Publications by authors named "Panayiotis K Yiallouros"

29 Publications

  • Page 1 of 1

The MEDEA childhood asthma study design for mitigation of desert dust health effects: implementation of novel methods for assessment of air pollution exposure and lessons learned.

BMC Pediatr 2021 Jan 6;21(1):13. Epub 2021 Jan 6.

Respiratory Physiology Laboratory, Medical School, University of Cyprus, Nicosia, Cyprus.

Background: Desert dust events in Mediterranean countries, originating mostly from the Sahara and Arabian deserts, have been linked to climate change and are associated with significant increase in mortality and hospital admissions from respiratory causes. The MEDEA clinical intervention study in children with asthma is funded by EU LIFE+ program to evaluate the efficacy of recommendations aiming to reduce exposure to desert dust and related health effects.

Methods: This paper describes the design, methods, and challenges of the MEDEA childhood asthma study, which is performed in two highly exposed regions of the Eastern Mediterranean: Cyprus and Greece-Crete. Eligible children are recruited using screening surveys performed at primary schools and are randomized to three parallel intervention groups: a) no intervention for desert dust events, b) interventions for outdoor exposure reduction, and c) interventions for both outdoor and indoor exposure reduction. At baseline visits, participants are enrolled on MEDena® Health-Hub, which communicates, alerts and provides exposure reduction recommendations in anticipation of desert dust events. MEDEA employs novel environmental epidemiology and telemedicine methods including wearable GPS, actigraphy, health parameters sensors as well as indoor and outdoor air pollution samplers to assess study participants' compliance to recommendations, air pollutant exposures in homes and schools, and disease related clinical outcomes.

Discussion: The MEDEA study evaluates, for the first time, interventions aiming to reduce desert dust exposure and implement novel telemedicine methods in assessing clinical outcomes and personal compliance to recommendations. In Cyprus and Crete, during the first study period (February-May 2019), a total of 91 children participated in the trial while for the second study period (February-May 2020), another 120 children completed data collection. Recruitment for the third study period (February-May 2021) is underway. In this paper, we also present the unique challenges faced during the implementation of novel methodologies to reduce air pollution exposure in children. Engagement of families of asthmatic children, schools and local communities, is critical. Successful study completion will provide the knowledge for informed decision-making both at national and international level for mitigating the health effects of desert dust events in South-Eastern Europe.

Trial Registration: ClinicalTrials.gov: NCT03503812 , April 20, 2018.
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http://dx.doi.org/10.1186/s12887-020-02472-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786906PMC
January 2021

Nasal nitric oxide measurement for primary ciliary dyskinesia diagnosis: The impact of underlying genetic defects on diagnostic accuracy.

Pediatr Investig 2019 Dec 21;3(4):214-216. Epub 2019 Dec 21.

Respiratory Physiology Laboratory Medical School University of Cyprus Nicosia Cyprus.

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http://dx.doi.org/10.1002/ped4.12171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331326PMC
December 2019

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

Registries and collaborative studies for primary ciliary dyskinesia in Europe.

ERJ Open Res 2020 Apr 26;6(2). Epub 2020 May 26.

Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Primary ciliary dyskinesia (PCD) is a rare inherited disease characterised by malfunctioning cilia leading to a heterogeneous clinical phenotype with many organ systems affected. There is a lack of data on clinical presentation, prognosis and effectiveness of treatments, making it mandatory to improve the scientific evidence base. This article reviews the data resources that are available in Europe for clinical and epidemiological research in PCD, namely established national PCD registries and national cohort studies, plus two large collaborative efforts (the international PCD (iPCD) Cohort and the International PCD Registry), and discusses their strengths, limitations and perspectives. Denmark, Cyprus, Norway and Switzerland have national population-based registries, while England and France conduct multicentre cohort studies. Based on the data contained in these registries, the prevalence of diagnosed PCD is 3-7 per 100 000 in children and 0.2-6 per 100 000 in adults. All registries, together with other studies from Europe and beyond, contribute to the iPCD Cohort, a collaborative study including data from over 4000 PCD patients, and to the International PCD Registry, which is part of the ERN (European Reference Network)-LUNG network. This rich resource of readily available, standardised and contemporaneous data will allow obtaining fast answers to emerging clinical and research questions in PCD.
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http://dx.doi.org/10.1183/23120541.00005-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248350PMC
April 2020

Health related quality of life in adult primary Ciliary dyskinesia patients in Cyprus: development and validation of the Greek version of the QOL-PCD questionnaire.

Health Qual Life Outcomes 2020 Apr 22;18(1):105. Epub 2020 Apr 22.

Pediatric Pulmonology Unit, Hospital 'Archbishop Makarios III', Nicosia, Cyprus.

Background: The QOL-PCD questionnaire is a recently developed Health Related Quality of Life (HRQoL) instrument for Primary Ciliary Dyskinesia. The aim of this study was to translate the adult QOL-PCD questionnaire into Greek language and to conduct psychometric validation to assess its performance.

Methods: Forward translations to Greek and backward translation to English were performed, followed by cognitive interviews in 12 adult PCD patients. The finalized translated version was administered to a consecutive sample of 31 adult, Greek speaking PCD patients in Cyprus for psychometric validation, which included assessment of internal consistency, test-retest reliability, construct and convergent validity. Internal consistency was assessed by Cronbach's alpha test in terms of the overall and sub-scales. Test-retest reliability was assessed by repeat administration of the questionnaire within 2 weeks and calculation of the intra-class correlation (ICC). Construct validity was assessed by comparing different groups of patients based on a-priori hypotheses and convergent validity was evaluated by examining associations between the QOL-PCD and SF-36 questionnaires.

Results: Moderate to good internal consistency was observed (Cronbach's α: 0.46-0.88 across sub-scales) and test-retest reliability assessment demonstrated good repeatability for most scales (ICC: 0.67-0.91 across subscales). Patients of female gender, older age and lower lung function exhibited lower QOL-PCD scores in general, while high correlations for most QOL-PCD scales with corresponding SF-36 scales were observed, in particular for physical functioning (r = 0.78, p < 0.05).

Conclusion: The adult version of QoL-PCD questionnaire has been translated according to international guidelines resulting to a cross-culturally validated Greek version which exhibited moderate to good metric properties in terms of internal consistency, stability, known-group and convergent validity.
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http://dx.doi.org/10.1186/s12955-020-01360-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178983PMC
April 2020

Prevalence and course of disease after lung resection in primary ciliary dyskinesia: a cohort & nested case-control study.

Respir Res 2019 Sep 18;20(1):212. Epub 2019 Sep 18.

Respiratory Physiology Laboratory, Medical School, University of Cyprus, Nicosia, Cyprus.

Background: Lung resection is a controversial and understudied therapeutic modality in Primary Ciliary Dyskinesia (PCD). We assessed the prevalence of lung resection in PCD across countries and compared disease course in lobectomised and non-lobectomised patients.

Methods: In the international iPCD cohort, we identified lobectomised and non-lobectomised age and sex-matched PCD patients and compared their characteristics, lung function and BMI cross-sectionally and longitudinally.

Results: Among 2896 patients in the iPCD cohort, 163 from 20 centers (15 countries) underwent lung resection (5.6%). Among adult patients, prevalence of lung resection was 8.9%, demonstrating wide variation among countries. Compared to the rest of the iPCD cohort, lobectomised patients were more often females, older at diagnosis, and more often had situs solitus. In about half of the cases (45.6%) lung resection was performed before presentation to specialized PCD centers for diagnostic work-up. Compared to controls (n = 197), lobectomised patients had lower FVC z-scores (- 2.41 vs - 1.35, p = 0.0001) and FEV1 z-scores (- 2.79 vs - 1.99, p = 0.003) at their first post-lung resection assessment. After surgery, lung function continued to decline at a faster rate in lobectomised patients compared to controls (FVC z-score slope: - 0.037/year Vs - 0.009/year, p = 0.047 and FEV1 z-score slope: - 0.052/year Vs - 0.033/year, p = 0.235), although difference did not reach statistical significance for FEV1. Within cases, females and patients with multiple lobe resections had lower lung function.

Conclusions: Prevalence of lung resection in PCD varies widely between countries, is often performed before PCD diagnosis and overall is more frequent in patients with delayed diagnosis. After lung resection, compared to controls most lobectomised patients have poorer and continuing decline of lung function despite lung resection. Further studies benefiting from prospective data collection are needed to confirm these findings.
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http://dx.doi.org/10.1186/s12931-019-1183-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751891PMC
September 2019

Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases.

Authors:
J Jean Bousquet Holger J Schünemann Alkis Togias Marina Erhola Peter W Hellings Torsten Zuberbier Ioana Agache Ignacio J Ansotegui Josep M Anto Claus Bachert Sven Becker Martin Bedolla-Barajas Michael Bewick Sinthia Bosnic-Anticevich Isabelle Bosse Louis P Boulet Jean Marc Bourrez Guy Brusselle Niels Chavannes Elisio Costa Alvaro A Cruz Wienczyslawa Czarlewski Wytske J Fokkens Joao A Fonseca Mina Gaga Tari Haahtela Maddalena Illario Ludger Klimek Piotr Kuna Violeta Kvedariene L T T Le Desiree Larenas-Linnemann Daniel Laune Olga M Lourenço Enrica Menditto Joaquin Mullol Yashitaka Okamoto Nikos Papadopoulos Nhân Pham-Thi Robert Picard Hilary Pinnock Nicolas Roche Regina E Roller-Wirnsberger Christine Rolland Boleslaw Samolinski Aziz Sheikh Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Tuula Vasankari Maria-Teresa Ventura Samantha Walker Sian Williams Cezmi A Akdis Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagana Eric Bateman Anna Bedbrook K S Bennoor Samuel Benveniste Karl C Bergmann Slawomir Bialek Nils Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Mateo Bonini Philippe Bonniaud Jacques Bouchard Vitalis Briedis Christofer E Brightling Jan Brozek Roland Buhl Roland Buonaiuto Giorgo W Canonica Victoria Cardona Ana M Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Eka Chkhartishvili Derek K Chu Cemal Cingi Elaine Colgan Jaime Correia de Sousa Anne Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejand Dokic Yves Dauvilliers Antoni Dedeu Giulia De Feo Philippe Devillier Stefania Di Capua Marc Dykewickz Ruta Dubakiene Motohiro Ebisawa Yaya El-Gamal Esben Eller Regina Emuzyte John Farrell Antjie Fink-Wagner Alessandro Fiocchi Jean F Fontaine Bilun Gemicioğlu Peter Schmid-Grendelmeir Amiran Gamkrelidze Judith Garcia-Aymerich Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam John O'B Hourihane Marc Humbert Guido Iaccarino Despo Ierodiakonou Maddalena Illario Juan C Ivancevich Guy Joos Ki-Suck Jung Marek Jutel Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Mussa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Marek L Kowalski Vicky Kritikos Inger Kull Lisa Leonardini Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Claudia C Loureiro Renaud Louis Alpana Mair Gert Marien Bassam Mahboub Joao Malva Patrick Manning Esteban De Manuel Keenoy Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Eve Mathieu-Dupas Poalo M Matricardi Eric Melén Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Neven Miculinic Florin Mihaltan Branislava Milenkovic Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralf Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leila Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Enrico Novellino Dieudonné Nyembue Robin O'Hehir Ken Ohta Kimi Okubo Gabrielle Onorato Solange Ouedraogo Isabella Pali-Schöll Susanna Palkonen Peter Panzner Hae-Sim Park Jean-Louis Pépin Ana-Maria Pereira Oliver Pfaar Ema Paulino Jim Phillips Robert Picard Davor Plavec Ted A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Benoit Pugin Filip Raciborski Rojin Rajabian-Söderlund Sietze Reitsma Xavier Rodo Antonino Romano Nelson Rosario Menahenm Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Juan-Carlos Sisul Dirceu Solé David Somekh Talant Sooronbaev Milan Sova Otto Spranger Cristina Stellato Rafael Stelmach Charlotte Suppli Ulrik Michel Thibaudon Teresa To Ana Todo-Bom Peter V Tomazic Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Rianne van der Kleij Olivier Vandenplas Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Y Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heahter J Zar Stéphane Zeng Mario Zernotti Luo Zhang Nan S Zhong Mihaela Zidarn

Clin Transl Allergy 2019 9;9:44. Epub 2019 Sep 9.

260University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

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.
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http://dx.doi.org/10.1186/s13601-019-0279-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734297PMC
September 2019

Wide phenotypic variability in RSPH9-associated primary ciliary dyskinesia: review of a case-series from Cyprus.

J Thorac Dis 2019 May;11(5):2067-2075

Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.

Background: Primary ciliary dyskinesia (PCD) is an inherited ciliary motility disorder caused by mutations in at least 40 genes. gene mutations encoding aberrant radial spoke head proteins have been linked with PCD. The clinical spectrum extent of gene mutations remains to date largely unknown. We aimed to describe the diagnostic and clinical phenotype in a case-series of RSPH9-associated PCD.

Methods: We performed whole exome sequencing in suspect patients from Cyprus who on repeated cilia biopsies demonstrated loss of the central pair apparatus on Transmission Electron Microscopy (TEM) and rotary beating patterns on High Speed Video Microscopy (HSVM), compatible to findings described previously in PCD patients bearing pathogenic mutations. In cases confirmed by genetic testing, we reviewed diagnostic, demographic and clinical data, as well as anthropometric and spirometric measurements.

Results: We diagnosed 7 individuals (5 females) homozygous for the novel splice site mutation c.670+2T>C in intron 4, who originated from two families. Despite bearing the same genetic variant, patients presented a highly variable age (median 47.9 years; range, 6.6 to 51.4 years) and with a diverse clinical picture, all reporting a history of chronic or recurrent wet cough (100%), and at varying frequencies neonatal respiratory distress (43%), chronic rhinosinusitis (71%), and wheezing (43%). Complications such as bronchiectasis (71%), history of pneumonia(s) (57%) and surgical interventions (43%) clustered in some patients displaying typical PCD, but not in others with milder phenotypes. BMI-z scores (median: 0.53; range, -0.69 to 1.52), FEV1-z scores (median: -0.37; range: -1.79 to 0.22) and FVC z-scores (median: -0.80; range: -2.01 to 0.36) were on average within the normal range, although slightly reduced.

Conclusions: In conclusion, RSPH9-associated PCD disease demonstrates wide phenotypic variability. In some cases, mild clinical presentation is difficult to justify diagnostic work-up, highlighting the importance of wider adoption of genetic diagnostics. Larger studies are needed to assess variability of clinical spectrum associated to alterations of PCD genes.
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http://dx.doi.org/10.21037/jtd.2019.04.71DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588774PMC
May 2019

Cost-effectiveness analysis of three algorithms for diagnosing primary ciliary dyskinesia: a simulation study.

Orphanet J Rare Dis 2019 06 13;14(1):142. Epub 2019 Jun 13.

Respiratory Physiology Laboratory, Medical School, University of Cyprus, Nicosia, Cyprus.

Background: Primary Ciliary Dyskinesia (PCD) diagnosis relies on a combination of tests which may include (a) nasal Nitric Oxide (nNO), (b) High Speed Video Microscopy (HSVM) and (c) Transmission Electron Microscopy (TEM). There is variability in the availability of these tests and lack of universal agreement whether diagnostic tests should be performed in sequence or in parallel. We assessed three combinations of tests for PCD diagnosis and estimated net sensitivity and specificity as well as cost-effectiveness (CE) and incremental cost-effectiveness (ICE) ratios.

Methods And Results: A hypothetical initial population of 1000 referrals (expected 320 PCD patients) was followed through a probabilistic decision analysis model which was created to assess the CE of three diagnostic algorithms (a) nNO + TEM in sequence, (b) nNO + HSVM in sequence and (c) nNO/HSVM in parallel followed, in cases with conflicting results, by confirmatory TEM (nNO/HSVM+TEM). Number of PCD patients identified, CE and ICE ratios were calculated using Monte Carlo simulations. Out of 320 expected PCD patients, 313 were identified by nNO/HSVM+TEM, 274 with nNO + HSVM and 198 with nNO + TEM. The nNO/HSVM+TEM had the highest mean annual cost (€209 K) followed by nNO + TEM (€150 K) and nNO + HSVM (€136 K). The nNO + HSVM algorithm dominated the nNO + TEM algorithm (less costly and more effective). The ICE ratio for nNO/HSVM+TEM was €2.1 K per additional PCD patient identified.

Conclusions: The diagnostic algorithm (nNO/HSVM+TEM) with parallel testing outperforms algorithms with tests in sequence. These findings, can inform the dialogue on the development of evidence-based guidelines for PCD diagnostic testing. Future research in understudied aspects of the disease, such as PCD-related quality of life and PCD-associated costs, is needed to help the better implementation of these guidelines across various healthcare systems.
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http://dx.doi.org/10.1186/s13023-019-1116-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567920PMC
June 2019

ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Authors:
Sinthia Bosnic-Anticevich Elisio Costa Enrica Menditto Olga Lourenço Ettore Novellino Slawomir Bialek Vitalis Briedis Roland Buonaiuto Henry Chrystyn Biljana Cvetkovski Stefania Di Capua Vicky Kritikos Alpana Mair Valentina Orlando Ema Paulino Johanna Salimäki Rojin Söderlund Rachel Tan Dennis M Williams Piotr Wroczynski Ioana Agache Ignacio J Ansotegui Josep M Anto Anna Bedbrook Claus Bachert Mike Bewick Carsten Bindslev-Jensen Jan L Brozek Giorgio Walter Canonica Victoria Cardona Warner Carr Thomas B Casale Niels H Chavannes Jaime Correia de Sousa Alvaro A Cruz Wienczyslawa Czarlewski Giuseppe De Carlo Pascal Demoly Philippe Devillier Mark S Dykewicz Mina Gaga Yehia El-Gamal João Fonseca Wytske J Fokkens Maria Antonieta Guzmán Tari Haahtela Peter W Hellings Maddalena Illario Juan Carlos Ivancevich Jocelyne Just Igor Kaidashev Musa Khaitov Nikolai Khaltaev Thomas Keil Ludger Klimek Marek L Kowalski Piotr Kuna Violeta Kvedariene Désirée E Larenas-Linnemann Daniel Laune Lan T T Le Karin C Lodrup Carlsen Bassam Mahboub Dieter Maier Joao Malva Patrick J Manning Mário Morais-Almeida Ralph Mösges Joaquim Mullol Lars Münter Ruth Murray Robert Naclerio Leyla Namazova-Baranova Kristof Nekam Tshipukane Dieudonné Nyembue Kimi Okubo Robyn E O'Hehir Ken Ohta Yoshitaka Okamoto Gabrielle L Onorato Susanna Palkonen Petr Panzner Nikolaos G Papadopoulos Hae-Sim Park Ruby Pawankar Oliver Pfaar Jim Phillips Davor Plavec Todor A Popov Paul C Potter Emmanuel P Prokopakis Regina E Roller-Wirnsberger Menachem Rottem Dermot Ryan Bolesław Samolinski Mario Sanchez-Borges Holger J Schunemann Aziz Sheikh Juan Carlos Sisul David Somekh Cristiana Stellato Teresa To Ana Maria Todo-Bom Peter Valentin Tomazic Sanna Toppila-Salmi Antonio Valero Arunas Valiulis Errka Valovirta Maria Teresa Ventura Martin Wagenmann Dana Wallace Susan Waserman Magnus Wickman Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heather J Zar Mario E Zernotti Luo Zhang Mihaela Zidarn Torsten Zuberbier Jean Bousquet

Allergy 2019 07 30;74(7):1219-1236. Epub 2019 Apr 30.

MACVIA-France, Fondation Partenariale FMC VIA-LR, Montpellier, France.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.
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http://dx.doi.org/10.1111/all.13701DOI Listing
July 2019

Maternal socioeconomic factors and the risk of premature birth and low birth weight in Cyprus: a case-control study.

Reprod Health 2018 Sep 19;15(1):157. Epub 2018 Sep 19.

Faculty of Economics and Management, Open University of Cyprus, Nicosia, Cyprus.

Background: Prematurity and low birth weight are significant predictors of perinatal morbidity and mortality and are influenced by the overall health and socioeconomic status of the pregnant mother. Although Cyprus is characterized by the highest prematurity rate in Europe (13.1% in 2014), the relationship between maternal health and socioeconomic characteristics with prematurity and low birth weight has never been investigated. We aimed to investigate the association of maternal demographic, clinical and socioeconomic characteristics with premature delivery and low neonatal birth weight in Cyprus.

Methods: In a case-control design, questionnaire data were collected from 348 women who gave birth prematurely (cases) and 349 women who gave birth at term (controls). Information was obtained on gestation duration and birth weight as well as maternal demographic, socioeconomic and clinical profiles, including parameters such as smoking, body mass index, alcohol consumption, presence of gestational diabetes and mental health factors.

Results: Premature delivery was associated with greater maternal age (OR: 1.12, 95% CI: 1.06-1.18), absence of gestational diabetes (OR: 0.53, 95% CI: 0.30-0.97), long working hours (OR: 3.77, 95% CI: 2.08-6.84) and emotional stress (OR: 8.5, 95% CI: 3.03-23.89). Within the cases group, emotional stress was also associated with lower birth-weight (β: -323.68 (95% CI: -570.36, - 77.00).

Conclusions: The findings of this study demonstrate the positive association of maternal psychological factors, working conditions as well as maternal age with prematurity and low birth weight in Cyprus. Additional, prospective, studies are needed in the country to further investigate these associations and inform public health intervention measures.
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http://dx.doi.org/10.1186/s12978-018-0603-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146509PMC
September 2018

The effect of l-Arginine on Ciliary Beat Frequency in PCD patients, non-PCD respiratory patients and healthy controls.

Pulm Pharmacol Ther 2018 02 19;48:15-21. Epub 2017 Oct 19.

Medical School, University of Cyprus, Nicosia, Cyprus; Hospital 'Archbishop Makarios III', Nicosia, Cyprus. Electronic address:

Objectives: Few studies have examined the potentially therapeutic effect of increasing the production of endogenous nitric oxide (NO) in Primary Ciliary Dyskinesia (PCD) and other chronic respiratory conditions. Nasal NO is low in PCD and has been found to correlate with compromised Ciliary Beat Frequency (CBF). In this study we assessed the effect of increasing l-Arginine, as the substrate of NO synthases, on CBF in biopsies of human respiratory ciliated epithelium.

Methodology: A total of 28 suspect cases with chronic respiratory manifestations referred for PCD diagnostic testing and 8 healthy controls underwent nasal brushing. Obtained epithelial cells were divided between three culture medium 199 solutions, containing different levels of l-Arginine (0.33 mM as baseline, 1 mM and 10 Mm as increased levels). CBF measurements were obtained at 37 °C and 25 °C at 1, 3 and 24 h after sample acquisition.

Results: Among a total of 36 recruited subjects, 8 had PCD confirmed (PCD n = 8), 20 had PCD excluded (non-PCD n = 20) and 8 were healthy controls (Healthy Controls = 8). Among PCD subjects, ciliary motility was characterized by rotational (n = 5) or dyskinetic (n = 3) beating. At 37 °C, compared to baseline, higher levels of l-Arginine resulted in up to 9% CBF increase at 1 h (p = 0.007), up to 9% CBF increase at 3 h (p < 0.001) and up to 12% CBF increase at 24 h (p = 0.002). Similar although smaller scale increases were recorded at 25 °C. The effect of l-Arginine was time dependent (interaction p = 0.002) and was similar in PCD patients, non-PCD chronic respiratory patients and healthy controls (interaction p = 0.800).

Conclusions: l-Arginine increases CBF and merits to be evaluated as a potential stimulator of mucociliary clearance in chronic respiratory conditions and congenital ciliary disorders with residual motility. Larger human studies are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.pupt.2017.10.010DOI Listing
February 2018

Prevalence of primary ciliary dyskinesia in consecutive referrals of suspect cases and the transmission electron microscopy detection rate: a systematic review and meta-analysis.

Pediatr Res 2017 03 9;81(3):398-405. Epub 2016 Dec 9.

Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.

Diagnostic testing for primary ciliary dyskinesia (PCD) usually includes transmission electron microscopy (TEM), nasal nitric oxide, high-speed video microscopy, and genetics. Diagnostic performance of each test should be assessed toward the development of PCD diagnostic algorithms. We systematically reviewed the literature and quantified PCD prevalence among referrals and TEM detection rate in confirmed PCD patients. Major electronic databases were searched until December 2015 using appropriate terms. Included studies described cohorts of consecutive PCD referrals in which PCD was confirmed by at least TEM and one additional test, in order to compare the index test performance with other test(s). Meta-analyses of pooled PCD prevalence and TEM detection rate across studies were performed. PCD prevalence among referrals was 32% (95% CI: 25-39%, I = 92%). TEM detection rate among PCD patients was 83% (95% CI: 75-90%, I = 90%). Exclusion of studies reporting isolated inner dynein arm defects as PCD, reduced TEM detection rate and explained an important fraction of observed heterogeneity (74%, 95% CI: 66-83%, I = 66%). Approximately, one third of referrals, are diagnosed with PCD. Among PCD patients, a significant percentage, at least as high as 26%, is missed by TEM, a limitation that should be accounted toward the development of an efficacious PCD diagnostic algorithm.
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http://dx.doi.org/10.1038/pr.2016.263DOI Listing
March 2017

Shared genetic variants between serum levels of high-density lipoprotein cholesterol and wheezing in a cohort of children from Cyprus.

Ital J Pediatr 2016 Jul 13;42(1):67. Epub 2016 Jul 13.

Lebanese American University, School of Medicine, Beirut, Lebanon.

Background: In a cohort of children in Cyprus, we recently reported low levels of high density lipoprotein cholesterol (HDL-C) to be associated with asthma. We examined whether genetic polymorphisms that were previously linked individually to asthma, obesity, or HDL-C are associated with both asthma and HDL-C levels in the Cyprus cohort.

Methods: We assessed genotypes frequencies in current-wheezers (n = 190) and non-asthmatic controls (n = 671) and HDL-C levels across several genotypes. Binary logistic regression models were used to assess the effect of genotypes on wheezing risk and examined whether this effect is carried out through changes of HDL-C.

Results: Of the 16 polymorphisms tested, two polymorphisms TNFa rs3093664 and PRKCA rs9892651 presented significant differences in genotype distribution among current-wheezers and controls. Higher HDL-C levels were noted in carriers of genotype GG of polymorphism TNFa rs3093664 that was protective for wheezing Vs AG and AA genotypes (65.3 Vs 51.8 and 53.3 mg/dl, p-value < 0.001 and p-value for trend = 0.028). In polymorphism PRKCA rs9892651, HDL-C levels were lower in carriers of CC and TC genotypes that were more frequent in current-wheezers Vs TT genotype (52.2 and 52.7 Vs 55.2 mg/dl, p-value = 0.042 and p-value for trend = 0.02). The association of TNFa rs3093664 with wheezing is partly mediated by its effect on HDL-C whereas association of PRKCA rs9892651 with wheezing appeared to be independent of HDL-C.

Conclusions: We found evidence that two SNPs located in different genetic loci, are associated with both wheezing and HDL-C levels, although more studies in other populations are needed to confirm our results.
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http://dx.doi.org/10.1186/s13052-016-0276-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944514PMC
July 2016

Diagnostic accuracy of nasal nitric oxide for establishing diagnosis of primary ciliary dyskinesia: a meta-analysis.

BMC Pulm Med 2015 Dec 3;15:153. Epub 2015 Dec 3.

Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, 95 Irenes Street, 3041, Limassol, Cyprus.

Background: To date, diagnosis of Primary Ciliary Dyskinesia (PCD) remains difficult and challenging. We systematically evaluated the diagnostic performance of nasal Nitric Oxide (nNO) measurement for the detection of PCD, using either velum-closure (VC) or non-velum-closure (non-VC) techniques.

Methods: All major electronic databases were searched from inception until March 2015 using appropriate terms. The sensitivity and specificity of nNO measurement was calculated in PCD patients diagnosed by transmission electron microscopy, high speed video-microscopy or genetic testing. Summary receiver operating characteristic (HSROC) curves were drawn using the parameters of the fitted models.

Results: Twelve studies provided data for 13 different populations, including nine case-control (n = 793) and four prospective cohorts (n = 392). The overall sensitivity of nNO measured by VC techniques was 0.95 (95 % CI 0.91-0.97), while specificity was 0.94 (95 % CI 0.88-0.97). The positive likelihood ratio (LR+) of the test was 15.8 (95 % CI 8.1-30.6), whereas the negative likelihood ratio (LR-) was 0.06 (95 % CI 0.04-0.09). For non-VC techniques, the overall sensitivity of nNO measurement was 0.93 (95 % CI 0.89-0.96) whereas specificity was 0.95 (95 % CI 0.82-0.99). The LR+ of the test was 18.5 (95 % CI 4.6-73.8) whereas the LR- was 0.07 (95 % CI 0.04-0.12).

Conclusions: Diagnostic accuracy of nNO measurement both with VC and non-VC maneuvers is high and can be effectively employed in the clinical setting to detect PCD even in young children, thus potentiating early diagnosis. Measurement of nNO merits to be part of a revised diagnostic algorithm with the most efficacious combination of tests to achieve PCD diagnosis.
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http://dx.doi.org/10.1186/s12890-015-0147-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669667PMC
December 2015

Association of vitamin D receptor gene polymorphisms and vitamin D levels with asthma and atopy in Cypriot adolescents: a case-control study.

Multidiscip Respir Med 2015 4;10(1):26. Epub 2015 Sep 4.

Cyprus International Institute for Environmental & Public Health in association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus ; Department of Pediatrics, Hospital "Archbishop Makarios III", Nicosia, Cyprus ; 95 Irenes Street, 3041 Limassol, Cyprus.

Background: Polymorphisms in the vitamin D receptor (VDR) gene have been studied in immune-related disorders either as independent contributors or in combination with vitamin D concentration. Vitamin D and VDR have been independently linked to asthma susceptibility. We investigated whether VDR variants were associated independently or in relation to vitamin D levels with asthma in Cypriot adolescents.

Methods: We studied 190 current wheezers, 69 of which were categorized as active asthmatics and 671 healthy controls. We determined three VDR genotypes (BsmI, TaqI, ApaI) and measured serum 25(OH)D levels. Logistic regression and stratified analyses by the presence of hypovitaminosis D (≤20 ng/ml) were used to evaluate the association of the VDR variants with asthma.

Results: The distribution of TaqI genotypes was significantly different between controls and current wheezers (p = 0.030) or active asthmatics (p = 0.014). The tt genotype was over-represented in wheezers (19.2 %) and asthmatics (21.3 %) compared to respective controls (12.9 %). No difference was observed between controls, current wheezers and active asthmatics in the genotypic distribution of BsmI and ApaI polymorphic sites. After stratification by the presence of hypovitaminosis D, a significant association was detected between tt genotype of TaqI polymorphism with wheezing (OR: 1.97, 95 % CI: 1.12, 3.46) and asthma (OR: 2.37, 95CI%: 1.02, 5.52) only in those with normal vitamin D levels (>20 ng/ml) but not in subjects with low vitamin D.

Conclusions: The minor TaqI genotype of VDR is associated with asthma in Cypriot adolescents. This polymorphism may contribute to asthma susceptibility primarily under conditions of normal vitamin D levels (>20 ng/ml).
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http://dx.doi.org/10.1186/s40248-015-0025-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559891PMC
September 2015

Association of Serum Vitamin D with Asthma and Atopy in Childhood: Review of Epidemiological Observational Studies.

Mini Rev Med Chem 2015 ;15(11):881-99

Cyprus International Institute for Environmental & Public Health in association with Harvard School of Public Health, Cyprus University of Technology, 95 Irenes Street, 3041, Limassol, Cyprus.

During the last decades, vitamin D deficiency has re-emerged worldwide affecting not only population's bone health, but also several other conditions including asthma and allergies. Increasing number of published epidemiological studies in the last seven years have examined the role of vitamin D deficiency in childhood in several outcomes including asthma diagnosis, asthma disease severity, allergic sensitization and atopy. This review presents evidence on this association from a systematic search in the literature of all available observational studies and their limitations. A total of 33 studies were identified: 3 prospective, 16 case-control and 14 cross-sectional studies. Overall, most of the case-control studies tend to report that asthmatics have lower vitamin D levels/status as compared to healthy children, although most of these studies are mainly descriptive in nature and tend to provide only crude, unadjusted comparisons. Studies that investigated the association of vitamin D with the prevalence, development and/or severity of asthma gave mixed findings, with the exception of studies that focused on vitamin D and severity of asthma which suggest a positive association of vitamin D levels with better asthma control, reduced use of asthma medication, fewer asthma exacerbations and lower utilisation of health care facilities for urgent treatment. Insufficient evidence also exists for the association of inadequate vitamin D status with higher risk of atopic sensitization. The lack of adequate number of prospective studies, the variable definitions for case ascertainment, the wide age range of the participants, and commonly the inadequate control for confounders make inferences difficult. Future studies are needed with a prospective design and repeated measurements of vitamin D to provide critical information on the timing and dosage of future vitamin D supplementation interventions.
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http://dx.doi.org/10.2174/1389557515666150519105541DOI Listing
April 2016

Clinical features of primary ciliary dyskinesia in Cyprus with emphasis on lobectomized patients.

Respir Med 2015 Mar 31;109(3):347-56. Epub 2015 Jan 31.

Department of Electron Microscopy and Molecular Pathology, Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; Cyprus School of Molecular Medicine, Nicosia, Cyprus. Electronic address:

Background: Despite the manifestations of primary ciliary dyskinesia (PCD) in early life, the diagnosis is often much delayed. Since 1998 in Cyprus, we have established the only national diagnostic and clinical referral center for PCD.

Objective: To review the phenotypic features at presentation of PCD patients in Cyprus in relation to age at diagnosis, with emphasis on previously lobectomised patients.

Methods: The medical records of the diagnosed PCD patients were retrospectively reviewed to obtain clinical data on presentation.

Results: Thirty patients, aged 13.9 years (range 0.1, 58.4 years), were diagnosed with PCD. Twelve of them presented after the age of 18. The most common manifestations were chronic cough (100%), chronic rhinorrhea (96.7%), sputum production (92.9%), laterality defects (63.3%), a history of pneumonia (53.3%) and neonatal respiratory distress (50%). A history of lobectomy in the past was recorded in 16.7% (5 patients). Patients who presented in adulthood had significantly higher frequency of lobectomy (41.7% vs 0%, p-value = 0.006) and had more frequently low FEV1 (58.3% vs 0%, p-value = 0.015) than those who presented before. Serial measurements of FEV1 and FVC indicated significantly lower intercepts in lobectomised compared to the adult non-lobectomised patients both in terms of FEV1 (-4.90 vs -1.80, p-value = 0.022) and FVC (-5.43 vs -1.91, p-value = 0.029) z-score levels. Change in FEV1 and FVC across time was not statistically significant in either group.

Conclusions: PCD often remains undiagnosed up to adulthood accompanied by appearance of advanced lung disease. Performance of lobectomies seems to be a poor prognostic factor for PCD in adulthood.
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http://dx.doi.org/10.1016/j.rmed.2015.01.015DOI Listing
March 2015

Vitamin D levels and status amongst asthmatic and non-asthmatic adolescents in Cyprus: a comparative cross-sectional study.

BMC Public Health 2015 Jan 31;15:48. Epub 2015 Jan 31.

Cyprus International Institute for Environmental & Public Health in association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.

Background: Emerging evidence suggests that vitamin D might be implicated in asthma pathophysiology. This study aims to compare Vitamin D mean serum levels and status between asthmatic and non-asthmatic adolescents and investigate the association of vitamin D with asthma severity.

Methods: In a cohort of adolescents aged 16-17 years, those reporting wheezing in the past 12 months and Ever asthma on the ISAAC questionnaire were invited to participate and formed the Active Asthmatics group. Controls were selected amongst Never Wheezers/Never Asthmatics (NWNA). Differences in mean 25(OH)D serum levels and vitamin D status between AA and NWNA were examined in multivariate linear and logistic regression models respectively, adjusting for potential confounders. Within AA, differences in vitamin D levels were assessed across asthma severity indicators.

Results: A total of 69 AA and 671 NWNA participated in the study. Unadjusted mean 25(OH)D serum levels were 22.90 (SD 6.41), and 21.15 (SD 5.59) ng/mL in NWNA and AA respectively (p = 0.03). In adjusted models, mean 25(OH)D levels remained significantly lower amongst AA compared to NWNA (adjusted beta coefficient -1.68, 95% CI -3.24, -0.13). Severe (<12 ng/mL), moderate (<25 ng/mL) or insufficient (<30 ng/mL) vitamin D status was more prevalent among AA who were 1.6 times (95% CI 1.01, 2.53) more likely to belong to a lower vitamin D category compared to NWNA. Within AA, there was a negative trend between vitamin D levels and the number of reported asthma severity indicators.

Conclusions: Levels of vitamin D tend to be lower among asthmatic compared to non-asthmatic children and in those with severe asthma independent of important confounders.
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http://dx.doi.org/10.1186/s12889-015-1385-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318540PMC
January 2015

PM10 concentration levels at an urban and background site in Cyprus: the impact of urban sources and dust storms.

J Air Waste Manag Assoc 2014 Dec;64(12):1352-60

Harvard University, Boston, MA, USA.

Air quality in Cyprus is influenced by both local and transported pollution, including desert dust storms. We examined PM10 concentration data collected in Nicosia (urban representative) from April 1, 1993, through December 11, 2008, and in Ayia Marina (rural background representative) from January 1, 1999, through December 31, 2008. Measurements were conducted using a Tapered Element Oscillating Micro-balance (TEOM). PM10 concentrations, meteorological records, and satellite data were used to identify dust storm days. We investigated long-term trends using a Generalized Additive Model (GAM) after controlling for day of week, month, temperature, wind speed, and relative humidity. In Nicosia, annual PM10 concentrations ranged from 50.4 to 63.8 μg/m3 and exceeded the EU annual standard limit enacted in 2005 of 40 μg/m3 every year A large, statistically significant impact of urban sources (defined as the difference between urban and background levels) was seen in Nicosia over the period 2000-2008, and was highest during traffic hours, weekdays, cold months, and low wind conditions. Our estimate of the mean (standard error) contribution of urban sources to the daily ambient PM10 was 24.0 (0.4) μg/m3. The study of yearly trends showed that PM10 levels in Nicosia decreased from 59.4 μg/m3 in 1993 to 49.0 μg/m3 in 2008, probably in part as a result of traffic emission control policies in Cyprus. In Ayia Marina, annual concentrations ranged from 27.3 to 35.6 μg/m3, and no obvious time trends were observed. The levels measured at the Cyprus background site are comparable to background concentrations reported in other Eastern Mediterranean countries. Average daily PM10 concentrations during desert dust storms were around 100 μg/m3 since 2000 and much higher in earlier years. Despite the large impact ofdust storms and their increasing frequency over time, dust storms were responsible for a small fraction of the exceedances of the daily PM10 limit. Implications: This paper examines PM10 concentrations in Nicosia, Cyprus, from 1993 to 2008. The decrease in PM10 levels in Nicosia suggests that the implementation of traffic emission control policies in Cyprus has been effective. However, particle levels still exceeded the European Uion annual standard, and dust storms were responsible for a small fraction of the daily PM10 limit exceedances. Other natural particles that are not assessed in this study, such as resuspended soil and sea salt, may be responsible in part for the hig particle levels.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739785PMC
http://dx.doi.org/10.1080/10962247.2014.923061DOI Listing
December 2014

Asthma: the role of low high-density-lipoprotein cholesterol in childhood and adolescence.

Int Arch Allergy Immunol 2014 1;165(2):91-9. Epub 2014 Nov 1.

Cyprus International Institute for Environmental and Public Health in association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.

Background: Several studies have examined the relationship of asthma with serum dyslipidemia and reported positive, negative or no association. Most studies were limited by their cross-sectional design and the wide age range of the participants. In a cohort of children in Cyprus, we explored the association of asthma with serum high-density-lipoprotein cholesterol (HDL-C) at age 16-18 years (follow-up) independently of and in relation to HDL-C at age 11-12 years (baseline).

Methods: In a case-control design, we recruited active asthmatics (AA; n = 68), current wheezers only (CWO; n = 123) and non-asthmatic controls (n = 660). Logistic regression models were used to evaluate associations of asthma with follow-up serum HDL-C and the role of baseline HDL-C.

Results: At follow-up, mean HDL-C levels in AA and CWO patients were significantly lower than in the controls (47.9 and 49.7 vs. 53.4 mg/dl; p = 0.001 and p = 0.011). We observed significant associations of AA patients with low HDL-C (<15th percentile; OR 2.32, 95% CI 1.16-4.47) that remained significant after further adjustment for baseline HDL-C (OR 2.14, 95% CI 1.06-4.14). Stratification by baseline HDL-C indicated that the association was significant only in those with high baseline HDL-C (OR 2.40, 95% CI 1.03-5.20). Stratification by IgE sensitization showed that the association was pronounced only in subjects who were sensitized (OR 3.41, 95% CI 1.12-9.88).

Conclusions: Adolescent asthma is associated with low serum HDL-C independent of previous HDL-C levels in childhood. The association appears pronounced in those with a drop in HDL-C levels between childhood and adolescence and in those who have IgE sensitization.
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http://dx.doi.org/10.1159/000368405DOI Listing
February 2015

Gender differences in objectively assessed physical activity in asthmatic and non-asthmatic children.

Pediatr Pulmonol 2015 Apr 28;50(4):317-26. Epub 2014 Mar 28.

Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus; Department of Pediatrics, Hospital "Archbishop Makarios III", Nicosia, Cyprus.

Objective: To compare objectively assessed physical activity levels, between asthmatic children and non-asthmatic controls.

Methods: From a random community sample of 794 children aged 8-9 years, in a case-control design, 104 children with ever doctor's diagnosis of asthma and 99 non-asthmatic controls were recruited and had assessment of physical activity with biaxial accelerometers for 7 days.

Results: Children with active (also reporting at least one episode of wheezing in the last 12 months) and inactive (no wheezing in past 12 months) asthma appeared to have similar physical activity and sedentary activity levels compared to non-asthmatic children. However, girls with active asthma had significantly lower moderate-to-vigorous physical activity (MVPA) levels than their peers with adjusted geometric mean ratio of 0.59 (95% CI: 0.369, 0.929, P-value = 0.024). No difference in physical and sedentary activity levels was observed between asthmatic and non-asthmatic boys. The difference between genders in the comparison of MVPA levels in asthmatics and controls was statistically significant (P-value of likelihood ratio test [LRT] for effect modification by gender = 0.034).

Conclusions: Unlike boys, girls with active asthma appear to be less active than their healthy peers, and this gender difference might explain the inconsistent evidence from previous reports on physical activity levels in asthmatic children. Further studies are needed to confirm the gender interaction in the childhood asthma-physical activity relation and the implications on current guidelines for physical exercise prescriptions in asthmatic children.
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http://dx.doi.org/10.1002/ppul.23045DOI Listing
April 2015

Apparent Homozygosity of p.Phe508del in CFTR due to a Large Gene Deletion of Exons 4-11.

Case Rep Genet 2014 6;2014:613863. Epub 2014 Feb 6.

Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.

We report a classic cystic fibrosis (CF) boy with a large deletion of exons 4-11 in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on one allele and p.Phe508del in exon 10 on the second allele. Both parents of Georgian and Ukrainian background had no personal or family history of the disease. The initial molecular diagnostic investigation identified the patient as homozygous for the p.Phe508del and not compatible with his parent's genetic status. The possibility of nonpaternity or uniparental disomy (UPD7) was investigated and excluded using microsatellite analysis of highly polymorphic markers on chromosome 7. Array-CGH was also performed on the patient and revealed a male profile with a subtle deletion within the CFTR gene on the long arm (q-arm) of chromosome 7 (7q31.2). The deletion was confirmed by MLPA extending from probe L02380 to probe L14978 (28.7 kb) and that was inherited from his father, while p.PheF508del was inherited from his mother. These data highlight the need for additional testing for large deletions in patients with apparent homozygosity for a mutated CFTR allele that do not match the carrier status of the parents. Not testing can lead to misdiagnosis and misinterpretation of mutation carrier status and the expected penetrance of the disorder.
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http://dx.doi.org/10.1155/2014/613863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932727PMC
March 2014

Association of vitamin D with adiposity measures and other determinants in a cross-sectional study of Cypriot adolescents.

Public Health Nutr 2015 Jan 17;18(1):112-21. Epub 2014 Jan 17.

2Department of Nursing,School of Health Sciences,Cyprus University of Technology,Limassol,Cyprus.

Objective: To assess vitamin D status among Cypriot adolescents and investigate potential determinants including BMI and body fat percentage (BF%).

Design: Participants had cross-sectional assessments of serum vitamin D, physical activity, dietary vitamin D intake and sun exposure. Linear and logistic regression models were used to explore the associations of vitamin D with potential predictors.

Setting: Hospitals, Cyprus, November 2007-May 2008.

Subjects: Adolescents (n 671) aged 16-18 years.

Results: Mean serum vitamin D was 22·90 (sd 6·41) ng/ml. Only one in ten children had sufficient levels of vitamin D (≥30 ng/ml), while the prevalence of vitamin D deficiency (12-20 ng/ml) and severe deficiency (<12 ng/ml) was 31·7 % and 4·0 %, respectively. Lower vitamin D was associated with winter and spring season, female gender, reduced sun exposure in winter and darker skin. Participants with highest BMI and BF% when compared with a middle reference group had increased adjusted odds of vitamin D insufficiency (OR = 3·00; 95 % CI 1·21, 7·45 and OR = 5·02; 95 % CI 1·80, 13·97, respectively). A similar pattern, although not as strong, was shown for vitamin D deficiency with BF% (OR = 1·81; 95 % CI 1·04, 3·16) and BMI (OR = 1·51; 95 % CI 0·85, 2·67). Participants in the lowest BMI and BF% groups also displayed compromised vitamin D status, suggesting a U-shaped association.

Conclusions: Vitamin D deficiency in adolescence is very prevalent in sunny Cyprus, particularly among females, those with darker skin and those with reduced sun exposure in winter. Furthermore, vitamin D status appears to have a U-shaped association with adiposity measures.
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http://dx.doi.org/10.1017/S1368980013003480DOI Listing
January 2015

Prevalence of asthma and allergies in children from the Greek-Cypriot and Turkish-Cypriot communities in Cyprus: a bi-communal cross-sectional study.

BMC Public Health 2013 Jun 16;13:585. Epub 2013 Jun 16.

Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.

Background: The Greek-Cypriot (G/C) and Turkish-Cypriot (T/C) communities have lived apart since 1974, with the former presumably adopting a more westernized way of life. We estimated the prevalence of asthma and allergies among children in the two communities and investigated differences in socio-demographic and lifestyle risk factors.

Methods: The ISAAC questionnaire was completed by 10156 children aged 7-8 and 13-14 years. Relative differences in asthma and allergic symptoms between the two communities were expressed as odds ratios (OR), estimated in multivariable logistic regression models before and after adjusting for participants' risk characteristics.

Results: In contrast to our original speculation, consistently lower prevalence rates were observed for respiratory outcomes (but not eczema) among G/C compared to T/C children in both age-groups. For instance, the prevalence of current wheeze among 7-8 year-olds was 8.7% vs 11.4% (OR = 0.74, 95%, CI: 0.61, 0.90) and of current rhinoconjuctivitis 2.6% vs 4.9% (OR = 0.52, 95% CI: 0.37, 0.71). Surprisingly, the proportion reporting family history of allergy was almost double in the G/C community. With the exception of early life nursery attendance, several protective factors were more prevalent amongst T/C, such as bedroom sharing, less urbanized environment and exposure to farm animals. In contrast, exposure to tobacco smoke was more frequent in the T/C community. Controlling for risk factors did not account for the observed lower prevalence of current wheeze (in the younger age-group) and rhinoconjuctivitis (in both age-groups) among G/C children while differences in the prevalence of eczema between the two communities were no longer statistically significant.

Conclusions: A mixed picture of potential risk factors was observed in the two communities of Cyprus, not consistently favoring one over the other community since, for example, bedroom sharing and rural living but also exposure to tobacco smoke were more common among T/C children. Investigated risk factors do not fully account for the lower prevalence of asthma and allergies among G/C children, especially against a background of higher family history of allergy in this community.
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http://dx.doi.org/10.1186/1471-2458-13-585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698153PMC
June 2013

Associations of body fat percent and body mass index with childhood asthma by age and gender.

Obesity (Silver Spring) 2013 Sep 21;21(9):E474-82. Epub 2013 May 21.

Cyprus International Institute for Environmental & Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.

Objective: High body mass index (BMI) has been shown to be associated with asthma, but the pattern of this association is still unclear and may differ by gender or stage of puberty. BMI is only a proxy of adiposity, whereas estimation of body fat percent (BF%) by the bioimpedance technique is considered an accurate measure of adiposity. We investigated whether BMI and BF% behave differently in their association with asthma between genders, before and during adolescence.

Design And Methods: In this cross-sectional study of 10,981 schoolchildren, we used logistic regression models to examine the pattern of association of BMI and BF% with asthma.

Results: In the case of BF%, both the highest (odds ratio [OR]: 1.68, 95% confidence interval [95% CI]: 1.21-2.30) and lowest (OR: 1.59, 95% CI: 1.13-2.23) z-score categories conferred an increased adjusted risk for active asthma. The likelihood ratio test (LRT) of nonlinearity yielded significant results (P < 0.01) for BF%. In contrast, the LRT for BMI yielded a nonsignificant result (P = 0.45) indicating a linear association of asthma with BMI. A unit increase in BMI z-score conferred an increase in the adjusted odds of active asthma (OR: 1.14, 95% CI: 1.02-1.27). In the case of BF%, the adjusted ORs for active asthma at the highest and lowest z-score categories in both genders, before and during adolescence, were similarly elevated, exhibiting a U-shape pattern.

Conclusions: In contrast to the linear association observed with BMI, BF% displayed a U-shaped association with asthma and may be the preferred measure of adiposity in epidemiological studies of asthma in children.
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http://dx.doi.org/10.1002/oby.20284DOI Listing
September 2013

First outbreak of nosocomial Legionella infection in term neonates caused by a cold mist ultrasonic humidifier.

Clin Infect Dis 2013 Jul 19;57(1):48-56. Epub 2013 Mar 19.

Neonatal Intensive Care Unit, Hospital Archbishop Makarios III, Nicosia, Cyprus.

Background: To date, all descriptions of legionellosis in neonates have emerged from a small number of isolated case reports in newborns with unusually severe pneumonia. In December 2008, a large outbreak of Legionella infection occurred in term neonates in Cyprus, providing new information on the epidemiological and clinical features of Legionellosis in this age group.

Methods: An environmental investigation was performed at a small private hospital where the infected neonates were delivered. The medical records of the infected neonates were retrospectively reviewed to obtain clinical data on presentation, complications, and course of disease.

Results: Nine of the 32 (28%) newborns who were exposed to the contaminated source at the private nursery were infected with Legionella. Six subjects had pulmonary infiltrates, but in 3 cases there were no abnormal radiological findings and clinical presentation was mild. In 4 neonates, pulmonary infiltrates at presentation were bilateral and extensive and 3 died, conferring a mortality rate of 50% in subjects with pulmonary infiltrates and an overall mortality of 33.3%. Legionella pneumophila serogroup 3 was recovered in neonatal biological samples, although in some patients there was implication of a second strain, serogroup 1. It was determined that the neonates were infected while in the nursery at the private hospital by aerosol produced by a recently installed cold-mist humidifier that was filled with contaminated water.

Conclusions: Use of humidifiers in nursery units must be avoided as the risk of disseminating Legionella in neonates is very high. In neonates legionellosis should be suspected when signs of infection first appear and take an unusual course, even when no pulmonary infiltrates appear.
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http://dx.doi.org/10.1093/cid/cit176DOI Listing
July 2013

Asthma and atopy in children born by caesarean section: effect modification by family history of allergies - a population based cross-sectional study.

BMC Pediatr 2012 Nov 16;12:179. Epub 2012 Nov 16.

Cyprus International Institute for Environmental and Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.

Background: Studies on the association of birth by caesarean section (C/S) and allergies have produced conflicting findings. Furthermore, evidence on whether this association may differ in those at risk of atopy is limited. This study aims to investigate the association of mode of delivery with asthma and atopic sensitization and the extent to which any effect is modified by family history of allergies.

Methods: Asthma outcomes were assessed cross-sectionally in 2216 children at age 8 on the basis of parents' responses to the ISAAC questionnaire whilst skin prick tests to eleven aeroallergens were also performed in a subgroup of 746 children. Adjusted odds ratios of asthma and atopy by mode of delivery were estimated in multivariable logistic models while evidence of effect modification was examined by introducing interaction terms in the models.

Results: After adjusting for potential confounders, children born by C/S appeared significantly more likely than those born vaginally to report ever wheezing (OR 1.36, 95% CI 1.07-1.71), asthma diagnosis (OR 1.41, 95% CI 1.09-1.83) and be atopic (OR 1.67, 95% CI 1.08-2.60). There was modest evidence that family history of allergies may modify the effect of C/S delivery on atopy (p for effect modification=0.06) but this was not the case for the asthma outcomes. Specifically, while more than a two-fold increase in the odds of being a topic was observed in children with a family history of allergies if born by C/S (OR 2.62, 95% CI 1.38-5.00), no association was observed in children without a family history of allergies (OR 1.16, 95% CI 0.64-2.11).

Conclusions: Birth by C/S is associated with asthma and atopic sensitization in childhood. The association of C/S and atopy appears more pronounced in children with family history of allergies.
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http://dx.doi.org/10.1186/1471-2431-12-179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511167PMC
November 2012

Temporal changes in the prevalence of childhood asthma and allergies in urban and rural areas of Cyprus: results from two cross sectional studies.

BMC Public Health 2011 Nov 11;11:858. Epub 2011 Nov 11.

Cyprus International Institute for Environmental and Public Health in Association with Harvard School of Public Health, Cyprus University of Technology, Limassol, Cyprus.

Background: The prevalence of childhood asthma and allergies in Cyprus was significantly higher in urban compared to rural areas back in the year 2000, against a background of an overall low prevalence (e.g. current wheeze 6.9%) by comparison to northern European countries. In this study we aimed to assess temporal changes in the prevalence of asthma and allergies in Cyprus after an 8-year interval and to examine whether any differential changes have occurred in urban and rural parts of the island.

Methods: During the academic years 1999-2000 and 2007-2008, the parents of 7-8 year old children residing in the same set of urban and rural areas completed the ISAAC core questionnaire. In addition to providing prevalence estimates of allergic diseases in 2000 and 2008, changes between the two periods were expressed as odds ratios estimated in multiple logistic regression models adjusting for survey participants' characteristics.

Results: The prevalence of current wheeze was higher in 2008 (8.7%, 95% confidence interval 7.5%-9.9%, n = 2216) than the previously recorded figure in 2000 (6.9%, 95% CI 6.2%-7.6%, OR = 1.25, 95% CI: 1.02-1.53, n = 4944). Significant increases were also seen in the prevalence of lifetime asthma (11.3% vs. 17.4%, OR = 1.59, CI: 1.36-1.86), eczema (6.8% vs. 13.5%, OR = 1.91, CI: 1.59-2.29) and allergic rhinoconjuctivitis (2.6% vs. 5.2%, OR = 1.82, CI: 1.39-2.41). The prevalence of current wheeze nearly doubled between 2000 and 2008 in rural areas (5.4% vs. 9.7%, OR 1.81, CI: 1.24-2.64) while no significant change was observed in urban areas (7.5% vs. 8.4%, OR 1.08, CI: 0.84-1.37); p value for effect modification = 0.04. Rises in asthma and rhinitis prevalence, but not eczema were also more pronounced in rural compared to urban areas.

Conclusions: The prevalence of allergic diseases in Cyprus is still on the rise; recent increases appear more pronounced among children living in rural areas possibly indicating recent environmental and lifestyle changes in these communities.
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http://dx.doi.org/10.1186/1471-2458-11-858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3247303PMC
November 2011