Showing papers by "Scott H. Sicherer published in 2018"
TL;DR: This review provides general information to serve as a primer for those embarking on understanding food allergy and also details advances and updates in epidemiology, pathogenesis, diagnosis, and treatment that have occurred over the 4 years since the last comprehensive review.
Abstract: This review provides general information to serve as a primer for those embarking on understanding food allergy and also details advances and updates in epidemiology, pathogenesis, diagnosis, and treatment that have occurred over the 4 years since our last comprehensive review. Although firm prevalence data are lacking, there is a strong impression that food allergy has increased, and rates as high as approximately 10% have been documented. Genetic, epigenetic, and environmental risk factors are being elucidated increasingly, creating potential for improved prevention and treatment strategies targeted to those at risk. Insights on pathophysiology reveal a complex interplay of the epithelial barrier, mucosal and systemic immune response, route of exposure, and microbiome among other influences resulting in allergy or tolerance. The diagnosis of food allergy is largely reliant on medical history, tests for sensitization, and oral food challenges, but emerging use of component-resolved diagnostics is improving diagnostic accuracy. Additional novel diagnostics, such as basophil activation tests, determination of epitope binding, DNA methylation signatures, and bioinformatics approaches, will further change the landscape. A number of prevention strategies are under investigation, but early introduction of peanut has been advised as a public health measure based on existing data. Management remains largely based on allergen avoidance, but a panoply of promising treatment strategies are in phase 2 and 3 studies, providing immense hope that better treatment will be imminently and widely available, whereas numerous additional promising treatments are in the preclinical and clinical pipeline.
938 citations
TL;DR: This work sought to examine the association between early‐life gut microbiota and egg allergy and found that gut microbiota may play a role in egg allergy.
Abstract: Background Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. Methods We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. Results Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10-4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis Padj = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10-4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. Conclusion The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention.
122 citations
TL;DR: The results demonstrate the presence of highly differentiated TH2 cells producing TH2‐associated cytokines with functions beyond IgE class‐switching in patients with PA, and a multifunctional TH2 response was more evident than a Treg cell deficit among peanut‐responsive T cells.
Abstract: Background The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood Objectives Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of subjects with and without peanut allergy (PA) Methods We obtained samples from patients with PA, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (Consortium of Food Allergy Research [CoFAR] 6) Subjects were confirmed as having PA, or if they passed a 1-g peanut challenge, they were termed high-threshold subjects Healthy control (HC) subjects were also recruited Peanut-responsive T cells were identified based on CD154 expression after 6 to 18 hours of stimulation with peanut extract Cells were analyzed by using flow cytometry and single-cell RNA sequencing Results Patients with PA had tissue- and follicle-homing peanut-responsive CD4 + T cells with a heterogeneous pattern of T H 2 differentiation, whereas control subjects had undetectable T-cell responses to peanut The PA group had a delayed and IL-2–dependent upregulation of CD154 on cells expressing regulatory T (Treg) cell markers, which was absent in HC or high-threshold subjects Depletion of Treg cells enhanced cytokine production in HC subjects and patients with PA in vitro , but cytokines associated with highly differentiated T H 2 cells were more resistant to Treg cell suppression in patients with PA Analysis of gene expression by means of single-cell RNA sequencing identified T cells with highly correlated expression of IL4 , IL5 , IL9 , IL13 , and the IL-25 receptor IL17RB Conclusions These results demonstrate the presence of highly differentiated T H 2 cells producing T H 2-associated cytokines with functions beyond IgE class-switching in patients with PA A multifunctional T H 2 response was more evident than a Treg cell deficit among peanut-responsive T cells
83 citations
TL;DR: TN-specific skin tests and serum immunoglobulin E levels can help aid in the diagnosis of TN allergy, but a careful medical history is important because a positive test in isolation is not typically diagnostic.
Abstract: Tree nut (TN) allergy is common and often severe. It has become an important health concern as availability and consumption have increased. Prevalence varies by age and geographic region and appears to have increased in children. Accidental ingestion of TNs is common. Unfortunately, there is a lower likelihood of resolution of TN allergy, roughly 10%. TN-specific skin tests and serum immunoglobulin E levels can help aid in the diagnosis of TN allergy, but a careful medical history is important because a positive test in isolation is not typically diagnostic. Component-resolved diagnostic tests are being increasingly utilized and may improve accuracy. Management consists of strict avoidance of the causal nut(s) and prompt treatment of symptoms upon accidental exposure. A specific consideration with regard to the management of TN allergy is the decision to avoid all TNs or only the TNs to which a patient is clinically allergic. There are currently no data on the primary or secondary prevention of TN allergy. Treatment strategies are being evaluated.
77 citations
TL;DR: Gastrointestinal eosinophilia is present in approximately 10% of patients with EoE; the symptom-diagnosis time gap is influenced by age, race, food allergy, and atopic dermatitis; symptoms vary with race; concurrent infectious/immunologic disorders and mental health disorders are common; and the level of esophageal eOSinophils is comparable in patients with and without fibrostenotic features.
69 citations
TL;DR: Caregivers of peanut allergic children strongly desire that OIT and EPIT result in a buffer against an unintentional reaction, although most admitted that this would not significantly change their anxiety and family's current lifestyle.
Abstract: Background Both oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) are emerging potential treatments for peanut allergy. Caregiver goals and expectations of these therapies are poorly defined. Objective To determine caregiver goals and expectations of food allergy therapy. Methods Twenty-two detailed, semistructured interviews of OIT and EPIT caregivers were conducted, allowing caregivers to describe their motivations for and experiences with food allergy therapy and life with a peanut allergic child. Results In this sample, caregivers of peanut allergic children enrolled in OIT or EPIT phase 3 trials expressed a primary goal for their child to develop a buffer against an unintentional peanut exposure. The perception of the buffer varied, representing a decreased reaction severity on exposure, increased time to react to allow for assessment, or increased threshold of peanut exposure tolerated. Although caregivers expressed that a buffer may increase their confidence in travel and dining outside the home, they do not anticipate this buffer would lessen their overall level of pretherapy anxiety, allergen-associated vigilance, or avoidance practices. Most of the caregivers hope the buffer will increase their and their child's perceived sense of freedom for the child's actions and social interactions, translating to quality of life improvement, while still respecting the limitations of having a severe allergy that has been partially treated. No caregiver viewed these therapies as a cure, and most viewed treatment as a supplement to their current avoidance practices. Conclusion Caregivers of peanut allergic children strongly desire that OIT and EPIT result in a buffer against an unintentional reaction, although most admitted that this would not significantly change their anxiety and family's current lifestyle.
59 citations
TL;DR: Egg‐specific antibody and basophil responses, but not T‐cell responses, are greater in those with reactivity versus tolerance to BE, and the clinical implications of this immune heterogeneity will need to be studied longitudinally.
Abstract: Background Egg allergy is phenotypically heterogeneous. A subset of patients with egg allergy can tolerate egg in an extensively heated form. Inclusion of baked egg (BE) into the diet accelerates resolution of egg allergy. Conversely, BE reactivity is associated with persistent disease. The immune basis of this clinical heterogeneity is unknown. Objectives We sought to study egg-specific antibody, basophil, and T-cell responses in children with reactivity or tolerance to BE. Methods All participants underwent double-blind, placebo-controlled challenges to BE, and those who tolerated BE were challenged with unheated egg white protein to confirm clinical egg reactivity. Laboratory studies included serum antibody measurements, basophil activation tests, and CD154-based detection of egg-responsive T cells by using flow cytometry. Results Of the 129 children studied, BE-reactive participants had significantly greater levels of egg-, ovalbumin-, and ovomucoid-specific IgE; lower ratios of egg-specific IgG 4 /IgE; and increased basophil activation in response to egg. Among all participants, CD154-based profiling revealed egg-responsive T cells producing IL-4 and IL-13 but little IL-10 or IFN-γ, as well as the presence of egg-responsive Foxp3 + CD25 + CD127 low regulatory T cells. Egg-responsive T cells expressed CCR4, CCR6, and CXCR5, indicating capacity for homing to the skin, mucosa, and B-cell follicles. However, neither the frequency nor phenotype of egg-responsive T cells was different in those with tolerance or reactivity to BE. Conclusions Egg-specific antibody and basophil responses, but not T-cell responses, are greater in those with reactivity versus tolerance to BE. Egg-specific antibody and T-cell responses were highly heterogeneous in this cohort. The clinical implications of this immune heterogeneity will need to be studied longitudinally.
38 citations
Johns Hopkins University1, University of Texas Southwestern Medical Center2, Cleveland Clinic3, Roy J. and Lucille A. Carver College of Medicine4, University of North Carolina at Chapel Hill5, Icahn School of Medicine at Mount Sinai6, National Institutes of Health7, Stanford University8, Nationwide Children's Hospital9, Children's Hospital of Philadelphia10, University of South Florida11
TL;DR: This study highlights the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals, not necessarily belonging to the same breeds.
Abstract: University, Budapest, Hungary), P. Howarth (NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences and Human Development and Health, Southampton, UK), A. J. James (Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden), R. Knowles (Arachos Pharma, Stevenge, UK), A. J. Knox (Respiratory Research Unit, University of Nottingham, Nottingham, UK), N. Krug (Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany), D. Lefaudeux (European Institute for Systems Biology and Medicine, CNRS‐ENS‐UCBL‐ INSERM, Lyon, France), M. J. Loza (Janssen R&D, USA), R. Lutter (Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands), A. Manta (Roche Diagnostics GmbH, Mannheim, Germany), S. Masefield (European Lung Foundation, Sheffield, UK), J. G. Matthews (Respiratory and Allergy Diseases, Genentech, San Francisco, CA), A. Mazein (European Institute for Systems Biology and Medicine, CNRS‐ENS‐UCBL‐INSERM, Lyon, France), A. Meiser (Data Science Institute, Imperial College, London, UK), R. J. M. Middelveld (Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden), M. Miralpeix (Almirall, Barcelona, Spain), P. Montuschi (Università Cattolica del Sacro Cuore, Milan, Italy), N. Mores (Università Cattolica del Sacro Cuore, Milan, Italy), C. S. Murray (Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester Academic Health Sciences Centre, Manchester, UK), J. Musial (Department of Medicine, Jagiellonian University Medical College, Krakow, Poland), D. Myles (Respiratory Therapeutic Unit, GSK, London, UK), L. Pahus (Assistance Publique des Hôpitaux de Marseille, Clinique des Bronches, Allergies et Sommeil, Espace Éthique Méditerranéen, Aix‐Marseille Université, Marseille, France), I. Pandis (Data Science Institute, Imperial College, London, UK), S. Pavlidis (National Heart and Lung Institute, Imperial College, London, UK), A. Postle (University of Southampton, UK), P. Powel (European Lung Foundation, Sheffield, UK), G. Praticò (CROMSOURCE, Verona, Italy), M. Puig Valls (CROMSOURCE, Barcelona, Spain), N. Rao (Janssen R&D, USA), J. Riley (Respiratory Therapeutic Unit, GSK, London, UK), A. Roberts (Asthma UK, London, UK), G. Roberts (NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences and Human Development and Health, Southampton, UK), A. Rowe (Janssen R&D, UK), T. Sandström (Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden), J. P. R. Schofield (Centre for Proteomic Research, Institute for Life Sciences, University of Southampton, Southampton,UK), W. Seibold (Boehringer Ingelheim Pharma GmbH, Biberach, Germany), A. Selby (NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences and Human Development and Health, Southampton, UK), D. E. Shaw (Respiratory Research Unit, University of Nottingham, UK), R. Sigmund (Boehringer Ingelheim Pharma GmbH & Co. KG; Biberach, Germany), F. Singer (University Children's Hospital, Zurich, Switzerland), P. J. Skipp (Centre for Proteomic Research, Institute for Life Sciences, University of Southampton, Southampton, UK), A. R. Sousa (Respiratory Therapeutic Unit, GSK, London, UK), P. J. Sterk (Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands), K. Sun (Data Science Institute, Imperial College, London, UK), B. Thornton (MSD, USA), W. M. van Aalderen (Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands), M. van Geest (AstraZeneca, Mölndal, Sweden), J. Vestbo (Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester Academic Health Sciences Centre, Manchester, UK), N. H. Vissing (COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark), A. H. Wagener (Academic Medical Center Amsterdam, Amsterdam, The Netherlands), S. S. Wagers (BioSci Consulting, Maasmechelen, Belgium), Z. Weiszhart (Semmelweis University, Budapest, Hungary), C. E. Wheelock (Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden), S. J. Wilson (Histochemistry Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK).
13 citations
TL;DR: An impressive number of clinically impactful studies and reviews were published in The Journal of Allergy and Clinical Immunology: In Practice in 2017, and it is hoped this review will help readers consolidate and use this extensive and practical knowledge for the benefit of patients.
9 citations
8 citations
TL;DR: Critically appraise the debated issues in this topic, providing a practical approach to this common clinical dilemma and suggesting that families are reluctant to introduce peanut in siblings without testing.
TL;DR: Peanut allergy in children is on the rise in North America, with a self-reported prevalence of 1.4% in 2008, up from 0.8% in 1997; a recent guideline recommends early introduction of EpiPen.
Abstract: KEY POINTS
Peanut allergy in children is on the rise in North America, with a self-reported prevalence of 1.4% in 2008, up from 0.4% in 1997 ( p < 0.001).[1][1] As a result, prevention of peanut allergy has become an important public health goal. A recent guideline recommends early introduction of
TL;DR: The authors compared the relative effectiveness of step-up treatment to fixed-dose combination (FDC) ICSs and long-acting β2-agonists as opposed to an increased dose of inhaled corticosteroids (i-ICSs) or adding a leukotriene receptor antagonist (LTRA).
Abstract: CS Murray. M Thomas. K Richardson. DB Price. SW Turner. J Allergy Clin Immunol Pract. 2017;5(4):1082–1090.e7
Current guidelines offer a number of different choices for step-up treatment of uncontrolled asthma in children on low-dose inhaled corticosteroids (ICSs). In this study, the authors compared the relative effectiveness of step-up treatment to fixed-dose combination (FDC) ICSs and long-acting β2-agonists as opposed to an increased dose of inhaled corticosteroids (i-ICSs) or adding a leukotriene receptor antagonist (LTRA).
This matched cohort study included children with uncontrolled persistent asthma aged 5 to 12 years from 2 UK primary-care databases who were receiving …