Publications by authors named "Tomás Chivato"

34 Publications

Vaccines and Allergic reactions: the past, the current COVID-19 pandemic, and future perspectives.

Allergy 2021 Apr 2. Epub 2021 Apr 2.

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur aftervaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.
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http://dx.doi.org/10.1111/all.14840DOI Listing
April 2021

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Authors:
Jean Bousquet Ioana Agache Hubert Blain Marek Jutel Maria Teresa Ventura Margitta Worm Stefano Del Giacco Athanasios Benetos M Beatrice Bilo Wienczyslawa Czarlewski Amir Hamzah Abdul Latiff Mona Al-Ahmad Elizabeth Angier Isabella Annesi-Maesano Marina Atanaskovic-Markovic Claus Bachert Annick Barbaud Anna Bedbrook Kazi S Bennoor Elena Camelia Berghea Carsten Bindslev-Jensen Sergio Bonini Sinthia Bosnic-Anticevich Knut Brockow Luisa Brussino Paulo Camargos G Walter Canonica Victoria Cardona Pedro Carreiro-Martins Ana Carriazo Thomas Casale Jean-Christoph Caubet Lorenzo Cecchi Antonio Cherubini George Christoff Derek K Chu Alvaro A Cruz Dejan Dokic Yehia El-Gamal Motohiro Ebisawa Bernadette Eberlein John Farrell Montserrat Fernandez-Rivas Wytske J Fokkens Joao A Fonseca Yadong Gao Gaëtan Gavazzi Radolslaw Gawlik Asli Gelincik Bilun Gemicioğlu Maia Gotua Olivier Guérin Tari Haahtela Karin Hoffmann-Sommergruber Hans Jürgen Hoffmann Maja Hofmann Martin Hrubisko Madda lenaIllario Carla Irani Zhanat Ispayeva Juan Carlos Ivancevich Kaja Julge Igor Kaidashev Musa Khaitov Edward Knol Helga Kraxner Piotr Kuna Violeta Kvedariene Antti Lauerma Lan Tt Le Vincent Le Moing Michael Levin Renaud Louis Olga Lourenco Vera Mahler Finbarr C Martin Andrea Matucci Branislava Milenkovic Stéphanie Miot Emma Montella Mario Morais-Almeida Charlotte G Mortz Joaquim Mullol Leyla Namazova-Baranova Hugo Neffen Kristof Nekam Marek Niedoszytko Mikaëla Odemyr Robyn E O'Hehir Yoshitaka Okamoto Markus Ollert Oscar Palomares Nikolaos G Papadopoulos Petr Panzner Gianni Passalacqua Vincenzo Patella Mirko Petrovic Oliver Pfaar Nhân Pham-Thi Davor Plavec Todor A Popov Marysia T Recto Frederico S Regateiro Jacques Reynes Regina E Roller-Winsberger Yves Rolland Antonino Romano Carmen Rondon Menachem Rottem Philip W Rouadi Nathalie Salles Boleslaw Samolinski Alexandra F Santos Faradiba Sarquis Serpa Joaquin Sastre Jos M G A Schols Nicola Scichilone Anna Sediva Mohamed H Shamji Aziz Sheikh Isabel Skypala Sylwia Smolinska Milena Sokolowska Bernardo Sousa-Pinto Milan Sova Rafael Stelmach Gunter Sturm Charlotte Suppli Ulrik Ana Maria Todo-Bom Sanna Toppila-Salmi Ioanna Tsiligianni Maria Torres Eva Untersmayr Marilyn Urrutia Pereira Arunas Valiulis Joana Vitte Alessandra Vultaggio Dana Wallace Jolanta Walusiak-Skorupa De-Yun Wang Susan Waserman Arzu Yorgancioglu Osman M Yusuf Mario Zernotti Mihaela Zidarn Tomas Chivato Cezmi A Akdis Torsten Zuberbier Ludger Klimek

Allergy 2021 Apr 2. Epub 2021 Apr 2.

Department of Otolaryngology, Head and Neck Surgery, Universitätsmedizin Mainz, Mainz, and Center for Rhinology and Allergology, Wiesbaden, Germany.

Older adults, especially men and/or those with diabetes, hypertension and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritised to receive COVID-19 vaccines due to high risk of death. In very rare instances,the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society)Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
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http://dx.doi.org/10.1111/all.14838DOI Listing
April 2021

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold- An ARIA-EAACI-GA LENconsensus.

Authors:
Jan Hagemann Gabrielle L Onorato Marek Jutel Cezmi A Akdis Ioana Agache Torsten Zuberbier Wienczyslawa Czarlewski Joaquim Mullol Anna Bedbrook Claus Bachert Kazi S Bennoor Karl-Christian Bergmann Fulvio Braido Paulo Camargos Luis Caraballo Victoria Cardona Thomas Casale Lorenzo Cecchi Tomas Chivato Derek K Chu Cemal Cingi Jaime Correia-de-Sousa Stefano Del Giacco Dejan Dokic Mark Dykewicz Motohiro Ebisawa Yehia El-Gamal Regina Emuzyte Jean-Luc Fauquert Alessandro Fiocchi Wytske J Fokkens Joao A Fonseca Bilun Gemicioglu Maximiliano Gomez Gotua Maia Tari Haahtela Eckard Hamelmann Tomohisa Iinuma Juan Carlos Ivancevich Ewa Jassem Omer Kalayci Przemyslaw Kardas Musa Khaitov Piotr Kuna Violeta Kvedariene Desiree E Larenas-Linnemann Brian Lipworth Michael Makris Jorge F Maspero Neven Miculinic Florin Mihaltan Yousser Mohammad Stephen Montefort Mario Morais-Almeida Ralph Mösges Robert Naclerio Hugo Neffen Marek Niedoszytko Robyn E O'Hehir Ken Ohta Yoshitaka Okamoto Kimi Okubo Petr Panzner Nikolaos G Papadopoulos Giovanni Passalacqua Vincenzo Patella Ana Pereira Oliver Pfaar Davor Plavec Todor A Popov Emmanuel P Prokopakis Francesca Puggioni Filip Raciborski Jere Reijula Frederico S Regateiro Sietze Reitsma Antonino Romano Nelson Rosario Menachem Rottem Dermot Ryan Boleslaw Samolinski Joaquin Sastre Dirceu Solé Milan Sova Cristiana Stellato Charlotte Suppli-Ulrik Ioanna Tsiligianni Antonio Valero Arunas Valiulis Erkka Valovirta Tuula Vasankari Maria Teresa Ventura Dana Wallace De Yun Wang Iân Williams Arzu Yorgancioglu Osman M Yusuf Mario Zernotti Jean Bousquet Ludger Klimek

Allergy 2021 Mar 17. Epub 2021 Mar 17.

Department of Otolaryngology, Head and Neck Surgery, Universitätsmedizin Mainz, Mainz, Germany.

Background: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken withthe common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms betweenthe three diseases.

Methods: A modified Delphi process was used and ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold andallergic rhinitis.

Results: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded. 87 questionnaires were analysed. The consensus was then reported.A two-way ANOVA analysis revealed significant differences inthe symptom intensity between the three diseases (p<0.001).

Conclusions: This modified Delphi approach enabled thedifferentiationof upper respiratory symptoms betweenCOVID-19, common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
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http://dx.doi.org/10.1111/all.14815DOI Listing
March 2021

Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: A systematic review for the EAACI guidelines.

Allergy 2021 Mar 8. Epub 2021 Mar 8.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.
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http://dx.doi.org/10.1111/all.14809DOI Listing
March 2021

COVID-19 pandemic and allergen immunotherapy - an EAACI survey.

Allergy 2021 Mar 2. Epub 2021 Mar 2.

Institut de Recerca Sant Joan de Déu, Barcelona, Spain.

Background: As in many fields of medical care, the coronavirus disease 2019 (COVID-19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and systematically collect all information available regarding tolerability and possible amendments in daily practice of sublingual AIT (SLIT), subcutaneous AIT (SCIT) for inhalant allergies and venom AIT.

Method: Under the framework of the EAACI, a panel of experts in the field of AIT coordinated by the Immunotherapy Interest Group (IT IG) set-up a web-based retrospective survey (SurveyMonkey®) including 27 standardized questions on practical and safety aspects on AIT in worldwide clinical routine.

Results: 417 respondents providing AIT to their patients in daily routine answered the survey. For patients (without any current symptoms to suspect COVID-19), 60% of the respondents informed of not having initiated SCIT (40% venom AIT, 35% SLIT) whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID-19 and/or a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Conclusions: This first international retrospective survey in atopic diseases investigated practical aspects and tolerability of AIT during the COVID-19 pandemic and gave no concerns regarding reduced tolerability under real-life circumstances. However, the data indicate an undertreatment of AIT, which may be temporary, but could have a long-lasting negative impact on the clinical care of allergic patients.
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http://dx.doi.org/10.1111/all.14793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013670PMC
March 2021

EAACI Biologicals Guidelines - dupilumab for children and adults with moderate-to-severe atopic dermatitis.

Allergy 2020 Dec 7. Epub 2020 Dec 7.

University of Wroclaw, Department of Clinical Immunology, Wroclaw, Poland.

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, comorbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. Theseincludethe definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumabin atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed.
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http://dx.doi.org/10.1111/all.14690DOI Listing
December 2020

Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics.

Allergy 2020 Aug 19. Epub 2020 Aug 19.

Facultad de Medicina, Departamento de Ciencias Médicas Básicas, Instituto de Medicina Molecular Aplicada (IMMA), Universidad San Pablo-CEU, CEU Universities, Madrid, España.

Background: Sublingual allergen-specific immunotherapy (SLIT) intervention improves the control of grass pollen allergy by maintaining allergen tolerance after cessation. Despite its widespread use, little is known about systemic effects and kinetics associated to SLIT, as well as the influence of the patient sensitization phenotype (Mono- or Poly-sensitized). In this quest, omics sciences could help to gain new insights to understand SLIT effects.

Methods: 47 grass-pollen-allergic patients were enrolled in a double-blind, placebo-controlled, multicenter trial using GRAZAX® during 2 years. Immunological assays (sIgE, sIgG4, and ISAC) were carried out to 31 patients who finished the trial. Additionally, serum and PBMCs samples were analyzed by metabolomics and transcriptomics, respectively. Based on their sensitization level, 22 patients were allocated in Mono- or Poly-sensitized groups, excluding patients allergic to epithelia. Individuals were compared based on their treatment (Active/Placebo) and sensitization level (Mono/Poly).

Results: Kinetics of serological changes agreed with those previously described. At two years of SLIT, there are scarce systemic changes that could be associated to improvement in systemic inflammation. Poly-sensitized patients presented a higher inflammation at inclusion, while Mono-sensitized patients presented a reduced activity of mast cells and phagocytes as an effect of the treatment.

Conclusions: The most relevant systemic change detected after two years of SLIT was the desensitization of effector cells, which was only detected in Mono-sensitized patients. This change may be related to the clinical improvement, as previously reported, and, together with the other results, may explain why clinical effect is lost if SLIT is discontinued at this point.
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http://dx.doi.org/10.1111/all.14565DOI Listing
August 2020

Efficacy and safety of treatment with omalizumab for chronic spontaneous urticaria: A systematic review for the EAACI Biologicals Guidelines.

Allergy 2021 01 7;76(1):59-70. Epub 2020 Sep 7.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CSU-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Ten RCTs including 1620 subjects aged 12 to 75 years old treated with omalizumab for 16 to 40 weeks were evaluated. Omalizumab 150 mg does not result in clinically meaningful improvement (high certainty) of the urticaria activity score (UAS)7 (mean difference (MD) -5; 95%CI -7.75 to -2.25), and the itch severity score (ISS)7 (MD -2.15; 95% CI -3.2 to -1.1) does not increase (moderate certainty) quality of life (QoL) (Dermatology Life Quality Index (DLQI); MD -2.01; 95%CI -3.22 to -0.81) and decreases (moderate certainty) rescue medication use (MD -1.68; 95%CI -2.95 to -0.4). Omalizumab 300 mg results in clinically meaningful improvements (moderate certainty) of the UAS7 (MD -11.05; 95%CI -12.87 to -9.24), the ISS7 (MD -4.45; 95%CI -5.39 to -3.51), and QoL (high certainty) (DLQI; MD -4.03; 95% CI -5.56 to -2.5) and decreases (moderate certainty) rescue medication use (MD -2.04; 95%CI -3.19 to -0.88) and drug-related serious AEs (RR 0.77; 95%CI 0.20 to 2.91).
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http://dx.doi.org/10.1111/all.14547DOI Listing
January 2021

Cross-sectional pilot study exploring the feasibility of a rapid SARS-CoV-2 immunization test in health and nonhealthcare workers.

Allergy 2021 03 20;76(3):896-899. Epub 2020 Aug 20.

Department of Basic Medical Sciences, Faculty of Medicine, Institute of Applied Molecular Medicine, Universidad San Pablo CEU, CEU Universities, Madrid, Spain.

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http://dx.doi.org/10.1111/all.14545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436513PMC
March 2021

Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines.

Allergy 2021 01 4;76(1):45-58. Epub 2020 Oct 4.

Department of Clinical Immunology, Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate-to-severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects >12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD -30,72; 95% CI -34,65% to -26,79%) and EASI-75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD -7.29; 95% CI -8.23 to -6.35) and anxiety/depression (MD -3.08; 95% CI -4.41 to -1.75) and improves quality of life (MD -4.80; 95% CI -5.55 to -4.06). The efficacy for adolescents is similar. Dupilumab-related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab-related serious AE is uncertain. The incremental cost-effectiveness ratio ranged from 28 500 £ (low certainty) to 124 541 US$ (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population. Registration: PROSPERO (CRD42020153645).
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http://dx.doi.org/10.1111/all.14510DOI Listing
January 2021

ARIA-EAACI statement on asthma and COVID-19 (June 2, 2020).

Authors:
Jean Bousquet Marek Jutel Cezmi A Akdis Ludger Klimek Oliver Pfaar Kari C Nadeau Thomas Eiwegger Anna Bedbrook Ignacio J Ansotegui Josep M Anto Claus Bachert Eric D Bateman Kazi S Bennoor Elena Camelia Berghea Karl-Christian Bergmann Hubert Blain Mateo Bonini Sinthia Bosnic-Anticevich Louis-Philippe Boulet Luisa Brussino Roland Buhl Paulo Camargos Giorgio Walter Canonica Victoria Cardona Thomas Casale Sharon Chinthrajah Mübeccel Akdis Tomas Chivato George Christoff Alvaro A Cruz Wienczyslawa Czarlewski Stefano Del Giacco Hui Du Yehia El-Gamal Wytske J Fokkens Joao A Fonseca Yadong Gao Mina Gaga Bilun Gemicioglu Maia Gotua Tari Haahtela David Halpin Eckard Hamelmann Karin Hoffmann-Sommergruber Marc Humbert Nataliya Ilina Juan-Carlos Ivancevich Guy Joos Musa Khaitov Bruce Kirenga Edward F Knol Fanny W Ko Seppo Koskinen Marek L Kowalski Helga Kraxner Dmitry Kudlay Piotr Kuna Maciej Kupczyk Violeta Kvedariene Amir H Abdul Latiff Lan T Le Michael Levin Desiree Larenas-Linnemann Renaud Louis Mohammad R Masjedi Erik Melén Florin Mihaltan Branislava Milenkovic Yousser Mohammad Mario Morais-Almeida Joaquim Mullol Leyla Namazova Hugo Neffen Elisabete Nunes Paul O'Byrne Robyn O'Hehir Liam O'Mahony Ken Ohta Yoshitaka Okamoto Gabrielle L Onorato Petr Panzner Nikos G Papadopoulos Gianni Passalacqua Vincenzo Patella Ruby Pawankar Nhân Pham-Thi Bernard Pigearias Todor A Popov Francesca Puggioni Frederico S Regateiro Giovanni Rolla Menachem Rottem Boleslaw Samolinski Joaquin Sastre Jurgen Schwarze Aziz Sheikh Nicola Scichilone Manuel Soto-Quiros Manuel Soto-Martinez Milan Sova Stefania Nicola Rafael Stelmach Charlotte Suppli-Ulrik Luis Taborda-Barata Teresa To Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Omar Usmani Arunas Valiulis Maria Teresa Ventura Giovanni Viegi Theodor Vontetsianos De Yun Wang Sian Williams Gary W K Wong Arzu Yorgancioglu Mario Zernotti Mihaela Zidarn Torsten Zuberbier Ioana Agache

Allergy 2021 03 21;76(3):689-697. Epub 2020 Sep 21.

Transylvania University Brasov, Brasov, Romania.

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http://dx.doi.org/10.1111/all.14471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361514PMC
March 2021

Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemie: Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H.

Allergo J 2020 24;29(4):14-27. Epub 2020 Jun 24.

Zentrum für Rhinologie & Allergologie, An den Quellen 10, 65183 Wiesbaden, Germany.

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http://dx.doi.org/10.1007/s15007-020-2553-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289636PMC
June 2020

COVID-19 pandemic: Practical considerations on the organization of an allergy clinic-An EAACI/ARIA Position Paper.

Allergy 2021 03;76(3):648-676

Transylvania University, Brasov, Romania.

Background: The coronavirus disease 2019 (COVID-19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.

Method: The scientific information on COVID-19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet.

Results: Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the "Allergic Rhinitis and its Impact on Asthma (ARIA)" initiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.

Conclusions: This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID-19 pandemic.
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http://dx.doi.org/10.1111/all.14453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323448PMC
March 2021

EAACI Biologicals Guidelines-Recommendations for severe asthma.

Allergy 2021 01 10;76(1):14-44. Epub 2020 Aug 10.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities.
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http://dx.doi.org/10.1111/all.14425DOI Listing
January 2021

Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines-Recommendations on the use of biologicals in severe asthma.

Allergy 2020 05 1;75(5):1058-1068. Epub 2020 Apr 1.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor α, is approved as add-on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24-52 weeks of follow-up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45-0.59) and the percentage use of oral corticosteroid use (mean difference (MD) -28.2 mg/d; 95% CI -40.7 to -15.7). Asthma control (ACQ-5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ-5 MD -0.28 (95% CI -0.39 to -0.17); AQLQ MD +0.28 (95% CI 0.20-0.37); and rescue medication MD -0.35 (95% CI -0.73 to +0.02). FEV increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab-related adverse events (AEs) (moderate certainty) and of drug-related serious AEs (low certainty). The incremental cost-effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.
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http://dx.doi.org/10.1111/all.14268DOI Listing
May 2020

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.

Allergy 2020 05;75(5):1043-1057

University of Wroclaw, Department of Clinical Immunology, Wroclaw, Poland.

Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50 - 0.81); dupilumab IRR 0.58 (95%CI 0.47 - 0.73); and omalizumab IRR 0.56 (95%CI 0.42 - 0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug-related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6-12 years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45-0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 -1.83)], reduced ICS [mean difference (MD) -0.45 (95% CI -0.58 to -0.32)] and rescue medication use [ MD -0.41 (95%CI -0.66 to -0.15)].
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http://dx.doi.org/10.1111/all.14235DOI Listing
May 2020

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.

Allergy 2020 05 24;75(5):1023-1042. Epub 2020 Feb 24.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV . More data on long-term safety are needed together with more efficacy data in the paediatric population.
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http://dx.doi.org/10.1111/all.14221DOI Listing
May 2020

[Clinical Practice Guide for Anaphylaxis in Latin America (Galaxia-Latam)].

Rev Alerg Mex 2019 ;66 Suppl 2:1-39

Universitat Autónoma de Barcelona, Hospital Universitario Vall d'Hebron, Servicio de Medicina Interna, Sección de Alergología, Barcelona, España.

Anaphylaxis is a severe allergic reaction with a rapid onset and it is potentially life-threatening. Its clinical manifestations are varied; they may affect the skin, the cardiovascular system, the respiratory system, and the digestive system, among others. The treatment of choice, which is an intra-muscular injection of epinephrine (adrenaline), must be applied promptly. Therefore, being prepared to recognize it properly is of crucial importance. The objective of this clinical practice guide is to improve the knowledge of health professionals about anaphylaxis and, consequently, to optimize the treatment and long-term management of this reaction. This guide is adapted to the peculiarities of Latin America; especially in matters regarding the treatment. The need to introduce epinephrine auto-injectors in countries that don't have them yet is highlighted.
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http://dx.doi.org/10.29262/ram.v66i6.588DOI Listing
February 2020

Prioritizing research challenges and funding for allergy and asthma and the need for translational research-The European Strategic Forum on Allergic Diseases.

Allergy 2019 11 2;74(11):2064-2076. Epub 2019 Jun 2.

Institute of Translational Pharmacology, Italian National Research Council, Rome, Italy.

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients' organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.
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http://dx.doi.org/10.1111/all.13856DOI Listing
November 2019

Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.

Allergy 2018 11 9;73(11):2137-2149. Epub 2018 Aug 9.

IMMA, Instituto de Medicina Molecular Aplicada, Facultad de Medicina, Universidad San Pablo CEU, Madrid, España.

Background: Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics.

Methods: Twenty-five subjects were included in the study. Plasma samples were analyzed using gas and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively). Individuals were classified in four groups-"nonallergic," "mild," "moderate," and "severe"-based on their clinical history, their response to an oral challenge test with profilin, and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis.

Results: We found a set of transcripts and metabolites that were specific for the "severe" phenotype. By metabolomics, a decrease in carbohydrates and pyruvate and an increase in lactate were detected, suggesting aerobic glycolysis. Other metabolites were incremented in "severe" group: lysophospholipids, sphingosine-1-phosphate, sphinganine-1-phosphate, and lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the "severe" group were found to be downregulated and were associated with platelet functions, protein synthesis, histone modification, and fatty acid metabolism.

Conclusion: We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.
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http://dx.doi.org/10.1111/all.13563DOI Listing
November 2018

Alternative Anaphylactic Routes: The Potential Role of Macrophages.

Front Immunol 2017 8;8:515. Epub 2017 May 8.

Faculty of Medicine, IMMA Applied Molecular Medicine Institute, CEU San Pablo University, Madrid, Spain.

Anaphylaxis is an acute, life-threatening, multisystem syndrome resulting from the sudden release of mediators from effector cells. There are two potential pathways for anaphylaxis. The first one, IgE-dependent anaphylaxis, is induced by antigen (Ag) cross-linking of Ag-specific IgE bound to the high-affinity IgE receptor (FcεRI) on mast cells and basophils. The second one, IgG-dependent anaphylaxis is induced by Ag cross-linking of Ag-specific IgG bound to IgG receptors (FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, and FcγRIIIA) on macrophages, neutrophils, and basophils. Macrophages exhibit a huge functional plasticity and are capable of exerting their scavenging, bactericidal, and regulatory functions under a wide variety of tissue conditions. Herein, we will review their potential role in the triggering and development of anaphylaxis. Thereby, macrophages, among other immune cells, play a role in both anaphylactic pathways (1) by responding to anaphylactic mediators secreted by mast cells after specific IgE cross-linking or (2) by acting as effector cells in the anaphylactic response mediated by IgG. In this review, we will go over the cellular and molecular mechanisms that take place in the above-mentioned anaphylactic pathways and will discuss the clinical implications in human allergic reactions.
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http://dx.doi.org/10.3389/fimmu.2017.00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421149PMC
May 2017

Clinical management, expectations, and satisfaction of patients with moderate to severe allergic rhinoconjunctivitis treated with SQ-standardized grass-allergen tablet under routine clinical practice conditions in Spain.

Clin Mol Allergy 2017 6;15. Epub 2017 Jan 6.

ALK-Abelló, S.A, Madrid, Spain.

Background: Sublingual immunotherapy has been proven as a well-tolerated and effective treatment for allergic rhinitis. Within this type of treatment, GRAZAX is the most documented product in terms of safety and efficacy. The objective of this study was to identify the patients' expectations and level of treatment satisfaction, as well as the clinical management of patients with moderate/severe allergic rhinoconjunctivitis treated with GRAZAX.

Methods: This was a non-interventional, observational, multi-centre, open-label study involving a total of 131 adult patients aged 18-66 years with confirmed diagnosis of grass-allergy and initiated treatment with GRAZAX between June 2010 and April 2011.

Results: In the pollen season after starting treatment, 56.6% of patients stated that their symptoms were much less/less intense, 86% needed less symptomatic medication for control of their symptoms, and 74.4% manifested to have improved (quite/a lot) as regards their allergic disease since treatment was initiated as compared with previous grass pollen season. The patient satisfaction with GRAZAX was measured using a visual analogue scale (VAS) between 0 (minimum satisfaction) and 100 (maximum satisfaction) comprising five different items: effectiveness, tolerability, cost, convenience and overall satisfaction. The results obtained for each item were [mean (SD)]: 74.7 (18.1), 70.3 (36.1), 39.3 (25.8), 86.2 (12.6), 78.4 (15.8) respectively. The patient's level of satisfaction is highly influenced, especially in terms of assessment of effectiveness, tolerability and convenience, by the information provided by the specialist.

Conclusions: In summary, it can be concluded that improved communication leads to increased patient knowledge, greater patient compliance, and increased patient satisfaction.
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http://dx.doi.org/10.1186/s12948-016-0057-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234098PMC
January 2017

Quantification of the chromosomal radiation damage induced by labelling of leukocytes with [18F]FDG.

Nucl Med Biol 2015 Sep 14;42(9):720-3. Epub 2015 May 14.

Unidad de Radiofarmacia, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.

Introduction: The aim of our work is to quantify the radiation damage in lymphocytes after labelling with [18F]FDG. Comparison with gold standard [99mTc]HMPAO labelling is established. An approach to cellular dosimetry is proposed.

Methods: Mixed leukocytes were separated from fresh venous blood and labelled with [18F]FDG and [99mTc]HMPAO following published guidelines. Cytokinesis-block micronucleus (CBMN) assay was performed for both sets of experiments. Tests for quality control of labelling described in guidelines were followed. Cellular dosimetry was calculated according to MIRD.

Results: MN scored after labelling with 37 MBq of [18F]FDG were 956 ± 172 and 347 ± 26 for [99mTc]HMPAO (p < 0.05). Absorbed dose in cell nucleus was of 0.23 Gy for [18F]FDG and 0.08 Gy for [99mTc]HMPAO labelling. The CBMN assay after labelling with ~290 MBq of [18F]FDG showed radiation induced inhibition of proliferation capacity of the lymphocytes, confirmed by proliferation study.

Conclusions: [18F]FDG labelling of mixed leukocytes causes severe radiation damage to the cell, higher than with [99mTc]HMPAO in accordance with the absorbed dose. Labelling of mixed leukocytes for clinical purpose induces high cytotoxicity reflected in the loss of proliferation capacity in lymphocytes this statement allows us to consider a low oncogenic risk however the association between MN formation in the PBL and subsequent risk of cancer is not well established.

Advances In Knowledge: This is the first work about radiation damage with [18F]FDG labelled cells. We focused on [18F]FDG labelling of leukocytes due to the growing number of research and review articles about this technique.

Implications For Patient Care: The possibility of an increased risk of lymphoid malignancies associated with the administration of radiolabelled lymphocytes is a very controversial subject. Studies on radiation damage on new labelling procedures as the one exposed in this work must be considered.
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http://dx.doi.org/10.1016/j.nucmedbio.2015.05.002DOI Listing
September 2015

Challenges for allergy diagnosis in regions with complex pollen exposures.

Curr Allergy Asthma Rep 2015 Feb;15(2):496

Institute for Applied Molecular Medicine (IMMA) School of Medicine, Universidad CEU San Pablo, 28668, Madrid, Spain,

Over the past few decades, significant scientific progress has influenced clinical allergy practice. The biological standardization of extracts was followed by the massive identification and characterization of new allergens and their progressive use as diagnostic tools including allergen micro arrays that facilitate the simultaneous testing of more than 100 allergen components. Specific diagnosis is the basis of allergy practice and is always aiming to select the best therapeutic or avoidance intervention. As a consequence, redundant or irrelevant information might be adding unnecessary cost and complexity to daily clinical practice. A rational use of the different diagnostic alternatives would allow a significant improvement in the diagnosis and treatment of allergic patients, especially for those residing in complex pollen exposure areas.
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http://dx.doi.org/10.1007/s11882-014-0496-7DOI Listing
February 2015

Does intravenous saline infusion compromise the stability of [123I] meta-iodobenzylguanidine?

Nucl Med Commun 2014 Jun;35(6):683-5

aRadiopharmacy Unit, Santa Lucia's Hospital, Cartagena bRadiopharmacy Unit, Virgen de la Arrixaca Hospital, Murcia, Spain.

To avoid adverse effects during the administration of [(123)I] meta-iodobenzylguanidine (MIBG), infusion of the drug that has been previously diluted is proposed. Stability of [(123)I] MIBG in sodium chloride solutions is studied, looking for incompatibilities in the formulation. Stability was tested on the basis of the percentage of free [(123)I] iodide on solid-phase extraction. No increase in percentages of free [(123)I] iodide was found in diluted and undiluted samples over time (P>0.05). Intravenous saline infusion of [(123)I] MIBG could be a useful tool for controlling the administration rate, minimizing the side effects and lowering the exposure of the staff to ionizing radiation.
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http://dx.doi.org/10.1097/MNM.0000000000000103DOI Listing
June 2014

Diagnosis and treatment of grass pollen-induced allergic rhinitis in specialized current clinical practice in Spain.

Allergy Asthma Proc 2011 Sep-Oct;32(5):384-9

Allergy Unit, Hospital Clinic Barcelona, Barcelona, Spain.

Allergic rhinitis (AR) is the leading cause of consultation at the allergy specialist's office, but detailed, reliable, and validated clinical data on this condition are limited. This study was designed to define the clinical features, diagnostic methods, and therapeutic approaches of patients with AR induced by grass pollen in Spain. Two hundred twelve specialists participated in a multicenter, observational, epidemiologic, questionnaire-based study. Each investigator had to recruit at least two patients consulting for the first time and with a diagnosis of AR induced by grass pollen. Five hundred twenty-four patients (52% men; mean age, 29.3 years) with grass pollen-induced rhinitis (mean disease duration, 8.7 years) were recruited. Just 18.4% of patients reported that their symptom status had improved since the beginning of the condition, 89.4% had moderate-severe rhinitis (Allergic Rhinitis and Its Impact on Asthma classification) and 35.1% had concomitant bronchial asthma. For 52.1% of patients, control of symptoms with previous drug treatment was poor. Most of the patients were polysensitized to other pollens (sensitization to olive tree pollen, 57.1%). Oral antihistamines (97.3%) and nasal corticosteroids (82.3%) were the most frequently prescribed drugs and 43.1% of patients received specific immunotherapy. The clinical profile for the majority of Spanish patients consulting an allergy specialist for AR induced by grass pollen corresponds to a young adult with a lengthy moderate-severe rhinitis, often accompanied by bronchial asthma. Their symptoms progressively worsen and rhinitis is poorly controlled by symptomatic treatment. Oral antihistamines and nasal corticosteroids are the most frequently used therapeutic approaches and less than one-half receive specific immunotherapy.
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http://dx.doi.org/10.2500/aap.2011.32.3480DOI Listing
April 2012