for Journals by Title or ISSN
for Articles by Keywords

Publisher: John Wiley and Sons   (Total: 1597 journals)

 A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  Q  R  S  T  U  V  W  X  Y  Z  

        1 2 3 4 5 6 7 8 | Last   [Sort by number of followers]   [Restore default list]

Showing 1 - 200 of 1597 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 13, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 67, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 49, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 55, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 175, 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: 14, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 7, 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: 37, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 5)
Addiction     Hybrid Journal   (Followers: 36, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 15, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 26, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 28, 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: 283, 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: 18, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 14, 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: 11)
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: 17, 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: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 50, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 153, 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: 93, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 30, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 35, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 13, 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: 17, 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: 38, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 302, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 14, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 4, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 19, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 10, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 146, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 20)
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: 176)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 239, 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 Gastroenterological Surgery     Open Access  
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 49, 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: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 26, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 18, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 94, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 54, 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: 74, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 167, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 53, 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: 12, 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: 12, 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: 31, 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: 29, 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: 13, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 273, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 56, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 29, 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: 16)
Asia & the Pacific Policy Studies     Open Access   (Followers: 17)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 329, 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   (Followers: 1, 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: 6, 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: 3, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 30, 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: 46, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 13, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 6, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 6, 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: 15, 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: 443, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 6, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 75, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 23, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 38, 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: 10, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 23, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 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: 18, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 5, 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: 7, 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: 161, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 15, 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: 8, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)

        1 2 3 4 5 6 7 8 | Last   [Sort by number of followers]   [Restore default list]

Journal Cover Allergy
  [SJR: 3.048]   [H-I: 129]   [50 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  [1597 journals]
  • ILC2 frequency and activity are inhibited by glucocorticoid treatment via
           STAT pathway in patients with asthma
    • Authors: Q.N Yu; Y.B Guo, X Li, C.L Li, W.P Tan, X.L Fan, Z.L Qin, D Chen, W.P Wen, S.G Zheng, Q.L Fu
      Abstract: BackgroundGroup 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients.MethodsThe asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signaling pathways were investigated in vitro.ResultsThe patients were well-controlled and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL-5, IL-13 and IL-9 in response to IL-25, IL-33 plus IL-2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL-5, IL-13 and IL-9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signaling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment.ConclusionsThe data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK-STAT signaling pathways. This provides a new understanding of glucocorticoid application in regards to allergic diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-15T00:00:31.045771-05:
      DOI: 10.1111/all.13438
  • The IL-13/periostin/IL-24 pathway causes epidermal barrier dysfunction in
           allergic skin inflammation
    • Authors: Yasutaka Mitamura; Satoshi Nunomura, Yasuhiro Nanri, Masahiro Ogawa, Tomohito Yoshihara, Miho Masuoka, Gaku Tsuji, Takeshi Nakahara, Akiko Hashimoto-Hachiya, Simon J. Conway, Masutaka Furue, Kenji Izuhara
      Abstract: BackgroundBarrier dysfunction is an important feature of atopic dermatitis (AD) in which IL-4 and IL-13, signature type 2 cytokines, are involved. Periostin, a matricellular protein induced by IL-4 or IL-13, plays a crucial role in the onset of allergic skin inflammation, including barrier dysfunction. However, it remains elusive how periostin causes barrier dysfunction downstream of the IL-13 signal.MethodsWe systematically identified periostin-dependent expression profile using DNA microarrays. We then investigated whether IL-24 downregulates filaggrin expression downstream of the IL-13 signals and whether IL-13–induced IL-24 expression and IL-24–induced downregulation of filaggrin expression are dependent on the JAK/STAT pathway. To build on the significance of in vitro findings, we investigated expression of IL-24 and activation of STAT3 in mite-treated mice and in AD patients.ResultsWe identified IL-24 as an IL-13–induced molecule in a periostin-dependent manner. Keratinocytes are the main IL-24–producing tissue-resident cells stimulated by IL-13 in a periostin-dependent manner via STAT6. IL-24 significantly downregulated filaggrin expression via STAT3, contributing to barrier dysfunction downstream of the IL-13/periostin pathway. Wild-type mite-treated mice showed significantly enhanced expression of IL-24 and activation of STAT3 in the epidermis, which disappeared in both STAT6-deficient and periostin-deficient mice, suggesting that these events are downstream of both STAT6 and periostin. Moreover, IL-24 expression was enhanced in the epidermis of skin tissues taken from AD patients.ConclusionsThe IL-13/periostin pathway induces IL-24 production in keratinocytes, playing an important role in barrier dysfunction in AD.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-12T09:36:49.448703-05:
      DOI: 10.1111/all.13437
  • Identification of specifically reduced Th2 cell subsets in allergic
           rhinitis patients after sublingual immunotherapy
    • Authors: Fumie Ihara; Daiju Sakurai, Syuji Yonekura, Tomohisa Iinuma, Ryoji Yagi, Toshioki Sakurai, Toshihiro Ito, Asaka Matsuura, Yuki Morimoto, Tomoyuki Arai, Satoshi Suzuki, Kazufumi Katayama, Toshinori Nakayama, Yoshitaka Okamoto
      Abstract: BackgroundAlthough Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, which Th2 cell subsets are important in house dust mite-induced AR (HDM-AR), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified.MethodsThe cytokine production and frequency of HDM-reactive T cell subsets in peripheral blood mononuclear cells (PBMCs) were evaluated using flow cytometry in 89 HDM-AR patients (placebo (n=43) and HDM 300 IR (n=46)) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. The PBMCs were stained with CellTrace™ Violet (CTV) before culture with HDM extract, and HDM-reactive T cells were detected as the proliferated cells with diminished CTV.ResultsHDM-reactive IL-5+IL-13+CD27−CD161+CD4+ cells and ST2+CD45RO+CD4+ cells were observed in the peripheral blood from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2+CD45RO+CD4+ cells were significantly lower in active-responders.ConclusionAllergen-reactive ST2+CD45RO+CD4+ cells or those combined with IL-5+IL-13+CD27−CD161+CD4+ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-08T10:20:21.07318-05:0
      DOI: 10.1111/all.13436
  • Chronic urticaria can be caused by cancer and resolves with its cure
    • Authors: Désirée Larenas-Linnemann; Sarbjit S. Saini, Amyra Ali Azamar-Jácome, Marcus Maurer
      Abstract: We present 26 cases (ours and 25 from an extended literature review) in which chronic spontaneous urticaria (CSU) seems to be caused by a malignancy (mostly carcinoma or hematologic malignancy): the CSU precedes the neoplasia diagnosis by some months (2-8mo in 80%) and resolved days after chemotherapy/ surgical resection of the malignancy. In three patients, the urticaria flare-up alerted the treating physician of neoplasia recurrence. There could be publication bias, but the narrow time-span between cancer remission and urticaria resolution and especially the recurrence of urticaria that led to detection of cancer relapse in some of our cases are arguments in favor of a causal relationship. Physicians treating CSU should be aware of this. As in all CSU, complete blood count, C reactive protein and erythrocyte sedimentation rate should form part of the initial work-up. As age-indicated screening, over 45 years, a mastography/prostate antigen test should be taken and in recalcitrant, treatment-resistant CSU i.a. a thyroid gland ultrasound could be considered to rule out the most frequently associated malignancies.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-08T10:10:44.481982-05:
      DOI: 10.1111/all.13434
  • Incidence of cephalosporin-induced anaphylaxis and clinical efficacy of
           screening intradermal tests with cephalosporins: a large multicenter
           retrospective cohort study
    • Authors: Min-Suk Yang; Dong-Yoon Kang, Bomi Seo, Hye Jung Park, So-Young Park, Mi-Yeong Kim, Kyung Hee Park, So-My Koo, Young-Hee Nam, Sujeong Kim, Jae-Woo Jung, Tae-Bum Kim, Gwang Cheon Jang, Hyeon-Jong Yang, Young-Min Ahn, Jung-Won Park, Hye-Ryun Kang,
      Abstract: BackgroundFew studies have investigated the incidence of anaphylaxis induced by individual or structurally similar cephalosporins. The aims of the study were to assess the incidence of cephalosporin-induced anaphylaxis and evaluate the clinical efficacy of screening skin tests.MethodsIn this retrospective cohort study, we obtained information on total cephalosporin use and cephalosporin-induced anaphylaxis in intravenous cephalosporin recipients in 12 general hospitals between 2013 and 2015. Cephalosporins were divided into four groups according to similar side-chain structures. The incidence of cephalosporin-induced anaphylaxis was assessed for each cephalosporin, cephalosporin generation and side-chain group. To verify the efficacy of screening intradermal tests (IDT) with cephalosporin, the 12 hospitals were assigned to the intervention or control group depending on whether they performed screening IDT before the administration of cephalosporins.ResultsWe identified 76 cases of cephalosporin-induced anaphylaxis with 1,123,345 exposures to intravenous cephalosporins (6.8 per 100,000 exposures) and the incidence of fatal anaphylaxis by cephalosporin was 0.1 cases per 100,000 exposures. The highest incidences of anaphylaxis occurred in the ceftizoxime (13.0 cases per 100,000 exposures) and side-chain group 1 (cefepime, cefotaxime, ceftizoxime, ceftriaxone and cefuroxime; 9.3 per 100,000). There was no case of anaphylaxis induced by cefoxitin, cefmetazole, cefminox and cefotiam. The clinical effectiveness of routine screening IDT was not significant (p = 0.06).ConclusionsThe incidence of cephalosporin-induced anaphylaxis differed according to individual drugs and side-chain structure. Although screening IDT showed no clinical efficacy in general, it may be useful for certain cephalosporins.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-08T10:10:21.27671-05:0
      DOI: 10.1111/all.13435
  • Short-course of grass allergen peptides immunotherapy over three weeks
           reduces seasonal symptoms in allergic rhinoconjunctivitis with/without
    • Authors: Ralph Mösges; Claus Bachert, Petr Panzner, Moises A. Calderon, Ludo Haazen, Sabine Pirotton, Nathalie Wathelet, Stephen R Durham, Marie-Alix Bonny, Thierry Legon, Remy von Frenckell, Oliver Pfaar, Mohamed H Shamji
      Abstract: BackgroundImmunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 μg LPP administered subcutaneously over 3 weeks.MethodsIn a randomized, double blind, placebo-controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 μg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) were assessed as secondary endpoints.ResultsThe mean reduction in CSMS in the LPP vs. placebo group was −15.5% (p=0.041) during the peak period and −17.9% (p= 0.029) over the entire pollen season. LPP treated group had a reduced reactivity to CPT (p
      PubDate: 2018-03-07T07:50:27.534161-05:
      DOI: 10.1111/all.13433
  • Higher mortality of adults with asthma: a 15 year follow-up of
           apopulation-based cohort
    • Authors: Riikka E. Lemmetyinen; Jussi V. Karjalainen, Anna But, Risto L.O. Renkonen, Juha R. Pekkanen, Sanna K. Toppila-Salmi, Jari K. Haukka
      Abstract: BackgroundHigher all-cause mortality in asthmatics has been shown previously. Polysensitization is associated with higher morbidity among asthmatic children, and allergic rhinitis and/or allergic conjunctivitis (AR/AC) is associated with higher morbidity in adult asthmatics. Little is known about the effect of AR/AC and other factors on mortality among adult asthmatics. The aim was to study mortality and its risk factors in adults with and without asthma.MethodsWe randomly selected 1648 asthmatics with age over 30 years from national registers and matched the asthma sample with one or two controls. Baseline information was obtained by a questionnaire in 1997, and the study population was linked with the death certificate information of Statistics Finland from 1997 to 2013. Overall and cause-specific survival between the groups was compared in several adjusted models.ResultsDuring a mean follow-up period of 15.6 years, 221 deaths among 1052 asthma patients and 335 deaths among 1889 non-asthmatics were observed. Cardiovascular diseases were the main cause of death in both groups. Asthma was associated with increased all-cause mortality (adjusted HR 1.25; 95% CI 1.05-1.49, P=0.011); as well as mortality from chronic obstructive pulmonary disease (HR 12.0, 4.18–34.2, P
      PubDate: 2018-02-20T08:55:22.300433-05:
      DOI: 10.1111/all.13431
  • Angioedema in Chronic Spontaneous Urticaria Is Underdiagnosed and Has a
           Substantial Impact: Analyses From ASSURE-CSU
    • Authors: Gordon Sussman; Mohamed Abuzakouk, Frédéric Bérard, Walter Canonica, Hanneke Oude Elberink, Ana Giménez-Arnau, Clive Grattan, Kelly Hollis, Shannon Hunter, André Knulst, Jean-Philippe Lacour, Charles Lynde, Alexander Marsland, Doreen McBride, Marcus Maurer, Alla Nakonechna, Javier Ortiz de Frutos, Maria Reynolds, Carolyn Sweeney, Haijun Tian, Karsten Weller, Daniel Wolin, Maria-Magdalena Balp
      Abstract: BackgroundASSURE-CSU revealed differences in physician and patient reporting of angioedema. This post-hoc analysis was conducted to evaluate the actual rate of angioedema in the study population and explore differences between patients with and without angioedema.MethodsThis international observational study assessed 673 patients with inadequately controlled chronic spontaneous urticaria (CSU). Physicians abstracted angioedema data from medical records, which were compared with patient-reported data. Patients in the Yes-angioedema category had angioedema reported in the medical record and a patient-reported source. For those in the No-angioedema category, angioedema was reported in neither the medical record nor a patient-reported source. Those in the Misaligned category had angioedema reported in only one source. Statistical comparisons between Yes-angioedema and No-angioedema categories were conducted for measures of CSU activity, health-related quality of life (HRQoL), productivity, and healthcare resource utilisation (HCRU). Regression analyses explored the relationship between Dermatology Life Quality Index (DLQI) score and angioedema, adjusting for important covariates.ResultsAmong evaluable patients, 259 (40.3%), 173 (26.9%), and 211 (32.8%) were in the Yes-angioedema, No-angioedema, and Misaligned category, respectively. CSU activity and impact on HRQoL, productivity, and HCRU were greater for Yes-angioedema patients than No-angioedema patients. After covariate adjustment, mean DLQI score was significantly higher (indicating worse HRQoL) for patients with angioedema versus no angioedema (9.88 vs. 7.27, P 
      PubDate: 2018-02-20T07:50:39.636496-05:
      DOI: 10.1111/all.13430
  • Association of stat6 gene variants with food allergy diagnosed by
           double-blind placebo-controlled food challenges
    • Authors: C.D. van Ginkel; M.E. Pettersson, A.E.J. Dubois, G.H. Koppelman
      Abstract: This study describes the role of two STAT6 gene variants in food allergy using data of patients and their parents who underwent double-blind placebo-controlled food challenges (DBPCFCs). After quality control, 369 trios were analyzed including 262 children (71.0%) with food allergy. Associations were tested by family based association testing (FBAT). The A alleles of both SNPs were associated with food allergy (p=0.036 and p=0.013 for rs324015 and rs1059513, respectively). Furthermore, these A alleles were associated with peanut allergy, higher sIgE levels to both peanut and cow's milk, more severe symptoms and higher eliciting doses during peanut and cow's milk DBPCFCs (all p
      PubDate: 2018-02-19T02:47:39.315836-05:
      DOI: 10.1111/all.13432
  • Clinical trials in allergen immunotherapy: current concepts and future
    • Authors: O. Pfaar; M. Alvaro, V. Cardona, E. Hamelmann, R. Mösges, J. Kleine-Tebbe
      Abstract: Allergen immunotherapy (AIT) is a safe, effective treatment for allergic rhinoconjunctivitis and allergic asthma. However, AIT's clinical effect is still contested - primarily due to heterogeneity in clinical trial designs, study populations, therapeutic formulations and efficacy criteria. After discussing current concepts and unmet needs, an international panel of experts made several recommendations: (i) explore and validate definitions for [clinical] responders in AIT-trials; (ii) use of well-documented, standardized provocation tests prior to inclusion of subjects with relevant diseases in AIT trials; (iii) monitoring neo-sensitizations and occurrence of new allergy in extended AIT trials, and exclusion of polyallergic participants; (iv) validation of allergen exposure chambers with regard to natural exposure; (v) in studies of seasonal allergies, focus on peak exposure but also consider organising two parallel, geographically distinct but otherwise identical trials; (vi) discuss adaptive trial designs with the regulatory authorities; (vii) use e-health and m-health technologies to capture more information on individual exposure to allergens; (viii) initiate research on potential psychological, biochemical, immune, neural and even genomic markers of the placebo response; (ix) identify trial designs and primary endpoints that will give children with allergies easier, faster access to AIT formulations; and (x) promote and apply standardized methods for reporting systemic and local adverse events. The latest technologies and trial designs may provide novel, ethical ways of reducing bias and heterogeneity in AIT clinical trials. There is scope for physicians, patient organizations, companies and regulators to improve clinical trials in AIT and, ultimately, to provide patients with better treatments.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-15T08:25:23.909756-05:
      DOI: 10.1111/all.13429
  • Chitotriosidase inhibits allergic asthmatic airways via regulation of
           TGF-β expression and Foxp3+ Treg cells
    • Authors: Jung Yeon Hong; Mina Kim, In Suk Sol, Kyung Won Kim, Chang-Min Lee, Jack A. Elias, Myung Hyun Sohn, Chun Geun Lee
      Abstract: BackgroundChitotriosidase (Chitnase 1, Chit1), a major true chitinase in humans, is induced in childhood asthma and has been implicated in the pathogenesis of a variety of inflammatory and tissue remodeling responses. We hypothesized that Chit1 plays a significant role in the pathogenesis of allergic asthma. To identify the role of Chit1, the mechanisms that underlie these contributions and the relevance of these murine findings to childhood asthma.MethodsWild type and Chit1-deficient mice and cells in culture were used to define the roles of Chit1 in models of allergic adaptive Th2 inflammation. In addition, the levels of sputum Chit1 were evaluated in pediatric asthma patients and compared to control.ResultsThe levels of sputum Chit1 were significantly increased in the patients with childhood asthma. Mice with Chit1 null mutation demonstrated enhanced allergic Th2 inflammatory and cytokine and IgE responses to OVA or house dust mite allergen sensitization and challenge. However, the expression levels of TGF-β1 were significantly decreased with a diminished number of Foxp3+ regulatory T cells (Treg) in the lungs of Chit1-/- mice compared to WT controls. In vitro, the absence of Chit1 significantly reduced TGF-β-stimulated conversion of CD4+CD25- naïve T cells to CD4+Foxp3+ Treg cells, suggesting Chit1 is required for optimal effect of TGF-β1 in Treg cell differentiation.ConclusionChit1 plays a protective role in the pathogenesis of allergic inflammation and asthmatic airway responses via regulation of TGF-β expression and Foxp3+ Treg cells.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-08T14:51:05.628726-05:
      DOI: 10.1111/all.13426
  • Role of IL-13Rα2 in modulating IL-13 induced MUC5AC and ciliary changes
           in healthy and CRSwNP mucosa
    • Authors: Jing Liu; YingYing Li, Anand Kumar Andiappan, Yan Yan, Tan Kai Sen, Hsiao Hui Ong, Kim Thye Thong, Yew Kwang Ong, Feng Gang Yu, Heng Boon Low, Yong Liang Zhang, Li Shi, De Yun Wang
      Abstract: BackgroundThe IL-13 receptor α2 (IL-13Rα2) is a receptor for IL-13 which has conflicting roles in mediating IL-13 responses in the lower airway; with little known about its impact on upper airway diseases. We sought to investigate the expression of IL-13 receptors, IL-13Rα1 and IL-13Rα2, in chronically inflamed nasal epithelium, and explore IL-13 induced signaling pathways in an in vitro model of human nasal epithelial cells (hNECs).MethodsThe protein and mRNA expression levels of IL-13 and its receptors in nasal biopsies of patients with nasal polyps (NP) and healthy controls were evaluated. We investigated goblet cell stimulation with mucus hypersecretion induced by IL-13 (10 ng/mL, 72 hours) treatment in hNECs using a pseudo-stratified epithelium in air-liquid interface (ALI) culture.ResultsThere were significant increases in IL-13, IL-13Rα1 and IL-13Rα2 mRNA and protein levels in NP epithelium with healthy controls as baseline. MUC5AC mRNA positively correlated with IL-13Rα2 (r=0.5886, p=0.002) but not with IL-13Rα1 in primary hNECs. IL-13 treatment resulted in a significant increase in mRNA and protein levels of IL-13Rα2 only in hNECs.. IL-13 treatment induced an activation of extracellular signal-regulated kinases (ERK)1/2 and an upregulation of C-JUN; where the IL-13 induced effects on hNECs could be attenuated by ERK1/2 inhibitor (50 μMol/L) or dexamethasone (10-4-10-7 Mol/L) treatment.ConclusionsIL-13Rα2 has a potential role in IL-13 induced MUC5AC and ciliary changes through ERK1/2 signal pathway in the nasal epithelium. IL-13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-06T06:35:50.826527-05:
      DOI: 10.1111/all.13424
  • Development and Validation of the Mastocytosis Activity Score: MAS
    • Authors: Frank Siebenhaar; Benno Sander, Huyen Tram, André Ellrich, Marcus Maurer, Karsten Weller
      Abstract: BackgroundMastocytosis is a heterogeneous disease characterized by a clonal expansion of mast cells in various organs. The vast majority of patients suffer from signs and symptoms caused by mediator release from mast cells. Although the disease burden is high, there is currently no specific and validated instrument to measure and monitor signs and symptoms in patients with mastocytosis.ObjectiveTo develop and validate a disease-specific tool to measure and monitor the activity of signs and symptoms in patients with mastocytosis, the Mastocytosis Activity Score (MAS).MethodsNineteen potential MAS items were developed in a combined approach consisting of semi-structured patient interviews, expert input, and literature research. Item selection was performed by impact analysis with 76 patients followed by a review for face validity. The resulting MAS was tested for validity, reliability and influence factors. In parallel, a US American-English version of the MAS was developed.Results68 mastocytosis patients took part in the MAS validation study. The final 9-item MAS was found to have a three-domain structure (‘skin’, ‘gastrointestinal tract’, ‘other’), a valid total score and an excellent test-retest-reliability. Multiple regression analysis revealed that disease duration, age, or gender are no significant determinant of the MAS results.ConclusionsThe MAS is a disease-specific, valid and reliable patient reported outcome measure for adult patients with cutaneous and indolent systemic mastocytosis. It may serve as a valuable tool to measure and monitor mastocytosis activity, both, in clinical trials and in routine care.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-06T01:41:55.249001-05:
      DOI: 10.1111/all.13425
  • Asthma and IgE associated polymorphisms affect expression of TH17 genes
    • Authors: Luise Worth; Sven Michel, Vincent D. Gaertner, Michael Kabesch, Maximilian Schieck
      Abstract: TH17 cells contribute to the pathogenesis of chronic inflammatory diseases such as asthma and TH17 pathway tagging SNPs were associated with asthma and total serum IgE levels in childhood. In this study genotype-specific effects of these SNPs on the expression of TH17 related molecules were analyzed in peripheral blood mononuclear cells (PBMCs) before and after allergen stimulation in 61 individuals. After correction for multiple testing, protein or mRNA expression levels of several molecules, including IL-17A, IL17-F, IL-23 and IL-23 receptor, were significantly correlated with asthma-associated SNPs (located in IL17F, IL22, IL23R and IL23A) and IgE-associated polymorphisms (located in IL17A and three SNPs in IL12B). Most extensive effects on TH17 pathway expression were observed for the asthma-associated polymorphism IL17F rs7741835. In conclusion, genetic variants in IL17F and, to a smaller degree, IL17A and IL-23 signaling genes associated with asthma and IgE levels seem functional in influencing expression of TH17 related molecules, indicating a contribution of these mechanisms to genetic susceptibility towards asthma and atopy.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-30T06:56:14.868246-05:
      DOI: 10.1111/all.13422
  • IgE-expressing memory B cells and plasmablasts are increased in blood of
           children with asthma, food allergy and atopic dermatitis
    • Authors: J. J Heeringa; L. Rijvers, N. J Arends, G. J Driessen, S. G. Pasmans, J. J. M. van Dongen, J. C. de Jongste, M. C. van Zelm
      Abstract: Despite the critical role of soluble IgE in the pathology of IgE-mediated allergic disease, little is known about abnormalities in the memory B-cells and plasma cells that produce IgE in allergic patients. We here applied a flowcytometric approach to cross-sectionally study blood IgE+ memory B-cells and plasmablasts in 149 children with atopic dermatitis, food allergy and/or asthma, and correlated these to helper-T(h)2 cells and eosinophils. Children with allergic disease had increased numbers of IgE+CD27- and IgE+CD27+ memory B-cells and IgE+ plasmablasts, as well as increased numbers of eosinophils and Th2 cells. IgE+ plasmablast numbers correlated positively with Th2 cell numbers. These findings open new possibilities for diagnosis and monitoring of treatment in patients with allergic diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-30T06:52:23.153513-05:
      DOI: 10.1111/all.13421
  • EAACI Guidelines on Allergen Immunotherapy: Executive Statement
    • Authors: A Muraro; G Roberts, S Halken, A Agache, L Angier, M Fernandez–Rivas, R Gerth van Wijk, M Jutel, S Lau, G Pajno, O Pfaar, D Ryan, G J Sturm, R van Ree, E-M Varga, C Bachert, M Calderon, G W Canonica, S R Durham, H J Malling, U Wahn, A Sheikh
      Abstract: The allergist's community has recently celebrated 100 year of Allergen Immunotherapy (AIT). Unfortunately the implemention of this treatment is still impaired by some challenges. With the diversity of definitions, methodology and different allergen products used, research studies have produced conflicting outcomes. This has resulted in confusion about the benefits and risks of AIT amongst policymakers and professionals, as well as in the variable availability of AIT products, regulation and reimbursement policies globally. In 2015 EAACI initiated the AIT Guidelines project as part of the Presidential plan in order to settle the controversies.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-30T03:15:41.302681-05:
      DOI: 10.1111/all.13420
  • Prediction of the severity of allergic reactions to foods
    • Authors: M. Eleonore Pettersson; Gerard H. Koppelman, Bertine MJ. Flokstra-de Blok, Boudewijn J. Kollen, Anthony EJ. Dubois
      Abstract: BackgroundThere is currently considerable uncertainty regarding what the predictors of the severity of diagnostic or accidental food allergic reactions are, and to what extent the severity of such reactions can be predicted.ObjectiveTo identify predictors for the severity of diagnostic and accidental food allergic reactions and to quantify their impact.MethodsThe study population consisted of children with a double-blind, placebo-controlled food challenge (DBPCFC) confirmed food allergy to milk, egg, peanut, cashew nut and/or hazelnut. The data was analyzed using multiple linear regression analysis. Missing values were imputed using multiple imputation techniques. Two scoring systems were used to determine the severity of the reactions.Results734 children were included. Independent predictors for the severity of the DBPCFC reaction were: age (B=0.04, p=0.001), skin prick test ratio (B=0.30, p
      PubDate: 2018-01-30T03:11:17.586192-05:
      DOI: 10.1111/all.13423
  • Position Paper on the Standardization of Nasal Allergen Challenges
    • Authors: J Augé; J Vent, I Agache, L Airaksinen, P Campo Mozo, A Chaker, C Cingi, S R Durham, W J Fokkens, P Gevaert, A I Giotakis, P Hellings, M Herknerova, V Hox, L Klimek, C La Melia, J Mullol, N B Muluk, A Muraro, K Naito, O Pfaar, H Riechelmann, C Rondon, M Rudenko, B Samolinski, I Tasca, P V Tomazic, K Vogt, M Wagenmann, G Yeryomenko, L Zhang, R Mösges
      Abstract: Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution, however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge.On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice.Besides an update on indications, contraindications and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 ml per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure.The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-27T05:05:19.847237-05:
      DOI: 10.1111/all.13416
  • A novel glycocluster molecule prevents timothy induced allergic airway
           inflammation in mice
    • Authors: Maili Lehto; Henrik Wolff, Reko Leino, Harri Alenius, Johannes Savolainen
      Abstract: BackgroundAllergen specific immunotherapy (SIT) effectively alleviates type I allergic diseases characterized by T helper (Th) 2-type immunity. Our recent studies have shown that a synthetic trivalent glycocluster, triacedimannose (TADM), suppresses the Th2-type allergic inflammation. The aim of this study was to compare TADM with two well-known adjuvants, unmethylated cytocine-phosphate-guanine oligodeoxynucleotide (CpG) and monophosphoryl lipid A (MPLA) in a grass allergen induced chronic allergic inflammation model in mice.MethodsFemale BALB/c mice were intranasally sensitized with 50 μl of timothy grass pollen extract (TE) twice a week for a period of 15 weeks. Therapeutic intranasal treatments were then performed once a week after the tenth intranasal TE instillation using TADM (10 or 25μg/50 μl), CpG-ODN (20μg/50 μl) or MPLA (2μg/50μl). Groups of 9-10 animals per treatment were sacrificed 24 h after the last timothy dosage. Blood, bronchoalveolar lavage (BAL) fluids and lung biopsies were taken for subsequent analysis.ResultsWhen mice were repeatedly exposed to TE for 15 weeks, the number of eosinophils and lymphocytes increased in the BAL fluids. The eosinophil and lymphocyte counts decreased dose-dependently, and were practically abolished in the mice treated with TADM. Treatments with MPLA or CpG significantly increased the numbers of neutrophils, while CpG nonsignificantly decreased eosinophilia compared to timothy exposure.ConclusionsA novel synthetic glycocluster molecule inhibited the development of grass induced eosinophilic pulmonary inflammation in mice when administrated in the airways. This compound could be a candidate to be used either as an adjuvant in SIT or as a topical anti-inflammatory treatment.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-26T09:08:07.293318-05:
      DOI: 10.1111/all.13419
  • Identification of T-cell epitopes from benzylpenicillin conjugated to
           human serum albumin and implication in penicillin allergy
    • Authors: Marie Eliane Azoury; Lucia Filì, Rami Bechara, Noémie Scornet, Luc de Chaisemartin, Richard J. Weaver, Nancy Claude, Bernard Maillere, Paola Parronchi, Delphine Joseph, Marc Pallardy
      Abstract: BackgroundThere is in vitro evidence that T-cells from allergic patients react to benzylpenicillin-human serum albumin (BP-HSA) bioconjugates. Our group has recently shown the existence of naïve CD4+ T lymphocytes recognizing BP-HSA in healthy donors. However, BP-haptenated peptides from HSA participating in the immunization of allergic patients have never been identified. The purpose of the present study is to identify immunodominant BP-haptenated peptides from HSA involved in immunization of patients to BP and to refine the frequency calculation of naïve CD4+ T-cells recognizing BP.MethodsCo-cultures were established with CD4+ T-cell from non-allergic donors and mature autologous dendritic cells (DCs) loaded with BP-HSA or BP-haptenated peptides from HSA. The CD4+ T-cell response specific for BP-HSA or for individual BP-haptenated peptides was measured using an interferon-γ (IFN-γ) ELISpot assay. Frequency of BP-specific CD4+ T-cell was then calculated using the Poisson distribution. BP-HSA and BP-haptenated peptides recognition by allergic patients was evaluated on peripheral blood mononuclear cells (PBMCs) using a lymphocyte transformation test (LTT).ResultsResults showed that BP-HSA and BP-haptenated peptides were recognized by naïve T-cells from 15/16 and 13/14 tested healthy donors respectively. Most donors responded to 3 peptides with BP covalently bound on lysines 159, 212 and 525. Two of these benzylpenicilloylated peptides (lysines 159 and 525) were also found to induce PBMCs proliferation in patients with allergic reaction to penicillins.ConclusionThis study identifies and characterizes for the first time the BP-haptenated peptides from HSA involved in the immunization of patients to penicillins.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-22T09:35:26.731026-05:
      DOI: 10.1111/all.13418
  • Molecular allergen profiling in horses by microarray reveals Fag e 2 from
           buckwheat as a frequent sensitizer
    • Authors: L Einhorn; G Hofstetter, S Brandt, E K Hainisch, I Fukuda, K Kusano, A Scheynius, I Mittermann, Y Resch-Marat, S Vrtala, R Valenta, E Marti, C Rhyner, R Crameri, R Satoh, R Teshima, A Tanaka, H Sato, H Matsuda, I Pali-Schöll, E Jensen-Jarolim
      Abstract: BackgroundCompanion animals are also affected by IgE-mediated allergies, but the eliciting molecules are largely unknown. We aimed at refining an allergen microarray to explore sensitization in horses and compare it to the human IgE reactivity profiles.MethodsCustom-designed allergen microarray was produced on the basis of the IimmunoCAP ISAC technology containing 131 allergens. Sera from 51 horses derived from Europe or Japan were tested for specific IgE reactivity. The included horse patients were diagnosed for eczema due to insect bite hypersensitivity, chronic coughing, recurrent airway obstruction, urticaria, or were clinically asymptomatic.ResultsHorses showed individual IgE binding patterns irrespective of their health status, indicating sensitization. In contrast to European and Japanese human sensitization patterns, frequently recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass, likely due to specific respiratory exposure around paddocks and near the ground. The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S-albumin Fag e 2 from buckwheat, which recently gained importance not only in human but also in horse diet.ConclusionIn line with the One Health concept, covering human health, animal health and environmental health, allergen microarrays provide novel information on the allergen sensitization patterns of the companion animals around us, which may form a basis for allergen-specific preventive and therapeutic concepts.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-19T09:25:27.934347-05:
      DOI: 10.1111/all.13417
  • Sputum cytology during late phase responses to inhalation challenge with
           different allergens
    • Authors: Joana A. Revez; Kieran J. Killian, Paul M. O'Byrne, Louis-Philippe Boulet, John W Upham, Gail M. Gauvreau, Manuel A.R. Ferreira
      Abstract: BackgroundIn mouse models of allergic asthma, exposure to different allergens can trigger distinct inflammatory subtypes in the airways. We investigated if this observation extends to humans.MethodsWe compared the frequency of sputum inflammatory subtypes between mild allergic asthma subjects (n=129) exposed to different allergens in inhalation challenge tests. These tests were performed using a standardized protocol as part of clinical trials of experimental treatments for asthma, prior to drug randomization. Five allergen types were represented: the house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, ragweed, grass and cat.ResultsOf 118 individuals with a sputum sample collected before allergen challenge (baseline), 45 (38%) had paucigranulocytic, 51 (43%) eosinophilic, 11 (9%) neutrophilic and 11 (9%) mixed granulocytic sputum. Of note, most individuals with baseline paucigranulocytic sputum developed eosinophilic (48%) or mixed granulocytic (43%) sputum seven hours after allergen challenge, highlighting the dynamic nature of sputum inflammatory subtype in asthma. Overall, there was no difference in the frequency of sputum inflammatory subtypes following challenge with different allergen types. Similar results were observed at 24 hours after allergen challenge.ConclusionsUnlike reported in mice, in humans the sputum inflammatory subtype observed after an allergen-induced asthma exacerbation is unlikely to be influenced by the type of allergen used.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-16T08:55:19.862615-05:
      DOI: 10.1111/all.13415
  • Executive summary: Methods and evidence report for the evidence – and
           consensus- based (S3) Guideline for the definition, classification,
           diagnosis, and management of urticaria – revision and update 2017
    • Authors: C Dressler; S Rosumeck, R N Werner, M Magerl, M Metz, M Maurer, A Nast, T Zuberbier
      Abstract: For the revision and update of the EAACI/GA²LEN/EDF/WAO guideline on urticaria we defined and followed a structured process as recommended by national and international guideline development manuals (1) and took the Appraisal of Guidelines Research and Evaluation (AGREE II) Instrument (2) into account. The full methods report can be found in the online appendix [please add link].This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-16T05:45:26.576128-05:
      DOI: 10.1111/all.13414
  • Treatment of allergic rhinitis using mobile technology with real world
           data: The MASK observational pilot study
    • Authors: J Bousquet; S Arnavielhe, A Bedbrook, G Alexis-Alexandre, M van Eerd, R Murray, G W Canonica, M Illario, E Menditto, G Passalacqua, C Stellato, M Triggiani, P Carreiro-Martins, J Fonseca, M Morais Almeida, L Nogueira-Silva, A M Pereira, A Todo Bom, I Bosse, D Caimmi, P Demoly, P Devillier, J F Fontaine, J Just, G L Onorato, M L Kowalski, P Kuna, B Samolinski, J M Anto, J Mullol, A Valero, P V Tomazic, K C Bergmann, T Keil, L Klimek, R Mösgues, S Shamai, T Zuberbier, E Murphy, Peter McDowall, D Price, D Ryan, A Sheikh, N H Chavannes, W J Fokkens, V Kvedariene, A Valiulis, C Bachert, P W Hellings, I Kull, E Melén, M Wickman, C Bindslev-Jensen, E Eller, T Haahtela, E Valovirta, N G Papadopoulos, I Annesi-Maesano, M Bewick, S Bosnic-Anticevich, A A Cruz, G De Vries, B Gemicioglu, D Larenas-Linnemann, D Laune, E Mathieu-Dupas, R E O'Hehir, F Portejoie, V Siroux, O Spranger, O VandenPlas, A Yorgancioglu
      Abstract: BackgroundLarge observational implementation studies are needed to triangulate the findings from randomized control trials (RCTs) as they reflect “real world” everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real life treatment of allergic rhinitis using mobile technology.MethodsA mobile phone app (Allergy Diary, freely available Google Play and Apple App stores) collects the data of daily visual analogue scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries.ResultsA total of 2,871 users filled in 17,091 days of VAS in 2015 and 2016. Medications were reported for 9,634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single or multiple treatments (worst control).ConclusionsThe present study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in allergic rhinitis. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings and generates new hypotheses.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-15T23:45:25.235252-05:
      DOI: 10.1111/all.13406
  • The EAACI/GA²LEN/EDF/WAO Guideline for the Definition, Classification,
           Diagnosis and Management of Urticaria. The 2017 Revision and Update
    • Authors: T. Zuberbier; W. Aberer, R. Asero, A.H. Abdul Latiff, D. Baker, B. Ballmer-Weber, J.A. Bernstein, C. Bindslev-Jensen, Z. Brzoza, R. Buense Bedrikow, G.W. Canonica, M.K. Church, T. Craig, I.V. Danilycheva, C. Dressler, L.F. Ensina, A. Giménez-Arnau, K. Godse, M. Gonçalo, C. Grattan, J. Hebert, M. Hide, A. Kaplan, A. Kapp, C.H. Katelaris, E. Kocatürk, K. Kulthanan, D. Larenas-Linnemann, T.A. Leslie, M. Magerl, P. Mathelier-Fusade, R.Y. Meshkova, M. Metz, A. Nast, E. Nettis, H. Oude-Elberink, S. Rosumeck, S.S. Saini, M. Sánchez-Borges, P. Schmid-Grendelmeier, P. Staubach, G. Sussman, E. Toubi, G.A. Vena, C. Vestergaard, B. Wedi, R.N. Werner, Z. Zhao, M. Maurer
      Abstract: This evidence and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on December 1st, 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life, and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-15T23:40:34.992031-05:
      DOI: 10.1111/all.13397
  • Outdoor pollen is a trigger of child and adolescent asthma ED
           presentations: a systematic review and meta-analysis
    • Authors: Bircan Erbas; Mitra Jazayeri, Katrina A Lambert, Constance H Katelaris, Luke A Prendergast, Rachel Tham, M Jeannette Parrodi, Janet Davies, Ed Newbigin, Michael J Abramson, Shyamali C Dharmage
      Abstract: BackgroundIn the context of increased asthma exacerbations associated with climatic changes such as thunderstorm asthma, interest in establishing the link between pollen exposure and asthma hospital admissions has intensified. Here, we systematically reviewed and performed a meta-analysis of studies on pollen and ED attendance.MethodsA search for studies with appropriate search strategy in Medline, Embase, Web of Science and CINAHL was conducted. Each study was assessed for quality and risk of bias. The available evidence was summarised both qualitatively and meta-analysed using random effects models when moderate heterogeneity was observed.ResultsFourteen studies were included. The pollen taxa investigated differed between studies, allowing meta-analysis only of the effect of grass pollen. A statistically significant increase in the percentage change in the mean number of asthma ED presentations (MPC) (pooled results from three studies) was observed for an increase in 10 grass pollen grains per cubic meter of exposure 1.88% (95%CI = 0.94%, 2.82%). Time series studies showed positive correlations between pollen concentrations and ED presentations. Age stratified studies found strongest associations in children aged 5 to 17 years old.ConclusionExposure to ambient grass pollen is an important trigger for childhood asthma exacerbations requiring ED attendance. As pollen exposure is increasingly a problem especially in relation to thunderstorm asthma, studies with uniform measures of pollen and similar analytical methods are necessary to fully understand its impact on human health.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-13T09:50:22.24738-05:0
      DOI: 10.1111/all.13407
  • How does dose impact on the severity of food-induced allergic reactions,
           and can this improve risk assessment for allergenic foods'
    • Authors: Anthony E.J. Dubois; Paul J. Turner, Jonathan Hourihane, Barbara Ballmer-Weber, Kirsten Beyer, Chan Chun-Han, M. Hazel Gowland, Sue O'Hagan, Lynne Regent, Ben Remington, Sabine Schnadt, Thomas Stroheker, René W.R. Crevel
      Abstract: Quantitative risk assessment for food allergens has made considerable progress in recent years, yet acceptability of its outcomes remains stymied because of the limited extent to which it has been possible to incorporate severity as a variable. Reaction severity, particularly following accidental exposure, depends on multiple factors, related to the allergen, the host and any treatments which might be administered. Some of these factors are plausibly still unknown. Quantitative risk assessment shows that limiting exposure through control of dose reduces the rates of reactions in allergic populations, but its impact on the relative frequency of severe reactions at different doses is unclear. Food challenge studies suggest that the relationship between dose of allergenic food and reaction severity is complex even under relatively controlled conditions. Because of these complexities, epidemiological studies provide very limited insight into this aspect of the dose-response relationship. Emerging data from single-dose challenges suggest that graded food challenges may overestimate the rate of severe reactions. It may be necessary to generate new data (such as those from single dose-challenges) to reliably identify the effect of dose on severity for use in quantitative risk assessment. Success will reduce uncertainty in the susceptible population and improve consumer choice.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-13T09:50:20.066279-05:
      DOI: 10.1111/all.13405
  • Characterization of CD34+ hematopoietic cells in systemic mastocytosis:
           potential role in disease dissemination
    • Authors: Andrea Mayado; Cristina Teodosio, Noelia Dasilva Freire, Maria Jara-Acevedo, Andrés C Garcia-Montero, Ivan Álvarez-Twose, Laura Sánchez-Muñoz, Almudena Matito, Carolina Caldas, Javier I Muñoz-González, Ana Henriques, José I Sánchez-Gallego, Luis Escribano, Alberto Orfao
      Abstract: BackgroundRecent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KIT D816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KIT D816V mutation and the distribution of different maturation-associated compartments of bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic precursors (HPC) in ISM, and identified the specific PB cell compartments that carry this mutation.MethodsThe distribution of different maturation-associated subsets of BM and PB CD34+ HPC from 64 newly-diagnosed (KIT-mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients distinct FACS-purified PB cell compartments were also investigated for the KIT mutation.ResultsISM patients showed higher percentages of both BM and PB MC-committed CD34+ HPC vs. controls, particularly among ISM cases with MC-restricted KIT mutation (ISMMC); this was associated with progressive blockade of maturation of CD34+ HPC to the neutrophil lineage from ISMMC to multilineage KIT-mutated cases (ISMML). Regarding the frequency of KIT-mutated cases and cell populations in PB, variable patterns were observed, the percentage of KIT-mutated PB CD34+ HPC, eosinophils, neutrophils, monocytes and T-cells increasing from ISMs-MC and ISMs+MC to ISMML patients.ConclusionThe presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34+ HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34+ HPC potentially contributing to early dissemination of the disease.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-13T06:15:28.430952-05:
      DOI: 10.1111/all.13413
  • Multidimensional endotypes of chronic rhinosinusitis and their association
           with treatment outcomes
    • Authors: Bo Liao; Jin-Xin Liu, Zhi-Yong Li, Zhen Zhen, Ping-Ping Cao, Yin Yao, Xiao-Bo Long, Heng Wang, Yan Wang, Robert Schleimer, Zheng Liu
      Abstract: BackgroundThe expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes.MethodsA total of 28 clinical variables and 39 mucosal cellular and molecular variables were analyzed using principal component analysis. Cluster analysis was performed on 246 prospectively recruited Chinese CRS patients with at least one-year post-operative follow-up. Difficult-to-treat CRS was characterized in each generated cluster.ResultsSeven subject clusters were identified. Cluster 1 (13.01%) was comparable to the classic well-defined eosinophilic CRS with polyps, having severe disease and the highest proportion of difficult-to-treat CRS. Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively lower proportions of presence of polyps and presented mild inflammation with moderate proportions of difficult-to-treat cases. Subjects in cluster 2 were highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by severe or moderate neutrophilic inflammation, respectively, and with elevated levels of IL-8 and high proportions of difficult-to-treat CRS. Cluster 5 (4.07%) was a unique group characterized by the highest levels of IL-10 and lacked difficult-to-treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom severity, a low proportion of difficult-to-treat CRS, and low inflammation load. Finally, we found that difficult-to-treat CRS was associated with distinct clinical features and biomarkers in the different clusters.ConclusionsDistinct clinicopathobiologic clusters of CRS display differences in clinical response to treatments and characteristics of difficult-to-treat CRS.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-13T06:15:21.670021-05:
      DOI: 10.1111/all.13411
  • The asthma-rhinitis multimorbidity is associated with IgE
           polysensitization in adolescents and adults
    • Authors: Valérie Siroux; Natalia Ballardini, Marion Soler, Christian Lupinek, Anne Boudier, Isabelle Pin, Jocelyne Just, Rachel Nadif, Josep M Anto, Erik Melen, Rudolf Valenta, Magnus Wickman, Jean Bousquet
      Abstract: BackgroundChildren with multimorbid asthma and rhinitis show IgE polysensitization to several allergen sources. This association remain poorly studied in adolescents and adults using defined allergen molecules. We investigated IgE sensitization patterns towards a broad panel of aeroallergen components in adults and adolescents with a focus on individuals with asthma and rhinitis multimorbidity.MethodsIgE reactivity to 64 microarrayed aeroallergen molecules was determined with the MeDALL-chip in samples from the French EGEA study (n=840, age=40.7±17.1) and the Swedish population-based birth cohort BAMSE (n=786, age=16±0.26). The age- and sex-adjusted associations between the number of IgE-reactive allergen molecules (≥0.3 ISU) and the asthma-rhinitis phenotypes were assessed using a negative binomial model.ResultsGroups representing four phenotypes were identified: no asthma-no rhinitis (A-R-; 30% in EGEA and 54% in BAMSE), asthma alone (A+R-; 11% and 8%), rhinitis alone (A-R+; 15% and 24%), and asthma-rhinitis (A+R+; 44% and 14%). The numbers of IgE-reactive aeroallergen molecules significantly differed between phenotypes (median in A-R-, A+R-, A-R+ and A+R+: 0, 1, 2 and 7 in EGEA and 0, 0, 3, and 5 in BAMSE). As compared to A-R- subjects, the adjusted ratio of the mean number of IgE-reactive molecules was higher in A+R+ than in A+R- or A-R+ (10.0, 5.4 and 5.0 in EGEA and 7.2, 0.7 and 4.8 in BAMSE).ConclusionThe A+R+ phenotype combined the sensitization pattern of both the A-R+ and A+R-phenotypes. This multimorbid polysensitized phenotype seems to be generalizable to various ages and allergenic environments and may be associated with specific mechanisms.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-13T06:10:25.137607-05:
      DOI: 10.1111/all.13410
  • Prevalence, severity, and risk factors for acute exacerbations of nasal
           and sinus symptoms by chronic rhinosinusitis status
    • Authors: Jordan R. Kuiper; Annemarie G. Hirsch, Karen Bandeen-Roche, Agnes S. Sundaresan, Bruce K. Tan, Robert P. Schleimer, Robert C. Kern, Walter F. Stewart, Brian S. Schwartz
      Abstract: BackgroundNasal and sinus symptoms (NSS) are common to many health conditions, including chronic rhinosinusitis (CRS). Few studies have investigated the occurrence and severity of, and risk factors for, acute exacerbations of NSS (AENSS) by CRS status (current, past, or never met European Position Paper on Rhinosinusitis [EPOS] criteria for CRS).MethodsFour seasonal questionnaires were mailed to a stratified random sample of Geisinger primary care patients. Logistic regression was used to identify individual characteristics associated with AENSS occurrence and severity by CRS status (current long-term, current recent, past, never) using EPOS subjective symptoms-only (EPOSS) CRS criteria. We operationalized three AENSS definitions based on prescribed antibiotics or oral corticosteroids, symptoms, and symptoms with purulence.ResultsBaseline and at least one follow-up questionnaires were available from 4,736 subjects. Self-reported NSS severity with exacerbation was worst in the current long-term CRS group. AENSS was common in all subgroups examined and generally more common among those with current EPOSS CRS. Seasonal prevalence of AENSS differed by AENSS definition and CRS status. Associations of risk factors with AENSS differed by definition, but CRS status, body mass index, asthma, hay fever, sinus surgery history, and winter season consistently predicted AENSS.ConclusionsIn this first longitudinal, population-based study of three AENSS definitions, NSS and AENSS were both common, sometimes severe, and differed by EPOSS CRS status. Contrasting associations of risk factors for AENSS by the different definitions suggest a need for a standardized approach to definition of AENSS.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-13T05:55:19.545054-05:
      DOI: 10.1111/all.13409
  • The urgent need for a harmonized severity scoring system for acute
           allergic reactions
    • Authors: Antonella Muraro; Montserrat Fernandez-Rivas, Kirsten Beyer, Victòria Cardona, Andrew Clark, Esben Eller, Jonathan O'B Hourihane, Marek Jutel, Aziz Sheikh, Ioana Agache, Katrina J Allen, Liz Angier, Barbara Ballmer-Weber, Maria Beatrice Bilò, Carsten Bindslev-Jensen, Carlos A. Camargo, Antonella Cianferoni, Audrey DunnGalvin, Philippe A Eigenmann, Susanne Halken, Karin Hoffmann-Sommergruber, Susanne Lau, Caroline Nilsson, Lars K. Poulsen, Franziska Rueff, Jonathan Spergel, Gunter Sturm, Frans Timmermans, Maria J Torres, Paul Turner, Ronald van Ree, Magnus Wickman, Margitta Worm, E. N. Clare Mills, Graham Roberts
      Abstract: The accurate assessment and communication of the severity of acute allergic reactions is important to patients, clinicians, researchers, the food industry, public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that works across the range of allergenic triggers and addresses the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders’ perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that is clinically meaningful and is useful for allergy healthcare professionals and researchers; and (ii) a three grade based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-13T05:45:20.306885-05:
      DOI: 10.1111/all.13408
  • Allergy - Committed to Progress in Allergy and Immunology
    • Authors: Hans-Uwe Simon; Thomas Bieber
      Abstract: After more than 8 years, our terms as Co-Editors-in-Chief have now reached an end. We are thankful for having had the privilege to serve the community in this position. We think that we have reached our original goal of increasing the overall quality of the journal (1). The science which is reported every month in Allergy is of high quality and wide interest, largely contributing to the development of the fields of Allergy and Immunology. The impact of the journal is high, as reflected by its present impact factor of 7.36.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-13T04:55:20.858643-05:
      DOI: 10.1111/all.13412
  • Prevalence of pollen-induced allergic rhinitis with high pollen exposure
           in grasslands of northern China
    • Authors: Xue-Yan Wang; Ting-Ting Ma, Xiao-Yan Wang, Yan Zhuang, Xiang-Dong Wang, Hui-Yu Ning, Hai-Yun Shi, Rui-Li Yu, Dan Yan, Hong-Dong Huang, Yong-Fei Bai, Guang-Liang Shan, Biao Zhang, Qing-Kun Song, Yan-Fen Zhang, Tie-Jun Zhang, Da-Zhong Jia, Xi-long Liu, Zhen-Xiang Kang, Wei-Jun Yan, Ba-te Yang, Xiu-Zhi Bao, Shu-Hua Sun, Fang-Fang Zhang, Wen-Hui Yu, Chao-Lu Bai, Tang Wei, Tong Yang, Tao-Qiong Ma, Xue-Bin Wu, Jian-Guo Liu, Hui Du, Luo Zhang, Yong Yan, De-Yun Wang
      Abstract: BackgroundThe aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China, and to study the impact of the intensity and time of pollen exposure on PiAR prevalence.MethodsA multistage, clustered and proportionately stratified random sampling with a field-interviewer administrated survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count.ResultsA total of 6043 subjects completed the study; with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P=0.024) but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P
      PubDate: 2018-01-10T20:56:37.417816-05:
      DOI: 10.1111/all.13388
  • Lolium perenne peptide immunotherapy is well tolerated and elicits a
           protective B-cell response in seasonal allergic rhinitis patients
    • Authors: R. Mösges; A.F. Koch, E. Raskopf, J. Singh, K. Shah-Hosseini, B. Hauswald, Y. Yarin, F. Corazza, L. Haazen, S. Pirotton, S. Allekotte, G. Zadoyan, T. Legon, S.R. Durham, M.H. Shamji
      Abstract: BackgroundSystemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short-course treatment with adjuvant-free Lolium perenne peptides (LPP) following a 6-week dose-escalation protocol.MethodsIn a prospective, dose-escalation study, 61 grass pollen–allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4, and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8).ResultsNo fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were
      PubDate: 2018-01-10T20:56:08.300537-05:
      DOI: 10.1111/all.13392
  • EAACI Guidelines on Allergen Immunotherapy – Out With the Old and In
           With the New
    • Authors: Ioana Agache
      Abstract: Occurring in both developed and developing countries and across all ethnic groups and ages allergic diseases represent a global health problem. During the last few decades, there has been an increase in the prevalence of allergic diseases and it has been predicted that by 2025 half of the entire EU population will be affected [1]. The three major management strategies are avoidance, symptom control by pharmacotherapy and allergen immunotherapy (AIT). By contrast with symptom control by pharmacotherapy AIT aims to modify the immune system via tolerance induction [2] and is potentially able to alter the course of allergic diseases [3]. The potential preventive effect of AIT is currently being explored for pollen [4].This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T11:40:27.031195-05:
      DOI: 10.1111/all.13393
  • Depressed mood is associated with loss of productivity in allergic
    • Authors: Adam P. Campbell; Lloyd P. Hoehle, Katie M. Phillips, David S. Caradonna, Stacey T. Gray, Ahmad R. Sedaghat
      Abstract: Allergic rhinitis (AR) is associated with significant decreases in quality of life and productivity losses. We hypothesized that symptoms of AR may differentially associate with lost productivity due to AR. We performed a cross-sectional cohort study of 105 prospectively recruited patients with persistent AR. AR control, severity of depressed mood and sinonasal symptoms were assessed with the Rhinitis Control Assessment Test (RCAT), Patient Health Questionnaire (PHQ-2), and the 22-item Sinonasal Outcome Test (SNOT-22) respectively. Lost productivity was assessed by asking the number of days of work/school missed due to AR in the last 3 months. Patients missed a mean of 1.5 days (SD:2.9) of work or school. Lost productivity was associated with PHQ-2 (adjusted linear regression coefficient [β]=0.68, 95%CI: 0.20–1.15, p=0.007) analysis but not SNOT-22 or RCAT scores. Productivity losses due to AR are associated with severity of depressed mood rather than classic nasal or extra-nasal symptoms of AR.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T11:40:25.748264-05:
      DOI: 10.1111/all.13387
  • With tree nut sensitization, take the current when it serves, or lose our
    • Authors: Matthew Greenhawt
      Abstract: Tree nut allergy affects approximately 1.4-2.3%, depending on the study methodology, patient age, and region in which the study was conducted.1,2 Tree nut allergy can be severe, and tends to persist throughout life.1,3 Tree nut is not a singular allergen like the other allergens—we use the term “tree nut” to refer to these items, but in essence it can refer to one nut, eight nuts, or per the US Food and Drug Agency classification, on the order of 19 items.1,4 Older, more conservative practice is to treat one nut as “all nuts”, and instruct avoidance of all tree nuts where there is a clinical allergy proven to just one. This is often supported by high rates of co-sensitization, which is high among tree nuts because of structural similarity, and fueled concerns of cross-contamination, proper identification, or labeling confusion.1,5This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T11:35:19.137712-05:
      DOI: 10.1111/all.13383
  • Similar localization of conformational IgE epitopes on the house dust mite
           allergens Der p 5 and Der p 21 despite limited IgE-cross-reactivity
    • Authors: M. Curin; T. Garmatiuk, Y. Resch-Marat, K. W. Chen, G. Hofer, K. Fauland, W. Keller, W. Hemmer, S. Vrtala, M. Focke-Tejkl, R. Valenta
      Abstract: BackgroundDue to high IgE recognition frequency and high allergenic activity, Der p 5 and Der p 21 are clinically important house dust mite (HDM) allergens. The objective of this study was to characterise the immunodominant IgE epitopes of Der p 5 and Der p 21 responsible for their high allergenic activity.MethodsA panel of 12 overlapping peptides spanning the Der p 5 and Der p 21 sequence were synthesized to search for sequential IgE epitopes by direct testing for allergic patients ' IgE reactivity. Peptide-specific antibodies raised in rabbits were used in inhibition studies for localizing conformational IgE epitopes which were visualized on the surfaces of the allergen structures by molecular modelling. IgE cross-reactivity between the allergens was studied by IgE inhibition studies.ResultsImmunodominant IgE epitopes defined by allergic patients' IgE on Der p 5 and Der p 21 were primarily of the conformational, discontinuous type including N- and C-terminal portions of the protein. They could be located on each allergen on one area with similar localization but despite similar structure of the allergens no relevant IgE cross-reactivity could be detected.ConclusionOur study shows that Der p 5 and Der p 21 contain a major conformational IgE epitope-containing area located on similar portions of their structure but they lack relevant IgE cross-reactivity. These data are important for the development of modern allergy vaccines based on defined molecules for allergen-specific immunotherapy of HDM allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T08:45:40.222227-05:
      DOI: 10.1111/all.13398
  • Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg
           responses upon sublingual delivery in mice
    • Authors: Irene Soria; Juan López-Relaño, Marcos Viñuela, José-Ignacio Tudela, Alba Angelina, Cristina Benito-Villalvilla, Carmen M. Díez-Rivero, Bárbara Cases, Ana I. Manzano, Enrique Fernández-Caldas, Miguel Casanovas, Oscar Palomares, José L. Subiza
      Abstract: BackgroundPolymerized allergoids coupled to nonoxidized mannan (PM-allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM-allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM-allergoids administered sublingually in comparison to native allergens.MethodsThree immunization protocols (4-8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells.ResultsA quick antibody response and higher IgG2a/IgE ratio was observed with PM-allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL-4 ratio with a quick IL-10 production by submandibular LN cells. An increase of CD4+CD25highFOXP3+ Treg cells was detected in LNs and spleen of mice treated with PM-allergoids. These allergoids were better captured than native allergens by antigen presenting (CD45+MHC-II+) cells obtained from the sublingual mucosa, including DCs (CD11b+) and macrophages (CD64+). Importantly, all the differential effects induced by PM-allergoids were abolished when using oxidized instead of nonoxidized PM-allergoids.ConclusionOur results demonstrate for the first time that PM-allergoids administered through the sublingual route promote the generation of Th1 and FOXP3+ Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen presenting cells.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T08:45:37.106717-05:
      DOI: 10.1111/all.13396
  • Skin inflammation exacerbates food allergy symptoms in epicutaneously
           sensitized mice
    • Authors: Akiko Kawasaki; Naohiro Ito, Hiroki Murai, Motoko Yasutomi, Hironobu Naiki, Yusei Ohshima
      Abstract: BackgroundCutaneous exposure to food antigen through impaired skin barrier has been shown to induce epicutaneous sensitization, thereby causing IgE-mediated food allergies.ObjectiveWe examined whether skin barrier impairment following epicutaneous sensitization exacerbates food allergies.MethodsBALB/c mice were epicutaneously sensitized by repeated application of ovalbumin (OVA) to MC903-pretreated ear skin for 48 hours weekly and then intragastrically challenged with OVA. After the first oral challenge, the skin barrier was disrupted with topical application of MC903 or by tape-stripping. Mice were monitored for changes in body temperature and the occurrence of diarrhea after undergoing the second oral challenge. Serum levels of mouse mast cell protease-1 (mmcp1) and OVA-specific IgE, IgG1, IgG2a antibodies and OVA-specific IgA levels in intestinal lavage fluid were measured by ELISA. Tissue accumulation of eosinophils was determined histologically.ResultsEpicutaneously sensitized mice developed anaphylaxis after intragastric challenge, as evidenced by diarrhea, decreased body temperature and increased serum mmcp1 levels. Skin barrier disruption by MC903 treatment or tape-stripping exacerbated allergic reactions induced by oral challenge. MC903 treatment increased serum baseline and post-challenge mmcp1 levels. Topical pretreatment with dexamethasone alleviated allergic reactions that were exacerbated by MC903-treatement.ConclusionEven after eliminating exposure to the antigen, inflammation from skin barrier disruption can exacerbate the severity of food allergy symptoms. Serum baseline mmcp1 levels might be an effective marker for predicting the severity of antigen-induced allergic symptoms.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T08:35:20.278421-05:
      DOI: 10.1111/all.13404
  • Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy
           suppresses experimental food allergy in mice through induction of mucosal
           regulatory T cells
    • Authors: Paola L. Smaldini; Fernando Trejo, José L Cohen, Eliane Piaggio, Guillermo H. Docena
      Abstract: Therapeutic tolerance restoration has been proven to modify food allergy in patients and animal models and although sublingual immunotherapy (SLIT) has showed promise, combined therapy may be necessary to achieve a strong and long-term tolerance. In this work, we combined SLIT with systemic administration of IL-2 associated with an anti-IL-2 monoclonal antibody (IL-2/anti-IL-2Ab complex or IL-2C) to reverse the IgE-mediated experimental allergy.Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged with allergen to elicit hypersensitivity reactions. Then, allergic mice were treated with a sublingual administration of very low amounts of milk proteins combined with intraperitoneal injection of low doses of IL-2C. The animals were next re-exposed to allergens and mucosal as well as systemic immunological parameters were assessed in vivo and in vitro.The treatment reduced serum specific IgE, IL-5 secretion by spleen cells and increased IL-10 and TGF-β in the lamina propria of buccal and duodenal mucosae. We found an augmented frequency of IL-10-secreting CD4+CD25+Foxp3+ regulatory T cells (Treg) in the submaxilar lymph nodes and buccal lamina propria. Tregs were sorted, characterized and adoptively transferred to naïve mice, which were subsequently sensitized. No allergy was experienced in these mice and we encouragingly discovered a faster and more efficient tolerance induction with the combined therapy compared with SLIT.In conclusion, the combination of two therapeutic strategies rendered Treg-mediated tolerance more efficient compared to individual treatments and reversed the established IgE-mediated food allergy. This approach highlights the ability of IL-2C to expand Tregs, and it may represent a promising disease-modifying therapy for managing food allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T08:30:56.795622-05:
      DOI: 10.1111/all.13402
  • IL-37 inhibits IL-4/IL-13-induced CCL11 production and lung eosinophilia
           in murine allergic asthma
    • Authors: Jiaoyan Lv; Yingluo Xiong, Wenjing Li, Xinyi Cui, Xunjia Cheng, Qibin Leng, Rui He
      Abstract: BackgroundIL-37 is emerging as an anti-inflammatory cytokine, particularly in innate inflammation. However, the role of IL-37 in Th2-mediated allergic lung inflammation remains uncertain. We sought to determine the role and the underlying mechanisms of IL-37 in the development of house dust mites (HDM)-induced murine asthma model.MethodsWe examined the effect of IL-37 administration during the sensitization or challenge phase on Th2-mediated allergic asthma induced by inhaled HDM. Cellular source of CCL11 and distribution of IL-37 receptors, IL-18Rα and IL-1R8, were determined in HDM-exposed lungs. Finally, we examined the effect of IL-37 on CCL11 production and STAT6 activation in different primary lung structural cell types upon IL-4/IL-13 stimulation.ResultsIL-37 had no effect on HDM sensitization, but when administrated during the challenge phase, significantly attenuated pulmonary eosinophilia, CCL11 production and airway hyper-reactivity (AHR). Interestingly, IL-37 treatment had no significant effects on lung infiltrating T cells and Th2 cytokine production. Intranasal co-administration of CCL11 reversed the inhibiting effect of IL-37 on HDM-induced pulmonary eosinophilia and AHR. Furthermore, we demonstrated that CCL11 was primarily expressed by fibroblasts and airway smooth muscle cells (AMSC), while IL-37 receptors by tracheobronchial epithelial cells (TEC). In vitro study showed that IL-37 inhibited IL-4/IL-13–induced STAT6 activation and CCL11 production by fibroblasts and AMSC, which was dependent on its direct action on TEC. Moreover, cell-contact was required for the inhibitory effect of IL-37-treated TEC.ConclusionsIL-37 attenuates HDM-induced asthma, possibly by inhibiting IL-4/IL-13-induced CCL11 production by fibroblasts and AMSC via its direct act on TEC.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T08:30:34.053941-05:
      DOI: 10.1111/all.13395
  • Usefulness of Asthma Predictive Index in Ascertaining Asthma Status of
           Children Using Medical Records: An Explorative Study
    • Authors: Chung-Il Wi; Elizabeth A. Krusemark, Gretchen Voge, Sunghwan Sohn, Hongfang Liu, Euijung Ryu, Miguel A. Park, Jose A. Castro-Rodriguez, Young J. Juhn
      Abstract: BackgroundFrequent wheezing in original Asthma Predictive Index (API) was defined by parental report of recurrent wheezing within 1 year during the first 3 years of life. The nature of frequent wheezing in children, particularly aged over 3 years has not been studied. We aimed to assess the frequency and interval of wheezing to define frequent wheezing in ascertaining asthma for children using medical records.MethodsAmong children who participated in a previous study (n=427), all wheezing episodes documented in medical records were collected for children who had ≥2wheezing episodes PLUS met one major criteria or two minor criteria of API. We compared the distribution of known risk factors for asthma between subjects having two consecutive wheezing episodes with shorter interval (≤1year) compared to those with longer interval (1to3 years).Results62 children met API at median age of 2.3 years. During follow-up period (median age: 11.3 years), a total of 198 wheezing episodes were observed. 81% of wheezing intervals were within 3 years from the earlier wheezing episode, including 60% within 1 year. Children who met API based on 1 year interval (n=40) vs. 1to3 year interval (n=13) appeared to be similar in regard to the known risk factors for asthma.ConclusionsOur exploratory study finding suggests that children who had frequent wheezing episodes with longer interval (
      PubDate: 2018-01-10T08:30:18.49299-05:0
      DOI: 10.1111/all.13403
  • Immunoprofile of α-Gal- and B-antigen-specific responses differentiate
           red meat allergic patients from healthy individuals
    • Authors: Danijela Apostolovic; Rui Da Silva Rodrigues, Preethi Thomas, Maria Starkhammar, Carl Hamsten, Marianne van Hage
      Abstract: BackgroundThe Galactose-α-1,3-galactose (α-Gal) epitope is involved in red meat allergy. As α-Gal is structurally similar to the blood group B antigen, we explored the relationship between the immune responses to α-Gal- and the B-antigen in red meat allergic patients compared to healthy A/O or B blood donors.MethodsSera from 51 red meat allergic patients IgE positive to α-Gal and 102 healthy blood donors (51 blood group A/O; 51 blood group B), were included. α-Gal and B-antigen specific IgE (ImmunoCAP) and IgG/IgG1-4 (ELISA) responses were determined. Basophil activation tests were performed.ResultsFifteen healthy donors were IgE positive to α-Gal, of which 3 had blood group B. The allergic patients had significantly higher α-Gal IgE levels compared to the healthy donors. The majority of the allergic patients, but none of the healthy donors, had IgE against the B-antigen. Inhibition studies revealed cross-reactivity between α-Gal and the B-antigen. The biological activity of the B-antigen was confirmed by basophil activation tests. Anti-α-Gal IgG1 and IgG4 levels were significantly higher in the patients compared to the healthy donors. Moreover, the IgG response to the B-antigen was comparable between the allergic patients and healthy A/O donors.ConclusionRed meat allergic patients showed significantly higher α-Gal IgE, IgG1 and IgG4 levels, reflecting a Th2 response, compared to healthy blood donors. Blood group B donors had significantly reduced antibody responses to α-Gal, due to similarities with the B-antigen, resulting in a lower risk of sensitization to α-Gal and development of red meat allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T08:25:45.523667-05:
      DOI: 10.1111/all.13400
  • Epidemiology of atopic dermatitis in adults: results from an international
    • Authors: S. Barbarot; S. Auziere, A. Gadkari, G. Girolomoni, L. Puig, E. L. Simpson, D. J. Margolis, M. de Bruin-Weller, L. Eckert
      Abstract: BackgroundThere are gaps in our knowledge of the prevalence of adult atopic dermatitis (AD).ObjectiveTo estimate prevalence of AD in adults and by disease severity.MethodsThis international, cross-sectional, web-based survey was performed in the United States, Canada, France, Germany, Italy, Spain, United Kingdom, and Japan. Adult members of online respondent panels were sent a questionnaire for AD identification and severity assessment; demographic quotas ensured population representativeness for each country. A diagnosis of AD required subjects to be positive on the modified UK Working Party/ISAAC criteria and self-report of ever having an AD diagnosis by a physician. The proportion of subjects with AD who reported being treated for their condition was determined and also used to estimate prevalence. Severity scales were Patient-Oriented SCORAD, Patient Oriented Eczema Measure, and Patient Global Assessment.ResultsAmong participants by region, the point prevalence of adult AD in the overall/treated populations was 4.9%/3.9% in the US, 3.5%/2.6% in Canada, 4.4%/3.5% in EU, and 2.1%/1.5% in Japan. The prevalence was generally lower for males vs females, and decreased with age. Regional variability was observed within countries. Severity varied by scale and region; however, regardless of the scale or region, proportion of subjects reporting severe disease was lower than mild or moderate disease.ConclusionsPrevalence of adult AD ranged from 2.1% to 4.9% across countries. Severe AD represented a small proportion of the overall AD population regardless of measure or region.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T08:25:33.354738-05:
      DOI: 10.1111/all.13401
  • House dust mite impairs antiviral response in asthma exacerbation models
           through its effects on TLR3
    • Authors: Hamid Akbarshahi; Mandy Menzel, Sangeetha Ramu, Irma Mahmutovic Persson, Leif Bjermer, Lena Uller
      Abstract: BackgroundImpaired antiviral interferon expression may be involved in asthma exacerbations commonly caused by rhinovirus infections. Allergy is a known risk factor for viral-induced asthma exacerbation, but little is known whether allergens may affect interferon responses.ObjectiveOur hypothesis is that house dust mite (HDM) impairs viral stimulus-induced antiviral signalling.MethodsExperimental asthma exacerbations were produced in vitro in human bronchial epithelial cells (HBECs) and in mice by using sequential challenges with HDM and a viral infection mimic, Poly(I:C). We examined rhinovirus pattern recognition receptors (PRRs) signalling pathways and potential mechanisms of impaired interferon response.ResultsHBECs and mice exposed to HDM prior to Poly(I:C) exhibited a reduced antiviral response compared to Poly(I:C) alone, including reduced IFN-β, IFN-lambda, TLR3, RIG-I, MDA5, IRF-3 and IRF-7. Heat-inactivation of HDM partially restored the TLR3-induced interferon response in vitro and in vivo. Our HBEC-data further showed that HDM directly affects TLR3 signalling by targeting the receptor glycosylation level.ConclusionsDirect effects of allergens such as HDM on PRRs can present as potential mechanism for defective antiviral airway responses. Accordingly, therapeutic measures targeting inhibitory effects of allergens on antiviral PRRs may find use as a strategy to boost antiviral response and ameliorate exacerbations in asthmatic patients.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T08:25:22.465298-05:
      DOI: 10.1111/all.13378
  • Diagnostic accuracy, risk assessment, and cost-effectiveness of
           component-resolved diagnostics for food allergy: a systematic review
    • Authors: Javier Flores Kim; Nicola McCleary, Bright I Nwaru, Andrew Stoddart, Aziz Sheikh
      Abstract: BackgroundComponent-resolved diagnostics (CRD) are promising tools for diagnosing food allergy, offering the potential to determine specific phenotypes and to develop patient-tailored risk profiles. Nevertheless, the diagnostic accuracy of these tests varies across studies; thus, their clinical utility remains unclear. Therefore, we synthesized the evidence from studies investigating the diagnostic accuracy, risk assessment ability, and cost-effectiveness of CRD for food allergy.MethodsWe systematically searched 10 electronic databases and four clinical trial registries for studies published January 2000-February 2017. The quality of included studies was assessed using QUADAS-2. Due to heterogeneity, we narratively synthesized the evidence.ResultsEleven studies met inclusion criteria, altogether recruiting 1,098 participants. The food allergies investigated were cow's milk, hen's egg, peanut, hazelnut, and shrimp. The components with the highest diagnostic accuracy for each allergen, along with their sensitivity-specificity pairs, were: Bos d 4 for cow's milk (62.0% and 87.5%), Gal d 1 for hen's egg (84.2% and 89.8% for heated egg, and 60.6% and 97.1% for raw egg), Ara h 2 for peanut (80.3% and 95.1%), Cor a 14 for hazelnut (100% and 93.8%), and Lit v 1 for shrimp (82.8% and 56.3%) allergy.ConclusionSelected components of cow's milk, hen's egg, peanut, hazelnut, and shrimp allergen showed high specificity, but lower sensitivity. However, few studies exist for each component, and studies vary widely regarding the cut-off values used, making it challenging to synthesize findings across studies. Further research is needed to determine clinically appropriate cut-off values, risk assessment abilities, and cost-effectiveness of CRD approaches.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T08:20:21.737159-05:
      DOI: 10.1111/all.13399
  • Factors increasing the risk for a severe reaction in anaphylaxis: An
           analysis of Data from The European Anaphylaxis Registry
    • Authors: Margitta Worm; Wojciech Francuzik, Jean-Marie Renaudin, Maria Beatrice Bilo, Victòria Cardona, Kathrin Scherer Hofmeier, Alice Köhli, Andrea Bauer, George Christoff, Ewa Cichocka-Jarosz, Thomas Hawranek, Jonathan O'B Hourihane, Lars Lange, Vera Mahler, Antonella Muraro, Nikolaos G Papadopoulos, Claudia Pföhler, Iwona Poziomkowska-Gęsicka, Franziska Ruëff, Thomas Spindler, Regina Treudler, Montserrat Fernandez-Rivas, Sabine Dölle
      Abstract: BackgroundPreventive measures to decrease the frequency and intensity of anaphylactic events are essential to provide optimal care for allergic patients. Aggravating factors may trigger or increase the severity of anaphylaxis and therefore need to be recognized and avoided.ObjectiveTo identify and prioritize factors associated with an increased risk of developing severe anaphylaxis.MethodsData from the Anaphylaxis Registry (122 centers in 11 European countries) was used in logistic regression models considering existing severity grading systems, elicitors, and symptoms to identify the relative risk of factors on the severity of anaphylaxis.ResultsWe identified higher age and concomitant mastocytosis (OR: 3.1, CI: 2.6 - 3.7) as the most important predictors for an increased risk of severe anaphylaxis. Vigorous physical exercise (OR: 1.5, CI: 1.3 - 1.7), male sex (OR: 1.2, CI: 1.1 - 1.3), and psychological burden (OR: 1.4, CI: 1.2 - 1.6) were more often associated with severe reactions. Additionally, intake of beta-blockers (OR: 1.9, CI: 1.5 - 2.2) and ACE-I (OR: 1.28, CI: 1.05, 1.51) in temporal proximity to allergen exposition were identified as important factors in logistic regression analysis.ConclusionOur data suggest it may be possible to identify patients who require intensified preventive measures due to their relatively higher risk for severe anaphylaxis by considering endogenous and exogenous factors.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T03:46:19.623706-05:
      DOI: 10.1111/all.13380
  • Consensus document on dog and cat allergy
    • Authors: Ignacio Davila; Javier Domínguez-Ortega, Ana Mª Navarro Pulido, Alicia Alonso, Dario Antolin-Amerigo, Eloina González-Mancebo, Cristina Martin Garcia, Beatriz Nuñez-Acevedo, Nieves Prior, Marta Reche, Ana Rosado, Javier Ruiz-Hornillos, María Cesárea Sánchez, Miguel Torrecillas
      Abstract: The prevalence of sensitisation to dogs and cats varies by country, exposure time and predisposition to atopy. It is estimated that, 26% of European adults coming to the clinic for suspected allergy to inhalant allergens are sensitised to cats and 27% to dogs. This document is intended to be a useful tool for clinicians involved in the management of people with dog or cat allergy. It was prepared from a consensus process based on the RAND/UCLA method. Following a literature review, it proposes various recommendations concerning the diagnosis and treatment of these patients, grounded in evidence and clinical experience. The diagnosis of dog and cat allergy is based on a medical history and physical examination that are consistent with each other, and is confirmed with positive results on specific IgE skin tests. Sometimes, especially in polysensitised patients, molecular diagnosis is strongly recommended. Although the most advisable measure would be to avoid the animal, this is often impossible and associated with a major emotional impact. Furthermore, indirect exposure to allergens occurs in environments in which animals are not present. Immunotherapy is emerging as a potential solution to this problem, although further supporting studies are needed.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T03:27:15.550335-05:
      DOI: 10.1111/all.13391
  • Fish oil in infancy protects against food allergy in Iceland – results
           from a birth cohort study
    • Authors: Michael Clausen; Kristjan Jonasson, Thomas Keil, Kirsten Beyer, Sigurveig T. Sigurdardottir
      Abstract: BackgroundConsumption of oily fish or fish oil during pregnancy, lactation, and infancy has been linked to a reduction in the development of allergic diseases in childhood.MethodsIn an observational study, Icelandic children (n = 1304) were prospectively followed from birth to 2.5 years with detailed questionnaires administered at birth and at one and two years of age, including questions about fish oil supplementation. Children with suspected food allergy were invited for physical examinations, allergic sensitization tests, and a double-blind, placebo-controlled food challenge if the allergy testing or clinical history indicated food allergy. The study investigated the development of sensitization to food and confirmed food allergy according to age and frequency of postnatal fish oil supplementation using proportional hazards modelling.ResultsThe incidence of diagnosed food sensitization was significantly lower in children who received regular fish oil supplementation (relative risk 0.51, 95% confidence interval 0.32–0.82). The incidence of challenge-confirmed food allergy was also reduced, although not statistically significantly (0.57, 0.30–1.12). Children who began to receive fish oil in their first half year of life were significantly more protected than those who began later (p = 0.045 for sensitization, p = 0.018 for allergy). Indicators of allergy severity decreased with increased fish oil consumption (p = 0.013). Adjusting for parent education and allergic family history did not change the results.ConclusionPostnatal fish oil consumption is associated with decreased food sensitization and food allergies in infants and may provide an intervention strategy for allergy prevention.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T03:26:40.681648-05:
      DOI: 10.1111/all.13385
  • Early-life gut microbiome and egg allergy
    • Authors: Mina Fazlollahi; Yoojin Chun, Alexander Grishin, Robert A. Wood, A. Wesley Burks, Peter Dawson, Stacie M. Jones, Donald Y.M. Leung, Hugh A. Sampson, Scott H. Sicherer, Supinda Bunyavanich
      Abstract: BackgroundGut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy.MethodsWe studied 141 children with egg allergy and controls from the multi-center Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected and clinical evaluation, egg specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP).ResultsCompared to controls, increased alpha diversity and distinct taxa (PERMANOVA P=5.0x10-4) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg allergic subjects (Kruskal Wallis Padj=0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0x10-4). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years.ConclusionThe distinct early-life gut microbiota in egg allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T03:26:11.014177-05:
      DOI: 10.1111/all.13389
  • Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type-2
           immunity in a murine asthma model
    • Authors: Laura Hesse; Nienke Ieperen, Corine Habraken, Arjen H. Petersen, Silvia Korn, Tim Smilda, Betty Goedewaagen, Marcel H. Ruiters, Adrianus C. van der Graaf, Martijn C. Nawijn
      Abstract: Allergen-specific immunotherapy can induce long-term suppression of allergic symptoms, reduce medication use and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β-glucans, chitins and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment. Here, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM) driven mouse model of allergic asthma.HDM-sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen-induced ear swelling (ESR), airway hyperresponsiveness (AHR) and inflammation in broncho-alveolar lavage fluid (BAL) and lung tissue.ESR measurement shows suppression of early allergic response in HDM- and DerP1/2-SCIT treated mice. Both HDM-SCIT and DerP1/2-SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2-SCIT is able to significantly suppress type-2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2-SCIT treatment is uniquely able suppress CCL20 and showed a trend towards suppression of IL-33, CCL17 and eotaxin levels in lung tissue.Taken together, these data show that purified DerP1/2-SCIT is able to not only suppress AHR and inflammation, but also has superior activity towards suppression of Th2 cells and HDM-induced activation of lung structural cells including airway epithelium. We postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T03:25:36.450675-05:
      DOI: 10.1111/all.13382
  • The international WAO/EAACI guideline for the management of hereditary
           angioedema – the 2017 revision and update
    • Authors: Marcus Maurer; Markus Magerl, Ignacio Ansotegui, Emel Aygören Pürsün, Stephen Betschel, Konrad Bork, Tom Bowen, Henrik Balle Boysen, Henriette Farkas, Anete Grumach, Michihiro Hide, Constance Katelaris, Richard Lockey, Hilary Longhurst, William Lumry, Inmaculada Martinez-Saguer, Dumitru Moldovan, Alexander Nast, Ruby Pawankar, Paul Potter, Marc Riedl, Bruce Ritchie, Lanny Rosenwasser, Mario Sánchez-Borges, Yuxiang Zhi, Bruce Zuraw, Timothy Craig
      Abstract: Hereditary angioedema (HAE) is a rare disease and a serious health problem, globally and for affected patients and their families. The pathophysiological background is primarily a vascular reaction to an overshooting local production of bradykinin. Evidence-based recommendations are needed to inform and guide clinical decision makers. This is the first revision and update of the global guideline for the diagnosis and management of HAE[5]. It was developed by the World Allergy Organization (WAO) in collaboration with the European Academy of Allergy and Clinical Immunology (EAACI).This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-10T03:25:32.433454-05:
      DOI: 10.1111/all.13384
  • Circulating 25-hydroxyvitamin D, nasopharyngeal airway metabolome, and
           bronchiolitis severity
    • Authors: Kohei Hasegawa; Christopher J. Stewart, Juan C. Celedón, Jonathan M. Mansbach, Courtney Tierney, Carlos A Camargo
      Abstract: Low circulating 25-hydroxyvitamin D (25OHD) levels are a risk factor for acute respiratory infection (e.g., bronchiolitis) in children. However, little is known about the relation of circulating 25OHD with the many downstream functional molecules in target organs – such as the airway – and with clinical outcomes. In this prospective multicenter study of infants (age
      PubDate: 2018-01-09T08:36:42.01155-05:0
      DOI: 10.1111/all.13379
  • TNF Family Member LIGHT Acts with IL-1β and TGF-β to Promote Airway
           Remodeling During Rhinovirus Infection
    • Authors: Amit K. Mehta; Taylor Doherty, David Broide, Michael Croft
      Abstract: BackgroundRhinovirus (RV) can exacerbate allergen-driven asthma. However, it has been suggested that serial infections with RV may also lead to asthma-like features in childhood without prior allergen exposure.AimWe sought to test the effects of RV infection in the absence of allergen challenge on lung tissue remodeling and to understand if RV induced factors in common with allergen that promote remodeling.MethodsWe infected C57BL/6 mice multiple times with RV in the absence or presence of allergen to assess airway remodeling. We used knockout mice and blocking reagents to determine the participation of LIGHT (TNFSF14), as well as IL-1β and TGF-β, each previously shown to contribute to lung remodeling driven by allergen.ResultsRecurrent RV infection without allergen challenge induced an increase in peribronchial smooth muscle mass and subepithelial fibrosis. RV induced LIGHT expression in mouse lungs after infection, and alveolar epithelial cells and neutrophils were found to be potential sources of LIGHT. Accordingly, LIGHT-deficient mice, or mice where LIGHT was neutralized, displayed reduced smooth muscle mass and lung fibrosis. Recurrent RV infection also exacerbated the airway remodeling response to house dust mite allergen and this was significantly reduced in LIGHT deficient mice. Furthermore, neutralizing IL-1β or TGF-β also limited subepithelial fibrosis and/or smooth muscle thickness induced by RV.ConclusionRhinovirus can promote airway remodeling in the absence of allergen through upregulating common factors that also contribute to allergen-associated airway remodeling.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T08:36:09.740884-05:
      DOI: 10.1111/all.13390
  • Food allergen-sensitized CCR9+ lymphocytes enhance airways allergic
           inflammation in mice
    • Authors: Laure Castan; Marie-Aude Cheminant, Luc Colas, Sophie Brouard, Antoine Magnan, Grégory Bouchaud
      Abstract: BackgroundThe mechanisms of the atopic march, characterized by a natural progression from food and cutaneous allergies to rhinitis and asthma, are still unknown. However, as several organs can be involved, chemokines and their receptors might be implicated in this process and may be instrumental factors.ObjectivesWe hypothesized that the T-cell gut-homing receptor CCR9 could be implicated in the evolution of allergic diseases.Methods: We characterized the immune response and the role of CCR9 in a murine model combining food allergy to wheat gliadin and a model of acute airways inflammation in response to house dust mite.ResultsCompared with solely asthmatic-like mice, we demonstrated that the aggravation of pulmonary symptoms in consecutive food and respiratory allergies, characterized by an increase in pulmonary resistance and a higher Th17/ Treg ratio, was abrogated in CCR9 knock-out mice. Moreover, transfer of food-allergic CD4+ T cells from wild-type but not from CCR9-/- aggravated airways inflammation demonstrating that CCR9 is involved in food allergy-enhanced allergic airway inflammation to unrelated allergens.ConclusionTaken together, our results demonstrated a crucial role of the T-cell homing receptor CCR9 in this model and validated its potential for use in the development of therapeutic strategies for allergic diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T08:35:56.851661-05:
      DOI: 10.1111/all.13386
  • Isolation of a high affinity Bet v 1-specific IgG-derived ScFv from a
           subject vaccinated with hypoallergenic Bet v 1 fragments
    • Authors: Elisabeth Gadermaier; Katharina Marth, Christian Lupinek, Raffaela Campana, Gerhard Hofer, Katharina Blatt, Dubravka Smiljkovic, Uwe Roder, Margarete Focke-Tejkl, Susanne Vrtala, Walter Keller, Peter Valent, Rudolf Valenta, Sabine Flicker
      Abstract: BackgroundRecombinant hypoallergenic allergen derivatives have been used in clinical immunotherapy studies and clinical efficacy seems to be related to the induction of blocking IgG antibodies recognizing the wild type allergens. However, so far no treatment-induced IgG antibodies have been characterized.ObjectiveTo clone, express and characterize IgG antibodies induced by vaccination with two hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1 in a non-allergic subject.MethodsA phage-displayed combinatorial single chain fragment (ScFv) library was constructed from blood of the immunized subject and screened for Bet v 1-reactive antibody fragments. ScFvs were tested for specificity and cross-reactivity to native Bet v 1 and related pollen and food allergens and epitope mapping was performed. Germline ancestor genes of the antibody were analyzed with the ImMunoGeneTics (IMGT) database. The affinity to Bet v 1 and cross-reactive allergens was determined by surface plasmon resonance measurements. The ability to inhibit patients’ IgE binding to ELISA plate-bound allergens and allergen-induced basophil activation was assessed.ResultsA combinatorial ScFv library was obtained from the vaccinated donor after three injections with the Bet v 1 fragments. Despite being almost in germline configuration, ScFv (clone H3-1) reacted with high affinity to native Bet v 1 and homologous allergens, inhibited allergic patients’ polyclonal IgE binding to Bet v 1 and partially suppressed allergen-induced basophil activation.ConclusionImmunization with unfolded hypoallergenic allergen derivatives induces high affinity antibodies even in non-allergic subjects which recognize the folded wild-type allergens and inhibit polyclonal IgE binding of allergic patients.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-09T08:33:11.74728-05:0
      DOI: 10.1111/all.13394
  • In chronic spontaneous urticaria, IgE against staphylococcal enterotoxins
           is common and functional
    • Authors: S Altrichter; T Hawro, M. Liedtke, G. Holtappels, C. Bachert, P. S. Skov, M Maurer
      Abstract: BackgroundChronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema. Despite the known effectiveness of omalizumab therapy, the relevant IgE antigens are largely unknown. Recently, increased rates of elevated levels of IgE towards Staphylococcus aureus enterotoxins (SEs) were described in CSU.AimTo assess the prevalence and functional relevance of IgE to SEs in CSU.Method: We investigated serum levels of IgE against SEs in 49 CSU patients and in 15 CSU patients additional specific IgE to SE components and basophil histamine release (BHR). Sera of15 healthy controls (HCs) served as control group.Results25 (51%) of the CSU patients had detectable levels of SE-IgE as compared to 5 (33%) of HCs. Specific IgE to one of the SEs, Staphylococcus enterotoxin B (SEB), was present in 5 (33%) of 15 randomly selected CSU patients vs 3 (20%) of HC. Total IgE serum levels in CSU patients were significantly correlated with SE-IgE (r = 0.52, p
      PubDate: 2018-01-09T08:32:57.906804-05:
      DOI: 10.1111/all.13381
  • Issue Information - Cover and Editorial Board
    • Pages: 521 - 521
      PubDate: 2018-02-21T01:39:27.034384-05:
      DOI: 10.1111/all.13278
  • Issue Information - TOC
    • Pages: 523 - 524
      PubDate: 2018-02-21T01:39:25.424287-05:
      DOI: 10.1111/all.13277
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Clinical implications of mast cell involvement in allergic conjunctivitis
    • Authors: D. Elieh Ali Komi; T. Rambasek, L. Bielory
      Pages: 528 - 539
      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.
      PubDate: 2017-11-20T20:57:56.867488-05:
      DOI: 10.1111/all.13334
  • 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. Tsilochristou, N. Muelleneisen
      Pages: 540 - 548
      Abstract: The vision of European Academy of Allergy and Clinical Immunology (EAACI) and the Union of European Medical Specialists Section and Board 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.
      PubDate: 2017-10-26T03:10:40.041195-05:
      DOI: 10.1111/all.13321
  • Component-resolved diagnosis and beyond: Multivariable regression models
           to predict severity of hazelnut allergy
    • Authors: M. R. Datema; R. Ree, R. Asero, L. Barreales, S. Belohlavkova, F. Blay, M. Clausen, R. Dubakiene, C. Fernández-Perez, P. Fritsche, D. Gislason, K. Hoffmann-Sommergruber, M. Jedrzejczak-Czechowicz, L. Jongejan, A. C. Knulst, M. Kowalski, T. Z. Kralimarkova, T.-M. Le, J. Lidholm, N. G. Papadopoulos, T. A. Popov, N. Prado, A. Purohit, I. Reig, S. L. Seneviratne, A. Sinaniotis, S. A. Versteeg, S. Vieths, A. H. Zwinderman, E. N. C. Mills, M. Fernández-Rivas, B. Ballmer-Weber
      Pages: 549 - 559
      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 Double-blind placebo-controlled food challenge [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 (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) 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.
      PubDate: 2017-11-24T00:35:33.668012-05:
      DOI: 10.1111/all.13328
  • The longitudinal impact of probiotic and peanut oral immunotherapy on
           health-related quality of life
    • Authors: A. Dunn Galvin; S. McMahon, A.-L. Ponsonby, K.-C. Hsiao, M. L. K. Tang,
      Pages: 560 - 568
      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. A total of 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.ResultsProbiotic and peanut oral immunotherapy was associated with significant improvement in FAQLQ-PF (F = 3.63, P = .02), with mean difference 0.8 at 3 months post-treatment (P = .05) and 1.3 at 12 months post-treatment (P = .005), exceeding the 0.5 minimal clinically important difference for FAQLQ-PF. For FAIM, mean difference was 0.5 (P = .03) at 3 months and 0.4 (P = .04) at 12 months post-treatment. In placebo group, post-treatment FAQLQ and FAIM remained unchanged from pretreatment. 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.ConclusionsProbiotic and peanut oral immunotherapy has a sustained beneficial effect on psychosocial impact of food allergy at 3 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 well-being was not negatively impacted. Improved HRQL was specifically associated with acquisition of sustained unresponsiveness.
      PubDate: 2017-11-13T04:06:19.105137-05:
      DOI: 10.1111/all.13330
  • Serine protease allergen favours Th2 responses via PAR-2 and STAT3
           activation in murine model
    • Authors: K. Agrawal; N. Arora
      Pages: 569 - 575
      Abstract: BackgroundProtease activity of Per a 10 favours Th2 responses by differential regulation of IL-12p70 and IL-23 cytokine subunits. This study aimed 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 pretreated with SAM11 or isotype control or stattic and stimulated with Per a 10. p-STAT3 levels were measured using Western blot. Transcript levels of IL-12p35, IL-12/23p40 and IL-23p19 were measured using RT-PCR. Cytokine levels were analysed using ELISA.ResultsProtease activity of Per a 10 increased p-STAT3 levels in mouse lungs, which was reduced upon PAR-2 blockage. Percentage of p-STAT3+ CD11c+ cells was higher in Per a 10-administered mice and was reduced upon PAR-2 blockage. IL-12p35 and IL-12p70 levels were higher, and IL-23p19 and IL-23 levels were lower in both SAM11-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 SAM11-administered mice. Inhibiting STAT3 activation via stattic also leads to lower levels of IL-23p19 and IL-23 and higher levels 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.
      PubDate: 2017-10-16T02:40:49.43277-05:0
      DOI: 10.1111/all.13315
  • The sex-shift in single disease and multimorbid asthma and rhinitis during
           puberty - a study by MeDALL
    • Authors: T. Keller; C. Hohmann, M. Standl, A. H. Wijga, U. Gehring, E. Melén, C. Almqvist, S. Lau, E. Eller, U. Wahn, E. S. Christiansen, A. von Berg, J. Heinrich, I. Lehmann, D. Maier, D. S. Postma, J. M. Antó, J. Bousquet, T. Keil, S. Roll
      Pages: 602 - 614
      Abstract: BackgroundCross-sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether 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 cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, 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 = .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 = .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: 2017-11-07T04:45:27.728716-05:
      DOI: 10.1111/all.13312
  • Increased attention-deficit/hyperactivity symptoms in atopic dermatitis
           are associated with history of antihistamine use
    • Authors: J. Schmitt; A. Buske-Kirschbaum, F. Tesch, K. Trikojat, V. Stephan, S. Abraham, A. Bauer, K. Nemat, F. Plessow, V. Roessner
      Pages: 615 - 626
      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 and to investigate aspects of AD related to ADHD symptoms.MethodsApplying a factorial design, we investigated 4 groups of children aged 6-12 years: AD-only (ie, without ADHD), ADHD-only (ie, without AD), AD + ADHD and healthy controls (HC; ie, 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.
      PubDate: 2017-11-20T20:55:35.8926-05:00
      DOI: 10.1111/all.13326
  • A composite of exhaled LTB4, LXA4, FeNO, and FEV1 as an “asthma
           classification ratio” characterizes childhood asthma
    • Authors: L.-C. Chen; H.-M. Tseng, M.-L. Kuo, C.-Y. Chiu, S.-L. Liao, K.-W. Su, M.-H. Tsai, M.-C. Hua, S.-H. Lai, T.-C. Yao, K.-W. Yeh, A.-H. Wu, J.-L. Huang, S.-K. Huang
      Pages: 627 - 634
      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 was 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.
      PubDate: 2017-11-27T03:15:36.649667-05:
      DOI: 10.1111/all.13318
  • Airway pathology in severe asthma is related to airflow obstruction but
           not symptom control
    • Authors: D. S. Ferreira; R. M. Carvalho-Pinto, M. G. Gregório, R. Annoni, A. M. Teles, M. Buttignol, B. B. Araújo-Paulino, E. H. Katayama, B. L. Oliveira, H. S. Del Frari, A. Cukier, M. Dolhnikoff, R. Stelmach, K. F. Rabe, T. Mauad
      Pages: 635 - 643
      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.MethodsFifty severe asthmatics received prednisone 40 mg/d 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 nonpersistent 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.
      PubDate: 2017-10-23T01:47:55.20385-05:0
      DOI: 10.1111/all.13323
  • Different functional genes of upper airway microbiome associated with
           natural course of childhood asthma
    • Authors: B.-S. Kim; E. Lee, M.-J. Lee, M.-J. Kang, J. Yoon, H.-J. Cho, J. Park, S. Won, S. Y. Lee, S. J. Hong
      Pages: 644 - 652
      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 = .023) and that of Staphylococcus was negatively associated with methacholine PC20 (P = .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 (PGE2) 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.
      PubDate: 2017-11-20T20:55:48.910208-05:
      DOI: 10.1111/all.13331
  • Nasal protein profiles in work-related asthma caused by different
    • Authors: H. Suojalehto; I. Lindström, H. Wolff, A. Puustinen
      Pages: 653 - 663
      Abstract: BackgroundThe mechanisms of work-related asthma (WRA) 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 WRA caused by different kind of exposures.MethodsWe collected nasal brush samples from 82 nonsmoking participants, including healthy controls and WRA patients exposed to (i) protein allergens, (ii) isocyanates and (iii) 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.
      PubDate: 2017-10-16T02:41:00.686757-05:
      DOI: 10.1111/all.13325
  • 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
      Pages: 664 - 672
      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 underused.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 to 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%) and post-2010 GLs scored 2.1-6 (30%-86%), on a 7-point Likert scale. The highest scores went to: 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.Clinical ImplicationsWe here evaluate allergen immunotherapy guideline (AIT-GL) quality. Only high-quality AIT-GLs should be consulted for AIT management decisions. In low-resource settings, transculturization of these is preferred over developing low-quality guidelines.
      PubDate: 2017-10-17T01:40:30.558939-05:
      DOI: 10.1111/all.13316
  • RItA: The Italian severe/uncontrolled asthma registry
    • Authors: S. Maio; S. Baldacci, M. Bresciani, M. Simoni, M. Latorre, N. Murgia, F. Spinozzi, M. Braschi, L. Antonicelli, B. Brunetto, P. Iacovacci, P. Roazzi, C. Pini, M. Pata, L. La Grasta, P. Paggiaro, G. Viegi,
      Pages: 683 - 695
      Abstract: BackgroundThe Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care.MethodsFour hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed.ResultsMean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 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, and 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%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 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), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter 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 socioeconomic burden for health services.
      PubDate: 2017-11-22T03:35:37.686738-05:
      DOI: 10.1111/all.13342
  • The prevalence of atopic dermatitis beyond childhood: A systematic review
           and meta-analysis of longitudinal studies
    • Authors: K. Abuabara; A. M. Yu, J.-P. Okhovat, I. E. Allen, S. M. Langan
      Pages: 696 - 704
      Abstract: BackgroundThere are sparse and conflicting data regarding the long-term clinical course of atopic dermatitis (AD). Although often described as a childhood disease, newer population-based estimates suggest the prevalence of pediatric and adult disease may be similar.MethodsOur 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).ResultsOf 2080 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%-5%). Similar results were found with other age cut-offs.ConclusionThe prevalence of AD in longitudinal birth cohort studies is similar in childhood and adolescence/early adulthood.
      PubDate: 2017-11-24T00:35:27.115576-05:
      DOI: 10.1111/all.13320
  • Quantitative analysis of multiple elements in healthy and remodeled
           epithelium from human upper airway mucosa using nuclear microscopy
    • Authors: M.-Q. Ren; Y.-T. Zhou, H.-X. Chen, T.-Y. Li, S. K. Vajandar, T. Osipowicz, F. Watt, C.-W. Li
      Pages: 724 - 727
      Abstract: Elements are vital in airway mucosal physiology and pathology, but their distribution and levels in the mucosa remain unclear. This 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 subepithelial regions; more importantly, our results reveal decreased amounts of Cu and Zn in the remodeled 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.
      PubDate: 2017-11-03T01:21:51.658196-05:
      DOI: 10.1111/all.13329
  • 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
      Pages: 728 - 732
      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 1 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 analyze the possibility of introducing the culprit fish or other nonrelated fish to avoid unnecessary restricted diets.
      PubDate: 2017-11-07T04:45:34.921859-05:
      DOI: 10.1111/all.13336
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-