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Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro . It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen., (© 2019 The Authors.)

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy., Main Body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care., Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement., Competing Interests: Competing interestsDr. Ansotegui reports personal fees from Mundipharma, Roxall, Sanofi, MSD, Faes Farma, Hikma, UCB, Astra Zeneca, outside the submitted work. Dr. Bosnic-Anticevich reports grants from TEVA, personal fees from TEVA, Boehringer Ingelheim, AstraZeneca, Sanofi, Mylan, outside the submitted work. Dr. Bousquet reports personal fees and others from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi-Aventis, Takeda, Teva, Uriach, others from Kyomed, outside the submitted work. Dr. Boulet reports and Disclosure of potential conflicts of interest—last 3 years. Research grants for participation to multicentre studies, AstraZeneca, Boston Scientific, GlaxoSmithKline, Hoffman La Roche, Novartis, Ono Pharma, Sanofi, Takeda. Support for research projects introduced by the investigator AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Takeda. Consulting and advisory boards Astra Zeneca, Novartis, Methapharm. Royalties Co-author of “Up-To-Date” (occupational asthma). Nonprofit grants for production of educational materials AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck Frosst, Novartis. Conference fees AstraZeneca, GlaxoSmithKline, Merck, Novartis. Support for participation in conferences and meetings Novartis, Takeda. Other participations Past president and Member of the Canadian Thoracic Society Respiratory Guidelines Committee; Chair of the Board of Directors of the Global Initiative for Asthma (GINA). Chair of Global Initiative for Asthma (GINA) Guidelines Dissemination and Implementation Committee; Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health; Member of scientific committees for the American College of Chest Physicians, American Thoracic Society, European Respiratory Society and the World Allergy Organization; 1st Vice-President of the Global Asthma Organization “InterAsma”. Dr. Casale reports grants and non-financial support from Stallergenes, outside the submitted work. Dr. Cruz reports grants and personal fees from GlaxoSmithKline, personal fees from Boehrinher Ingelheim, AstraZeneca, Novartis, Merk, Sharp & Dohme, MEDA Pharma, EUROFARMA, Sanofi Aventis, outside the submitted work. Dr. Ebisawa reports personal fees from DBV Technologies, Mylan EPD maruho, Shionogi & CO., Ltd., Kyorin Pharmaceutical Co., Ltd., Thermofisher Diagnostics, Pfizer, Beyer, Nippon Chemifar, Takeda Pharmaceutical Co., Ltd., MSD, outside the submitted work. Dr. Ivancevich reports personal fees from Euro Farma Argentina, Faes Farma, non-financial support from Laboratorios Casasco, outside the submitted work. Dr. Haahtela reports personal fees from Mundipharma, Novartis, and Orion Pharma, outside the submitted work. Dr. Klimek reports grants and personal fees from ALK Abelló, Denmark, Novartis, Switzerland, Allergopharma, Germany, Bionorica, Germany, GSK, Great Britain, Lofarma, Italy, personal fees from MEDA, Sweden, Boehringer Ingelheim, Germany, grants from Biomay, Austria, HAL, Netherlands, LETI, Spain, Roxall, Germany, Bencard, Great Britain, outside the submitted work. V.KV has received payment for consultancy from GSK and for lectures from StallergensGreer, Berlin-CHemie and sponsorship from MYLAN for in the following professional training: ARIA masterclass in allergic rhinitis participation. Dr. Larenas Linnemann reports personal fees from GSK, Astrazeneca, MEDA, Boehringer Ingelheim, Novartis, Grunenthal, UCB, Amstrong, Siegfried, DBV Technologies, MSD, Pfizer., grants from Sanofi, Astrazeneca, Novartis, UCB, GSK, TEVA, Chiesi, Boehringer Ingelheim, outside the submitted work. Dr. Mösges reports personal fees from ALK, grants from ASIT biotech, Leti, BitopAG, Hulka, Ursapharm, Optima; personal fees from allergopharma, Nuvo, Meda, Friulchem, Hexal, Servier, Bayer, Johnson & Johnson, Klosterfrau, GSK, MSD, FAES, Stada, UCB, Allergy Therapeutics; grants and personal fees from Bencard, Stallergenes; grants, personal fees and non-financial support from Lofarma; non-financial support from Roxall, Atmos, Bionorica, Otonomy, Ferrero; personal fees and non-financial support from Novartis; Dr. Okamoto reports personal fees from Eizai Co., Ltd., Shionogi Co., Ltd., Torii Co., Ltd., GSK, MSD, Kyowa Co., Ltd., grants and personal fees from Kyorin Co., Ltd., Tiho Co., Ltd., grants from Yakuruto Co., Ltd., Yamada Bee Farm, outside the submitted work. Dr. Papadopoulos reports grants from Gerolymatos, personal fees from Hal Allergy B.V., Novartis Pharma AG, Menarini, Hal Allergy B.V., outside the submitted work. Dr. Pépin reports grants from AIR LIQUIDE FOUNDATION, AGIR à dom, ASTRA ZENECA, FISHER & PAYKEL, MUTUALIA, PHILIPS, RESMED, VITALAIRE, other from AGIR à dom, ASTRA ZENECA, BOEHRINGER INGELHEIM, JAZZ PHARMACEUTICAL, NIGHT BALANCE, PHILIPS, RESMED, SEFAM, outside the submitted work. Dr. Pfaar reports grants and personal fees from ALK-Abelló, Allergopharma Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, grants from Biomay, ASIT Biotech Tools S.A, Laboratorios LETI/LETI Pharma, Anergis S.A., grants from Nuvo, Circassia, Glaxo Smith Kline, personal fees from Novartis Pharma, MEDA Pharma, Mobile Chamber Experts (a GA2LEN Partner), Pohl-Boskamp, Indoor Biotechnologies, grants from, outside the submitted work. Dr. Todo-Bom reports grants and personal fees from Novartis, Mundipharma, GSK Teva Pharma, personal fees from AstraZeneca, grants from Leti, outside the submitted work. Dr. Tsiligianni reports advisory boards from Boehringer Ingelheim and Novartis and a grant from GSK, outside the submitted work. Dr. Wallace reports and Indicates that she is the co-chair of the Joint Task Force on Practice Parameters, a task force composed of 12 members of the American Academy of Allergy, Asthma, and Immunology and the American College of Allergy, Asthma, and Immunology. Dr. Waserman reports other from CSL Behring, Shire, AstraZeneca,Teva, Meda, Merck, outside the submitted work. Dr. Zuberbier reports and Organizational affiliations: Commitee member: WHO-Initiative “Allergic Rhinitis and Its Impact on Asthma” (ARIA). Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI). Head: European Centre for Allergy Research Foundation (ECARF). Secretary General: Global Allergy and Asthma European Network (GA2LEN). Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO).

Using a digoxygenin-labelled DNA probe derived from the porcine repeat element PRE-1, we have developed a protocol for the detection of transplanted porcine islets and hepatocytes against a background of murine host tissue. Analysis of this probe by Southern blotting indicated that PRE-1 hybridizes to pig genomic DNA but not to human or mouse DNA. On tissue sections, hybridizing probe was detected using alkaline phosphatase-conjugated antidigoxygenin antibody visualized with 5-bromo-4-chloro-3-indolyl-phosphate/4-nitro-blue tetrazolium chloride (BCIP/NBT) substrate. We have demonstrated sensitive and highly specific staining of porcine nuclei in fixed, paraffin embedded tissue sections, and have applied the technique to detect porcine pancreatic islets and hepatocytes transplanted into murine kidney and spleen. Application of this technique include detection of transplanted cells or organs across the variety of xenogeneic barriers.