prevalence and improvements in diagnosis and management continue. Finally, a report of vaccine anaphylaxis cases among a large database was reported. SUMMARY: Allergic disorders comprise a major component of pediatric practice. Advances continue in understanding the origins and natural history of these disorders and treatments are now available that allow effective management in most cases. Patient and parent education remains key to prevent unnecessary restrictions on these children and ensure optimal treatment success.     

Respiratory allergies in childhood: Recent advances and future challenges

The burden of allergic airway diseases still represents a major health problem in childhood. Despite many different options are currently available for the diagnostic work‐up and management, the overall disease control in terms of impact on quality of life, morbidity and mortality, is not yet satisfactory. The extreme variability of individual risk factors and severity determinants may account for it. On the other side, the knowledge of the multifaceted allergy background could pave the way to primary prevention, early intervention and disease course modification. In fact, most of current research is focusing on the identification of biological and clinical predictive markers of allergy and asthma onset. This review aims at summarizing the latest achievements concerning the complex inter‐relation between genetic predisposition and environmental factors, and their impact on prevention strategies and early identification of at risk subjects. An update on the diagnostic and monitoring tools as well as an insight into the newest treatments options is also provided.     

Vaccines: could asthma in young children be a preventable disease? ‬‬‬‬‬‬‬

?The long battle with asthma is far from over in developed countries. Its incidence, prevalence, and severity have been increasing for decades. By reducing the risk for asthma, significant healthcare costs can be saved. The desire to create a vaccine that might prevent asthma in young children is attractive and widely considered one of the main goals in translational asthma research. Several vaccination strategies have been tested. These include allergen‐specific immunotherapy, vaccination against infectious pathogens, and modification of cell and cytokine responses. The lack of success in the prevention of asthma in young children lies on the complexity of the disease, which involves many genetic, epigenetic, and environmental interactions. This review provides a summary of current literature and aims to address key questions how to develop vaccines to prevent asthma in young children. ??????????????     

Fifty years of allergy: 1965–2015

The last 50 years in allergy could almost be considered the first 50 years. Over this time period, we have witnessed the emergence of allergy as a subspecialty, have seen and continue to observe a tremendous change in prevalence of allergic disease and have gained insight into the mechanisms that underlie allergic predisposition and disease manifestation. We have improved the care of children with many forms of allergic disease and now sit poised to be able to alter the natural history of allergic disease with the use of specific immunotherapy. There is much left to do in the next 50 years including understanding what underlies both the predisposition to atopic disease and its natural resolution and identifying the environmental cofactors involved in the ‘allergic epidemic’ and therefore targets for effective primary prevention.     

Prevalence and risk factors of allergies in Turkey: Results of a multicentric cross-sectional study in children

The Prevalence And Risk Factors of Allergies in Turkey (PARFAIT) study was planned to evaluate prevalence and risk factors of asthma and allergic diseases and also to find out which geographical variables and/or climatic conditions play a role determining the prevalence of allergic diseases in Turkish school children. Study was planned as cross-sectional questionnaire-based. About 25,843 questionnaires from 14 centers were appropriate for analysis. Parental history of allergy, having an atopic sibling and other atopic disease in index case was significant risk factors for all allergic diseases. Breast feeding decreased the risk of current asthma (OR: 0.92, CI: 0.86-0.99) and wheezing (OR: 0.93, CI: 0.87-0.99) but not allergic rhinitis and eczema. Respiratory infection in the past was an important risk factor for the occurrence of allergic diseases especially for asthma which was increased 4.53-fold. Children exposed to household smoke were significantly at higher risk of asthma, wheezing, and allergic rhinitis (OR: 1.20, CI: 1.08-1.33; OR: 1.21, CI: 1.09-1.34; and OR: 1.32, CI: 1.21-1.43, respectively). All allergic diseases were increased in those children living in areas which have altitude of below 1000 m and mean yearly atmospheric pressure above 1000 mb. The study has suggested that household and country-specific environmental factors are associated with asthma, wheezing, allergic rhinitis, and eczema risk during childhood in Turkey.     

Therapeutic strategies for allergic airways diseases

Asthma and allergic rhinitis are airways allergic diseases and different aspects of these diseases are discussed in this paper. Both diseases require specific treatment but the airways are a continuum and it has been shown that concomitant treatment in patients suffering from both diseases has a better effect than treating only one of the diseases. Furthermore, treatment of allergic rhinitis in asthmatic patients reduces the risk of hospital admission due to asthma and improves bronchial hyper-responsiveness. Anti-inflammatory therapy, particularly with local steroids, is the single most important treatment for airways allergic diseases. Some studies have shown the importance of starting early after diagnosing asthma but the issue of how early in life to start inhaled steroids is still being debated. Also leukotriene antagonists have been shown to have beneficial effects in many patients and can be used in conjunction with inhaled steroids. Combination therapy with inhaled steroids and inhaled beta(2)-agonists has been shown to be effective in adults but this has not yet been fully documented in children. Optimal treatment of exercise-induced asthma is important to enable children and adolescents to fulfill their developmental possibilities. Allergy vaccination has traditionally been used for treating airways allergic diseases. It is often given for allergic rhinitis when pharmacotherapy is not providing full symptom control. One recent study has suggested that allergy vaccination may possibly help to prevent the development of asthma in the child with allergic rhinitis. More research is needed on asthma allergy vaccination. Concordance with treatment may often be difficult and efforts should be taken to ensure the best concordance possible.     

Paediatric allergy in review

This will provide an overview of allergy to facilitate an understanding of the epidemiology, immuno-pathology, and the early life origins of the allergic diseases, which are increasing in prevalence worldwide. This veritable allergy epidemic poses a significant public health burden in both the developed and the developing worlds and makes optimal allergy care in both primary and tertiary settings a priority. A clear body of literature supports the commonly observed evolution of early food allergies and atopic dermatitis to the later development of the airways allergic diseases, namely allergic rhinitis and asthma. The main hypotheses behind these concepts are described. A typical clinical case is discussed in order to highlight this allergic march in the clinical setting and current and future strategies for allergy prevention are explored.     

OPINION: Primary prevention of allergy – Will it soon become a reality?

It is generally accepted that allergic diseases are not curable and not preventable, but mainly controllable using pharmacotherapy (i.e. symptomatic medication). Recent research, however, demonstrated that a number of specific interventions can lead to (partial) primary prevention of allergy, especially of atopic dermatitis (AD) and food allergy (FA). Three types of primary prevention strategies have been successfully studied: early administration of bacterial products (most studies are on probiotics), early moisturizing in infants at risk for AD and early exposure to allergenic foods (peanut and egg). Results of these studies indicate that the stage might have been set. Surely, much more research needs to be carried out before advice can be given in clinical practice. This opinion article discusses the three types of beneficial interventions and gives ideas for future research, which might show the way for better strategies in primary prevention of allergic diseases.     

Elevated cord blood IgE is associated with recurrent wheeze and atopy at 7 yrs in a high risk cohort

There is considerable interest in identifying children at high risk for developing atopic diseases for primary prevention. This study evaluates risk factors for detectable cord blood IgE and assesses CB‐IgE in predicting asthma and other IgE‐mediated allergic diseases in children at high risk because of family history. Cord blood was obtained as part of a randomized controlled trial assessing the efficacy of an intervention program in the primary prevention of IgE‐mediated allergic diseases. CB‐IgE was measured and the degree to which this was associated with perinatal risk factors was assessed. The cohort was then evaluated for atopic disorders at 7 yrs of age to assess the predictive value of CB‐IgE. Fifty‐five (19.3%) of infants had detectable CB‐IgE (≥0.5 kU/l). Maternal atopy and birth in winter months were risk factors associated with detectable CB‐IgE. CB‐IgE was found to be significantly associated with allergic sensitization (OR 2.22; 95% CI 1.11, 4.41) and recurrent wheeze at 7 yrs (OR 2.51, 95% CI 1.09, 5.76) but not with other outcomes. CB‐IgE may be a useful measure for identifying children at high risk of atopic diseases for the purpose of primary prevention.     

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.