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Showing 1 - 200 of 1589 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: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 52, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 164, 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: 6, 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: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 4)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 14, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 27, 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: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 268, 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: 7, 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: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 10)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, 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: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 148, 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: 92, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 34, 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: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 276, 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: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 138, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 9, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 18)
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: 220)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 222, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, 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: 7, 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: 47, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, 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: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, 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: 89, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 49, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, 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: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 206, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 49, 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: 36, 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: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
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: 245, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 52, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, 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: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 320, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, 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: 4, 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: 6, 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: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, 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: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, 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: 47, 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: 5, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, 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: 14, 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: 406, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 21, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, 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: 11, 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: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, 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: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 4, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, 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: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 141, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, 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: 6, 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: 243, SJR: 2.083, h-index: 125)

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Journal Cover Allergy
  [SJR: 3.048]   [H-I: 129]   [51 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  [1589 journals]
  • Monocytes enhance neutrophil-induced blister formation in an ex vivo model
           of bullous pemphigoid
    • Authors: E. de Graauw; C. Sitaru, M.P. Horn, L. Borradori, S. Yousefi, D. Simon, H.-U. Simon
      Abstract: BackgroundLesions of bullous pemphigoid (BP), an autoimmune subepidermal blistering disease characterized by the presence of tissue-bound and circulating autoantibodies to hemidesmosomal antigens, harbour a mixed inflammatory cellular infiltrate. In various models, neutrophils, eosinophils, mast cells, monocytes as well as B and T cells have been shown to be involved in the pathogenesis of BP. However, their interactions with and effective role in blister formation remains uncertain. This study was aimed at investigating the effect of monocyte/neutrophil interaction on blister formation in an ex vivo BP model.MethodsSkin cryosections were incubated with purified human neutrophils and monocytes, in the presence or absence of BP autoantibodies. Production of reactive oxygen species (ROS), degranulation, mediator release (neutrophil elastase (NE), myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9)), binding of Fcγ receptor (CD16, CD32, CD64), and cell adhesion (CD18, ICAM-1) were investigated using appropriate inhibitors. Dermal-epidermal separation (DES) was assessed by light microscopy and quantified by Fiji software.ResultsMonocytes and neutrophils synergistically interact resulting in a significantly higher DES compared to either monocytes or neutrophils separately (P < 0.0001). Monocyte/neutrophil-induced DES was associated with increased ROS production and was dependent on adhesion and FcγRIII binding. Upon stimulation by the granule-poor fraction of monocyte supernatants, neutrophils increased their release of MMP-9, thereby also DES at the dermal-epidermal junction of skin cryosections.ConclusionOur observations suggest that the interaction of cells, as shown here for monocytes and neutrophils, enhances mediator release resulting in an increased subepidermal blister formation. Thus, blocking intercellular cross-talk promises a new therapeutic approach for blocking tissue damage in BP.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-08T20:25:53.36691-05:0
      DOI: 10.1111/all.13376
  • Identification of a 62 kDa major allergen from Artemisia pollen as a
           putative galactose oxidase
    • Authors: Wanyi Fu; Zhongshan Gao, Ling Gao, Jing Jin, Meiling Liu, Yuemei Sun, Shandong Wu, Lingying Wu, Hongshan Ma, Yimin Dong, Xuefeng Wang, Biyuan Gao, Huiying Wang, Jaap H. Akkerdaas, Serge A. Versteeg, Ronald van Ree
      Abstract: BackgroundAround 20 years ago, a 60-70 kDa protein was reported as a major allergen of mugwort (Artemisia vulgaris) pollen. This study was to identify and characterize its molecular properties.MethodsSera from 113 Chinese and 20 Dutch Artemisia allergic/sensitized subjects (and pools thereof) were used to identify the 60-70 kDa allergen. Pollen extracts of seven Artemisia species were compared by immunoblotting. Transcriptomics and proteomics (mass spectrometry) of A. annua pollen were used to identify the putative 60-70 kDa Artemisia allergen. Both the natural purified and recombinant allergens were evaluated for IgE reactivity by ImmunoCAP. Fourteen Chinese Artemisia allergic patients were tested intradermally with purified natural allergen.ResultsImmunoblots revealed two major bands at 12 and 25 kDa, and a weak band at 70 kDa for all seven Artemisia species. Using a combined transcriptomic and proteomic approach, the high molecular mass allergen in A. annua pollen was shown to be a 62 kDa putative galactose oxidase, with a putative N-glycosylation site. More than 94% of Artemisia pollen allergic patients had IgE response to this allergen. Although recognition of a non-glycosylated recombinant version was only confirmed in a minority (16%) and at much lower IgE levels, this discrepancy cannot be explained simply by reactivity to the carbohydrate moiety on the natural allergen. Intradermal testing with the natural allergen was positive in five out of nine sensitized patients.ConclusionsThe previously reported 60-70 kDa allergen of Artemisia pollen is most likely a 62 kD putative galactose oxidase here designated Art an 7.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-08T09:10:33.448711-05:
      DOI: 10.1111/all.13375
  • EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy
    • Authors: G. B. Pajno; M. Fernandez-Rivas, S. Arasi, G. Roberts, C. A. Akdis, M. Alvaro-Lozano, K. Beyer, C. Bindslev-Jensen, W. Burks, M. Ebisawa, P. Eigenmann, E. Knol, K. C. Nadeau, L. K. Poulsen, R. van Ree, A. F. Santos, G. du Toit, S. Dhami, U. Nurmatov, Y. Boloh, M. Makela, L. O'Mahony, N. Papadopoulos, C. Sackesen, I. Agache, E. Angier, S. Halken, M. Jutel, S. Lau, O. Pfaar, D. Ryan, G. Sturm, E.-M. Varga, R. G. van Wijk, A. Sheikh, A. Muraro,
      Abstract: Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.
      PubDate: 2017-12-05T02:16:30.66099-05:0
      DOI: 10.1111/all.13319
  • Identification of patterns of factors preceding severe or life-threating
           asthma exacerbations in a nationwide study
    • Authors: H. Tanaka; E. Nakatani, Y. Fukutom, K. Sekiya, H. Kaneda, M. Iikura, M. Yoshida, K. Takahashi, K. Tomii, M. Nishikawa, N. Kaneko, Y. Sugino, M. Shinkai, T. Ueda, Y. Tanikawa, T Shirai, M. Hirabayashi, T. Aoki, T. Kato, K Iizuka, M. Fujii, M. Taniguchi
      Abstract: BackgroundReducing near-fatal asthma exacerbations is a critical problem in asthma management.ObjectivesTo determine patterns of factors preceding asthma exacerbations in a real-world setting.MethodsIn a nationwide prospective study of 190 patients who had experienced near-fatal asthma exacerbation, cluster analysis was performed using asthma symptoms over the two-week period before admission.ResultsThree distinct clusters of symptoms were defined employing the self-reporting of a visual analogue scale. Cluster A (42.1%): rapid worsening within 7.4 hours from moderate attack to admission, young to middle-aged patients with low BMI and tendency to depression who had stopped anti-asthma medications, smoked, were hypersensitive to environmental triggers and furred pets. Cluster B (40.0%): fairly-rapid worsening within 48 hours, mostly middle-aged and older, relatively good ICS or ICS/LABA compliance, and low perception of dyspnea. Cluster C (17.9%): slow worsening over 10 days before admission, high perception of dyspnea, smokers, and chronic daily mild-moderate symptoms. There were no differences in overuse of short-acting beta-agonists, baseline asthma severity, or outcomes after admission for patients in these three clusters.ConclusionTo reduce severe or life-threatening asthma exacerbation, personalized asthma management plans should be considered for each cluster. Improvement of ICS and ICS/LABA compliance and cessation of smoking are important in cluster A. To compensate for low perception of dyspnea, asthma monitoring of peak expiratory flow rate and/or exhaled nitric oxide would be useful for patients in cluster B. Avoidance of environmental triggers, increased standard therapy or new anti-type 2 response-targeted therapies should be considered for cluster C.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T22:55:21.539338-05:
      DOI: 10.1111/all.13374
  • Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis
           and chronic rhinosinusitis: the one airway concept revisited
    • Authors: Konstantinos Samitas; Alison Carter, Harsha H. Kariyawasam, Georgina Xanthou
      Abstract: Allergic rhinitis (AR), chronic rhinosinusitis (CRS) and asthma often co-exist. The one airway model proposes that disease mechanisms occurring in the upper airway may mirror lower airway events. Airway remodelling is the term used to describe tissue structural changes that occur in a disease setting and reflect the dynamic process of tissue restructuring during wound repair. Remodelling has been long identified in the lower airways in asthma and is characterized by epithelial shedding, goblet cell hyperplasia, basement membrane thickening, subepithelial fibrosis, airway smooth muscle hyperplasia and increased angiogenesis. The concept of upper airway remodelling has only recently been introduced, and data so far is limited and often conflicting, an indication that more detailed studies are needed. Whilst remodelling changes in AR are limited, CRS phenotypes demonstrate epithelial hyperplasia, increased matrix deposition and degradation along with accumulation of plasma proteins. Despite extensive research over the past years, the precise cellular and molecular mechanisms involved in airway remodelling remain incompletely defined. This review describes our current rather limited understanding of airway remodelling processes in AR, CRS and asthma, and presents mechanisms both shared and distinct between the upper and lower airways. Delineation of shared and disease-specific pathogenic mechanisms of remodelling between the sinonasal system and the lung may guide the rational design of more effective therapeutic strategies targeting upper and lower airways concomitantly and improving the health of individuals with inflammatory airway diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-01T22:50:25.964171-05:
      DOI: 10.1111/all.13373
  • Indoor allergen levels in settled airborne dust are higher in day-care
           centres than at home
    • Authors: I Sander; A Lotz, H D Neumann², C Czibor, A Flagge, E Zahradnik, M Raulf
      Abstract: BackgroundEarly life sensitization to indoor allergens predicts asthma development. Aim of study was to compare allergen concentrations in day-care centres (DCC) to those in private homes.MethodsSettled airborne dust was collected four times a year from 20 German DCC (620 samples), and from the homes of children and day-care workers (602 samples) using electrostatic dust collectors (EDC). The samples were analysed with fluorescence-enzyme-immunoassays recognising domestic mite allergens (DM), Fel d 1, Can f 1 and Mus m 1. Pet allergen thresholds that discriminate samples from homes with cats or dogs to those without were calculated using receiver-operator characteristics. Influences on allergen levels were analysed using multilevel models.ResultsAllergen loads were on average higher in DCC than in homes. In DCC, 96% of the samples were positive for DM, 95% for Can f 1, 90% for Fel d 1, and 83% for Mus m 1. In homes, 84% contained DM, 48.5% Can f 1, 33% Fel d 1, and 43% Mus m 1. The threshold level for homes with dogs was 75 ng/m² Can f 1 (96.8% sensitivity, 96% specificity), and 46 ng/m² Fel d 1 for homes with cats (92% sensitivity, 94.9% specificity). In DCC, Can f 1 and Fel d 1 loads were higher than these thresholds in 37% and 54% of the samples, respectively. Allergen levels were significantly influenced by the season and room type; however, carpets on floors had no influence.ConclusionsMite, mouse, cat and dog allergens were mostly higher in DCC than in homes. Exposure to dog and cat allergens in DCC often reached levels of households with pets.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-29T11:46:01.429131-05:
      DOI: 10.1111/all.13371
  • Pregnancy and perinatal conditions and atopic disease prevalence in
           childhood and adulthood
    • Authors: Jessica Gerlich; Nora Benecke, Astrid S. Peters-Weist, Sabine Heinrich, Diana Roller, Jon Genuneit, Gudrun Weinmayr, Doris Windstetter, Holger Dressel, U Range, Dennis Nowak, Erika von Mutius, Katja Radon, Christian Vogelberg
      Abstract: BackgroundPrevious studies showed controversial results for the influence of pregnancy-related and perinatal factors on subsequent respiratory and atopic diseases in children. The aim of this study was to assess the association between perinatal variables and the prevalence of asthma, bronchial hyperreactivity, flexural eczema, allergic rhinitis, and sensitization in childhood and early adulthood.MethodsThe studied population was first examined in Munich and Dresden in 1995/1996 at age 9-11 yrs. Participants were followed until age 19-24 yrs. using questionnaires and clinical examinations. Associations between perinatal data and subsequent atopic diseases were examined using logistic regression analyses adjusting for potential confounders.ResultsCesarean section was statistically significantly associated with BHR in early adulthood (Odds Ratio 4.8, 95% confidence interval 1.5-15.2), while assisted birth was associated with presence of asthma symptoms in childhood (2.2, 1.2-3.9), flexural eczema symptoms (2.2, 1.2-4.3) and doctor's diagnosis of atopic dermatitis (1.9, 1.0-3.4) in childhood, and sensitization in early adulthood (2.2, 1.1-4.3). Lower birth length (1.9, 1.1-3.2), lower birth weight (0.5, 0.3-0.9) and higher birth weight (0.6 (0.4-1.0)) were predictive of sensitization in early adulthood compared to average birth length and birth weight, respectively. None of the other perinatal factors showed statistically significant associations with the outcomes.ConclusionsOur results indicate that children, who are born by Cesarean section and especially by assisted birth, might be at greater risk for developing asthma, flexural eczema and sensitization and should hence be monitored. Prenatal maternal stress might partly explain these associations, which should be further investigated.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-29T11:45:35.210271-05:
      DOI: 10.1111/all.13372
  • Comorbid ‘treatable traits’ in difficult asthma: Current evidence and
           clinical evaluation
    • Authors: Tunn Ren Tay; Mark Hew
      Abstract: The care of patients with difficult-to-control asthma (‘difficult asthma’) is challenging and costly. Despite high-intensity asthma treatment, these patients experience poor asthma control and face the greatest risk for asthma morbidity and mortality. Poor asthma control is often driven by severe asthma biology, which has appropriately been the focus of intense research and phenotype-driven therapies. However, it is increasing apparent that extra-pulmonary comorbidities also contribute substantially to poor asthma control and a heightened disease burden. These comorbidities have been proposed as “treatable traits” in chronic airways disease, adding impetus to their evaluation and management in difficult asthma.In this review, eight major asthma-related comorbidities are discussed; rhinitis, chronic rhinosinusitis, gastroesophageal reflux, obstructive sleep apnoea, vocal cord dysfunction, obesity, dysfunctional breathing, and anxiety/depression. We describe the prevalence, impact, and treatment-effects of these comorbidities in the difficult asthma population, emphasizing gaps in the current literature. We examine the associations between individual comorbidities, and highlight the potential for comorbidity clusters to exert combined effects on asthma outcomes. We conclude by outlining a pragmatic clinical approach to assess comorbidities in difficult asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-27T11:20:23.179784-05:
      DOI: 10.1111/all.13370
  • Macrophages-common culprit in obesity and asthma
    • Authors: Nikunj Sharma; Mustafa Akkoyunlu, Ronald L. Rabin
      Abstract: Macrophages are essential innate immune cells that also regulate local metabolism. Endogenous or exogenous stimuli may polarize macrophages towards phenotypes that serve distinct innate immunological metabolic functions. IFNγ or lipopolysaccharide (LPS) polarizes macrophages towards the M1, or “classically activated” phenotype that participates in defense against intracellular pathogens. IL-4, IL-13, or chitin polarizes macrophages towards the M2, or “alternatively activated” phenotype, which defends against multicellular nematodes and fungi. Since macrophages polarize in local environments, M1 and M2 macrophages may coexist in different organs and may differentially affect asthma and obesity, two comorbid diseases where polarized macrophages contribute to their pathogenesis. While M1 macrophages are considered beneficial in asthma and contribute to the pathology of obesity, M2 macrophages contribute to the pathology of asthma, but limit metabolic syndrome associated with obesity. Here we discuss the roles for M1 and M2 macrophages in asthma and obesity, and propose a model by which M1-mediated inflammation in adipose tissue enhances M2-mediated inflammation in the asthmatic lung.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-27T09:15:26.806524-05:
      DOI: 10.1111/all.13369
  • Characterization of epitope specificities of reference antibodies used for
           the quantification of the birch pollen allergen Bet v 1
    • Authors: Sébastien Brier; Maxime Le Mignon, Karine Jain, Constance Lebrun, François Peurois, Christine Kellenberger, Véronique Bordas-Le Floch, Laurent Mascarell, Emmanuel Nony, Philippe Moingeon
      Abstract: BackgroundAccurate allergen quantification is needed to document the consistency of allergen extracts used for immunotherapy. Herein, we characterize the epitope specificities of two monoclonal antibodies used in an ELISA for the quantification of the major birch pollen allergen Bet v 1, established as a reference by the BSP090 European project.MethodsThe ability of mAbs 5B4 and 6H4 to recognize Bet v 1 isoforms was addressed by immunochromatography. The capacity of each mAb to compete with patients’ IgE for binding to Bet v 1 was measured by ELISA inhibition. Epitope mapping was performed by pepscan analysis, site-directed mutagenesis and hydrogen/deuterium exchange-mass spectrometry.ResultsThe 5B4 epitope corresponds to a peptide sequence (I56-K68) overlapping with the binding sites of patients’ serum IgEs. Mutation of residues P59, E60 and K65 abolishes 5B4 binding to Bet v 1 and reduces the level of IgE recognition. In contrast, 6H4 recognizes a conformational epitope lying opposite to the 5B4 binding site, involving residues located in segments I44-K55 and R70-F79. Substitution of E45 reduces the binding capacity of 6H4, confirming that it is critical for the interaction. Both mAbs interact with>90% of Bet v 1 content present in the birch pollen extract, while displaying a weak cross-reactivity with other allergens of the PR-10 family.ConclusionsMAbs 5B4 and 6H4 recognize structurally distinct epitopes present in the vast majority of Bet v 1 isoforms. These results support the relevance as a reference method of the Bet v 1-specific quantitative ELISA adopted by the European Pharmacopoeia.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-24T11:25:32.03458-05:0
      DOI: 10.1111/all.13364
  • Perspectives in allergen immunotherapy: 2017 and beyond
    • Authors: O Pfaar; S Bonini, V Cardona, P Demoly, T Jakob, M Jutel, J Kleine-Tebbe, L Klimek, S Klysner, M V Kopp, P Kuna, M Larché, A Muraro, C B Schmidt-Weber, M Shamji, K Simonsen, C Somoza, E Valovirta, P Zieglmayer, T Zuberbier, U Wahn,
      Abstract: The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalised AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase III studies in the field, the future role of allergen exposure chambers in AIT-studies, and specific considerations in performing AIT-studies in the paediatric population.Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardisation of practice in the treatment of allergies. This supplement presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-24T06:45:51.335737-05:
      DOI: 10.1111/all.13355
  • Immunological differences between insect venom-allergic patients with and
           without immunotherapy and asymptomatically sensitized subjects
    • Authors: Lisa Arzt; Danijela Bokanovic, Christoph Schrautzer, Karin Laipold, Christian Möbs, Wolfgang Pfützner, Sereina Annik Herzog, Jutta Vollmann, Norbert Reider, Barbara Bohle, Werner Aberer, Gunter Sturm
      Abstract: BackgroundCurrently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy (VIT) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings.MethodsWe included 77 asymptomatically-sensitized subjects, 85 allergic-patients with acute systemic sting reactions, and 61 allergic-patients currently treated with VIT. Levels of sIgE and sIgG4 to bee and vespid venom, rApi-m-1 and rVes-v-5 were measured immediately after allergic sting-reactions or before sting-challenges and four weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT-inhibition and ELIFAB-assay.ResultsMedian sIgG4 levels were 96-fold higher in VIT patients (p
      PubDate: 2017-11-23T21:35:29.470279-05:
      DOI: 10.1111/all.13368
  • Oral tolerance modulates the skin transcriptome in mice with induced
           atopic dermatitis
    • Authors: Jin Ok Baek; Jong Rok Lee, Joo Young Roh, YunJae Jung
      Abstract: Defective gut immune reactions have been implicated in the development of atopic dermatitis (AD), whereas oral tolerance (OT), i.e., the immune unresponsiveness induced by oral antigen administration, protects mice against AD. To investigate this protective role of OT, the transcriptomic profiles of skin were obtained by RNA sequencing from mice that were epicutaneously sensitized, orally tolerized prior to epicutaneous sensitization, or neither (control). OT inhibited the upregulation of keratin- and allergic inflammation-associated genes that occurred in the epicutaneously sensitized group. Compared to the controls, mice that were orally tolerized and epicutaneously sensitized showed an upregulation of genes that regulate inflammation or keratinocyte differentiation. Knocking down two of those genes, SCGB1A1 and TSC22D3, upregulated Th2 inflammatory mediators and downregulated a cornified cell envelope-related gene. Based on our findings, OT may protect skin against allergic inflammation by promoting the expression of genes that regulate Th2 inflammatory responses and skin barrier function.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-23T11:23:11.53139-05:0
      DOI: 10.1111/all.13367
  • Specific Immunotherapy in LAR: a randomized, double-blind placebo
    • Authors: Carmen Rondón; Natalia Blanca-López, Paloma Campo, Cristobalina Mayorga, Raquel Jurado-Escobar, Maria J Torres, Gabriela Canto, Miguel Blanca
      Abstract: BackgroundAllergen immunotherapy has been shown to be an effective treatment for local allergic rhinitis (LAR) to house dust mites. Studies with pollen allergen immunotherapy are limited to observational studies. The aim of this study was to evaluate the clinical efficacy and safety of Phleum pratense subcutaneous immunotherapy (Phl-SCIT) in LAR.MethodsIn a randomized double-blind placebo-controlled study, 56 patients with moderate-severe LAR to grass pollen received Phl-SCIT with a depigmented-polymerized pollen vaccine or placebo for the first year, and Phl-SCIT the second one. The blind was maintained throughout the study. Primary outcome was combined symptoms-medication score (CSMS) during grass pollen season (GPS). Secondary clinical outcomes included organ-specific symptoms, medication free days, rhinitis severity, and asthma control. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal allergen provocation test (NAPT), skin testing, serum levels of specific-IgG4 and specific-IgE, and safety were also evaluated.ResultsSCIT had a short-term and sustained effect with significant improvements of all primary and secondary clinical outcomes and RQLQ score. SCIT significantly increased serum sIgG4 levels and allergen tolerance, from the 6th to 24th months of treatment. At the end of the study 83% of patients treated with ≥6 months of SCIT tolerated a concentration of Phl over 50 times higher than baseline, and 56% gave a negative NAPT. SCIT was well-tolerated; six mild local reactions occurred, and there were no serious adverse events related to the study medication.ConclusionsSubcutaneous immunotherapy with depigmented-polymerized allergen extracts is a safe and clinically effective treatment for LAR to Phleum pratense.clinicaltrials. gov identifier: NCT02126111.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-23T04:55:37.358243-05:
      DOI: 10.1111/all.13350
  • Identification of alpha-gal sensitivity in patients with a diagnosis of
           idiopathic anaphylaxis
    • Authors: Melody C. Carter; Karina N. Ruiz-Esteves, Lisa Workman, Philip Lieberman, Thomas A. E. Platts-Mills, Dean D. Metcalfe
      Abstract: IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs 3 to 6 hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha-gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T18:25:27.318176-05:
      DOI: 10.1111/all.13366
  • RCAT reflects symptom control and quality of life in allergic
           rhinoconjunctivitis patients
    • Authors: J.-P. Liedtke; A. Mandl, J. Köther, J. Chwieralski, K. Shah-Hosseini, U. Pieper-Fürst, S. Allekotte, R. Mösges
      Abstract: BackgroundThe Global Allergy and Asthma European Network (GA2LEN) Taskforce has requested more data on correlations between various Patient Reported Outcomes (PROs) in clinical trials on allergy. We compared three tools—the Rhinitis Control Assessment Test (RCAT), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Rhinitis Total Symptom Score (RTSS)—to determine whether the RCAT alone is a sufficient primary outcome parameter in clinical trials on allergic rhinoconjunctivitis.MethodsIn two double-blind, placebo-controlled immunotherapy studies, 33 patients allergic to grass pollen and 94 to birch pollen completed two questionnaires (RCAT and RQLQ) and kept their own symptom diary from which the RTSS was calculated.ResultsUpon comparing RCAT and RQLQ results, we found strong correlations of r = –0.871 for grass pollen–allergic patients and r = –0.795 for birch pollen–allergic patients. The comparison between RCAT and RTSS results showed a strong correlation of r = –0.811 (grass pollen–allergic patients) and a moderate correlation of r = –0.539 (birch pollen–allergic patients). In the RCAT, 69.7% of grass pollen–allergic patients and 45.7% of birch pollen–allergic patients receiving guideline-concordant therapy were regarded as having insufficiently controlled symptoms.ConclusionThe strong correlation suggests that the RCAT alone is equivalent to the RQLQ with respect to patients’ symptom control and quality of life. Patients with uncontrolled symptoms can be identified using the RCAT. Hence, the physician can decide whether symptomatic therapy can be intensified or allergy immunotherapy should be administered.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T02:21:15.786256-05:
      DOI: 10.1111/all.13362
  • Maternal hypothyroidism in the perinatal period and childhood asthma in
           the offspring
    • Authors: Xiaoqin Liu; Stine Linding Andersen, Jørn Olsen, Esben Agerbo, Vivi Schlünssen, Shyamali Chandrika Dharmage, Trine Munk-Olsen
      Abstract: BackgroundThere is increasing interest in the possible link between maternal hypothyroidism in the perinatal period and childhood asthma risk. We explored this in the present study while accounting for the timing of hypothyroidism diagnosis. Further, we evaluated whether the risk was moderated by thyroid hormone treatment during pregnancy.MethodsWe conducted a population-based cohort study using Danish national registers. All liveborn singletons in Denmark from 1998 to 2007 were identified. Maternal hypothyroidism and asthma in the children were defined by data from the Patient Register and Prescription Registry. We estimated incidence rate ratios (IRRs) of asthma among children born to hypothyroid mothers versus children born to mothers with no recorded thyroid dysfunction using Poisson regression models.ResultsOf 595,669 children, 3,524 children were born to mothers with hypothyroidism diagnosed before delivery and 4,664 diagnosed after delivery. Overall 48,990 children received treatment for asthma. The IRRs of asthma was 1.16 (95% confidence interval (CI): 1.03–1.30) and 1.12 (95% CI: 1.02–1.24) for children born to mothers with hypothyroidism diagnosed before and after delivery, compared to children born to mothers with no thyroid dysfunction. The highest risk was observed among children born to mothers with hypothyroidism diagnosed before delivery who did not receive thyroid hormone treatment during pregnancy (IRR=1.37, 95% CI: 1.04–1.80).ConclusionOur findings suggest that maternal hypothyroidism, especially when it is untreated, increases childhood asthma risk. Early detection and appropriate treatment of hypothyroidism in pregnant women may be an area for possible prevention of childhood asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T02:21:14.474062-05:
      DOI: 10.1111/all.13365
  • Blocking antibodies induced by allergen-specific immunotherapy ameliorate
           allergic airway disease in a human/mouse chimeric model
    • Authors: Caterina Vizzardelli; Miriam Gindl, Simone Roos, Christian Möbs, Birgit Nagl, Felix Zimmann, Veronika Sexl, Lukas Kenner, Alina Neunkirchner, Gerhard J. Zlabinger, Winfried F. Pickl, Wolfgang Pfützner, Barbara Bohle
      Abstract: BackgroundAllergen-specific immunotherapy (AIT) induces specific blocking antibodies (Ab) which are claimed to prevent IgE-mediated reactions to allergens. Additionally, AIT modulates cellular responses to allergens, e.g. by desensitizing effector cells, inducing regulatory T and B lymphocytes and immune deviation. It is still enigmatic which of these mechanisms mediate(s) clinical tolerance. We sought to address the role of AIT-induced blocking Ab separately from cellular responses in a chimeric human/mouse model of respiratory allergy.MethodsNon-obese diabetic severe combined immunodeficient γc-/- (NSG) mice received intraperitoneally allergen-reactive PBMC from birch pollen-allergic patients together with birch pollen extract and human IL-4. Engraftment was assessed by flow cytometry. Airway hyperresponsiveness (AHR) and bronchial inflammation were analyzed after intranasal challenges with allergen or PBS. Sera collected from patients before and during AIT with birch pollen were added to the allergen prior to intranasal challenge. The IgE-blocking activity of post-AIT sera was assessed in vitro.ResultsHuman cells were detected in cell suspensions of murine lungs and spleens indicating successful humanization. Humanized mice displayed a more pronounced AHR and bronchial inflammation when challenged with allergen compared to negative controls. Post-AIT sera excerted IgE-blocking activity. In contrast to pre-AIT sera, the presence of heterologous and autologous post-AIT sera significantly reduced the allergic airway inflammation and matched their IgE-blocking activity determined in vitro.ConclusionOur data demonstrate that post-AIT sera with IgE-blocking activity ameliorate allergic airway inflammation in a human/mouse chimeric model of respiratory allergy independently of AIT-induced cellular changes.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T02:15:25.837069-05:
      DOI: 10.1111/all.13363
  • Circadian profiling reveals higher histamine plasma levels and lower
           diamine oxidase serum activities in 24% of patients with suspected
           histamine intolerance compared to food allergy and controls
    • Authors: Theresa C. Pinzer; Esther Tietz, Elisabeth Waldmann, Monic Schink, Markus F. Neurath, Yurdagül Zopf
      Abstract: BackgroundHistamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls.MethodsWe determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory-chemical parameters were evaluated.Results24% (8 of 33) suspected histamine intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food allergy and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance.ConclusionsWe determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms, and strongly suggests the presence of histamine intolerance.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-20T05:21:06.853621-05:
      DOI: 10.1111/all.13361
  • Poor agreement in questionnaire-based diagnostic criteria for adult atopic
           dermatitis is a challenge when examining cardiovascular comorbidity
    • Authors: Yuki M.F. Andersen; Alexander Egeberg, Carsten R. Hamann, Lone Skov, Gunnar H. Gislason, Tea Skaaby, Allan Linneberg, Jacob P. Thyssen
      Abstract: BackgroundThe association between atopic dermatitis (AD) and cardio-metabolic risk factors is not yet established. Furthermore, no validated questionnaire-based method of identifying adults with AD is currently available.ObjectivesTo assess the cardio-metabolic risk in adults with a history of AD by using three different questionnaire-based diagnostic criteria.MethodsWe utilized data from a general population study including questionnaire data and objective measurements of 9,656 Danish adults. To identify adults with a history of AD, we used a question regarding physician-diagnosed AD, and two versions of the UK Working Party Diagnostic Criteria. Associations between AD status and cardio-metabolic endpoints were estimated using survey weighted logistic and linear regression analysis.ResultsWe identified 462 (4.8%) adults with self-reported physician-diagnosed AD, whereas 903 (9.4%) and 226 (2.3%) had AD according to the UK Working Party Criteria when at least two and three of four minor criteria were fulfilled. The populations were not comparable in terms of occurrence of cardio-metabolic risk factors. For example, the prevalence of obesity was lower in participants with physician-diagnosed AD but overall higher in UK 2/4 and UK 3/4.ConclusionDue to the heterogeneity in the captured study populations in terms of the studied outcomes and absence of a gold standard, no conclusions regarding the cardio-metabolic risk in adults with AD in a general population could be made. This study serves as an example of the challenges that are often encountered in questionnaire-based epidemiologic studies and highlights the need of better definitions for this patient group.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-18T02:55:20.845939-05:
      DOI: 10.1111/all.13360
  • Rhinitis and its Impact on Quality of Life in Swimmers
    • Authors: Pavol Surda; Matus Putala, Pavel Siarnik, Abigail Walker, Ana Bernic, Wytske Fokkens
      Abstract: IntroductionLimited data suggest that swimmers might be affected by rhinitis significantly more often than the general population. This can have impact on quality of life but also on performance. The aim of the present study was to determine the prevalence and impact of QOL of rhinitis in swimming compared to non-swimming athletes and controls.Materials and methodsThis was an observational case control, questionnaire based study involving elite (n=101) and non-elite swimming athletes (n=107), non-swimming athletes (n = 38) and sex and age-matched controls (n = 50). The survey instrument consisted of a general and the miniRQLQ questionnaire. Main question used to assess the prevalence of rhinitis was from the ISAAC study.ResultsRhinitis was reported significantly more often by the elite swimmers (45%) than non-elite swimmers (31%), non-swimming athletes (32%) and controls (24%). Allergic rhinitis prevalence was similar in all groups (12-18%). The prevalence of non-allergic rhinitis was significantly higher in elite swimmers (33%) and non-elite swimmers (22%) compared to non-swimming athlethes and controls. Overall mean miniRQLQ score and all subdomains except the “eye” domain showed significantly reduced QOL in elite and non-elite swimmers compared to non-swimming athletes and controls. Regular nasal medication was used significantly less by elite swimmers (18%) compared to controls (67%) and non-swimming athletes (42%).ConclusionThis study revealed a high prevalence of non-allergic rhinitis in swimmers and related impact on QoL. These findings highlight the importance to increase the awareness toward upper airway disorders in the swimming athletes and to ensure adequate management.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-18T02:25:22.698399-05:
      DOI: 10.1111/all.13359
  • A randomized, double-blind, placebo-controlled, dose-finding trial with
           Lolium perenne peptide immunotherapy
    • Authors: Ralph Mösges; Elena M. Kasche, Esther Raskopf, Jaswinder Singh, Lea Sohlich, Anatoli Astvatsatourov, Kija Shah-Hosseini, Sabine Pirotton, Ludo Haazen, Stephen R. Durham, Thierry Legon, Gregor Zadoyan, Mohamed H. Shamji
      Abstract: BackgroundA novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen–induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity, and safety.MethodsThis prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen–allergic adults to receive placebo or cumulative doses of 70, 170, or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3, and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks, and after completion. Grass pollen–specific immunoglobulins were analysed before and after treatment.ResultsCPT response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP versus 25.6% of patients receiving placebo (modified per protocol set). Also, 39% of patients in the 170 μg-group became non-reactive to CPT versus 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG4 levels increased to 1.6-fold (70 μg), 3.1-fold (170 μg), and 3.9-fold (370 μg) (mPP).ConclusionThree-week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-18T02:20:40.504582-05:
      DOI: 10.1111/all.13358
  • Allergen manufacturing and quality aspects for allergen immunotherapy in
           Europe and the United States: An analysis from the EAACI AIT Guidelines
    • Authors: A. Bonertz; G. Roberts, J.E. Slater, J. Bridgewater, R.L. Rabin, M. Hoefnagel, M. Timon, C. Pini, O. Pfaar, A. Sheikh, D. Ryan, C. Akdis, J. Goldstein, L. K. Poulsen, R. van Ree, C. Rhyner, D. Barber, O. Palomares, 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. M. Varga, R. Gerth van Wijk, S. Bonini, A. Muraro, S. Vieths
      Abstract: Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. Since the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-17T23:45:27.080359-05:
      DOI: 10.1111/all.13357
  • Gluten sensitivities and the allergist: Threshing the grain from the husks
    • Authors: J. G. Burkhardt; A. Chapa-Rodriguez, S. L. Bahna
      Abstract: “Gluten sensitivity” has become commonplace among the public. Wheat allergy (WA) and celiac disease (CD) are well-defined entities, but are becoming a fraction of individuals following a gluten-free diet. WA has a prevalence of
      PubDate: 2017-11-13T07:55:21.885854-05:
      DOI: 10.1111/all.13354
  • Quality of life is significantly impaired in non-allergic rhinitis
    • Authors: Christine L Segboer; Ingrid Terreehorst, Artur Gevorgyan, Peter W. Hellings, Cornelis M van Drunen, Wytske J Fokkens
      Abstract: BackgroundIn contrast to the well-known significant impairment of quality of life (QoL) in allergic rhinitis (AR), the degree of impairment in QoL in non-allergic rhinitis (NAR) remained unknown for a long time, due to a lack of a validated questionnaire to assess QoL in the NAR patient group.In this study a validation for the mini-RQLQ questionnaire in NAR patients was performed, followed by an assessment of QoL in NAR patients compared to AR and healthy controls.Secondly, use of medication and treatment satisfaction in AR and NAR was assessed.MethodsThe study was an observational cohort study in 287 AR and 160 NAR patients.Patients with symptoms of rhinitis were recruited from a tertiary care outpatient clinic of the Otorhinolaryngology Department. AR was defined as one or more positive results on skin prick testing and clinically relevant symptoms of rhinitis related to their sensitization. NAR was defined as clinically relevant symptoms of rhinitis but without positive results on skin prick testing.The mini-RQLQ was successfully validated in this study for NAR patients.ResultsQoL in NAR patients was equally -and for some aspects even more- impaired compared to AR. More than half of both AR and NAR patients were unsatisfied with treatment.ConclusionThese results demonstrate a significant impairment in both AR and NAR patients in their QoL combined with a low treatment satisfaction, emphasizing the need for adequate treatment, especially in the NAR patient group.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-13T07:45:49.192144-05:
      DOI: 10.1111/all.13356
  • CRP is linked to disease activity, impact and response to treatment in
           patients with chronic spontaneous urticaria
    • Authors: Pavel Kolkhir; Sabine Altrichter, Tomasz Hawro, Marcus Maurer
      Abstract: BackgroundElevated levels of C-reactive protein (CRP), a sensitive marker of inflammation, have been consistently reported in chronic spontaneous urticaria. Here, we retrospectively analyzed data from 1,253 CSU patients from two centers to answer the following questions: 1) What is the prevalence of elevated levels of CRP in CSU' 2) Why do CSU patients show elevated levels of CRP' 3) Are elevated CRP levels relevant'MethodsSerum levels of CRP were measured by the nephelometric method. We collected information regarding various laboratory tests including ESR, CBC with differential, D-dimer, fibrinogen, C3, C4, IL-6 etc. For most patients, we also collected data on age, gender, duration of CSU, presence of angioedema, activity (UAS at the time of blood sampling and for 7 days), quality of life (CU-Q2oL and/or DLQI), comorbidities and possible causes of CSU, and autologous serum skin test (ASST) response. The efficacy of second generation antihistamines was evaluated at the day of blood collecting.ResultsOne third of CSU patients had elevated levels of CRP. Higher levels of CRP were associated with ASST positivity (p=0.009) and arterial hypertension (p=0.005), but not with other possible causes or comorbidities of CSU. CRP correlated with urticaria activity (p
      PubDate: 2017-11-12T07:15:22.955994-05:
      DOI: 10.1111/all.13352
  • NUT Co Reactivity - Acquiring Knowledge for Elimination Recommendations
           (NUT CRACKER) Study
    • Authors: Arnon Elizur; Michael Y Appel, Liat Nachshon, Michael B Levy, Naama Epstein-Rigby, Keren Golobov, Michael Goldberg
      Abstract: BackgroundAmbiguities exist regarding the diagnosis of tree-nut allergy, necessitating either elimination or performance of oral food challenges (OFC).ObjectiveTo examine the co-incidences of allergies among tree-nuts and improve diagnostic testing to minimize the need for OFC.MethodsEighty three patients prospectively evaluated for walnut, pecan, cashew, pistachio, hazelnut and almond allergy. A history of previous reactions was obtained and standardized skin prick tests (SPT) using finely ground tree-nut solution and basophil activation tests (BAT) were performed. Patients underwent OFC for each tree-nut they eliminated and to which a reaction in the previous 2 years was not documented.ResultsWhile most patients were sensitized to 5-6 tree-nuts, over 50% were allergic to only 1-2 tree-nuts. The highest rate of allergy in sensitized patients was observed for walnut (74.6%) and cashew (65.6%). The rate of co-allergy for most tree-nuts was < 30%. Two thirds of walnut- and cashew-allergic patients were also allergic to pecan and pistachio, respectively, while all pecan- and pistachio-allergic patients were allergic to walnut and cashew, respectively. Receiver operating characteristic analysis for SPT and BAT was tree-nut dependent and yielded area under the curve (AUC) values ranging from 0.75-0.94. Knowledge of co-incident allergies in these pairs along with the combination of SPT and BAT correctly distinguished allergic from tolerant patients for walnut (87%), pecan (66%), cashew (71%) and pistachio (79%).ConclusionThe data presented here should assist in differentiating between allergic and tolerant patients, decrease the need for OFC and allow for appropriate elimination recommendations.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-11T07:30:34.079464-05:
      DOI: 10.1111/all.13353
  • MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with
           house dust mite allergic rhinitis
    • Authors: Inge Kortekaas Krohn; Ina Callebaut, Yeranddy A. Alpizar, Brecht Steelant, Laura Van Gerven, Per Stahl Skov, Ahmad Kasran, Karel Talavera, Mira M Wouters, Jan L Ceuppens, Sven F Seys, Peter W Hellings
      Abstract: BackgroundNasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate (FP)) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function.MethodsA 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR. The presence of NHR was evaluated by measuring reduction of nasal flow upon cold dry air exposure. The effects of AZE+/-FP on barrier integrity and airway inflammation were studied in a murine model of HDM induced NHR and on reduced activation of murine sensory neurons and human mast cells.ResultsMP29-02 but not placebo reduced NHR (p
      PubDate: 2017-11-09T14:30:19.898164-05:
      DOI: 10.1111/all.13349
  • Strong and frequent T-cell responses to the minor allergen Phl p 12 in
           Spanish patients IgE-sensitized to Profilins
    • Authors: Gitte Lund; Stephanie Brand, Tania Ramos, Lucia Jimeno, Patrice Boissy, Francisco Vega, Maria Arina, Lars Harder Christensen, Ilka Hoof, Kåre Hvalsøe Meno, Domingo Barber, Carlos Blanco, Peter Adler Würtzen, Peter Sejer Andersen
      Abstract: BackgroundProfilins are dominant pan-allergens known to cause cross-sensitization, leading to clinical symptoms such as the pollen food syndrome. This study aims to determine the T-cell response to Phl p 12 in profilin-sensitized patients, by measuring the prevalence, strength and cross-reactivity to clinically relevant profilins.MethodsThe release of Phl p allergens from pollen was determined by mass spectrometry and immunochemistry. T-cell responses, epitope mapping and cross-reactivity to profilins (Phl p 12, Ole e 2, Bet v 2, and Mal d 4) were measured in-vitro using PBMCs from 26 Spanish grass allergic donors IgE-sensitized to profilin. Cross-reactivity was addressed in-vivo using two different mouse strains (BALB/c and C3H).ResultsPhl p 12 and Phl p 1 are released from pollen simultaneously and in similar amounts. Both T cell response frequency (17/26 donors) and strength were comparable between Phl p 12 and Phl p 1. T-cell cross-reactivity to other profilins correlated with overall sequence homology, and two immunodominant epitope regions of Phl p 12 were identified. Data from mice immunized with Phl p 12 showed that cross-reactivity to Bet v 2 was mediated by conserved epitopes, and further influenced by additional genetic factors, likely to be MHC II.ConclusionThe strength, prevalence and cross reactivity of T-cell responses towards Phl p 12 is comparable to the major allergen Phl p 1, which supports the hypothesis that T-cells to Phl p 12 can play an important role in development of allergic symptoms, such as those associated with the pollen-food syndrome.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-09T14:25:44.780103-05:
      DOI: 10.1111/all.13351
  • The Utility Of Monitoring Trimellitic Anhydride (TMA)-Specific IgG To
           Predict IgE-mediated Sensitization in An Immunosurveillance Program
    • Authors: Debajyoti Ghosh; Cory Clay, Jonathan A. Bernstein
      Abstract: BackgroundWorkplace exposure to Trimellitic Anhydride (TMA) can elicit TMA-specific IgE (sIgE), which may lead to occupational asthma (OA). An occupational immunosurveillance program (OISP) has been implemented to monitor TMA exposure and immunologic outcomes. The purpose of this study was to determine whether TMA-specific IgG (sIgG) responses can discriminate between TMA-exposed workers with and without sIgE responses.MethodsSerum TMA-specific antibody (IgG, IgG4 and IgE) levels were estimated longitudinally (years 2006 to 2014) in TMA-exposed workers recruited in low, medium and high exposure areas. sIgG and sIgE titers plotted against exposure duration were compared between workers with (a) sIgG only and (b) with sIgG who developed sIgE.ResultsAmong 92 TMA-exposed workers continuously monitored for sIgG and sIgE, 38 developed sIgG; 11 developed a sIgE response 342.38 ± 186.03 days post-hire and were removed from exposure. The average detection time of sIgG in removed workers (159±92 days) was significantly shorter than for actively exposed workers with only sIgG (346±187 days). Workers with earlier sIgG responses of higher titer (mean value 42.25 ug/ml) compared to delayed responders with lower sIgG titers (mean value 14.79 ug/ml) more frequently developed sIgE responses. Hierarchical clustering showed the initial magnitude and exposure time required for detectable sIgG production discriminated between workers with only sIgG from workers who subsequently produced sIgE.ConclusionsThis study demonstrates the utility of longitudinally monitoring TMA-specific antibodies in an OISP as exposed workers with early sIgG responses and of higher magnitude are more likely to develop TMA sIgE sensitization.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-08T12:10:54.010701-05:
      DOI: 10.1111/all.13348
  • What can we learn in drug allergy management from World Health
           Organization's International Classifications'
    • Authors: Luciana Kase Tanno; Maria Jose Torres, Mariana Castells, Pascal Demoly,
      Abstract: Drug hypersensitivity reactions (DHRs) represent growing health problem worldwide, affecting more than 7% of the general population and represent an important public health problem. However, knowledge in DHRs morbidity and mortality epidemiological data is still not optimal and international comparable standards remain poorly accessed. Institutional databases worldwide increasingly use the WHO International Classification of Diseases (ICD) system to classify diagnoses, health services utilization and death data. The misclassification of disorders in the ICD system contributes to a lack of ascertainment and recognition of their importance for healthcare planning and resource allocation. It also hampers clinical practice and prevention actions.To further inform the allergy community and to ensure that the revision process is transparent as advised in the WHO ICD-11 revision agenda, we report the advances and use of the pioneering “Drug hypersensitivity” subsection of ICD-11 and implementation in the WHO International Classification of Health Interventions (ICHI). The new classification addressed to DHRs will enable the collection of more accurate epidemiological data to support quality management of patients with drug allergies, and better facilitate health care planning and decision-making and public health measures to prevent and reduce the morbidity and mortality attributable to DHRs.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-06T07:15:36.791854-05:
      DOI: 10.1111/all.13335
  • Economic evidence for non-pharmacological asthma management interventions:
           A systematic review
    • Authors: Christina-Jane Crossman-Barnes; Adam Peel, Rebekah Fong-Soe-Khioe, Tracey Sach, Andrew Wilson, Garry Barton
      Abstract: Asthma management, education and environmental interventions have been reported as cost effective in a previous review, (Yong and Shafie et al, 2014), but methods used to estimate costs and outcomes were not discussed in detail. This review updates the previous review by providing economic evidence on the cost effectiveness of studies identified after 2012, and a detailed assessment of the methods used in all identified studies. Twelve databases were searched from 1990 to January 2016, and studies included economic evaluations, asthma subjects, and non-pharmacological interventions written in English. Sixty-four studies were included. Of these, fifteen were found in addition to the earlier review; 53% were rated fair in quality and 47% high. Education and self-management interventions were the most cost effective, in line with the earlier review. Self-reporting was the most common method used to gather resource use data, accompanied with bottom-up approaches to estimate costs. Main outcome measures were asthma-related hospitalizations (69%), quality of life (41%) and utility (38%), with AQLQ and the EQ-5D being the most common questionnaires measured prospectively at fixed time points. More rigorous costing methods are needed with a more common quality of life tool to aid greater replicability and comparability amongst asthma studies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-06T07:02:00.900801-05:
      DOI: 10.1111/all.13337
  • Influenza burden, prevention and treatment in asthma – a scoping review
           by the EAACI Influenza in Asthma Task Force
    • Authors: Jürgen Schwarze; Peter Openshaw, Akhilesh Jha, Stefano R del Giacco, Davide Firinu, Olympia Tsilochristou, Graham Roberts, Anna Selby, Cezmi Akdis, Ioana Agache, Adnan Custovic, Enrico Heffler, Georgia Pinna, Musa Khaitov, Alexandra Nikonova, Nikolaos Papadopoulos, Ather Akhlaq, Ulugbek Nurmatov, Harald Renz, Aziz Sheikh, Chrysanthi Skevaki
      Abstract: To address uncertainties in the prevention and management of influenza in people with asthma, we performed a scoping review of the published literature on influenza burden; current vaccine recommendations; vaccination coverage; immunogenicity, efficacy, effectiveness and safety of influenza vaccines; and the benefits of antiviral drugs in people with asthma. We found significant variation in the reported rates of influenza detection in individuals with acute asthma exacerbations making it unclear to what degree influenza causes exacerbations of underlying asthma. The strongest evidence of an association was seen in studies of children. Countries in the European Union currently recommend influenza vaccination of adults with asthma; however, coverage varied between regions. Coverage was lower among children with asthma. Limited data suggest that good seroprotection and seroconversion can be achieved in both children and adults with asthma and that vaccination confers a degree of protection against influenza illness and asthma related morbidity to children with asthma. There were insufficient data to determine efficacy in adults. Overall, influenza vaccines appeared to be safe for people with asthma. We identify knowledge gaps and make recommendations on future research needs in relation to influenza in patients with asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-06T06:35:25.955948-05:
      DOI: 10.1111/all.13333
  • Clinical implications of mast cell involvement in allergic conjunctivitis
    • Authors: Daniel Elieh Ali Komi; Todd Rambasek, Leonard Bielory
      Abstract: The conjunctiva is a common site for the allergic inflammatory response due to it being highly vascularized, having constant exposure to environmental pollutants and allergenic pollens and having a unique conjunctival associated lymphoid tissue. The primary morbidity of anterior surface conjunctival disorders that include allergic conjunctivitis and tear film disorders is associated with its high frequency of involvement rather than its severity, although the more chronic forms can involve the cornea and lead to sight threatening conditions. Ocular allergy is associated with IgE-mediated mast cell activation in conjunctival tissue leading to the release of preformed mediators including histamine and proteases and subsequent de novo formation of lipid-derived mediators and cytokines that trigger a cascade of cellular and molecular events leading to extensive migration and infiltration of inflammatory cells to the ocular surface. The trafficking of neutrophils, eosinophils, and lymphocytes to the ocular surface is due to establishing various chemokine gradients (mainly CCL11, CCL24, CCL5, MCP-3, and MCP-4), cell surface expression of adhesion molecules (such as VCAM-1 the ligand for VLA-4), and leukocyte adhesion to vascular endothelium. The release of preformed mediators underlies the acute ocular surface response while the secondary influx of inflammatory cells leading to the recruitment and activation of eosinophils and the subsequent activation of Th2 and Th1 lymphocytes at the level of the conjunctiva reflects the late-phase reaction.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-06T06:30:26.318182-05:
      DOI: 10.1111/all.13334
  • Early life antibiotic exposure increases the risk of developing allergic
           symptoms later in life: A meta-analysis
    • Authors: Fariba Ahmadizar; Susanne J. H. Vijverberg, Hubertus G. M. Arets, Anthonius de Boer, Jason E. Lang, Johan Garssen, Aletta Kraneveld, Anke H Maitland-van der Zee
      Abstract: This study systematically reviewed and quantified the relationship between exposure to antibiotics during the first 2 years of life and the risk of allergies/atopies including hay fever, eczema, food allergy, positive skin prick testing (SPT) or elevated allergen-specific serum/plasma immunoglobulin (Ig) E levels later in life. PubMed and Web of Science databases were searched for observational studies published from January 1966 through November 11, 2015. Overall pooled estimates of the odds ratios (ORs) were obtained using fixed or random-effects models.Early life exposure to antibiotics appears to be related with an increased risk of allergic symptoms of hay fever, eczema and food allergy later in life. The summary OR for the risk of hay fever (22 studies) was 1.23, 95% confidence interval (CI):1.13-1.34; I2: 77.0%. The summary OR for the risk of eczema (22 studies) was 1.26, 95% CI: 1.15-1.37; I2: 74.2% and the summary OR for food allergy (3 studies) was 1.42, 95% CI: 1.08-1.87; I2: 80.8%. However, no association was found for antibiotics exposure early in life and objective atopy measurements including positive SPT or elevated allergen-specific serum/plasma IgE levels.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-06T06:25:21.446522-05:
      DOI: 10.1111/all.13332
  • Risk factors for asthma after infant bronchiolitis
    • Authors: S. Törmänen; E. Lauhkonen, R. Riikonen, Petri Koponen, H. Huhtala, M. Helminen, M. Korppi, K. Nuolivirta
      Abstract: BackgroundFive studies carried out after bronchiolitis at less than 24 months of age, with a follow up of more than 10 years, reported that atopic dermatitis, family asthma, early-life exposure to tobacco smoke and rhinovirus aetiology were early-life risk factors for later asthma. This study evaluated the long-term outcome at 11-13 years of age of children who were hospitalised for bronchiolitis in early infancy.MethodsWe previously prospectively followed 166 children hospitalised for bronchiolitis at less than six months of age until 5-7 years of age. The current study included a structured questionnaire, parental interviews, clinical examinations and bronchodilation test of 138 of those children at 11-13 years of age.ResultsRespiratory syncytial virus caused 66% of the bronchiolitis cases and nearly half of the patients were exposed to tobacco smoke in early life. Doctor-diagnosed asthma was present in 13% of the former bronchiolitis patients at 11-13 years of age. Maternal asthma was the only independently significant risk factor in early life (adjusted OR 3.45, 95% CI 1.07-11.74), as was allergic rhinitis at 5-7 years of age (adjusted OR 4.06, 95% CI 1.35-12.25).ConclusionsAfter bronchiolitis at less than six months of age, the risk of doctor-diagnosed asthma at 11-13 years was about twice that of the general Finnish population. Maternal asthma was the only independently significant early-life risk factor for current asthma at 11-13 years of age.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-04T02:30:28.413208-05:
      DOI: 10.1111/all.13347
  • The clinical response to omalizumab in CSU patients is linked to and
           predicted by IgE levels and their change
    • Authors: Ragip Ertas; Kemal Ozyurt, Mustafa Atasoy, Tomasz Hawro, Marcus Maurer
      Abstract: BackgroundOmalizumab is an effective and well-tolerated treatment for chronic spontaneous urticaria (CSU). Markers and predictors of response are largely unknown, but needed to optimize omalizumab treatment. Omalizumab targets IgE, and IgE levels may be linked to the effects of treatment. We evaluated if response rates to treatment with omalizumab in patients with CSU are linked to their baseline IgE levels, their IgE levels after omalizumab treatment, and the ratio of on treatment IgE and baseline IgE levels.MethodsCSU patients (n=113) were treated with omalizumab 300 mg/4 weeks for 12 weeks, when their treatment responses, i.e. no, partial, or complete response, were assessed by use of the urticaria activity score, physician and patient visual analog scale, and treatment effectiveness score. Total IgE levels were measured before treatment (bIgE) with omalizumab and 4 weeks thereafter (w4IgE).ResultsNon-responders to omalizumab had significantly lower bIgE levels (17.9IU/ml, 17.0-55.0IU/ml) than partial responders (82.0IU/ml, 46.2-126.5IU/ml, p=0.008) and complete responders (73.7IU/ml, 19.45-153.8IU/ml, p=0.032). Non-responders also had lower w4IgE levels and lower ratios of w4IgE/bIgE levels than partial and complete responders (p
      PubDate: 2017-10-30T10:00:32.651066-05:
      DOI: 10.1111/all.13345
  • Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22,
           within the skin-homing and systemic T-cell populations
    • Authors: Tali Czarnowicki; Helen Y He, Huei-Chi Wen, Peter W Hashim, John K Nia, Kunal Malik, Yeriel Estrada, Grace W Kimmel, Mark Taliercio, James G Krueger, Emma Guttman-Yassky
      Abstract: BackgroundCharacterizing blood profile of alopecia areata (AA) is not only important for treatment advancements, but also for possibly identifying peripheral biomarkers that will eliminate the need for scalp biopsies. We aimed to compare frequencies of skin homing (CLA+) vs. systemic (CLA-) “polar” CD4+ and CD8+ and activated T-cell subsets in AA vs. AD and control blood.MethodsFlow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+ and CD8+ T-cells. ICOS and HLA-DR were used to define mid and long term T-cell activation. We compared peripheral blood from 32 moderate-to-severe AA adults with 43 moderate-to-severe AD patients and 30 age-matched controls.ResultsAA patients had increased CLA+/CLA- Th2 (P
      PubDate: 2017-10-30T09:40:36.138633-05:
      DOI: 10.1111/all.13346
  • Pigeon tick bite: a neglected cause of idiopathic nocturnal anaphylaxis
    • Authors: Giovanni Rolla; Enrico Heffler, Monica Boita, Virginie Doyen, Michel Mairesse, Milada Cvackova, Sébastien Debarbieux, Jörg Kleine-Tebbe, Markus Ollert, Monika Raulf, Andreas J. Bircher, Christiane Hilger
      Abstract: Anaphylaxis is a serious systemic allergic reaction with rapid onset and potentially life-threatening. We report in detail a case of severe nocturnal anaphylaxis due to pigeon tick bite showing the diagnostic value of the extract and the recombinant allergen in the diagnostic procedures (basophil activation test, IgE-immunoblot and experimental ImmunoCAP). Apart from the presented case we describe that, during the last 10 years, we have collected 28 cases of allergy to Argas reflexus from several European countries. We suspect that this allergy is underdiagnosed because of the lack of diagnostic reagents. Because of the growing number of pigeons in Middle and Southern Europe cities, some cases of idiopathic anaphylaxis could potentially be caused by Argas reflexus in those countries. The identification of pigeon ticks as a trigger of anaphylaxis would greatly improve medical care and advice for these patients as the parasite can be exterminated by eradication measures in order to avoid further incidents.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-30T09:30:20.611457-05:
      DOI: 10.1111/all.13344
  • Intranasal administration of allergen increases specific IgE whereas
           intranasal Omalizumab does not increase serum IgE levels – a pilot study
    • Authors: Julia Eckl-Dorna; Renate Fröschl, Christian Lupinek, Renata Kiss, Pia Gattinger, Katharina Marth, Raffaela Campana, Katharina Blatt, Peter Valent, Regina Selb, Andrea Mayer, Katharina Gangl, Irene Steiner, Jutta Gamper, Thomas Perkmann, Petra Zieglmayer, Philippe Gevaert, Rudolf Valenta, Verena Niederberger
      Abstract: BackgroundAdministration of the therapeutic anti-IgE antibody omalizumab to patients induces strong increases of IgE antibody levels.ObjectiveTo investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen-specific IgE in patients with birch pollen allergy.MethodsBased on the fact that intranasal allergen application induces rises of systemic allergen-specific IgE we performed a double-blind placebo-controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen-specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen-specific IgE levels and omalizumab-IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL-4/anti-CD40-treated PBMCs from allergic patients were studied in vitro.ResultsIntranasal challenge with Bet v 1 induced increases of Bet v 1-specific IgE levels by a median of 59.2% and this change differed significantly from the other treatment groups (p=0.016). No relevant change of allergen-specific and total IgE levels were observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL-4/anti-CD40-induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE-omalizumab complexes were observed after subcutaneous administration of omalizumab.ConclusionIntranasal administration of allergen induced rises of allergen-specific IgE levels whereas intranasal administration of omalizumab did not enhance systemic total or allergen-specific IgE levels.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-30T09:15:36.644082-05:
      DOI: 10.1111/all.13343
  • EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis
    • Authors: G. Roberts; O. Pfaar, C. A. Akdis, I. J. Ansotegui, S. R. Durham, R. Wijk, S. Halken, D. Larenas-Linnemann, R. Pawankar, C. Pitsios, A. Sheikh, M. Worm, S. Arasi, M. A. Calderon, C. Cingi, S. Dhami, J. L. Fauquert, E. Hamelmann, P. Hellings, L. Jacobsen, E. F. Knol, S. Y. Lin, P. Maggina, R. Mösges, J. N. G. Oude Elberink, G. B. Pajno, E. A. Pastorello, M. Penagos, G. Rotiroti, C. B. Schmidt-Weber, F. Timmermans, O. Tsilochristou, E.-M. Varga, J. N. Wilkinson, A. Williams, L. Zhang, I. Agache, E. Angier, M. Fernandez-Rivas, M. Jutel, S. Lau, R. van Ree, D. Ryan, G. J. Sturm, A. Muraro
      Abstract: Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project “EAACI Guidelines on Allergen Immunotherapy.” It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.
      PubDate: 2017-10-30T01:20:40.122272-05:
      DOI: 10.1111/all.13317
  • RItA: The Italian severe/uncontrolled asthma registry
    • Authors: Sara Maio; Sandra Baldacci, Megon Bresciani, Marzia Simoni, Manuela Latorre, Nicola Murgia, Fabrizio Spinozzi, Mariachiara Braschi, Leonardo Antonicelli, Barbara Brunetto, Patrizia Iacovacci, Paolo Roazzi, Carlo Pini, Mario Pata, Lidia La Grasta, Pierluigi Paggiaro, Giovanni Viegi,
      Abstract: BackgroundThe Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care.Methods493 adult patients from 27 Italian centres (recruited in 2011-2014) were analyzed.ResultsMean age was 53.8yrs. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40yrs); the mean age for asthma symptoms onset was 30.2yrs and for asthma diagnosis 34.4yrs. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, 16.0% oral corticosteroids.Mean FEV1% pred of 75.1%, median values of 300/mm3 of blood eosinophil count, 323 kU/l of serum total IgE, 24 ppb of FENO were shown.Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), allergic conjunctivitis (30.2%).55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, 7.3% hospitalizations.Factors associated with exacerbation risk were: obesity (OR, 95%CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30 - borderline), nasal polyps (1.86, 0.88-3.89 - borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67 - borderline), anti-IgE use in a protective way (0.26, 0.12-0.53).Comparisons to severe asthma multicentre studies and available registries showed data consistency across European and American populations.ConclusionsAn international effort in the implementation of SUA patients registries could help to better understand the clinical features and to manage severe asthma, representing a non negligible socio-economic burden for health services.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-26T11:05:24.331159-05:
      DOI: 10.1111/all.13342
  • Cockroach is a major cross-reactive allergen source in shrimp-sensitized
           rural children in southern China
    • Authors: Zhaowei Yang; Jiefeng Zhao, Nili Wei, Mulin Feng, Mo Xian, Xu Shi, Zhenyu Zheng, Qiujuan Su, Gary W K Wong, Jing Li
      Abstract: BackgroundLittle is known about the prevalence of food allergy (FA) in China.ObjectiveTo investigate the prevalence of FA and its disparity between urban and rural areas in southern China.MethodsEuroprevall questionnaire responses were obtained from 5,542 school-age-children in urban Guangzhou and 5,319 in rural Shaoguan. A case-control study enrolled 190 children with adverse reactions (ARs) after food intake as cases, and 212 controls in Guangzhou; 116 cases and 233 controls in Shaoguan. These subjects underwent skin-prick test (SPT) and serum IgE measurements to food and inhalant allergens. Allergen extracts from shrimp, house dust mite (HDM), and cockroach were prepared for IgE cross-relativity testing in 23 Guangzhou and 20 Shaoguan shrimp-sensitized subjects.ResultsThe prevalence of ARs to shrimp was higher in Guangzhou than Shaoguan children (3.5% vs. 1.4%, p
      PubDate: 2017-10-26T11:00:22.422181-05:
      DOI: 10.1111/all.13341
  • Emerging roles of innate lymphoid cells in inflammatory diseases: clinical
    • Authors: Inge Kortekaas Krohn; Medya Mara Shikhagaie, Korneliusz Golebski, Jochem H J Bernink, Christine Breynaert, Brecht Creyns, Zuzana Diamant, Wytske J Fokkens, Philippe Gevaert, Peter Hellings, Rudi W Hendriks, Ludger Klimek, Jenny Mjösberg, Hideaki Morita, Graham Ogg, Liam O'Mahony, Jürgen Schwarze, Sven F Seys, Mohamed H Shamji, Suzanne M Bal
      Abstract: Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and non-allergic inflammatory diseases due to their location at barrier surfaces within the airways, gut and skin and they respond to cytokines produced by activated cells in their local environment. ILCs contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging.This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI) encompassing clinicians and researchers, highlights the role of ILCs in human allergic and non-allergic diseases in the airways, gastrointestinal tract and skin, with a focus on new insights into clinical implications, therapeutic options and future research opportunities.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-25T11:10:26.41362-05:0
      DOI: 10.1111/all.13340
  • Omalizumab Rapidly Improves Angioedema-Related Quality of Life in Adult
           Patients with Chronic Spontaneous Urticaria: X-ACT Study Data
    • Authors: Petra Staubach; Martin Metz, Nadine Chapman-Rothe, Christian Sieder, Matthias Bräutigam, Marcus Maurer, Karsten Weller
      Abstract: BackgroundThe X-ACT study aims to examine the effect of omalizumab treatment on quality of life (QoL) in chronic spontaneous urticaria (CSU) patients with angioedema refractory to high doses of H1-antihistamines.MethodsIn X-ACT, a phase III, double-blind, placebo-controlled study, CSU patients (18–75 years) with ≥4 angioedema episodes during the 6 months before inclusion were randomized (1:1) to receive omalizumab 300 mg or placebo every 4 weeks for 28 weeks. Angioedema-related QoL, skin-related QoL impairment, and psychological well-being were assessed.ResultsNinety-one patients were randomized and 68 (omalizumab, n=35; placebo, n=33) completed the 28-week treatment period. At baseline, the mean (SD) total Angioedema QoL (AE-QoL; 56.2 [18.7] and 59.9 [19.2]) and Dermatology Life Quality Index (DLQI; 14.6 [5.7] and 16.6 [7.3]) score was high in the omalizumab and placebo group, respectively. At Week 4 (after the first treatment), the least squares mean difference in the AE-QoL and DLQI score between groups was −17.6 (P
      PubDate: 2017-10-23T10:56:09.969841-05:
      DOI: 10.1111/all.13339
  • Diagnostic relevance of IgE sensitization profiles to eight recombinant
           Phleum pratense molecules
    • Authors: Francesca Cipriani; Carla Mastrorilli, Salvatore Tripodi, Giampaolo Ricci, Serena Perna, Valentina Panetta, Riccardo Asero, Arianna Dondi, Annamaria Bianchi, Nunzia Maiello, Michele Miraglia del Giudice, Tullio Frediani, Francesco Macrì, Sandra Lucarelli, Iride Dello Iacono, Maria Francesca Patria, Elena Varin, Diego Peroni, Loredana Chini, Viviana Moschese, Roberto Bernardini, Giuseppe Pingitore, Umberto Pelosi, Mariangela Tosca, Francesco Paravati, Ifigenia Sfika, Andrea Di Rienzo Businco, Calotta Povesi Dascola, Pasquale Comberiati, Simone Frediani, Caterina Lambiase, Maria Carmen Verga, Diego Faggian, Mario Plebani, Mauro Calvani, Carlo Caffarelli, Paolo Maria Matricardi,
      Abstract: BackgroundGrass pollen–related seasonal allergic rhinoconjunctivitis (SARg) is clinically heterogeneous in severity, comorbidities and response to treatment. The component-resolved diagnostics disclosed also a high heterogeneity at molecular level. Our study aimed at analyzing the characteristics of the IgE sensitization to Phleum pratense molecules and investigating the diagnostic relevance of such molecules in childhood.MethodsWe examined 1120 children (age 4–18y) with SARg. Standardized questionnaires on atopy were acquired through informatics platform (AllergyCARD™). Skin prick tests were performed with pollen extracts. Serum IgE to airborne allergens and eight Phleum pratense molecules (rPhl p 1, rPhl p 2, rPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12) were tested by ImmunoCAP FEIA.ResultsThe analysis of IgE responses against eight Phleum pratense molecules showed 87profiles. According to the number of molecules recognized by IgE, the more complex profiles were characterized by higher serum total IgE, higher grass-specific serum IgE and higher number and degree of sensitization to pollens. The most frequent IgE sensitization profile was the monomolecular Phl p 1. Sensitization to Phl p 7 was a reliable biomarker of asthma, whereas Phl p 12 of oral allergy syndrome. Sensitization to Phl p 7 was associated with a higher severity of SAR, and complex profiles were associated with longer disease duration.ConclusionsIn a large pediatric population, the complexity of IgE sensitization profiles against Phleum pratense molecules is related to high atopic features although useless for predicting the clinical severity. The detection of serum IgE to Phl p 1, Phl p 7 and Phl p 12 can be used as clinical biomarkers of SARg and comorbidities. Further studies in different areas are required to test the impact of different IgE molecular profiles on AIT response.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-20T21:32:35.473687-05:
      DOI: 10.1111/all.13338
  • Food protein-induced enterocolitis syndrome by fish: Not necessarily a
           restricted diet
    • Authors: S Infante; G Marco-Martín, M Sánchez-Domínguez, A Rodríguez-Fernández, V Fuentes-Aparicio, A Alvarez-Perea, P Cabrera-Freitag, C Morales-Cabeza, J M Zubeldia, L Zapatero
      Abstract: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity usually due to cow′s milk or soy. Recent researches show that fish is one of the most important triggers of FPIES in the Mediterranean countries. Due to the risk of multiple-food-FPIES, avoiding foods in the same category or that often occur together may be reasonable.The aim of this study was to evaluate the evolution and follow-up of FPIES related to fish over a period of 20 years. We describe the clinical features of our population, discuss different approaches to oral food challenges and analyse the possibility of introducing the culprit fish or other non-related fish in order to avoid unnecessary restricted diets.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-20T02:30:19.322952-05:
      DOI: 10.1111/all.13336
  • The longitudinal impact of Probiotic and Peanut Oral Immunotherapy (PPOIT)
           on health related quality of life (HRQL)
    • Authors: Audrey Dunn Galvin; Suzanne McMahon, Anne-Louise Ponsonby, Kuang-Chih Hsiao, Mimi L K Tang,
      Abstract: BackgroundWe previously reported that Probiotic and Peanut Oral Immunotherapy (PPOIT) was effective at inducing sustained unresponsiveness compared with placebo in a double-blind, placebo-controlled randomized trial. This study evaluated the impact of PPOIT on health related quality of life (HRQL).MethodFifty-one participants (PPOIT 24; Placebo 27) from the PPOIT trial completed Food Allergy Quality of Life Questionnaire (FAQLQ-PF) and Food Allergy Independent Measure (FAIM) at pre-treatment, end-of-treatment and 3-months after end-of-treatment. 42 participants (20 PPOIT; 22 Placebo) completed measures at 12 months post-treatment. Changes over time in PPOIT and Placebo groups were examined by repeated measures analysis of variance and paired t-tests.ResultsPPOIT was associated with significant improvement in FAQLQ-PF (F=3.63, p=0.02), with Mean Difference 0.8 at 3 months post-treatment (p=0.05) and 1.3 at 12 months post-treatment (p=0.005), exceeding the 0.5 minimal clinically important difference for FAQLQ-PF. For FAIM, mean difference was 0.5 (p=0.03) at 3 months and 0.4 (p=0.04) at 12 months. In placebo group, post-treatment FAQLQ and FAIM remained unchanged from pre-treatment. Improvement in FAQLQ-PF and FAIM scores related specifically to acquisition of sustained unresponsiveness rather than to receiving PPOIT treatment or participation in the trial.ConclusionsPPOIT has a sustained beneficial effect on psychosocial impact of food allergy at 3 months and 12 months after end-of-treatment. Treatment was not associated with reduced HRQL relative to baseline in either PPOIT or placebo groups, indicating that PPOIT was well tolerated and psychological wellbeing was not negatively impacted. Improved HRQL was specifically associated with acquisition of sustained unresponsiveness.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-20T02:25:47.006947-05:
      DOI: 10.1111/all.13330
  • Different Functional Genes of Upper Airway Microbiome Associated with
           Natural Course of Childhood Asthma
    • Authors: Bong-Soo Kim; Eun Lee, Min-Jung Lee, Mi-Jin Kang, Jisun Yoon, Hyun-Ju Cho, Jaehyun Park, Sungho Won, So Yeon Lee, Soo-Jong Hong
      Abstract: BackgroundMicrobial colonization of the airway plays a role in the pathogenesis of asthma; however, the effect of the upper airway microbiome on childhood asthma is not fully understood. We analyzed the metagenome of airway microbiome to understand the associated role of upper airway microbiome with the natural course of childhood asthma.MethodsNasopharyngeal swabs were collected from children with asthma, those in asthma remission, and control groups. High-throughput sequencing was used to examine the structure and functional dynamics of the airway microbiome with respect to asthma phenotypes.ResultsThe composition of microbiota differed among healthy control, asthma, and remission groups. The relative abundance of Streptococcus was negatively associated with FEV1% predicted (p = 0.023), and that of Staphylococcus was negatively associated with methacholine PC20 (p = 0.013). Genes related to arachidonic acid metabolites, lysine residues, and glycosaminoglycans in the microbiome could be associated with airway inflammation. In particular, genes related to synthesis of anti-inflammatory prostaglandin E2 were not detected from the airway microbiome in the asthma group.ConclusionsThese data suggest that alterations in the composition and function of the upper airway microbiome could be related with the natural course of asthma in children.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-20T02:25:33.810352-05:
      DOI: 10.1111/all.13331
  • Quantitative analysis of multiple elements in healthy and remodeled
           epithelium from human upper airway mucosa by using nuclear microscopy
    • Authors: Min-Qin Ren; Yu-Tao Zhou, He-Xin Chen, Tian-Ying Li, Saumitra K Vajandar, Thomas Osipowicz, Frank Watt, Chun-Wei Li
      Abstract: Elements are vital in airway mucosal physiology and pathology; but their distribution and levels in the mucosa remain unclear. The present study uses the state-of-the-art nuclear microscopy facility to map and quantify multiple elements in the histology sections of nasal mucosa from patients with nasal polyps or inverted papilloma. Our results demonstrate that P and Ca are the most abundant elements in mucosa and their distinct difference between epithelial and sub-epithelial regions; more importantly, our results reveal decreased amounts of Cu and Zn in the remodelled epithelium as compared to the normal epithelium. These findings suggest that Cu and Zn may be beneficial targets to regulate aberrant epithelial remodeling in airway inflammation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-11T02:05:25.953303-05:
      DOI: 10.1111/all.13329
  • CRD and beyond: multivariable regression models to predict severity of
           hazelnut allergy
    • Authors: Mareen R. Datema; Ronald van Ree, Riccardo Asero, Laura Barreales, Simona Belohlavkova, Frédéric de Blay, Michael Clausen, Ruta Dubakiene, Cristina Fernández-Perez, Philipp Fritsche, David Gislason, Karin Hoffmann-Sommergruber, Monika Jedrzejczak-Czechowicz, Laurian Jongejan, André C. Knulst, Marek Kowalski, Tanya Z. Kralimarkova, Thuy-My Le, Jonas Lidholm, Nikolaos G. Papadopoulos, Todor A. Popov, Nayade del Prado, Ashok Purohit, Isabel Reig, Suranjith L. Seneviratne, Athanassios Sinaniotis, Serge A. Versteeg, Stefan Vieths, A.H. Zwinderman, E.N. Clare Mills, Montserrat Fernández-Rivas, Barbara Ballmer-Weber
      Abstract: BackgroundComponent-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity.AimTo analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy.MethodsPatients reporting hazelnut allergy (n=423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during DBPCFC) were categorized in mild, moderate and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (OR) and areas under receiver operating characteristic (ROC) curves (AUC) were used to evaluate their predictive value.ResultsCor a 9 and 14 were positively (OR 10.5 and 10.1 respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk), increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3% and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker.ConclusionA model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-07T10:35:34.512109-05:
      DOI: 10.1111/all.13328
  • Complete kinetic follow-up of symptoms and complement parameters during a
           hereditary angioedema attack
    • Authors: Nóra Veszeli; Kinga Viktória Kőhalmi, Erika Kajdácsi, Dominik Gulyás, György Temesszentandrási, László Cervenak, Henriette Farkas, Lilian Varga
      Abstract: We studied the kinetics of C1-inhibitor (C1-INH) and other complement parameters in a self-limited edematous attack (EA) in a patient with hereditary angioedema due to C1-INH deficiency to better understand the pathomechanism of the evolution, course, and complete resolution of EAs. C1-INH concentration and functional activity (C1-INHc+f), C1(q,r,s), C3, C4, C3a, C4a, C5a and SC5b-9 levels were measured in blood samples obtained during the 96-hour observation period. The highest C1-INHc+f, C4, and C1(q,r,s) levels were measured at baseline, and their continuous decrease was observed during the entire observation period. C4 depletion started at prodromal phase and C4 was lowest after the maximum severity peak. Compared to baseline, C4a level was four times higher 7 hours before the onset of the attack. C1-INH did not increase after resolution of the attack suggesting that factors other than C1-INH may be important in this process. C4a may be a useful biomarker for the prediction of EAs.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-07T07:24:15.772108-05:
      DOI: 10.1111/all.13327
  • Increased attention-deficit/hyperactivity symptoms in atopic dermatitis
           are associated with history of antihistamine use
    • Authors: Jochen Schmitt; Angelika Buske-Kirschbaum, Falko Tesch, Katharina Trikojat, Victoria Stephan, Susanne Abraham, Andrea Bauer, Katja Nemat, Franziska Plessow, Veit Roessner
      Abstract: BackgroundEpidemiologic evidence indicates a relevant association between atopic dermatitis (AD) and attention-deficit/hyperactivity disorder (ADHD). Underlying mechanisms and ways to best identify subgroups of AD patients at risk for ADHD are poorly understood.Aims of the studyTo compare sociodemographic, clinical, and psychosocial characteristics of children with AD, ADHD, comorbid AD/ADHD, and age-matched healthy controls. To investigate aspects of AD related to ADHD symptoms.MethodsApplying a factorial design we investigated 4 groups of children age 6 to 12 years: AD-only (i.e. without ADHD), ADHD-only (i.e. without AD), AD+ADHD, healthy controls (HC; i.e. no AD/no ADHD). Using validated instruments, ADHD symptoms and other behavioural problems, quality of life, parenting stress, and sleeping problems were compared between groups. In children with AD-only, clinical signs (objective SCORAD), symptoms (POEM, VAS pruritus, VAS sleeping problems), and previous treatment of AD were assessed to investigate disease patterns related to ADHD symptoms.ResultsCompared to HC (n=47), children with AD-only (n=42), ADHD-only (n=34) and comorbid AD+ADHD (n=31) had significantly increased behavioural problems and decreased quality of life. Children with AD-only had significantly higher levels of ADHD symptoms than HC. In children with AD-only, previous use of antihistamines was significantly associated with increased ADHD symptoms (OR 1.88; 95%-CI 1.04-3.39). Current clinical signs and AD-symptoms were unrelated to the level of ADHD symptoms.ConclusionsEven if the clinical diagnosis of ADHD is excluded, children with AD show increased levels of ADHD symptoms. Further investigations need to determine whether early antihistamine exposure is a major risk factor for ADHD or a surrogate for previous AD severity and/or associated sleeping problems.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-04T01:05:33.117042-05:
      DOI: 10.1111/all.13326
  • Nasal protein profiles in work-related asthma caused by different
    • Authors: Hille Suojalehto; Irmeli Lindström, Henrik Wolff, Anne Puustinen
      Abstract: BackgroundThe mechanisms of work-related asthma are incompletely delineated. Nasal cell samples may be informative about processes in the lower airways. Our aim was to determine the nasal protein expression profiles of work-related asthma caused by different kind of exposures.MethodsWe collected nasal brush samples from 82 non-smoking participants, including healthy controls and work-related asthma patients exposed to 1) protein allergens, 2) isocyanates, and 3) welding fumes the day after relevant exposure. The proteome changes in samples were analysed by two-dimensional difference gel electrophoresis and the differentially regulated proteins found were identified by mass spectrometry. Immunological comparison was carried out using Western blot.ResultsWe detected an average of 2500 spots per protein gel. Altogether 228 protein spots were chosen for identification, yielding 77 different proteins. Compared to the controls exposure to protein allergens had the largest effects on the proteome. Hierarchical clustering revealed that protein allergen and isocyanate related asthma had similar profiles, whereas asthma related to welding fumes differed. The highly overrepresented functional categories in the asthma groups were defence response, protease inhibitor activity, inflammatory and calcium signalling, complement activation, and cellular response to oxidative stress. Immunological analysis confirmed the found abundance differences in Galectin 10 and Protein S100-A9 between the groups.ConclusionsWork-related asthma patients exposed to protein allergens and isocyanates elicit similar nasal proteome responses and the profiles of welders and healthy controls were alike. Revealed biological activities of the protein expression changes are associated with allergic inflammation and asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-28T08:50:30.797086-05:
      DOI: 10.1111/all.13325
  • The sex-shift in single disease and multimorbid asthma and rhinitis during
    • Authors: Theresa Keller; C Hohmann, M Standl, A H Wijga, U Gehring, E Melén, C Almqvist, S Lau, E Eller, U Wahn, E Soegaard Christiansen, A v.Berg, J Heinrich, I Lehmann, D Maier, D S Postma, J M Antó, J Bousquet, T Keil, S Roll
      Abstract: BackgroundCross-sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear if this inequality changes after puberty. We examined the sex-specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty-onset in longitudinal cohort data.MethodsIn six European population-based birth cohort studies we assessed the outcomes current rhinitis, current asthma, current allergic multimorbidity (i.e. concurrent asthma and rhinitis), puberty status, and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero-allergens. With generalized estimating equations we analysed the effects of sex, age, puberty (yes/no), and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta-analysis.FindingsWe included data from 19,013 participants from birth to age 14-20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs. males 0.79 (95%-confidence interval 0.73-0.86) and 0.86 (0.79-0.94) respectively (sex-puberty interaction p= 0.089).Similarly, for current asthma only, females were less often affected than boys both before and after puberty-onset: 0.71, 0.63-0.81 and 0.81, 0.64-1.02, respectively (sex-puberty interaction p=0.327).The prevalence of allergic multimorbidity showed the strongest sex-effect before puberty onset (female-male-OR 0.55, 0.46-0.64) and a considerable shift towards a sex-balanced prevalence after puberty onset (0.89, 0.74-1.04); sex-puberty interaction: p
      PubDate: 2017-09-27T12:55:20.926528-05:
      DOI: 10.1111/all.13312
  • The pruritogenic mediator endothelin-1 shifts the dendritic cell–T-cell
           response toward Th17/Th1 polarization
    • Authors: T. Nakahara; M. Kido-Nakahara, F. Ohno, D. Ulzii, T. Chiba, G. Tsuji, M. Furue
      Abstract: Endothelin-1 (ET-1) is associated with skin diseases such as atopic dermatitis (AD) and psoriasis. ET-1 is enhanced in the skin of AD and psoriasis patients. In addition, plasma levels of ET-1 are elevated in AD and psoriasis. Although both AD and psoriasis are T cell–mediated skin diseases, the association between ET-1 and the T-cell immune response has not been clarified. To evaluate the role of ET-1 in inflammatory skin disease, we sought to investigate the effects of ET-1 on the functions of dendritic cells (DCs) and subsequent immune responses. For this purpose, we immunohistochemically confirmed the upregulation of ET-1 in the epidermis of patients with AD or psoriasis. ET-1 directly induced phenotypic maturation of bone marrow-derived DCs (BMDCs). In addition, ET-1 augmented the production of several cytokines and allogeneic stimulatory capacity of BMDCs. Interestingly, ET-1–activated BMDCs primed T cells to produce Th1 and Th17 cytokines, but not Th2 cytokines. These findings indicate that ET-1 polarizes the DC–T-cell response towards Th17/1 differentiation and may augment the persistent course of inflammatory skin diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-27T12:50:29.417311-05:
      DOI: 10.1111/all.13322
  • The prevalence of atopic dermatitis beyond childhood: A systematic review
           and meta-analysis of longitudinal studies
    • Authors: Katrina Abuabara; Ashley M. Yu, Jean-Phillip Okhovat, Elaine Allen, Sinéad M. Langan
      Abstract: There are sparse and conflicting data regarding the long-term clinical course of atopic dermatitis (AD). Although often described as a primarily childhood disease, newer population-based estimates suggest the prevalence of pediatric and adult disease may be similar. Our objective was to determine whether there is a decline in the prevalence of AD in population-based cohorts of patients followed longitudinally beyond childhood. We conducted a systematic review and meta-analysis including studies assessing AD prevalence across 3 or more points in time. The primary outcome was weighted overall risk difference (percentage decrease in AD prevalence). Of 2,080 references reviewed, 7 studies with 13,515 participants were included. Participants were assessed at 3-6 time points, ranging from age 3 months to 26 years. The percentage decrease in prevalence after age 12 was 1%, which was not significantly different from zero (95% confidence interval -2% to 5%). Similar results were found with other age cut-offs. In conclusion, the prevalence of AD in longitudinal birth cohort studies is similar in childhood and early adulthood.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-27T12:50:27.135982-05:
      DOI: 10.1111/all.13320
  • Airway pathology in severe asthma is related to airflow obstruction but
           not symptom control
    • Authors: Diogenes S. Ferreira; Regina M. Carvalho-Pinto, Marcelo G. Gregório, Raquel Annoni, Aila M. Teles, Monique Buttignol, Bianca B. Araújo-Paulino, Edgard H. Katayama, Bianca L. Oliveira, Heloisa S. Del Frari, Alberto Cukier, Marisa Dolhnikoff, Rafael Stelmach, Klaus F. Rabe, Thais Mauad
      Abstract: BackgroundPatients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment.Methods50 severe asthmatics received prednisone 40 mg/day for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 μg twice daily + budesonide/formoterol 200/6 μg as needed for 12 weeks. Endobronchial biopsies were performed at the end of 12 weeks. We performed extensive immunopathological analyses of airway tissue inflammation and remodeling features in patients stratified by asthma symptom control and by airflow obstruction.ResultsAirway tissue inflammation and remodeling were not associated with symptom control. Asthmatics with persistent airflow obstruction had greater airway smooth muscle (Asm) area with decreased periostin and transforming growth factor beta positive cells within Asm bundles, in addition to lower numbers of chymase positive mast cells in the submucosa compared to patients with non-persistent obstruction.ConclusionsSymptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-27T08:15:23.84731-05:0
      DOI: 10.1111/all.13323
  • The roadmap for Allergology in Europe: the subspecialty of Allergology as
           ‘stop-over’ on the way to a full specialty. An EAACI position
    • Authors: R Gerth van Wijk; I Eguiluz-Gracia, J Gayraud, J Gutermuth, E Hamelmann, E Heffler, T. A Popov, P Schmid-Grendelmeier, P. V Tomazic, O Tsilochistrou, N Muelleneisen
      Abstract: The vision of EAACI and the UEMS Section and Board (S&B) on allergology is to promote and to establish a full specialty of allergology in all European countries. In many European countries a full specialty does not exist. In those countries organ-based (sub)specialists or paediatricians and internists with an expertise in allergology may deliver allergy care. There are no generally accepted requirements for the training of subspecialists available. To fill the gap between the need and availability of experienced and accredited physicians who can deliver optimal care to the allergic patients the EAACI Specialty Committee proposes the minimal requirements for training and certification of subspecialists in allergology. This paper describes the required theoretical knowledge, skills, competences and training facilities (staff and institution). The subspecialist as described in this paper should ideally show the necessary competence in providing good quality care to patients in an environment lacking those full specialists in allergology or tertiary care paediatric subspecialists in allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-27T08:05:21.694912-05:
      DOI: 10.1111/all.13321
  • Distinct epitope structures of defensin-like proteins linked to
           proline-rich regions give rise to differences in their allergenic activity
    • Authors: I. Pablos; S. Eichhorn, Y. Machado, P. Briza, A. Neunkirchner, B. Jahn-Schmid, S. Wildner, W. T. Soh, C. Ebner, J.-W. Park, W. F. Pickl, N. Arora, S. Vieths, F. Ferreira, G. Gadermaier
      Abstract: BackgroundArt v 1, Amb a 4, and Par h 1 are allergenic defensin-polyproline–linked proteins present in mugwort, ragweed, and feverfew pollen, respectively. We aimed to investigate the physicochemical and immunological features underlying the different allergenic capacities of those allergens.MethodsRecombinant defensin-polyproline–linked proteins were expressed in E. coli and physicochemically characterized in detail regarding identity, secondary structure, and aggregation status. Allergenic activity was assessed by mediator releases assay, serum IgE reactivity, and IgE inhibition ELISA using sera of patients from Austria, Canada, and Korea. Endolysosomal protein degradation and T-cell cross-reactivity were studied in vitro.ResultsDespite variations in the proline-rich region, similar secondary structure elements were observed in the defensin-like domains. Seventy-four percent and 52% of the Austrian and Canadian patients reacted to all three allergens, while Korean patients were almost exclusively sensitized to Art v 1. This was reflected by IgE inhibition assays demonstrating high cross-reactivity for Austrian, medium for Canadian, and low for Korean sera. In a subgroup of patients, IgE reactivity toward structurally altered Amb a 4 and Par h 1 was not changed suggesting involvement of linear epitopes. Immunologically relevant endolysosomal stability of the defensin-like domain was limited to Art v 1 and no T-cell cross-reactivity with Art v 125-36 was observed.ConclusionsDespite structural similarity, different IgE-binding profiles and proteolytic processing impacted the allergenic capacity of defensin-polyproline–linked molecules. Based on the fact that Amb a 4 demonstrated distinct IgE-binding epitopes, we suggest inclusion in molecule-based allergy diagnosis.
      PubDate: 2017-09-27T02:30:34.88154-05:0
      DOI: 10.1111/all.13298
  • A composite of exhaled LTB4, LXA4, FeNO and FEV1 as an “asthma
           classification ratio” characterizes childhood asthma
    • Authors: Li-Chen Chen; Hsu-Min Tseng, Ming-Ling Kuo, Chih-Yung Chiu, Sui-Ling Liao, Kuan-Wen Su, Ming-Han Tsai, Man-Chin Hua, Shen-Hao Lai, Tsung-Chieh Yao, Kuo-Wei Yeh, Ai-Hsuan Wu, Jing-Long Huang, Shau-Ku Huang
      Abstract: BackgroundAberrant generation of eicosanoids is associated with asthma, but the evidence remains incomplete and its potential utility as biomarkers is unclear. Major eicosanoids in exhaled breath condensates (EBCs) were assessed as candidate markers for childhood asthma.MethodsTen exhaled eicosanoid species was evaluated using ELISA in the discovery phase, followed by prediction model-building and validation phases.ResultsExhaled LTB4, LTE4, PGE2 and LXA4 showed significant difference between asthmatics (N=60) and controls (N=20). For validation, an expanded study population consisting of 626 subjects with asthma and 161 healthy controls were partitioned into a training subset to establish a prediction model and a test sample subset for validation. Receiver Operating Characteristic (ROC) analyses of the training subset revealed the level of exhaled LTB4 to be the most discriminative among all parameters, including FeNO, and a composite of exhaled LTB4, LXA4, together with FeNO and FEV1, distinguishing asthma with high sensitivity and specificity. Further, the Youden index (J) indicated the cut point value of 0.598 for this composite of markers as having the strongest discriminatory ability (sensitivity = 85.2% and specificity = 83.6%). The predictive algorithm as “asthma classification ratio” was further validated in an independent test sample with sensitivity and specificity being 84.4% and 84.8%, respectively.ConclusionsIn a pediatric study population in Taiwan, the levels of exhaled LTB4, LTE4, LXA4 and PGE2 in asthmatic children were significantly different from those of healthy controls, and the combination of exhaled LTB4 and LXA4, together with FeNO and FEV1, best characterized childhood asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-25T02:55:31.394339-05:
      DOI: 10.1111/all.13318
  • National clinical practice guidelines for Allergen Immunotherapy: an
           international assessment applying AGREE-II
    • Authors: D E S Larenas-Linnemann; D Antolín-Amérigo, C Parisi, A Nakonechna, J A Luna-Pech, B Wedi, I Davila, M Gómez, M Levin, J A Ortega-Martell, L Klimek, N Rosario, A M Muraro, I Agache, J Bousquet, A Sheikh, , O Pfaar
      Abstract: BackgroundSince 1988 numerous allergen immunotherapy guidelines (AIT-GLs) have been developed by national and international organizations to guide physicians in AIT. Even so, AIT is still severely under-used.Objectiveto evaluate AIT-GLs with AGREE-II, developed in 2010 by McMaster University methodologists to comprehensively evaluate GL-quality.MethodsAllergist, from different continents, knowledgeable in AIT and AGREE-II trained were selected into the project team. The project received methodologists’ guidance. AIT-GLs in any language were sought from 1980-2016; AIT-GLs were AGREE II evaluated by at least 2 team-members, independently; discrepancies were resolved in a second round, by team-discussion or methodologists’ consulting.ResultsWe found 31 AIT-GLs (15 post-2010), ranging from local consensus reports to international position papers (EAACI, AAAAI-ACAAI, WAO). Pre-2010 GLs’ scored 1.6-4.6 (23-67%); post-2010 GLs’ 2.1-6 (30-86%), on a 7-point Likert-scale. Best evaluated were: German-Austrian-Swiss (6.0), Mexican (5.1) and the AAAAI/ACAAI AIT-GL (4.7). These were also the only 3 GLs that received ‘yes’ of both evaluators to the item: ‘I would recommend this GL for use’. The domains of ‘Stakeholder involvement’ and ‘Rigor of Development’ only scored 3/7, and ‘Applicability’ scored the lowest. Strikingly, newer GLs only scored clearly better in ‘Editorial independence’ and ‘Global evaluation’.ConclusionsIn AIT-GLs there is still a lot of room for improvement, especially in domains crucial for the dissemination. For some GLs, the ‘Scientific rigor’ domain flawed. When resources are limited, transculturizing a high-quality GL might be preferable over developing a GL from zero. Our study and AGREE-II could help to select the best candidate.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-21T09:26:42.826378-05:
      DOI: 10.1111/all.13316
  • Protease-Activated Receptor-2 blockade inhibits changes seen in a chronic
           murine asthma model
    • Authors: Muhammad Asaduzzaman; Courtney Davidson, Drew Nahirney, Yahya Fiteih, Lakshmi Puttagunta, Harissios Vliagoftis
      Abstract: Proteinase-Activated Receptor-2 (PAR2) is a G protein-coupled receptor activated by serine proteinases. We have shown that PAR2 activation in the airways is involved in the development of allergic inflammation and airway hyperresponsiveness (AHR) in acute murine models. We hypothesize that functional inhibition of PAR2 prevents allergic inflammation, AHR and airway remodeling in chronic allergic airway inflammation models. We developed a 12 week model of cockroach extract (CE)-mediated AHR, airway inflammation and remodeling in BALB/c. These mice exhibit AHR, increased numbers of eosinophils in bronchoalveolar lavage (BAL) and increased collagen content in the lung tissue compared to saline controls. Administration of an anti-PAR2 antibody, SAM-11, after the initial development of airway inflammation significantly inhibited all these parameters. Our data demonstrate that PAR2 signaling plays a key role in CE-induced AHR and airway inflammation/remodeling and that targeting PAR2 activation may be a successful therapeutic strategy for allergic asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-20T05:21:17.596123-05:
      DOI: 10.1111/all.13313
  • Serine protease allergen favours Th2 responses via PAR-2 and STAT-3
           activation in murine model
    • Authors: Komal Agrawal; Naveen Arora
      Abstract: BackgroundProtease activity of Per a 10 favours Th2 responses by differential regulation of IL-12p70 and IL-23 cytokine subunits. The present study aims to elucidate the underlying mechanism of differential regulation of IL-12p70 and IL-23.MethodsPAR-2 activation was blocked in murine model by administering SAM11 before each sensitization. CD11c+ p-STAT3+ cells were measured in lungs by flow cytometry. BMDCs were pre-treated with SAM-11 or isotype control or stattic and stimulated with Per a 10. p-STAT3 levels were measured using Western blot. Transcript levels of IL-12p35, IL12/23p40 and IL-23p19 were measured using RT PCR. Cytokine levels were analysed using ELISA.ResultsProtease activity of Per a 10 increases p-STAT3 levels in mice lungs, which gets reduced on PAR-2 blockage. Percentage of p-STAT3+ CD11c+ cells was higher in Per a 10 administered mice and gets reduced upon PAR-2 blockage. IL-12p35 and IL-12p70 levels were higher, IL-23p19 and IL-23 levels were lower in both SAM-11 treated mice and BMDCs indicating a role of PAR-2 mediated signalling. IL-4, TSLP, IL-17A, EPO activity, total cell count and specific IgE and IgG1 levels were lower in SAM-11 administered mice. Inhibiting STAT3 activation via stattic also leads to lower levels of IL-23p19, IL-23 and higher level of IL-12p35.ConclusionsPer a 10 leads to PAR-2 activation on BMDCs resulting in downstream activation of STAT3 to regulate the balance between IL-12/IL-23 subunits causing a cytokine milieu rich in IL-23 to favour Th2 polarization.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-20T05:16:08.683083-05:
      DOI: 10.1111/all.13315
  • Neonatal BCG-vaccination and atopic dermatitis before 13 months of age. A
           randomised clinical trial
    • Authors: Lisbeth Marianne Thøstesen; Jesper Kjærgaard, Gitte Thybo Pihl, Nina Marie Birk, Thomas Nørrelykke Nissen, Peter Aaby, Aksel Karl Georg Jensen, Annette Wind Olesen, Lone Graff Stensballe, Dorthe Lisbeth Jeppesen, Christine Stabell Benn, Poul-Erik Kofoed
      Abstract: Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis.The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational age
      PubDate: 2017-09-20T03:50:28.913046-05:
      DOI: 10.1111/all.13314
  • AllergoOncology: Opposite Outcomes of Immune Tolerance in Allergy and
    • Authors: E Jensen-Jarolim; H J Bax, R Bianchini, S Crescioli, T R Daniels-Wells, D Dombrowicz, E Fiebiger, H J Gould, S Irshad, J Janda, D H Josephs, F Levi-Schaffer, L O′Mahony, G Pellizzari, M L Penichet, F Redegeld, F Roth-Walter, J Singer, E Untersmayr, L Vangelista, S N Karagiannis
      Abstract: While desired for the cure of allergy, regulatory immune cell subsets and non-classical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-16T17:30:35.466711-05:
      DOI: 10.1111/all.13311
  • Mucocutaneous Inflammation in the Ikaros Family Zinc Finger 1 (IKZF1) -
           keratin 5 specifc transgenic mice
    • Authors: Mayumi Ueta; Junji Hamuro, Hiromi Nishigaki, Naomi Nakamura, Katsuhiko Shinomiya, Katsura Mizushima, Yuki Hitomi, Risa Tamagawa-Mineoka, Norihiko Yokoi, Yuji Naito, Katsushi Tokunaga, Norito Katoh, Chie Sotozono, Shigeru Kinoshita
      Abstract: BackgroundOur genome-wide association study documented an association between cold medicine related Stevens-Johnson syndrome / toxic epidermal necrolysis (CM-SJS/TEN) and Ikaros Family Zinc Finger 1 (IKZF1). Few studies examined biological and pathological functions of IKZF1 in mucosal immunity. We hypothesized that IKZF1 contributes to the mucocutaneous inflammation.MethodsHuman skin and conjunctival tissues were obtained for immunohistological studies. Primary human conjunctival epithelial cells (PHCjECs) and adult human epidermal keratinocytes (HEKa) also used for gene expression analysis. We also generated K5-Ikzf1-EGFP transgenic mice (Ikzf1 Tg) by introducing the Ik1 isoform into cells expressing keratin 5, which is expressed in epithelial tissues such as the epidermis and conjunctiva and then examined them histologically and investigated gene expression of the epidermis. Moreover, Ikzf1 Tg were induced allergic contact dermatitis.ResultsWe found that human epidermis and conjunctival epithelium expressed IKZF1, and in PHCjECs and HEKa, the expression of IKZF1 mRNA was up-regulated by stimulation with polyI:C, a TLR3 ligand. In Ikzf1 Tg, we observed dermatitis and mucosal inflammation including the ocular surface. In contact dermatitis model, inflammatory infiltrates in the skin of Ikzf1 Tg were significantly increased compared with wild type. Microarray analysis showed that Lcn2, Adh7, Epgn, Ifi202b, Cdo1, Gpr37, Duoxa1, Tnfrsf4, and Enpp5 genes were significantly up-regulated in the epidermis of Ikzf1 Tg compared with wild-type.ConclusionOur findings support the hypothesis that Ikaros might participate in mucocutaneous inflammation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-15T10:30:20.658949-05:
      DOI: 10.1111/all.13308
  • The ARIA score of allergic rhinitis using mobile technology correlates
           with quality-of-life: The MASK study
    • Authors: J Bousquet; S Arnavielhe, A Bedbrook, J Fonseca, M Morais Almeida, A Todo Bom, I Annesi-Maesano, D Caimmi, P Demoly, P Devillier, V Siroux, E Menditto, G Passalacqua, C Stellato, M T Ventura, A A Cruz, F S Serpa, J da Silva, D Larenas-Linnemann, M Rodriguez Gonzalez, M T Burguete Cabañas, K C Bergmann, T Keil, L Klimek, R Mösges, S Shamai, T Zuberbier, M Bewick, D Price, D Ryan, A Sheikh, J M Anto, J Mullol, A Valero, T Haahtela, E Valovirta, W J Fokkens, P Kuna, B Samolinski, C Bindslev-Jensen, E Eller, S Bosnic-Anticevich, R E O'Hehir, PV Tomazic, A Yorgancioglu, B Gemicioglu, C Bachert, P W Hellings, I Kull, E Melén, M Wickman, M van Eerd, G De Vries,
      Abstract: Mobile technology has been used to appraise allergic rhinitis control but more data are needed. In order to better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1,288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-14T04:06:27.586892-05:
      DOI: 10.1111/all.13307
  • Validation of patient-reported global severity of atopic dermatitis in
    • Authors: Paras P. Vakharia; Rishi Chopra, Ryan Sacotte, Neha Patel, Supriya Immaneni, Takeshia White, Robert Kantor, Derek Y. Hsu, Jonathan I. Silverberg
      Abstract: BackgroundAtopic dermatitis (AD) is associated with a heterogeneous presentation and clinical course. There is a lack of simple and validated severity assessments that are feasible for clinical practice and epidemiological research.ObjectivesWe sought to validate patient-reported global AD severity in adults.MethodsWe performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n=265).ResultsAt baseline and follow-up, patient-reported global AD severity significantly correlated with oSCORAD (Spearman rho=0.56 and 0.49), SCORAD (0.64 and 0.56), EASI (0.56 and 0.50), BSA (0.52 and 0.45), NRS-itch (0.60 and 0.53), POEM (0.50 and 0.48), and DLQI (0.50 and 0.49) (P
      PubDate: 2017-09-14T04:03:16.249451-05:
      DOI: 10.1111/all.13309
  • Mast cells and sphingosine-1-phosphate underlie prelesional remodeling in
           a mouse model of eczema
    • Authors: Piper A. Wedman; Ahmed Aladhami, Alena P. Chumanevich, John W. Fuseler, Carole A. Oskeritzian
      Abstract: Atopic dermatitis (AD) is a chronic skin inflammation that affects children and adults worldwide, but its pathogenesis remains ill-understood. We show that a single application of OVA to mouse skin initiates remodeling and cellular infiltration of the hypodermis measured by a newly developed computer-aided method. Importantly, we demonstrate that skin mast cell (MC) activation and local sphingosine-1-phosphate (S1P) are significantly augmented after OVA treatment in mice. Deficiency in sphingosine kinase (SphK)1, the S1P-producing enzyme, or in MC, remarkably mitigates all signs of OVA-mediated remodeling and MC activation. Furthermore, skin S1P levels remain unchanged in MC-deficient mice exposed to OVA. LPS-free OVA does not recapitulate any of the precursor signs of AD, supporting a triggering contribution of LPS in AD that, per se, suffice to activate local MC and elevate skin S1P. We describe MC and S1P as novel pathogenic effectors that initiate remodeling in AD prior to any skin lesions and reveal the significance of LPS in OVA used in most studies, thus mimicking natural antigen (Ag) exposure.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-14T04:03:10.904811-05:
      DOI: 10.1111/all.13310
  • Current practice of allergy diagnosis and the potential impact of
           regulation in Europe
    • Authors: Victoria Cardona; Pascal Demoly, Sten Dreborg, A. Fusun Kalpaklioglu, Ludger Klimek, Antonella Muraro, Oliver Pfaar, Todor A. Popov, Hans Jürgen Hoffmann
      Abstract: In the European Union (EU), the regulatory framework regarding diagnostic allergen extracts is currently in the process of being implemented at the national level. Due to these regulations, the initial and periodic renewal expenses for the registration of diagnostic allergen extracts may render extract production unprofitable. Consequently, many extracts may be at risk of removal from the market. The current survey, which was conducted by a task force of the European Academy of Allergy and Clinical Immunology, aimed to assess the current practice of allergy diagnosis in Europe. This survey revealed that skin tests continue to be the main diagnostic procedure and are used as the first option in almost 2/3 of all types of allergic diseases and in 90% of individuals suffering from respiratory allergies. Therefore, there is a need to ensure the availability of high-quality allergen extracts to maintain the common diagnostic procedures used by EU professionals. To reach this goal, it is necessary to align efforts and establish active partnerships between manufacturers, relevant scientific societies, consumer organizations and authorities to maintain the availability of these diagnostic tools.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-14T03:12:11.41958-05:0
      DOI: 10.1111/all.13306
  • Drug Repurposing to treat Asthma and Allergic Disorders: Progress and
    • Authors: Robert L. Kruse; Kristine Vanijcharoenkarn
      Abstract: Allergy and atopic asthma have continued to become more prevalent in modern society despite the advent of new treatments, representing a major global health problem. Common medications such as antihistamines and steroids may have undesirable long-term side effects and lack efficacy in some resistant patients. Biologic medications are increasingly given to treat resistant patients, but they can represent high costs, complex dosing and management, and are not widely available around the world. The field needs new, cheap and convenient treatment options in order to bring better symptom relief to patients. Beyond continued research and development of new drugs, a focus on drug repurposing could alleviate this problem by repositioning effective and safe small molecule drugs from other fields of medicine and applying them toward the treatment of asthma and allergy. Herein, preclinical models, case reports, and clinical trials of drug repurposing efficacy in allergic disease are reviewed. Novel drugs are also proposed for repositioning based on their mechanism of action to treat asthma and allergy. Overall, drug repurposing could become increasingly important as a way of advancing allergy and atopic asthma treatment, filling a need in treatment for patients today.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-07T02:25:22.472083-05:
      DOI: 10.1111/all.13305
  • Targeting histone-acetyltransferase Tip60 inhibits intestinal allergy
    • Authors: Gui Yang; Bao-Hui Cheng, Shao-Bo Yang, Zhi-Qiang Liu, Shu-Qi Qiu, Li-Tao Yang, Rui-Di Xie, Xiao-Rui Geng, Mao-Gang Li, Lin Gao, Zhi-Gang Liu, Ping-Chang Yang
      Abstract: BackgroundThe over production of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone acetyltransferase (HAT) activities are required in gene transcription of a large number of molecules in the immune system of the body.ObjectivesThis study tests a hypothesis that HAT Tat-interactive protein 60 (Tip60) plays an important role in the initiation of IgE-mediated allergy.MethodsThe effects of Tip60 on regulating IgE expression were assessed with B cells. An intestinal allergy mouse model was developed to assess the role of Tip60 in the induction of IgE-mediated allergic inflammation.ResultsHigh levels of Tip60 were observed in the peripheral B cells of patients with FA. Tip60 was required in the expression of IgE and IgG1 in B cells by inducing the chromatin remolding at the gene locus, in which histone acetylation, signal transducer and activator of transcription 6 (STAT6) and nuclear factor-κB at the locus of Iε promoter were markedly increased. Blocking Tip60 significantly attenuated the allergic inflammation in the mouse intestinal mucosa.ConclusionsTip60 plays an important role in the induction of IgE in B cells. Blocking Tip60 inhibits the allergic inflammation in the intestine, suggesting Tip60 inhibitor may be a potential anti-allergy drug.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-04T21:21:32.519411-05:
      DOI: 10.1111/all.13304
  • Association of Breast Milk Fatty Acids and Allergic Disease Outcomes
           – a Systematic Review
    • Authors: Nilakshi T Waidyatillake; Shyamali C Dharmage, Katrina J. Allen, Caroline J Lodge, Julie A Simpson, Gayan Bowatte, Michael J. Abramson, Adrian J Lowe
      Abstract: IntroductionDietary poly unsaturated fatty acids (PUFA) have immune regulatory properties. Breast milk is rich in PUFA, and it has been hypothesised that these PUFAs may be important in the aetiology of allergic diseases. Despite a growing body of evidence, the associations between breast milk PUFA and allergic disease have not previously been systematically reviewed.MethodsThe search was performed in PubMed and EMBASE databases using breastfeeding, fatty acid and allergic disease terms. Two authors were involved in selecting papers for review according to the inclusion criteria and extracting information on study characteristics and measures of association. Only studies that reported numeric associations between concentration of breast-milk fatty acids and allergic disease outcomes were included.ResultsA total of 18 papers met the inclusion criteria, reporting results from 15 study populations. The majority were cohort studies (n=11), with data from only two case control and two cross sectional studies. Sample size varied between 30 and 352 participants and follow-up time of the cohorts varied between three months and 14 years. Nine studies reported on eczema, seven on sensitisation and only five reported on asthma/wheeze. There was heterogeneity among studies in terms of presenting the association between PUFA and allergy, therefore estimates could not be pooled. Only a few studies observed associations between n-3 and n-6 PUFAs and allergic disease, and the magnitude of this effect varied greatly.ConclusionsThere is insufficient evidence to suggest that colostrum or breast milk poly unsaturated fatty acids influence the risk of childhood allergic diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-04T13:50:49.984054-05:
      DOI: 10.1111/all.13300
  • Hen's egg allergen in house and bed dust is significantly increased after
           hen's egg consumption – a pilot study
    • Authors: Valérie Trendelenburg; Sebastian Tschirner, Bodo Niggemann, Kirsten Beyer
      Abstract: Environmental exposure to food allergens may be a risk factor for cutaneous sensitization. Previous studies could detect peanut allergen in house dust. In this pilot study, we wanted to investigate whether hen's egg allergen is detectable in house dust collected from different household areas and whether levels are increased after intentional hen's egg consumption. Hen's egg protein levels of dust samples were measured using ELISA. In 8/8 households, hen's egg was detectable in dust samples of eating area and bed. 48 hours after intentional hen's egg consumption, hen's egg protein levels were significantly increased in both. Still, further research is necessary to investigate whether hen's egg allergen in house and bed dust plays a role in sensitization via skin.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-02T09:55:23.037145-05:
      DOI: 10.1111/all.13303
  • Response to omalizumab using patient enrichment criteria from trials of
           novel biologics in asthma
    • Authors: Thomas B. Casale; Bradley E. Chipps, Karin Rosén, Benjamin Trzaskoma, Tmirah Haselkorn, Theodore A. Omachi, Steven Greenberg, Nicola A. Hanania
      Abstract: BackgroundRecent efficacy studies of asthma biologics have included highly enriched patient populations. Using a similar approach, we examined factors that predict response to omalizumab to facilitate selection of patients most likely to derive the greatest clinical benefit from therapy.MethodsData from two phase III clinical trials of omalizumab in patients with allergic asthma were examined. Differences in rates of asthma exacerbations between omalizumab and placebo groups during the 16-week inhaled corticosteroid (ICS) dose-stable phase were evaluated with respect to baseline blood eosinophil counts (eosinophils
      PubDate: 2017-08-31T16:55:29.380888-05:
      DOI: 10.1111/all.13302
  • Allergic FcεRI- and pseudo-allergic MRGPRX2-triggered mast cell
           activation routes are independent and inversely regulated by SCF
    • Authors: Magda Babina; Sven Guhl, Metin Artuc, Torsten Zuberbier
      Abstract: While allergic mast cell (MC) degranulation occurs by FcεRI-aggregation and varies in strength among subjects, the analogous pseudo-allergic route was recently uncovered to proceed via MRGPRX2. Here, we examine inter-individual variability in skin MC responses to FcεRI-triggering versus those evoked by MRGPRX2. While population-based variability is comparable between the routes, FcεRI- and MRGPRX2-stimulated pathways are completely independent from each other, and responsiveness to one has therefore no predictive value for the other. Conversely, degranulation triggered by compound 48/80 is highly correlated to the process elicited by Substance P. MRGPRX2 mRNA shows pronounced population-based variability (coefficient of variation 102.9%). Surprisingly, SCF as the MC-supportive mediator par excellence potently inhibits pseudo-allergic degranulation, while it simultaneously promotes allergic stimulation via FcεRI. We conclude that SCF can have selective MC-dampening functions. Clinically, the data imply that subjects highly reactive in one pathway are not automatically hyper-responsive in terms of the alternative route.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-31T16:55:27.456066-05:
      DOI: 10.1111/all.13301
  • 12-OH-17,18-epoxyeicosatetraenoic acid alleviates eosinophilic airway
           inflammation in murine lungs
    • Authors: Takao Mochimaru; Koichi Fukunaga, Jun Miyata, Masako Matsusaka, Katsunori Masaki, Hiroki Kabata, Soichiro Ueda, Yusuke Suzuki, Tomomi Goto, Daisuke Urabe, Masayuki Inoue, Yosuke Isobe, Makoto Arita, Tomoko Betsuyaku
      Abstract: BackgroundAsthma is characterized by airway inflammation and obstruction with eosinophil infiltration into the airway. Arachidonic acid, an omega-6 fatty acid, is metabolized into cysteinyl leukotriene with pro-inflammatory properties for allergic inflammation, whereas the omega-3 fatty acid eicosapentaenoic acid (EPA) and its downstream metabolites are known to have anti-inflammatory effects. In this study, we investigated the mechanism underlying the counter-regulatory roles of EPA in inflamed lungs.MethodsMale C57BL6 mice were sensitized and challenged by OVA. After EPA treatment, we evaluated the cell count of BALF, mRNA expressions in the lungs by q-PCR, and the amounts of lipid mediators by Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomics. We investigated the effect of the metabolite of EPA in vivo and vitro study.ResultsEPA treatment reduced accumulation of eosinophils in the airway and decreased mRNA expression of selected inflammatory mediators in the lung. Lipidomics clarified the metabolomic profile in the lungs. Among EPA-derived metabolites, 12-hydroxy-17,18-epoxyeicosatetraenoic acid (12-OH-17,18-EpETE) was identified as one of the major biosynthesized molecules; the production of this molecule was amplified by EPA administration and allergic inflammation. Intravenous administration of 12-OH-17,18-EpETE attenuated airway eosinophilic inflammation through downregulation of C-C chemokine motif 11 (CCL11) mRNA expression in the lungs. In vitro, this molecule also inhibited the release of CCL11 from human airway epithelial cells stimulated with interleukin-4.ConclusionThese results demonstrated that EPA alleviated airway eosinophilic inflammation through its conversion into bioactive metabolites. Additionally, our results suggest that 12-OH-17,18-EpETE is a potential therapeutic target for the management of asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-30T10:45:50.841587-05:
      DOI: 10.1111/all.13297
  • Altered miR-193a-5p expression in children with cow's milk allergy
    • Authors: Valeria D'Argenio; Valentina Del Monaco, Lorella Paparo, Fatima Domenica Elisa De Palma, Rita Nocerino, Francesca D'Alessio, Feliciano Visconte, Valentina Discepolo, Luigi Del Vecchio, Francesco Salvatore, Roberto Berni Canani
      Abstract: BackgroundCow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggest that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls.MethodsPeripheral blood mononuclear cells were obtained from children aged 4-18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next-generation sequencing-based approach. Functional assessment of IL-4 expression was also performed.ResultsAmong the miRNAs differently expressed, 2 were up-regulated and 14 were down-regulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most down-regulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted up-regulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a-5 inhibitor showed a significant up-regulation of IL-4 mRNA and its protein expression. Children who outgrew CMA showed miRNA-193a-5p level, and its related targets expression, similar to that observed in healthy controls.ConclusionsOur results suggest that miR-193a-5p is a post-transcriptional regulator of IL-4 expression and could have a role in IgE-mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-30T09:55:23.21213-05:0
      DOI: 10.1111/all.13299
  • 5-/12-lipoxygenase-linked cascade contributes to the IL-33-induced
           synthesis of IL-13 in mast cells, thus promoting asthma development
    • Authors: MyungJa Ro; A-Jin Lee, Jae-Hong Kim
      Abstract: BackgroundAs asthma progresses, the levels of IL-33 in serum are markedly increased and contribute to asthmatic development and exacerbation. Mast cells, one of the principal effector cells in the pathogenesis of asthma, express high levels of the IL-33 receptor ST2 and have been shown to be activated by IL-33. Thus, IL-33 stimulates mast cells to produce Th2-type cytokines such as IL-13, thus contributing to asthmatic development. However, the signaling mechanism for IL-33-induced synthesis of Th2 cytokines, particularly IL-13, has not been fully elucidated in mast cells.MethodsThe role of 5- or 12-LO in the IL-33-induced synthesis of IL-13 was investigated using knockdown or pharmacological inhibitors in BMMCs and animal model.ResultsBlockade of 5- or 12-LO significantly suppressed IL-33-induced synthesis of IL-13 in BMMCs. The subsequent action of 5- and 12-LO metabolites through their specific receptor, BLT2, was also critical for IL-33-induced synthesis of IL-13. We also demonstrated that the MyD88-p38 kinase cascade lies upstream of 5-/12-LO and that NF-κB lies downstream of 5-/12-LO to mediate the IL-33-induced synthesis of IL-13 in mast cells. Consistent with these findings, we observed that in an IL-33-administered asthmatic airway inflammation model, IL-13 levels were markedly increased in bronchoalveolar lavage fluid, but its levels were markedly suppressed by treatment with inhibitors of 5-LO, 12-LO or BLT2, further suggesting roles of 5-/12-LO in IL-33-induced IL-13 production.ConclusionOur results suggest that ‘MyD88-5-/12-LO-BLT2-NF-κB’ cascade significantly contributes to the IL-33-induced synthesis of IL-13 in mast cells, thus potentially contributing to asthmatic development and exacerbation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-30T09:50:45.874536-05:
      DOI: 10.1111/all.13294
  • Pathogenicity of memory Th2 cells is linked to stage of allergic rhinitis
    • Authors: Tomohisa Iinuma; Yoshitaka Okamoto, Yuki Morimoto, Tomoyuki Arai, Toshioki Sakurai, Syuji Yonekura, Daiju Sakurai, Kiyoshi Hirahara, Toshinori Nakayama
      Abstract: BackgroundAllergic rhinitis (AR) consists of three developmental stages that are based on the presence/absence of antigen-specific IgE and symptoms. The pathogenic Th2 (Tpath2) cells constitute a population of Th2 cells with additional potentially pathogenic characteristics. We examined the relationship between Tpath2 cells and the stages of allergic rhinitis by focusing on ST2, which is an IL-33 receptor.MethodsPatients with Japanese cedar pollen-induced AR (JCP-AR) and healthy volunteers were divided into “non-sensitized,” “asymptomatic sensitized (AS),” and “JCP-AR” groups. We analyzed the ST2 expression and the Th2 function of cultured CD4+ T cells. Next, we observed the progress of patients in the AS stage around the time of seasonal pollen dispersal, with the characteristics of Th2 cells.ResultsThe ST2 expression of T cells was only upregulated in the AR group. The production of IL-4 and IL-13 was found in CD4+ T cells obtained from AS by stimulation with JCP, but reactivity to IL-33 was not observed. Although IL-33 did not induce the elevation of IL-4 production in the JCP-AR group, IL-33 substantially increased the production of IL-5 and IL-13 in comparison to antigen stimulation alone. In newly afflicted patients, the increased expression of ST2 and elevated reactivity to IL-33 was observed, even before the pollen dispersal season.ConclusionsOur study demonstrated that the pathogenicity of memory Th2 cells is linked to sensitization and the stage of allergic rhinitis. Therefore, Tpath2 cells may provide useful insights into the mechanism of the onset and progression of allergic rhinitis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-30T09:50:36.50883-05:0
      DOI: 10.1111/all.13295
  • Simultaneous induction of HSP70 expression, and degranulation, in
           IgE/Ag-stimulated or extracellular HSP70-stimulated mast cells (129/200)
    • Authors: Xian Li; Shiro Kanegasaki, Fansi Jin, Yifeng Deng, Jae-Ryong Kim, Hyeun Wook Chang, Tomoko Tsuchiya
      Abstract: BackgroundIn mast cells, induction of HSP70 expression during antigen stimulation has not been reported.MethodsMouse bone marrow derived mast cells (BMMC) were stimulated with IgE/Ag or HSP70. Induction of HSP70 expression, and signaling protein phosphorylation, were evaluated by immunoblotting.ResultsHSP70 expression is induced in BMMC at an early stage of IgE/Ag-dependent stimulation, some of which is released from the cells in a granule-associated form. Induction of HSP70 expression was also observed with an IgE/Ag-stimulated human basophilic cell line, indicating that the phenomenon is not restricted to mouse BMMC. The induction of HSP70 expression, and its release, followed a similar time course to that of degranulation. Released HSP70 seems to be responsible for degranulation and production of eicosanoids, at least in part, since a neutralizing anti-HSP70 antibody mitigated these activities, and since exogenous HSP70 not only induced immediate degranulation followed by autocrine HSP70 expression but also enhanced degranulation in IgE/Ag stimulated BMMC. Extracellular HSP70 was found to induce phosphorylation of Linker for activation of T cells (LAT) and a series of downstream signaling molecules in BMMC. We further found that Fyn, Lyn and spleen tyrosine kinase (Syk), which are known to concern LAT phosphorylation in IgE/Ag stimulated BMMC, were not phosphorylated in HSP70-stimulated BMMC, whereas lymphocyte-specific-protein tyrosine kinase (Lck) was phosphorylated.ConclusionFcεRI stimulation in BMMC and basophils induces HSP70 expression and its release. Extracellular HSP70 induces degranulation and mediator release via phosphorylation of LAT.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-30T09:50:24.361171-05:
      DOI: 10.1111/all.13296
  • Challenges in the implementation of the EAACI AIT guidelines: A
           situational analysis of current provision of allergen immunotherapy
    • Authors: D Ryan; R Gerth van Wijk, E Angier, M Kristiansen, H Zaman, A Sheikh, V Cardona, C Vidal, A Warner, I Agache, S Arasi, M Fernandez-Rivas, S Halken, M Jutel, S Lau, G Pajno, O Pfaar, G Roberts, G Sturm, E M Varga, R Van Ree, A Muraro
      Abstract: PurposeThe European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe.MethodsWe undertook a mixed-methods, situational analysis. This involved a purposeful literature search, and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe.ResultsThe 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers.ConclusionsSuccessful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-29T02:31:23.647522-05:
      DOI: 10.1111/all.13264
  • Local allergic rhinitis is an independent rhinitis phenotype: The results
           of a 10-years follow-up study
    • Authors: Carmen Rondon; Paloma Campo, Ibon Eguiluz Gracia, Carmen Plaza, Gador Bogas, Pedro Galindo, C Mayorga, M J Torres
      Abstract: BackgroundThe knowledge about the natural history of local allergic rhinitis (LAR) is limited. One unmeet question is to demonstrate whether LAR should be considered the first step in the development of allergic rhinitis (AR) or an independent phenotype. The aim of this study was to prospectively evaluate the natural history of a population with LAR, the potential conversion to AR with systemic atopy, and the development of asthma during 10 years.MethodsThis is the second phase of a 10 year follow-up study of a cohort of 176 patients with LAR of recent onset and 115 age- and sex-matched healthy controls prospectively evaluated from 2005 to 2016. Clinical-demographic questionnaire, spirometry, skin prick-test, and specific-IgE were evaluated yearly. Nasal allergen provocation tests (NAPT) with D. pteronyssinus, Alternaria alternata, Olea europaea, and grass pollen were performed at baseline, and after 5 and 10 years.ResultsAfter 10 years LAR patients experienced a significant and clinically relevant worsening of the rhinitis, with increase of emergency assistance, development of asthma, loss of allergen tolerance, and impairment of the quality of life. This worsening became significant after 5 years and progressed throughout 10 years.A similar rate of development of AR with systemic atopy was detected in patients and controls (9.7% vs 7.8%, Log-rank p=0.623). In 5 patients conversion to systemic atopy occurred>10 years (3%).ConclusionsLAR is a well-differentiated clinical entity with a low rate of development of systemic atopy, a natural evolution towards worsening and a risk factor for suffering asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-08-22T20:25:28.551386-05:
      DOI: 10.1111/all.13272
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Allergen immunotherapy for allergic asthma: A systematic review and
    • Authors: S. Dhami; A. Kakourou, F. Asamoah, I. Agache, S. Lau, M. Jutel, A. Muraro, G. Roberts, C. A. Akdis, M. Bonini, O. Cavkaytar, B. Flood, P. Gajdanowicz, K. Izuhara, Ö. Kalayci, R. Mosges, O. Palomares, O. Pfaar, S. Smolinska, M. Sokolowska, M. Asaria, G. Netuveli, H. Zaman, A. Akhlaq, A. Sheikh
      Pages: 1825 - 1848
      Abstract: BackgroundTo inform the development of the European Academy of Allergy and Clinical Immunology'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 predefined 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 prespecified 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 airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific 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.
      PubDate: 2017-07-06T01:40:39.437295-05:
      DOI: 10.1111/all.13208
  • Poaceae pollen as the leading aeroallergen worldwide: A review
    • Authors: H. García-Mozo
      Pages: 1849 - 1858
      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 subfamilies 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 are governed by species genetics, but plant phenology is also influenced by climate; as a result, climate changes may affect airborne pollen concentrations. This article 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.
      PubDate: 2017-06-20T01:17:30.309295-05:
      DOI: 10.1111/all.13210
  • 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
      Pages: 1859 - 1867
      Abstract: The prevalence of allergic diseases and asthma has dramatically increased over the last decades, resulting in a high burden for patients and healthcare 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 (eg, birth by cesarean 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 with bacteria to prevent allergic diseases are still rare and to some extent contradicting. A detailed mechanistic understanding of 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.
      PubDate: 2017-06-28T01:25:45.428501-05:
      DOI: 10.1111/all.13220
  • 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. Gevaert, B. Wollenberg
      Pages: 1868 - 1873
      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.
      PubDate: 2017-07-03T03:20:33.097669-05:
      DOI: 10.1111/all.13221
  • Amb a 1 isoforms: Unequal siblings with distinct immunological features
    • Authors: M. Wolf; T. E. Twaroch, S. Huber, M. Reithofer, M. Steiner, L. Aglas, M. Hauser, I. Aloisi, C. Asam, H. Hofer, M. A. Parigiani, C. Ebner, B. Bohle, P. Briza, A. Neubauer, F. Stolz, B. Jahn-Schmid, M. Wallner, F. Ferreira
      Pages: 1874 - 1882
      Abstract: BackgroundRagweed pollen represents a major allergy risk factor. Ragweed extracts contain five different isoforms of the major allergen Amb a 1. However, the immunological 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 immunological 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 for 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.
      PubDate: 2017-06-14T23:55:41.790299-05:
      DOI: 10.1111/all.13196
  • Changes in patient quality of life during oral immunotherapy for food
    • Authors: N. Epstein Rigbi; M. R. Goldberg, M. B. Levy, L. Nachshon, K. Golobov, A. Elizur
      Pages: 1883 - 1890
      Abstract: BackgroundQuality of life (QOL) is 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=.001, P=.018, and P=.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 the number or severity of reactions experienced. The total FAQLQ-PF score was inversely associated with the score at baseline on multivariate analysis (regression coefficient=−0.56, P
      PubDate: 2017-06-15T00:00:25.339224-05:
      DOI: 10.1111/all.13211
  • Targeting PP2A and proteasome activity ameliorates features of allergic
           airway disease in mice
    • Authors: P. M. Nair; M. R. Starkey, T. J. Haw, G. Liu, J. C. Horvat, J. C. Morris, N. M. Verrills, A. R. Clark, A. J. Ammit, P. M. Hansbro
      Pages: 1891 - 1903
      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 whether 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 sensitization 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.
      PubDate: 2017-06-21T03:31:13.084707-05:
      DOI: 10.1111/all.13212
  • Functional and phenotypic analysis of basophils allows determining
           distinct subtypes in patients with chronic urticaria
    • Authors: M. M. Rauber; J. Pickert, L. Holiangu, C. Möbs, W. Pfützner
      Pages: 1904 - 1911
      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 with 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 immunologic phenotypes. One subgroup of patients’ basophils reacted to FcεRI stimulation, whereas the others had anti-FcεRI nonreactive 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.ConclusionsPatients with CU can be categorized into three immunologic 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.
      PubDate: 2017-07-12T03:40:36.167236-05:
      DOI: 10.1111/all.13215
  • Omalizumab effectively protects against early and late allergic responses
           in asthma after 4 weeks
    • Authors: J. Trischler; A. Lieb, M. Arnold, J. Schulze, M. Rosewich, R. Schubert, I. Bottoli, S. Zielen
      Pages: 1912 - 1915
      Abstract: BackgroundOmalizumab is licensed for therapy in severe allergic asthma with an effect demonstrated after 8 weeks or longer treatment. As 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).Materials and MethodsTen patients (IgE>300 IU/mL and
      PubDate: 2017-06-28T01:25:36.192674-05:
      DOI: 10.1111/all.13217
  • Spontaneous food allergy in Was−/− mice occurs independent of
           FcεRI-mediated mast cell activation
    • Authors: W. S. Lexmond; J. A. Goettel, B. F. Sallis, K. McCann, E. H. H. M. Rings, E. Jensen-Jarolim, S. Nurko, S. B. Snapper, E. Fiebiger
      Pages: 1916 - 1924
      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 ovalbumin (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 (MCs) 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.
      PubDate: 2017-07-14T03:10:57.300358-05:
      DOI: 10.1111/all.13219
  • 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, R. Lauener, C.A. Akdis, L. O'Mahony
      Pages: 1925 - 1935
      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 (αGalCer 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 diseases 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, αGalCer-stimulated iNKT cells from H2R-deficient mice secreted higher levels of IL-4, IL-5, and GM-CSF. In vivo, αGalCer 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 is contributing to the pathology.
      PubDate: 2017-06-30T03:36:02.79347-05:0
      DOI: 10.1111/all.13227
  • Duration and exclusiveness of breastfeeding and risk of childhood atopic
    • Authors: N. J. Elbert; E. R. Meel, H. T. Dekker, N. W. Jong, T. E. C. Nijsten, V. W. V. Jaddoe, J. C. Jongste, S. G. M. A. Pasmans, L. Duijts
      Pages: 1936 - 1943
      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 allergy, eczema, or asthma.MethodsThis study among 5828 children was performed in a population-based prospective cohort from fetal life onwards. We collected information on duration (
      PubDate: 2017-06-02T02:45:37.045439-05:
      DOI: 10.1111/all.13195
  • Patterns of anaphylaxis after diagnostic workup: A follow-up study of 226
           patients with suspected anaphylaxis
    • Authors: A. Ruiz Oropeza; C. Bindslev-Jensen, S. Broesby-Olsen, T. Kristensen, M. B. Møller, H. Vestergaard, H. F. Kjaer, S. Halken, A. Lassen, C. G. Mortz
      Pages: 1944 - 1952
      Abstract: BackgroundMost published studies on anaphylaxis are retrospective or register based. Data on subsequent diagnostic workup are sparse. We aimed to characterize patients seen with suspected anaphylaxis at the emergency care setting (ECS), after subsequent diagnostic workup 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 workup; 118 of the 124 fulfilled WAO/EAACI criteria of anaphylaxis at the ECS, while six were found among 46 patients 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. Cofactors were present in 58.1% and were significantly associated with severe anaphylaxis.ConclusionA broad search profile in the ECS and subsequent diagnostic workup is important for identification and classification of patients with anaphylaxis. Evaluation of comorbidities and cofactors is important.
      PubDate: 2017-06-20T01:11:06.410557-05:
      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
      Pages: 1953 - 1961
      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 nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months.MethodsA multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator 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 prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and −0.1±0.4 L, respectively, P
      PubDate: 2017-06-14T23:55:22.100304-05:
      DOI: 10.1111/all.13202
  • Identification of a plasma miRNA biomarker signature for allergic asthma:
           A translational approach
    • Authors: K. Milger; J. Götschke, L. Krause, P. Nathan, F. Alessandrini, A. Tufman, R. Fischer, S. Bartel, F. J. Theis, J. Behr, S. Dehmel, N. S. Mueller, N. Kneidinger, S. Krauss-Etschmann
      Pages: 1962 - 1971
      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 prescreened 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.ResultsTen 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 five 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 in 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.
      PubDate: 2017-06-19T01:41:08.448495-05:
      DOI: 10.1111/all.13205
  • Heme oxygenase-1 directly binds STAT3 to control the generation of
           pathogenic Th17 cells during neutrophilic airway inflammation
    • Authors: X. L. Lin; J. J. Lv, J. Lv, C. X. Di, Y. J. Zhang, T. Zhou, J. L. Liu, Z. W. Xia
      Pages: 1972 - 1987
      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 in 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 molecules 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 overexpression 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.
      PubDate: 2017-07-03T03:21:32.477117-05:
      DOI: 10.1111/all.13216
  • Beyond epithelial-to-mesenchymal transition: Common suppression of
           differentiation programs underlies epithelial barrier dysfunction in mild,
           moderate, and severe asthma
    • Authors: L. F. Loffredo; H. Abdala-Valencia, K. R. Anekalla, L. Cuervo-Pardo, C. J. Gottardi, S. Berdnikovs
      Pages: 1988 - 2004
      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.
      PubDate: 2017-07-06T01:51:01.265972-05:
      DOI: 10.1111/all.13222
  • The burden of chronic spontaneous urticaria is substantial: Real-world
           evidence from ASSURE-CSU
    • Authors: M. Maurer; M. Abuzakouk, F. Bérard, W. Canonica, H. Oude Elberink, A. Giménez-Arnau, C. Grattan, K. Hollis, A. Knulst, J.-P. Lacour, C. Lynde, A. Marsland, D. McBride, A. Nakonechna, J. Ortiz de Frutos, C. Proctor, G. Sussman, C. Sweeney, H. Tian, K. Weller, D. Wolin, M.-M. Balp
      Pages: 2005 - 2016
      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 healthcare resource use 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. Chronic spontaneous urticaria 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 increasing disease activity. Significant healthcare resources and costs were incurred to treat CSU.ConclusionsChronic spontaneous urticaria has considerable humanistic and economic impacts. Patients with greater disease activity and with angioedema experience greater HRQoL impairments.
      PubDate: 2017-07-10T02:35:37.164371-05:
      DOI: 10.1111/all.13209
  • Nonlesional atopic dermatitis skin shares similar T-cell clones with
           lesional tissues
    • Authors: P. M. Brunner; R. O. Emerson, C. Tipton, S. Garcet, S. Khattri, I. Coats, J. G. Krueger, E. Guttman-Yassky
      Pages: 2017 - 2025
      Abstract: BackgroundAtopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and nonlesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to nonlesional skin remains unclear.MethodsWe performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 nonlesional AD biopsies, compared to six healthy control and six cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts.ResultsWhile greater T-cell infiltrates were observed in lesional vs nonlesional AD, TCR repertoire diversity was similar in lesional and nonlesional 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 nonlesional tissues, and they were largely maintained after 16 weeks of successful treatment with topical triamcinolone. Nevertheless, both lesional and nonlesional 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 nonlesional 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.
      PubDate: 2017-06-28T01:33:40.731678-05:
      DOI: 10.1111/all.13223
  • What's in a name' Atopic dermatitis or atopic eczema, but not eczema
    • Authors: J. I. Silverberg; J. P. Thyssen, A. S. Paller, A. M. Drucker, A. Wollenberg, K. H. Lee, K. Kabashima, G. Todd, P. Schmid-Grendelmeier, T. Bieber
      Pages: 2026 - 2030
      Abstract: BackgroundThe ideal nomenclature of atopic dermatitis (AD) / atopic eczema (AE) has long been contested. However, it is becoming increasingly clear that the disparate nomenclature of this disease may have important deleterious ramifications for clinical care and research.Materials and MethodsAn electronic questionnaire regarding the preferred nomenclature for AD was sent to councilors of the International Eczema Council (IEC) (n=77), an international group of clinicians and researchers with expertise in AD/AE. The survey consisted of 2 questions for consensus regarding the preference for an atopic prefix, and preference for the term AD or AE, and an exploratory question about the acceptability of the terms AD, AE or eczema. Consensus was defined a priori as at least 90% agreement for each question with a response rate of at least 90%.ResultsSeventy-one of 77 (92.2%) IEC councilors and associates responded to the survey, with all respondents completing the entire survey. Consensus was reached for question 1, with 69 of 71 respondents (97.2%) preferring the atopic prefix. However, consensus was not reached for question 2, with 40 respondents (58.0%) preferring the term AD and 30 (43,5%) preferring AE. 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.ConclusionsThe IEC noted that the term eczema is imprecise, and its use is confusing. The consensus of the IEC was to recommend use of the prefix “atopic” (i.e., AD or AE) in all publications, presentations and discussions about the disorder.
      PubDate: 2017-06-30T03:35:30.194615-05:
      DOI: 10.1111/all.13225
  • Validation of international consensus equation for acute serum total
           tryptase in mast cell activation: A perioperative perspective
    • Authors: R. L. Baretto; S. Beck, J. Heslegrave, C. Melchior, O. Mohamed, A. Ekbote, A. P. Huissoon, M. T. Krishna
      Pages: 2031 - 2034
      Abstract: There is no standardized method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2× baseline tryptase+2 mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS). To validate consensus equation in a perioperative setting analyses of cases of suspected perioperative anaphylaxis during general anaesthesia (GA) were performed. 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. A total of 82 patients (60 females, mean age 56.5 years±SD17.2) underwent investigation. Sixty (73%) patients fulfilled WAO criteria for anaphylaxis, and 22 patients did not. Aetiology included 59% IgE-mediated anaphylaxis, 2% non-IgE-mediated anaphylaxis, 12% anaphylaxis of unknown cause and 27% deemed non-anaphylaxis. IgE-mediated anaphylaxis included the following: NMBA (35%), antibiotics (46%), chlorhexidine (8%), patent blue dye (8%) and others (8%). An acute MCT with a comparable baseline was available in 71 of 82 (87%) patients (60 anaphylaxis and 11 controls). The median interquartile range (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=.0001). This equation has a high specificity, PPV with a moderate NPV and sensitivity in perioperative anaphylaxis.
      PubDate: 2017-07-12T03:40:20.000452-05:
      DOI: 10.1111/all.13226
  • Cytomegalovirus DNA is highly prevalent in the blood of patients with
           asthma and is associated with age and asthma traits
    • Authors: M. L. Kowalski; A. Wardzynska, M. Studzinska, M. Pawelczyk, Z. J. Lesnikowski, E. Paradowska
      Pages: 2035 - 2038
      Abstract: Cytomegalovirus (CMV) IgG antibodies have been associated with inflammaging 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 < .001). Presence of CMV DNA was associated with an increased risk of asthma and CMV DNA copy numbers correlated with some asthma traits, including respiratory parameters and exhaled breath nitric oxide. We conclude that CMV infection is associated with asthma and may contribute to the pathogenesis of asthmatic inflammation.
      PubDate: 2017-07-12T03:45:29.055216-05:
      DOI: 10.1111/all.13233
  • Immediate moxifloxacin hypersensitivity: Is there more than currently
           meets the eye'
    • Authors: A. L. Van Gasse; V. Sabato, A. P. Uyttebroek, J. Elst, M. A. Faber, M. M. Hagendorens, C. Mertens, C. H. Bridts, L. S. De Clerck, D. G. Ebo
      Pages: 2039 - 2043
      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 nine 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 seven of 15 patients. Only two of these seven patients demonstrated appearance of CD63 and release of histamine. In the remainder eight 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.
      PubDate: 2017-07-26T02:30:25.901548-05:
      DOI: 10.1111/all.13236
  • Prevalence of type I sensitization to alpha-gal in forest service
           employees and hunters: Is the blood type an overlooked risk factor in
           epidemiological studies of the α-Gal syndrome'
    • Authors: A. Cabezas-Cruz; J. Fuente, J. Fischer, J. Hebsaker, E. Lupberger, G. Blumenstock, E. Aichinger, A. S. Yazdi, S. Enkel, R. Oehme, T. Biedermann
      Pages: 2044 - 2047
      PubDate: 2017-11-21T00:34:55.135252-05:
      DOI: 10.1111/all.13206
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