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Natural history, phenotypes and disease classification in primary ciliary dyskinesia (phase 2)

English title Natural history, phenotypes and disease classification in primary ciliary dyskinesia (phase 2)
Applicant Kühni Claudia
Number 192804
Funding scheme Project funding (Div. I-III)
Research institution Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Congenital Disorders
Start/End 01.05.2020 - 30.04.2023
Approved amount 447'055.00
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Keywords (5)

multiorgan disease; phenotypes; rare disease; childhood; primary ciliary dyskinesia

Lay Summary (German)

Lead
Die Primäre Ciliäre Dyskinesie (PCD) ist eine seltene Lungenerkrankung, bei welcher sich die Flimmerhärchen in den Atemwegen nicht richtig bewegen. Betroffene Personen entwickeln eine chronische Atemwegserkrankung mit Husten und wiederholten Lungen- und Mittelohrentzündungen sowie Hörproblemen. Dieses Projekt untersucht den klinischen Verlauf von PCD mit verschiedenen Datenquellen - einer Internationalen Langzeitstudie, einer nationalen Registerstudie in der Schweiz, und der Befragungen von betroffenen Menschen.
Lay summary

Inhalte und Ziele des Forschungsprojekts

Der klinische Phänotyp von PCD - Ausprägung und der Schweregrad der Erkrankung - unterscheiden sich stark zwischen PCD-Betroffenen. Wir wissen jedoch wenig darüber, welche typische Krankheitsbilder existieren und wie sich diese im Verlauf unterscheiden.

Diese Studie untersucht internationale Daten von über 3000 PCD Patienten aus 18 Ländern. Erste Ergebnisse, die vor allem Daten aus Krankenhausakten nutzen, haben illustriert, wie PCD die Lungenfunktion und das Wachstum von Kindern beeinflusst. Neu werden Information auch via Fragebogen direkt von Patienten erhoben, um ihre Beschwerden detaillierter zu erfassen und den Einfluss von Lebensstil und Umweltfaktoren zu untersuchen. Die Erforschung der Symptomatik bei Säuglingen soll erlauben, die Diagnose in Zukunft früher zu stellen.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Dieses Projekt bietet eine einzigartige Möglichkeit, die klinische Epidemiologie einer seltenen Lungenkrankheit zu erforschen. Langfristig soll dies ermöglichen, dass die Behandlung der betroffenen Patienten an ihre Krankheitsausprägung (Phänotyp)  angepasst und individueller geplant werden kann, um die Lebensqualität betroffener Menschen zu optimieren.

Direct link to Lay Summary Last update: 06.05.2020

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Phenotype–genotype associations in primary ciliary dyskinesia: where do we stand?
Goutaki Myrofora, Pedersen Eva S.L. (2021), Phenotype–genotype associations in primary ciliary dyskinesia: where do we stand?, 58(2), 2100392-2100392, European Respiratory Society, United Kingdom 58(2), 2100392-2100392.
SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe
Pedersen Eva S.L., Goutaki Myrofora, Harris Amanda L., Dixon Lucy, Manion Michele, Rindlisbacher Bernhard, Lucas Jane S., Kuehni Claudia E (2021), SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe, in European Respiratory Journal, 2004548-2004548.
COVID-PCD – a participatory research study on the impact of COVID-19 in people with Primary Ciliary Dyskinesia
Pedersen Eva SL, Collaud Eugénie NR, 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), 1-9.
Motile ciliopathies
WallmeierJulia, NielsenKim G, KuehniClaudia E, LucasJane S, LeighMargaret W, ZariwalaMaimoona A, OmranHeymut (2020), Motile ciliopathies, in Nature Reviews Disease Primers, 6(77), 1-29.
Access to medicines for rare diseases: beating the drum for primary ciliary dyskinesia
Crowley Suzanne, Azevedo Inês, Boon Mieke, Bush Andrew, Eber Ernst, Haarman Eric, Karadag Bulent, Kötz Karsten, Leigh Margaret, Moreno-Galdó Antonio, Mussaffi Huda, Nielsen Kim G., Omran Heymut, Papon Jean-François, Pohunek Petr, Priftis Kostas, Rindlisbacher Bernhard, Santamaria Francesca, Valiulis Arunas, Witt Michal, Yiallouros Panayiotis, Zivkovic Zorica, Kuehni Claudia E., Lucas Jane S. (2020), Access to medicines for rare diseases: beating the drum for primary ciliary dyskinesia, in ERJ Open Research, 6(3), 00377-2020-00377-2020.
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, Claire Hogg (2020), Proceedings of the 4th BEAT-PCD Conference and 5th PCD Training School, in BMC Proceedings, Springer Nature 14(S8), 7-7, BMC Proceedings, The Netherlands 14(S8), 7-7.
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Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
BEAT-PCD annual meeting, 2020 Individual talk COVID-19 in people with Primary Ciliary Dyskinesia 10.09.2020 Bern, Switzerland Pedersen Eva Sophie Lunde;


Communication with the public

Communication Title Media Place Year
Print (books, brochures, leaflets) Newsletter, COVID-PCD: by and for people with PCD Italian-speaking Switzerland Western Switzerland International German-speaking Switzerland 2021
New media (web, blogs, podcasts, news feeds etc.) COVID-19 infections in people with PCD, website International 2020

Associated projects

Number Title Start Funding scheme
182628 Phenotypes and prognostic modelling in childhood asthma: moving towards clinical applications (Phase II) 01.10.2018 Project funding (Div. I-III)
173044 Natural history, phenotypes and disease classification in primary ciliary dyskinesia 01.05.2017 Project funding (Div. I-III)
185923 From the nose to the lungs: the importance of upper respiratory disease in Primary Ciliary Dyskinesia 01.10.2019 Ambizione

Abstract

Background: PCD is a rare genetic disease characterised by dysfunctional cilia and leading to chronic upper and lower airways disease, situs inversus, congenital heart defects, subfertility and other health problems. PCD is genetically heterogeneous. Mutations in >40 genes result in a variety of ultrastructural and functional defects, which influence the clinical phenotype and disease course. Most previous publications were based on smallish studies of patients from specialised clinics, with clinical data extracted retrospectively from charts. We therefore know little about the phenotypic heterogeneity, clinical course, and its influencing factors; and treatment recommendations are based on expert opinion or extrapolated from other diseases.In the previous grant period, we published mainly on specific traits relevant to PCD such as lung function and growth and their association with ultrastructural defects. This project is a direct continuation of the SNSF project #320030_173044 which aims to improve the evidence base on the epidemiology of primary ciliary dyskinesia (PCD) by analysing data from our multicentre longitudinal cohort study, the iPCD cohort. In the next period, we will be able to analyse an enriched dataset with dense clinical information, to progress with phenotype definition, disease classification and prognostic studies, and contribute to evidence-based management. Specifically, we aim to:1)Define distinct disease subgroups (phenotypes) and propose a classification model for PCD2)Define predictors of disease severity and prognosis such as environmental exposures, smoking and exercise practices. Methods: The core dataset for this project remains the iPCD cohort, which we described in detail in the original application. The cohort will be enriched with prospective data from national PCD registries and the national French prospective cohort RaDiCo PCD. An important new data source is FOLLOW-PCD, a standardised form for documentation of routine care, which will be used by iPCD cohort collaborators to document clinical visits. Its modular architecture includes patient-reported questionnaires on symptoms, exposures and lifestyle. Statistical methods have been described in detail in the SNSF 320030_173044 application.Significance: The project will be the first study on patients with PCD that has detailed standardised patient-reported clinical, environmental and lifestyle data available from large numbers of patients. Precise characterisation of the different clinical phenotypes in PCD will contribute to understanding the mechanisms behind the clinical heterogeneity of the disease and the factors that influence long-term course. This could inform management of patients, allowing for more tailored approaches based on each patient’s phenotype, including earlier diagnosis and development of targeted therapies.
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