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Showing 1 - 200 of 1583 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 55, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 44, SJR: 0.547, h-index: 30)
ACEP NOW     Free  
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 50, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 143, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 54, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 7, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 5, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 2)
Addiction     Hybrid Journal   (Followers: 32, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 11, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 24, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 25, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 49, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 253, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 5, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 4)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 14, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 9, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 14, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 44, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 29, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 49, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 129, 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: 90, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 28, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 31, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 15, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 3, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 5, SJR: 2.315, h-index: 79)
American J. of Orthopsychiatry     Hybrid Journal   (Followers: 4, SJR: 0.756, h-index: 69)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 36, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 250, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 15, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 118, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 11, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 16)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 157)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 212, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 34, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 8, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 43, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 24, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 16, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 14)
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: 93, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 44, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 6, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 67, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 138, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 48, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 13, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 34, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 14, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 215, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 49, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 28, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 14)
Asia & the Pacific Policy Studies     Open Access   (Followers: 14)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 313, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 7, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 3, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 3, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 4, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 13, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 12, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 10, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 7, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 13, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 4, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 43, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 6, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 22, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 13, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 17, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 386, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 4, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 66, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 31, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 3, 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: 8, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 23, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 14, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 3, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 42, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 36, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 136, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 13, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 18, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 10, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 34, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 5, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)

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Journal Cover Allergy
  [SJR: 3.048]   [H-I: 129]   [49 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0105-4538 - ISSN (Online) 1398-9995
   Published by John Wiley and Sons Homepage  [1583 journals]
  • Fibroblast-derived exosomes promote epithelial cell proliferation through
           TGF-β2 signaling pathway in severe asthma
    • Authors: Ikhlass haj-Salem; Sophie Plante, Abdelilah S. Gounni, Mahmoud Rouabhia, Jamila Chakir
      Abstract: BackgroundBronchial fibroblasts play a key role in airway remodeling in asthma. They regulate epithelial cell functions such as proliferation through growth factors, cytokines, chemokines and exosomes. The role of exosomes in the communication between epithelial cells and fibroblasts by vehiculing these mediators in asthma remains to be determined.ObjectiveTo evaluate the role of exosomes released by bronchial fibroblasts on epithelial cell proliferation in severe asthma.MethodsExosomes were obtained from culture media of primary bronchial fibroblasts and characterized using Western blot, electron microscopy and flow cytometry. Uptake profile of fluorescent-labeled exosomes in epithelial cells was assessed by flow cytometry. Exosome cytokine content was analysed by Cytokine Arrays. Bronchial epithelial cell proliferation was evaluated by BrdU incorporation test. Exosomes biogenesis/release was blocked by using sphingomyelinase inhibitor. Plasmid transfection was used to modulate TGF-β2 gene expression.ResultsWe showed that bronchial fibroblasts secreted exosomes, which were internalized by bronchial epithelial cells. Exosomes of severe asthmatic subjects’ fibroblasts showed a lower level of TGF-β2 and significantly increased the epithelial cells proliferation of both healthy and severe asthmatic subjects compared to healthy controls’ exosomes. Overexpression of TGF-β2 in severe asthmatics’ fibroblasts induced enhanced TGF-β2 in exosomes leading to a reduced proliferation of epithelial cells, whereas knockdown of TGF-β2 enhanced epithelial cell proliferation.ConclusionOur study shows that exosomes are involved in fine-tuning intercellular communication in asthma. Exosomes of severe eosinophilic asthmatics’ fibroblasts can contribute to airway remodeling, at least in part, by modulating epithelial cell proliferation observed in severe asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-26T01:42:31.525685-05:
      DOI: 10.1111/all.13234
  • Cytomegalovirus DNA is highly prevalent in the blood of patients with
           asthma and is associated with age and asthma traits
    • Authors: Marek L. Kowalski; Aleksandra Wardzynska, Miroslawa Studzinska, Malgorzata Pawelczyk, Zbigniew Jan Lesnikowski, Edyta Paradowska
      Abstract: CMV IgG antibodies have been associated with inflammageing and immunosenescence. We aimed to assess the presence of CMV DNA in the blood of adult and elderly patients with bronchial asthma to establish potential association of CMV DNAemia with asthma and asthma characteristics. Eighty-five elderly asthmatics, 74 younger asthma patients and 114 age-matched controls were recruited. The CMV DNA was detected using commercial artus assay in 10.7% of asthma patients, but was negative in all control individuals. The secondary assay identified CMV DNA in 41.5% of asthmatics and 13.3% of control subjects (p
      PubDate: 2017-06-22T21:20:28.258004-05:
      DOI: 10.1111/all.13233
  • Atopic dermatitis is associated with anxiety, depression, and suicidal
           ideation, but not with hospitalization or suicide
    • Authors: Jacob P. Thyssen; Carsten R. Hamann, Allan Linneberg, Thomas Meinertz Dantoft, Lone Skov, Gunnar H. Gislason, Jashin J. Wu, Alexander Egeberg
      Abstract: BackgroundAtopic dermatitis (AD) has been linked with psychiatric disease in adults. However, the exact relationship and its consequences have been insufficiently studied. Our aim in this study was to assess the association between depression, anxiety and AD in adults, and examine the risk of hospitalization and suicide.MethodsWe utilized questionnaire data from a large general population study with data on social habits and psychiatric symptoms to compare prevalences of depression, anxiety, suicidal ideation, and anxiety attacks, in adults with and without a history of AD. Additionally we used nationwide hospital/clinic registry and prescription data to examine the risk of anxiety and depression in Danish adults with mild and moderate-severe AD, as well as the risk of hospitalization and suicide.ResultsIn the general population study, those with AD reported clinician-diagnosed depression and anxiety more often than non-AD subjects, and had an increased prevalence of suicidal ideation and depressive symptoms. In the health registry study, moderate-severe AD patients had increased risk of antidepressant and anxiolytic medication use, while patients with mild AD only had increased risk of anxiolytic medication use. There was no increased risk of hospitalization or outpatient contacts due to depression or anxiety, or risk of suicide in AD patients.ConclusionsDepression, anxiety, and suicidal ideation are more common among AD individuals, but do not to lead to psychiatric consultations, hospitalization, or suicide.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-20T13:16:04.878-05:00
      DOI: 10.1111/all.13231
  • A prospective microbiome-wide association study of food sensitization and
           food allergy in early childhood
    • Authors: Jessica H. Savage; Kathleen A. Lee-Sarwar, Joanne Sordillo, Supinda Bunyavanich, Yanjiao Zhou, George O'Connor, Megan Sandel, Leonard Bacharier, Robert Zeiger, Erica Sodergren, George M Weinstock, Diane R. Gold, Scott T. Weiss, Augusto A. Litonjua
      Abstract: BackgroundAlterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development.MethodsIntestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high dose Vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 with evidence of IgE sensitization. Analysis was performed using Phyloseq and DESeq2; p-values were adjusted for multiple comparisons.ResultsComplete data were available for 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases and controls. The genera Haemophilus (log2 fold change -2.15, p=0.003), Dialister (log2 fold change -2.22, p=0.009), Dorea (log2 fold change -1.65, p=0.02) and Clostridium (log2 fold change -1.47, p=0.002) were underrepresented among subjects with food sensitization. The genera Citrobacter (log2 fold change -3.41, p=0.03), Oscillospira (log2 fold change -2.80, p=0.03), Lactococcus (log2 fold change -3.19, p=0.05) and Dorea (log2 fold change -3.00, p=0.05) were underrepresented among subjects with food allergy.ConclusionsThe temporal association between bacterial colonization and food sensitization and allergy suggests that the microbiome may have a causal role in the development of food allergy. Our findings have therapeutic implications for the prevention and treatment of food allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-20T13:16:01.451215-05:
      DOI: 10.1111/all.13232
  • Histamine Receptor 2 Modifies iNKT Cell Activity within the Inflamed Lung
    • Authors: R. Ferstl; R. Frei, W. Barcik, E. Schiavi, K. Wanke, M. Ziegler, N. Rodriguez-Perez, D. Groeger, P. Konieczna, S. Zeiter, D. Nehrbass, Roger Lauener, C.A. Akdis, L. O'Mahony
      Abstract: BackgroundHistamine is a key immunoregulatory mediator and can dampen proinflammatory responses via activation of histamine receptor 2 (H2R). The aim of this study was to determine the role of H2R in modulating lung inflammatory responses.MethodsH2R was blocked using famotidine or activated using dimaprit in both the ovalbumin (OVA) and house dust mite extract (HDM) murine models of respiratory inflammation. H2R-deficient animals and CD1d/ H2R-deficient animals were utilized to examine the CD1d presentation of lipid antigens (αGal-Cer or OCH) to invariant Natural Killer T (iNKT) cells.ResultsFamotidine treatment resulted in more severe airway disease in the OVA model, while dimaprit treatment significantly reduced disease severity. Both OVA and HDM-induced airway disease were more severe in H2R-deficient animals. Flow cytometric analysis of lung tissue from H2R-deficient animals revealed increased numbers of CD1d+ dendritic cells and increased numbers of iNKT cells. In vitro, αGal-Cer-stimulated iNKT cells from H2R-deficient mice secreted higher levels of IL-4, IL-5 and GM-CSF. In vivo, αGal-Cer or OCH administration to the lung resulted in enhanced mucus secretion, inflammatory cell recruitment and cytokine production in H2R-deficient or famotidine-treated animals, while dimaprit dampened the lung iNKT cell response to αGalCer. Removal of iNKT cells in H2R-deficient (CD1d-/-H2R-/-) animals normalized the lung response to HDM.ConclusionThe deliberate activation of H2R, or its downstream signaling molecules, may represent a novel therapeutic target for chronic lung inflammatory diseases, especially when CD1d-mediated presentation of lipid antigens to iNKT cells are contributing to the pathology.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-15T05:20:22.702153-05:
      DOI: 10.1111/all.13227
  • Is the atopic march related to confounding by genetics and early life
           environment' A systematic review of sibship and twin data
    • Authors: Sabria J. Khan; Shyamali C. Dharmage, Melanie C. Matheson, Lyle C. Gurrin
      Abstract: A popular hypothesis known as the atopic march proposes a set of sequential allergy and respiratory disorders in early childhood contributes enormously to the burden of disease in developed countries. Although the concept of the atopic march has been refined and strengthened by many cross-sectional and longitudinal studies linking eczema as the initial manifestation with progression to hay fever and then asthma, there is yet no definitive proof that the atopic march is the primary causal factor in childhood allergic disease. This debate is mainly related to the controversy around potential confounding of these associations by genetic and environmental factors. Family studies are ideally suited to unravelling the role of these factors. While multiple reviews have synthesised evidence from studies investigating this question, no review to date has explored specific evidence generated by twin and sibling studies to understand the aetiology of atopic march diseases. Our aim was to conduct a systematic review of twin and sibling studies that examine the allergic phenotypes that form the atopic march, to determine whether such analyses of data from these studies attempt to control for the effect confounding by shared factors, and to report estimates the magnitude of associations between multiple phenotypes. Our review suggests that (1) genetics play a bigger role predisposing eczema to hay fever and eczema to asthma than environmental factors; and (2) the link between eczema, and asthma and hay fever is independent of shared early life environmental factors and genetics.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-15T05:15:22.798184-05:
      DOI: 10.1111/all.13228
  • Validation of International consensus equation for acute serum total
           tryptase in mast cell activation: A perioperative perspective
    • Authors: Richard L Baretto; Sarah Beck, Jane Heslegrave, Cathryn Melchior, Omar Mohamed, Anjali Ekbote, Aarnoud P Huissoon, Mamidipudi T Krishna
      Abstract: IntroductionThere is no standardised method for assessing serum total mast cell tryptase (MCT) in anaphylaxis. The consensus equation (peak MCT should be>1.2x baseline tryptase+2mg/L) has been proposed to interpret acute MCT in mast cell activation syndrome (MCAS).AimTo validate consensus equation in a setting of perioperative anaphylaxis.MethodsAnalyses of suspected perioperative anaphylaxis during general anaesthesia (GA). Anaphylaxis was defined as per World Allergy Organisation (WAO) criteria. Timed serial MCT measurements were mapped against the consensus equation and receiver operating characteristic (ROC) curves produced.Results82 patients (60 females, mean age 56.5 years ± SD17.2) underwent investigation. 60 (73%) patients fulfilled WAO criteria for anaphylaxis and 22 patients did not (controls). Aetiology: 59% IgE-mediated anaphylaxis, 2% non-IgE mediated anaphylaxis, 12% anaphylaxis of unknown cause, and 27% deemed non-anaphylaxis. IgE-mediated anaphylaxis included - NMBA (35%), antibiotics (46%), chlorhexidine (8%), patent blue dye (8%) and others (8%). An acute MCT with a comparable baseline was available in 71/82 (87%) patients (60-anaphylaxis and 11-controls).The median (IQR) time from reaction to peak MCT was 1.34 (0.82-2.51) hours. Analyses confirmed that a rise in acute MCT greater than that defined by the equation had a sensitivity, specificity, positive predictive value (PPV) and negative (N) PV of 78%, 91%, 98%, and 44% respectively. The magnitude of increase in acute MCT above the threshold predicted by consensus equation was higher in the anaphylaxis group compared to controls (P=0.0001).ConclusionThis equation has a high specificity, PPV with a moderate NPV and sensitivity in perioperative anaphylaxis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-13T14:35:19.144206-05:
      DOI: 10.1111/all.13226
  • What's in a name': Atopic dermatitis or atopic eczema, but not eczema
    • Authors: Jonathan I Silverberg; Jacob P Thyssen, Amy S Paller, Aaron Drucker, Andreas Wollenberg, Kwang Hoon Lee, Kenji Kabashima, Gail Todd, Peter Schmid-Grendelmeier, Thomas Bieber
      Abstract: BackgroundThe ideal nomenclature of atopic dermatitis or atopic eczema (AD/AE) has long been contested. It is becoming increasingly clear that the disparate nomenclature of this disease may have important deleterious ramifications for clinical care, research and drug development.ObjectiveTo reach consensus among an international group of experts in AD/AE on the nomenclature for AD/AE.MethodsA 3-question survey was sent to the councilors and associates of the International Eczema Council. Consensus was reached with at least 90% response and more than 90% agreement on nomenclature.ResultsSeventy-one of 77 (92.2%) IEC councilors and associates responded to the survey. Consensus was reached on the preference for the atopic prefix, i.e. AD or AE (69 of 71 [97.2%]). However, consensus was not reached preference of AD (40 [58.0%]) or AE (30 [43,5%]). Sixty-three respondents (88.7%) and 55 (77.5%) felt that the terms AD and AE were acceptable, whereas only 11 (15.5%) felt that eczema was acceptable.ConclusionsUse of the atopic prefix, i.e. either AE or AD, is recommended. Whereas, use of the term eczema is not recommended. We encourage physicians in all specialties and in every country to shift their own use of terminology to AD or AE in writing, presentations and discussions with patients and other health care personnel as a first step.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-12T06:35:29.105232-05:
      DOI: 10.1111/all.13225
  • Transfer of innovation on allergic rhinitis and asthma multimorbidity in
           the elderly (MACVIA-ARIA) - Reference Site Twinning (EIP on AHA)
    • Authors: J Bousquet; I Agache, M R Aliberti, R Angles, I Annesi-Maesano, J M Anto, S Arnavielhe, E Asayag, E Bacci, A Bedbrook, C Bachert, I Baroni, B A Barreto, M Bedolla-Barajas, K C Bergmann, L Bertorello, M Bewick, T Bieber, S Birov, C Bindslev-Jensen, A Blua, M Bochenska Marciniak, I Bogus-Buczynska, S Bosnic-Anticevich, I Bosse, R Bourret, C Bucca, R Buonaiuto, D Caiazza, D Caillot, D P Caimmi, P Camargos, G Canfora, V Cardona, A M Carriazo, C Cartier, G Castellano, N H Chavannes, M M Ciaravolo, C Cingi, A Ciceran, L Colas, E Colgan, J Coll, D Conforti, J Correira de Sousa, R M Cortés-Grimaldo, F Corti, E Costa, A L Courbis, E Cousein, A A Cruz, A Custovic, B Cvetkovski, C Dario, M da Silva, Y Dauvilliers, F De Blay, T Dedeu, G De Feo, B De Martino, P Demoly, G De Vries, S Di Capua Ercolano, N Di Carluccio, M Doulapsi, G Dray, R Dubakiene, E Eller, R Emuzyte, J M Espinoza-Contreras, A Estrada-Cardona, J Farrell, J Ferrero, W J Fokkens, J Fonseca, J F Fontaine, S Forti, J L Gálvez-Romero, C I García-Cobas, M H Garcia Cruz, B Gemicioğlu, R Gerth van Wijk, M Guidacci, J Gómez-Vera, N A Guldemond, Z Gutter, T Haahtela, J Hajjam, P W Hellings, L Hernández-Velázquez, M Illario, J C Ivancevich, E Jares, G Joos, J Just, O Kalayci, A F Kalyoncu, J Karjalainen, T Keil, N Khaltaev, L Klimek, V Kritikos, I Kull, P Kuna, V Kvedariene, V Kolek, E Krzych-Fałta, M Kupczyk, P Lacwik, D Larenas-Linnemann, D Laune, D Lauri, J Lavrut, M Lessa, G Levato, L Lewis, I Lieten, A Lipiec, R Louis, J A Luna-Pech, A Magnan, J Malva, J F Maspero, J J Matta-Campos, O Mayora, M A Medina-Ávalos, E Melén, E Menditto, J Millot-Keurinck, G Moda, M Morais-Almeida, R Mösges, A Mota-Pinto, J Mullol, A Muraro, R Murray, M Noguès, M Nalin, L Napoli, H Neffen, R E O'Hehir, G Onorato, S Palkonen, N G Papadopoulos, G Passalacqua, J L Pépin, A M Pereira, M Persico, O Pfaar, A C Pozzi, E Prokopakis, F Raciborski, J Rimmer, J A Rizzo, C Robalo-Cordeiro, M Rodríguez-González, G Rolla, R E Roller-Wirnsberger, A Romano, M Romano, J Salimäki, B Samolinski, F S Serpa, S Shamai, M Sierra, M Sova, M Sorlini, C Stellato, R Stelmach, T Strandberg, V Stroetmann, R Stukas, A Szylling, R Tan, V Tibaldi, A Todo-Bom, S Toppila-Salmi, P Tomazic, U Trama, M Triggiani, A Valero, E Valovirta, A Valiulis, M van Eerd, T Vasankari, A Vatrella, M T Ventura, M T Verissimo, F Viart, S Williams, M Wagenmann, C Wanscher, M Westman, M Wickman, I Young, A Yorgancioglu, E Zernotti, T Zurbierber, A Zurkuhlen, B De Oliviera, A Senn
      Abstract: The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives while ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study is to transfer innovation from an App developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will: (i) assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) study phenotypic characteristics and treatment over a period of one year of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-10T09:50:20.718726-05:
      DOI: 10.1111/all.13218
  • Influences of environmental bacteria and their metabolites on allergies,
           asthma and host microbiota
    • Authors: G Jatzlauk; S Bartel, H Heine, M Schloter, S Krauss-Etschmann
      Abstract: The prevalence of allergic diseases and asthma has dramatically increased over the last decades, resulting in a high burden for patients and health care systems. Thus, there is an unmet need to develop preventative strategies for these diseases.Epidemiological studies show that reduced exposure to environmental bacteria in early life (e.g birth by cesarian section, being formula-fed, growing up in an urban environment or with less contact to various persons) is associated with an increased risk to develop allergies and asthma later in life. Conversely, a reduced risk for asthma is consistently found in children growing up on traditional farms, thereby being exposed to a wide spectrum of microbes. However, clinical studies are still rare and to some extent contradicting. A detailed mechanistic understanding how environmental microbes influence the development of the human microbiome and the immune system is important to enable the development of novel preventative approaches that are based on the early modulation of the host microbiota and immunity.In this mini-review we summarize current knowledge and experimental evidence for the potential of bacteria and their metabolites to be used for the prevention of asthma and allergic diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-10T09:35:20.296902-05:
      DOI: 10.1111/all.13220
  • Spontaneous food allergy in Was-/- mice occurs independent of
           FcεRI-mediated mast cell activation
    • Authors: Willem S. Lexmond; Jeremy A. Goettel, Benjamin F. Sallis, Katelyn McCann, Edmond H. H. M. Rings, Erika Jensen-Jarolim, Samuel Nurko, Scott B. Snapper, Edda Fiebiger
      Abstract: BackgroundFood allergies are a growing health problem and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was-/- mice recapitulates the pathology of a conventional disease model and/or human food allergy.MethodsComparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was-/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed and the role of the high affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was-/-Fcer1a-/- mice.ResultsPolysensitization to food was detected in both WAS and food allergic patients which was recapitulated in the Was-/- model. Oral administration of OVA in Was-/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was-/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was-/- mice (95%) with a mortality rate>50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells and basophils.ConclusionsWas-/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-10T09:30:21.088787-05:
      DOI: 10.1111/all.13219
  • Beyond epithelial-to-mesenchymal transition: common suppression of
           differentiation programs underlies epithelial barrier dysfunction in mild,
           moderate and severe asthma
    • Authors: Lucas F. Loffredo; Hiam Abdala-Valencia, Kishore R. Anekalla, Lyda Cuervo-Pardo, Cara J. Gottardi, Sergejs Berdnikovs
      Abstract: BackgroundEpithelial barrier dysfunction is a central feature in the pathogenesis of allergic disease. Epithelial-to-mesenchymal transition (EMT) has been proposed as one mechanism afflicting barrier in asthma. However, genes and pathways involved in aberrant epithelial-mesenchymal signaling, and their relationship to asthma severity, are poorly understood.MethodsWe used unbiased gene network analysis to evaluate functional convergence in epithelial gene expression signatures across multiple public access transcriptomics datasets of human asthma, followed by text mining to evaluate functional marker relevance of discovered genes. We objectively confirmed these findings in epithelial brushings and primary asthmatic epithelial cells cultured in different biological contexts.ResultsWe found a striking suppression of epithelial differentiation in asthma, overrepresented by insufficiency in insulin and Notch signaling, but with the absence of conventional EMT markers. We identified EFNB2, FGFR1, FGFR2, INSR, IRS2, NOTCH2, TLE1, and NTRK2 as novel markers central to dysregulation of epithelial-mesenchymal signaling, but surprisingly overlooked in asthma research. We found that this “core” signature of asthma is shared by mild, moderate, and severe forms of disease, progressing with severity. Loss of epithelial differentiation induced by insulin deprivation in normal human bronchial epithelial cells cultured in organotypic conditions closely approximated gene expression in asthmatic epithelial brushings.ConclusionsThe comparative analysis of publically available transcriptomes demonstrated that epithelial barrier dysfunction in asthma is characterized by persistent underlying de-differentiation program with complex etiology. The lasting alteration of the asthmatic epithelial cell transcriptome implicates regulation involving metabolism and epigenetics, beyond EMT driven by injury and repair in chronic inflammation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-09T12:42:08.868088-05:
      DOI: 10.1111/all.13222
  • Non-lesional atopic dermatitis skin shares similar T-cell clones with
           lesional tissues
    • Authors: Patrick M. Brunner; Ryan O. Emerson, Christopher Tipton, Sandra Garcet, Saakshi Khattri, Israel Coats, James G. Krueger, Emma Guttman-Yassky
      Abstract: BackgroundAtopic dermatitis (AD) is characterized by robust immune activation. Various T-cell subsets, including Th2/Th22 cells, are increased in lesional and non-lesional skin. However, there is conflicting literature on the diversity of the T-cell receptor (TCR) repertoire in lesional AD, and its relation to non-lesional skin remains unclear.MethodsWe performed high-throughput deep sequencing of the β-TCR repertoire in 29 lesional and 19 non-lesional AD biopsies, compared to 6 healthy control and 6 cutaneous T-cell lymphoma (CTCL) samples from previously published cohorts.ResultsWhile greater T-cell infiltrates were observed in lesional vs. non-lesional AD, TCR repertoire diversity was similar in lesional and non-lesional tissues, and absolute numbers of unique T-cell clones correlated with respective T-cell counts. Most (87%) top expanded lesional T-cell clones were shared with non-lesional tissues, and they were largely maintained after 16 weeks of successful treatment with topical triamcinolone. Nevertheless, both lesional and non-lesional AD showed a highly polyclonal TCR pattern, without evidence of oligoclonal expansion, or a preferred usage of certain V-β genes in AD skin. Size of the overall T-cell infiltrate, but not the level of clonality, correlated with mRNA levels of key inflammatory mediators (e.g. IL-13, CCL17, IL23p19, CXCL10).ConclusionWhile AD harbors a highly polyclonal T-cell receptor repertoire, and despite the lack of information on TCR antigen specificity, the sharing of top abundant clones between lesional and non-lesional skin, and their persistence after months of therapy, points to the continuous presence of potentially pathogenic skin resident memory T-cells well beyond clinically inflamed lesions.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-09T12:42:06.366339-05:
      DOI: 10.1111/all.13223
  • Mechanisms of exercise-induced bronchoconstriction in athletes: current
           perspectives and future challenges
    • Authors: Mariana Couto; Marcin Kurowski, André Moreira, Dominique M.A. Bullens, Kai-Håkon Carlsen, Luís Delgado, Marek L. Kowalski, Sven F. Seys
      Abstract: The evidence of exercise-induced bronchoconstriction (EIB) without asthma (EIBwA) occurring in athletes led to speculate about different endotypes inducing respiratory symptoms within athletes. Classical postulated mechanisms for bronchial obstruction in this population include the osmotic and the thermal hypotheses. More recently, the presence of epithelial injury and inflammation in the airways of athletes was demonstrated. In addition, neuronal activation has been suggested as a potential modulator of bronchoconstriction. Investigation of these emerging mechanisms are of major importance since EIB is a significant problem for both recreational and competitive athletes and is the most common chronic condition among Olympic athletes, with obvious implications for their competing performance, health and quality of life. Hereby we summarize the latest achievements in this area and identify the current gaps of knowledge so that future research heads towards better defining the etiologic factors and mechanisms involved in development of EIB in elite athletes as well as essential aspects to ultimately propose preventive and therapeutic measures.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-09T12:42:02.935532-05:
      DOI: 10.1111/all.13224
  • A possible role of stem cells in nasal polyposis
    • Authors: L. Klimek; M. Koennecke, J. Mullol, P.W. Hellings, D.Y. Wang, W. Fokkens, P h. Gevaert, B. Wollenberg
      Abstract: Since its discovery, the understanding of stem/progenitor cells raised dramatically in the last decade. Their regenerative potential is important to develop new therapeutic applications, but the identification advanced much faster than our understanding of stem/progenitor cells. In nasal polyposis, little is known about stem cells/progenitor cells and their ability. However, the further characterization of stem cells/progenitor cells may provide new treatment options for combating nasal polyposis. This review highlights the knowledge of the current literature about stem cells/progenitor cells in nasal polyposis and how this may be exploited in the development of novel treatment strategies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-09T12:35:19.145655-05:
      DOI: 10.1111/all.13221
  • Functional and phenotypic analysis of basophils allows determining
           distinct subtypes in patients with chronic urticaria
    • Authors: Michèle Myriam Rauber; Julia Pickert, Lily Holiangu, Christian Möbs, Wolfgang Pfützner
      Abstract: BackgroundChronic urticaria (CU) is a frequent skin disease characterized by relapsing appearance of pruritic hives. While clinical symptoms are due to the release of histamine by cutaneous mast cells, the underlying pathophysiology is still unknown. However, previous studies indicate that basophils might be of relevance. Besides, the occurrence of autoantibodies against IgE or its receptor, FcεRI, and the therapeutic efficacy of anti-IgE antibodies imply that IgE-mediated mechanisms also play an important role in CU.MethodsReactivity of CU patients’ peripheral blood basophils (n=60) to specific anti-FcεRI and IgE-independent fMLP stimulation was determined by basophil activation test in comparison to patients suffering from IgE-mediated allergic rhinitis (n=10) and healthy controls (n=10). In addition, immunoglobulin receptor (FcεRI, FcγRII) expression and surface bound antibodies (IgE, IgG) were quantified on basophils. Furthermore, the autoreactive capacity of CU sera was evaluated and urticaria-related symptoms were assessed by both UCT and CU-Q2oL.ResultsStimulating CU patients’ basophils via FcεRI, we identified three distinct immunological phenotypes. One subgroup of patients' basophils reacted to FcεRI stimulation, whereas the others had anti-FcεRI non-reactive basophils. Among the latter a subgroup with pronounced basopenia was identified. Of note, this group was characterized by augmented serum-induced basophil activation, increased levels of autoantibodies against thyroid peroxidase and also exhibited the strongest disease impact on their quality of life.ConclusionsCU patients can be categorized into three immunological subgroups based on their basophil reactivity and frequency. These phenotypes are associated with different clinical characteristics, pointing to basophils as important players in CU pathophysiology.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-05T22:43:37.265921-05:
      DOI: 10.1111/all.13215
  • Omalizumab effectively protects against early- and late allergic responses
           in asthma after 4 weeks
    • Authors: Jordis Trischler; Adrian Lieb, Melina Arnold, Johannes Schulze, Martin Rosewich, Ralf Schubert, Ivan Bottoli, Stefan Zielen
      Abstract: Omalizumab is licensed for therapy in severe allergic asthma with an effect demonstrated after 8 weeks or longer treatment. Since new applications for omalizumab demand precise knowledge of the onset of effects, the objective of this study was to determine the time course of the early (EAR) and late allergic reaction (LAR). Ten patients (IgE>300 IU/mL and
      PubDate: 2017-06-05T04:17:38.525584-05:
      DOI: 10.1111/all.13217
  • Heme oxygenase-1 directly binds STAT3 to control the generation of
           pathogenic Th17 cells during neutrophilic airway inflammation
    • Authors: Xiaoliang Lin; Jiajia Lv, Jie Lv, Caixia Di, Yanjie Zhang, Tong Zhou, Junling Liu, Zhenwei Xia
      Abstract: BackgroundSpecific JAK/STAT pathways play a critical role in the functional differentiation of distinct Th subsets. Previously, we showed that HO-1, a stress-inducible protein, inhibits Th17 cell differentiation and alleviates neutrophilic airway inflammation, but the responsible molecular basis remains unclear.MethodsWe employed Th17-skewing differentiation and NEA mouse models to study the role of HO-1 regulating IL-6-STAT3-RORγt/SOCS3 signaling pathway to control Th17 cell-mediated neutrophilic airway inflammation. The levels of cytokines and expressions of relative signaling molecular were measured by ELISA, western blot and qPCR, respectively. Frequency of CD4+IL-17A+, CD4+IL-6R+ and CD4+IL-23R+ cells was analyzed by FCM. The interaction between HO-1 and signaling pathway-related proteins was determined by Co-Immunoprecipitation and western blot.ResultsHere, we show that hemin-induced HO-1 over-expression is required to mediate this process. Specifically, HO-1 decreased STAT3 phosphorylation but not IL-6R/IL-23R expression or JAK1/JAK2 activation in CD4+ T cells. The effect was accompanied by co-inhibition of SOCS3, a negative feedback factor of STAT3 activation. HO-1 bound to three domains on STAT3, (DNA-binding, linker and transactivation domains) to directly regulate STAT3 activation. Conversely, either forced expression of a constitutively active STAT3 mutant or application of small interfering RNA (siRNA) for HO-1 reversed these effects.ConclusionsOur data suggest that HO-1 exerts its inhibitory effect on Th17 cell differentiation by directly associating and blocking STAT3 phosphorylation. We speculate that hemin may be a potential therapeutic candidate for the treatment of other types of immune and pulmonary inflammatory-related diseases.This article is protected by copyright. All rights reserved.
      PubDate: 2017-06-05T00:40:22.016457-05:
      DOI: 10.1111/all.13216
  • Sputum Basophils and Asthma Diagnosis: Dawn of a New Era'
    • Authors: Michaela Fux; Christophe von Garnier
      Abstract: More than 40 years ago, Kimura et al. discovered that basophils are enriched in sputum samples of asthma patients (1). Since then, various scientific approaches have attempted to elucidate the role of basophils in the pathophysiology of asthma. The scarcity of basophils and technical limitations of earlier studies have made it difficult to increase our understanding how basophils affect the disease course in asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-31T07:17:23.900031-05:
      DOI: 10.1111/all.13214
  • Sublingual immunotherapy provides long-term relief in allergic rhinitis
           and reduces the risk of asthma: a retrospective, real-world database
    • Authors: S Zielen; P Devillier, J Heinrich, H Richter, U Wahn
      Abstract: BackgroundAllergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long-term efficacy. However, there are few real-life data on the progression of AR and/or AA in patients receiving AIT.ObjectivesTo assess the real-world, long-term efficacy of grass-pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression.MethodsIn a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups.ResultsAfter applying all selection criteria, 2851 SLIT and 71275 Control patients were selected for the study.After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pre-treatment period) in SLIT tablet group than in the non AIT group (p
      PubDate: 2017-05-31T07:17:18.788984-05:
      DOI: 10.1111/all.13213
  • Targeting PP2A and proteasome activity ameliorates features of allergic
           airway disease in mice
    • Authors: Prema M. Nair; Malcolm R. Starkey, Tatt Jhong Haw, Gang Liu, Jay C. Horvat, Jonathan C. Morris, Nikki M. Verrills, Andrew R. Clark, Alaina J. Ammit, Philip M. Hansbro
      Abstract: BackgroundAsthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed if enhancing PP2A activity with Fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S)), or inhibiting proteasome activity with Bortezomib (BORT) could suppress experimental AAD.MethodsAcute AAD was induced in C57BL/6 mice by intraperitoneal sensitisation with ovalbumin (OVA) in combination with intranasal (i.n) exposure to OVA. Chronic AAD was induced in mice with prolonged i.n exposure to crude house dust mite (HDM) extract. Mice were treated with vehicle, FTY720, AAL(S), BORT or AAL(S)+BORT and hallmark features of AAD assessed.ResultsAAL(S) reduced the severity of acute AAD by suppressing tissue eosinophils and inflammation, mucus secreting cell (MSC) numbers, type-2 associated cytokines (Interleukin (IL)-33, thymic stromal lymphopoietin, IL-5 and IL-13), serum immunoglobulin (Ig)E, and airway hyper-responsiveness (AHR). FTY720 only suppressed tissue inflammation and IgE. BORT reduced bronchoalveolar lavage fluid (BALF) and tissue eosinophils and inflammation, IL-5, IL-13, and AHR. Combined treatment with AAL(S)+BORT had complementary effects and suppressed BALF and tissue eosinophils and inflammation, MSC numbers, reduced the production of type-2 cytokines and AHR. AAL(S), BORT and AAL(S)+BORT also reduced airway remodelling in chronic AAD.ConclusionThese findings highlight the potential of combination therapies that enhance PP2A and inhibit proteasome activity as novel therapeutic strategies for asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-24T18:20:26.085747-05:
      DOI: 10.1111/all.13212
  • Poaceae pollen as the leading aeroallergen worldwide: a review
    • Authors: H. García-Mozo
      Abstract: The Poaceae family comprises over 12,000 wind-pollinated species which release large amounts of pollen into the atmosphere. Poaceae pollen is currently regarded as the leading airborne biological pollutant and the chief cause of pollen-allergy worldwide. Sensitization rates vary by country, and those variations are reviewed here.Grass pollen allergens are grouped according to their protein structure and function. In Poaceae, although species belonging to different sub-families are characterized by distinct allergen subsets, there is a considerable degree of cross-reactivity between many species. Cross-reactivity between grass-pollen protein and fresh fruit pan-allergens is associated with the appearance of food allergies. The additional influence of urban pollution may prompt a more severe immunological response.The timing and the intensity of the pollen season is governed by species genetics, but plant phenology is also influenced by climate; as a result, climate changes may affect airborne pollen concentrations. This paper reviews the findings of worldwide research which has highlighted the major impact of climate change on plant phenology and also on the prevalence and severity of allergic disease.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-22T03:00:29.190916-05:
      DOI: 10.1111/all.13210
  • Changes in patient quality of life during oral immunotherapy for food
    • Authors: Na'ama Epstein Rigbi; Michael R Goldberg, Michael B Levy, Liat Nachshon, Keren Golobov, Arnon Elizur
      Abstract: BackgroundQuality of life is (QOL) impaired in patients with food allergy and improves following oral immunotherapy (OIT). However, the treatment itself is prolonged and demanding. We examined changes in patient QOL during OIT for food allergy.MethodsThe FAQLQ-PF was administered to children aged 4-12 years undergoing OIT for milk, peanut or egg allergy, at the beginning and after 4 months of treatment. Patients were categorized as improved, unchanged, or diminished FAQLQ-PF (>0.5 point decrease, a change of ≤0.5 points, or>0.5 increase, respectively) and compared. Food-allergic patients not undergoing OIT served as controls.ResultsThe Food Anxiety, Social and Dietary limitation and total FAQLQ-PF scores improved significantly during the study period (p=0.001, p=0.018 and p=0.01, respectively) in treated but not in control patients, while the Emotional Impact did not. The change in the FAQLQ-PF was independent of the maximal tolerated dose at baseline or following four months of treatment, the pace of dose-increase or of number or severity of reactions experienced. The total FAQLQ-PF score was inversely associated with the score at baseline on multi-variate analysis (regression coefficient = -0.56, p
      PubDate: 2017-05-22T03:00:26.799962-05:
      DOI: 10.1111/all.13211
  • Allergen immunotherapy for allergic asthma: a systematic review and
    • Authors: Sangeeta Dhami; Artemisia Kakourou, Felix Asamoah, Ioana Agache, Susanne Lau, Jutel Marek, Antonella Muraro, Graham Roberts, Cezmi A. Akdis, Matteo Bonini, Ozlem Cavkaytar, Breda Flood, Pawel Gajdanowicz, Kenji Izuhara, Ömer Kalayci, Ralph Mosges, Oscar Palomares, Oliver Pfaar, Sylwia Smolinska, Milena Sokolowska, Miqdad Asaria, Gopal Netuveli, Hader Zaman, Ather Akhlaq, Aziz Sheikh
      Abstract: BackgroundTo inform the development of the European Academy of Allergy and Clinical Immunonology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT.MethodsWe performed a systematic review, which involved searching nine databases. Studies were screened against pre-defined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses.Results98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of -1.11 (95%CI -1.66, -0.56). This was robust to a pre-specified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD -1.21 (95%CI -1.87, -0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95%CI -0.23, 0.58), but one study showed a beneficial long-term effect.For secondary outcomes subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen specific airways hyperreactivity (AHR) but this was not the case for sub-lingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and non-specific AHR.AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported.The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective.ConclusionsAIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiveness and cost-effectiveness.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-19T10:35:25.924075-05:
      DOI: 10.1111/all.13208
  • The Burden of Chronic Spontaneous Urticaria Is Substantial: Real-World
           Evidence From ASSURE-CSU
    • Authors: Marcus Maurer; Mohamed Abuzakouk, Frédéric Bérard, Walter  Canonica, Hanneke Oude Elberink, Ana Giménez-Arnau, Clive  Grattan, Kelly Hollis, André Knulst, Jean-Philippe Lacour, Charles Lynde, Alexander Marsland, Doreen McBride, Alla  Nakonechna, Javier Ortiz de Frutos, Christina Proctor, Gordon  Sussman, Carolyn Sweeney, Haijun Tian, Karsten Weller, Daniel Wolin, Maria-Magdalena Balp
      Abstract: BackgroundChronic spontaneous urticaria (CSU) can be debilitating, difficult to treat, and frustrating for patients and physicians. Real-world evidence for the burden of CSU is limited. The objective of this study was to document disease duration, treatment history, and disease activity, as well as impact on health-related quality of life (HRQoL) and work among patients with inadequately controlled CSU, and to describe its humanistic, societal, and economic burden.MethodsThis international observational study assessed a cohort of 673 adult patients with CSU whose symptoms persisted for ≥12 months despite treatment. Demographics, disease characteristics, and health care resources in the previous 12 months were collected from medical records. Patient-reported data on urticaria and angioedema symptoms, HRQoL, and work productivity and activity impairment were collected from a survey and a diary.ResultsAlmost 50% of patients had moderate-to-severe disease activity as reported by Urticaria Activity Score. Mean (SD) Dermatology Life Quality Index and Chronic Urticaria Quality of Life Questionnaire scores were 9.1 (6.62) and 33.6 (20.99), respectively. CSU markedly interfered with sleep and daily activities. Angioedema in the previous 12 months was reported by 66% of enrolled patients and significantly affected HRQoL. More than 20% of patients reported ≥1 hour per week of missed work; productivity impairment was 27%. These effects increased with greater disease activity. Significant health care resources and costs were incurred to treat CSU.ConclusionsCSU has considerable humanistic and economic impacts. Patients with greater disease activity and with angioedema experience greater HRQoL impairments.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-19T10:30:29.507441-05:
      DOI: 10.1111/all.13209
  • Patterns of anaphylaxis after diagnostic work-up: a follow-up study of 226
           patients with suspected anaphylaxis
    • Authors: Athamaica Ruiz Oropeza; Carsten Bindslev-Jensen, Sigurd Broesby-Olsen, Thomas Kristensen, Michael Boe Møller, Hanne Vestergaard, Henrik Fomsgaard Kjaer, Susanne Halken, Annmarie Lassen, Charlotte G. Mortz
      Abstract: BackgroundMost published studies on anaphylaxis are retrospective or register based. Data on subsequent diagnostic work-up are sparse. We aimed to characterize patients seen with suspected anaphylaxis at the emergency care setting (ECS), after subsequent diagnostic work-up at our Allergy Center (AC).MethodsProspective study including patients from the ECS, Odense University Hospital, during May 2013–April 2014. Possible anaphylaxis cases were daily identified based on a broad search profile including history and symptoms in patient records, diagnostic codes and pharmacological treatments. At the AC, all patients were evaluated according to international guidelines.ResultsAmong 226 patients with suspected anaphylaxis, the diagnosis was confirmed in 124 (54.9%) after diagnostic work-up; 118 of the 124 fulfilled WAO/EAACI criteria of anaphylaxis at the ECS, while 6 were found among 46 patient with clinical suspicion but not fulfilling the WAO/EAACI criteria at the ECS. The estimated incidence rate of anaphylaxis was 26 cases per 100,000 person years and the one year period prevalence was 0.04%. The most common elicitor was drugs (41.1%) followed by venom (27.4%) and food (20.6%). In 13 patients (10.5%) no elicitor could be identified. Mastocytosis was diagnosed in 7.7% of adult patients and was significantly associated with severe anaphylaxis. Atopic diseases were significantly associated only with food-induced anaphylaxis. Co-factors were present in 58.1% and were significantly associated with severe anaphylaxis.ConclusionA broad search profile in the ECS and subsequent diagnostic work-up is important for identification and classification of patients with anaphylaxis. Evaluation of co-morbidities and co-factors are important.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-19T09:12:37.434179-05:
      DOI: 10.1111/all.13207
  • Lung function parameters in omalizumab responder patients: an interesting
    • Authors: F. Paganin; G. Mangiapan, A. Proust, A. Prudhomme, J. Attia, S. Marchand-Adam, F. Pellet, F. Milhe, B. Melloni, A. Bernady, C. Raspaud, C. Nocent, P. Berger, L. Guilleminault
      Abstract: BackgroundOmalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and non-responder patients remain inconclusive. The objective of this real-life study was to compare the changes in FEV1 of omalizumab responders and non-responders at 6 months.MethodsA multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and post-bronchodilator FEV1, residual volume (RV) and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18 and 24 months.ResultsMean pre-bronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in non-responders (+0.2 ± 0.4L and -0.1 ± 0.4L respectively, p
      PubDate: 2017-05-18T05:27:15.154838-05:
      DOI: 10.1111/all.13202
  • Identification of a plasma miRNA biomarker-signature for allergic asthma:
           a translational approach
    • Authors: Katrin Milger; Jeremias Götschke, Linda Krause, Petra Nathan, Francesca Alessandrini, Amanda Tufman, Rainald Fischer, Sabine Bartel, Fabian J. Theis, Jürgen Behr, Stefan Dehmel, Nikola S. Mueller, Nikolaus Kneidinger, Susanne Krauss-Etschmann
      Abstract: BackgroundAsthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers.This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach.MethodsWe pre-screened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthma patients and 12 healthy controls.Results10 miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of 5 miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use.ConclusionDistinct plasma miRNAs are differentially regulated both in murine and human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-17T07:30:26.498613-05:
      DOI: 10.1111/all.13205
  • Aspergillus fumigatus in cystic fibrosis: an update on immune interactions
           and molecular diagnostics in ABPA
    • Authors: Ania Carsin; Thomas Romain, Stéphane Ranque, Martine Reynaud-Gaubert, Jean-Christophe Dubus, Jean-Louis Mège, J Vitte
      Abstract: A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe Aspergillus fumigatus-related diseases due to possible evolution towards pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8 to 10% of cystic fibrosis patients experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host-pathogen interactions in Aspergillus fumigatus and cystic fibrosis patients and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-17T07:10:40.586524-05:
      DOI: 10.1111/all.13204
  • Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic
           review and meta-analysis
    • Authors: Sangeeta Dhami; Ulugbek Nurmatov, Stefania Arasi, Tahir Khan, Miqdad Asaria, Hadar Zaman, Arnav Agarwal, Gopal Netuveli, Graham Roberts, Oliver Pfaar, Antonella Muraro, Ignacio J. Ansotegui, Moises Calderon, Cemal Cingi, Stephen Durham, Ronald Gerth van Wijk, Susanne Halken, Eckard Hamelmann, Peter Hellings, Lars Jacobsen, Edward Knol, Desiree Larenas Linnemann, Sandra Lin, Paraskevi Maggina, Ralph Mösges, Hanneke Oude Elberink, Giovanni Pajno, Ruby Panwankar, Elide Pastorello, Martin Penagos, Constantinos Pitsios, Giuseppina Rotiroti, Frans Timmermans, Olympia Tsilochristou, Eva-Maria Varga, Carsten Schmidt-Weber, Jamie Wilkinson, Andrew Williams, Margitta Worm, Luo Zhang, Aziz Sheikh
      Abstract: BackgroundThe European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. In order to inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic rhinoconjunctivitisMethodsWe searched 15 international biomedical databases for published, in progress and unpublished evidence. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses.ResultsWe identified 5932 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95%CI -0.63, -0.42), medication (SMD -0.37, 95%CI -0.49, -0.26) and combined symptom and medication (SMD -0.49, 95%CI -0.69, -0.30) scores whilst on treatment that were robust to pre-specified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, this suggesting a benefit in relation to symptom scores.ConclusionsAIT is effective in improving symptom, medication and combined symptom and medication scores in patients with allergic rhinoconjunctivitis whilst on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T10:05:39.858587-05:
      DOI: 10.1111/all.13201
  • Non-Allergic Rhinitis: Position paper of the European Academy of
           Allergology and Clinical Immunology
    • Authors: P. W. Hellings; L. Klimek, C. Cingi, I. Agache, C. Akdis, C. Bachert, J. Bousquet, P. Demoly, P. Gevaert, V. Hox, C. Hupin, L. Kalogjera, F. Manole, R. Mösges, J. Mullol, N. B. Muluk, A. Muraro, N. Papadopoulos, R. Pawankar, C. Rondon, M. Rundenko, S. F. Seys, E. Toskala, L. Van Gerven, L. Zhang, N. Zhang, W. J Fokkens
      Abstract: This EAACI position paper aims at providing a state-of-the-art overview on non-allergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as non-allergic non-infectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of minimal 2 nasal symptoms like nasal obstruction, rhinorrhoea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity, and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug-induced rhinitis, (non-allergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called ‘entopy’ or local allergic rhinitis (LAR).We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm and defining the unmet needs in this neglected area of research.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T06:18:20.2166-05:00
      DOI: 10.1111/all.13200
  • Minimal impact of extensive heating of hen's egg and cow's milk in a food
           matrix on threshold dose-distribution curves
    • Authors: Benjamin C. Remington; Joost Westerhout, Dianne E Campbell, Paul J. Turner
      Abstract: We analyzed reaction threshold data from 352 children undergoing open food challenges to hen's egg or cow's milk, either fresh or extensively heated into a muffin. There was no significant shift in dose-distribution curves due to the baking process, implying that existing threshold data for these allergens can be applied to allergen risk management, even when these allergens are heat-processed into baked foods.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T03:05:43.818627-05:
      DOI: 10.1111/all.13198
  • Recent Advances in the Use of Nanoparticles for Allergen-specific
    • Authors: Hannah Pohlit; Iris Bellinghausen, Holger Frey, Joachim Saloga
      Abstract: The number of patients suffering from allergic asthma and rhino-conjunctivitis has increased dramatically within the last decades. Allergen-specific immunotherapy (AIT) is the only available cause-oriented therapy so far. AIT reduces symptoms, but has also a disease modifying effect. Disadvantages are a long-lasting procedure, and in a few cases potential systemic adverse reactions. Encapsulation of allergens or DNA vaccines into nanostructures may provide advantages compared to the conventional AIT with non-capsulated allergen extracts: The protein/DNA molecule can be protected from degradation, higher local concentrations and targeted delivery to the site of action appears possible and most importantly, recognition of encapsulated allergen by the immune system, especially by IgE antibodies is prevented. AIT with nanoparticles (NPs) may offer a safer and potentially more efficient way of treatment for allergic diseases. In this review we summarize the use of biodegradable NPs consisting of synthetic or natural polymers, liposomes and virus-like particles as well as non-biodegradable NPs like dendrimers, carbon- or metal-based NPs for AIT. More or less successful applications of these NPs in prophylactic as well as therapeutic vaccination approaches in rodents or other animals as well as first human clinical trials are discussed in detail.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T03:05:41.333256-05:
      DOI: 10.1111/all.13199
  • Airway basophils are increased and activated in eosinophilic asthma
    • Authors: Yoshihiro Suzuki; Keiko Wakahara, Tomoko Nishio, Satoru Ito, Yoshinori Hasegawa
      Abstract: BackgroundThe impact of basophils on asthma pathogenesis remains largely unexplored, particularly in humans. Here, we evaluated the frequencies and activation status of basophils in the sputum of adult asthmatic patients and related our findings to other parameters of eosinophilic airway inflammation.MethodsWe enrolled 44 adult asthmatic patients who were being treated with inhaled corticosteroids (ICS). Analysis of the induced sputum, exhaled nitric oxide fraction (FeNO) measurement, and Asthma Control Test (ACT) were carried out together with standard blood and pulmonary function tests. The cellular composition of the sputum was examined by flow cytometry, and the phenotypes of blood and sputum basophils were compared.ResultsBasophils were increased in the sputum of asthmatic patients. The expression of CD203c on sputum basophils was significantly higher than that on blood basophils. The percentage of sputum basophils was positively correlated with those of eosinophils and mast cells; it was also correlated with that of blood eosinophils and FeNO. However, sputum basophils were not correlated with serum IgE, lung function, or the percentage of blood basophils. A receiver operating characteristics (ROC) curve showed the superiority of sputum basophils as a surrogate marker of the percentages of sputum eosinophils compared with absolute numbers of blood eosinophils and FeNO.ConclusionThe number of activated basophils was increased in the sputum of patients with eosinophilic asthma and correlated with airway and blood eosinophils. Our observations suggest that sputum basophils may serve as a biomarker to monitor new therapeutic approaches for the treatment of eosinophilic asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-05T03:00:27.597456-05:
      DOI: 10.1111/all.13197
  • Amb a 1 isoforms: unequal siblings with distinct immunological features
    • Authors: Martin Wolf; Teresa E. Twaroch, Sara Huber, Manuel Reithofer, Markus Steiner, Lorenz Aglas, Michael Hauser, Iris Aloisi, Claudia Asam, Heidi Hofer, Maria A. Parigiani, Christof Ebner, Barbara Bohle, Peter Briza, Neubauer Angela, Frank Stolz, Beatrice Jahn-Schmid, Michael Wallner, Fatima Ferreira
      Abstract: BackgroundRagweed pollen represents a major allergy risk factor. Ragweed extracts contain five different isoforms of the major allergen Amb a 1. However, the immunologic characteristics of Amb a 1 isoforms are not fully investigated. Here we compared the physicochemical and immunological properties of three most important Amb a 1 isoforms.MethodsAfter purification, the isoforms were physicochemically characterized, tested for antibody-binding and induction of human T cell proliferative responses. Their immunologic properties were further evaluated in vitro and in vivo in a mouse model.ResultsAmb a 1 isoforms exhibited distinct patterns of IgE-binding and immunogenicity. Compared to Amb a 1.02 or 03 isoforms, Amb a 1.01 showed higher IgE-binding activity. Isoforms 01 and 03 were the most potent stimulators of patients’ T cells. In a mouse model of immunization, Amb a 1.01 induced higher levels of IgG and IgE antibodies when compared to isoforms 02 and 03. Interestingly, ragweed-sensitized patients also displayed an IgG response to Amb a 1 isoforms. However, unlike therapy-induced antibodies, sensitization-induced IgG did not show IgE-blocking activity.ConclusionThe present study showed that naturally occurring isoforms of Amb a 1 possess different immunogenic and sensitizing properties. These findings should be considered when selecting sequences for molecule-based diagnosis and therapy of ragweed allergy. Due to its high IgE-binding activity, isoform Amb a 1.01 should be included in diagnostic tests. In contrast, due to their limited B and T cell cross-reactivity patterns, a combination of different isoforms might be a more attractive strategy for ragweed immunotherapy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-02T10:36:52.464335-05:
      DOI: 10.1111/all.13196
  • Duration and exclusiveness of breastfeeding and risk of childhood atopic
    • Authors: Niels J. Elbert; Evelien R. van Meel, Herman T. den Dekker, Nicolette W. de Jong, Tamar E.C. Nijsten, Vincent W.V. Jaddoe, Johan C. de Jongste, Suzanne G.M.A. Pasmans, Liesbeth Duijts
      Abstract: BackgroundBreastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease-related modification of the exposure or modified by maternal history of maternal history of allergy, eczema or asthma.MethodsThis study among 5,828 children was performed in a population-based prospective cohort from fetal life onwards. We collected information on duration (
      PubDate: 2017-04-27T18:38:26.364071-05:
      DOI: 10.1111/all.13195
  • Birth decade affects the sensitization pattern and asthma-risk in Finnish
           adult population
    • Authors: S Toppila-Salmi; A Luukkainen, R Lemmetyinen, J Karjalainen, H Huhtala, R Renkonen, D Y Wang, M J Mäkelä, J Pekkanen
      Abstract: BackgroundWe have previously shown that sensitizations to several types of allergens distinguishes subjects with and without adult-onset asthma in Finland. The aim was to analyze how age affects sensitization and asthma-risk.MethodsWe used previous population-based case-control data (N=523) from Finnish adult asthma patients with one or two matched controls. Asthma was diagnosed based on a typical history of asthmatic symptoms and lung function tests. Allergic sensitization was determined by skin prick test (SPT) to 17 aeroallergens. Information on demographics was obtained by a questionnaire.ResultsSensitization to more than one allergen type and the number of positive SPT reactions associated with younger age and asthma. Atopic subjects aged 65 or over were characterized by sensitization to only 1-2 allergens, with very few animal danders and without an association with asthma.ConclusionsMultiple sensitizations and animal dander sensitization are more common among Finnish asthmatic adults aged under 56 than among older asthmatics. Cohort studies are needed to understand timing of host-environmental interactions behind this.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-26T09:57:41.760018-05:
      DOI: 10.1111/all.13194
  • Predictive value of serum sST2 in preschool wheezers for development of
           asthma with high FeNO
    • Authors: Maria E. Ketelaar; Kim D. G van de Kant, F Nicole Dijk, Ester M.M. Klaassen, Néomi Grotenboer, Martijn C Nawijn, Edward Dompeling, Gerard H. Koppelman
      Abstract: Wheezing is common in childhood. However, current prediction models of paediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-Like-1 is a well-replicated asthma-gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (FeNO), compared to the commonly used Asthma Prediction Index (API). Using logistic regression modeling, we found that serum sST2 levels in 2-3y old wheezers do not predict doctors’ diagnosed asthma at age 6y. Instead sST2 predicts a subphenotype of asthma characterized by increased levels of FeNO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API (AUC=0.70, 95CI 0.56-0.84), but had also significant predictive value on its own (AUC=0.65, 95CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T02:00:42.725832-05:
      DOI: 10.1111/all.13193
  • Der f 35: an MD-2−like house dust mite allergen that cross-reacts
           with Der f 2 and Pso o 2
    • Authors: Takashi Fujimura; Tsunehiro Aki, Toshihide Isobe, Akito Matsuoka, Takaharu Hayashi, Kazuhisa Ono, Seiji Kawamoto
      Abstract: BackgroundDermatophagoides farinae is a source of airborne house dust mite (HDM) allergens. We elucidated IgE-reactive allergens from D. farinae by two-dimensional immunoblotting−based allergenome analysis, and identified one new allergen, named Der f 35, that possesses IgE-binding capacity comparable to that of Der f 2. The aim of this study is to clarify the allergenic capacity of new HDM allergen Der f 35.MethodsWe cloned der f 35 from D. farinae mRNA and produced recombinant Der f 35 in Escherichia coli. The IgE-binding capacity of Der f 35 and its cross-reactivity with group 2 allergens from D. farinae and Psoroptes ovis were determined by ELISA and ELISA inhibition assays, respectively.ResultsThe deduced amino acid sequence for der f 35, which possesses the MD-2−related lipid-recognition domain, showed higher identity with group 2 allergens from P. ovis (61.5%) and Blomia tropicalis (50.7%) than with Der f 2 (40.8%). Der f 35 showed IgE-binding frequencies of 77.5% (31/40) for the native form upon allergenome analysis and 51.4% (18/35) for recombinant structure by ELISA. Der f 35 showed cross-reactivity with Der f 2 and Pso o 2 in reaction with HDM-allergic patients’ IgE by ELISA inhibition assay.ConclusionDer f 35 is a candidate major allergen from D. farinae, which is more similar to group 2 allergens from sheep scab mite and storage mites. Der f 35 could be responsible for the cross-reactivity among group 2 mite allergens.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T01:55:39.743146-05:
      DOI: 10.1111/all.13192
  • Identification of a polygalacturonase (Cup s 2) as the major CCD-bearing
           allergen in Cupressus sempervirens pollen
    • Authors: Youcef Shahali; Jean-Pierre Sutra, Christiane Hilger, Kyria Swiontek, Iman Haddad, Joelle Vinh, Laurence Guilloux, Denis Charpin, Hélène Sénéchal, Pascal Poncet
      Abstract: Since IgE glyco-epitopes, also referred to as cross-reactive carbohydrate determinants (CCDs), can share significant structural homologies between different plants, they are prone to extensive cross-reactivity among allergen pollen extracts. Here, cypress pollen allergens, especially a polygalacturonase (PG), were further characterized using double one dimensional electrophoresis (D1-DE). The presence of specific IgE directed against CCDs was investigated by bromelain IgE inhibition and concanavalin A binding assays using sera of cypress pollen sensitized patients. Our results showed that IgE reactivity to CCDs in Cupressus sempervirens pollen extracts is mainly related to bromelain-type epitopes of a newly-identified cypress PG. This glycoprotein has been further characterized through an immunoproteomic approach and officially indexed as Cup s 2 by the WHO/IUIS allergen nomenclature. Cup s 2 could thus be associated with the increased prevalence of IgE reactivity to cypress pollen extracts because of CCD interference.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T01:50:39.507138-05:
      DOI: 10.1111/all.13191
  • Topical corticosteroid phobia in atopic dermatitis: international
           feasibility study of the TOPICOP score
    • Authors: Jean-Francois Stalder; Hélène Aubert, Emmanuelle Anthoine, Leila Moret, Sebastien Barbarot, Masaki Futamura, Danielle Marcoux, Marie-Anne Morren, Magdalena Trzeciak, Zsuzsanna Szalai, Klára Veres, Mette Deleuran, Christian Vestergaard, Franck Boralevi, Chua-Yu Chu, Linda De Raeve, Åke Svensson, Regina Fölster-Holst, Matthias Buchner, Roberto Takaoka, Valeria Aoki, Pavel Chernyshov, Luidmyla Chernyshova, Dedee F. Murrell, Cathy Zhao, Carola Duran Mckinster, Laura Von Kobyletzky, Laurence Eichenfield, Christine Totri, Peter Lio, Julien Seneschal
      Abstract: BackgroundAdherence to topical corticosteroids (TCS) is essential for the effective treatment of atopic dermatitis but can be limited by concerns about their use. This study examined the feasibility of applying the validated TOPICOP score for assessing TCS phobia across different countries.MethodsThis was a prospective multicenter feasibility study conducted in 21 hospitals in 17 countries. Patients >3 months of age with atopic dermatitis or their parents or legal representatives completed a validated translation of the TOPICOP questionnaire in the country's native language. Respondents also completed questionnaires collecting opinions about the feasibility and acceptability of the TOPICOP questionnaire.Results1564 participants in 15 countries were included in the analysis. 81% of respondents considered the questions clear or very clear and 79% reported that it took less than 5 min to complete. Each of the individual items in the TOPICOP questionnaire was considered to be not at all difficult to answer by 49% to 74% of participants. The mean global TOPICOP score was 44.7% ± 20.5. Mean TOPICOP subscores were 37.0 ± 22.8% for knowledge and beliefs, 54.7 ± 27.8% for fears, and 50.1 ± 29.1% for behaviours. Global scores and subscores differed between countries, although the subscores did not always vary in parallel, suggesting different levels of TCS phobia and different drivers for each country.ConclusionsThe TOPICOP score can be feasibly applied across countries and may therefore be useful for obtaining qualitative and quantitative data from international studies and for adapting patient education and treatment.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T01:46:14.388731-05:
      DOI: 10.1111/all.13189
  • Effect of anti-IgE in occupational asthma caused by exposure to low
           molecular weight agents
    • Authors: M Ollé-Monge; M J Cruz, S Gomez-Ollés, I Ojanguren, J Vanoirbeek, X Muñoz
      Abstract: BackgroundThe role of immunoglobulin (Ig)-E in occupational asthma (OA) due to low molecular weight (LMW) agents is not well established compared to classical atopic asthma. In the present study we evaluate whether anti-IgE monoclonal antibody (mAb) has an effect in a mouse model of OA, using persulfate salts.MethodsOn days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate (AP) or dimethyl sulfoxide (DMSO). On days 15, 18 and 21 animals were injected intraperitoneally with anti-IgE mAb or PBS 6 hours before challenge with AP or saline. Airway hyperresponsiveness (AHR) using a methacholine test, airway inflammation in bronchoalveolar lavage (BAL) and lung tissue and total free IgE in serum samples were analyzed 24, 48 and 96 hours after the last challenge.ResultsAnti-IgE mAb treatment almost completely neutralized free serum IgE. In AP sensitized and challenged mice, anti-IgE mAb treatment abolished AHR 24h and 48h after the last challenge and significantly reduced the total number of eosinophils and neutrophils 48h and 96h after the last AP challenge compared with non-treated mice. Levels of interleukin (IL)-13 in BAL were also significantly decreased after anti-IgE administration 24h and 48h after the last AP challenge. Histological analysis of the lung sections from anti-IgE-treated mice revealed normal inflammatory patterns similar to control groups 48h after the last challenge.ConclusionsAnti-IgE-treated mice showed a significant improvement in asthma features related to the AHR and airway inflammation. Anti-IgE mAb has positive effects in OA induced by persulfate salts.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T01:46:09.580547-05:
      DOI: 10.1111/all.13190
  • Prospective evaluation of the diagnostic value of sensitive KIT D816V
    • Authors: Thomas Kristensen; Hanne Vestergaard, Carsten Bindslev-Jensen, Charlotte Gotthard Mortz, Henrik Fomsgaard Kjaer, Markus Ollert, Michael Boe Møller, Sigurd Broesby-Olsen,
      Abstract: BackgroundSensitive KIT D816V mutation analysis of blood has been proposed to guide bone marrow (BM) investigation in suspected systemic mastocytosis (SM). The aim of this prospective study was for the first time to compare the D816V-status of the “screening blood sample” used to guide BM biopsy in suspected SM to the outcome of the subsequent BM investigation.Methods58 adult patients with suspected SM were included. The outcome of sensitive KIT D816V-analysis of blood was compared to the result of the BM investigation.ResultsScreening blood samples from 44 of 58 patients tested D816V-positive. In 43 of these, SM was subsequently diagnosed in the BM investigation. One patient with a D816V-positive screening sample was diagnosed with monoclonal MC activation syndrome. Screening blood samples from 14 patients tested D816V-negative. SM was subsequently diagnosed in five of these, whereas nine patients did not fulfil any diagnostic SM criteria (excluding tryptase-criterion). Of the 48 SM patients, 90% tested D816V-positive. Thirteen SM patients presented with hymenoptera venom-induced anaphylaxis, no skin lesions and baseline serum-tryptase ≤20 ng/mL. Of these, 92% tested D816V-positive in the screening blood sample.ConclusionThis prospective study demonstrates that a D816V-positive result in a screening blood sample identifies SM among patients with hymenoptera venom-induced anaphylaxis in whom the diagnosis would most probably have been missed, with potential severe implications. The observed false negative screening results also underline that BM investigation is mandatory in all adult patients with clear signs of, or highly suspected SM, regardless of the KIT mutation status.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-22T02:15:55.867386-05:
      DOI: 10.1111/all.13187
  • Sputum basophils are increased in eosinophilic asthma compared with
           non-eosinophilic asthma phenotypes
    • Authors: Collin R Brooks; Christine J Dalen, Ian F Hermans, Peter G Gibson, Jodie L Simpson, Jeroen Douwes
      Abstract: Sputum basophil numbers are increased in allergic asthmatics, but it is unclear what role airway basophils play in “TH2-low” asthma phenotypes. Using flow cytometry we found that basophils were significantly increased in all asthmatics (n=26) compared with healthy controls (n=8) (p=0.007) with highest levels observed in eosinophilic asthma (EA; median 0.22%, IQR 0.11-0.47%; n=14) compared with non-EA (0.06%, 0.00-0.20%; n=12; p
      PubDate: 2017-04-20T08:22:08.97523-05:0
      DOI: 10.1111/all.13185
  • Protease-activated receptor-2 suppresses interleukin (IL)-10 expression in
           B cells via up regulating Bcl2L12 in patients with allergic rhinitis
    • Authors: Jin-Mei Xue; Li-Tao Yang, Gui Yang, Xiao-Rui Geng, Zhi-Qiang Liu, Shuai Wang, Hai-Liang Zhao, Zhi-Gang Liu, Chang-Qing Zhao, Ping-Chang Yang
      Abstract: Background and aimsThe function of interleukin (IL)-10 producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immune regulatory functions. This study aims to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells.MethodsPeripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2 like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed.ResultsWe observed that the expression of IL-10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10 expression, which was abolished by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12-shRNA carrying liposomes reversed the capability of IL-10 expression and the immune suppressor function. Administration of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice.ConclusionsActivation of PAR2 inhibits the expression of IL-10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment of AR.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-20T08:21:58.09584-05:0
      DOI: 10.1111/all.13186
  • BTK inhibition is a potent approach to block IgE-mediated histamine
           release in human basophils
    • Authors: D. Smiljkovic; K. Blatt, G. Stefanzl, Y. Dorofeeva, C. Skrabs, M. Focke-Tejkl, W. R. Sperr, U. Jaeger, R. Valenta, P. Valent
      Abstract: BackgroundRecent data suggest that Bruton's tyrosine kinase (BTK) is an emerging therapeutic target in IgE receptor (IgER)-cross-linked basophils.MethodsWe examined the effects of four BTK inhibitors (ibrutinib, dasatinib, AVL-292, and CNX-774) on IgE-dependent activation and histamine release in blood basophils obtained from allergic patients (n=11) and nonallergic donors (n=5). In addition, we examined the effects of these drugs on the growth of the human basophil cell line KU812 and the human mast cell line HMC-1.ResultsAll four BTK blockers were found to inhibit anti-IgE-induced histamine release from basophils in nonallergic subjects and allergen-induced histamine liberation from basophils in allergic donors. Drug effects on allergen-induced histamine release were dose dependent, with IC50 values ranging between 0.001 and 0.5 μmol/L, and the following rank order of potency: ibrutinib>AVL-292>dasatinib>CNX-774. The basophil-targeting effect of ibrutinib was confirmed by demonstrating that IgE-dependent histamine release in ex vivo blood basophils is largely suppressed in a leukemia patient treated with ibrutinib. Dasatinib and ibrutinib were also found to counteract anti-IgE-induced and allergen-induced upregulation of CD13, CD63, CD164, and CD203c on basophils, whereas AVL-292 and CNX-774 showed no significant effects. Whereas dasatinib and CNX-774 were found to inhibit the growth of HMC-1 cells and KU812 cells, no substantial effects were seen with ibrutinib or AVL-292.ConclusionsBTK-targeting drugs are potent inhibitors of IgE-dependent histamine release in human basophils. The clinical value of BTK inhibition in the context of allergic diseases remains to be determined.
      PubDate: 2017-04-20T03:43:55.451794-05:
      DOI: 10.1111/all.13166
  • Dysregulation of interleukin 5 expression in familial eosinophilia
    • Authors: S. Prakash Babu; Y.-Y. K. Chen, S. Bonne-Annee, J. Yang, I. Maric, T. G. Myers, T. B. Nutman, A. D. Klion
      Abstract: BackgroundFamilial eosinophilia (FE) is a rare autosomal dominant inherited disorder characterized by the presence of lifelong peripheral eosinophilia (>1500/μL). Mapped to chromosome 5q31-q33, the genetic cause of FE is unknown, and prior studies have failed to demonstrate a primary abnormality in the eosinophil lineage.ObjectiveThe aim of this study was to identify the cells driving the eosinophilia in FE.MethodsMicroarray analysis and real-time PCR were used to examine transcriptional differences in peripheral blood mononuclear cells (PBMC), and in purified cell subsets from affected and unaffected family members belonging to a single large kindred. Cytokine levels in serum and PBMC culture supernatants were assessed by suspension array multiplexed immunoassays.ResultsWhereas IL-5 mRNA expression was significantly increased in freshly isolated PBMC from affected family members, this was not accompanied by increased mRNA expression of other Th2 cytokines (IL-4 or IL-13). Serum levels of IL-5 and IL-5 receptor α, but not IgE, were similarly increased in affected family members. Of note, IL-5 mRNA expression was significantly increased in purified CD3+ CD4+, CD14+, CD19+, and ILC2 cells from affected family members, as were IL-5 protein levels in supernatants from both stimulated PBMC and ILC2 cultures.ConclusionsThese data are consistent with the hypothesis that the eosinophilia in FE is secondary to dysregulation of IL-5 production in PBMC (and their component subsets).
      PubDate: 2017-04-18T03:55:57.33405-05:0
      DOI: 10.1111/all.13146
  • Allergenome characterization of the mosquito Aedes aegypti
    • Authors: J. F. Cantillo; L. Puerta, P. Puchalska, S. Lafosse-Marin, J. L. Subiza, E. Fernández-Caldas
      Abstract: BackgroundSaliva and muscle-derived mosquito allergens have been purified and characterized. However, the complete set of allergens remains to be elucidated. In this study, we identified and characterized IgE-binding proteins from the mosquito species Aedes aegypti.MethodsSerum was obtained from 15 allergic individuals with asthma and/or rhinitis and sensitized to mosquito. IgE binding was determined by ELISA. Total proteins from freeze-dried bodies of A. aegypti were extracted and IgE-reactive proteins were identified by 2D gel electrophoresis, followed by Western blot with pooled or individual sera. IgE-reactive spots were further characterized by mass spectrometry.ResultsTwenty-five IgE-reactive spots were identified, corresponding to 10 different proteins, some of which appeared as different variants or isoforms. Heat-shock cognate 70 (HSC-70) and tropomyosin showed IgE reactivity with 60% of the sera, lysosomal aspartic protease, and “AAEL006070-PA” (Uniprot: Q177P3) with 40% and the other proteins with
      PubDate: 2017-04-18T03:55:54.631142-05:
      DOI: 10.1111/all.13150
  • Clinical, functional and inflammatory characteristics in patients with
           pauci-granulocytic stable asthma: comparison with different sputum
    • Authors: Polyxeni Ntontsi; Stelios Loukides, Petros Bakakos, Konstantinos Kostikas, Georgios Papatheodorou, Evgenia Papathanassiou, Georgios Hillas, Nikolaos Koulouris, Spyros Papiris, Andriana I Papaioannou
      Abstract: BackgroundAccording to induced sputum cell count, four different asthma phenotypes have been recognised(eosinophilic, neutrophilic, mixed and pauci-granulocytic). The aim of the present study was to detect functional and inflammatory characteristics of patients with pauci-granulocytic asthma.Methods240 asthmatic patients were categorised in the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of FeNO. The levels of IL-8, IL-13, and ECP were also measured in sputum supernatant. Treatment, asthma control and the presence of Severe Refractory Asthma(SRA) were also recorded.ResultsPatients were categorized in the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and pauci-granulocytic (47.9%). Although ACT did not differ between groups (p=0.288) patients with pauci-granulocytic asthma had better lung function (FEV1%pred) (median (IQR):71.5(59.0-88.75) vs 69.0(59.0-77.6) vs 68.0(60.0-85.5) vs 80.5(69.7-95.0), p=0.009] for eosinophilic, mixed, neutrophilic and pauci-granulocytic asthma respectively, p=0.009). SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7% respectively) and less frequently in the neutrophilic and pauci-granulocytic phenotype (25% and 21.7% respectively, p=0.01). FeNO, ECP and IL-8 were all low in the pauci-granulocytic, whereas as expected FeNO and ECP were higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with neutrophilic and mixed asthma(p
      PubDate: 2017-04-13T12:41:49.281462-05:
      DOI: 10.1111/all.13184
  • Comorbidity of chronic spontaneous urticaria and autoimmune thyroid
           diseases: a systematic review
    • Authors: Pavel Kolkhir; Martin Metz, Sabine Altrichter, Marcus Maurer
      Abstract: Chronic spontaneous urticaria (CSU) patients are widely held to often have other autoimmune disorders, including autoimmune thyroid disease. Here, we systematically evaluated the literature on the prevalence of thyroid autoimmunity in CSU and vice versa. There is a strong link between CSU and elevated levels of IgG anti-thyroid autoantibodies (AAbs), with most of a large number of studies reporting rates of ≥10%. Levels of IgG against thyroid peroxidase (TPO) are more often elevated in CSU than those of other IgG anti-thyroid AAbs (strong evidence). Levels of IgG anti-thyroid AAbs are more often elevated in adult CSU patients than in children (strong evidence). CSU patients exhibit significantly higher levels of IgG anti-thyroid AAbs (strong evidence) and IgE-anti-TPO (weak evidence) than controls. Elevated IgG anti-thyroid AAbs in CSU are linked to the use of glucocorticoids (weak evidence) but not to disease duration or severity/activity, gender, age or ASST response (inconsistent evidence). Thyroid dysfunction rates are increased in CSU patients (strong evidence). Hypothyroidism and Hashimoto's thyroiditis are more common than hyperthyroidism and Graves’ disease (strong evidence). Thyroid dysfunction is more common in adult CSU patients than in children (strong evidence) and in female than male CSU patients (weak evidence). Urticaria including CSU is more prevalent in patients with thyroid autoimmunity than in healthy controls (weak evidence). CSU can improve in response to treatment with levothyroxine or other thyroid drugs (strong evidence). Pathogenic mechanisms in CSU patients with thyroid autoimmunity may include IgE against autoantigens, immune complexes and complement.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-13T12:41:33.628924-05:
      DOI: 10.1111/all.13182
  • Transcriptome analysis of severely active chronic spontaneous urticaria
           shows an overall immunological skin involvement
    • Authors: A. Giménez-Arnau; L. Curto-Barredo, L. Nonell, E. Puigdecanet, J. Yelamos, R. Gimeno, S. Rüberg, L. Santamaria-Babi, R. M. Pujol
      Abstract: BackgroundThe knowledge about chronic spontaneous urticaria (CSU) phenotypes is based on its clinical characteristics, associated comorbidities, course of the disease and its response to the available effective drugs. Genotype expression and its further correlation with CSU phenotypes are still unknown. We describe the cutaneous transcriptome of patients suffering a severely active CSU refractory to antihistamine treatment.MethodsThrough the bioinformatic analysis of the whole Human Genome with Oligo Microarrays and Quantitative real-time polymerase chain reaction (qPCR), relevant genes expressed in non-lesional [NLS-CSU] and lesional skin [LS-CSU]) and peripheral blood were identified in 20 patients suffering from severely active CSU and 10 healthy controls (HCs)ResultsFrom 39 genes differentially expressed in NLS-CSU when compared with HCs, 31 (79.48%) were confirmed by qPCR corresponding to genes involved in epidermal homeostasis and dermal repair. From the analysis comparing LS-CSU with NLS-CSU, a selection of 142 genes was studied with qPCR, and 103 (72.53%) were confirmed. Differentially expressed genes in the phenomenon of wheal development are involved in a variety of biological functions as, epidermal differentiation, intracellular signal function, transcriptional factors cell cycle differentiation, inflammation or coagulation. Differentially expressed genes that uniformly increase or decrease along the skin worsening until the wheal appearance are shown.ConclusionThe skin of CSU patients with a severely active disease shows an overall immunological skin involvement showing a peculiar gene profile.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-13T12:36:53.231232-05:
      DOI: 10.1111/all.13183
  • Skin prick tests and specific IgE in 10-year-old children: Agreement and
           association with allergic diseases
    • Authors: A. Chauveau; M.-L. Dalphin, F. Mauny, V. Kaulek, E. Schmausser-Hechfellner, H. Renz, J. Riedler, J. Pekkanen, A. M. Karvonen, R. Lauener, C. Roduit, D. A. Vuitton, E. von Mutius, J.-C. Dalphin,
      Abstract: BackgroundAccurate assessment of atopic sensitization is pivotal to clinical practice and research. Skin prick test (SPT) and specific IgE (sIgE) are often used interchangeably. Some studies have suggested a disagreement between these two methods, and little is known about their association with allergic diseases. The aims of our study were to evaluate agreement between SPT and sIgE, and to compare their association with allergic diseases in 10-year-old children.MethodsSkin prick test, sIgE measurements, and assessment of allergic diseases were performed in children aged 10 years in the Protection against Allergy: STUdy in Rural Environments (PASTURE) cohort. The agreement between SPT and sIgE was assessed by Cohen's kappa coefficient with different cutoff values.ResultsSkin prick tests and sIgE were performed in 529 children. The highest agreement (κ=.44) was found with a cutoff value of 3 and 5 mm for SPT, and 3.5 IU/mL for sIgE. The area under the curve (AUC) obtained with SPT was not significantly different from that obtained with sIgE. For asthma and hay fever, SPT (cutoff value at 3 mm) had a significantly higher specificity (P
      PubDate: 2017-04-12T02:55:38.911621-05:
      DOI: 10.1111/all.13148
  • The relationship between nasopharyngeal CCL5 and microbiota on disease
           severity among infants with bronchiolitis
    • Authors: K. Hasegawa; J. M. Mansbach, N. J. Ajami, J. F Petrosino, R. J. Freishtat, S. J. Teach, P. A. Piedra, C. A. Camargo 
      Abstract: Emerging evidence suggests that the airway microbiota plays an important role in viral bronchiolitis pathobiology. However, little is known about the combined role of airway microbiota and CCL5 in infants with bronchiolitis. In this multicenter prospective cohort study of 1005 infants (age
      PubDate: 2017-04-12T02:55:37.028652-05:
      DOI: 10.1111/all.13160
  • Occupational respiratory allergy in peach crop workers
    • Authors: R. Pérez-Calderón; M. Á. Gonzalo-Garijo, F. J. Rodríguez-Velasco, S. Sánchez-Vega, B. Bartolomé-Zavala
      Abstract: BackgroundOccupational respiratory diseases in workers of peach tree crops have been reported punctually and have been associated with sensitization to proteins present in both pollen and leaf tree. We report the study of 37 workers with respiratory symptoms related to occupational exposure to peach trees.MethodsPrick tests and specific IgE determinations were performed with extracts from leaves and branches of peach tree. Immunodetection in leaf extract was realized by sodium dodecyl sulfate–polyacrylamide gel electrophoresis SDS-PAGE-immunoblotting with patient sera and rabbit serum anti-Pru p 3. Immunodetection inhibition was performed with rPru p 3 and pollen profilins. The clinical relevance of sensitization was demonstrated by specific bronchial challenge test (SBCT) with peach leaf extract.ResultsMost patients suffered symptoms when peach trees had leaves, specifically during thinning and harvesting fruit (rhinoconjunctivitis: 100% and asthma: 67.5%). Sensitization to leaf extract was demonstrated in 86% of patients. IgE-immunoblotting with peach leaf extract revealed in six patient sera a pair of bands of 10 and 16 kDa, and in nine a 16-kDa band. Those bands could be two isoforms of peach leaf lipid transfer proteins( LTP), so the recognition frequency of some LTP isoform by our patient sera was 42%. 33% of the sera recognized a doubled band of about 14.5 kDa and this recognition was inhibited by nPho d 2. The SBCT with peach leaf extract was positive in the asthmatic sensitized patients tested.ConclusionsSensitization to peach leaves was the cause of occupational respiratory symptoms in our patients. Some patient sera revealed IgE-binding proteins matching LTP and/or profilin.
      PubDate: 2017-04-12T02:55:35.341772-05:
      DOI: 10.1111/all.13163
  • Precision medicine in allergic disease—food allergy, drug allergy, and
           anaphylaxis—PRACTALL document of the European Academy of Allergy and
           Clinical Immunology and the American Academy of Allergy, Asthma and
    • Authors: A. Muraro; R. F. Lemanske, M. Castells, M. J. Torres, D. Khan, H.-U. Simon, C. Bindslev-Jensen, W. Burks, L. K. Poulsen, H. A. Sampson, M. Worm, K. C. Nadeau
      Abstract: This consensus document summarizes the current knowledge on the potential for precision medicine in food allergy, drug allergy, and anaphylaxis under the auspices of the PRACTALL collaboration platform. PRACTALL is a joint effort of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology, which aims to synchronize the European and American approaches to allergy care. Precision medicine is an emerging approach for disease treatment based on disease endotypes, which are phenotypic subclasses associated with specific mechanisms underlying the disease. Although significant progress has been made in defining endotypes for asthma, definitions of endotypes for food and drug allergy or for anaphylaxis lag behind. Progress has been made in discovery of biomarkers to guide a precision medicine approach to treatment of food and drug allergy, but further validation and quantification of these biomarkers are needed to allow their translation into practice in the clinical management of allergic disease.
      PubDate: 2017-04-12T02:51:12.738887-05:
      DOI: 10.1111/all.13132
  • Serum periostin relates to type-2 inflammation and lung function in
           asthma; data from the large population-based cohort Swedish GA(2)LEN
    • Authors: Anna James; Christer Janson, Andrei Malinovschi, Cecile Holweg, Kjell Alving, Junya Ono, Shoichiro Ohta, Alexandra Ek, Roelinde Middelveld, Barbro Dahlén, Bertil Forsberg, Kenji Izuhara, Sven-Erik Dahlén
      Abstract: BackgroundPeriostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type-2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear.AimTo examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics.MethodsSerum periostin was examined by ELISA in 1091 subjects aged 17-76 from the Swedish GA(2)LEN study, which included 460 asthmatics with/without chronic rhinosinusitis (CRS), 97 individuals with CRS only, and 203 healthy controls. Clinical tests included measurement of lung function, FeNO, IgE, urinary eosinophil derived neurotoxin (U-EDN) and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication and quality of life.ResultsAlthough median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower BMI related to higher periostin levels in subjects both with and without asthma.ConclusionWe confirm associations between periostin and markers of type-2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-11T09:35:30.069017-05:
      DOI: 10.1111/all.13181
  • Altered Fatty Acid Metabolism and Reduced Stearoyl-Coenzyme A Desaturase
           Activity in Asthma
    • Authors: N. Rodriguez-Perez; E. Schiavi, R. Frei, R. Ferstl, P. Wawrzyniak, S. Smolinska, M. Sokolowska, N.A. Sievi, M. Kohler, P. Schmid-Grendelmeier, D. Michalovich, K.D. Simpson, E.M. Hessel, M. Jutel, M. Martin-Fontecha, O. Palomares, C.A. Akdis, L. O'Mahony
      Abstract: BackgroundFatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely under-explored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and non-obese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models.MethodsMedium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity was evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity.ResultsThe serum desaturation index (an indirect measure of SCD) was significantly reduced in non-obese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyperresponsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers.ConclusionsThis is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyperresponsiveness and reduced anti-viral defense. SCD may represent a new target for therapeutic intervention in asthma patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-11T02:10:50.364001-05:
      DOI: 10.1111/all.13180
  • Clinical benefits of treatment with SQ house dust mite sublingual tablet
           in house dust mite allergic rhinitis
    • Authors: P. Demoly; J. Kleine-Tebbe, D. Rehm
      Abstract: Treatment with SQ (standardised quality) house dust mite sublingual tablet for 1 year resulted in a decreased probability of having an allergic rhinitis (AR) exacerbation day (from 11% [placebo] to 5% [SQ house dust mite sublingual tablet]) and an increased probability of having a mild AR day (from 16% [placebo] to 34% [SQ house dust mite sublingual tablet]).
      PubDate: 2017-04-11T01:20:57.035796-05:
      DOI: 10.1111/all.13155
  • New approach shows no association between maternal milk fatty acid
           composition and childhood wheeze or asthma
    • Authors: C. A. Logan; S. Brandt, M. Wabitsch, H. Brenner, F. Wiens, B. Stahl, T. Marosvölgyi, T. Decsi, D. Rothenbacher, J. Genuneit
      Abstract: BackgroundPrevious observational studies have implied breastmilk fatty acid composition may play a role in the development of atopic eczema or atopic sensitization in breastfed infants and toddlers. However, studies investigating associations with wheeze and asthma in later childhood are scarce and did not account for inherent correlation of compositional data. Our aim was to explore the association of maternal milk fatty acid composition with childhood wheezing phenotypes and asthma up to age 13 years using a new statistical approach.MethodsBreastmilk was collected 6 weeks and 6 months postdelivery in the Ulm Birth Cohort Study (n=720 and n=454, respectively). Concentrations of 28 fatty acids were measured by high-resolution capillary gas-liquid chromatography. To control for constant-sum constraint, concentration data were transformed using the centered log ratio method. Compositional biplots and correlation matrices were used to group centered log ratio transformed fatty acids. Adjusted risk ratios with parent-reported wheezing phenotypes and doctor-diagnosed asthma were computed using a modified Poisson regression.ResultsWe observed no straightforward evidence of associations between overall breastmilk fatty acid composition and specific wheeze phenotypes or doctor-diagnosed asthma.ConclusionUsing appropriate statistical methodology, we report null associations. These findings may partly be attributable to several cohort-specific factors associated with breastfeeding and breastmilk collection. Further studies could improve on ours by analyzing samples of breastmilk and formula and by including all children for whom these are exclusively or together the major source of fatty acids in the first months of life.
      PubDate: 2017-04-11T01:20:52.972998-05:
      DOI: 10.1111/all.13161
  • Comparing immediate type food allergy in humans and companion animals
           – revealing unmet needs
    • Authors: I. Pali-Schöll; M. De Lucia, H. Jackson, J. Janda, R.S. Mueller, E. Jensen-Jarolim
      Abstract: Adverse food reactions occur in human as well as veterinary patients and systematic comparison may lead to improved recommendations for prevention and treatment in both. In this position paper, we summarize the current knowledge on immediate type food allergy versus other food-adverse reactions in companion animals, and compare this to the human situation. While the prevalence of food allergy in humans has been well studied for some allergens, this remains to be investigated for animal patients, where owner-reported as well as veterinarian-diagnosed food adverse reactions are on the increase. The characteristics of the disease in humans versus dogs, cats, and horses are most often caused by similar, but sometimes species-dependent different, pathophysiological mechanisms, prompting the specific clinical symptoms, diagnoses and treatments. Furthermore, little is known about the allergen molecules causative for type I food allergy in animals which, like in human patients, could represent predictive biomarkers for risk evaluation. The definite diagnosis of food allergy relies -as in humans- on elimination diet and provocation tests. Besides allergen avoidance in daily practice, novel treatment options and tolerization strategies are underway.Taken together, numerous knowledge gaps were identified in veterinary food allergy, which need to be filled by systematic comparative studies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-10T09:02:12.818144-05:
      DOI: 10.1111/all.13179
  • Diagnostic Tools in Ocular Allergy
    • Authors: Andrea Leonardi; Serge Doan, Jean Luc Fauquert, Banu Bozkurt, Pia Allegri, Farid Marmouz, Carmen Rondon, Monica Jedrzejczak, Peter Hellings, Luis Delgado, Virginia Calder
      Abstract: Ocular allergy (OA) includes a group of common and less frequent hypersensitivity disorders frequently misdiagnosed and not properly managed. The diagnosis of OA is usually based on clinical history and signs and symptoms, with the support of in vivo and in vitro tests when identification of the specific allergen is required. To date, no specific test is available for the diagnosis of the whole spectrum of the different forms of OA. The lack of recommendations on diagnosis of OA is considered a medical need not only for allergists but also for ophthalmologists.This position paper aims to provide a comprehensive overview of the currently available tools for diagnosing OA to promote a common nomenclature and procedures to be used by different specialists. Questionnaires, sign and symptom grading scales, tests and potential biomarkers for OA are reviewed. We also identified several unmet needs in the diagnostic tools to generate interest, increase understanding and inspire further investigations. Tools, recommendations and algorithms for the diagnosis of OA are proposed for use by both allergists and ophthalmologists. Several unmet needs in the diagnostic tools should be further improved by specific clinical research in OA.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-07T10:30:46.357134-05:
      DOI: 10.1111/all.13178
  • Work productivity in rhinitis using cell phones: The MASK pilot study
    • Authors: J Bousquet; M Bewick, S Arnavielhe, E Mathieu-Dupas, R Murray, A Bedbrook, D P Caimmi, O VandenPlas, P W Hellings, C Bachert, J M Anto, KC Bergmann, C Bindslev-Jensen, S Bosnic-Anticevitch, J Bouchard, GW Canonica, N H Chavannes, A A Cruz, R Dahl, P Demoly, G De Vries, P Devillier, A Fink-Wagner, W J Fokkens, J Fonseca, N Guldemond, T Haahtela, B Hellqvist-Dahl, J Just, T Keil, L Klimek, M L Kowalski, P Kuna, V Kvedariene, D Laune, D Larenas-Linnemann, J Mullol, A M Pereira, P Carreiro-Martins, E Melén, M Morais-Almeida, L Nogueira-Silva, R E O'Hehir, N G Papadopoulos, G Passalacqua, F Portejoie, D Price, D Ryan, B Samolinski, A Sheikh, F E R Simons, O Spranger, A Todo Bom, PV Tomazic, M Triggiani, A Valero, E Valovirta, A Valiulis, M van Eerd, M Wickman, I Young, T Zuberbier
      Abstract: Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to assess the impact of uncontrolled rhinitis assessed by visual analogue score VAS on work productivity using cell phone data collection.A mobile phone app Allergy Diary, Android and Apple stores collects daily visual analogue scales VAS data for overall allergic symptoms VAS-global measured, nasal VAS-nasal, ocular VAS-ocular, asthma symptoms VAS-asthma and work VAS-work. A combined nasal-ocular score is calculated. Allergy Diary is available in 20 countries. The App includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire WPAI:AS questionnaire in 6 EU countries. All consecutive users who filled the VAS-work from June 1 to October 31, 2016 were included in the study.A total of 1,136 users filled in 5,818 days of VAS-work. Symptoms of allergic rhinitis were controlled VAS-global50. There was a significant correlation between VAS-global calculated and VAS-work Rho=0.83, p
      PubDate: 2017-04-07T10:20:35.876721-05:
      DOI: 10.1111/all.13177
  • Biomarkers for monitoring clinical efficacy of allergen immunotherapy for
    • Authors: M. H. Shamji; J. H. Kappen, M. Akdis, E. Jensen-Jarolim, E. F. Knol, J. Kleine-Tebbe, B. Bohle, A. M. Chaker, S. J. Till, R. Valenta, L. K. Poulsen, M. A. Calderon, P. Demoly, O. Pfaar, L. Jacobsen, S. R. Durham, C. B. Schmidt-Weber
      Abstract: BackgroundAllergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers.MethodThe EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?).ResultsAll biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed.ConclusionsIt is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.
      PubDate: 2017-04-06T02:03:48.417236-05:
      DOI: 10.1111/all.13138
  • Serum levels of 9α,11β-PGF2 and apolipoprotein A1 achieve high
           predictive power as biomarkers of anaphylaxis
    • Authors: Marcel Wittenberg; Maria Nassiri, Wojciech Francuzik, Karola Lehmann, Magda Babina, Margitta Worm
      Abstract: Anaphylaxis is a life-threatening hypersensitivity reaction. To identify biomarkers for the condition, we assessed serum levels of apolipoprotein (Apo)A and ApoE. We found a reduction of both lipoproteins in anaphylactic mice as well as in orally challenged food allergic patients. We then compared patients after acute anaphylaxis with several control groups (non-allergic, history of allergen-triggered anaphylaxis, acute cardiovascular/febrile reactions). In this unpaired setting, ApoE levels were unaltered, while ApoA1 was reduced in the anaphylactic group. Though unable to discriminate between anaphylaxis and cardiovascular/febrile reactions, ROC curve analysis revealed a reasonably high area under the curve (AUC) of 0.91 for ApoA1. Serum 9α,11ß-PGF2, recently identified as a suitable biomarker for anaphylaxis, outperformed ApoA1 with AUC=0.95. Intriguingly however, its power further increased upon combination of both mediators reaching AUC=1. Our data suggest that ApoA1 combined with 9α,11ß-PGF2 represents a useful composite biomarker of anaphylaxis, achieving superior diagnostic power over either factor alone.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-05T02:51:12.451829-05:
      DOI: 10.1111/all.13176
  • Staphylococcus aureus enterotoxin-sensitization is associated with
           allergic poly-sensitization and allergic multimorbidity in adolescents
    • Authors: Martin Sørensen; Claus Klingenberg, Magnus Wickman, Johanna U E. Sollid, Anne-Sofie Furberg, Claus Bachert, Jean Bousquet
      Abstract: BackgroundStaphylococcus aureus (S. aureus) carriage and sensitization to S. aureus enterotoxins (SEs) has been associated with allergic diseases. From the Tromsø Study Fit Futures 2, we have previously shown an association between S. aureus carriage and severe allergic disease and allergic multimorbidity. However, the role of S. aureus carriage and SE-sensitization on allergic multimorbidity and allergic sensitization is unclear.ObjectiveTo study associations of both nasal S. aureus carriage and SE-sensitization to allergic disease and allergic sensitization.MethodsA cross-sectional study of a school-based cohort in late adolescence (age 18-19 years: The Tromsø Study Fit Futures 2). Self-reported allergic diseases were assessed using the Mechanisms of the Development of ALLergy questionnaire (MeDALL). Participants were tested for nasal S. aureus carriage, serum total IgE and specific IgE to SEs and food and inhalant allergens.Results868 participants were studied. Sensitization to at least one food or inhalant allergen was found in 319/765 (41.7%), and to at least one SE in 173/656 (26.2%) of the participants. SE-sensitization, but not S. aureus carriage, was associated with poly-sensitization to food and inhalant allergens. SE-sensitized participants had higher median specific IgE to inhalant allergens (41.4 kUA/L, IQR 10.1-118.4) compared to non-SE-sensitized participants (18.0 kUA/L, IQR 5.5-48.6, p=0.004), but not to food allergens. SE-sensitization was associated to allergic multimorbidity.ConclusionSensitization to SEs may play a role in the development of allergen poly-sensitization and allergic multimorbidity.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-05T02:35:46.79587-05:0
      DOI: 10.1111/all.13175
  • Interferon-γ-induced insufficient autophagy contributes to p62-dependent
    • Authors: B-F. Wang; P-P. Cao, Z-C. Wang, Z-Y. Li, Z-Z. Wang, J. Ma, B. Liao, Y-K. Deng, X-B. Long, K. Xu, H. Wang, H. Wang, M. Zeng, X. Lu, Z. Liu
      Abstract: BackgroundAutophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, and homeostasis. This study aimed to investigate the contribution of autophagy to the pathogenesis of CRS with nasal polyps (CRSwNP).MethodsThe expression of autophagic proteins [microtubule-associated protein 1 light chain 3B (LC3B)-II, autophagy-related proteins (Atg), and Beclin 1], substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling molecules [cysteine-aspartic protease-3 and cysteine-aspartic protease-8, and poly-ADP-ribose polymerase] in the sinonasal mucosa and nasal epithelial cells (NECs) was detected by immunohistochemistry and Western blotting. Autophagic vacuoles were observed with transmission electron microscopy. BEAS-2B cells and NECs were treated with rapamycin, bafilomycin A1, or various cytokines. In some experiments, cultured NECs were transfected with small interfering RNA targeting p62 (sip62) or Atg5 (siAtg5). Cultured cells were analyzed with Western blotting and flow cytometry.ResultsAlthough autophagic protein expression and autophagic vacuole formation were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in NECs, there was also an up-regulation of substrate proteins and apoptotic signaling molecules. IFN-γ, but not IL-4, IL-13, or IL-17A, simultaneously enhanced LC3B-II and p62 levels as well as cell apoptosis in BEAS-2B cells and/or normal NECs. Bafilomycin A1 up-regulated the levels of LC3B-II and p62 in polyp NECs and IFN-γ-treated normal NECs. IFN-γ-induced apoptosis of normal NECs was exaggerated by bafilomycin A1 and siAtg5. Sip62 suppressed apoptosis of polyp NECs and IFN-γ-treated NECs. IFN-γ protein levels were increased in both eosinophilic and noneosinophilic CRSwNP.ConclusionsIFN-γ induces activated but insufficient autophagy and thus contributes to a degree to p62-dependent apoptosis of NECs in CRSwNP.
      PubDate: 2017-04-04T23:40:53.270456-05:
      DOI: 10.1111/all.13153
  • Children with atopic dermatitis and frequent emollient use have increased
    • Authors: L. E. K. Overgaard; K. M. Main, H. Frederiksen, S. Stender, P. B. Szecsi, H. C. Williams, J. P. Thyssen
      Abstract: BackgroundParabens may be added to cosmetic and personal care products for preservation purposes. Low-molecular weight (LMW) phthalate diesters function as plasticizers, fixatives or solvents in such products, but may also be found in small quantities as contaminants from plastic containers.ObjectiveTo evaluate the association between emollient use, atopic dermatitis and FLG mutations, respectively, with urinary concentrations of phthalate metabolites and parabens in Danish children.MethodsEight hundred and forty-five Danish children 4-9 years of age were studied. Urinary concentrations of phthalate metabolites and parabens were determined, and children were genotyped for common FLG loss-of-function mutations. Information about atopic dermatitis and use of emollients was obtained from questionnaires completed by parents.ResultsThe prevalence of atopic dermatitis was 16.1%. Phthalate metabolite and paraben levels were generally higher in children with frequent use of emollients compared to uncommon users, reaching statistical significance for some LMW phthalates and parabens. While there was no association with common FLG mutations, children with atopic dermatitis had significantly higher urinary levels of one LMW phthalate and two parabens, respectively, when compared to children without atopic dermatitis.ConclusionEmollient use and atopic dermatitis were associated with modestly increased internal LMW phthalate and paraben exposure in 4-9 year old children. It is unknown whether the difference is explained by increased use of the specific emollients that are used to treat pruritic and inflamed skin, and/or whether the impaired skin barrier allows chemicals to penetrate more easily. Moreover, the putative toxicological burden is unknown.
      PubDate: 2017-04-04T23:40:27.475567-05:
      DOI: 10.1111/all.13157
  • A randomized controlled phase II clinical trial comparing ONO-4053, a
           novel DP1 antagonist, with a leukotriene receptor antagonist pranlukast in
           patients with seasonal allergic rhinitis
    • Authors: Kimihiro Okubo; Kazuhiro Hashiguchi, Tetsuo Takeda, Kanji Baba, Hideto Kitagoh, Hitoshi Miho, Hideo Tomomatsu, Shinsuke Yamaguchi, Motoi Odani, Hajime Yamamotoya
      Abstract: BackgroundProstaglandin D2 (PGD2) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea.ObjectiveThis study aimed to evaluate the efficacy and safety of a novel PGD2 receptor 1 (DP1) antagonist, ONO-4053, in patients with seasonal allergic rhinitis (SAR).MethodsThis study was a multicenter, randomized, double-blind, parallel-group study of patients with SAR. Following a one-week period of placebo run-in, patients who met the study criteria were randomized to either the ONO-4053, leukotriene receptor antagonist pranlukast, or placebo group for a two-week treatment period. 200 patients were planned to be randomly assigned to receive ONO-4053, pranlukast, or placebo in a 2:2:1 ratio. Nasal and eye symptoms were evaluated.ResultsBoth ONO-4053 and pranlukast had higher efficacy than placebo on all nasal and eye symptoms. ONO-4053 outperformed pranlukast in a total of three nasal symptom scores (T3NSS) as well as in individual scores for sneezing, rhinorrhea, and nasal itching. For T3NSS, the Bayesian posterior probabilities that pranlukast was better than placebo and ONO-4053 was better than pranlukast were 70.0% and 81.6%, respectively, suggesting that ONO-4053 has a higher efficacy compared with pranlukast. There was no safety-related issue in this study.ConclusionsWe demonstrated that the efficacy of ONO-4053 was greater than that of pranlukast with a similar safety profile. This study indicates the potential of ONO-4053 for use as a treatment for SAR (JapicCTI-142706).This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-04T19:10:26.828121-05:
      DOI: 10.1111/all.13174
  • RNase 7 downregulates TH2 cytokine production by activated human T-cells
    • Authors: Verena Kopfnagel; Sylvia Wagenknecht, Lena Brand, Jana Zeitvogel, Jürgen Harder, Karsten Hofmann, Michael Kleine, Thomas Werfel
      Abstract: BackgroundThe antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T-cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity immunoregulatory functions have been published for several AMPs. In this study we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T-cells.MethodsIsolated human CD3+ T-cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T-cells and in polarised TH2 cells using skin derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay.ResultsTreatment of activated human CD4+ T-cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T-cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T-cells with RNase7.ConclusionOur data indicate that RNase 7 has immunomodulatory functions on TH2-cells and decreases the production of TH2 cytokines in the skinThis article is protected by copyright. All rights reserved.
      PubDate: 2017-04-04T19:10:25.827191-05:
      DOI: 10.1111/all.13173
  • AhR mediates an anti-inflammatory feed-back mechanism in human Langerhans
           cells involving FcεRI and IDO
    • Authors: Susanne Koch; Tim J. Stroisch, Julia Vorac, Nadine Herrmann, Nicole Leib, Sylvia Schnautz, Helene Kirins, Irmgard Förster, Heike Weighardt, Thomas Bieber
      Abstract: BackgroundAryl hydrocarbon receptor (AhR), an important regulator of immune responses, is activated by UVB irradiation in the skin. Langerhans cells (LC) in the epidermis of atopic dermatitis (AD) patients carry the high affinity receptor for IgE, FcεRI, and are crucially involved in the pathogenesis of AD by inducing inflammatory responses and regulating tolerogenic processes.ObjectivesWe investigated AhR and AhR repressor (AhRR) expression and functional consequences of AhR activation in human ex vivo skin cells and in in vitro generated LC.MethodsEpidermal cells from healthy skin were analyzed for their expression of AhR and AhRR. LC generated from CD34+ hematopoietic stem cells (CD34LC) were treated with the UV photoproduct and AhR ligand 6-formylindolo[3,2-b]carbazole (FICZ). Cell surface receptors, transcription factors and the tolerogenic tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) were analyzed using flow cytometry and quantitative PCR.ResultsEpidermal LC and CD34LC express AhR and AhRR. AhR was also found in keratinocytes, which lack AhRR. AhR activation of LC by FICZ caused down-regulation of FcεRI in CD34LC without affecting their maturation. AhR-mediated regulation of FcεRI did not involve any known transcription factors related to this receptor. Furthermore, we could show up-regulation of IDO mediated by AhR engagement.ConclusionsOur study shows that AhR activation by FICZ reduces FcεRI and up-regulates IDO expression in LC. This AhR-mediated anti-inflammatory feedback mechanism may dampen the allergen-induced inflammation in AD.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-04T12:15:53.948348-05:
      DOI: 10.1111/all.13170
  • Pru p 3, a marker allergen for lipid transfer protein sensitization also
           in Central Europe
    • Authors: N. Mothes-Luksch; M. Raith, G. Stingl, M. Focke-Tejkl, E. Razzazi-Fazeli, R. Zieglmayer, S. Wöhrl, I. Swoboda
      Abstract: In the Mediterranean area, lipid transfer proteins (LTPs) are important causes of plant-food allergies often associated with severe allergic reactions. There, peach LTP (Pru p 3) seems to be the primary sensitizer, whereas in Central Europe, little is known about the importance of LTP sensitization. In this region, allergen extract-based diagnosis is often complicated by co-sensitization to Bet v 1, the major birch pollen allergen, its cross-reactive food allergens, and profilins. We investigated the role of LTP sensitization in Central European patients displaying strong allergic reactions to plant-derived food. Analysis of IgE reactivity revealed that ten of thirteen patients were sensitized to Pru p 3, nine to Bet v 1, and two to profilin. Our results showed that LTP sensitization represents a risk factor for severe allergic symptoms in Central Europe. Furthermore, the strong IgE reactivity detected in immunoblots of plant-food extracts indicated that Pru p 3 can be used as a marker allergen for LTP sensitization also in Central European patients.
      PubDate: 2017-04-03T23:30:31.124472-05:
      DOI: 10.1111/all.13151
  • Oxidative stress serves as a key checkpoint for IL-33 release by airway
    • Authors: M. Uchida; E. L. Anderson, D. L. Squillace, N. Patil, P. J. Maniak, K. Iijima, H. Kita, S. M. O'Grady
      Abstract: BackgroundInterleukin (IL)-33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL-33 release is controlled. The transcription factor nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a key role in antioxidant response regulation.ObjectiveThe goal of this project was to investigate the role of cellular oxidative stress in controlling IL-33 release in airway epithelium.MethodsComplementary approaches were used that included human bronchial epithelial cells and mouse models of airway type-2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me) was used to evaluate the role of Nrf2-induced antioxidant molecules.ResultsHuman bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N-acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL-33 release. Administration of CDDO-Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO-Me treatment reduced allergen-induced ATP secretion and IL-33 release by airway epithelial cells in vitro and protected mice from IL-33 release and asthma-like pathological changes in the lungs.ConclusionsThe balance between oxidative stress and antioxidant responses plays a key role in controlling IL-33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.
      PubDate: 2017-03-31T03:00:41.537457-05:
      DOI: 10.1111/all.13158
  • Questionable diagnostic benefit of the commercially available panel of bee
           venom components
    • Authors: L. Arzt; D. Bokanovic, C. Schrautzer, I. Schwarz, K. Laipold, W. Aberer, G. J. Sturm
      Abstract: For many years, only the major allergen rApi m 1 has been available on the ImmunoCAP system for routine diagnosis of bee venom (BV) allergy. Now, there are five components available, and we aimed to detect the sensitivity and specificity of rApi m 1, 2, 3, 5, and 10 in BV-allergic patients. We further evaluated the sensitivity of rApi m 1 and 2 of an alternative platform and investigated possible differences in the sensitization profile between monosensitization and clinically relevant double sensitization. Analysis of the whole panel of BV allergens of the CAP system still resulted in a lower sensitivity than analysis of the combination of rApi m 1 and 2 of the Immulite (71.6% vs 85.8%). Sensitization rate of rApi m 5 was more than doubled in double-sensitized patients, while there was no difference for rApi m 2. The benefit of the commercially available panel of BV components is questionable, due to the insufficient sensitivity and still unavailable important cross-reacting allergens.
      PubDate: 2017-03-31T03:00:25.414835-05:
      DOI: 10.1111/all.13154
  • Possible effect of landscape design on IgE recognition profiles of two
           generations revealed with micro-arrayed allergens
    • Authors: Victoria Garib; Eva Wollmann, Gulnara Djambekova, Patrick Lemell, Maximilian Kmenta, Uwe Berger, Petra Zieglmayer, Rudolf Valenta
      Abstract: Aim of this study was to investigate possible effects of landscape design on IgE-sensitization profile towards inhalant allergens in patients with respiratory allergy from Uzbekistan where green areas have been changed during the last 2 decades by a State program. Sera from two different generations of Uzbek (n=58) and, for control purposes, from two generations of Austrian (n=58) patients were analyzed for IgE reactivity to 112 different micro-arrayed allergen molecules by ImmunoCAP ISAC technology. Changes of molecular IgE sensitization profiles to pollen allergens in the young versus the middle-aged Uzbek population were associated with replanting whereas those in the Vienna populations reflected natural changes of plant growth. Our data indicate that anthropologic as well as natural changes of the biome may have effects on IgE sensitization profiles already from one to another generation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-29T09:36:03.59202-05:0
      DOI: 10.1111/all.13169
  • Clinical Outcomes following Inpatient Penicillin Allergy Testing: A
           Systematic Review and Meta-analysis
    • Authors: Keith A. Sacco; Allan Bates, Tara J. Brigham, J. Saadi-Imam, M Caroline Burton
      Abstract: BackgroundA documented penicillin allergy is associated with increased morbidity including length of hospital stay and an increased incidence of resistant infections attributed to use of broader-spectrum antibiotics. The aim of the systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization.MethodsWe performed an electronic search of Ovid Medline/PubMed, Embase, Web of Science, Scopus and the Cochrane Library over the past 20 years. Inpatients having a documented penicillin allergy that underwent penicillin allergy testing were included.ResultsTwenty-four studies met eligibility criteria. Study sample size was between 24 and 252 patients in exclusively inpatient cohorts. Penicillin skin testing (PST) with or without oral amoxicillin challenge was the main intervention described (18 studies). The population-weighted mean for a negative PST was 95.1% [CI 93.8-96.1]. Inpatient penicillin allergy testing led to a change in antibiotic selection that was greater in the intensive care unit (77.97% [CI 72.0-83.1] vs 54.73% [CI 51.2-58.2], p
      PubDate: 2017-03-29T09:20:28.771434-05:
      DOI: 10.1111/all.13168
  • Dysregulation of metabolic pathways in a mouse model of allergic asthma
    • Authors: K. D. Quinn; M. Schedel, Y. Nkrumah-Elie, A. Joetham, M. Armstrong, C. Cruickshank-Quinn, R. Reisdorph, E. W. Gelfand, N. Reisdorph
      Abstract: BackgroundAsthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function.MethodsIn this experimental model of allergic asthma, matched bronchoalveolar lavage (BAL) fluid and plasma were collected from three groups of C57BL6 mice (control vs sensitized and/or challenged with ovalbumin, n=3-5/group) 6 hour, 24 hour, and 48 hour after the last challenge. Samples were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Airway hyper-responsiveness (AHR) measurements and differential cell counts were performed.ResultsIn total, 398 and 368 dysregulated metabolites in the BAL fluid and plasma of sensitized and challenged mice were identified, respectively. These belonged to four, interconnected pathways relevant to asthma pathogenesis: sphingolipid metabolism (P=6.6×10−5), arginine and proline metabolism (P=1.12×10−7), glycerophospholipid metabolism (P=1.3×10−10), and the neurotrophin signaling pathway (P=7.0×10−6). Furthermore, within the arginine and proline metabolism pathway, a positive correlation between urea-1-carboxylate and AHR was observed in plasma metabolites, while ornithine revealed a reciprocal effect. In addition, agmatine positively correlated with lung eosinophilia.ConclusionThese findings point to potential targets and pathways that may be central to asthma pathogenesis and can serve as novel therapeutic targets.
      PubDate: 2017-03-29T04:49:46.226808-05:
      DOI: 10.1111/all.13144
  • Natural tolerance development in cow's milk allergic children:IgE and IgG4
           epitope binding
    • Authors: Jean Christoph Caubet; Jing Lin, Birgit Ahrens, Gustavo Gimenez, Luda Bardina, Bodo Niggemann, Hugh A. Sampson, Kirsten Beyer
      Abstract: BackgroundAlthough most of cow's milk (CM) allergic children will outgrow their allergy, the pathomechanism of the natural development of tolerance remains poorly understood. It has been suggested that the balance between milk specific IgE and IgG4 plays a major role.ObjectiveWe aimed to investigate differences in IgE and IgG4 antibody binding to cow's milk (CM) epitopes between patients with persistent CM allergy (CMA) and those that naturally became tolerant.MethodsSera from thirty-five children with proven CMA (median age at inclusion of 10 months) were analysed retrospectively; 22 patients have become tolerant (median age at tolerance acquisition of 51 months) during the study period as confirmed by a negative oral food challenge. IgE and IgG4 binding to sequential epitopes derived from 5 major CM proteins were measured with a peptide microarray-based immunoassay.ResultsAt baselines, greater intensity and broader diversity of IgE and IgG4 binding have been found in children with persistent CMA beyond 5 years of age compared to patients with transient CMA. Moreover, children with transient CMA had IgE and IgG4 antibodies that more often recognized the same epitopes, compared to those with persistent CMA. From baseline to the time of tolerance development, both IgE and IgG4 binding intensity decreased significantly, particularly in areas of α-s- and β-casein (p
      PubDate: 2017-03-27T04:09:47.840022-05:
      DOI: 10.1111/all.13167
  • Asthma management: A new phenotype-based approach using presence of
           eosinophilia and allergy
    • Authors: Milan Terl; Vratislav Sedlák, Petr Cap, Renata Dvořáková, Viktor Kašák, Tomáš Kočí, Bronislava Novotna, Ester Seberova, Petr Panzner, Vladimir Zindr
      Abstract: Asthma is a heterogeneous disease. The Czech Pneumology and Allergology Societies commissioned 10 experts to review the literature and create joint national guidelines for managing asthma, reflecting this heterogeneity. The aim was to develop an easy-to-use diagnostic strategy as a rational approach to the widening opportunities for the use of phenotype-targeted therapy. The guidelines were presented on websites for public comments by members of both the societies. The reviewers’ comments contributed to creating the final version of the guidelines. The key hallmark of the diagnostic approach is the pragmatic concept, which assesses the presence of allergy and eosinophilia in each asthmatic patient. The guidelines define three clinically relevant asthma phenotypes: eosinophilic allergic asthma, eosinophilic non-allergic asthma and non-eosinophilic non-allergic asthma. The resulting multifunctional classification describing the severity, level of control and phenotype is the starting point for a comprehensive treatment strategy. The level of control is constantly confronted with the intensity of the common stepwise pharmacotherapy, and the concurrently included phenotyping is essential for phenotype-specific therapy. The concept of the asthma approach with assessing the presence of eosinophilia and allergy provides a way for more precise diagnosis, which is a prerequisite for using widening options of personalised therapy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-22T09:36:40.805693-05:
      DOI: 10.1111/all.13165
  • Characterization of maize chitinase-A, a tough allergenic molecule
    • Authors: Mariateresa Volpicella; Claudia Leoni, Immacolata Fanizza, Marco Distaso, Guido Leoni, Laura Farioli, Todd Naumann, Elide Pastorello, Luigi Ruggiero Ceci
      Abstract: BackgroundFood allergies are recognized as an increasing health concern. They are caused by specific proteins called food allergens. Proteins commonly identified as food allergens tend to have one of about 30 different biochemical activities. This leads to the assumption that food allergens must have specific structural features which causes their allergenicity. But these structural features are not completely understood. Uncovering the structural basis of allergenicity would allow improved diagnosis and therapy of allergies and would provide insights for safer food production. The availability of recombinant food allergens can accelerate their structural analysis, and benefit specific studies in allergology. Plant chitinases are an example of food allergenic proteins for which structural analysis of allergenicity has only partially been reported.MethodsThe recombinant maize chitinase, rChiA, was purified from Pichia pastoris extracellular medium by differential precipitation and cation exchange chromatography. Enzyme activity was evaluated by halo-assays and microcalorimetric procedures. rChiA modeling was performed by a two-step procedure, using the Swissmodel server and Modeller software. Allergenicity of rChiA was verified by immunoblot assays with sera from allergic subjects.ResultsrChiA is active in the hydrolysis of glycol chitin and N-acetylchitotetraose, and maintains its activity at high temperatures (70 °C) and low pH (pH 3). The molecule is also reactive with IgE from sera of maize allergic subjects.ConclusionsrChiA is a valuable molecule for further studies on structure-allergenicity relationships and as a tool for diagnosing allergies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-22T09:28:49.449364-05:
      DOI: 10.1111/all.13164
  • Positioning the Principles of Precision Medicine in Care Pathways for
           Allergic Rhinitis and Chronic Rhinosinusitis - an
           EUFOREA-ARIA-EPOS-AIRWAYS ICP statement
    • Authors: P.W. Hellings; W.J. Fokkens, C. Bachert, C.A. Akdis, T. Bieber, I. Agache, M. Bernal-Sprekelsen, G.W. Canonica, P. Gevaert, G. Joos, V. Lund, A. Muraro, M. Onerci, T. Zuberbier, B. Pugin, S.F. Seys, J. Bousquet,
      Abstract: Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies.The aim of the current document is to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its’ implementation and the high cost of molecular diagnosis and biological treatment.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-17T10:11:20.590657-05:
      DOI: 10.1111/all.13162
  • Results of an allergy educational needs questionnaire for primary care
    • Authors: D. Ryan; E. Angier, M. Gomez, D. Church, M. Batsiou, K. Nekam, N. Lomidze, R. Gawlik
      Abstract: It is well recognized that knowledge of allergic conditions is suboptimal in primary care. The Primary Care Interest Group of the European Academy of Allergy and Clinical Immunology undertook an educational needs survey to better understand what they were and how best to meet them, in the primary care environment. An electronic questionnaire was devised and distributed as widely as possible. A total of 2226 people from 63 countries opened the e-questionnaire of which 692 provided evaluable responses. In total, 81% were medical doctors with 299 possessing additional qualifications. Self-declared gaps in knowledge were expressed for most manifestations of allergy with a correspondingly high self-expressed educational need. The preferred learning modalities were online guidelines (69.6%) and courses (68.8%) followed closely by workshops (68%), structured online modules (63.9%) and small local working groups (59.75%). Podcasts and webinars scored poorly with only 25% expressing these as preferred learning modes although there was an age gradient. The preferred electronic platform was the personal computer (82.6%). A better understanding of the needs of primary care should help guide the design of educational initiatives to meet those needs.
      PubDate: 2017-03-17T00:40:34.290471-05:
      DOI: 10.1111/all.13134
  • Long-term future risk of severe exacerbations: distinct 5-year
           trajectories of problematic asthma
    • Authors: Anthony C.A. Yii; Jessica H.Y. Tan, Therese S. Lapperre, Adrian K.W. Chan, Su Y. Low, Thun H. Ong, Keng L. Tan, Sanjay H. Chotirmall, Peter J. Sterk, Mariko S. Koh
      Abstract: BackgroundAssessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short-, but not long-term risk. Problematic asthma patients with unfavorable long-term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment.MethodsSevere exacerbation rates over five years for 177 “problematic asthma” patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group-based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory.ResultsThree distinct trajectories were found: 58.5% had rare intermittent severe exacerbations (“infrequent”), 32.0% had frequent severe exacerbations at baseline but improved subsequently (“non-persistently frequent”), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near-fatal asthma (“persistently frequent”). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near-fatal asthma (+1 point), body mass index≥25kg/m2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point) and depression (+1 point) was predictive of the “persistently frequent” trajectory (area under the receiver operating characteristic curve: 0.84; sensitivity 72.2%, specificity 81.1% using cut-off ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort.ConclusionsPatients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently frequent severe exacerbations in the future.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-11T03:06:55.605306-05:
      DOI: 10.1111/all.13159
  • Prevalence of type I sensitization to alpha-gal in forest service
           employees and hunters
    • Authors: Jörg Fischer; Elena Lupberger, Johanna Hebsaker, Gunnar Blumenstock, Elisabeth Aichinger, Amir S Yazdi, Doris Reick, Rainer Oehme, Tilo Biedermann
      Abstract: BackgroundThe production of IgE molecules specific to the carbohydrate galactose-α-1,3-galactose (alpha-gal) is known to induce delayed anaphylaxis against mammalian meat. Tick bites constitute the primary sensitization source, as ticks transfer alpha-gal in their saliva to a host during a bite. The reported prevalence of alpha-gal-specific IgE (alpha-gal-sIgE) positivity varies between different populations from diverse geographic regions.ObjectiveTo investigate the prevalence of alpha-gal-sIgE positivity in a population of forest service employees who are highly exposed to ticks in comparison with a residential population and a historic sample.MethodsA cross-sectional study evaluating 300 forest service employees and hunters from Southwest Germany was performed. Alpha-gal-sIgE levels were assessed by ImmunoCAP assay. The prevalence of alpha-gal-sIgE-positive individuals was compared with a matched cohort composed of a residential population and blood samples from forest service employees collected 15 years ago.ResultsIn the study population, the prevalence of alpha-gal-sIgE-positive (>0.10 kUA/L) individuals was 35.0%, whereas the prevalence of individuals with alpha-gal-sIgE levels >0.35 kUA/L was 19.3%. Alpha-gal-sIgE positivity was associated with total IgE levels and recent tick bites. Mammalian meat-induced delayed anaphylaxis was found in 8.6% of the participants with alpha-gal-sIgE levels >0.35 kUA/L. For forest service employees and hunters, the odds ratio for alpha-gal-sIgE positivity was 2.48 compared to the residential population. The prevalence of alpha-gal-sIgE positivity in the current and historic cohort was comparable.ConclusionForest service employees and hunters compose a population with a high prevalence of alpha-gal-sIgE positivity and carry a considerable risk of red meat allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-08T16:20:26.326573-05:
      DOI: 10.1111/all.13156
  • Evidence for a role of eosinophils in blister formation in bullous
    • Authors: E. Graauw; C. Sitaru, M. Horn, L. Borradori, S. Yousefi, H.-U. Simon, D. Simon
      Abstract: BackgroundBullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear.ObjectiveTo investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal–epidermal separation (DES).MethodsIn an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab′)2 fragments to CD16, CD18, CD32 and CD64. Dermal–epidermal separation was assessed by light microscopy studies and quantified using Fiji software.ResultsFollowing activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal–epidermal junction of ex vivo skin. Dermal–epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P < 0.0001) or eosinophil extracellular trap (EET) formation (P = 0.048).ConclusionsOur results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal–epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP.
      PubDate: 2017-03-01T03:15:41.276429-05:
      DOI: 10.1111/all.13131
  • Current status in diagnosis of atopic dermatitis in China
    • Authors: Ruhong Cheng; Yifeng Guo, Linting Huang, Fei Hao, Xinhua Gao, Thomas Bieber, Zhirong Yao
      Abstract: In China, eczema and atopic dermatitis (AD) have been traditionally considered as 2 distinct entities. Eczema typically referred to the milder phenotypes or to phenotypes with atypical morphology and distribution of lesions and many dermatologists have ever recognized that the “eczema” diagnosed clinically by them is actually milder phenotypes or phenotypes with atypical morphology and distribution of lesions of AD. Moreover, AD, contact dermatitis, diaper dermatitis, perioral dermatitis, halo dermatitis, pompholyx, seborrheic dermatitis, etc. are not included in category of “eczema” in Chinese textbook of dermatology2.This article is protected by copyright. All rights reserved.
      PubDate: 2017-02-24T15:10:30.632307-05:
      DOI: 10.1111/all.13149
  • The skin barrier function gene SPINK5 is associated with challenge proven
           IgE-mediated food allergy in infants
    • Authors: Sarah E Ashley; Hern-Tze Tina Tan, Peter Vuillermin, Shyamali C Dharmage, Mimi L K Tang, Jennifer Koplin, Lyle C Gurrin, Adrian Lowe, Caroline Lodge, Anne-Louise Ponsonby, John Molloy, Pamela Martin, Melanie C Matheson, Richard Saffery, Katrina J Allen, Justine A Ellis, David Martino,
      Abstract: BackgroundA defective skin barrier is hypothesised to be an important route of sensitisation to dietary antigens, and may lead to food allergy in some children. Missense mutations in the Serine peptidase inhibitor kazal type 5 (SPINK5) skin barrier gene have previously been associated with allergic conditions.ObjectiveTo determine whether genetic variants in and around SPINK5 are associated with IgE mediated food allergy.MethodWe genotyped 71 ‘tag’ single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kilobases (kb) including SPINK5 (~61kb) in n=722 (n=367 food allergic, n=199 food sensitised, tolerant and n=156 non-food allergic controls) 12-month infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge (OFC). Transepidermal water loss (TEWL) measures were collected at 12-months from a subset (n=150) of these individuals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Associations analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food allergic, n=330 non-food allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components.ResultsSPINK5 variant rs9325071 (A⟶G) was associated with challenge proven food allergy in the discovery sample (P=0.001 OR=2.95 CI=1.49-5.83). This association was further supported by replication (P=0.007 OR=1.58 CI=1.13-2.20) and by meta-analysis (P=0.0004 OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also.ConclusionsWe report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-02-18T02:50:37.122171-05:
      DOI: 10.1111/all.13143
  • Novel Approaches and Perspectives in Allergen Immunotherapy
    • Authors: Hans Jürgen Hoffmann; Erkka Valovirta, Oliver Pfaar, Philippe Moingeon, Johannes Martin Schmid, Søren Helbo Skaarup, Lars-Olaf Cardell, Kim Simonsen, Mark Larche, Stephen R Durham, Poul Sørensen
      Abstract: In this review we report on relevant current topics in allergen immunotherapy (AIT) which were broadly discussed during the 1st Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December, 2015 by leading clinicians, scientists and industry representatives in the field. The aim of this symposium was to highlight AIT-related aspects of public health, clinical efficacy evaluation, mechanisms, development of new biomarkers and an overview of novel therapeutic approaches. Allergy is a public health issue of high socioeconomic relevance, and development of evidence-based action plans to address allergy as a public health issue ought to be on national and regional agendae. The underlying mechanisms are in the focus of current research that lays the ground for innovative therapies. Standardization and harmonization of clinical endpoints in AIT trials as well as current knowledge about potential biomarkers have substantiated proof of effectiveness of this disease-modifying therapeutic option. Novel treatments like peptide immunotherapy, intralymphatic immunotherapy and use of recombinant allergens herald a new age in which AIT may address treatment of allergy as a public health issue by reaching a large fraction of patients.This article is protected by copyright. All rights reserved.
      PubDate: 2017-01-25T15:30:25.457835-05:
      DOI: 10.1111/all.13135
  • Allergen Exposure Chambers (AEC): harmonizing current concepts and
           projecting the needs for the future - an EAACI Position Paper
    • Authors: O Pfaar; M A Calderon, C P Andrews, E Angjeli, K C Bergmann, J H Bønløkke, F de Blay, P Devillier, A K Ellis, R Gerth van Wijk, J Hohlfeld, F Horak, M Jutel, R L Jacobs, L Jacobsen, S Kaul, M Larché, D Larenas-Linnemann, R Mösges, H Nolte, P Patel, L Peoples, R L Rabin, C Rather, A M Salapatek, T Sigsgaard, S Thaarup, J Yang, P Zieglmayer, T Zuberbier, P Demoly
      Abstract: BackgoundAllergen exposure chambers (AEC) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AEC have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multi-centre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each center. Because there are technical differences among AEC, it may be necessary to define parameters to standardize the AEC so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities.MethodsFor this task force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation.ResultsThe latter covered the validation process, standardization of challenges and outcomes, intra- and inter-chamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues.ConclusionThis EAACI Position Paper aims to harmonize current concepts in AEC and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future.This article is protected by copyright. All rights reserved.
      PubDate: 2017-01-25T15:30:23.70069-05:0
      DOI: 10.1111/all.13133
  • Targeting IκBNS in allergic asthma: Where it resides, matters
    • Authors: Shaon Sengupta; Angela Haczku
      Abstract: The activity NF-κB, a pro-inflammatory transcription factor, and its complex modulation play a central role in in inflammatory airways disease such as allergic airway hyperresponsiveness. In a new study, Yokota and colleagues investigated IκBNS – an atypical inhibitor of NF-kB (IκB). Using elegant bone marrow chimera studies in mice, they found that IκBNS differentially modulated NF-κB activity in hematopoietic and non-hematopoietic cells. They also showed that by binding to the promoter region, this nuclear protein directly induced the MUC5AC gene in airway epithelial cells. This study enhances our understanding of how atypical IκB proteins work in regulating NF-κB activity and allergic airway conditions. It also emphasizes that targeting specific molecular pathways of airway inflammation may result in differential effects depending on the targeted tissue compartment. This is important in the search of novel asthma treatments and supports the fact that global anti-inflammatory approaches alone may not provide sufficient therapy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-01-18T18:50:27.172939-05:
      DOI: 10.1111/all.13126
  • Allergen immunotherapy for IgE-mediated food allergy: a systematic review
           and meta-analysis
    • Authors: Ulugbek Nurmatov; Sangeeta Dhami, Stefania Arasi, Giovanni Battista Pajno, Montserrat Fernandez-Rivas, Antonella Muraro, Graham Roberts, Cezmi Akdis, Montserrat Alvaro-Lozano, Kirsten Beyer, Carsten Bindslev-Jensen, Wesley Burks, George du Toit, Motohiro Ebisawa, Philippe Eigenmann, Edward Knol, Mika Makela, Kari Christine Nadeau, Liam O'Mahony, Nikolaos Papadopoulos, Lars K. Poulsen, Cansin Sackesen, Hugh Sampson, Alexandra Santos, Ronald van Ree, Frans Timmermans, Aziz Sheikh
      Abstract: BackgroundThe European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy.MethodsWe undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and non-randomized studies (NRS). Eligible studies were independently assessed by two reviewers against pre-defined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses.ResultsWe identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy (SLIT) and one study evaluated epicutaneous immunotherapy (EPIT). The majority of these studies were in children. Twenty-seven studies assessed desensitization and nine studies investigated sustained unresponsiveness post-discontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR)=0.19, 95%CI 0.12, 0.29) and sustained unresponsiveness (RR=0.20, 95%CI 0.10, 0.59). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses.ConclusionsAIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is however associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, the impact on QoL and the cost-effectiveness of AIT.This article is protected by copyright. All rights reserved.
      PubDate: 2017-01-06T02:25:24.08894-05:0
      DOI: 10.1111/all.13124
  • Coping strategies, alexithymia and anxiety in young patients with food
    • Authors: L. Polloni; A. DunnGalvin, E. Ferruzza, R. Bonaguro, F. Lazzarotto, A. Toniolo, N. Celegato, A. Muraro
      Pages: 1054 - 1060
      Abstract: BackgroundFood allergy is major public health concern affecting nearly 15 million Americans and 80 million Europeans. Risk of anaphylaxis and implications for social activities affect patients' quality of life and psychological well-being. We previously found that young patients reported higher levels of alexithymia (difficulty in recognizing and expressing emotions) compared with healthy peers and may influence affect, management style and clinical outcomes. This study aimed to explore links between coping strategies, alexithymia and anxiety among food-allergic adolescents and young adults.MethodsNinety-two patients with IgE-mediated food allergy (mean age 18.6 years) completed Coping Orientation to Problems Experienced Inventory, Toronto Alexithymia Scale and Trait Anxiety subscale of State-Trait Anxiety Inventory. Multivariate analyses of variance assessed differences and associations between subgroups on the scales.ResultsSignificant differences found between alexithymia levels in coping style were explained by Avoidance strategies. ‘Avoidance’ had the highest contribution in explaining alexithymia, followed by trait anxiety, age, anaphylaxis and social support. Respondents with higher alexithymia use avoidance as coping strategy over and above other coping strategies such as problem-solving and positive thinking, are younger, will have experienced anaphylaxis and will have lower social support.ConclusionsRecognizing the specific role of affect regulation in health behaviours may constitute an important step in supporting patients to explore more adaptive strategies.
      PubDate: 2017-01-11T06:35:26.752935-05:
      DOI: 10.1111/all.13097
  • Spleen tyrosine kinase inhibition blocks airway constriction and protects
           from Th2-induced airway inflammation and remodeling
    • Authors: C. Tabeling; J. Herbert, A. C. Hocke, D. J. Lamb, S. L. Wollin, K. J. Erb, E. Boiarina, H. Movassagh, J. Scheffel, J. M. Doehn, S. Hippenstiel, M. Maurer, A. S. Gounni, W. M. Kuebler, N. Suttorp, M. Witzenrath
      Pages: 1061 - 1072
      Abstract: BackgroundSpleen tyrosine kinase (Syk) is an intracellular nonreceptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive.MethodsSpectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression. The effects of prophylactic or therapeutic Syk inhibition on allergic airway inflammation, hyperresponsiveness, and airway remodeling were analyzed in allergen-sensitized and airway-challenged mice. The effects of Syk inhibitors BAY 61-3606 or BI 1002494 on airway function were investigated in isolated lungs of wild-type, PKCα-deficient, mast cell-deficient, or eNOS-deficient mice.ResultsSpleen tyrosine kinase expression was found in human and murine airway smooth muscle cells. Syk inhibition reduced allergic airway inflammation, airway hyperresponsiveness, and pulmonary collagen deposition. In naïve mice, Syk inhibition diminished airway responsiveness independently of mast cells, or PKCα or eNOS expression and rapidly reversed established bronchoconstriction independently of NO. Simultaneous inhibition of Syk and PKC revealed additive dilatory effects, whereas combined inhibition of Syk and rho kinase or Syk and p38 MAPK did not cause additive bronchodilation.ConclusionsSpleen tyrosine kinase inhibition directly attenuates airway smooth muscle cell contraction independent of its protective immunomodulatory effects on allergic airway inflammation, hyperresponsiveness, and airway remodeling. Syk mediates bronchoconstriction in a NO-independent manner, presumably via rho kinase and p38 MAPK, and Syk inhibition might present a promising therapeutic approach in chronic asthma as well as acute asthma attacks.
      PubDate: 2017-01-12T04:00:38.038503-05:
      DOI: 10.1111/all.13101
  • Allergic sensitization at school age is a systemic low-grade inflammatory
    • Authors: B. L. Chawes; J. Stokholm, A.-M. M. Schoos, N. R. Fink, S. Brix, H. Bisgaard
      Pages: 1073 - 1080
      Abstract: BackgroundSystemic low-grade inflammation has been demonstrated in a range of the frequent noncommunicable diseases (NCDs) proposing a shared mechanism, but is largely unexplored in relation to allergic sensitization. We therefore aimed to investigate the possible association with childhood allergic sensitization.MethodsHigh-sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and chemokine (C-X-C motif) ligand 8 (CXCL8) were measured in plasma at age 6 months (N = 214) and 7 years (N = 277) in children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) birth cohort. Allergic sensitization against common inhalant and food allergens was determined longitudinally at ages ½, 1½, 4 and 6 years by specific IgE assessments and skin prick tests. Associations between inflammatory biomarkers and sensitization phenotypes were tested with logistic regression and principal component analyses (PCAs).ResultsAdjusted for gender, recent infections, and a CRP genetic risk score, hs-CRP at 7 years was associated with concurrent elevated specific IgE against any allergen [adjusted OR (aOR) = 1.40; 95% CI, 1.14–1.72; P = 0.001], aeroallergens (aOR, 1.43; 1.15–1.77; P = 0.001), food allergens (aOR, 1.31; 95% CI, 1.02–1.67; P = 0.04), sensitization without any clinical allergy symptoms (aOR = 1.40; 1.06–1.85; P = 0.02), and with similar findings for skin prick tests. The other inflammatory markers were not univariately associated with sensitization, but multiparametric PCA suggested a specific inflammatory response among sensitized children. Inflammatory markers at age 6 months were not associated with subsequent development of sensitization phenotypes.ConclusionsElevated hs-CRP is associated with allergic sensitization in school-aged children suggesting systemic low-grade inflammation as a phenotypic characteristic of this early-onset NCD.
      PubDate: 2017-01-17T02:42:59.996828-05:
      DOI: 10.1111/all.13108
  • The immunoglobulin superfamily member CD200R identifies cells involved in
           type 2 immune responses
    • Authors: L. H. Blom; B. C. Martel, L. F. Larsen, C. V. Hansen, M. P. Christensen, N. Juel-Berg, T. Litman, L. K. Poulsen
      Pages: 1081 - 1090
      Abstract: BackgroundThe pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation.MethodsNaïve human CD4+ T cells were short-term activated in the presence or absence of IL-4 and analyzed for expression of>300 cell-surface proteins. Ex vivo-isolated peripheral blood mononuclear cells (PBMCs) from peanut-allergic (PA) and nonallergic subjects were stimulated (14–16 h) with peanut extract to detect peanut-specific CD4+CD154+ T cells. Biopsies were obtained for transcriptomic analysis from healthy controls and patients with extrinsic or intrinsic atopic dermatitis (AD) and psoriasis.ResultsExpression analysis of>300 surface proteins enabled identification of IL-4-upregulated surface proteins, such as CD90, CD108, CD109, and CD200R (CD200R1). Additional analysis of in vitro-differentiated Th0, Th1, and Th2 cultures identified CD200R as upregulated on Th2 cells. From ex vivo-isolated PBMCs, we found high expression of CD200R on Th2 and ILC2 cells and basophils. In PA subjects, the peanut-specific Th2 (CD154+CRTh2+) cells expressed more CD200R than the non-allergen-specific Th2 (CD154−CRTh2+) cells. Moreover, costaining of CD161 and CD200R identified peanut-specific highly differentiated IL-4+IL-5+ Th2 cells. Finally, transcriptomic analysis revealed upregulation of CD200R in lesional skin from subjects with an extrinsic AD phenotype compared to healthy skin.ConclusionThese results indicate that CD200R expression strongly correlates with Th2 pathology; though, the mechanism is as yet elusive.
      PubDate: 2017-02-21T01:45:35.771279-05:
      DOI: 10.1111/all.13129
  • Validation of International Classification of Disease Ninth Revision codes
           for atopic dermatitis
    • Authors: D. Y. Hsu; P. Dalal, K. A. Sable, N. Voruganti, B. Nardone, D. P. West, J. I. Silverberg
      Pages: 1091 - 1095
      Abstract: BackgroundEvaluation of large-scale data sets is needed to better understand the epidemiology, cost, and burden of atopic dermatitis (AD). We sought to validate the use of ICD-9-CM codes for identifying AD.MethodsPatients from a large metropolitan quaternary care medical center with a diagnostic code of either 691.8 (AD) or 692.9 (eczema and contact dermatitis) were queried. Medical records were reviewed for demographics, Hanifin & Rajka (H&R) and United Kingdom Working Party (UKWP) criteria. Sensitivity, specificity, and positive predictive values (PPV) of the codes were calculated.ResultsOf 43 278 patients identified with associated ICD-9 codes of 691.8 or 692.9, 519 and 253 with 691.8 and 692.9 were randomly selected for chart review. There was extensive overlap: 34.3% had ≥1 occurrences of 691.8 and 692.9 and 25.6% had multiple occurrences of both codes. Among patients with ≥1 occurrence of 691.8, 29.9% and 30.8% met the H&R and UKWP criteria, respectively. Similarly, among patients with ≥1 occurrence of 692.9, 33.7% and 32.2% met the H&R and UKWP criteria. Increased PPV was associated with concomitant diagnoses of asthma, hay fever, and food allergy and increased disease severity.ConclusionsIn the outpatient setting, the ICD-9-CM codes 691.8 and 692.9 alone have poor PPV. Incorporation of diagnoses of asthma, hay fever, and food allergy improves PPV and specificity. In the inpatient setting, a primary discharge diagnosis of 691.8 had excellent PPV. Although ICD-10 has been adopted in Europe and more recently in the USA, the same systematic errors would likely occur unless providers standardize their coding.
      PubDate: 2017-01-17T02:45:40.94189-05:0
      DOI: 10.1111/all.13113
  • Opisthorchis felineus negatively associates with skin test reactivity in
           Russia—EuroPrevall-International Cooperation study
    • Authors: O. S. Fedorova; J. J. Janse, L. M. Ogorodova, M. M. Fedotova, R. A. Achterberg, J. J. Verweij, M. Fernández-Rivas, S. A. Versteeg, J. Potts, C. Minelli, R. Ree, P. Burney, M. Yazdanbakhsh
      Pages: 1096 - 1104
      Abstract: BackgroundMost studies on the relationship between helminth infections and atopic disorders have been conducted in (sub)tropical developing countries where exposure to multiple parasites and lifestyle can confound the relationship. We aimed to study the relationship between infection with the fish-borne helminth Opishorchis felineus and specific IgE, skin prick testing, and atopic symptoms in Western Siberia, with lifestyle and hygiene standards of a developed country.MethodsSchoolchildren aged 7–11 years were sampled from one urban and two rural regions. Skin prick tests (SPT) and specific IgE (sIgE) against food and aeroallergens were measured, and data on allergic symptoms and on demographic and socioeconomic factors were collected by questionnaire. Diagnosis of opisthorchiasis was based on PCR performed on stool samples.ResultsOf the 732 children included, 34.9% had opisthorchiasis. The sensitization to any allergen when estimated by positive SPT was 12.8%, while much higher, 24.0%, when measured by sIgE. Atopic symptoms in the past year (flexural eczema and/or rhinoconjunctivitis) were reported in 12.4% of the children. SPT was positively related to flexural eczema and rhinoconjunctivitis, but not to wheezing. Opisthorchiasis showed association with lower SPT response, as well as borderline association with low IgE reactivity to any allergen. However, the effect of opisthorchiasis on SPT response was not mediated by IgE, suggesting that opisthorchiasis influences SPT response through another mechanism. Opisthorchiasis also showed borderline association with lower atopic symptoms.ConclusionsThere is a negative association between a chronic helminth infection and skin prick test reactivity even in a developed country.
      PubDate: 2017-01-25T03:41:29.047703-05:
      DOI: 10.1111/all.13120
  • Green, Yellow, and Red risk perception in everyday life – a
           communication tool
    • Authors: A. Stensgaard; A. DunnGalvin, D. Nielsen, M. Munch, C. Bindslev-Jensen
      Pages: 1114 - 1122
      Abstract: BackgroundAdolescents have the highest risk for food allergy-related fatalities. Our main aim was to investigate the level of risk in everyday social situations as perceived by adolescents/young adults with peanut allergy, their families, and their friends.MethodsThe web-based ‘Colours Of Risks’ (COR) questionnaire was completed by 70 patients (aged 12–23 years), 103 mothers and fathers, 31 siblings (aged 12–26 years), and 42 friends (aged 12–24 years). COR deals with six main contexts (home, school/university, work, visiting/social activities, special occasions/parties, and vacations), each with 1-12 items. Response categories are green (I feel safe), yellow (I feel uncertain), or red (I feel everything is risky).ResultsThere was a high level of agreement between participants in defining situations as safe, uncertain, or risky, but female patients and mothers rated fewer situations as safe compared to male patients and fathers. Being with close friends and family, and attending planned parties without alcohol were perceived as situations of low risk. While 94% of patients took an epinephrine auto-injector (EAI) into risky situations, only 65% took it into safe situations. In contrast to the close family, 31% of the friends did not know the patient had an EAI, and fewer knew how to administer the EAI.ConclusionYoung adults with peanut allergy face challenges when moving from the safe home with ready assistance if needed, to independence with unpredictable surroundings and less certain help. Perceived ‘safe’ situations may in fact be the riskiest, as patients often do not take the EAI with them.
      PubDate: 2017-01-24T01:20:43.213628-05:
      DOI: 10.1111/all.13095
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