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1.
Probiotics' efficacy in paediatric diseases: which is the evidence? A critical review on behalf of the Italian Society of Pediatrics.
Martinelli, M, Banderali, G, Bobbio, M, Civardi, E, Chiara, A, D'Elios, S, Lo Vecchio, A, Olivero, M, Peroni, D, Romano, C, et al
Italian journal of pediatrics. 2020;(1):104
Abstract
During the last decade several paediatric studies have been published with different possible indications for probiotics, leading to a global increase of probiotics' market. Nevertheless, different study designs, multiple single/combined strains and small sample size still leave many uncertainties regarding their efficacy. In addition, different regulatory and quality control issues make still very difficult the interpretation of the clinical data. The objective of this review is to critically summarise the current evidence on probiotics' efficacy and safety on a different number of pathologies, including necrotizing enterocolitis, acute infectious diarrhoea, allergic diseases and functional gastrointestinal disorders in order to guide paediatric healthcare professionals on using evidence-based probiotics' strains. To identify relevant data, literature searches were performed including Medline-PubMed, the Cochrane Library and EMBASE databases. Considering probiotics strain-specific effects, the main focus was on individual probiotic strains and not on probiotics in general.
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2.
Pediatric allergic diseases in the Indian subcontinent-Epidemiology, risk factors and current challenges.
Krishna, MT, Mahesh, PA, Vedanthan, PK, Mehta, V, Moitra, S, Christopher, DJ
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2020;(7):735-744
Abstract
INTRODUCTION India is low-middle-income country (LMIC) with a population of 1.3bn, comprising about 20% of the global population. While the high-income Western countries faced an "allergy epidemic" during the last three decades, there has been a gradual rise in prevalence of allergic diseases in India. METHODS Narrative review. RESULTS AND DISCUSSION Allergic diseases occur as a consequence of a complex interplay between genetic and environmental factors. There are multiple contrasting determinants that are important to consider in India including high levels of air pollution, in particular PM2.5 due to burning of fossil fuels and biomass fuels, diverse aero-biology, tropical climate, cultural and social diversity, religious beliefs/myths, linguistic diversity, literacy level, breastfeeding and weaning, diet (large proportion vegetarian), and high incidence rates of TB, HIV, malaria, filariasis, parasitic infestations, and others, that not only shape the immune system early in life, but also impact on biomarkers relevant to allergic diseases. India has a relatively weak and heterogeneous healthcare framework, and allergology has not yet been recognized as an independent specialty. There are very few post-graduate training programs, and allergic diseases are managed by primary care physicians, organ-based specialists, and general pediatricians. Adrenaline auto-injectors are not available, there is patient unaffordability for inhalers, nasal sprays, and biologics, and this is compounded by poor compliance leading to 40%-50% of asthmatic children having uncontrolled disease and high rates of oral corticosteroid use. Standardized allergen extracts are not available for skin tests and desensitization. This article provides a critical analysis of pediatric allergic diseases in India.
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3.
The origins of allergy from a systems approach.
Krempski, JW, Dant, C, Nadeau, KC
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2020;(5):507-516
Abstract
OBJECTIVE The origins of allergic diseases have traditionally been explained by immunoglobulin E-mediated immune responses to account for asthma, atopic dermatitis, atopic rhinitis, and food allergy. Research insights into disease origins support a broader array of factors that predispose, initiate, or exacerbate altered immunity in allergic diseases, such as (1) inherent epithelial barrier dysfunction; (2) loss of immune tolerance; (3) disturbances in the gut; and (4) organ-specific microbiomes, diet, and age. Here, we discuss these influences that together form a better understanding of allergy as a systems disease. DATA SOURCES We summarize recent advances in epithelial dysfunction, environmental influences, inflammation, infection, alterations in the specific microbiome, and inherent genetic predisposition. STUDY SELECTIONS We performed a literature search targeting primary and review articles. RESULTS We explored microbial-epithelial-immune interactions underlying the early-life origins of allergic disorders and evaluated immune mechanisms suggesting novel disease prevention or intervention strategies. Damage to epithelial surfaces lies at the origin of various manifestations of allergic disease. As a sensor of environmental stimuli, the epithelium of the lungs, gut, and skin is affected by an altered microbiome, air pollution, food allergens in a changed diet, and chemicals in modern detergents. This collectively leads to alterations of lung, skin, or gut epithelial surfaces, driving a type 2 immune response that underlies atopic diseases. Treatment and prevention of allergic diseases include biologics, oral desensitization, targeted gut microbiome alterations, and changes in behavior. CONCLUSION Understanding the spectrum of allergy as a systems disease will allow us to better define the mechanisms of allergic disorders and improve their treatment.
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4.
Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections.
van Sadelhoff, JHJ, Wiertsema, SP, Garssen, J, Hogenkamp, A
Frontiers in immunology. 2020;:1007
Abstract
Breastfeeding is indicated to support neonatal immune development and to protect against neonatal infections and allergies. Human milk composition is widely studied in relation to these unique abilities, which has led to the identification of various immunomodulating components in human milk, including various bioactive proteins. In addition to proteins, human milk contains free amino acids (FAAs), which have not been well-studied. Of those, the FAAs glutamate and glutamine are by far the most abundant. Levels of these FAAs in human milk sharply increase during the first months of lactation, in contrast to most other FAAs. These unique dynamics are globally consistent, suggesting that their levels in human milk are tightly regulated throughout lactation and, consequently, that they might have specific roles in the developing neonate. Interestingly, free glutamine and glutamate are reported to exhibit immunomodulating capacities, indicating that these FAAs could contribute to neonatal immune development and to the unique protective effects of breastfeeding. This review describes the current understanding of the FAA composition in human milk. Moreover, it provides an overview of the effects of free glutamine and glutamate on immune parameters relevant for allergic sensitization and infections in early life. The data reviewed provide rationale to study the role of free glutamine and glutamate in human milk in the protection against neonatal allergies and infections.
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5.
The potential role of folate metabolism in interstitial cystitis.
Keagy, CD
International urogynecology journal. 2019;(3):363-370
Abstract
The topic of interstitial cystitis (IC), also known as painful bladder syndrome (PBS), and folate/one carbon metabolism has previously been unaddressed in research. This narrative review highlights a potential connection for those with mast cell-related IC and histamine-mediated pain that is explored through four conceptual sections. The first section focuses on the nature of mast cell involvement and histamine-mediated pain in some interstitial cystitis patients. The second section reviews the literature on folate status in wider allergic conditions. The third section addresses the role of folate and methylation in general in histamine excretion. Finally, folate metabolism and vascular function are addressed because of the vascular abnormalities present in some IC bladders.
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6.
Pegvaliase: Immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy.
Hausmann, O, Daha, M, Longo, N, Knol, E, Müller, I, Northrup, H, Brockow, K
Molecular genetics and metabolism. 2019;(1-2):84-91
Abstract
OBJECTIVE To provide recommendations for managing hypersensitivity adverse events (HAEs) to an injectable enzyme substitution therapy (pegvaliase, a PEGylated phenylalanine ammonia lyase enzyme) in adult patients with phenylketonuria (PKU). METHODS Eight European academic immunology experts with a broad range of experience in hypersensitivity, anaphylaxis, and/or drug reactions, and two geneticists from the USA with pegvaliase experience convened for two advisory board meetings. Efficacy, safety, and immunological profile of pegvaliase were discussed with the objective of developing recommendations for the clinical management of HAEs associated with pegvaliase treatment. RESULTS Based on available immunogenicity data, it was concluded that pegvaliase induces a Type III hypersensitivity reaction, causing HAEs with peak event rates during induction/titration and a decline over time during maintenance therapy. The decline in HAEs with longer duration of therapy was considered to likely be driven by anti-drug antibody affinity maturation, reduced immune complex formation, and decreased complement activation over time. Immunology and PKU experts unanimously supported that the use of an induction, titration, and maintenance dosing regimen and implementation of several risk mitigation strategies contributed to the improvement of tolerability over time. Key risk mitigation strategies utilized in the Phase 3 clinical trials such as premedication with H1-receptor antagonists, allowance for a longer titration period after an HAE, patient education, and requirement to carry auto-injectable adrenaline (epinephrine) should be continued in clinical practice. A tool for administration of auto-injectable adrenaline in patients using pegvaliase was suggested. It was added that after the occurrence of a severe HAE a temporary dose reduction is more likely to improve tolerability than treatment interruption. CONCLUSIONS Overall, it was agreed that pegvaliase has a generally tolerable safety profile in adults with PKU. Importantly, the risk mitigation strategies utilized in the clinical trials were considered to support the continued use of key strategies for management in the commercial setting, such as a slow induction/titration dosing paradigm and premedication with H1-receptor antagonists. However, physicians and patients need to be aware of the risk of HAEs associated with pegvaliase; presence of a trained observer during early treatment may be beneficial in certain circumstances, and a requirement to carry auto-injectable adrenaline is recommended. Because pegvaliase offers the possibility to normalize diet, while maintaining blood phenylalanine within the recommended therapeutic range, safe use of this medication in the clinical setting is important. Ongoing monitoring of long-term clinical safety of patients on pegvaliase treatment in the commercial setting was recommended.
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7.
Early-life antibiotic exposure increases the risk of developing allergic symptoms later in life: A meta-analysis.
Ahmadizar, F, Vijverberg, SJH, Arets, HGM, de Boer, A, Lang, JE, Garssen, J, Kraneveld, A, Maitland-van der Zee, AH
Allergy. 2018;(5):971-986
Abstract
This study systematically reviewed and quantified the relationship between exposure to antibiotics during the first 2 years of life and the risk of allergies/atopies including hay fever, eczema, food allergy, positive skin prick testing (SPT), or elevated allergen-specific serum/plasma immunoglobulin (Ig) E levels later in life. PubMed and Web of Science databases were searched for observational studies published from January 1966 through November 11, 2015. Overall pooled estimates of the odds ratios (ORs) were obtained using fixed or random-effects models. Early-life exposure to antibiotics appears to be related to an increased risk of allergic symptoms of hay fever, eczema, and food allergy later in life. The summary OR for the risk of hay fever (22 studies) was 1.23, 95% confidence interval (CI):1.13-1.34; I2 : 77.0%. The summary OR for the risk of eczema (22 studies) was 1.26, 95% CI: 1.15-1.37; I2 : 74.2%, and the summary OR for food allergy (3 studies) was 1.42, 95% CI: 1.08-1.87; I2 : 80.8%. However, no association was found for antibiotics exposure early in life and objective atopy measurements including positive SPT or elevated allergen-specific serum/plasma IgE levels.
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8.
SAM syndrome is characterized by extensive phenotypic heterogeneity.
Taiber, S, Samuelov, L, Mohamad, J, Barak, EC, Sarig, O, Shalev, SA, Lestringant, G, Sprecher, E
Experimental dermatology. 2018;(7):787-790
Abstract
Severe skin dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a rare life-threatening inherited condition caused by bi-allelic mutations in DSG1 encoding desmoglein 1. The disease was initially reported to manifest with severe erythroderma, failure to thrive, atopic manifestations, recurrent infections, hypotrichosis and palmoplantar keratoderma. We present 3 new cases of SAM syndrome in 2 families and review the cases published so far. Whole exome and direct sequencing were used to identify SAM syndrome-causing mutations. Consistent with previous data, SAM syndrome was found in all 3 patients to result from homozygous mutations in DSG1 predicted to result in premature termination of translation. In contrast, as compared with patients previously reported, the present cases were found to display a wide range of clinical presentations of variable degrees of severity. The present data emphasize the fact that SAM syndrome is characterized by extensive phenotypic heterogeneity, suggesting the existence of potent modifier traits.
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9.
Management of anaphylaxis and allergies in patients with long QT syndrome: A review of the current evidence.
Welzel, T, Ziesenitz, VC, Seitz, S, Donner, B, van den Anker, JN
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2018;(5):545-551
Abstract
OBJECTIVE To develop a treatment algorithm for patients with long QT syndrome (LQTS) in case they need antiallergic medications for allergic reactions, including asthma and anaphylaxis. DATA SOURCES A literature review was performed to assess safety and to develop antiallergic treatment strategies for patients with LQTS. STUDY SELECTIONS LQTS is a heterogeneous group of myocardial repolarization disorders characterized by prolongation of the QT interval that potentially results in life-threatening torsades de pointes tachycardia. Data on pharmacologic treatment in case of anaphylaxis in LQTS are sparse. For this narrative review, all currently available articles on the use of antiallergic drugs for allergic reactions, anaphylaxis, and asthma in patients with LQTS were used. RESULTS Local allergic symptoms can be safely treated primarily with fexofenadine, levocetirizine, desloratadine, or cetirizine and, if needed, a short course of corticosteroids. In case of systemic symptoms, epinephrine should be administered. It may be less effective in patients with LQTS treated with β-blockers, necessitating the use of glucagon as add-on treatment. In case of lower airway obstruction, ipratropium bromide should be used, but if not effective, inhaled β2-adrenergic agents may be used. Continuous cardiac monitoring is indicated with the use of epinephrine and inhaled β2-adrenergic agents. The use of the latter also warrants intense monitoring of serum potassium levels. Clemastine and dimetindene should be avoided in patients with LQTS. CONCLUSION Patients with LQTS have a higher risk of life-threatening complications during the treatment of their allergic reactions because of the underlying disease and concomitant treatment with β-blockers. Treatment algorithms will certainly decrease these complications.
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10.
Food allergy.
Renz, H, Allen, KJ, Sicherer, SH, Sampson, HA, Lack, G, Beyer, K, Oettgen, HC
Nature reviews. Disease primers. 2018;:17098
Abstract
Food allergies manifest in a variety of clinical conditions within the gastrointestinal tract, skin and lungs, with the most dramatic and sometimes fatal manifestation being anaphylactic shock. Major progress has been made in basic, translational and clinical research, leading to a better understanding of the underlying immunological mechanisms that lead to the breakdown of clinical and immunological tolerance against food antigens, which can result in either immunoglobulin E (IgE)-mediated reactions or non-IgE-mediated reactions. Lifestyle factors, dietary habits and maternal-neonatal interactions play a pivotal part in triggering the onset of food allergies, including qualitative and quantitative composition of the microbiota. These factors seem to have the greatest influence early in life, an observation that has led to the generation of hypotheses to explain the food allergy epidemic, including the dual-allergen exposure hypothesis. These hypotheses have fuelled research in preventive strategies that seek to establish desensitization to allergens and/or tolerance to allergens in affected individuals. Allergen-nonspecific therapeutic strategies have also been investigated in a number of clinical trials, which will eventually improve the treatment options for patients with food allergy.