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Showing 1 - 200 of 1577 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 61, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 46, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 49, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 144, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 6, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 3)
Addiction     Hybrid Journal   (Followers: 33, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 12, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 24, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 50, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 254, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 5, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 35, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 15, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 10, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 14, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 44, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 30, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 49, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 134, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 91, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 27, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 31, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 15, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 3, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 5, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 36, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 254, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 16, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 128, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 16)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 160)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 213, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 36, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 8, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 44, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 24, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 94, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 45, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 6, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 69, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 139, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 48, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 34, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 14, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 224, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 50, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 28, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 14)
Asia & the Pacific Policy Studies     Open Access   (Followers: 14)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 317, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 7, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 3, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 4, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 13, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 10, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 7, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 13, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 4, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 43, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 25, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 13, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 402, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 4, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 68, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 31, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 23, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 15, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 3, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 37, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 136, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 13, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 18, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 35, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 5, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 224, SJR: 2.083, h-index: 125)

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Journal Cover Allergy
  [SJR: 3.048]   [H-I: 129]   [49 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0105-4538 - ISSN (Online) 1398-9995
   Published by John Wiley and Sons Homepage  [1577 journals]
  • Comparison and Interpretability of the available Urticaria Activity Scores
    • Authors: T. Hawro; T. Ohanyan, N. Schoepke, M. Metz, A. Peveling-Oberhag, P. Staubach, M. Maurer, K. Weller
      Abstract: The urticaria activity score (UAS) is the gold standard for assessing disease activity in patients with chronic spontaneous urticaria (CSU). Two different versions, the UAS7 and UAS7TD, are currently used in clinical trials and routine care. To compare both versions and to obtain data on their interpretability, 130 CSU patients applied both versions and globally rated their disease activity as none, mild, moderate, or severe. UAS7 and UAS7TD values correlated strongly (r=0.90, P
      PubDate: 2017-08-16T04:25:20.036967-05:
      DOI: 10.1111/all.13271
  • Hereditary angioedema with a mutation in the plasminogen gene
    • Authors: K. Bork; K. Wulff, L. Steinmüller-Magin, I. Braenne, P. Staubach-Renz, G. Witzke, J. Hardt
      Abstract: BackgroundHereditary angioedema (HAE) with normal C1-INH (HAEnCI) may be linked to specific mutations in the coagulation factor 12 (FXII) gene (HAE-FXII) or functional mutations in other genes that are still unknown. We sought to identify and characterize a hitherto unknown type of HAE with normal C1-INH and without mutation in the F12 gene.MethodsThe study comprised analysis of whole exome sequencing, Sanger sequencing, and clinical data of patients.ResultsWe detected a mutation in the plasminogen gene in patients with HAEnCI. The mutation c.9886A>G was located in exon 9 leading to the missense mutation p.Lys330Glu (K330E) in the kringle 3 domain of the plasminogen protein. The mutation was identified by next generation sequencing in 14 patients with HAEnCI belonging to 4 of 7 families. Family studies revealed that this type of HAE was transmitted as an autosomal dominant trait. The plasminogen gene mutation was present in all studied symptomatic patients and was also found in 9 out of 38 index patients from 38 further families with HAEnCI. Most patients had swelling of face/lips (78.3%) and tongue (78.3%). 331 out of all 3.795 tongue swellings (8.7%) were associated with dyspnea, voice changes and imminent asphyxiation. Two women died by asphyxiation due to a tongue swelling.ConclusionsHAE with a mutation in the plasminogen gene is a novel type of HAE. It is associated with a high risk of tongue swellings.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-10T04:45:22.173062-05:
      DOI: 10.1111/all.13270
  • Evolution of the IgE and IgG repertoire to a comprehensive array of
           allergen molecules in the first decade of life
    • Authors: Xinyuan Huang; Olympia Tsilochristou, Serena Perna, Stephanie Hofmaier, Antonio Cappella, Carl-Peter Bauer, Ute Hoffman, Johannes Forster, Fred Zepp, Antje Schuster, Raffaele D'Amelio, Ulrich Wahn, Thomas Keil, Susanne Lau, Paolo Maria Matricardi
      Abstract: BackgroundIn early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood.ObjectiveTo investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10yrs.MethodsWe examined the sera collected between birth and age 10yrs from participants in the German Multicentre Allergy Study, a birth cohort born in 1990. The IgE (cut-off ≥0.30 ISU) and IgG (cut-off ≥0.10 ISU) responses to 35 genuine allergenic molecules were measured with a multiplex microarray approach (ImmunoCAP ISAC™).ResultsIgE responses were mostly directed against a restricted group of airborne molecules, with a sequence and prevalence hierarchy (Phl p 1> Bet v 1> Fel d 1> Phl p 5> Der p 2> Der p 1) largely maintained over time. Conversely, the IgG repertoire was much broader, starting with animal foodborne, then spreading to vegetable foodborne and finally to airborne molecules. A strong and persistent IgG response to a given airborne molecule almost invariably preceded or accompanied an IgE response to that molecule.ConclusionsThe evolution of IgG and IgE responses throughout childhood differs widely at population level. IgG responses are mostly directed to animal food allergens while IgE responses are dominated by airborne allergens. However, a strong IgG response almost invariably precedes or accompanies the appearance of IgE to the same molecule in specifically sensitized subjects.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-08T19:00:44.103373-05:
      DOI: 10.1111/all.13269
  • Allergens displayed on Virus-Like Particles are highly immunogenic but
           fail to activate human mast cells
    • Authors: Paul Engeroff; Flurin Caviezel, Federico Storni, Franziska Thoms, Monique Vogel, Martin F. Bachmann
      Abstract: The goal of allergen-specific immunotherapy is the induction of protective immune responses in the absence of anaphylactic reactions. We have previously shown that Fel d 1, the major cat allergen, displayed in a repetitive fashion on virus-like particles (VLPs) may fulfill these criteria. Specifically, Fel d 1 on VLPs induced strongly increased IgG responses compared to the free allergen in mice while anaphylactic reactions were essentially abolished. Here we extend these findings to human mast cells and offer a mechanistic explanation for the reduced anaphylactic activity. By performing allergen binding studies and cellular activation assays, we demonstrate that the inability of Fel d 1 displayed on VLPs to activate mast cells is based on a biophysical as well as a biochemical mechanism. Firstly, Fel d 1 on VLPs showed a strongly impaired ability to bind to surface-bound IgE as assessed by Surface Plasmon Resonance (SPR) as well as flow cytometry. Secondly, despite residual binding, repetitively displayed allergen on VLPs failed to cause mast cell activation.These findings indicate that repetitively displaying allergens on VLPs increases their immunogenicity while reducing their potential to cause anaphylactic reactions by essentially eliminating IgE-mediated activation of mast cells.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-08T18:34:18.870268-05:
      DOI: 10.1111/all.13268
  • Local IL-25 contributes to Th2-biased inflammatory profiles in nasal
    • Authors: H.-Y. Hong; F.-H. Chen, Y.-Q. Sun, X.-T. Hu, Y. Wei, Y.-P. Fan, J. Zhang, D.-H. Wang, R. Xu, H.-B. Li, J.-B. Shi
      Abstract: BackgroundIL-25 has been proposed to play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aims to evaluate the association of IL-25 with the Th2-biased inflammatory profiles in CRSwNP.MethodsNasal polyp (NP) tissues and control uncinate process tissues were collected from 92 patients with CRSwNP, 20 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 16 normal control subjects. IL-25 expression was examined using immunohistochemistry and immunofluorescence staining, flow cytometry, RT-qPCR, and ELISA. The inflammatory profiles and clinical characteristics of 2 NP subtypes (IL-25high and IL-25low) were evaluated, and the effects of IL-25 on Th2 cytokine production in cultured dispersed polyp cells were examined in vitro.ResultsThe mRNA and protein levels of IL-25 were significantly increased in the polyp tissues compared with the control uncinate process tissues. The IL-25high subtype showed greater computed tomography scores, endoscopic scores, and Th2 response. Exposure to IL-25 activated type 2 innate lymphoid cells and Th2 cells in NP simultaneously which further increased Th2 cytokine production in vitro.ConclusionsLocal IL-25 plays a crucial role in promoting Th2-biased inflammatory profiles in NP, and may serve as a promising therapeutic target in CRSwNP patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-03T12:55:22.909768-05:
      DOI: 10.1111/all.13267
  • Challenges in the implementation of EAACI Guidelines on Allergen
           Immunotherapy: A global perspective on the regulation of allergen products
    • Authors: A. Bonertz; G. Roberts, M. Hoefnagel, M. Timon, J. Slater, R. Rabin, J. Bridgewater, C. Pini, O. Pfaar, C. Akdis, J. Goldstein, L. K. Poulsen, R. van Ree, C. Rhyner, D. Barber, O. Palomares, A. Sheikh, R. Pawankar, D. Hamerlijnk, L. Klimek, I. Agache, E. Angier, T. Casale, M. Fernandez-Rivas, S. Halken, M. Jutel, S. Lau, G. Pajno, G. Sturm, E. Maria Varga, R. Gerth Wijk, S. Bonini, A. Muraro, S. Vieths
      Abstract: Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly by either obtaining a marketing authorisation or by being distributed as named patient products. Exemptions from marketing authorisations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-03T12:45:20.306224-05:
      DOI: 10.1111/all.13266
  • Assessment of eosinophilic airway inflammation as a contribution to the
           diagnosis of occupational asthma
    • Authors: Carolina Beretta; Catherine Rifflart, Geneviève Evrard, Jacques Jamart, Joël Thimpont, Olivier Vandenplas
      Abstract: BackgroundAscertaining the presence of asthma through the assessment of nonspecific bronchial hyperresponsiveness (NSBH) is a key step in the diagnosis of occupational asthma (OA). We aimed at investigating whether indices of airway inflammation including fractional exhaled nitric oxide (FeNO) and sputum eosinophils would be useful adjuncts to the measurement of NSBH in diagnosing OA defined as a positive specific inhalation challenge (SIC).MethodsThe study included 240 consecutive subjects with a suspicion of OA who completed a SIC, of whom 133 showed a positive response. The sensitivity, specificity, and predictive values of NSBH, and FeNO, as well as sputum eosinophil counts assessed at baseline of the SIC were determined.ResultsA concentration of histamine inducing a 20% decline in FEV1 (PC20) ≤16 mg/mL showed a sensitivity of 87% and a specificity of 36%. A FeNO level ≥25 ppb and a sputum eosinophil count ≥ 2% provided lower sensitivity rates (47% and 39%, respectively) than the PC20 value. Eight of the 17 subjects without baseline NSBH despite a positive SIC showed a sputum eosinophil count ≥2%, a FeNO level ≥25 ppb or both outcomes. Combining either a PC20 value ≤16mg/mL or a FeNO ≥25 ppb increased the sensitivity to 91%. Using either a PC20 ≤16mg/mL or a sputum eosinophil count ≥1% increased the sensitivity to 94%.ConclusionAdding the assessment of FeNO level and sputum eosinophils to NSBH improves the identification of subjects who may have OA and require further objective testing before excluding the possibility of OA.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-03T12:40:19.836433-05:
      DOI: 10.1111/all.13265
  • Blood and Nasal Epigenetics Correlate to Allergic Rhinitis Symptom
           Development in the Environmental Exposure Unit
    • Authors: Michelle L. North; Meaghan J. Jones, Julia L. MacIsaac, Alexander M. Morin, Lisa M. Steacy, Alexander Gregor, Michael S. Kobor, Anne K. Ellis
      Abstract: BackgroundEpigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis (AR). Our aim was to examine genome-wide epigenetic changes induced by controlled pollen exposure in the Environmental Exposure Unit (EEU).Methods38 AR-sufferers and 8 non-allergic controls were exposed to grass pollen for 3h on two consecutive days. We interrogated DNA methylation at baseline and 3h in peripheral blood mononuclear cells (PBMCs) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini-Hochberg), and verified hits using bisulfite PCR-pyrosequencing and qPCR. To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 (MUC4), in nasal brushings from a separate validation cohort exposed to birch pollen.ResultsIn PBMCs of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 (TPSG1), schlafen 12 (SLFN12) and MUC4 in response to exposure were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated with symptoms (p
      PubDate: 2017-07-29T09:50:33.932439-05:
      DOI: 10.1111/all.13263
  • EAACI Guidelines on Allergen Immunotherapy: Hymenoptera venom allergy
    • Authors: Gunter J Sturm; Eva-Maria Varga, Graham Roberts, Holger Mosbech, M. Beatrice Bilò, Cezmi A Akdis, Darío Antolín-Amérigo, Ewa Cichocka-Jarosz, Radoslaw Gawlik, Thilo Jakob, Mitja Kosnik, Joanna Lange, Ervin Mingomataj, Dimitris I Mitsias, Markus Ollert, Joanna N.G. Oude Elberink, Oliver Pfaar, Constantinos Pitsios, Valerio Pravettoni, Franziska Ruëff, Betül Ayşe Sin, Ioana Agache, Elizabeth Angier, Stefania Arasi, Moises A Calderón, Montserrat Fernandez-Rivas, Susanne Halken, Marek Jutel, Susanne Lau, Giovanni B Pajno, Ronald van Ree, Dermot Ryan, Otto Spranger, Roy Gerth van Wijk, Sangeeta Dhami, Hadar Zaman, Aziz Sheikh, Antonella Muraro
      Abstract: Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid or ant sting. Systemic allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate-to-severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1-antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom allergic children and adults to prevent further moderate to severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline auto-injector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-27T03:05:35.002498-05:
      DOI: 10.1111/all.13262
  • ADAM10 and Notch1 on murine dendritic cells control the development of
           type 2 immunity and IgE production
    • Authors: Sheela R. Damle; Rebecca K. Martin, Chelsea L. Cockburn, Joseph C. Lownik, Jason A. Carlyon, Allen D. Smith, Daniel H. Conrad
      Abstract: BackgroundAllergy and allergic asthma are significant health burdens in developed countries and are increasing in prevalence. Dendritic cells (DCs) initiate immune responses to common aeroallergens and ADAM10 has been demonstrated to be important for the development of adaptive responses. This study's objective was to understand the role of ADAM10 on DCs in the development of allergic and anaphylactic responses.MethodsIn this study we used mouse models of allergic airway inflammation (house dust mice and Alternaria alternata) and OVA-induced models of active anaphylaxis to determine the DC-specific function of ADAM10 and Notch signaling. To examine TH1 and TH17 immunity infection with Anaplasma phagocytophilum and Citrobacter rodentium were used.ResultsMice, which have ADAM10 deleted from DCs, have dramatic reductions in IgE production and do not develop significant TH2 immune responses. Further, ADAM10DC-/- mice are resistant to IgE-mediated anaphylaxis. This response is selective for TH2 immunity as TH1 and TH17 immunity are largely unaffected. Notch1, a known ADAM10 substrate, when knocked out of DCs (Notch1DC-/-) demonstrated a similar reduction in anaphylaxis and IgE. Without ADAM10 and Notch1 signaling, DCs were unable to make cytokines that stimulate TH2 cells and cytokines. Anaphylaxis and allergic lung inflammation were restored in ADAM10DC-/- with the overexpression of the Notch1-intracellular domain, confirming the role of Notch signaling.ConclusionsTargeting ADAM10 and Notch1 on DCs represent a novel strategy for modulating TH2 immune responses and IgE production.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-26T03:12:45.294422-05:
      DOI: 10.1111/all.13261
  • House dust mites as potential carriers for IgE sensitisation to bacterial
    • Authors: Sheron Dzoro; Irene Mittermann, Yvonne Resch, Susanne Vrtala, Marion Nehr, Alexander M. Hirschl, Gustav Wikberg, Lena Lundeberg, Catharina Johansson, Annika Scheynius, Rudolf Valenta
      Abstract: BackgroundIgE-reactivity to antigens from gram-positive and negative bacteria is common in patients suffering from respiratory and skin manifestations of allergy, but the routes and mechanisms of sensitisation are not fully understood. The analysis of the genome, transcriptome and microbiome of house dust mites (HDM) has shown that S. aureus and E. coli species are abundant bacteria within the HDM microbiome. Therefore, our aim was to investigate if HDM are carriers of bacterial antigens leading to IgE sensitisation in patients suffering from atopic dermatitis.MethodsPlasma samples from AD patients (n=179) were analysed for IgE-reactivity to a comprehensive panel of micro-arrayed HDM allergen molecules and to S. aureus and E. coli by IgE immunoblotting. Antibodies specific for S. aureus and E. coli antigens were tested for reactivity to nitrocellulose-blotted extract from purified HDM bodies and the IgE-reactive antigens were detected by IgE-immunoblot inhibition experiments. IgE antibodies directed to bacterial antigens in HDM were quantified by IgE ImmunoCAP™ inhibition experiments.ResultsIgE-reactivity to bacterial antigens was significantly more frequent in AD patients sensitised to HDM than in AD patients without HDM sensitisation. S. aureus and E. coli antigens were detected in immune-blotted HDM extract and the presence of IgE-reactive antigens in HDM was demonstrated by qualitative and quantitative IgE inhibition experiments.ConclusionHDM may serve as carriers of bacteria responsible for the induction of IgE sensitisation to microbial antigens.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-25T03:45:19.982048-05:
      DOI: 10.1111/all.13260
  • Asthma in the Elderly and Late-onset Adult Asthma
    • Authors: Ryan M. Dunn; Paula J. Busse, Michael E. Wechsler
      Abstract: Elderly asthmatics are at a higher risk for morbidity and mortality from their asthma than younger patients. There are important age-related physiologic and immunologic changes that complicate the presentation, diagnosis and management of asthma in the aged population. Evidence suggests that elderly asthmatics are more likely to be under-diagnosed and under-treated. Additionally, elderly patients with asthma have highest rates of morbidity and mortality from their disease than younger patients. The underlying airway inflammation of asthma in this age group likely differs from younger patients and is felt to be non-Type 2 mediated. While elderly patients are underrepresented in clinical trials, subgroup analysis of large clinical trials suggests they may be less likely to respond to traditional asthma therapies (i.e., corticosteroids). As the armamentarium of pharmacologic asthma therapies expands, it will be critical to include elderly asthmatics in large clinical trials so that therapy may be better tailored to this at-risk and growing population.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-19T10:15:36.971033-05:
      DOI: 10.1111/all.13258
  • The potential of anti-infectives and immunomodulators as therapies for
           asthma and asthma exacerbations
    • Authors: Michael R Edwards; Ross P Walton, David J Jackson, Wojciech Feleszko, Chrysanthi Skevaki, Tuomas Jartti, Heidi Makrinoti, Alexandra Nikonova, Igor Shilovskiy, Jurgen Schwarze, Sebastian L. Johnston, Musa Khaitov
      Abstract: Asthma is responsible for approximately 25,000 deaths annually in Europe despite available medicines that maintain asthma control and reduce asthma exacerbations. Better treatments are urgently needed for the control of chronic asthma and reduction of asthma exacerbations, the major cause of asthma mortality. Much research spanning>20 years shows a strong association between microorganisms including pathogens in asthma onset, severity and exacerbation, yet with the exception of antibiotics, few treatments are available that specifically target the offending pathogens. Recent insights into the microbiome suggest that modulating commensal organisms within the gut or lung may also be a possible way to treat/prevent asthma. The European Academy of Allergy & Clinical Immunology Task Force on Anti-infectives in Asthma was initiated to investigate the potential of anti-infectives and immunomodulators in asthma. This review provides a concise summary of the current literature and aims to identify and address key questions that concern the use of anti-infectives and both microbe and host based immunomodulators and their feasibility for use in asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-19T10:15:34.019993-05:
      DOI: 10.1111/all.13257
  • Computational validation of the recently proposed pollen season definition
    • Authors: K. Karatzas; M. Riga, U. Berger, M. Werchan, O. Pfaar, K.Ch. Bergmann
      Abstract: In a recently published paper (Pfaar et al., 2016), a Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI suggested specific criteria for the definition of pollen exposure times for three types of pollen events: (a) Pollen Season (PS) start and end, (b) high pollen season (or Peak Pollen Period-PPP) start and end, and (c) high pollen days. Species addressed included Birch, Grasses, Cypress, Olive, and Ragweed. Two important questions arise from the aforementioned definitions: (i) do they lead to a narrow (thus well defined) time interval identifying start and end event dates (robustness of the criteria) and (ii) if slightly altered, will they result to a narrow (thus again well defined) fluctuation of start and end event dates (sensitivity of the criteria)' In an effort to provide with responses to aforementioned questions, we analyzed Poaceae pollen count data coming from Germany (up to 40 pollen monitoring stations, years 2012-2016). The analysis addressed all pollen events for the first question, and focused on the PS and PPP start and end events for the second question.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-18T10:29:39.437808-05:
      DOI: 10.1111/all.13255
  • Long term effects: Galectin-1 and specific immunotherapy for allergic
           responses in the intestine
    • Authors: Li-Tao Yang; Qing Shu, Xiang-Qian Luo, Zhi-Qiang Liu, Shu-Qi Qiu, Jiang-Qi Liu, Hai-Jian Guo, Lin-Jing Li, Mao-Gang Li, Da-Bo Liu, Li-Xin Xia, Zhi-Gang Liu, Ping-Chang Yang
      Abstract: Background and aimsMast cell activation interferes with the effects of allergen-specific immunotherapy (SIT). Galectin-1 (Gal-1) is capable of regulating immune cells’ functions. This study tests the hypothesis that administration of Gal-1 promotes and prolongs the efficacy of SIT via suppressing mast cell activation.MethodsAn intestinal allergy mouse model was developed. The co-administration of SIT and Gal-1 on suppression of the allergic responses, prevention of mast cell activation, and generation of antigen-specific regulatory T cells (Treg) in the intestine were observed in sensitized mice.ResultsThe coadministration of Gal-1 and SIT markedly suppressed the allergic responses in the mouse intestine vs. the use of either SIT alone or Gal-1 alone. The Gal-1 binds to the IgE/FcɛRI complexes on the surface of mast cells to prevent mast cell activation during SIT. Gal-1 promoted the SIT-generated allergen-specific Tregs in the intestine of sensitized mice. Coadministration of Gal-1 and SIT significantly enhanced the efficacy of immunotherapy in suppressing allergic responses in the intestine, which lasted for at least for 12 months.ConclusionsLong term effects of specific immunotherapy on intestinal allergy can be achieved with Gal-1/SIT therapy by inhibiting mast cell activation and facilitating Treg development.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-18T10:29:33.724806-05:
      DOI: 10.1111/all.13256
  • Health Economic Analysis of Allergen Immunotherapy (AIT) for the
           Management of Allergic Rhinitis, Asthma, Food Allergy and Venom Allergy: A
           Systematic Overview
    • Authors: Miqdad Asaria; Sangeeta Dhami, Ronald van Ree, Roy Gerth van Wijk, Antonella Muraro, Graham Roberts, Aziz Sheikh
      Abstract: BackgroundThe European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE-mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT for these conditions. This paper focusses on synthesizing data and gaps in the evidence on the cost-effectiveness of AIT for these conditions.MethodsWe produced summaries of evidence in each domain and then synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies were independently assessed using the Critical Appraisal Skills Programme (CASP) tool for health economic evaluations.Results23 studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost-effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost-effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost-effectiveness threshold of £20,000/quality adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost-effective with an incremental cost-effectiveness ratio (ICER) of £10,726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost-effective for very high risk groups who may be exposed to multiple exposures to venom/year (e.g., bee keepers). We found no eligible studies investigating the cost-effectiveness of AIT for food allergy.ConclusionsOverall the evidence to support the cost-effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost-effective for people with allergic rhinitis with or without asthma and in high risk subgroups for venom allergy. We were unable to draw any conclusions on the cost-effectiveness of AIT for food allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-18T10:29:30.320786-05:
      DOI: 10.1111/all.13254
  • Therapeutic effect of capsaicin nasal treatment in patients with mixed
           rhinitis unresponsive to intranasal steroids
    • Authors: Laura Van Gerven; B Steelant, Y. A. Alpizar, Karel Talavera, Peter W Hellings
      Abstract: Literature is convincing regarding the efficacy of capsaicin nasal treatment in idiopathic rhinitis (IR). However, up to 50% of IR patients do not meet the strict inclusion criteria of the trials conducted so far. As a consequence, the efficacy of capsaicin is unknown in a significant number of IR patients that do not meet the strict inclusion/exclusion criteria (1)(2). ‘Mixed rhinitis’ (MR) patients have more than one major etiologic factor involved in the mucosal pathology. We have no idea about the efficacy of capsaicin nasal spray in these patients nor about the time interval to seek a second application. We report here that capsaicin nasal spray is effective in a broader group of IR than the purely selected ones described before, that subjective nasal hyperreactivity is a good predictor of positive outcome and that the time interval for seeking a second treatment is likely to be shorter in MR patients than in the strictly selected IR patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-16T08:05:25.013486-05:
      DOI: 10.1111/all.13245
  • Evidence of an abnormal epithelial barrier in active, untreated and
           corticosteroid-treated eosinophilic esophagitis
    • Authors: Dagmar Simon; Basile Page, Monique Vogel, Christian Bussmann, Carine Blanchard, Alex Straumann, Hans-Uwe Simon
      Abstract: BackgroundEosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated disease characterized by symptoms related to esophageal dysfunction and an eosinophil-predominant inflammation. This study has aimed to investigate whether the recently observed sensitization to Candida albicans in EoE patients is owing to pre-existing disease and its underlying abnormal epithelial barrier or, alternatively, is linked to corticosteroid (CS) therapy.MethodsMedical histories, as well as serum and tissue samples of 60 EoE patients (15 CS-naive, 45 with current or previous CS therapy) and 20 controls, stored in the Swiss Eosinophilic Esophagitis Database (SEED) and Biobank, were analyzed. We applied ImmunoCAP to measure IgE levels and immunofluorescence techniques to examine epithelial barrier components.ResultsEoE patients had higher total IgE levels and were more frequently sensitized to Candida albicans than controls. In EoE tissue specimens, increased numbers of eosinophils and mast cells, a higher expression levels of thymic stromal lymphopoietin (TSLP), cathelicidin, proteases, i.e. the kallikreins (KLK)-5 and KLK-7, were observed as compared with controls, while reduced expression of lympho-epithelial Kazal-type-related inhibitor (LEKTI), filaggrin, E-cadherin, claudin, occludin, demoglein-1 was found, independent of CS therapy. In CS-treated EoE, significantly lower numbers of CD1a+ cells and cathelicidin expression were noted as compared to CS-naive EoE.ConclusionThis study provides further evidence that EoE is associated with an abnormal epithelial barrier and postulates that CS therapy, by reducing innate immune mechanisms, may promote Candida albicans colonization and likely subsequent sensitization.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-16T08:05:22.863863-05:
      DOI: 10.1111/all.13244
  • A comparative study on basophil activation test, histamine release assay
           and passive sensitization histamine release assay in the diagnosis of
           peanut allergy
    • Authors: Lau Fabricius Larsen; Nanna Juel-Berg, Kirsten Skamstrup Hansen, E. N. Clare Mills, Ronald Ree, Lars K. Poulsen, Bettina M. Jensen
      Abstract: BackgroundAllergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release assay (HR) and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy.MethodsBAT, HR, and passive HR were performed on eleven peanut allergic and fourteen non-allergic subjects. Blood was incubated with peanut extract or anti-IgE and tests performed as follows: BAT - CD63-upregulation assessed by flow cytometry; HR - released histamine quantified by a glass fiber-based fluorometric method; Passive HR - IgE-stripped donor basophils were incubated with participants’ serum and histamine release quantified as HR.ResultsCDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1 ± 17.4) compared to HR (23.4 ± 10.31) and passive HR (11.1 ± 2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82%, and specificity of 100%, 100%, and 100%, respectively when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10 and passive HR 9. Likewise, BAT recognized 12 of 14 non-allergic subjects, HR 10 and passive HR 13. However, the tests’ diagnostic performances were not statistically different. Interestingly, non-releasers in HR but not in BAT had lower basophil count compared to releasers (249 vs. 630 counts/min).ConclusionBAT displayed a significant higher CDsens compared to HR and passive HR. The basophil tests’ diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-07T08:15:29.642544-05:
      DOI: 10.1111/all.13243
  • Vitamin D supplementation in primary allergy prevention: systematic review
           of randomized and non-randomized studies
    • Authors: Juan José Yepes-Nuñez; Jan L. Brożek, Alessandro Fiocchi, Ruby Pawankar, Carlos Cuello-García, Yuan Zhang, Gian Paolo Morgano, Arnav Agarwal, Shreyas Gandhi, Luigi Terracciano, Holger J. Schünemann
      Abstract: BackgroundTo date, a systematic review of the evidence regarding the association between Vitamin D and allergic diseases development has not yet been undertaken.ObjectiveTo review the efficacy and safety of Vitamin D supplementation when compared to no supplementation in pregnant women, breastfeeding women, infants and children for the prevention of allergies.MethodsThree databases were searched through 30 January 2016 including randomized (RCT) and non-randomized studies (NRS). Two reviewers independently extracted data and assessed the certainty in the body of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsAmong the 1932 articles identified, one RCT and four NRS were eligible. Very low certainty in the body of evidence across examined studies suggests that Vitamin D supplementation for pregnant women, breastfeeding women and infants may not decrease the risk of developing allergic diseases such as atopic dermatitis (in pregnant women), allergic rhinitis (in pregnant women, and infants), asthma and/or wheezing (in pregnant women, breastfeeding women, and infants), or food allergies (in pregnant women). We found no studies of primary prevention of allergic diseases in children.ConclusionLimited information is available addressing primary prevention of allergic diseases after Vitamin D supplementation and its potential impact remains uncertain.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-04T13:10:37.198216-05:
      DOI: 10.1111/all.13241
  • Estimating the causal effect of body mass index on hay fever, asthma, and
           lung function using Mendelian randomization
    • Authors: Tea Skaaby; Amy E. Taylor, Betina H. Thuesen, Rikke K. Jacobsen, Nele Friedrich, Line Tang Møllehave, Susanne Hansen, Sofus C. Larsen, Uwe Völker, Matthias Nauck, Henry Völzke, Torben Hansen, Oluf Pedersen, Torben Jørgensen, Lavinia Paternoster, Marcus Munafò, Niels Grarup, Allan Linneberg
      Abstract: BackgroundObservational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as un-confounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC).MethodsWe included 490,497 participants in the observational and 162,124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI).ResultsThe GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002), or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 ml decrease), and a 16 ml decrease in FVC (95% CI: 7.0-24 ml decrease) per 1 kg/m2 higher BMI.ConclusionsThe results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-04T13:10:29.03563-05:0
      DOI: 10.1111/all.13242
  • Ultra-short-course booster is effective in recurrent grass
           pollen–induced allergic rhinitis
    • Authors: O. Pfaar; S. Lang, U. Pieper-Fürst, A. Astvatsatourov, F. Gerich, L. Klimek, M. F. Kramer, Y. Reydelet, K. Shah-Hosseini, R. Mösges
      Abstract: BackgroundA relevant proportion of allergic rhinitis (AR) patients experience recurrent symptoms after successfully completing allergen immunotherapy (AIT). This prospective, controlled, non-interventional study used internationally standardised instruments to determine the clinical effects of a preseasonal, ultra-short-course booster AIT on clinical outcome parameters.MethodsThis two-arm study included patients aged ≥12 years with recurrent grass pollen–induced seasonal AR who had completed a successful course of any grass pollen AIT at least five years before enrolment. Overall, 56 patients received one preseasonal short-course booster AIT using tyrosine-absorbed grass pollen allergoids containing the adjuvant monophosphoryl lipid A (MPL®); 51 control patients received symptomatic medication. The combined symptom and medication score (CSMS) was recorded in the (peak) grass pollen season. Furthermore, concomitant (antiallergic) medication use, the patients'state of health, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) results, and safety/tolerability of the treatment were assessed.ResultsThe CSMS in the peak grass pollen season was significantly lower in the booster AIT group (Δ=38.4%, P
      PubDate: 2017-07-04T02:20:41.796844-05:
      DOI: 10.1111/all.13240
  • Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in
           atopic dermatitis
    • Authors: Masutaka Furue; Kazuhiko Yamamura, Makiko Kido-Nakahara, Takeshi Nakahara, Yoshinori Fukui
      Abstract: Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder associated with skin barrier dysfunction. The lesional skin of AD exhibits T helper 2 (TH2)-deviated immune reactions. Interleukin-31 (IL-31), preferentially produced from TH2 cells, is a potent pruritogenic cytokine, and its systemic and local administration induces scratching behavior in rodents, dogs and monkeys. Recent clinical trials have revealed that administration of an anti-IL-31 receptor antibody significantly alleviates pruritus in patients with AD. In this review, we summarize recent topics related to IL-31 and its receptor with special references to atopic itch.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-03T02:26:52.735656-05:
      DOI: 10.1111/all.13239
  • Meat allergy associated with α-Gal – Closing diagnostic gaps by
           anti-α-Gal IgE immune profiling
    • Authors: U. Jappe; S. Minge, B. Kreft, A. Ludwig, B. Przybilla, A. Walker, R. Varga, P. Seidel, T. Biedermann, W. Anemüller, A. Kromminga, F. Ruëff, H. Merk, N. Wagner, R. Treudler, M. Worm, I. Waldmann, J. Saloga, W. M. Becker, T. Goldmann, T. A. Platts-Mills, A. Homann
      Abstract: BackgroundGlycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-α-(1,3)-galactose (α-Gal). It is known that α-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. α-Gal is part of the IgE-reactive monoclonal therapeutic antibody cetuximab and is associated with delayed anaphylaxis to red meat. In this study, different alpha-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α-Gal.MethodsThree serum groups, α-Gal-associated meat allergy (MA) patients, idiopathic anaphylaxis (IA) patients with suspected meat allergy and non-meat-allergic healthy control individuals (HC), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for α-Gal-containing analytes cetuximab, bovine thyroglobulin and HSA-conjugated α-Gal.ResultsSingleplex allergy diagnostics using the α-Gal-analytes cetuximab and bovine thyroglobulin confirms the history of meat allergy patients in 91% and 88% of the cases, respectively. A novel dot-blot-based assay system for the detection of IgE against α-Gal reveals individual IgE sensitization profiles for α-Gal-containing analytes. An α-Gal-associated IgE cross-reactivity profile (IgE against cetuximab, bovine thyroglobulin and HSA-α-Gal) was identified, which is associated with meat allergy.ConclusionsDetection of individual sensitization patterns with different α-Gal-containing analytes provides the basis for an individual allergy diagnosis for α-Gal sensitized patients. Higher amounts of α-Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.This article is protected by copyright. All rights reserved.
      PubDate: 2017-07-03T02:20:24.596553-05:
      DOI: 10.1111/all.13238
  • Omalizumab prevents anaphylaxis and improves symptoms in systemic
           mastocytosis; efficacy and safety observations
    • Authors: Sigurd Broesby-Olsen; Hanne Vestergaard, Charlotte Gotthard Mortz, Britt Jensen, Troels Havelund, Anne Pernille Hermann, Frank Siebenhaar, Michael Boe Møller, Thomas Kielsgaard Kristensen, Carsten Bindslev-Jensen,
      Abstract: BackgroundPatients with systemic mastocytosis (SM) may suffer from mast cell (MC) mediator-related symptoms insufficiently controlled by conventional therapy. Omalizumab is an established treatment in other MC-driven diseases, but experiences in SM are limited.ObjectiveTo assess the efficacy and safety of omalizumab in SM.MethodsIn our patient cohort we evaluated all SM patients treated with omalizumab. A physician global assessment of type and severity of symptoms was performed at baseline, at 3 and 6 months and at latest follow-up. Quality-of-life was assessed by visual analogue scale. S-tryptase and KIT D816V allele burden were monitored.ResultsA total of 14 adult SM patients (10 ISM, 2 BMM, 1 SSM and 1 ASM-AHN) received omalizumab with a median duration of 17 months (range: 1-73 months). One patient was excluded due to concomitant cytoreductive therapy. In the remaining 13 patients we observed a significant reduction of symptoms, with complete symptom control in five (38.5%), major response in three (23.1%) and a partial response in three (23.1%) patients, whereas two patients (15.4%) withdrew due to subjective side-effects at first dose. The treatment was most effective for recurrent anaphylaxis and skin symptoms, less for gastrointestinal, musculoskeletal and neuropsychiatric symptoms. Patient-reported quality-of-life showed significant improvement. No significant changes in s-tryptase/KIT D816V allele burden were observed. No severe adverse events were recorded.ConclusionsOmalizumab appears to be a promising treatment option in SM, effectively preventing anaphylaxis and improving chronic MC mediator-related symptoms, insufficiently controlled by conventional therapy. Controlled studies are needed to substantiate findings.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-29T14:55:18.685173-05:
      DOI: 10.1111/all.13237
  • Immediate moxifloxacin hypersensitivity: is there more than currently
           meets the eye'
    • Authors: Athina L Van Gasse; Vito Sabato, A P Uyttebroek, Jessy Elst, Margaretha A Faber, Margo M Hagendorens, Christel Mertens, Chris H Bridts, Luc S De Clerck, Didier G Ebo
      Abstract: Immediate drug hypersensitivity reactions (IDHR) to moxifloxacin constitute a pathomechanistic conundrum and a diagnostic challenge. Our objective was to study whether simultaneous phenotyping and quantification of histamine release might add to our knowledge about the basophil activation properties of moxifloxacin and constitute a reliable diagnostic aid. Fifteen patients with an IDHR to moxifloxacin and 9 moxifloxacin challenged controls were selected. All had a basophil activation test (BAT) with moxifloxacin. Flow cytometric analysis of basophil responses implied labeling for CD63, CD203c and intracellular histamine. Unlike tolerant challenged controls, basophilic upregulation of CD203c in response to moxifloxacin was observed in 7/15 patients. Only 2 of these 7 patients demonstrated appearance of CD63 and release of histamine. In the remainder 8 patients no basophil responses were demonstrable. In conclusion, immediate hypersensitivity to moxifloxacin might involve mechanisms difficult to capture by traditional CD63/CD203c-based BAT. Deciphering the complexity of quinolone IDHR seems mandatory.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-28T11:31:28.045139-05:
      DOI: 10.1111/all.13236
  • Delayed type hypersensitivity reactions induced by proton pump inhibitors:
           a clinical and in vitro T cell reactivity study
    • Authors: Chien-yio Lin; Chuang-Wei Wang, Chung-Yee Rosaline Hui, Ya-Ching Chang, Chih-Hsun Yang, Chi-Yuan Cheng, Wen-Wen Chen, Wei-Ming Ke, Wen-Hung Chung
      Abstract: BackgroundProton pump inhibitors (PPI) has been known to induce type I hypersensitivity reactions. However, severe delayed type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T cell reactivity to PPI in PPI-related DHR patients.MethodsWe retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities.ResultsThere were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay.ConclusionsPPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-28T11:31:24.405618-05:
      DOI: 10.1111/all.13235
  • Fibroblast-derived exosomes promote epithelial cell proliferation through
           TGF-β2 signaling pathway in severe asthma
    • Authors: Ikhlass haj-Salem; Sophie Plante, Abdelilah S. Gounni, Mahmoud Rouabhia, Jamila Chakir
      Abstract: BackgroundBronchial fibroblasts play a key role in airway remodeling in asthma. They regulate epithelial cell functions such as proliferation through growth factors, cytokines, chemokines and exosomes. The role of exosomes in the communication between epithelial cells and fibroblasts by vehiculing these mediators in asthma remains to be determined.ObjectiveTo evaluate the role of exosomes released by bronchial fibroblasts on epithelial cell proliferation in severe asthma.MethodsExosomes were obtained from culture media of primary bronchial fibroblasts and characterized using Western blot, electron microscopy and flow cytometry. Uptake profile of fluorescent-labeled exosomes in epithelial cells was assessed by flow cytometry. Exosome cytokine content was analysed by Cytokine Arrays. Bronchial epithelial cell proliferation was evaluated by BrdU incorporation test. Exosomes biogenesis/release was blocked by using sphingomyelinase inhibitor. Plasmid transfection was used to modulate TGF-β2 gene expression.ResultsWe showed that bronchial fibroblasts secreted exosomes, which were internalized by bronchial epithelial cells. Exosomes of severe asthmatic subjects’ fibroblasts showed a lower level of TGF-β2 and significantly increased the epithelial cells proliferation of both healthy and severe asthmatic subjects compared to healthy controls’ exosomes. Overexpression of TGF-β2 in severe asthmatics’ fibroblasts induced enhanced TGF-β2 in exosomes leading to a reduced proliferation of epithelial cells, whereas knockdown of TGF-β2 enhanced epithelial cell proliferation.ConclusionOur study shows that exosomes are involved in fine-tuning intercellular communication in asthma. Exosomes of severe eosinophilic asthmatics’ fibroblasts can contribute to airway remodeling, at least in part, by modulating epithelial cell proliferation observed in severe asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-26T01:42:31.525685-05:
      DOI: 10.1111/all.13234
  • Cytomegalovirus DNA is highly prevalent in the blood of patients with
           asthma and is associated with age and asthma traits
    • Authors: Marek L. Kowalski; Aleksandra Wardzynska, Miroslawa Studzinska, Malgorzata Pawelczyk, Zbigniew Jan Lesnikowski, Edyta Paradowska
      Abstract: CMV IgG antibodies have been associated with inflammageing and immunosenescence. We aimed to assess the presence of CMV DNA in the blood of adult and elderly patients with bronchial asthma to establish potential association of CMV DNAemia with asthma and asthma characteristics. Eighty-five elderly asthmatics, 74 younger asthma patients and 114 age-matched controls were recruited. The CMV DNA was detected using commercial artus assay in 10.7% of asthma patients, but was negative in all control individuals. The secondary assay identified CMV DNA in 41.5% of asthmatics and 13.3% of control subjects (p
      PubDate: 2017-06-22T21:20:28.258004-05:
      DOI: 10.1111/all.13233
  • Atopic dermatitis is associated with anxiety, depression, and suicidal
           ideation, but not with hospitalization or suicide
    • Authors: Jacob P. Thyssen; Carsten R. Hamann, Allan Linneberg, Thomas Meinertz Dantoft, Lone Skov, Gunnar H. Gislason, Jashin J. Wu, Alexander Egeberg
      Abstract: BackgroundAtopic dermatitis (AD) has been linked with psychiatric disease in adults. However, the exact relationship and its consequences have been insufficiently studied. Our aim in this study was to assess the association between depression, anxiety and AD in adults, and examine the risk of hospitalization and suicide.MethodsWe utilized questionnaire data from a large general population study with data on social habits and psychiatric symptoms to compare prevalences of depression, anxiety, suicidal ideation, and anxiety attacks, in adults with and without a history of AD. Additionally we used nationwide hospital/clinic registry and prescription data to examine the risk of anxiety and depression in Danish adults with mild and moderate-severe AD, as well as the risk of hospitalization and suicide.ResultsIn the general population study, those with AD reported clinician-diagnosed depression and anxiety more often than non-AD subjects, and had an increased prevalence of suicidal ideation and depressive symptoms. In the health registry study, moderate-severe AD patients had increased risk of antidepressant and anxiolytic medication use, while patients with mild AD only had increased risk of anxiolytic medication use. There was no increased risk of hospitalization or outpatient contacts due to depression or anxiety, or risk of suicide in AD patients.ConclusionsDepression, anxiety, and suicidal ideation are more common among AD individuals, but do not to lead to psychiatric consultations, hospitalization, or suicide.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-20T13:16:04.878-05:00
      DOI: 10.1111/all.13231
  • A prospective microbiome-wide association study of food sensitization and
           food allergy in early childhood
    • Authors: Jessica H. Savage; Kathleen A. Lee-Sarwar, Joanne Sordillo, Supinda Bunyavanich, Yanjiao Zhou, George O'Connor, Megan Sandel, Leonard Bacharier, Robert Zeiger, Erica Sodergren, George M Weinstock, Diane R. Gold, Scott T. Weiss, Augusto A. Litonjua
      Abstract: BackgroundAlterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development.MethodsIntestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high dose Vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 with evidence of IgE sensitization. Analysis was performed using Phyloseq and DESeq2; p-values were adjusted for multiple comparisons.ResultsComplete data were available for 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases and controls. The genera Haemophilus (log2 fold change -2.15, p=0.003), Dialister (log2 fold change -2.22, p=0.009), Dorea (log2 fold change -1.65, p=0.02) and Clostridium (log2 fold change -1.47, p=0.002) were underrepresented among subjects with food sensitization. The genera Citrobacter (log2 fold change -3.41, p=0.03), Oscillospira (log2 fold change -2.80, p=0.03), Lactococcus (log2 fold change -3.19, p=0.05) and Dorea (log2 fold change -3.00, p=0.05) were underrepresented among subjects with food allergy.ConclusionsThe temporal association between bacterial colonization and food sensitization and allergy suggests that the microbiome may have a causal role in the development of food allergy. Our findings have therapeutic implications for the prevention and treatment of food allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-20T13:16:01.451215-05:
      DOI: 10.1111/all.13232
  • Histamine Receptor 2 Modifies iNKT Cell Activity within the Inflamed Lung
    • Authors: R. Ferstl; R. Frei, W. Barcik, E. Schiavi, K. Wanke, M. Ziegler, N. Rodriguez-Perez, D. Groeger, P. Konieczna, S. Zeiter, D. Nehrbass, Roger Lauener, C.A. Akdis, L. O'Mahony
      Abstract: BackgroundHistamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2R). The aim of this study was to determine the role of H2R in modulating lung inflammatory responses.MethodsH2R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2R-deficient animals and CD1d/ H2R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGal-Cer or OCH) to invariant Natural Killer T (iNKT) cells.ResultsFamotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM-induced airway disease were more severe in H2R-deficient animals. Flow cytometric analysis of lung tissue from H2R-deficient animals revealed increased numbers of CD1d+ dendritic cells and increased numbers of iNKT cells. In vitro, αGal-Cer-stimulated iNKT cells from H2R-deficient mice secreted higher levels of IL-4, IL-5 and GM-CSF. In vivo, αGal-Cer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment and cytokine production in H2R-deficient or famotidine-treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H2R-deficient (CD1d-/-H2R-/-) animals normalized the lung response to HDM.ConclusionThe deliberate activation of H2R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD1d-mediated presentation of lipid antigens to iNKT cells are contributing to the pathology.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-15T05:20:22.702153-05:
      DOI: 10.1111/all.13227
  • Is the atopic march related to confounding by genetics and early life
           environment' A systematic review of sibship and twin data
    • Authors: Sabria J. Khan; Shyamali C. Dharmage, Melanie C. Matheson, Lyle C. Gurrin
      Abstract: A popular hypothesis known as the atopic march proposes a set of sequential allergy and respiratory disorders in early childhood contributes enormously to the burden of disease in developed countries. Although the concept of the atopic march has been refined and strengthened by many cross-sectional and longitudinal studies linking eczema as the initial manifestation with progression to hay fever and then asthma, there is yet no definitive proof that the atopic march is the primary causal factor in childhood allergic disease. This debate is mainly related to the controversy around potential confounding of these associations by genetic and environmental factors. Family studies are ideally suited to unravelling the role of these factors. While multiple reviews have synthesised evidence from studies investigating this question, no review to date has explored specific evidence generated by twin and sibling studies to understand the aetiology of atopic march diseases. Our aim was to conduct a systematic review of twin and sibling studies that examine the allergic phenotypes that form the atopic march, to determine whether such analyses of data from these studies attempt to control for the effect confounding by shared factors, and to report estimates the magnitude of associations between multiple phenotypes. Our review suggests that (1) genetics play a bigger role predisposing eczema to hay fever and eczema to asthma than environmental factors; and (2) the link between eczema, and asthma and hay fever is independent of shared early life environmental factors and genetics.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-15T05:15:22.798184-05:
      DOI: 10.1111/all.13228
  • Validation of International consensus equation for acute serum total
           tryptase in mast cell activation: A perioperative perspective
    • Authors: Richard L Baretto; Sarah Beck, Jane Heslegrave, Cathryn Melchior, Omar Mohamed, Anjali Ekbote, Aarnoud P Huissoon, Mamidipudi T Krishna
      Abstract: IntroductionThere is no standardised method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2x baseline tryptase+2mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS).AimTo validate consensus equation in a setting of perioperative anaphylaxis.MethodsAnalyses of suspected perioperative anaphylaxis during general anaesthesia (GA). Anaphylaxis was defined as per World Allergy Organisation (WAO) criteria. Timed serial MCT measurements were mapped against the consensus equation and receiver operating characteristic (ROC) curves produced.Results82 patients (60 females, mean age 56.5 years ± SD17.2) underwent investigation. 60 (73%) patients fulfilled WAO criteria for anaphylaxis and 22 patients did not (controls). Aetiology: 59% IgE-mediated anaphylaxis, 2% non-IgE mediated anaphylaxis, 12% anaphylaxis of unknown cause, and 27% deemed non-anaphylaxis. IgE-mediated anaphylaxis included - NMBA (35%), antibiotics (46%), chlorhexidine (8%), patent blue dye (8%) and others (8%). An acute MCT with a comparable baseline was available in 71/82 (87%) patients (60-anaphylaxis and 11-controls).The median (IQR) time from reaction to peak MCT was 1.34 (0.82-2.51) hours. Analyses confirmed that a rise in acute MCT greater than that defined by the equation had a sensitivity, specificity, positive predictive value (PPV) and negative (N) PV of 78%, 91%, 98%, and 44% respectively. The magnitude of increase in acute MCT above the threshold predicted by consensus equation was higher in the anaphylaxis group compared to controls (P=0.0001).ConclusionThis equation has a high specificity, PPV with a moderate NPV and sensitivity in perioperative anaphylaxis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T14:35:19.144206-05:
      DOI: 10.1111/all.13226
  • What's in a name': Atopic dermatitis or atopic eczema, but not eczema
    • Authors: Jonathan I Silverberg; Jacob P Thyssen, Amy S Paller, Aaron Drucker, Andreas Wollenberg, Kwang Hoon Lee, Kenji Kabashima, Gail Todd, Peter Schmid-Grendelmeier, Thomas Bieber
      Abstract: BackgroundThe ideal nomenclature of atopic dermatitis or atopic eczema (AD/AE) has long been contested. It is becoming increasingly clear that the disparate nomenclature of this disease may have important deleterious ramifications for clinical care, research and drug development.ObjectiveTo reach consensus among an international group of experts in AD/AE on the nomenclature for AD/AE.MethodsA 3-question survey was sent to the councilors and associates of the International Eczema Council. Consensus was reached with at least 90% response and more than 90% agreement on nomenclature.ResultsSeventy-one of 77 (92.2%) IEC councilors and associates responded to the survey. Consensus was reached on the preference for the atopic prefix, i.e. AD or AE (69 of 71 [97.2%]). However, consensus was not reached preference of AD (40 [58.0%]) or AE (30 [43,5%]). Sixty-three respondents (88.7%) and 55 (77.5%) felt that the terms AD and AE were acceptable, whereas only 11 (15.5%) felt that eczema was acceptable.ConclusionsUse of the atopic prefix, i.e. either AE or AD, is recommended. Whereas, use of the term eczema is not recommended. We encourage physicians in all specialties and in every country to shift their own use of terminology to AD or AE in writing, presentations and discussions with patients and other health care personnel as a first step.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-12T06:35:29.105232-05:
      DOI: 10.1111/all.13225
  • Transfer of innovation on allergic rhinitis and asthma multimorbidity in
           the elderly (MACVIA-ARIA) - Reference Site Twinning (EIP on AHA)
    • Authors: J Bousquet; I Agache, M R Aliberti, R Angles, I Annesi-Maesano, J M Anto, S Arnavielhe, E Asayag, E Bacci, A Bedbrook, C Bachert, I Baroni, B A Barreto, M Bedolla-Barajas, K C Bergmann, L Bertorello, M Bewick, T Bieber, S Birov, C Bindslev-Jensen, A Blua, M Bochenska Marciniak, I Bogus-Buczynska, S Bosnic-Anticevich, I Bosse, R Bourret, C Bucca, R Buonaiuto, D Caiazza, D Caillot, D P Caimmi, P Camargos, G Canfora, V Cardona, A M Carriazo, C Cartier, G Castellano, N H Chavannes, M M Ciaravolo, C Cingi, A Ciceran, L Colas, E Colgan, J Coll, D Conforti, J Correira de Sousa, R M Cortés-Grimaldo, F Corti, E Costa, A L Courbis, E Cousein, A A Cruz, A Custovic, B Cvetkovski, C Dario, M da Silva, Y Dauvilliers, F De Blay, T Dedeu, G De Feo, B De Martino, P Demoly, G De Vries, S Di Capua Ercolano, N Di Carluccio, M Doulapsi, G Dray, R Dubakiene, E Eller, R Emuzyte, J M Espinoza-Contreras, A Estrada-Cardona, J Farrell, J Ferrero, W J Fokkens, J Fonseca, J F Fontaine, S Forti, J L Gálvez-Romero, C I García-Cobas, M H Garcia Cruz, B Gemicioğlu, R Gerth van Wijk, M Guidacci, J Gómez-Vera, N A Guldemond, Z Gutter, T Haahtela, J Hajjam, P W Hellings, L Hernández-Velázquez, M Illario, J C Ivancevich, E Jares, G Joos, J Just, O Kalayci, A F Kalyoncu, J Karjalainen, T Keil, N Khaltaev, L Klimek, V Kritikos, I Kull, P Kuna, V Kvedariene, V Kolek, E Krzych-Fałta, M Kupczyk, P Lacwik, D Larenas-Linnemann, D Laune, D Lauri, J Lavrut, M Lessa, G Levato, L Lewis, I Lieten, A Lipiec, R Louis, J A Luna-Pech, A Magnan, J Malva, J F Maspero, J J Matta-Campos, O Mayora, M A Medina-Ávalos, E Melén, E Menditto, J Millot-Keurinck, G Moda, M Morais-Almeida, R Mösges, A Mota-Pinto, J Mullol, A Muraro, R Murray, M Noguès, M Nalin, L Napoli, H Neffen, R E O'Hehir, G Onorato, S Palkonen, N G Papadopoulos, G Passalacqua, J L Pépin, A M Pereira, M Persico, O Pfaar, A C Pozzi, E Prokopakis, F Raciborski, J Rimmer, J A Rizzo, C Robalo-Cordeiro, M Rodríguez-González, G Rolla, R E Roller-Wirnsberger, A Romano, M Romano, J Salimäki, B Samolinski, F S Serpa, S Shamai, M Sierra, M Sova, M Sorlini, C Stellato, R Stelmach, T Strandberg, V Stroetmann, R Stukas, A Szylling, R Tan, V Tibaldi, A Todo-Bom, S Toppila-Salmi, P Tomazic, U Trama, M Triggiani, A Valero, E Valovirta, A Valiulis, M van Eerd, T Vasankari, A Vatrella, M T Ventura, M T Verissimo, F Viart, S Williams, M Wagenmann, C Wanscher, M Westman, M Wickman, I Young, A Yorgancioglu, E Zernotti, T Zurbierber, A Zurkuhlen, B De Oliviera, A Senn
      Abstract: The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives while ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study is to transfer innovation from an App developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will: (i) assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) study phenotypic characteristics and treatment over a period of one year of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-10T09:50:20.718726-05:
      DOI: 10.1111/all.13218
  • Influences of environmental bacteria and their metabolites on allergies,
           asthma and host microbiota
    • Authors: G Jatzlauk; S Bartel, H Heine, M Schloter, S Krauss-Etschmann
      Abstract: The prevalence of allergic diseases and asthma has dramatically increased over the last decades, resulting in a high burden for patients and health care systems. Thus, there is an unmet need to develop preventative strategies for these diseases.Epidemiological studies show that reduced exposure to environmental bacteria in early life (e.g birth by cesarian section, being formula-fed, growing up in an urban environment or with less contact to various persons) is associated with an increased risk to develop allergies and asthma later in life. Conversely, a reduced risk for asthma is consistently found in children growing up on traditional farms, thereby being exposed to a wide spectrum of microbes. However, clinical studies are still rare and to some extent contradicting. A detailed mechanistic understanding how environmental microbes influence the development of the human microbiome and the immune system is important to enable the development of novel preventative approaches that are based on the early modulation of the host microbiota and immunity.In this mini-review we summarize current knowledge and experimental evidence for the potential of bacteria and their metabolites to be used for the prevention of asthma and allergic diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-10T09:35:20.296902-05:
      DOI: 10.1111/all.13220
  • Spontaneous food allergy in Was-/- mice occurs independent of
           FcεRI-mediated mast cell activation
    • Authors: Willem S. Lexmond; Jeremy A. Goettel, Benjamin F. Sallis, Katelyn McCann, Edmond H. H. M. Rings, Erika Jensen-Jarolim, Samuel Nurko, Scott B. Snapper, Edda Fiebiger
      Abstract: BackgroundFood allergies are a growing health problem and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was-/- mice recapitulates the pathology of a conventional disease model and/or human food allergy.MethodsComparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was-/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed and the role of the high affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was-/-Fcer1a-/- mice.ResultsPolysensitization to food was detected in both WAS and food allergic patients which was recapitulated in the Was-/- model. Oral administration of OVA in Was-/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was-/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was-/- mice (95%) with a mortality rate>50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells and basophils.ConclusionsWas-/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-10T09:30:21.088787-05:
      DOI: 10.1111/all.13219
  • Beyond epithelial-to-mesenchymal transition: common suppression of
           differentiation programs underlies epithelial barrier dysfunction in mild,
           moderate and severe asthma
    • Authors: Lucas F. Loffredo; Hiam Abdala-Valencia, Kishore R. Anekalla, Lyda Cuervo-Pardo, Cara J. Gottardi, Sergejs Berdnikovs
      Abstract: BackgroundEpithelial barrier dysfunction is a central feature in the pathogenesis of allergic disease. Epithelial-to-mesenchymal transition (EMT) has been proposed as one mechanism afflicting barrier in asthma. However, genes and pathways involved in aberrant epithelial-mesenchymal signaling, and their relationship to asthma severity, are poorly understood.MethodsWe used unbiased gene network analysis to evaluate functional convergence in epithelial gene expression signatures across multiple public access transcriptomics datasets of human asthma, followed by text mining to evaluate functional marker relevance of discovered genes. We objectively confirmed these findings in epithelial brushings and primary asthmatic epithelial cells cultured in different biological contexts.ResultsWe found a striking suppression of epithelial differentiation in asthma, overrepresented by insufficiency in insulin and Notch signaling, but with the absence of conventional EMT markers. We identified EFNB2, FGFR1, FGFR2, INSR, IRS2, NOTCH2, TLE1, and NTRK2 as novel markers central to dysregulation of epithelial-mesenchymal signaling, but surprisingly overlooked in asthma research. We found that this “core” signature of asthma is shared by mild, moderate, and severe forms of disease, progressing with severity. Loss of epithelial differentiation induced by insulin deprivation in normal human bronchial epithelial cells cultured in organotypic conditions closely approximated gene expression in asthmatic epithelial brushings.ConclusionsThe comparative analysis of publically available transcriptomes demonstrated that epithelial barrier dysfunction in asthma is characterized by persistent underlying de-differentiation program with complex etiology. The lasting alteration of the asthmatic epithelial cell transcriptome implicates regulation involving metabolism and epigenetics, beyond EMT driven by injury and repair in chronic inflammation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-09T12:42:08.868088-05:
      DOI: 10.1111/all.13222
  • Non-lesional atopic dermatitis skin shares similar T-cell clones with
           lesional tissues
    • Authors: Patrick M. Brunner; Ryan O. Emerson, Christopher Tipton, Sandra Garcet, Saakshi Khattri, Israel Coats, James G. Krueger, Emma Guttman-Yassky
      Abstract: BackgroundAtopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and non-lesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to non-lesional skin remains unclear.MethodsWe performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 non-lesional AD biopsies, compared to 6 healthy control and 6 cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts.ResultsWhile greater T-cell infiltrates were observed in lesional vs. non-lesional AD, TCR repertoire diversity was similar in lesional and non-lesional tissues, and absolute numbers of unique T-cell clones correlated with respective T-cell counts. Most (87%) top expanded lesional T-cell clones were shared with non-lesional tissues, and they were largely maintained after 16 weeks of successful treatment with topical triamcinolone. Nevertheless, both lesional and non-lesional AD showed a highly polyclonal TCR pattern, without evidence of oligoclonal expansion, or a preferred usage of certain V-β genes in AD skin. Size of the overall T-cell infiltrate, but not the level of clonality, correlated with mRNA levels of key inflammatory mediators (e.g. IL-13, CCL17, IL23p19, CXCL10).ConclusionWhile AD harbors a highly polyclonal T-cell receptor repertoire, and despite the lack of information on TCR antigen specificity, the sharing of top abundant clones between lesional and non-lesional skin, and their persistence after months of therapy, points to the continuous presence of potentially pathogenic skin resident memory T-cells well beyond clinically inflamed lesions.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-09T12:42:06.366339-05:
      DOI: 10.1111/all.13223
  • Mechanisms of exercise-induced bronchoconstriction in athletes: current
           perspectives and future challenges
    • Authors: Mariana Couto; Marcin Kurowski, André Moreira, Dominique M.A. Bullens, Kai-Håkon Carlsen, Luís Delgado, Marek L. Kowalski, Sven F. Seys
      Abstract: The evidence of exercise-induced bronchoconstriction (EIB) without asthma (EIBwA) occurring in athletes led to speculate about different endotypes inducing respiratory symptoms within athletes. Classical postulated mechanisms for bronchial obstruction in this population include the osmotic and the thermal hypotheses. More recently, the presence of epithelial injury and inflammation in the airways of athletes was demonstrated. In addition, neuronal activation has been suggested as a potential modulator of bronchoconstriction. Investigation of these emerging mechanisms are of major importance since EIB is a significant problem for both recreational and competitive athletes and is the most common chronic condition among Olympic athletes, with obvious implications for their competing performance, health and quality of life. Hereby we summarize the latest achievements in this area and identify the current gaps of knowledge so that future research heads towards better defining the etiologic factors and mechanisms involved in development of EIB in elite athletes as well as essential aspects to ultimately propose preventive and therapeutic measures.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-09T12:42:02.935532-05:
      DOI: 10.1111/all.13224
  • A possible role of stem cells in nasal polyposis
    • Authors: L. Klimek; M. Koennecke, J. Mullol, P.W. Hellings, D.Y. Wang, W. Fokkens, P h. Gevaert, B. Wollenberg
      Abstract: Since its discovery, the understanding of stem/progenitor cells raised dramatically in the last decade. Their regenerative potential is important to develop new therapeutic applications, but the identification advanced much faster than our understanding of stem/progenitor cells. In nasal polyposis, little is known about stem cells/progenitor cells and their ability. However, the further characterization of stem cells/progenitor cells may provide new treatment options for combating nasal polyposis. This review highlights the knowledge of the current literature about stem cells/progenitor cells in nasal polyposis and how this may be exploited in the development of novel treatment strategies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-09T12:35:19.145655-05:
      DOI: 10.1111/all.13221
  • Functional and phenotypic analysis of basophils allows determining
           distinct subtypes in patients with chronic urticaria
    • Authors: Michèle Myriam Rauber; Julia Pickert, Lily Holiangu, Christian Möbs, Wolfgang Pfützner
      Abstract: BackgroundChronic urticaria (CU) is a frequent skin disease characterized by relapsing appearance of pruritic hives. While clinical symptoms are due to the release of histamine by cutaneous mast cells, the underlying pathophysiology is still unknown. However, previous studies indicate that basophils might be of relevance. Besides, the occurrence of autoantibodies against IgE or its receptor, FcεRI, and the therapeutic efficacy of anti-IgE antibodies imply that IgE-mediated mechanisms also play an important role in CU.MethodsReactivity of CU patients’ peripheral blood basophils (n=60) to specific anti-FcεRI and IgE-independent fMLP stimulation was determined by basophil activation test in comparison to patients suffering from IgE-mediated allergic rhinitis (n=10) and healthy controls (n=10). In addition, immunoglobulin receptor (FcεRI, FcγRII) expression and surface bound antibodies (IgE, IgG) were quantified on basophils. Furthermore, the autoreactive capacity of CU sera was evaluated and urticaria-related symptoms were assessed by both UCT and CU-Q2oL.ResultsStimulating CU patients’ basophils via FcεRI, we identified three distinct immunological phenotypes. One subgroup of patients' basophils reacted to FcεRI stimulation, whereas the others had anti-FcεRI non-reactive basophils. Among the latter a subgroup with pronounced basopenia was identified. Of note, this group was characterized by augmented serum-induced basophil activation, increased levels of autoantibodies against thyroid peroxidase and also exhibited the strongest disease impact on their quality of life.ConclusionsCU patients can be categorized into three immunological subgroups based on their basophil reactivity and frequency. These phenotypes are associated with different clinical characteristics, pointing to basophils as important players in CU pathophysiology.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-05T22:43:37.265921-05:
      DOI: 10.1111/all.13215
  • Omalizumab effectively protects against early- and late allergic responses
           in asthma after 4 weeks
    • Authors: Jordis Trischler; Adrian Lieb, Melina Arnold, Johannes Schulze, Martin Rosewich, Ralf Schubert, Ivan Bottoli, Stefan Zielen
      Abstract: Omalizumab is licensed for therapy in severe allergic asthma with an effect demonstrated after 8 weeks or longer treatment. Since new applications for omalizumab demand precise knowledge of the onset of effects, the objective of this study was to determine the time course of the early (EAR) and late allergic reaction (LAR). Ten patients (IgE>300 IU/mL and
      PubDate: 2017-06-05T04:17:38.525584-05:
      DOI: 10.1111/all.13217
  • Heme oxygenase-1 directly binds STAT3 to control the generation of
           pathogenic Th17 cells during neutrophilic airway inflammation
    • Authors: Xiaoliang Lin; Jiajia Lv, Jie Lv, Caixia Di, Yanjie Zhang, Tong Zhou, Junling Liu, Zhenwei Xia
      Abstract: BackgroundSpecific JAK/STAT pathways play a critical role in the functional differentiation of distinct Th subsets. Previously, we showed that HO-1, a stress-inducible protein, inhibits Th17 cell differentiation and alleviates neutrophilic airway inflammation, but the responsible molecular basis remains unclear.MethodsWe employed Th17-skewing differentiation and NEA mouse models to study the role of HO-1 regulating IL-6-STAT3-RORγt/SOCS3 signaling pathway to control Th17 cell-mediated neutrophilic airway inflammation. The levels of cytokines and expressions of relative signaling molecular were measured by ELISA, western blot and qPCR, respectively. Frequency of CD4+IL-17A+, CD4+IL-6R+ and CD4+IL-23R+ cells was analyzed by FCM. The interaction between HO-1 and signaling pathway-related proteins was determined by Co-Immunoprecipitation and western blot.ResultsHere, we show that hemin-induced HO-1 over-expression is required to mediate this process. Specifically, HO-1 decreased STAT3 phosphorylation but not IL-6R/IL-23R expression or JAK1/JAK2 activation in CD4+ T cells. The effect was accompanied by co-inhibition of SOCS3, a negative feedback factor of STAT3 activation. HO-1 bound to three domains on STAT3, (DNA-binding, linker and transactivation domains) to directly regulate STAT3 activation. Conversely, either forced expression of a constitutively active STAT3 mutant or application of small interfering RNA (siRNA) for HO-1 reversed these effects.ConclusionsOur data suggest that HO-1 exerts its inhibitory effect on Th17 cell differentiation by directly associating and blocking STAT3 phosphorylation. We speculate that hemin may be a potential therapeutic candidate for the treatment of other types of immune and pulmonary inflammatory-related diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-05T00:40:22.016457-05:
      DOI: 10.1111/all.13216
  • Sputum Basophils and Asthma Diagnosis: Dawn of a New Era'
    • Authors: Michaela Fux; Christophe von Garnier
      Abstract: More than 40 years ago, Kimura et al. discovered that basophils are enriched in sputum samples of asthma patients (1). Since then, various scientific approaches have attempted to elucidate the role of basophils in the pathophysiology of asthma. The scarcity of basophils and technical limitations of earlier studies have made it difficult to increase our understanding how basophils affect the disease course in asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-31T07:17:23.900031-05:
      DOI: 10.1111/all.13214
  • Sublingual immunotherapy provides long-term relief in allergic rhinitis
           and reduces the risk of asthma: a retrospective, real-world database
    • Authors: S Zielen; P Devillier, J Heinrich, H Richter, U Wahn
      Abstract: BackgroundAllergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long-term efficacy. However, there are few real-life data on the progression of AR and/or AA in patients receiving AIT.ObjectivesTo assess the real-world, long-term efficacy of grass-pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression.MethodsIn a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups.ResultsAfter applying all selection criteria, 2851 SLIT and 71275 Control patients were selected for the study.After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pre-treatment period) in SLIT tablet group than in the non AIT group (p
      PubDate: 2017-05-31T07:17:18.788984-05:
      DOI: 10.1111/all.13213
  • Targeting PP2A and proteasome activity ameliorates features of allergic
           airway disease in mice
    • Authors: Prema M. Nair; Malcolm R. Starkey, Tatt Jhong Haw, Gang Liu, Jay C. Horvat, Jonathan C. Morris, Nikki M. Verrills, Andrew R. Clark, Alaina J. Ammit, Philip M. Hansbro
      Abstract: BackgroundAsthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed if enhancing PP2A activity with Fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S)), or inhibiting proteasome activity with Bortezomib (BORT) could suppress experimental AAD.MethodsAcute AAD was induced in C57BL/6 mice by intraperitoneal sensitisation with ovalbumin (OVA) in combination with intranasal (i.n) exposure to OVA. Chronic AAD was induced in mice with prolonged i.n exposure to crude house dust mite (HDM) extract. Mice were treated with vehicle, FTY720, AAL(S), BORT or AAL(S)+BORT and hallmark features of AAD assessed.ResultsAAL(S) reduced the severity of acute AAD by suppressing tissue eosinophils and inflammation, mucus secreting cell (MSC) numbers, type-2 associated cytokines (Interleukin (IL)-33, thymic stromal lymphopoietin, IL-5 and IL-13), serum immunoglobulin (Ig)E, and airway hyper-responsiveness (AHR). FTY720 only suppressed tissue inflammation and IgE. BORT reduced bronchoalveolar lavage fluid (BALF) and tissue eosinophils and inflammation, IL-5, IL-13, and AHR. Combined treatment with AAL(S)+BORT had complementary effects and suppressed BALF and tissue eosinophils and inflammation, MSC numbers, reduced the production of type-2 cytokines and AHR. AAL(S), BORT and AAL(S)+BORT also reduced airway remodelling in chronic AAD.ConclusionThese findings highlight the potential of combination therapies that enhance PP2A and inhibit proteasome activity as novel therapeutic strategies for asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-24T18:20:26.085747-05:
      DOI: 10.1111/all.13212
  • Poaceae pollen as the leading aeroallergen worldwide: a review
    • Authors: H. García-Mozo
      Abstract: The Poaceae family comprises over 12,000 wind-pollinated species which release large amounts of pollen into the atmosphere. Poaceae pollen is currently regarded as the leading airborne biological pollutant and the chief cause of pollen-allergy worldwide. Sensitization rates vary by country, and those variations are reviewed here.Grass pollen allergens are grouped according to their protein structure and function. In Poaceae, although species belonging to different sub-families are characterized by distinct allergen subsets, there is a considerable degree of cross-reactivity between many species. Cross-reactivity between grass-pollen protein and fresh fruit pan-allergens is associated with the appearance of food allergies. The additional influence of urban pollution may prompt a more severe immunological response.The timing and the intensity of the pollen season is governed by species genetics, but plant phenology is also influenced by climate; as a result, climate changes may affect airborne pollen concentrations. This paper reviews the findings of worldwide research which has highlighted the major impact of climate change on plant phenology and also on the prevalence and severity of allergic disease.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-22T03:00:29.190916-05:
      DOI: 10.1111/all.13210
  • Changes in patient quality of life during oral immunotherapy for food
    • Authors: Na'ama Epstein Rigbi; Michael R Goldberg, Michael B Levy, Liat Nachshon, Keren Golobov, Arnon Elizur
      Abstract: BackgroundQuality of life is (QOL) impaired in patients with food allergy and improves following oral immunotherapy (OIT). However, the treatment itself is prolonged and demanding. We examined changes in patient QOL during OIT for food allergy.MethodsThe FAQLQ-PF was administered to children aged 4-12 years undergoing OIT for milk, peanut or egg allergy, at the beginning and after 4 months of treatment. Patients were categorized as improved, unchanged, or diminished FAQLQ-PF (>0.5 point decrease, a change of ≤0.5 points, or>0.5 increase, respectively) and compared. Food-allergic patients not undergoing OIT served as controls.ResultsThe Food Anxiety, Social and Dietary limitation and total FAQLQ-PF scores improved significantly during the study period (p=0.001, p=0.018 and p=0.01, respectively) in treated but not in control patients, while the Emotional Impact did not. The change in the FAQLQ-PF was independent of the maximal tolerated dose at baseline or following four months of treatment, the pace of dose-increase or of number or severity of reactions experienced. The total FAQLQ-PF score was inversely associated with the score at baseline on multi-variate analysis (regression coefficient = -0.56, p
      PubDate: 2017-05-22T03:00:26.799962-05:
      DOI: 10.1111/all.13211
  • Allergen immunotherapy for allergic asthma: a systematic review and
    • Authors: Sangeeta Dhami; Artemisia Kakourou, Felix Asamoah, Ioana Agache, Susanne Lau, Jutel Marek, Antonella Muraro, Graham Roberts, Cezmi A. Akdis, Matteo Bonini, Ozlem Cavkaytar, Breda Flood, Pawel Gajdanowicz, Kenji Izuhara, Ömer Kalayci, Ralph Mosges, Oscar Palomares, Oliver Pfaar, Sylwia Smolinska, Milena Sokolowska, Miqdad Asaria, Gopal Netuveli, Hader Zaman, Ather Akhlaq, Aziz Sheikh
      Abstract: BackgroundTo inform the development of the European Academy of Allergy and Clinical Immunonology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT.MethodsWe performed a systematic review, which involved searching nine databases. Studies were screened against pre-defined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses.Results98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of -1.11 (95%CI -1.66, -0.56). This was robust to a pre-specified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD -1.21 (95%CI -1.87, -0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95%CI -0.23, 0.58), but one study showed a beneficial long-term effect.For secondary outcomes subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen specific airways hyperreactivity (AHR) but this was not the case for sub-lingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and non-specific AHR.AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported.The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective.ConclusionsAIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiveness and cost-effectiveness.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-19T10:35:25.924075-05:
      DOI: 10.1111/all.13208
  • The Burden of Chronic Spontaneous Urticaria Is Substantial: Real-World
           Evidence From ASSURE-CSU
    • Authors: Marcus Maurer; Mohamed Abuzakouk, Frédéric Bérard, Walter  Canonica, Hanneke Oude Elberink, Ana Giménez-Arnau, Clive  Grattan, Kelly Hollis, André Knulst, Jean-Philippe Lacour, Charles Lynde, Alexander Marsland, Doreen McBride, Alla  Nakonechna, Javier Ortiz de Frutos, Christina Proctor, Gordon  Sussman, Carolyn Sweeney, Haijun Tian, Karsten Weller, Daniel Wolin, Maria-Magdalena Balp
      Abstract: BackgroundChronic spontaneous urticaria (CSU) can be debilitating, difficult to treat, and frustrating for patients and physicians. Real-world evidence for the burden of CSU is limited. The objective of this study was to document disease duration, treatment history, and disease activity, as well as impact on health-related quality of life (HRQoL) and work among patients with inadequately controlled CSU, and to describe its humanistic, societal, and economic burden.MethodsThis international observational study assessed a cohort of 673 adult patients with CSU whose symptoms persisted for ≥12 months despite treatment. Demographics, disease characteristics, and health care resources in the previous 12 months were collected from medical records. Patient-reported data on urticaria and angioedema symptoms, HRQoL, and work productivity and activity impairment were collected from a survey and a diary.ResultsAlmost 50% of patients had moderate-to-severe disease activity as reported by Urticaria Activity Score. Mean (SD) Dermatology Life Quality Index and Chronic Urticaria Quality of Life Questionnaire scores were 9.1 (6.62) and 33.6 (20.99), respectively. CSU markedly interfered with sleep and daily activities. Angioedema in the previous 12 months was reported by 66% of enrolled patients and significantly affected HRQoL. More than 20% of patients reported ≥1 hour per week of missed work; productivity impairment was 27%. These effects increased with greater disease activity. Significant health care resources and costs were incurred to treat CSU.ConclusionsCSU has considerable humanistic and economic impacts. Patients with greater disease activity and with angioedema experience greater HRQoL impairments.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-19T10:30:29.507441-05:
      DOI: 10.1111/all.13209
  • Patterns of anaphylaxis after diagnostic work-up: a follow-up study of 226
           patients with suspected anaphylaxis
    • Authors: Athamaica Ruiz Oropeza; Carsten Bindslev-Jensen, Sigurd Broesby-Olsen, Thomas Kristensen, Michael Boe Møller, Hanne Vestergaard, Henrik Fomsgaard Kjaer, Susanne Halken, Annmarie Lassen, Charlotte G. Mortz
      Abstract: BackgroundMost published studies on anaphylaxis are retrospective or register based. Data on subsequent diagnostic work-up are sparse. We aimed to characterize patients seen with suspected anaphylaxis at the emergency care setting (ECS), after subsequent diagnostic work-up at our Allergy Center (AC).MethodsProspective study including patients from the ECS, Odense University Hospital, during May 2013–April 2014. Possible anaphylaxis cases were daily identified based on a broad search profile including history and symptoms in patient records, diagnostic codes and pharmacological treatments. At the AC, all patients were evaluated according to international guidelines.ResultsAmong 226 patients with suspected anaphylaxis, the diagnosis was confirmed in 124 (54.9%) after diagnostic work-up; 118 of the 124 fulfilled WAO/EAACI criteria of anaphylaxis at the ECS, while 6 were found among 46 patient with clinical suspicion but not fulfilling the WAO/EAACI criteria at the ECS. The estimated incidence rate of anaphylaxis was 26 cases per 100,000 person years and the one year period prevalence was 0.04%. The most common elicitor was drugs (41.1%) followed by venom (27.4%) and food (20.6%). In 13 patients (10.5%) no elicitor could be identified. Mastocytosis was diagnosed in 7.7% of adult patients and was significantly associated with severe anaphylaxis. Atopic diseases were significantly associated only with food-induced anaphylaxis. Co-factors were present in 58.1% and were significantly associated with severe anaphylaxis.ConclusionA broad search profile in the ECS and subsequent diagnostic work-up is important for identification and classification of patients with anaphylaxis. Evaluation of co-morbidities and co-factors are important.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-19T09:12:37.434179-05:
      DOI: 10.1111/all.13207
  • Lung function parameters in omalizumab responder patients: an interesting
    • Authors: F. Paganin; G. Mangiapan, A. Proust, A. Prudhomme, J. Attia, S. Marchand-Adam, F. Pellet, F. Milhe, B. Melloni, A. Bernady, C. Raspaud, C. Nocent, P. Berger, L. Guilleminault
      Abstract: BackgroundOmalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and non-responder patients remain inconclusive. The objective of this real-life study was to compare the changes in FEV1 of omalizumab responders and non-responders at 6 months.MethodsA multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and post-bronchodilator FEV1, residual volume (RV) and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18 and 24 months.ResultsMean pre-bronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in non-responders (+0.2 ± 0.4L and -0.1 ± 0.4L respectively, p
      PubDate: 2017-05-18T05:27:15.154838-05:
      DOI: 10.1111/all.13202
  • Identification of a plasma miRNA biomarker-signature for allergic asthma:
           a translational approach
    • Authors: Katrin Milger; Jeremias Götschke, Linda Krause, Petra Nathan, Francesca Alessandrini, Amanda Tufman, Rainald Fischer, Sabine Bartel, Fabian J. Theis, Jürgen Behr, Stefan Dehmel, Nikola S. Mueller, Nikolaus Kneidinger, Susanne Krauss-Etschmann
      Abstract: BackgroundAsthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers.This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach.MethodsWe pre-screened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthma patients and 12 healthy controls.Results10 miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of 5 miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use.ConclusionDistinct plasma miRNAs are differentially regulated both in murine and human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-17T07:30:26.498613-05:
      DOI: 10.1111/all.13205
  • Aspergillus fumigatus in cystic fibrosis: an update on immune interactions
           and molecular diagnostics in ABPA
    • Authors: Ania Carsin; Thomas Romain, Stéphane Ranque, Martine Reynaud-Gaubert, Jean-Christophe Dubus, Jean-Louis Mège, J Vitte
      Abstract: A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe Aspergillus fumigatus-related diseases due to possible evolution towards pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8 to 10% of cystic fibrosis patients experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host-pathogen interactions in Aspergillus fumigatus and cystic fibrosis patients and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-17T07:10:40.586524-05:
      DOI: 10.1111/all.13204
  • Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic
           review and meta-analysis
    • Authors: Sangeeta Dhami; Ulugbek Nurmatov, Stefania Arasi, Tahir Khan, Miqdad Asaria, Hadar Zaman, Arnav Agarwal, Gopal Netuveli, Graham Roberts, Oliver Pfaar, Antonella Muraro, Ignacio J. Ansotegui, Moises Calderon, Cemal Cingi, Stephen Durham, Ronald Gerth van Wijk, Susanne Halken, Eckard Hamelmann, Peter Hellings, Lars Jacobsen, Edward Knol, Desiree Larenas Linnemann, Sandra Lin, Paraskevi Maggina, Ralph Mösges, Hanneke Oude Elberink, Giovanni Pajno, Ruby Panwankar, Elide Pastorello, Martin Penagos, Constantinos Pitsios, Giuseppina Rotiroti, Frans Timmermans, Olympia Tsilochristou, Eva-Maria Varga, Carsten Schmidt-Weber, Jamie Wilkinson, Andrew Williams, Margitta Worm, Luo Zhang, Aziz Sheikh
      Abstract: BackgroundThe European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. In order to inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic rhinoconjunctivitisMethodsWe searched 15 international biomedical databases for published, in progress and unpublished evidence. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses.ResultsWe identified 5932 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95%CI -0.63, -0.42), medication (SMD -0.37, 95%CI -0.49, -0.26) and combined symptom and medication (SMD -0.49, 95%CI -0.69, -0.30) scores whilst on treatment that were robust to pre-specified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, this suggesting a benefit in relation to symptom scores.ConclusionsAIT is effective in improving symptom, medication and combined symptom and medication scores in patients with allergic rhinoconjunctivitis whilst on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T10:05:39.858587-05:
      DOI: 10.1111/all.13201
  • Non-Allergic Rhinitis: Position paper of the European Academy of
           Allergology and Clinical Immunology
    • Authors: P. W. Hellings; L. Klimek, C. Cingi, I. Agache, C. Akdis, C. Bachert, J. Bousquet, P. Demoly, P. Gevaert, V. Hox, C. Hupin, L. Kalogjera, F. Manole, R. Mösges, J. Mullol, N. B. Muluk, A. Muraro, N. Papadopoulos, R. Pawankar, C. Rondon, M. Rundenko, S. F. Seys, E. Toskala, L. Van Gerven, L. Zhang, N. Zhang, W. J Fokkens
      Abstract: This EAACI position paper aims at providing a state-of-the-art overview on non-allergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as non-allergic non-infectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of minimal 2 nasal symptoms like nasal obstruction, rhinorrhoea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity, and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug-induced rhinitis, (non-allergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called ‘entopy’ or local allergic rhinitis (LAR).We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm and defining the unmet needs in this neglected area of research.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T06:18:20.2166-05:00
      DOI: 10.1111/all.13200
  • Minimal impact of extensive heating of hen's egg and cow's milk in a food
           matrix on threshold dose-distribution curves
    • Authors: Benjamin C. Remington; Joost Westerhout, Dianne E Campbell, Paul J. Turner
      Abstract: We analyzed reaction threshold data from 352 children undergoing open food challenges to hen's egg or cow's milk, either fresh or extensively heated into a muffin. There was no significant shift in dose-distribution curves due to the baking process, implying that existing threshold data for these allergens can be applied to allergen risk management, even when these allergens are heat-processed into baked foods.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T03:05:43.818627-05:
      DOI: 10.1111/all.13198
  • Recent Advances in the Use of Nanoparticles for Allergen-specific
    • Authors: Hannah Pohlit; Iris Bellinghausen, Holger Frey, Joachim Saloga
      Abstract: The number of patients suffering from allergic asthma and rhino-conjunctivitis has increased dramatically within the last decades. Allergen-specific immunotherapy (AIT) is the only available cause-oriented therapy so far. AIT reduces symptoms, but has also a disease modifying effect. Disadvantages are a long-lasting procedure, and in a few cases potential systemic adverse reactions. Encapsulation of allergens or DNA vaccines into nanostructures may provide advantages compared to the conventional AIT with non-capsulated allergen extracts: The protein/DNA molecule can be protected from degradation, higher local concentrations and targeted delivery to the site of action appears possible and most importantly, recognition of encapsulated allergen by the immune system, especially by IgE antibodies is prevented. AIT with nanoparticles (NPs) may offer a safer and potentially more efficient way of treatment for allergic diseases. In this review we summarize the use of biodegradable NPs consisting of synthetic or natural polymers, liposomes and virus-like particles as well as non-biodegradable NPs like dendrimers, carbon- or metal-based NPs for AIT. More or less successful applications of these NPs in prophylactic as well as therapeutic vaccination approaches in rodents or other animals as well as first human clinical trials are discussed in detail.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T03:05:41.333256-05:
      DOI: 10.1111/all.13199
  • Airway basophils are increased and activated in eosinophilic asthma
    • Authors: Yoshihiro Suzuki; Keiko Wakahara, Tomoko Nishio, Satoru Ito, Yoshinori Hasegawa
      Abstract: BackgroundThe impact of basophils on asthma pathogenesis remains largely unexplored, particularly in humans. Here, we evaluated the frequencies and activation status of basophils in the sputum of adult asthmatic patients and related our findings to other parameters of eosinophilic airway inflammation.MethodsWe enrolled 44 adult asthmatic patients who were being treated with inhaled corticosteroids (ICS). Analysis of the induced sputum, exhaled nitric oxide fraction (FeNO) measurement, and Asthma Control Test (ACT) were carried out together with standard blood and pulmonary function tests. The cellular composition of the sputum was examined by flow cytometry, and the phenotypes of blood and sputum basophils were compared.ResultsBasophils were increased in the sputum of asthmatic patients. The expression of CD203c on sputum basophils was significantly higher than that on blood basophils. The percentage of sputum basophils was positively correlated with those of eosinophils and mast cells; it was also correlated with that of blood eosinophils and FeNO. However, sputum basophils were not correlated with serum IgE, lung function, or the percentage of blood basophils. A receiver operating characteristics (ROC) curve showed the superiority of sputum basophils as a surrogate marker of the percentages of sputum eosinophils compared with absolute numbers of blood eosinophils and FeNO.ConclusionThe number of activated basophils was increased in the sputum of patients with eosinophilic asthma and correlated with airway and blood eosinophils. Our observations suggest that sputum basophils may serve as a biomarker to monitor new therapeutic approaches for the treatment of eosinophilic asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T03:00:27.597456-05:
      DOI: 10.1111/all.13197
  • Amb a 1 isoforms: unequal siblings with distinct immunological features
    • Authors: Martin Wolf; Teresa E. Twaroch, Sara Huber, Manuel Reithofer, Markus Steiner, Lorenz Aglas, Michael Hauser, Iris Aloisi, Claudia Asam, Heidi Hofer, Maria A. Parigiani, Christof Ebner, Barbara Bohle, Peter Briza, Neubauer Angela, Frank Stolz, Beatrice Jahn-Schmid, Michael Wallner, Fatima Ferreira
      Abstract: BackgroundRagweed pollen represents a major allergy risk factor. Ragweed extracts contain five different isoforms of the major allergen Amb a 1. However, the immunologic characteristics of Amb a 1 isoforms are not fully investigated. Here we compared the physicochemical and immunological properties of three most important Amb a 1 isoforms.MethodsAfter purification, the isoforms were physicochemically characterized, tested for antibody-binding and induction of human T cell proliferative responses. Their immunologic properties were further evaluated in vitro and in vivo in a mouse model.ResultsAmb a 1 isoforms exhibited distinct patterns of IgE-binding and immunogenicity. Compared to Amb a 1.02 or 03 isoforms, Amb a 1.01 showed higher IgE-binding activity. Isoforms 01 and 03 were the most potent stimulators of patients’ T cells. In a mouse model of immunization, Amb a 1.01 induced higher levels of IgG and IgE antibodies when compared to isoforms 02 and 03. Interestingly, ragweed-sensitized patients also displayed an IgG response to Amb a 1 isoforms. However, unlike therapy-induced antibodies, sensitization-induced IgG did not show IgE-blocking activity.ConclusionThe present study showed that naturally occurring isoforms of Amb a 1 possess different immunogenic and sensitizing properties. These findings should be considered when selecting sequences for molecule-based diagnosis and therapy of ragweed allergy. Due to its high IgE-binding activity, isoform Amb a 1.01 should be included in diagnostic tests. In contrast, due to their limited B and T cell cross-reactivity patterns, a combination of different isoforms might be a more attractive strategy for ragweed immunotherapy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-02T10:36:52.464335-05:
      DOI: 10.1111/all.13196
  • Duration and exclusiveness of breastfeeding and risk of childhood atopic
    • Authors: Niels J. Elbert; Evelien R. van Meel, Herman T. den Dekker, Nicolette W. de Jong, Tamar E.C. Nijsten, Vincent W.V. Jaddoe, Johan C. de Jongste, Suzanne G.M.A. Pasmans, Liesbeth Duijts
      Abstract: BackgroundBreastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease-related modification of the exposure or modified by maternal history of maternal history of allergy, eczema or asthma.MethodsThis study among 5,828 children was performed in a population-based prospective cohort from fetal life onwards. We collected information on duration (
      PubDate: 2017-04-27T18:38:26.364071-05:
      DOI: 10.1111/all.13195
  • Birth decade affects the sensitization pattern and asthma-risk in Finnish
           adult population
    • Authors: S Toppila-Salmi; A Luukkainen, R Lemmetyinen, J Karjalainen, H Huhtala, R Renkonen, D Y Wang, M J Mäkelä, J Pekkanen
      Abstract: BackgroundWe have previously shown that sensitizations to several types of allergens distinguishes subjects with and without adult-onset asthma in Finland. The aim was to analyze how age affects sensitization and asthma-risk.MethodsWe used previous population-based case-control data (N=523) from Finnish adult asthma patients with one or two matched controls. Asthma was diagnosed based on a typical history of asthmatic symptoms and lung function tests. Allergic sensitization was determined by skin prick test (SPT) to 17 aeroallergens. Information on demographics was obtained by a questionnaire.ResultsSensitization to more than one allergen type and the number of positive SPT reactions associated with younger age and asthma. Atopic subjects aged 65 or over were characterized by sensitization to only 1-2 allergens, with very few animal danders and without an association with asthma.ConclusionsMultiple sensitizations and animal dander sensitization are more common among Finnish asthmatic adults aged under 56 than among older asthmatics. Cohort studies are needed to understand timing of host-environmental interactions behind this.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-26T09:57:41.760018-05:
      DOI: 10.1111/all.13194
  • Predictive value of serum sST2 in preschool wheezers for development of
           asthma with high FeNO
    • Authors: Maria E. Ketelaar; Kim D. G van de Kant, F Nicole Dijk, Ester M.M. Klaassen, Néomi Grotenboer, Martijn C Nawijn, Edward Dompeling, Gerard H. Koppelman
      Abstract: Wheezing is common in childhood. However, current prediction models of paediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-Like-1 is a well-replicated asthma-gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3y old wheezers do not predict doctors’ diagnosed asthma at age 6y. Instead sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95CI 0.56-0.84), but had also significant predictive value on its own (AUC=0.65, 95CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T02:00:42.725832-05:
      DOI: 10.1111/all.13193
  • Der f 35: an MD-2−like house dust mite allergen that cross-reacts
           with Der f 2 and Pso o 2
    • Authors: Takashi Fujimura; Tsunehiro Aki, Toshihide Isobe, Akito Matsuoka, Takaharu Hayashi, Kazuhisa Ono, Seiji Kawamoto
      Abstract: BackgroundDermatophagoides farinae is a source of airborne house dust mite (HDM) allergens. We elucidated IgE-reactive allergens from D. farinae by two-dimensional immunoblotting−based allergenome analysis, and identified one new allergen, named Der f 35, that possesses IgE-binding capacity comparable to that of Der f 2. The aim of this study is to clarify the allergenic capacity of new HDM allergen Der f 35.MethodsWe cloned der f 35 from D. farinae mRNA and produced recombinant Der f 35 in Escherichia coli. The IgE-binding capacity of Der f 35 and its cross-reactivity with group 2 allergens from D. farinae and Psoroptes ovis were determined by ELISA and ELISA inhibition assays, respectively.ResultsThe deduced amino acid sequence for der f 35, which possesses the MD-2−related lipid-recognition domain, showed higher identity with group 2 allergens from P. ovis (61.5%) and Blomia tropicalis (50.7%) than with Der f 2 (40.8%). Der f 35 showed IgE-binding frequencies of 77.5% (31/40) for the native form upon allergenome analysis and 51.4% (18/35) for recombinant structure by ELISA. Der f 35 showed cross-reactivity with Der f 2 and Pso o 2 in reaction with HDM-allergic patients’ IgE by ELISA inhibition assay.ConclusionDer f 35 is a candidate major allergen from D. farinae, which is more similar to group 2 allergens from sheep scab mite and storage mites. Der f 35 could be responsible for the cross-reactivity among group 2 mite allergens.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T01:55:39.743146-05:
      DOI: 10.1111/all.13192
  • Identification of a polygalacturonase (Cup s 2) as the major CCD-bearing
           allergen in Cupressus sempervirens pollen
    • Authors: Youcef Shahali; Jean-Pierre Sutra, Christiane Hilger, Kyria Swiontek, Iman Haddad, Joelle Vinh, Laurence Guilloux, Denis Charpin, Hélène Sénéchal, Pascal Poncet
      Abstract: Since IgE glyco-epitopes, also referred to as cross-reactive carbohydrate determinants (CCDs), can share significant structural homologies between different plants, they are prone to extensive cross-reactivity among allergen pollen extracts. Here, cypress pollen allergens, especially a polygalacturonase (PG), were further characterized using double one dimensional electrophoresis (D1-DE). The presence of specific IgE directed against CCDs was investigated by bromelain IgE inhibition and concanavalin A binding assays using sera of cypress pollen sensitized patients. Our results showed that IgE reactivity to CCDs in Cupressus sempervirens pollen extracts is mainly related to bromelain-type epitopes of a newly-identified cypress PG. This glycoprotein has been further characterized through an immunoproteomic approach and officially indexed as Cup s 2 by the WHO/IUIS allergen nomenclature. Cup s 2 could thus be associated with the increased prevalence of IgE reactivity to cypress pollen extracts because of CCD interference.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T01:50:39.507138-05:
      DOI: 10.1111/all.13191
  • Topical corticosteroid phobia in atopic dermatitis: international
           feasibility study of the TOPICOP score
    • Authors: Jean-Francois Stalder; Hélène Aubert, Emmanuelle Anthoine, Leila Moret, Sebastien Barbarot, Masaki Futamura, Danielle Marcoux, Marie-Anne Morren, Magdalena Trzeciak, Zsuzsanna Szalai, Klára Veres, Mette Deleuran, Christian Vestergaard, Franck Boralevi, Chua-Yu Chu, Linda De Raeve, Åke Svensson, Regina Fölster-Holst, Matthias Buchner, Roberto Takaoka, Valeria Aoki, Pavel Chernyshov, Luidmyla Chernyshova, Dedee F. Murrell, Cathy Zhao, Carola Duran Mckinster, Laura Von Kobyletzky, Laurence Eichenfield, Christine Totri, Peter Lio, Julien Seneschal
      Abstract: BackgroundAdherence to topical corticosteroids (TCS) is essential for the effective treatment of atopic dermatitis but can be limited by concerns about their use. This study examined the feasibility of applying the validated TOPICOP score for assessing TCS phobia across different countries.MethodsThis was a prospective multicenter feasibility study conducted in 21 hospitals in 17 countries. Patients >3 months of age with atopic dermatitis or their parents or legal representatives completed a validated translation of the TOPICOP questionnaire in the country's native language. Respondents also completed questionnaires collecting opinions about the feasibility and acceptability of the TOPICOP questionnaire.Results1564 participants in 15 countries were included in the analysis. 81% of respondents considered the questions clear or very clear and 79% reported that it took less than 5 min to complete. Each of the individual items in the TOPICOP questionnaire was considered to be not at all difficult to answer by 49% to 74% of participants. The mean global TOPICOP score was 44.7% ± 20.5. Mean TOPICOP subscores were 37.0 ± 22.8% for knowledge and beliefs, 54.7 ± 27.8% for fears, and 50.1 ± 29.1% for behaviours. Global scores and subscores differed between countries, although the subscores did not always vary in parallel, suggesting different levels of TCS phobia and different drivers for each country.ConclusionsThe TOPICOP score can be feasibly applied across countries and may therefore be useful for obtaining qualitative and quantitative data from international studies and for adapting patient education and treatment.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T01:46:14.388731-05:
      DOI: 10.1111/all.13189
  • Effect of anti-IgE in occupational asthma caused by exposure to low
           molecular weight agents
    • Authors: M Ollé-Monge; M J Cruz, S Gomez-Ollés, I Ojanguren, J Vanoirbeek, X Muñoz
      Abstract: BackgroundThe role of immunoglobulin (Ig)-E in occupational asthma (OA) due to low molecular weight (LMW) agents is not well established compared to classical atopic asthma. In the present study we evaluate whether anti-IgE monoclonal antibody (mAb) has an effect in a mouse model of OA, using persulfate salts.MethodsOn days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate (AP) or dimethyl sulfoxide (DMSO). On days 15, 18 and 21 animals were injected intraperitoneally with anti-IgE mAb or PBS 6 hours before challenge with AP or saline. Airway hyperresponsiveness (AHR) using a methacholine test, airway inflammation in bronchoalveolar lavage (BAL) and lung tissue and total free IgE in serum samples were analyzed 24, 48 and 96 hours after the last challenge.ResultsAnti-IgE mAb treatment almost completely neutralized free serum IgE. In AP sensitized and challenged mice, anti-IgE mAb treatment abolished AHR 24h and 48h after the last challenge and significantly reduced the total number of eosinophils and neutrophils 48h and 96h after the last AP challenge compared with non-treated mice. Levels of interleukin (IL)-13 in BAL were also significantly decreased after anti-IgE administration 24h and 48h after the last AP challenge. Histological analysis of the lung sections from anti-IgE-treated mice revealed normal inflammatory patterns similar to control groups 48h after the last challenge.ConclusionsAnti-IgE-treated mice showed a significant improvement in asthma features related to the AHR and airway inflammation. Anti-IgE mAb has positive effects in OA induced by persulfate salts.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T01:46:09.580547-05:
      DOI: 10.1111/all.13190
  • Sputum basophils are increased in eosinophilic asthma compared with
           non-eosinophilic asthma phenotypes
    • Authors: Collin R Brooks; Christine J Dalen, Ian F Hermans, Peter G Gibson, Jodie L Simpson, Jeroen Douwes
      Abstract: Sputum basophil numbers are increased in allergic asthmatics, but it is unclear what role airway basophils play in “TH2-low” asthma phenotypes. Using flow cytometry we found that basophils were significantly increased in all asthmatics (n=26) compared with healthy controls (n=8) (p=0.007) with highest levels observed in eosinophilic asthma (EA; median 0.22%, IQR 0.11-0.47%; n=14) compared with non-EA (0.06%, 0.00-0.20%; n=12; p
      PubDate: 2017-04-20T08:22:08.97523-05:0
      DOI: 10.1111/all.13185
  • Protease-activated receptor-2 suppresses interleukin (IL)-10 expression in
           B cells via up regulating Bcl2L12 in patients with allergic rhinitis
    • Authors: Jin-Mei Xue; Li-Tao Yang, Gui Yang, Xiao-Rui Geng, Zhi-Qiang Liu, Shuai Wang, Hai-Liang Zhao, Zhi-Gang Liu, Chang-Qing Zhao, Ping-Chang Yang
      Abstract: Background and aimsThe function of interleukin (IL)-10 producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immune regulatory functions. This study aims to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells.MethodsPeripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2 like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed.ResultsWe observed that the expression of IL-10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10 expression, which was abolished by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12-shRNA carrying liposomes reversed the capability of IL-10 expression and the immune suppressor function. Administration of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice.ConclusionsActivation of PAR2 inhibits the expression of IL-10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment of AR.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-20T08:21:58.09584-05:0
      DOI: 10.1111/all.13186
  • Comorbidity of chronic spontaneous urticaria and autoimmune thyroid
           diseases: a systematic review
    • Authors: Pavel Kolkhir; Martin Metz, Sabine Altrichter, Marcus Maurer
      Abstract: Chronic spontaneous urticaria (CSU) patients are widely held to often have other autoimmune disorders, including autoimmune thyroid disease. Here, we systematically evaluated the literature on the prevalence of thyroid autoimmunity in CSU and vice versa. There is a strong link between CSU and elevated levels of IgG anti-thyroid autoantibodies (AAbs), with most of a large number of studies reporting rates of ≥10%. Levels of IgG against thyroid peroxidase (TPO) are more often elevated in CSU than those of other IgG anti-thyroid AAbs (strong evidence). Levels of IgG anti-thyroid AAbs are more often elevated in adult CSU patients than in children (strong evidence). CSU patients exhibit significantly higher levels of IgG anti-thyroid AAbs (strong evidence) and IgE-anti-TPO (weak evidence) than controls. Elevated IgG anti-thyroid AAbs in CSU are linked to the use of glucocorticoids (weak evidence) but not to disease duration or severity/activity, gender, age or ASST response (inconsistent evidence). Thyroid dysfunction rates are increased in CSU patients (strong evidence). Hypothyroidism and Hashimoto's thyroiditis are more common than hyperthyroidism and Graves’ disease (strong evidence). Thyroid dysfunction is more common in adult CSU patients than in children (strong evidence) and in female than male CSU patients (weak evidence). Urticaria including CSU is more prevalent in patients with thyroid autoimmunity than in healthy controls (weak evidence). CSU can improve in response to treatment with levothyroxine or other thyroid drugs (strong evidence). Pathogenic mechanisms in CSU patients with thyroid autoimmunity may include IgE against autoantigens, immune complexes and complement.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-13T12:41:33.628924-05:
      DOI: 10.1111/all.13182
  • Transcriptome analysis of severely active chronic spontaneous urticaria
           shows an overall immunological skin involvement
    • Authors: A. Giménez-Arnau; L. Curto-Barredo, L. Nonell, E. Puigdecanet, J. Yelamos, R. Gimeno, S. Rüberg, L. Santamaria-Babi, R. M. Pujol
      Abstract: BackgroundThe knowledge about chronic spontaneous urticaria (CSU) phenotypes is based on its clinical characteristics, associated comorbidities, course of the disease and its response to the available effective drugs. Genotype expression and its further correlation with CSU phenotypes are still unknown. We describe the cutaneous transcriptome of patients suffering a severely active CSU refractory to antihistamine treatment.MethodsThrough the bioinformatic analysis of the whole Human Genome with Oligo Microarrays and Quantitative real-time polymerase chain reaction (qPCR), relevant genes expressed in non-lesional [NLS-CSU] and lesional skin [LS-CSU]) and peripheral blood were identified in 20 patients suffering from severely active CSU and 10 healthy controls (HCs)ResultsFrom 39 genes differentially expressed in NLS-CSU when compared with HCs, 31 (79.48%) were confirmed by qPCR corresponding to genes involved in epidermal homeostasis and dermal repair. From the analysis comparing LS-CSU with NLS-CSU, a selection of 142 genes was studied with qPCR, and 103 (72.53%) were confirmed. Differentially expressed genes in the phenomenon of wheal development are involved in a variety of biological functions as, epidermal differentiation, intracellular signal function, transcriptional factors cell cycle differentiation, inflammation or coagulation. Differentially expressed genes that uniformly increase or decrease along the skin worsening until the wheal appearance are shown.ConclusionThe skin of CSU patients with a severely active disease shows an overall immunological skin involvement showing a peculiar gene profile.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-13T12:36:53.231232-05:
      DOI: 10.1111/all.13183
  • Serum periostin relates to type-2 inflammation and lung function in
           asthma; data from the large population-based cohort Swedish GA(2)LEN
    • Authors: Anna James; Christer Janson, Andrei Malinovschi, Cecile Holweg, Kjell Alving, Junya Ono, Shoichiro Ohta, Alexandra Ek, Roelinde Middelveld, Barbro Dahlén, Bertil Forsberg, Kenji Izuhara, Sven-Erik Dahlén
      Abstract: BackgroundPeriostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type-2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear.AimTo examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics.MethodsSerum periostin was examined by ELISA in 1091 subjects aged 17-76 from the Swedish GA(2)LEN study, which included 460 asthmatics with/without chronic rhinosinusitis (CRS), 97 individuals with CRS only, and 203 healthy controls. Clinical tests included measurement of lung function, FeNO, IgE, urinary eosinophil derived neurotoxin (U-EDN) and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication and quality of life.ResultsAlthough median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower BMI related to higher periostin levels in subjects both with and without asthma.ConclusionWe confirm associations between periostin and markers of type-2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-11T09:35:30.069017-05:
      DOI: 10.1111/all.13181
  • Comparing immediate type food allergy in humans and companion animals
           – revealing unmet needs
    • Authors: I. Pali-Schöll; M. De Lucia, H. Jackson, J. Janda, R.S. Mueller, E. Jensen-Jarolim
      Abstract: Adverse food reactions occur in human as well as veterinary patients and systematic comparison may lead to improved recommendations for prevention and treatment in both. In this position paper, we summarize the current knowledge on immediate type food allergy versus other food-adverse reactions in companion animals, and compare this to the human situation. While the prevalence of food allergy in humans has been well studied for some allergens, this remains to be investigated for animal patients, where owner-reported as well as veterinarian-diagnosed food adverse reactions are on the increase. The characteristics of the disease in humans versus dogs, cats, and horses are most often caused by similar, but sometimes species-dependent different, pathophysiological mechanisms, prompting the specific clinical symptoms, diagnoses and treatments. Furthermore, little is known about the allergen molecules causative for type I food allergy in animals which, like in human patients, could represent predictive biomarkers for risk evaluation. The definite diagnosis of food allergy relies -as in humans- on elimination diet and provocation tests. Besides allergen avoidance in daily practice, novel treatment options and tolerization strategies are underway.Taken together, numerous knowledge gaps were identified in veterinary food allergy, which need to be filled by systematic comparative studies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-10T09:02:12.818144-05:
      DOI: 10.1111/all.13179
  • Work productivity in rhinitis using cell phones: The MASK pilot study
    • Authors: J Bousquet; M Bewick, S Arnavielhe, E Mathieu-Dupas, R Murray, A Bedbrook, D P Caimmi, O VandenPlas, P W Hellings, C Bachert, J M Anto, KC Bergmann, C Bindslev-Jensen, S Bosnic-Anticevitch, J Bouchard, GW Canonica, N H Chavannes, A A Cruz, R Dahl, P Demoly, G De Vries, P Devillier, A Fink-Wagner, W J Fokkens, J Fonseca, N Guldemond, T Haahtela, B Hellqvist-Dahl, J Just, T Keil, L Klimek, M L Kowalski, P Kuna, V Kvedariene, D Laune, D Larenas-Linnemann, J Mullol, A M Pereira, P Carreiro-Martins, E Melén, M Morais-Almeida, L Nogueira-Silva, R E O'Hehir, N G Papadopoulos, G Passalacqua, F Portejoie, D Price, D Ryan, B Samolinski, A Sheikh, F E R Simons, O Spranger, A Todo Bom, PV Tomazic, M Triggiani, A Valero, E Valovirta, A Valiulis, M van Eerd, M Wickman, I Young, T Zuberbier
      Abstract: Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to assess the impact of uncontrolled rhinitis assessed by visual analogue score VAS on work productivity using cell phone data collection.A mobile phone app Allergy Diary, Android and Apple stores collects daily visual analogue scales VAS data for overall allergic symptoms VAS-global measured, nasal VAS-nasal, ocular VAS-ocular, asthma symptoms VAS-asthma and work VAS-work. A combined nasal-ocular score is calculated. Allergy Diary is available in 20 countries. The App includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire WPAI:AS questionnaire in 6 EU countries. All consecutive users who filled the VAS-work from June 1 to October 31, 2016 were included in the study.A total of 1,136 users filled in 5,818 days of VAS-work. Symptoms of allergic rhinitis were controlled VAS-global50. There was a significant correlation between VAS-global calculated and VAS-work Rho=0.83, p
      PubDate: 2017-04-07T10:20:35.876721-05:
      DOI: 10.1111/all.13177
  • RNase 7 downregulates TH2 cytokine production by activated human T-cells
    • Authors: Verena Kopfnagel; Sylvia Wagenknecht, Lena Brand, Jana Zeitvogel, Jürgen Harder, Karsten Hofmann, Michael Kleine, Thomas Werfel
      Abstract: BackgroundThe antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T-cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity immunoregulatory functions have been published for several AMPs. In this study we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T-cells.MethodsIsolated human CD3+ T-cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T-cells and in polarised TH2 cells using skin derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay.ResultsTreatment of activated human CD4+ T-cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T-cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T-cells with RNase7.ConclusionOur data indicate that RNase 7 has immunomodulatory functions on TH2-cells and decreases the production of TH2 cytokines in the skinThis article is protected by copyright. All rights reserved.
      PubDate: 2017-04-04T19:10:25.827191-05:
      DOI: 10.1111/all.13173
  • Natural tolerance development in cow's milk allergic children:IgE and IgG4
           epitope binding
    • Authors: Jean Christoph Caubet; Jing Lin, Birgit Ahrens, Gustavo Gimenez, Luda Bardina, Bodo Niggemann, Hugh A. Sampson, Kirsten Beyer
      Abstract: BackgroundAlthough most of cow's milk (CM) allergic children will outgrow their allergy, the pathomechanism of the natural development of tolerance remains poorly understood. It has been suggested that the balance between milk specific IgE and IgG4 plays a major role.ObjectiveWe aimed to investigate differences in IgE and IgG4 antibody binding to cow's milk (CM) epitopes between patients with persistent CM allergy (CMA) and those that naturally became tolerant.MethodsSera from thirty-five children with proven CMA (median age at inclusion of 10 months) were analysed retrospectively; 22 patients have become tolerant (median age at tolerance acquisition of 51 months) during the study period as confirmed by a negative oral food challenge. IgE and IgG4 binding to sequential epitopes derived from 5 major CM proteins were measured with a peptide microarray-based immunoassay.ResultsAt baselines, greater intensity and broader diversity of IgE and IgG4 binding have been found in children with persistent CMA beyond 5 years of age compared to patients with transient CMA. Moreover, children with transient CMA had IgE and IgG4 antibodies that more often recognized the same epitopes, compared to those with persistent CMA. From baseline to the time of tolerance development, both IgE and IgG4 binding intensity decreased significantly, particularly in areas of α-s- and β-casein (p
      PubDate: 2017-03-27T04:09:47.840022-05:
      DOI: 10.1111/all.13167
  • Characterization of maize chitinase-A, a tough allergenic molecule
    • Authors: Mariateresa Volpicella; Claudia Leoni, Immacolata Fanizza, Marco Distaso, Guido Leoni, Laura Farioli, Todd Naumann, Elide Pastorello, Luigi Ruggiero Ceci
      Abstract: BackgroundFood allergies are recognized as an increasing health concern. They are caused by specific proteins called food allergens. Proteins commonly identified as food allergens tend to have one of about 30 different biochemical activities. This leads to the assumption that food allergens must have specific structural features which causes their allergenicity. But these structural features are not completely understood. Uncovering the structural basis of allergenicity would allow improved diagnosis and therapy of allergies and would provide insights for safer food production. The availability of recombinant food allergens can accelerate their structural analysis, and benefit specific studies in allergology. Plant chitinases are an example of food allergenic proteins for which structural analysis of allergenicity has only partially been reported.MethodsThe recombinant maize chitinase, rChiA, was purified from Pichia pastoris extracellular medium by differential precipitation and cation exchange chromatography. Enzyme activity was evaluated by halo-assays and microcalorimetric procedures. rChiA modeling was performed by a two-step procedure, using the Swissmodel server and Modeller software. Allergenicity of rChiA was verified by immunoblot assays with sera from allergic subjects.ResultsrChiA is active in the hydrolysis of glycol chitin and N-acetylchitotetraose, and maintains its activity at high temperatures (70 °C) and low pH (pH 3). The molecule is also reactive with IgE from sera of maize allergic subjects.ConclusionsrChiA is a valuable molecule for further studies on structure-allergenicity relationships and as a tool for diagnosing allergies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-22T09:28:49.449364-05:
      DOI: 10.1111/all.13164
  • Positioning the Principles of Precision Medicine in Care Pathways for
           Allergic Rhinitis and Chronic Rhinosinusitis - an
           EUFOREA-ARIA-EPOS-AIRWAYS ICP statement
    • Authors: P.W. Hellings; W.J. Fokkens, C. Bachert, C.A. Akdis, T. Bieber, I. Agache, M. Bernal-Sprekelsen, G.W. Canonica, P. Gevaert, G. Joos, V. Lund, A. Muraro, M. Onerci, T. Zuberbier, B. Pugin, S.F. Seys, J. Bousquet,
      Abstract: Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies.The aim of the current document is to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its’ implementation and the high cost of molecular diagnosis and biological treatment.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-17T10:11:20.590657-05:
      DOI: 10.1111/all.13162
  • Current status in diagnosis of atopic dermatitis in China
    • Authors: Ruhong Cheng; Yifeng Guo, Linting Huang, Fei Hao, Xinhua Gao, Thomas Bieber, Zhirong Yao
      Abstract: In China, eczema and atopic dermatitis (AD) have been traditionally considered as 2 distinct entities. Eczema typically referred to the milder phenotypes or to phenotypes with atypical morphology and distribution of lesions and many dermatologists have ever recognized that the “eczema” diagnosed clinically by them is actually milder phenotypes or phenotypes with atypical morphology and distribution of lesions of AD. Moreover, AD, contact dermatitis, diaper dermatitis, perioral dermatitis, halo dermatitis, pompholyx, seborrheic dermatitis, etc. are not included in category of “eczema” in Chinese textbook of dermatology2.This article is protected by copyright. All rights reserved.
      PubDate: 2017-02-24T15:10:30.632307-05:
      DOI: 10.1111/all.13149
  • Asthma management: A new phenotype-based approach using presence of
           eosinophilia and allergy
    • Authors: M. Terl; V. Sedlák, P. Cap, R. Dvořáková, V. Kašák, T. Kočí, B. Novotna, E. Seberova, P. Panzner, V. Zindr
      Pages: 1279 - 1287
      Abstract: Asthma is a heterogeneous disease. The Czech Pneumology and Allergology Societies commissioned 10 experts to review the literature and create joint national guidelines for managing asthma, reflecting this heterogeneity. The aim was to develop an easy-to-use diagnostic strategy as a rational approach to the widening opportunities for the use of phenotype-targeted therapy. The guidelines were presented on websites for public comments by members of both the societies. The reviewers’ comments contributed to creating the final version of the guidelines. The key hallmark of the diagnostic approach is the pragmatic concept, which assesses the presence of allergy and eosinophilia in each asthmatic patient. The guidelines define three clinically relevant asthma phenotypes: eosinophilic allergic asthma, eosinophilic nonallergic asthma and noneosinophilic nonallergic asthma. The resulting multifunctional classification describing the severity, level of control and phenotype is the starting point for a comprehensive treatment strategy. The level of control is constantly confronted with the intensity of the common stepwise pharmacotherapy, and the concurrently included phenotyping is essential for phenotype-specific therapy. The concept of the asthma approach with assessing the presence of eosinophilia and allergy provides a way for more precise diagnosis, which is a prerequisite for using widening options of personalized therapy.
      PubDate: 2017-04-26T03:30:43.13324-05:0
      DOI: 10.1111/all.13165
  • Clinical outcomes following inpatient penicillin allergy testing: A
           systematic review and meta-analysis
    • Authors: K. A. Sacco; A. Bates, T. J. Brigham, J. S. Imam, M. C. Burton
      Pages: 1288 - 1296
      Abstract: BackgroundA documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to use of broader-spectrum antibiotics. The aim of the systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization.MethodsWe performed an electronic search of Ovid MEDLINE/PubMed, Embase, Web of Science, Scopus, and the Cochrane Library over the past 20 years. Inpatients having a documented penicillin allergy that underwent penicillin allergy testing were included.ResultsTwenty-four studies met eligibility criteria. Study sample size was between 24 and 252 patients in exclusively inpatient cohorts. Penicillin skin testing (PST) with or without oral amoxicillin challenge was the main intervention described (18 studies). The population-weighted mean for a negative PST was 95.1% [CI 93.8-96.1]. Inpatient penicillin allergy testing led to a change in antibiotic selection that was greater in the intensive care unit (77.97% [CI 72.0-83.1] vs 54.73% [CI 51.2-58.2], P
      PubDate: 2017-04-26T03:36:00.846919-05:
      DOI: 10.1111/all.13168
  • Allergic respiratory disease: Different allergens, different symptoms
    • Authors: A. Valero; S. Quirce, I. Dávila, J. Delgado, J. Domínguez-Ortega
      Pages: 1306 - 1316
      Abstract: BackgroundSpanish population is rather homogeneous in its genetic and sociocultural characteristics, but allergen sensitization shows wide geographical variations. We aimed at assessing whether sensitization to different allergens in the diverse geographical areas induced different clinical and quality-of-life characteristics in adult patients with a first-time diagnosis of rhinitis and/or asthma.MethodsTwo sequential, identically designed studies were carried out to evaluate such associations (PERFILAR I and II). PERFILAR II was an extension of PERFILAR I with additional allergens being included. Both phases were epidemiological, descriptive, cross-sectional, nonintervention multicenter studies. Participants were required to have lived for at least the last 2 years in the geographical zone. Asthma control assessment was based on ACQ-5. Health-related quality of life was evaluated with validated scales for rhinitis (ESPRINT-15) and asthma (Mini-AQLQ). Skin prick tests were used to identify sensitization to involved allergens.ResultsA total of 301 physicians recruited 2711 patients for PERFILAR I+II. Sensitization to allergens was significantly different in patients with rhinitis with/without asthma. Seasonal allergens were associated with rhinitis, a longer time to asthma development, and more severe and commonly intermittent rhinitis. HDM were associated with more common rhinitis, and Alternaria was associated with asthma. The study confirms an association of geographical areas with relevant allergens and allergic clinical picture.ConclusionDifferent types of aeroallergens and specific sensitization profiles are associated with different allergic clinical pictures (rhinitis with/without asthma), different clinical symptoms, and different levels of severity. This could have implications to predict later clinical course and to select appropriate management approaches.
      PubDate: 2017-03-17T00:45:33.716536-05:
      DOI: 10.1111/all.13141
  • Attenuated airway hyperresponsiveness and mucus secretion in HDM-exposed
           Igf1r-deficient mice
    • Authors: S. Piñeiro-Hermida; J. A. Gregory, I. P. López, R. Torrens, C. Ruíz-Martínez, M. Adner, J. G. Pichel
      Pages: 1317 - 1326
      Abstract: BackgroundAsthma is a common chronic lung disease characterized by airflow obstruction, airway hyperresponsiveness (AHR), and airway inflammation. IGFs have been reported to play a role in asthma, but little is known about how the insulin-like growth factor 1 receptor (IGF1R) affects asthma pathobiology.MethodsFemale Igf1r-deficient and control mice were intranasally challenged with house dust mite (HDM) extract or PBS five days per week for four weeks. Lung function measurements, and bronchoalveolar lavage fluid (BALF), serum, and lungs were collected on day 28 for further cellular, histological, and molecular analysis.ResultsFollowing HDM exposure, the control mice responded with a marked AHR and airway inflammation. The Igf1r-deficient mice exhibited an increased expression of the IGF system and surfactant genes, which were decreased in a similar manner for control and Igf1r-deficient mice after HDM exposure. On the other hand, the Igf1r-deficient mice exhibited no AHR, and a selective decrease in blood and BALF eosinophils, lung Il13 levels, collagen, and smooth muscle, as well as a significant depletion of goblet cell metaplasia and mucus secretion markers after HDM exposure. The Igf1r-deficient mice displayed a distinctly thinner epithelial layer than control mice, but this was not altered by HDM.ConclusionsHerein, we demonstrate by the first time that the Igf1r plays an important role in murine asthma, mediating both AHR and mucus secretion after HDM exposure. Thus, our study identifies IGF1R as a potential therapeutic target, not only for asthma but also for hypersecretory airway diseases.
      PubDate: 2017-03-20T23:35:38.296416-05:
      DOI: 10.1111/all.13142
  • Dysregulation of metabolic pathways in a mouse model of allergic asthma
    • Authors: K. D. Quinn; M. Schedel, Y. Nkrumah-Elie, A. Joetham, M. Armstrong, C. Cruickshank-Quinn, R. Reisdorph, E. W. Gelfand, N. Reisdorph
      Pages: 1327 - 1337
      Abstract: BackgroundAsthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function.MethodsIn this experimental model of allergic asthma, matched bronchoalveolar lavage (BAL) fluid and plasma were collected from three groups of C57BL6 mice (control vs sensitized and/or challenged with ovalbumin, n=3-5/group) 6 hour, 24 hour, and 48 hour after the last challenge. Samples were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Airway hyper-responsiveness (AHR) measurements and differential cell counts were performed.ResultsIn total, 398 and 368 dysregulated metabolites in the BAL fluid and plasma of sensitized and challenged mice were identified, respectively. These belonged to four, interconnected pathways relevant to asthma pathogenesis: sphingolipid metabolism (P=6.6×10−5), arginine and proline metabolism (P=1.12×10−7), glycerophospholipid metabolism (P=1.3×10−10), and the neurotrophin signaling pathway (P=7.0×10−6). Furthermore, within the arginine and proline metabolism pathway, a positive correlation between urea-1-carboxylate and AHR was observed in plasma metabolites, while ornithine revealed a reciprocal effect. In addition, agmatine positively correlated with lung eosinophilia.ConclusionThese findings point to potential targets and pathways that may be central to asthma pathogenesis and can serve as novel therapeutic targets.
      PubDate: 2017-03-29T04:49:46.226808-05:
      DOI: 10.1111/all.13144
  • Dysregulation of interleukin 5 expression in familial eosinophilia
    • Authors: S. Prakash Babu; Y.-Y. K. Chen, S. Bonne-Annee, J. Yang, I. Maric, T. G. Myers, T. B. Nutman, A. D. Klion
      Pages: 1338 - 1345
      Abstract: BackgroundFamilial eosinophilia (FE) is a rare autosomal dominant inherited disorder characterized by the presence of lifelong peripheral eosinophilia (>1500/μL). Mapped to chromosome 5q31-q33, the genetic cause of FE is unknown, and prior studies have failed to demonstrate a primary abnormality in the eosinophil lineage.ObjectiveThe aim of this study was to identify the cells driving the eosinophilia in FE.MethodsMicroarray analysis and real-time PCR were used to examine transcriptional differences in peripheral blood mononuclear cells (PBMC), and in purified cell subsets from affected and unaffected family members belonging to a single large kindred. Cytokine levels in serum and PBMC culture supernatants were assessed by suspension array multiplexed immunoassays.ResultsWhereas IL-5 mRNA expression was significantly increased in freshly isolated PBMC from affected family members, this was not accompanied by increased mRNA expression of other Th2 cytokines (IL-4 or IL-13). Serum levels of IL-5 and IL-5 receptor α, but not IgE, were similarly increased in affected family members. Of note, IL-5 mRNA expression was significantly increased in purified CD3+ CD4+, CD14+, CD19+, and ILC2 cells from affected family members, as were IL-5 protein levels in supernatants from both stimulated PBMC and ILC2 cultures.ConclusionsThese data are consistent with the hypothesis that the eosinophilia in FE is secondary to dysregulation of IL-5 production in PBMC (and their component subsets).
      PubDate: 2017-04-18T03:55:57.33405-05:0
      DOI: 10.1111/all.13146
  • Natural evolution in patients with nonsteroidal anti-inflammatory
           drug-induced urticaria/angioedema
    • Authors: I. Doña; E. Barrionuevo, M. Salas, J. A. Cornejo-García, J. R. Perkins, G. Bogas, A. Prieto, M. J. Torres
      Pages: 1346 - 1355
      Abstract: BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent triggers of drug hypersensitivity with NSAIDs-induced urticaria/angioedema (NIUA) the most common phenotype. Loss of hypersensitivity has been reported for IgE-mediated reactions; however, it has not been assessed in nonimmunological reactions such as NIUA. We evaluated NSAID-hypersensitivity over time in NIUA patients.MethodsPatients confirmed as NIUA by positive drug provocation test (DPT) with acetylsalicylic acid (ASA) during 2005-2012 (V1) were included (n=38). Subjects were prospectively re-evaluated by DPT with ASA/other NSAIDs at two time points between 2013 and 2015 (V2 and V3). Atopy was assessed by skin prick test (SPT) using inhalant and food allergens.ResultsPatients were evaluated at V1 and re-evaluated after 60 months (V2; IR:48-81) and a further 18 months (V3; IR:14-24). At V2, the majority (24; 63.15%) tolerated ASA and other NSAIDs (Group A) while 14 (36.84%) still reacted (Group B). At V3, all Group A patients remained tolerant; all Group B patients remained hypersensitive. The number of previous episodes reported at V1 and the percentage of reactions induced by ASA/ibuprofen were significantly lower in Group A (P=.005 and P=.006, respectively). Group A patients developed tolerance 72 months (IR:45-87) after their last evaluated reaction (V1); this interval was shorter in nonatopics (P=.003), patients who experienced reactions over 1 hour after NSAIDs administration (P=.001), and those who experienced isolated urticaria after NSAID intake (P=.024).ConclusionsNIUA patients may develop tolerance to NSAIDs over time, a process that seems to be influenced by atopy and type of clinical reaction.
      PubDate: 2017-03-20T23:26:02.073953-05:
      DOI: 10.1111/all.13147
  • The skin barrier function gene SPINK5 is associated with challenge-proven
           IgE-mediated food allergy in infants
    • Authors: S. E. Ashley; H.-T. T. Tan, P. Vuillermin, S. C. Dharmage, M. L. K. Tang, J. Koplin, L. C. Gurrin, A. Lowe, C. Lodge, A.-L. Ponsonby, J. Molloy, P. Martin, M. C. Matheson, R. Saffery, K. J. Allen, J. A. Ellis, D. Martino, ,
      Pages: 1356 - 1364
      Abstract: BackgroundA defective skin barrier is hypothesized to be an important route of sensitization to dietary antigens and may lead to food allergy in some children. Missense mutations in the serine peptidase inhibitor Kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions.ObjectiveTo determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy.MethodWe genotyped 71 “tag” single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these individuals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components.ResultsSPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery sample (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also.ConclusionsWe report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.
      PubDate: 2017-04-04T23:40:29.953626-05:
      DOI: 10.1111/all.13143
  • Skin prick tests and specific IgE in 10-year-old children: Agreement and
           association with allergic diseases
    • Authors: A. Chauveau; M.-L. Dalphin, F. Mauny, V. Kaulek, E. Schmausser-Hechfellner, H. Renz, J. Riedler, J. Pekkanen, A. M. Karvonen, R. Lauener, C. Roduit, D. A. Vuitton, E. von Mutius, J.-C. Dalphin,
      Pages: 1365 - 1373
      Abstract: BackgroundAccurate assessment of atopic sensitization is pivotal to clinical practice and research. Skin prick test (SPT) and specific IgE (sIgE) are often used interchangeably. Some studies have suggested a disagreement between these two methods, and little is known about their association with allergic diseases. The aims of our study were to evaluate agreement between SPT and sIgE, and to compare their association with allergic diseases in 10-year-old children.MethodsSkin prick test, sIgE measurements, and assessment of allergic diseases were performed in children aged 10 years in the Protection against Allergy: STUdy in Rural Environments (PASTURE) cohort. The agreement between SPT and sIgE was assessed by Cohen's kappa coefficient with different cutoff values.ResultsSkin prick tests and sIgE were performed in 529 children. The highest agreement (κ=.44) was found with a cutoff value of 3 and 5 mm for SPT, and 3.5 IU/mL for sIgE. The area under the curve (AUC) obtained with SPT was not significantly different from that obtained with sIgE. For asthma and hay fever, SPT (cutoff value at 3 mm) had a significantly higher specificity (P
      PubDate: 2017-04-12T02:55:38.911621-05:
      DOI: 10.1111/all.13148
  • New approach shows no association between maternal milk fatty acid
           composition and childhood wheeze or asthma
    • Authors: C. A. Logan; S. Brandt, M. Wabitsch, H. Brenner, F. Wiens, B. Stahl, T. Marosvölgyi, T. Decsi, D. Rothenbacher, J. Genuneit
      Pages: 1374 - 1383
      Abstract: BackgroundPrevious observational studies have implied breastmilk fatty acid composition may play a role in the development of atopic eczema or atopic sensitization in breastfed infants and toddlers. However, studies investigating associations with wheeze and asthma in later childhood are scarce and did not account for inherent correlation of compositional data. Our aim was to explore the association of maternal milk fatty acid composition with childhood wheezing phenotypes and asthma up to age 13 years using a new statistical approach.MethodsBreastmilk was collected 6 weeks and 6 months postdelivery in the Ulm Birth Cohort Study (n=720 and n=454, respectively). Concentrations of 28 fatty acids were measured by high-resolution capillary gas-liquid chromatography. To control for constant-sum constraint, concentration data were transformed using the centered log ratio method. Compositional biplots and correlation matrices were used to group centered log ratio transformed fatty acids. Adjusted risk ratios with parent-reported wheezing phenotypes and doctor-diagnosed asthma were computed using a modified Poisson regression.ResultsWe observed no straightforward evidence of associations between overall breastmilk fatty acid composition and specific wheeze phenotypes or doctor-diagnosed asthma.ConclusionUsing appropriate statistical methodology, we report null associations. These findings may partly be attributable to several cohort-specific factors associated with breastfeeding and breastmilk collection. Further studies could improve on ours by analyzing samples of breastmilk and formula and by including all children for whom these are exclusively or together the major source of fatty acids in the first months of life.
      PubDate: 2017-04-11T01:20:52.972998-05:
      DOI: 10.1111/all.13161
  • Interferon-γ-induced insufficient autophagy contributes to p62-dependent
    • Authors: B-F. Wang; P-P. Cao, Z-C. Wang, Z-Y. Li, Z-Z. Wang, J. Ma, B. Liao, Y-K. Deng, X-B. Long, K. Xu, H. Wang, H. Wang, M. Zeng, X. Lu, Z. Liu
      Pages: 1384 - 1397
      Abstract: BackgroundAutophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the pathogenesis of CRS with nasal polyps (CRSwNP).MethodsThe expression of autophagic proteins [microtubule-associated protein 1 light chain 3B (LC3B)-II, autophagy-related proteins (Atg), and Beclin 1], substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling molecules [cysteine-aspartic protease-3 and cysteine-aspartic protease-8, and poly-ADP-ribose polymerase] in the sinonasal mucosa and nasal epithelial cells (NECs) was detected by immunohistochemistry and Western blotting. Autophagic vacuoles were observed with transmission electron microscopy. BEAS-2B cells and NECs were treated with rapamycin, bafilomycin A1, or various cytokines. In some experiments, cultured NECs were transfected with small interfering RNA targeting p62 (sip62) or Atg5 (siAtg5). Cultured cells were analyzed with Western blotting and flow cytometry.ResultsAlthough autophagic protein expression and autophagic vacuole formation were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in NECs, there was also an up-regulation of substrate proteins and apoptotic signaling molecules. IFN-γ, but not IL-4, IL-13, or IL-17A, simultaneously enhanced LC3B-II and p62 levels as well as cell apoptosis in BEAS-2B cells and/or normal NECs. Bafilomycin A1 up-regulated the levels of LC3B-II and p62 in polyp NECs and IFN-γ-treated normal NECs. IFN-γ-induced apoptosis of normal NECs was exaggerated by bafilomycin A1 and siAtg5. Sip62 suppressed apoptosis of polyp NECs and IFN-γ-treated NECs. IFN-γ protein levels were increased in both eosinophilic and noneosinophilic CRSwNP.ConclusionsIFN-γ induces activated but insufficient autophagy and thus contributes to a degree to p62-dependent apoptosis of NECs in CRSwNP.
      PubDate: 2017-04-04T23:40:53.270456-05:
      DOI: 10.1111/all.13153
  • Long-term future risk of severe exacerbations: Distinct 5-year
           trajectories of problematic asthma
    • Authors: A. C. A. Yii; J. H. Y. Tan, T. S. Lapperre, A. K. W. Chan, S. Y. Low, T. H. Ong, K. L. Tan, S. H. Chotirmall, P. J. Sterk, M. S. Koh
      Pages: 1398 - 1405
      Abstract: BackgroundAssessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short- but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment.AimTo identify distinct trajectories of severe exacerbation rates among “problematic asthma” patients and develop a risk score to predict the most unfavorable trajectory.MethodsSevere exacerbation rates over five years for 177 “problematic asthma” patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory.ResultsThree distinct trajectories were found: 58.5% had rare intermittent severe exacerbations (“infrequent”), 32.0% had frequent severe exacerbations at baseline but improved subsequently (“nonpersistently frequent”), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma (“persistently frequent”). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index ≥25kg/m2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the “persistently frequent” trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort.ConclusionsPatients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently frequent severe exacerbations in the future.
      PubDate: 2017-04-25T00:45:48.888598-05:
      DOI: 10.1111/all.13159
  • Differences in eosinophil molecular profiles between children and adults
           with eosinophilic esophagitis
    • Authors: C. Lingblom; T. Käppi, H. Bergquist, M. Bove, R. Arkel, R. Saalman, C. Wennerås
      Pages: 1406 - 1414
      Abstract: BackgroundEosinophilic esophagitis (EoE) afflicts both children and adults. It has been debated whether pediatric EoE and adult EoE represent different disease entities. The objectives of this study were to determine whether the blood eosinophil molecular pattern of children with EoE is (i) distinct from that of healthy children; and (ii) different from that of adults with EoE.MethodsBlood eosinophils from children and adults with EoE, and healthy controls, were analyzed with flow cytometry regarding levels of CD23, CD44, CD54, CRTH2, FOXP3, and galectin-10. Eosinophil FOXP3 and galectin-10 mRNA levels were determined by qPCR. The data were analyzed using a multivariate method of pattern recognition.ResultsAn eosinophil molecular pattern capable of distinguishing children with EoE from control children was identified. A smaller fraction of eosinophils from children with EoE expressed CD44 and a larger fraction expressed CRTH2 than the controls. Eosinophils from children with EoE also had higher levels of galectin-10 mRNA and lower levels of FOXP3 mRNA. The eosinophils from children with EoE had lower levels of surface CD54 and of FOXP3 mRNA compared with the eosinophils from the adult patients. A key finding was the detection in healthy individuals of age-related differences in the levels of several eosinophil markers.ConclusionsChildren with EoE can be distinguished from healthy children based on the molecular patterns of their blood eosinophils. Age-related physiologic differences in eosinophil molecular patterns may partly explain the different blood eosinophil phenotypes in children vs adults with EoE.
      PubDate: 2017-03-17T00:45:36.948667-05:
      DOI: 10.1111/all.13140
  • Pru p 3, a marker allergen for lipid transfer protein sensitization also
           in Central Europe
    • Authors: N. Mothes-Luksch; M. Raith, G. Stingl, M. Focke-Tejkl, E. Razzazi-Fazeli, R. Zieglmayer, S. Wöhrl, I. Swoboda
      Pages: 1415 - 1418
      Abstract: In the Mediterranean area, lipid transfer proteins (LTPs) are important causes of plant-food allergies often associated with severe allergic reactions. There, peach LTP (Pru p 3) seems to be the primary sensitizer, whereas in Central Europe, little is known about the importance of LTP sensitization. In this region, allergen extract-based diagnosis is often complicated by co-sensitization to Bet v 1, the major birch pollen allergen, its cross-reactive food allergens, and profilins. We investigated the role of LTP sensitization in Central European patients displaying strong allergic reactions to plant-derived food. Analysis of IgE reactivity revealed that ten of thirteen patients were sensitized to Pru p 3, nine to Bet v 1, and two to profilin. Our results showed that LTP sensitization represents a risk factor for severe allergic symptoms in Central Europe. Furthermore, the strong IgE reactivity detected in immunoblots of plant-food extracts indicated that Pru p 3 can be used as a marker allergen for LTP sensitization also in Central European patients.
      PubDate: 2017-04-03T23:30:31.124472-05:
      DOI: 10.1111/all.13151
  • Questionable diagnostic benefit of the commercially available panel of bee
           venom components
    • Authors: L. Arzt; D. Bokanovic, C. Schrautzer, I. Schwarz, K. Laipold, W. Aberer, G. J. Sturm
      Pages: 1419 - 1422
      Abstract: For many years, only the major allergen rApi m 1 has been available on the ImmunoCAP system for routine diagnosis of bee venom (BV) allergy. Now, there are five components available, and we aimed to detect the sensitivity and specificity of rApi m 1, 2, 3, 5, and 10 in BV-allergic patients. We further evaluated the sensitivity of rApi m 1 and 2 of an alternative platform and investigated possible differences in the sensitization profile between monosensitization and clinically relevant double sensitization. Analysis of the whole panel of BV allergens of the CAP system still resulted in a lower sensitivity than analysis of the combination of rApi m 1 and 2 of the Immulite (71.6% vs 85.8%). Sensitization rate of rApi m 5 was more than doubled in double-sensitized patients, while there was no difference for rApi m 2. The benefit of the commercially available panel of BV components is questionable, due to the insufficient sensitivity and still unavailable important cross-reacting allergens.
      PubDate: 2017-03-31T03:00:25.414835-05:
      DOI: 10.1111/all.13154
    • Pages: 1430 - 1430
      PubDate: 2017-08-07T00:58:14.459923-05:
      DOI: 10.1111/all.13171
    • Pages: 1431 - 1431
      PubDate: 2017-08-07T00:58:11.248878-05:
      DOI: 10.1111/all.13172
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