A BEAT-PCD consensus statement: a core outcome set for pulmonary disease interventions in primary ciliary dyskinesia

Renate Kos¹, Myrofora Goutaki^{2

3}, Helene E Kobbernagel^{4

5}, Bruna Rubbo^{6

7}, Amelia Shoemark⁸, Stefano Aliberti^{9

10}, Josje Altenburg¹, Pinelopi Anagnostopoulou¹¹, Rodrigo A Athanazio¹², Nicole Beydon^{13

14}, Sharon D Dell^{15

16}, Nagehan Emiralioglu¹⁷, Thomas W Ferkol¹⁸, Michael R Loebinger^{19

20}, Natalie Lorent²¹, Bernard Maître²², June Marthin⁴, Lucy C Morgan²³, Kim G Nielsen^{4

5}, Felix C Ringshausen^{24

25}, Michal Shteinberg^{26

27}, Harm A W M Tiddens^{28

29

30}, Anke H Maitland-Van der Zee^{1

31}, James D Chalmers⁸, Jane S A Lucas^{32

33}, Eric G Haarman³¹

Affiliations

¹ Dept of Pulmonary Medicine, Amsterdam University Medical Centres - loc. AMC, University of Amsterdam, Amsterdam, The Netherlands.
² Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
³ Paediatric Respiratory Medicine, Children's University Hospital of Bern, University of Bern, Bern, Switzerland.
⁴ Danish Primary Ciliary Dyskinesia Centre, Paediatric Pulmonary Service, Dept of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁵ Dept of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁶ School of Health Sciences, University of Southampton, Southampton, UK.
⁷ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁸ Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK.
⁹ Dept of Biomedical Sciences, Humanitas University, Milan, Italy.
¹⁰ Respiratory Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
¹¹ Medical School, University of Cyprus, Nicosia, Cyprus.
¹² Heart Institute (InCor) Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Brazil.
¹³ Pulmonary Division, Sorbonne Université, INSERM U938, Paris, France.
¹⁴ Unité d'Exploration Fonctionnelle Respiratoire, Hôpital Armand-Trousseau, Paris, France.
¹⁵ Dept of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
¹⁶ Pediatric Respiratory Medicine, Provincial Health Services Authority, BC Children's Hospital, Vancouver, Canada.
¹⁷ Dept of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
¹⁸ Dept of Pediatrics, University of North Carolina School of Medicine and Marsico Lung Institute, Chapel Hill, NC, USA.
¹⁹ Dept of Respiratory Medicine, Royal Brompton and Harefield Hospitals, London, UK.
²⁰ National Heart and Lung Institute, Imperial College London, London, UK.
²¹ Dept of Pediatrics, University Hospital Leuven, Leuven, Belgium.
²² Service de Pneumologie, Hôpital Henri Mondor et Centre Hospitalier Intercommunal de Créteil, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France.
²³ Dept of Microbiology and Infectious Diseases, Concord Repatriation and General Hospital, NSW Health Pathology, Sydney, Australia.
²⁴ Dept of Respiratory Medicine, Hannover Medical School (MHH), Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
²⁵ European Reference Network for Rare and Complex Lung Diseases (ERN-LUNG), Frankfurt am Main, Germany.
²⁶ Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
²⁷ Pulmonology Institute and CF Center, Carmel Medical Center, Haifa, Israel.
²⁸ Dept of Pediatric Pulmonology and Allergology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.
²⁹ Dept of Radiology, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands.
³⁰ Thirona, Nijmegen, The Netherlands.
³¹ Dept of Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Amsterdam University Medical Centres, Amsterdam, The Netherlands.
³² Faculty of Medicine, University of Southampton, School of Clinical and Experimental Sciences, Southampton, UK.
³³ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

PMID: 38196895
PMCID: PMC10772902
DOI: 10.1183/23120541.00115-2023

A BEAT-PCD consensus statement: a core outcome set for pulmonary disease interventions in primary ciliary dyskinesia

Renate Kos et al. ERJ Open Res. 2024.

. 2024 Jan 8;10(1):00115-2023.

doi: 10.1183/23120541.00115-2023. eCollection 2024 Jan.

Authors

Affiliations

¹ Dept of Pulmonary Medicine, Amsterdam University Medical Centres - loc. AMC, University of Amsterdam, Amsterdam, The Netherlands.
² Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
³ Paediatric Respiratory Medicine, Children's University Hospital of Bern, University of Bern, Bern, Switzerland.
⁴ Danish Primary Ciliary Dyskinesia Centre, Paediatric Pulmonary Service, Dept of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁵ Dept of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁶ School of Health Sciences, University of Southampton, Southampton, UK.
⁷ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁸ Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK.
⁹ Dept of Biomedical Sciences, Humanitas University, Milan, Italy.
¹⁰ Respiratory Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
¹¹ Medical School, University of Cyprus, Nicosia, Cyprus.
¹² Heart Institute (InCor) Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Brazil.
¹³ Pulmonary Division, Sorbonne Université, INSERM U938, Paris, France.
¹⁴ Unité d'Exploration Fonctionnelle Respiratoire, Hôpital Armand-Trousseau, Paris, France.
¹⁵ Dept of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
¹⁶ Pediatric Respiratory Medicine, Provincial Health Services Authority, BC Children's Hospital, Vancouver, Canada.
¹⁷ Dept of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
¹⁸ Dept of Pediatrics, University of North Carolina School of Medicine and Marsico Lung Institute, Chapel Hill, NC, USA.
¹⁹ Dept of Respiratory Medicine, Royal Brompton and Harefield Hospitals, London, UK.
²⁰ National Heart and Lung Institute, Imperial College London, London, UK.
²¹ Dept of Pediatrics, University Hospital Leuven, Leuven, Belgium.
²² Service de Pneumologie, Hôpital Henri Mondor et Centre Hospitalier Intercommunal de Créteil, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France.
²³ Dept of Microbiology and Infectious Diseases, Concord Repatriation and General Hospital, NSW Health Pathology, Sydney, Australia.
²⁴ Dept of Respiratory Medicine, Hannover Medical School (MHH), Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
²⁵ European Reference Network for Rare and Complex Lung Diseases (ERN-LUNG), Frankfurt am Main, Germany.
²⁶ Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
²⁷ Pulmonology Institute and CF Center, Carmel Medical Center, Haifa, Israel.
²⁸ Dept of Pediatric Pulmonology and Allergology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.
²⁹ Dept of Radiology, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands.
³⁰ Thirona, Nijmegen, The Netherlands.
³¹ Dept of Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Amsterdam University Medical Centres, Amsterdam, The Netherlands.
³² Faculty of Medicine, University of Southampton, School of Clinical and Experimental Sciences, Southampton, UK.
³³ Primary Ciliary Dyskinesia Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

PMID: 38196895
PMCID: PMC10772902
DOI: 10.1183/23120541.00115-2023

Abstract

Background: Consistent use of reliable and clinically appropriate outcome measures is a priority for clinical trials, with clear definitions to allow comparability. We aimed to develop a core outcome set (COS) for pulmonary disease interventions in primary ciliary dyskinesia (PCD).

Methods: A multidisciplinary international PCD expert panel was set up. A list of outcomes was created based on published literature. Using a modified three-round e-Delphi technique, the panel was asked to decide on relevant end-points related to pulmonary disease interventions and how they should be reported. First, inclusion of an outcome in the COS was determined. Second, the minimum information that should be reported per outcome. The third round finalised statements. Consensus was defined as ≥80% agreement among experts.

Results: During the first round, experts reached consensus on four out of 24 outcomes to be included in the COS. Five additional outcomes were discussed in subsequent rounds for their use in different subsettings. Consensus on standardised methods of reporting for the COS was reached. Spirometry, health-related quality-of-life scores, microbiology and exacerbations were included in the final COS.

Conclusion: This expert consensus resulted in a COS for clinical trials on pulmonary health among people with PCD.

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Conflict of interest statement

Conflict of interest: S. Aliberti has received fees outside of this work from Insmed, Zambon, AstraZeneca, CSL Behring GmbH, Grifols, Fondazione Internazionale MENARINI, MSD Italia S.r.l., Brahms, Physioassist SAS and GlaxoSmithKline. S.D. Dell has received grants outside of this work from Boehringer Ingelheim, Vertex and Sanofi, and she owns the copyright to the PCD-QOL Questionnaires. T.W. Ferkol has received consulting fees from Translate Bio and Arrowhead Pharmaceuticals. R.A. Athanazio has received personal fees outside of this work from Astrazeneca, Chiesi, GSK, Omron, Sanofi, Vertex and Zambon. K.G. Nielsen is part of the European Reference Network on respiratory diseases (ERN-LUNG) and director of PCD CTN. F.C. Ringshauen has received fees outside of this work from AstraZeneca, Boehringer Ingelheim, Celtaxsys, Corbus, Insmed, Novartis, Parion, University of Dundee, Vertex and Zambon. M. Shteinberg has received consulting fees from AstraZeneca, Boehringer Ingelheim, Dexcel, Kamada, Synchrony Medical, Trumed and Zambon. J.D. Chalmers has received grants outside of this work from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Gilead Sciences, Grifols, Insmed, Janssen, Novartis, Pfizer and Zambon; and is an associate editor of this journal. The remaining authors have nothing to disclose.

Figures

**FIGURE 1**
Results for selection of most suitable outcome parameters by the expert panel during round two, revisiting outcomes that did not reach consensus in round one. To be considered a parameter of interest, agreement had to be >80% among experts (black line). All answer options except “not relevant” and “other” were counted towards agreement. COS: core outcome set; PCD: primary ciliary dyskinesia; HRCT: high-resolution computed tomography; CT: computed tomography.

**FIGURE 2**
Results for agreement on the minimum that should be performed/reported for all outcomes in the core outcome set, from round 2. Experts used a five-point Likert scale to report agreement and used multiple choice boxes to indicate parameters of interest. Consensus demanded an 80% agreement (black line), including both the answer options “agree” and “strongly agree” or a checked box; outcome parameters that reached consensus are indicated in bold. PCD: primary ciliary dyskinesia; HRQoL: health-related quality of life; BEAT-PCD: Better Experimental Approaches to Treat Primary Ciliary Dyskinesia; QOL-PCD: Quality of Life instrument for Primary Ciliary Dyskinesia; SF36: 36-Item Short Form Health Survey; SGRQ: St George's Respiratory Questionnaire; FEV₁: forced expiratory volume in 1 s; GLI: Global Lung Initiative; FVC: forced vital capacity; FEF_25–75%: forced expiratory flow at 25–75% of FVC; *S. aureus*: *Staphylococcus aureus*; *P. aeruginosa*: *Pseudomonas aeruginosa*; *H. influenzae*: *Haemophilus influenzae*.

**FIGURE 3**
Results from round three, on choice of standardised method for reporting of outcomes. Experts were asked to choose between two exacerbation definitions, followed by the question whether they agreed or disagreed that these parameters should be included in the core outcome set. Outcome parameters that reached consensus are indicated in bold. BEAT-PCD: Better Experimental Approaches to Treat Primary Ciliary Dyskinesia; MSSA: methicillin-sensitive *Staphylococcus aureus*; MRSA: methicillin-resistant *S. aureus*; NTM: nontuberculous mycobacteria.

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A BEAT-PCD consensus statement: a core outcome set for pulmonary disease interventions in primary ciliary dyskinesia

Affiliations

A BEAT-PCD consensus statement: a core outcome set for pulmonary disease interventions in primary ciliary dyskinesia

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources