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Natural history, phenotypes and disease classification in primary ciliary dyskinesia

English title Natural history, phenotypes and disease classification in primary ciliary dyskinesia
Applicant Kühni Claudia
Number 173044
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 01.05.2017 - 30.04.2020
Approved amount 456'055.00
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Keywords (5)

phenotypes; multi-organ disease; rare disease; primary ciliary dyskinesia; childhood

Lay Summary (German)

Lead
Die primäre ziliäre Dyskinesie (PCD) ist eine seltene Lungenerkrankung mit gestörter Funktion der Flimmerhärchen in den Atemwegen. Es ist wenig bekannt zur Variabilität von Krankheitsbild und klinischem Verlauf. Diese Studie untersucht den Krankheitsverlauf in über 3000 Patienten mit PCD.
Lay summary

Inhalt und Ziele des Forschungsprojekts

PCD ist eine seltene Lungenkrankheit, bei welcher sich die Flimmerhärchen in den Atemwegen nicht richtig bewegen. Betroffene Personen entwickeln eine chronische Atemwegserkrankung mit dauerndem Husten und wiederholten Lungen- und Mittelohrentzündungen sowie Hörproblemen. Viele sind unfruchtbar. Ihre Lebensqualität ist eingeschränkt und die Lunge wird durch die Infekte geschädigt, so dass manche Sauerstoff oder eine Lungentransplantation benötigen. Weil PCD selten ist gibt es bisher wenig klinische Forschung.

Unter Schweizer Leitung wurden Daten zu über 3000 PCD Patienten aus 18 Ländern gesammelt. Dieser weltweit grösste Datensatz soll nun ausgewertet werden. Die vorliegende Studie will die Häufigkeit der verschiedenen Flimmerhaar-Defekte beschreiben und untersuchen, ob sich diese Patienten auch klinisch unterscheiden. Ausserdem soll der Krankheitsverlauf aufgezeigt und Faktoren identifiziert werden, welche die Prognose beeinflussen.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Dieses Projekt bietet eine einzigartige Möglichkeit in einem grossen Datensatz die klinische Epidemiologie einer seltenen Lungenkrankheit, zu erforschen. Langfristig kann dadurch die Behandlung der betroffenen Patienten an ihren Phänotyp angepasst und individueller geplant werden, was ihre Lebensqualität und Lebenserwartung verbessert.

Direct link to Lay Summary Last update: 05.04.2017

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia (BESTCILIA): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial
Kobbernagel Helene E, Buchvald Frederik F, Haarman Eric G, Casaulta Carmen, Collins Samuel A, Hogg Claire, Kuehni Claudia E, Lucas Jane S, Moser Claus E, Quittner Alexandra L, Raidt Johanna, Rosthøj Susanne, Sørensen Anne L, Thomsen Kim, Werner Claudius, Omran Heymut, Nielsen Kim G (2020), Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia (BESTCILIA): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial, in The Lancet Respiratory Medicine, 8(5), 493-505.
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.
Prevalence and course of disease after lung resection in primary ciliary dyskinesia: a cohort & nested case-control study
Kouis Panayiotis, Goutaki Myrofora, Halbeisen Florian S., Gioti Ifigeneia, Middleton Nicos, Amirav Israel, Barbato Angelo, Behan Laura, Boon Mieke, Emiralioglu Nagehan, Haarman Eric G., Karadag Bulent, Koerner-Rettberg Cordula, Lazor Romain, Loebinger Michael R., Maitre Bernard, Mazurek Henryk, Morgan Lucy, Nielsen Kim Gjerum, Omran Heymut, Özçelik Ugur, Price Mareike, Pogorzelski Andrzej, Snijders Deborah, et al. (2019), Prevalence and course of disease after lung resection in primary ciliary dyskinesia: a cohort & nested case-control study, in Respiratory Research, 20(1), 212-212.
Time trends in diagnostic testing for primary ciliary dyskinesia in Europe
Halbeisen Florian S., Shoemark Amelia, Barbato Angelo, Boon Mieke, Carr Siobhan, Crowley Suzanne, Hirst Rob, Karadag Bulent, Koerner-Rettberg Cordula, Loebinger Michael R., Lucas Jane S., Maitre Bernard, Mazurek Henryk, Özçelik Uğur, Martinů Vendula, Schwerk Nicolaus, Thouvenin Guillaume, Tschanz Stefan A., Yiallouros Panayiotis, Goutaki Myrofora, Kuehni Claudia E. (2019), Time trends in diagnostic testing for primary ciliary dyskinesia in Europe, in European Respiratory Journal, 54(4), 1900528-1900528.
The Swiss Primary Ciliary Dyskinesia registry: objectives, methods and first results
GoutakiMyrofora, Eich Marc O, HalbeisenFlorian, Barben Juerg, CasaultaCarmen, ClarenbachCristian, HafenGaudenz, LatzinPhilipp, RegameyNicolas, Lazor Romain, TschanzStefan, ZanolariMaura, MaurerElisabeth, KuehniClaudia E (2019), The Swiss Primary Ciliary Dyskinesia registry: objectives, methods and first results, in Swiss Medical Weekly, 20004.
Proceedings of the 3rd BEAT-PCD Conference and 4th PCD Training School
Farley Hannah, Rubbo Bruna, Bukowy-Bieryllo Zuzanna, Fassad Mahmoud, Goutaki Myrofora, Harman Katharine, Hogg Claire, Kuehni Claudia E., Lopes Susana, Nielsen Kim G., Norris Dominic P., Reula Ana, Rumman Nisreen, Shoemark Amelia, Wilkins Hannah, Wisse Agatha, Lucas Jane S., Marthin June K. (2018), Proceedings of the 3rd BEAT-PCD Conference and 4th PCD Training School, in BMC Proceedings, 12(S16), 64-64, Springer Nature, BMC Proceedings 12(S16), 64-64.
Structural and Functional Lung Impairment in Primary Ciliary Dyskinesia. Assessment with Magnetic Resonance Imaging and Multiple Breath Washout in Comparison to Spirometry
Nyilas Sylvia, Bauman Grzegorz, Pusterla Orso, Sommer Gregor, Singer Florian, Stranzinger Enno, Heyer Christoph, Ramsey Kathryn, Schlegtendal Anne, Benzrath Stefanie, Casaulta Carmen, Goutaki Myrofora, Kuehni Claudia E., Bieri Oliver, Koerner-Rettberg Cordula, Latzin Philipp (2018), Structural and Functional Lung Impairment in Primary Ciliary Dyskinesia. Assessment with Magnetic Resonance Imaging and Multiple Breath Washout in Comparison to Spirometry, in Annals of the American Thoracic Society, 15(12), 1434-1442.
Management of primary ciliary dyskinesia: current practice and future perspectives
Kuehni Claudia E., Goutaki Myrofora, Rubbo Bruna, Lucas Jane S. (2018), Management of primary ciliary dyskinesia: current practice and future perspectives, in Polverino Eva, Aliberti Stefano, Chalmers James D. (ed.), European Respiratory Society, Sheffield, United Kingdom, 282-299.
Lung function in patients with primary ciliary dyskinesia: an iPCD Cohort study
Halbeisen Florian S., Goutaki Myrofora, Spycher Ben D., Amirav Israel, Behan Laura, Boon Mieke, Hogg Claire, Casaulta Carmen, Crowley Suzanne, Haarman Eric G., Karadag Bulent, Koerner-Rettberg Cordula, Loebinger Michael R., Mazurek Henryk, Morgan Lucy, Nielsen Kim G., Omran Heymut, Santamaria Francesca, Schwerk Nicolaus, Thouvenin Guillaume, Yiallouros Panayiotis, Lucas Jane S., Latzin Philipp, Kuehni Claudia E. (2018), Lung function in patients with primary ciliary dyskinesia: an iPCD Cohort study, in European Respiratory Journal, 52(2), 1801040-1801040.
Proceedings of the 2nd BEAT-PCD conference and 3rd PCD training school: part 1
Halbeisen Florian, Hogg Claire, Alanin Mikkel C., Bukowy-Bieryllo Zuzanna, Dasi Francisco, Duncan Julie, Friend Amanda, Goutaki Myrofora, Jackson Claire, Keenan Victoria, Harris Amanda, Hirst Robert A., Latzin Philipp, Marsh Gemma, Nielsen Kim, Norris Dominic, Pellicer Daniel, Reula Ana, Rubbo Bruna, Rumman Nisreen, Shoemark Amelia, Walker Woolf T., Kuehni Claudia E., Lucas Jane S. (2018), Proceedings of the 2nd BEAT-PCD conference and 3rd PCD training school: part 1, in BMC Proceedings, 12(S2), 1-1, Springer Nature, BMC Proceedings 12(S2), 1-1.
Growth and nutritional status, and their association with lung function: a study from the international Primary Ciliary Dyskinesia Cohort
Goutaki Myrofora, Halbeisen Florian S., Spycher Ben D., Maurer Elisabeth, Belle Fabiën, Amirav Israel, Behan Laura, Boon Mieke, Carr Siobhan, Casaulta Carmen, Clement Annick, Crowley Suzanne, Dell Sharon, Ferkol Thomas, Haarman Eric G., Karadag Bulent, Knowles Michael, Koerner-Rettberg Cordula, Leigh Margaret W., Loebinger Michael R., Mazurek Henryk, Morgan Lucy, Nielsen Kim G., Phillipsen Maria, Sagel Scott D, Santamaria Francesca, Schwerk Nicolaus, Yiallouros Panayiotis, Lucas Jane S, Kuehni Claudia E (2017), Growth and nutritional status, and their association with lung function: a study from the international Primary Ciliary Dyskinesia Cohort, in European Respiratory Journal, 50(6), 1701659-1701659.
Diagnosis of primary ciliary dyskinesia: summary of the ERS Task Force report
Kuehni Claudia E., Lucas Jane S. (2017), Diagnosis of primary ciliary dyskinesia: summary of the ERS Task Force report, in Breathe, 13(3), 166-178.
The time is right for an international PCD disease registry: insight and ongoing research activities
GoutakiMyrofora, HalbeisenFlorian S, KuehniClaudia E (2017), The time is right for an international PCD disease registry: insight and ongoing research activities, in European Respiratory Society, 49, 1700357.
Primary Ciliary Dyskinesia
RubboBruna, GoutakiMyrofora, LucasJane S., Primary Ciliary Dyskinesia, in Midulla Fabio, Eber Ernst (ed.), European Respiratory Society, Sheffield, UK.
Pulmonary exacerbations in patients with primary ciliary dyskinesia: an expert consensus definition for use in clinical trials
Lucas Jane S, Gahleitner Florian, Amorim Adelina, Boon Mieke, Brown Philippa, Constant Carolina, Cook Simon, Crowley Suzanne, Destouches Damien MS, Eber Ernst, Mussaffi Huda, Haarman Eric, Harris Amanda, Koerner-Rettberg Cordula, Kuehni Claudia E, Latzin Philipp, Loebinger Michael R., Lorent Natalie, Maitre Bernard, Moreno-Galdó Antonio, Nielsen Kim G, Özçelik Uğur, Philipsen Lue KD, Pohunek Petr, Polverino Eva, Rademacher Jessica, Robinson Phil, Snijders Deborah, Yiallouros Panayiotis, Carr Siobhán B, Pulmonary exacerbations in patients with primary ciliary dyskinesia: an expert consensus definition for use in clinical trials, in ERJ Open Research, 00147.
Registries and collaborative studies for Primary Ciliary Dyskinesia in Europe
Ardura-Garcia Cristina, Goutaki Myrofora, Carr Siobhan, Crowley Suzanne, Halbeisen Florian, Nielsen Kim, Pennekamp Petra, Raidt Johanna, Thouvenin Guillaume, Yiallouros Panayiotis, Omran Heymut, Kuehni Claudia, Registries and collaborative studies for Primary Ciliary Dyskinesia in Europe, in ERJ Open Res.
Spirometric indices in primary ciliary dyskinesia: systematic review and meta-analysis
Halbeisen Florian S, Jose Anu, de JongCarmen, Nyilas Sylivia, LatzinPhilipp, KuehniClaudia E, GoutakiMyrofora, Spirometric indices in primary ciliary dyskinesia: systematic review and meta-analysis, in ERJ Open Research.

Collaboration

Group / person Country
Types of collaboration
Primary Ciliary Dyskinesia Centre, NIHR Respiratory Biomedical Research Centre, University of Southa Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Faculty of Pharmacy, University Business Academy, Novi Sad Serbien (Europe)
- Publication
Clinic for Paediatric Pulmonology, Allergiology and Neonatology, Hannover Medical School, Hannover Germany (Europe)
- Publication
Hopital intercommunal de Créteil, Service de Pneumologie, DHU ATVB, Université Paris Est Créteil France (Europe)
- Publication
Departamento de Pediatría, Fundación Santa Fe, Clínica de Neumología Pediátrica Compensar, Bogota Colombia (South America)
- Publication
Genetic Disorders of Mucociliary Clearance Consortium United States of America (North America)
- Publication
Italian PCD Consortium Italy (Europe)
- Publication
Host Defence Unit, Royal Brompton and Harefield NHS Foundation Trust, London, Great Britain and Northern Ireland (Europe)
- Publication
Unit for Paediatric Heart, Lung and Allergic Diseases, Rikshospitalet, Oslo Norway (Europe)
- Publication
Dept of Paediatric Pneumology, University Children's Hospital of Ruhr University Bochum, Bochum Germany (Europe)
- Publication
Paediatric Pulmonary Department, Trousseau Hospital APHP, Sorbonne Universities, Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Danish PCD Centre, Paediatric Pulmonary Service, Copenhagen University Hospital, Copenhagen Denmark (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dept of Paediatrics, University Hospital Gasthuisberg, Leuven Belgium (Europe)
- Publication
Dept of Paediatric Pulmonology, Marmara University, School of Medicine, Istanbul Turkey (Europe)
- Publication
Medical School, University of Cyprus, Nicosia Cyprus (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Dept of Respiratory Medicine, Concord Hospital Clinical School, University of Sydney, Sydney Australia (Oceania)
- Publication
Dept of Pediatrics, Faculty of Medicine, Bar IIan University, Ramat Gan Israel (Asia)
- Publication
Dept of General Paediatrics and Adolescent Medicine, University Hospital Muenster, Muenster, Germany Germany (Europe)
- Publication
Centro Respiratorio, Hospital de Niños Ricardo Gutierrez, Buenos Aires Argentina (South America)
- Publication
Dept of Pneumonology and Cystic Fibrosis, Institute of Tuberculosis and Lung Disorders, Rabka-Zdrój Poland (Europe)
- Publication
Department of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara Turkey (Europe)
- Publication
Dept of Paediatrics, Primary Ciliary Dyskinesia Centre, Royal Brompton and Harefield Foundation Trus Great Britain and Northern Ireland (Europe)
- Publication
Dept of Pediatric Pulmonology, VU University Medical Center, Amsterdam Netherlands (Europe)
- Publication
Pediatric Department, Charles University Prague and University Hospital Motol, Prague Czech Republic (Europe)
- Publication
Paediatric Respiratory Medicine, Children's University Hospital of Bern, University of Bern, Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Paediatric Pulmonology, 3rd Dept of Paediatrics, National and Kapodistrian University of Athens Greece (Europe)
- Publication
Dept of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester Great Britain and Northern Ireland (Europe)
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
European Respiratory Society Annual Conference 2019 Poster The Swiss Primary Ciliary Dyskinesia registry: an update 28.09.2019 Madrid, Spain Halbeisen Florian; Goutaki Myrofora; Kühni Claudia;
Joint Annual Conference of the Swiss Society of Pulmonology 2019 Talk given at a conference Epidemiology of PCD – improving data on a rare disease 09.05.2019 Montreaux, Switzerland Kühni Claudia;
4th BEAT-PCD Conference/5th PCD Training School Talk given at a conference Using the FOLLOW-PCD clinical form and QOL-PCD in clinical care and research 26.03.2019 Poznan, Poland Goutaki Myrofora;
4th BEAT-PCD Conference/5th PCD Training School Talk given at a conference Applying for ERS Fellowships, workshop 26.03.2019 Poznan, Poland Goutaki Myrofora; Kühni Claudia;
4th BEAT-PCD Conference/5th PCD Training School Talk given at a conference Nasal nitric oxide (nNO) in the diagnostic workup of PCD: Clinical decisions and hand-on workshop 26.03.2019 Poznan, Poland Kühni Claudia;
4th BEAT-PCD Conference/5th PCD Training School Talk given at a conference Highlights of BEAT-PCD WG2: Epidemiology 26.03.2019 Poznan, Poland Kühni Claudia; Goutaki Myrofora;
10ème journée RespiRare Talk given at a conference Primary ciliary dyskinesia and epidemiological studies: the experience of the first international cohort 14.01.2019 Paris, France Goutaki Myrofora;
European Respiratory Society Annual Conference 2018 Talk given at a conference Clinical characteristics of PCD (invited talk at Symposium: Recent advances in primary ciliary dyskinesia 15.09.2018 Paris, France Kühni Claudia;
European Respiratory Society Annual Conference 2018 Poster Prevalence and Impact of Lung Resection in Primary Ciliary Dyskinesia: a cohort and nested case-control study 15.09.2018 Paris, France Halbeisen Florian; Goutaki Myrofora; Kühni Claudia;
European Respiratory Society Annual Conference 2018 Poster Neonatal manifestations in Primary Ciliary Dyskinesia: a multinational cohort study 15.09.2018 Paris, France Goutaki Myrofora; Halbeisen Florian; Kühni Claudia; Wisse Agatha;
Joint Annual Conference of the Swiss Society of Pneumology 2018 Poster Evolution of diagnostics in primary ciliary dyskinesia 24.05.2018 St. Gallen, Switzerland Kühni Claudia; Halbeisen Florian; Goutaki Myrofora;
59. Kongress der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. Talk given at a conference Primary Ciliary Dyskinesia: Epidemiology and setting up of registries 14.03.2018 Dresden, Germany Goutaki Myrofora;
PCD Medical Board Meeting Talk given at a conference International studies on Primary Ciliary Dyskinesia 09.03.2018 London, Great Britain and Northern Ireland Goutaki Myrofora;
3rd BEAT-PCD Conference/4th PCD Training School Talk given at a conference Nasal nitric oxide (nNO) in the diagnostic workup of PCD: Clinical decisions and hands-on workshop 06.02.2018 Lisbon, Portugal Kühni Claudia;
European Respiratory Society Annual Conference 2017 Poster Towards standardized follow-up care for patients with Primary Ciliary Dyskinesia (PCD) 09.09.2017 Milan, Italy Kühni Claudia; Halbeisen Florian; Goutaki Myrofora;
European Respiratory Society Annual Conference 2017 Poster Evolution of Primary Ciliary Dyskinesia (PCD) diagnostic testing in Europe 09.09.2017 Milan, Italy Goutaki Myrofora; Halbeisen Florian; Kühni Claudia;


Self-organised

Title Date Place
pre-ERS BEAT-PCD meeting 2019 28.09.2019 Madrid, Spain
4th BEAT-PCD Conference/5th PCD Training School 26.03.2019 Poznan, Poland
pre-ERS BEAT-PCD meeting 2018 15.09.2018 Paris, France
Annual Swiss PCD meeting 28.06.2018 Bern, Switzerland
pre-ERS BEAT-PCD meeting 2017 09.09.2017 Milan, Italy

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Annual Swiss PCD Patients Organization meeting 2019 Talk 09.03.2019 Zurich, Switzerland Wisse Agatha; Halbeisen Florian;
Annual Swiss PCD Patients Organization meeting Talk 17.03.2018 Olten, Switzerland Halbeisen Florian; Wisse Agatha;


Communication with the public

Communication Title Media Place Year
New media (web, blogs, podcasts, news feeds etc.) BEAT-PCD Newsletter International 2017

Awards

Title Year
Award for outstanding contributions to the BEAT-PCD Cost Action 2019
European Respiratory Society Short-Term Research Fellowship awarded for the project: Identifying knowledge gaps for primary ciliary dyskinesia research: combining experts’ and patients’ perspective 2018
Award for outstanding contributions to the BEAT-PCD Cost Action network. 2017
BEAT-PCD COST Action Short Scientific Mission grant, awarded for the application: ENT symptoms in patients with PCD- development of epidemiological studies. 2017
Ewald Weibel Prize for lung research in Switzerland 2017
Manes-Kartagener prize for outstanding research in the field of primary ciliary dyskinesia at the 39th annual meeting of the Gesellschaft für Pädiatrische Pneumologie 2017

Associated projects

Number Title Start Funding scheme
163311 Integrating the impact of genetic and environmental factors on trajectories of respiratory disease from birth to school age 01.10.2015 Project funding (Div. I-III)
192804 Natural history, phenotypes and disease classification in primary ciliary dyskinesia (phase 2) 01.05.2020 Project funding (Div. I-III)
162820 Phenotypes and prognostic modelling in childhood asthma: moving towards clinical applications 01.10.2015 Project funding (Div. I-III)
163452 Socio-Economic Position, Pregnancy Outcomes and Infant Mortality: The Swiss National Cohort 01.07.2016 Project funding (special)

Abstract

Background. Primary ciliary dyskinesia (PCD) is a rare, genetic, multisystem disease affecting about 1 in 10,000 people. In PCD, the respiratory cilia are dysfunctional and mucus is not properly cleared, which leads to progressive upper and lower airway diseases and bronchiectasis, hearing impairment, and chronic sinusitis. PCD may affect other ciliated organs, causing situs inversus, congenital heart defects, infertility, renal disease, or hydrocephalus. PCD is heterogeneous: currently, mutations in >30 genes are known to account for about 65% of cases and a variety of ultrastructural and functional defects. There are few data on the clinical epidemiology of PCD. We lack knowledge about the spectrum and severity of the disease, its long-term course and risk factors, the variability of phenotypes, and responses to treatment. Our group has extensive expertise in analysis of longitudinal data of other diseases, in particular asthma and childhood cancer. We have experience in developing prediction models and phenotype definitions. The international PCD cohort (iPCD), set up in the framework of the EU FP7 project BESTCILIA and the COST Action BEAT-PCD, provides a unique opportunity to apply this expertise to a rare disease.This project aims to fill important knowledge gaps in the epidemiology of PCD. We propose to:1)Describe the clinical picture and natural history of PCD by characterising: a.The frequency of different defects in ciliary ultrastructure and function b.The prevalence and severity of clinical symptoms and physiological abnormalities, and how these vary by age, sex, age at diagnosis, clinical centre, country, and calendar period c.Disease progression over time, mortality, lung function, and predictors of favourable and poor prognosis2)Distinguish distinct disease subgroups (phenotypes) by latent class analysis, assess the utility of defined phenotypes by comparing long-term outcomes, and propose a simple disease classification model for use in clinical practice and intervention studies. Methods, study population. The iPCD cohort, hosted at the Institute of Social and Preventive Medicine (ISPM), Bern, currently contains data from 3077 PCD patients aged 0 to 77 years from 18 countries. The core dataset, available for all patients, has demographic and baseline clinical data, and results from diagnostic tests including detailed information on ciliary ultrastructure and function. Additional modules, available for several hundred patients, include data on neonatal symptoms, growth, lung function, imaging, sputum microbiology, and treatments. The dataset is continuously updated by participating centres.Analysis. We will analyse the outcomes of interest using one-stage random-effects regression models that combine individual patient data from different centres, and account for clustering of patients within centres. To define phenotypes, we will apply latent class analysis, a model-based clustering method, to data on ciliary defects, genetic data, and physiological and clinical characteristics. We will internally validate phenotypes by assessing robustness of model parameters across subsets of the population. Finally, we will simplify the model rules using classification tree methods such as CART (Classification and Regression Tree) to obtain a clinically useful classification system. Significance. This project exploits data from a multicentre longitudinal cohort, which is 10 to 100 times larger than any PCD dataset used so far, to generate the first representative estimates of burden and spectrum of clinical manifestations in children and adults with PCD. Knowledge of the natural history and risk factors for prognosis will improve our understanding of the disease. Evidence for distinct disease phenotypes, derived in an objective, data-driven manner, will inform future interventional and observational studies of response to treatments. Finally, our project will help physicians adapt therapies to individual patients and improve long-term outcomes.
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