Publications by authors named "Fotis Psarros"

11 Publications

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Deciphering the Genetics of Primary Angioedema with Normal Levels of C1 Inhibitor.

J Clin Med 2020 Oct 23;9(11). Epub 2020 Oct 23.

CeMIA SA, Makriyianni 31, GR-41334 Larissa, Greece.

The genetic alteration underlying the great majority of primary angioedema with normal C1 inhibitor (nl-C1-INH-HAE) cases remains unknown. To search for variants associated with nl-C1-INH-HAE, we genotyped 133 unrelated nl-C1-INH-HAE patients using a custom next-generation sequencing platform targeting 55 genes possibly involved in angioedema pathogenesis. Patients already diagnosed with alterations as well as those with histaminergic acquired angioedema were excluded. A variant pathogenicity curation strategy was followed, including a comparison of the results with those of genotyping 169 patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE), and only filtered-in variants were studied further. Among the examined nl-C1-INH-HAE patients, carriers of neither the p.Ala119Ser nor the p.Met379Lys variant were found, whereas the p.Lys330Glu was detected in four (3%) unrelated probands (one homozygote). In total, 182 different variants were curated, 21 of which represented novel mutations. Although the frequency of variants per gene was comparable between nl-C1-INH-HAE and C1-INH-HAE, variants of the and genes were detected only in nl-C1-INH-HAE patients (six and three, respectively). Twenty-seven filtered variants in 23 different genes were detected in nl-C1-INH-HAE more than once, whereas 69/133 nl-C1-INH-HAE patients had compound heterozygotes of filtered variants located in the same or different genes. Pedigree analysis was performed where feasible. Our results indicate the role that alterations in some genes, like , may play in disease pathogenesis, the complex trait that is possibly underlying in some cases, and the existence of hitherto unrecognized disease endotypes.
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http://dx.doi.org/10.3390/jcm9113402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690775PMC
October 2020

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Authors:
Jean Bousquet Josep M Anto Claus Bachert Tari Haahtela Torsten Zuberbier Wienczyslawa Czarlewski Anna Bedbrook Sinthia Bosnic-Anticevich G Walter Canonica Victoria Cardona Elisio Costa Alvaro A Cruz Marina Erhola Wytske J Fokkens Joao A Fonseca Maddalena Illario Juan-Carlos Ivancevich Marek Jutel Ludger Klimek Piotr Kuna Violeta Kvedariene Ltt Le Désirée E Larenas-Linnemann Daniel Laune Olga M Lourenço Erik Melén Joaquim Mullol Marek Niedoszytko Mikaëla Odemyr Yoshitaka Okamoto Nikos G Papadopoulos Vincenzo Patella Oliver Pfaar Nhân Pham-Thi Christine Rolland Boleslaw Samolinski Aziz Sheikh Mikhail Sofiev Charlotte Suppli Ulrik Ana Todo-Bom Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Samantha Walker Sian Williams Arzu Yorgancioglu Ioana Agache Cezmi A Akdis Rute Almeida Ignacio J Ansotegui Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagaña Eric D Bateman Annabelle Bédard Martin Bedolla-Barajas Sven Becker Kazi S Bennoor Samuel Benveniste Karl C Bergmann Michael Bewick Slawomir Bialek Nils E Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Matteo Bonini Philippe Bonniaud Isabelle Bosse Jacques Bouchard Louis-Philippe Boulet Rodolphe Bourret Koen Boussery Fluvio Braido Vitalis Briedis Andrew Briggs Christopher E Brightling Jan Brozek Guy Brusselle Luisa Brussino Roland Buhl Roland Buonaiuto Moises A Calderon Paulo Camargos Thierry Camuzat Luis Caraballo Ana-Maria Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Niels H Chavannes Ekaterine Chkhartishvili Derek K Chu Cemal Cingi Jaime Correia de Sousa David J Costa Anne-Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejan Dokic Yves Dauvilliers Giulia De Feo Govert De Vries Philippe Devillier Stefania Di Capua Gerard Dray Ruta Dubakiene Stephen R Durham Mark Dykewicz Motohiro Ebisawa Mina Gaga Yehia El-Gamal Enrico Heffler Regina Emuzyte John Farrell Jean-Luc Fauquert Alessandro Fiocchi Antje Fink-Wagner Jean-François Fontaine José M Fuentes Perez Bilun Gemicioğlu Amiran Gamkrelidze Judith Garcia-Aymerich Philippe Gevaert René Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam Yunuen R Huerta Villalobos Marc Humbert Guido Iaccarino Despo Ierodiakonou Tomohisa Iinuma Ewa Jassem Guy Joos Ki-Suck Jung Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Musa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Rostislav Kouznetsov Marek L Kowalski Vicky Kritikos Inger Kull Stefania La Grutta Lisa Leonardini Henrik Ljungberg Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Catarina Lopes-Pereira Claudia C Loureiro Renaud Louis Alpana Mair Bassam Mahboub Michaël Makris Joao Malva Patrick Manning Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Pedro Carreiro-Martins Mika Makela Eve Mathieu-Dupas Marcus Maurer Esteban De Manuel Keenoy Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Yann Micheli Neven Miculinic Florin Mihaltan Branislava Milenkovic Dimitirios I Mitsias Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralph Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leyla Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Björn Nordlund Ettore Novellino Dieudonné Nyembue Robyn O'Hehir Ken Ohta Kimi Okubo Gabrielle L Onorato Valentina Orlando Solange Ouedraogo Julia Palamarchuk Isabella Pali-Schöll Peter Panzner Hae-Sim Park Gianni Passalacqua Jean-Louis Pépin Ema Paulino Ruby Pawankar Jim Phillips Robert Picard Hilary Pinnock Davor Plavec Todor A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Fotis Psarros Benoit Pugin Francesca Puggioni Pablo Quinones-Delgado Filip Raciborski Rojin Rajabian-Söderlund Frederico S Regateiro Sietze Reitsma Daniela Rivero-Yeverino Graham Roberts Nicolas Roche Erendira Rodriguez-Zagal Christine Rolland Regina E Roller-Wirnsberger Nelson Rosario Antonino Romano Menachem Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Joaquin Sastre Glenis K Scadding Sophie Scheire Peter Schmid-Grendelmeier Holger J Schünemann Faradiba Sarquis Serpa Mohamed Shamji Juan-Carlos Sisul Mikhail Sofiev Dirceu Solé David Somekh Talant Sooronbaev Milan Sova François Spertini Otto Spranger Cristiana Stellato Rafael Stelmach Michel Thibaudon Teresa To Mondher Toumi Omar Usmani Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Marilyn Urrutia Pereira Rianne van der Kleij Michiel Van Eerd Olivier Vandenplas Tuula Vasankari Antonio Vaz Carneiro Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Yun Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Osman M Yusuf Heather J Zar Stéphane Zeng Mario E Zernotti Luo Zhang Nan Shan Zhong Mihaela Zidarn

Allergy 2021 01 23;76(1):168-190. Epub 2020 Oct 23.

University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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http://dx.doi.org/10.1111/all.14422DOI Listing
January 2021

A novel deep intronic SERPING1 variant as a cause of hereditary angioedema due to C1-inhibitor deficiency.

Allergol Int 2020 Jul 17;69(3):443-449. Epub 2020 Jan 17.

CeMIA SA, Larissa, Greece; Department of Immunology & Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Larissa, Greece. Electronic address:

Background: In about 5% of patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) no mutation in the SERPING1 gene is detected.

Methods: C1-INH-HAE cases with no mutation in the coding region of SERPING1 after conventional genotyping were examined for defects in the intronic or untranslated regions of the gene. Using a next-generation sequencing (NGS) platform targeting the entire SERPING1, 14 unrelated C1-INH-HAE patients with no detectable mutations in the coding region of the gene were sequenced. Detected variants with a global minor allele frequency lower than the frequency of C1-INH-HAE (0.002%), were submitted to in silico analysis using ten different bioinformatics tools. Pedigree analysis and examination of their pathogenic effect on the RNA level were performed for filtered in variants.

Results: In two unrelated patients, the novel mutation c.-22-155G > T was detected in intron 1 of the SERPING1 gene by the use NGS and confirmed by Sanger sequencing. All bioinformatics tools predicted that the variant causes a deleterious effect on the gene and pedigree analysis showed its co-segregation with the disease. Degradation of the mutated allele was demonstrated by the loss of heterozygosity on the cDNA level. According to the American College of Medical Genetics and Genomics 2015 guidelines the c.-22-155G > T was curated as pathogenic.

Conclusions: For the first time, a deep intronic mutation that was detected by NGS in the SERPING1 gene, was proven pathogenic for C1-INH-HAE. Therefore, advanced DNA sequencing methods should be performed in cases of C1-INH-HAE where standard approaches fail to uncover the genetic alteration.
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http://dx.doi.org/10.1016/j.alit.2019.12.009DOI Listing
July 2020

"Whole" vs. "fragmented" approach to EAACI pollen season definitions: A multicenter study in six Southern European cities.

Allergy 2020 07 11;75(7):1659-1671. Epub 2020 May 11.

Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe.

Objective: To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa.

Methods: As part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility.

Results: The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days).

Conclusion: The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.
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http://dx.doi.org/10.1111/all.14153DOI Listing
July 2020

Efficacy of a Quail Eggs-Based Dietary Supplement for Allergic Rhinitis: Results of a Single-Arm Trial.

J Diet Suppl 2021 25;18(1):17-30. Epub 2019 Nov 25.

3rd Department of Medicine, Medical School, National and Kapodistrian University of Athens, "Sotiria" Athens General Hospital, Athens, Greece.

Previous data suggested the potential treatment effect of a proprietary quail eggs-based blend on allergic rhinitis (AR) symptoms, induced by allergen challenge. We herein aimed to investigate the efficacy and safety of a similar dietary supplement, comprising the bioactive ingredients of quail eggs and the zinc mineral, in the setting of active AR. Adult patients ( = 77), aged 18- 60 years, with mild, intermittent AR were enrolled in this single-arm, open-label trial. Patients' responses were assessed based on peak nasal inspiratory flow (PNIF) measurements at two visits (Day 1/Visit 1 and Day 7/Visit 2) and self-rating of AR-associated symptoms on a Visual Analog Scale (VAS) throughout the entire 7-day study period. PNIF values at 15, 30, 60, 90 and 120 min (Visit 1) following administration of an oral dose of the study product were the primary efficacy endpoint. PNIF values (Visit 1) gradually increased from baseline (pre-treatment), with statistical significance first reached 30 min later ( = 0.002). VAS scores (Visit 1) for all AR symptoms gradually decreased with statistical significance first reached at 15 min (rhinorrhea,  = 0.042; itchy nose,  = 0.001; sneezing  < 0.001), 30 min (nasal congestion,  < 0.001; itchy eyes,  = 0.003) or 60 min (watery eyes,  = 0.04). PNIF improvement and decline of VAS scores were significantly more apparent at Visit one vs. Visit 2. Treatment-emergent adverse events were limited to cough and muscle strain (one patient each). Our results support the efficacy, rapid mode of action and tolerability of the investigated product for symptomatic treatment of mild intermittent AR.
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http://dx.doi.org/10.1080/19390211.2019.1694121DOI Listing
November 2019

Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study.

J Allergy Clin Immunol 2019 07 3;144(1):135-143.e6. Epub 2019 Apr 3.

MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France; University Hospital, Montpellier, France; INSERM U 1168, VIMA: Ageing and chronic diseases Epidemiological and Public Health Approaches, Villejuif, Université Versailles St-Quentin-en-Yvelines, Montigny le Bretonneux, and Euforea, Brussels, Belgium. Electronic address:

Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control.

Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR.

Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-antihistamines were studied.

Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-antihistamines were found.

Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.
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http://dx.doi.org/10.1016/j.jaci.2019.01.053DOI Listing
July 2019

Targeted next-generation sequencing for the molecular diagnosis of hereditary angioedema due to C1-inhibitor deficiency.

Gene 2018 Aug 16;667:76-82. Epub 2018 May 16.

CeMIA SA, 31 Makrigianni street, GR-41334 Larissa, Greece; Department of Immunology & Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, 3 Panepistimiou street, Biopolis, GR-41500 Larissa, Greece. Electronic address:

SERPING1 genotyping of subjects suspicious for hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) is important for clinical practice as well as for research reasons. Conventional approaches towards the detection of C1-INH-HAE-associated SERPING1 variants are cumbersome and time-demanding with many pitfalls. To take advantage of the benefits of next-generation sequencing (NGS) technology, we developed and validated a custom NGS platform that, by targeting the entire SERPING1 gene, facilitates genetic testing of C1-INH-HAE patients in clinical practice. In total, 135 different C1-INH-HAE-associated SERPING1 variants, out of the approximately 450 reported, along with 115 negative controls and 95 randomly selected DNA samples from affected family members of C1-INH-HAE index patients, were included in the forward and reverse validation processes of this platform. Our platform's performance, i.e. analytical sensitivity of 98.96%, a false negative rate of 1.05%, analytical specificity 100%, a false positive rate equal to zero, accuracy of 99.35%, and repeatability of 100% recommends its implementation as a first line approach for the genetic testing of C1-INH-HAE patients or as a confirmatory method. A noteworthy advantage of our platform is the concomitant detection of single nucleotide variants and copy number variations throughout the whole length of the SERPING1 gene, moreover providing information about the size and the localization of the latter. During our study, 15 novel C1-INH-HAE-related SERPING1 variants were detected.
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http://dx.doi.org/10.1016/j.gene.2018.05.029DOI Listing
August 2018

Genetic Determinants of C1 Inhibitor Deficiency Angioedema Age of Onset.

Int Arch Allergy Immunol 2017 9;174(3-4):200-204. Epub 2017 Nov 9.

Department of Immunology and Histocompatibility, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Background: In view of the large heterogeneity in the clinical presentation of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), great efforts are being made towards detecting measurable biological determinants of disease severity that can help to improve the management of the disease. Considering the central role that plasma kallikrein plays in bradykinin production, we investigated the contribution of the functional polymorphism KLKB1-428G/A to the disease phenotype.

Methods: We studied 249 C1-INH-HAE patients from 114 European families, and we explored possible associations of C1-INH-HAE clinical features with carriage of KLKB1-428G/A, combined or not with that of the functional F12-46C/T polymorphism.

Results: Carriers of the G allele of the KLKB1-428G/A polymorphism exhibited a significantly delayed disease onset (i.e., by 4.1 years [p < 0.001], depending on the zygocity status), while carriers of both the KLKB1-428G/A and the F12-46C/T polymorphism displayed an 8.8-year delay in disease onset (p < 0.001) and a 64% lower probability of needing long-term prophylactic treatment (p = 0.019).

Conclusions: These findings support our initial hypothesis that functional alterations in genes of proteins involved in bradykinin metabolism and function affect the clinical phenotype and possibly contribute to the pathogenesis of C1-INH-HAE. Given that an earlier onset of symptoms is inversely correlated with the subsequent course of the disease and, eventually, the need for long-term prophylaxis, these polymorphisms may be helpful prognostic biomarkers of disease severity.
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http://dx.doi.org/10.1159/000481987DOI Listing
December 2017

Hereditary angioedema in Greece: the first results of the greek hereditary angioedema registry.

Int Arch Allergy Immunol 2014 23;164(4):326-32. Epub 2014 Sep 23.

Allergy Department, Naval Hospital of Athens, Athens, Greece.

Background: No published data presently exist concerning hereditary angioedema (HAE) in Greece. The aim of this study was to present the results from patients recorded by the Greek Hereditary Angioedema Registry over the last 3 years (July 2010 to June 2013).

Methods: A systematic recording of HAE cases was undertaken following a physician awareness campaign and confirmation of diagnosis. A questionnaire was also used for the assessment of key parameters of the patients' disease-specific quality of life.

Results: One hundred and sixteen patients from 41 non-related families were recorded. There were 33 (80.5%) families with type I HAE, 7 (17%) with type II HAE and 1 (2.5%) with non-C1 inhibitor (C1-INH), non-FXII HAE. Two further non-C1-INH, non-FXII HAE sporadic cases were recorded. An investigation of non-symptomatic family members revealed another 6 asymptomatic individuals with C1-INH deficiency. The average delay in diagnosis was 16.5 years and the incidence of death in the families of patients was 1 for every 2 families. The use of newer therapeutic agents seems to fall significantly short of the existing needs. HAE was found to affect the quality of life slightly in 14%, greatly in 63% and significantly in 23% of the patients.

Conclusion: Until recently, there has been a significant degree of underdiagnosis of HAE in Greece. Very low compliance with the provisions of the applicable international guidelines and consensus positions, with adverse consequences on the patients' quality of life, was also observed. The centralized model we used to uncover the patients could be effective in other countries presenting with comparable disease characteristics.
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http://dx.doi.org/10.1159/000366276DOI Listing
December 2014

Hereditary angioedema: molecular and clinical differences among European populations.

J Allergy Clin Immunol 2015 Feb 23;135(2):570-3. Epub 2014 Sep 23.

Department of Immunology and Histocompatibility, University of Thessaly, School of Health Sciences, Faculty of Medicine, Larissa, Greece. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2014.08.007DOI Listing
February 2015