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From the nose to the lungs: the importance of upper respiratory disease in Primary Ciliary Dyskinesia

Applicant Goutaki Myrofora
Number 185923
Funding scheme Ambizione
Research institution Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Respiratory Diseases
Start/End 01.10.2019 - 30.09.2023
Approved amount 950'341.00
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All Disciplines (3)

Discipline
Respiratory Diseases
Congenital Disorders
Otorhinolaryngology

Keywords (5)

cohort study; rare disease; randomised controlled trial; primary ciliary dyskinesia ; upper respiratory disease

Lay Summary (German)

Lead
Die primäre ciliäre Dyskinesie (PCD) ist eine seltene Erbkrankheit, die mehrere Organsysteme betreffen kann. Fast alle Patienten haben Probleme mit den Ohren, der Nase und den Nasennebenhöhlen. Trotz grosser Fortschritte in der PCD-Forschung in den letzten Jahren gibt es nur wenig Informationen über Hals-Nasen-Ohren-Probleme und keine wissenschaftliche Grundlage für deren Behandlung.
Lay summary

Hintergrund und Ziele des Forschungsprojektes

PCD ist eine seltene Erkrankung, die vor allem die Atemwege betrifft. In der Regel haben die Patienten Lungenprobleme, aber auch die Ohren, Nase und Nasennebenhöhlen können betroffen sein. Probleme im Hals-Nasen-Ohren-Bereich können wiederkehrende Episoden von Mittelohrenentzündungen, chronische Schleimhautentzündungen der Nase und der Nasennebenhöhlen (Rhinosinusitis) oder ein Hörverlust sein. Der Alltag der Patienten ist durch diese Probleme stark beeinträchtigt. Trotzdem konzentrieren sich die meisten Studien auf die Verbesserung der Diagnosestellung und auf die Lungenprobleme. Wir wissen darum nur sehr wenig über die Hals-Nasen-Ohren-Probleme: Wie häufig sind sie? Wie verändern sie sich im Alter? Wie stark variieren sie von Patient zu Patient? Warum und vor allem, wie sind die Probleme zu behandeln?

Ziel dieses Projekts ist es, klinische Daten von PCD-Patienten in mehreren etablierten europäischen PCD-Zentren fortlaufend (prospektiv) zu sammeln und zu analysieren. Dabei konzentrieren wir uns auf die Hals-Nasen-Ohren-Probleme. Einerseits werden wir die Hals-Nasen-Ohren-Probleme und deren Zusammenhang mit Lungenproblemen untersuchen. Andererseits erfassen wir die Prognose selbst sowie Faktoren, die die Prognose beeinflussen. Das Projekt beinhaltet zusätzlich zur fortlaufenden Datensammlung eine klinische Studie. Das Ziel ist es, erste Hinweise zur Behandlung der chronischen Rhinosinusitis zu liefern, eines der häufigsten Symptome bei PCD. Dazu werden verschiedene Arten der Nasenspülung mit der Verabreichung von Kortison mittels Nasenspray verglichen.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

In diesem Projekt werden prospektive, standardisierte und damit qualitativ hochwertige Daten zu Hals-Nasen-Ohren-Problemen bei PCD-Patienten gesammelt und analysiert. Diese Daten schliessen klinische Untersuchungen und vom Patienten selber berichtete Beschwerden mit ein. Das Projekt wird grösstenteils in die reguläre Patientenversorgung integriert sein. Dadurch können die Daten direkt ohne Mehraufwand für das Projekt verwendet werden. Die klinische Studie wird ein auf diese seltene Krankheit zugeschnittenes Design haben.  Aus klinischer Sicht wird das Projekt wichtige Erkenntnisse für die Charakterisierung und Behandlung von PCD-Patienten liefern, um deren Lebensqualität zu verbessern. Das Design dieser Projektes kann als sehr gutes Beispiel für die Erforschung anderer seltener Krankheiten dienen, bei denen ebenfalls eine Kollaboration sowie ein pragmatisches Design notwendig sind.

Direct link to Lay Summary Last update: 26.08.2019

Responsible applicant and co-applicants

Employees

Publications

Publication
European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5–16 years
Gaillard Erol A., Kuehni Claudia E., Turner Steve, Goutaki Myrofora, Holden Karl A., de Jong Carmen C.M., Lex Christiane, Lo David K.H., Lucas Jane S., Midulla Fabio, Mozun Rebeca, Piacentini Giorgio, Rigau David, Rottier Bart, Thomas Mike, Tonia Thomy, Usemann Jakob, Yilmaz Ozge, Zacharasiewicz Angela, Moeller Alexander (2021), European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5–16 years, in European Respiratory Journal, 57(5), 2004173-2004173.
SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe
PedersenEva, GoutakiMyrofora, HarrisAmanda, DixonLucy, Manion Michele, RindlisbacherBernhard, LucasJane, KuehniClaudia (2021), SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe, in European Respiratory Journal.
COVID-PCD: a participatory research study on the impact of COVID-19 in people with primary ciliary dyskinesia
Pedersen Eva S.L., Collaud Eugénie N.R., Mozun Rebeca, Ardura-Garcia Cristina, Lam Yin Ting, Harris Amanda, Lucas Jane S., Copeland Fiona, Manion Michele, Rindlisbacher Bernhard, Silberschmidt Hansruedi, Goutaki Myrofora, Kuehni Claudia E. (2021), COVID-PCD: a participatory research study on the impact of COVID-19 in people with primary ciliary dyskinesia, in ERJ Open Research, 7(1), 00843-2020-00843-2020.
Primary ciliary dyskinesia
EberErnst, MidullaFabio (2021), Primary ciliary dyskinesia, European Respiratory Society, United Kingdom, 569-578.
The BEAT-PCD (Better Experimental Approaches to Treat Primary Ciliary Dyskinesia) Clinical Research Collaboration
Goutaki Myrofora, Crowley Suzanne, Dehlink Eleonora, Gaupmann René, Horton Katie L., Kouis Panayiotis, Lam Yin Ting, Loges Niki T., Lucas Jane S., Roehmel Jobst F., Shoemark Amelia (2021), The BEAT-PCD (Better Experimental Approaches to Treat Primary Ciliary Dyskinesia) Clinical Research Collaboration, in European Respiratory Journal, 57(2), 2004601-2004601.
Reported Symptoms Differentiate Diagnoses in Children with Exercise-Induced Respiratory Problems: Findings from the Swiss Paediatric Airway Cohort (SPAC)
Pedersen Eva S.L., de Jong Carmen C.M., Ardura-Garcia Cristina, Mallet Maria Christina, Barben Juerg, Casaulta Carmen, Hoyler Karin, Jochmann Anja, Moeller Alexander, Mueller-Suter Dominik, Regamey Nicolas, Singer Florian, Goutaki Myrofora, Kuehni Claudia E. (2021), Reported Symptoms Differentiate Diagnoses in Children with Exercise-Induced Respiratory Problems: Findings from the Swiss Paediatric Airway Cohort (SPAC), in The Journal of Allergy and Clinical Immunology: In Practice, 9(2), 881-889.e3.
Diagnosis in children with exercise‐induced respiratory symptoms: A multi‐center study
Pedersen Eva S. L., Ardura‐Garcia Cristina, Jong Carmen C. M., Jochmann Anja, Moeller Alexander, Mueller‐Suter Dominik, Regamey Nicolas, Singer Florian, Goutaki Myrofora, Kuehni Claudia E. (2021), Diagnosis in children with exercise‐induced respiratory symptoms: A multi‐center study, in Pediatric Pulmonology, 56(1), 217-225.
Paediatric cohort studies on lower respiratory diseases and their reporting quality: systematic review of the year 2018
Ardura-Garcia Cristina, Mozun Rebeca, Pedersen Eva S.L., Otth Maria, Mallet Maria Christina, Goutaki Myrofora, Kuehni Claudia E. (2020), Paediatric cohort studies on lower respiratory diseases and their reporting quality: systematic review of the year 2018, in European Respiratory Journal, 56(5), 2000168-2000168.
Isolated night cough in children: how does it differ from wheeze?
Jurca Maja, Goutaki Myrofora, Latzin Philipp, Gaillard Erol A., Spycher Ben D., Kuehni Claudia E. (2020), Isolated night cough in children: how does it differ from wheeze?, in ERJ Open Research, 6(4), 00217-2020-00217-2020.
Cigarette, shisha, and electronic smoking and respiratory symptoms in Swiss children: The LUIS study
Mozun Rebeca, Ardura‐Garcia Cristina, Jong Carmen C. M., Goutaki Myrofora, Usemann Jakob, Singer Florian, Latzin Philipp, Kuehni Claudia E., Moeller Alexander (2020), Cigarette, shisha, and electronic smoking and respiratory symptoms in Swiss children: The LUIS study, in Pediatric Pulmonology, 55(10), 2806-2815.
Late Diagnosis of Infants with PCD and Neonatal Respiratory Distress
Goutaki Myrofora, Halbeisen Florian S., Barbato Angelo, Crowley Suzanne, Harris Amanda, Hirst Robert A., Karadag Bülent, Martinu Vendula, Morgan Lucy, O’Callaghan Christopher, Ozçelik Ugur, Scigliano Sergio, Ucros Santiago, Yiallouros Panayiotis, Schulzke Sven M., Kuehni Claudia E. (2020), Late Diagnosis of Infants with PCD and Neonatal Respiratory Distress, in Journal of Clinical Medicine, 9(9), 2871-2871.
Proceedings of the 4th BEAT-PCD Conference and 5th PCD Training School
Gardner Laura E., Horton Katie L., Shoemark Amelia, Lucas Jane S., Nielsen Kim G., Kobbernagel Helene, Rubbo Bruna, Hirst Robert A., Kouis Panayiotis, Ullmann Nicola, Reula Ana, Rumman Nisreen, Mitchison Hannah M., Pinto Andreia, Richardson Charlotte, Schmidt Anne, Thompson James, Gaupmann René, Dabrowski Maciej, Mill Pleasantine, Carr Siobhan B., Norris Dominic P., Kuehni Claudia E., Goutaki Myrofora, et al. (2020), Proceedings of the 4th BEAT-PCD Conference and 5th PCD Training School, in BMC Proceedings, 14(S8), 7-7, BMC Proceedings, United Kingdom 14(S8), 7-7.
Registries and collaborative studies for primary ciliary dyskinesia in Europe
Ardura-Garcia Cristina, Goutaki Myrofora, Carr Siobhán B., Crowley Suzanne, Halbeisen Florian S., Nielsen Kim G., Pennekamp Petra, Raidt Johanna, Thouvenin Guillaume, Yiallouros Panayiotis K., Omran Heymut, Kuehni Claudia E. (2020), Registries and collaborative studies for primary ciliary dyskinesia in Europe, in ERJ Open Research, 6(2), 00005-2020-00005-2020.
Standardised clinical data from patients with primary ciliary dyskinesia: FOLLOW-PCD
Goutaki Myrofora, Papon Jean-François, Boon Mieke, Casaulta Carmen, Eber Ernst, Escudier Estelle, Halbeisen Florian S., Harris Amanda, Hogg Claire, Honore Isabelle, Jung Andreas, Karadag Bulent, Koerner-Rettberg Cordula, Legendre Marie, Maitre Bernard, Nielsen Kim G., Rubbo Bruna, Rumman Nisreen, Schofield Lynne, Shoemark Amelia, Thouvenin Guillaume, Willkins Hannah, Lucas Jane S., Kuehni Claudia E. (2020), Standardised clinical data from patients with primary ciliary dyskinesia: FOLLOW-PCD, in ERJ Open Research, 6(1), 00237-2019-00237-2019.
Phenotype-genotype associations in Primary Ciliary Dyskinesia: where do we stand?
Goutaki Myrofora, Pedersen Eva, Phenotype-genotype associations in Primary Ciliary Dyskinesia: where do we stand?, in Eur Respir J.

Collaboration

Group / person Country
Types of collaboration
Jean-François Papon, University hospital Bicêtre Paris-Sud France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Bülent Karadag, Marmara University, Istanbul Turkey (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Miguel Armengot, University and Politechnic Hospital le Fe, Valencia Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Mieke Boon, University Hospital Gasthuisberg, Leuven Belgium (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Jobst Röhmel, Charité - Universitätsmedizin Berlin Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Panayiotis Yiallouros, University of Cyprus, Limassol Cyprus (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Ugur Özçelikm, Hacettepe University, Ankara Turkey (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Ben Spycher, Institute of Social and Preventive Medicine, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Sven Trelle, Clinical Trials Unit, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
André Coste, Centre Hospitalier Intercommunal Creteil France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Philipp Latzin, Children's University hospital, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Jane Lucas, University Hospital Southampton (NHS Foundation Trust & University of Southampton) Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Suzanne Crowley, Oslo University Hospital Norway (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Céline Kempeneers, Centre hospitalier universitaire de Liège Belgium (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Eric G. Haarman, VU University Medical Centre, Amsterdam Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events



Self-organised

Title Date Place
EPIC-PCD group meeting 03.05.2021 online, Switzerland
BEAT-PCD ERS CRC advisory board meeting 30.03.2021 online, Switzerland
EPIC-PCD study group meeting 20.01.2021 online, Switzerland
BEAT-PCD ERS CRC management committee meeting 17.12.2020 online, Switzerland
BEAT-PCD ERS CRC inaugural international meeting 10.09.2020 online, Switzerland
BEAT-PCD ERS CRC advisory board meeting 06.07.2020 online, Switzerland
BEAT-PCD ERS CRC management committee meeting 29.06.2020 online, Switzerland
BEAT-PCD ERS CRC (Clinical Research Collaboration) management committee meeting 18.05.2020 online, Switzerland
BEAT-PCD ERS CRC management committee meeting 26.03.2020 online, Switzerland

Knowledge transfer events



Self-organised

Title Date Place
Selbsthilfegruppe PCD Deutschschweiz 22.02.2021 online, Switzerland
BEAT-PCD ERS CRC meeting with industry 21.02.2021 online, Switzerland
Selbsthilfegruppe PCD Deutschschweiz 21.11.2020 online, Switzerland
BEAT-PCD ERS CRC patient advisory group meeting 20.07.2020 online, Switzerland

Communication with the public

Communication Title Media Place Year
New media (web, blogs, podcasts, news feeds etc.) BEAT-PCD Clinical Research Collaboration website BEAT-PCD International 2020
New media (web, blogs, podcasts, news feeds etc.) BEAT-PCD Newsletter International 2020

Associated projects

Number Title Start Funding scheme
192804 Natural history, phenotypes and disease classification in primary ciliary dyskinesia (phase 2) 01.05.2020 Project funding (Div. I-III)

Abstract

Background: Primary Ciliary Dyskinesia (PCD) is a rare, genetic, multiorgan disease with an estimated prevalence of 1 in 10,000. Patients have symptoms in the ears, and the upper and lower airways where cilia play an important role in clearing respiratory secretions. PCD research has made important advances in recent years, though most clinical studies still focus on diagnosis and understanding of lower respiratory disease. Almost all patients have sinonasal or otologic (ear-nose-throat, ENT) problems. Despite that, data on ENT disease are scarce and based on a few small single-center studies. We lack knowledge about the spectrum and severity of ENT disease, its association with lung disease, its course over life, and its determinants of prognosis. Management of ENT disease such as chronic rhinosinusitis (CRS) is based on experts’ opinion or on evidence from other diseases despite the different pathophysiology of CRS in PCD. Large prospective studies and clinical trials are necessary to better characterize ENT disease in PCD and improve its management.Aims: My project includes the development of a prospective multicenter cohort and a nested randomised clinical trial (RCT), and thus is divided into an observational part, work package 1, and an interventional part, work package 2. It will:1) Characterise ENT disease in PCD patients and its association with lower respiratory disease, and identify determinants of prognosis using data from the prospective cohort, and2) Provide evidence for the medical management of CRS in PCD patients by evaluating the safety and efficacy of high volume hypertonic saline nasal irrigation and intranasal steroids compared to normal saline nasal irrigation in a factorial cross-over RCT. Methods: Patients of all ages, diagnosed with PCD according to recent guidelines and followed-up at one of the participating centers, will be recruited to participate in the ENT Prospective International Cohort of PCD patients (EPIC-PCD). The EPIC-PCD will be embedded in regular patient care. We will collect clinical information on symptoms and signs, quality of life (QoL), and examinations such as nasal endoscopy, tympanometry, audiometry, microbiology, and lung function using standardised, disease-specific data collection forms and the validated QoL-PCD questionnaire. Eligible patients with diagnosed CRS will be invited to participate in the nested four-period, four-treatment, factorial, cross-over, open-label RCT. Each included patient will undergo a standardized ENT examination at the randomization visit and at each trial visit. Main outcome measure will be the QoL-PCD scale for upper respiratory symptoms. Secondary outcomes include the sinonasal outcome test (SNOT-22), the QoL-PCD scale for ears and hearing, hearing impairment (measured by audiometry), and a nasal endoscopy score. We will analyse the data using state-of-the-art statistical approaches and report our findings following EQUATOR guidelines such as those of STROBE and CONSORT. Impact/Significance: This multicenter project aligns with national and European efforts to intensify collaborative research in rare diseases. It combines observational and interventional approaches to understand ENT disease in PCD and provide new, robust, clinically relevant evidence to better inform medical management. The cohort will become a valuable resource for the PCD research community extending beyond the end of this project. Finally, this project provides a unique opportunity for my development as an independent researcher.
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