Primary ciliary dyskinesia (PCD) presents with symptoms early in life and the disease course may be progressive, but longitudinal data on lung function are scarce. This multinational cohort study describes lung function trajectories in children, adolescents and young adults with PCD. We analysed data from 486 patients with repeated lung function measurements obtained between the age of 6 and 24 years from the International PCD Cohort and calculated z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio using the Global Lung Function Initiative 2012 references. We described baseline lung function and change of lung function over time and described their associations with possible determinants in mixed-effects linear regression models. Overall, FEV1, FVC and FEV1/FVC z-scores declined over time (average crude annual FEV1 decline was -0.07 z-scores), but not at the same rate for all patients. FEV1 z-scores improved over time in 21% of patients, remained stable in 40% and declined in 39%. Low body mass index was associated with poor baseline lung function and with further decline. Results differed by country and ultrastructural defect, but we found no evidence of differences by sex, calendar year of diagnosis, age at diagnosis, diagnostic certainty or laterality defect. Our study shows that on average lung function in PCD declines throughout the entire period of lung growth, from childhood to young adult age, even among patients treated in specialised centres. It is essential to develop strategies to reverse this tendency and improve prognosis.

Basel Institute for Clinical Epidemiology and Biostatistics Dept of Clinical Research University Hospital Basel University of Basel Basel Switzerland

Clinic for Paediatric Pneumology Allergology and Neonatology Hannover Medical School Hannover Germany

Danish PCD Centre Copenhagen Paediatric Pulmonary Service Copenhagen University Hospital Copenhagen Denmark

Dept of Clinical Medicine University of Copenhagen Copenhagen Denmark

Dept of Paediatric Pneumology University Children's Hospital of Ruhr University Bochum Bochum Germany

Dept of Paediatrics University Hospital Gasthuisberg Leuven Belgium

Dept of Pediatric Pulmonology Emma Children's Hospital Vrije Universiteit Amsterdam Amsterdam The Netherlands

Dept of Pediatric Pulmonology Hacettepe University Faculty of Medicine Ankara Turkey

Dept of Pediatric Pulmonology Marmara University School of Medicine Istanbul Turkey

Dept of Pediatrics Faculty of Medicine Tel Aviv University Tel Aviv Israel

Dept of Pediatrics University of Alberta Edmonton AB Canada

Dept of Pneumonology and Cystic Fibrosis Institute of Tuberculosis and Lung Disorders Rabka ‌ Zdrój Poland

Dept of Respiratory Medicine Concord Hospital Clinical School University of Sydney Sydney Australia

Dept of Translational Medical Sciences Federico 2 University Napoli Italy

Division of Paediatric Respiratory Medicine and Allergology Dept of Paediatrics Inselspital Bern University Hospital University of Bern Bern Switzerland

Host Defence Unit Royal Brompton and Harefield NHS Foundation Trust and Imperial College London London UK

Institute of Social and Preventive Medicine University of Bern Bern Switzerland

Medical School University of Cyprus Nicosia Cyprus

On behalf of the French Reference Centre for Rare Lung Diseases RespiRare

On behalf of the Swiss PCD Group

Paediatric Dept 2nd Faculty of Medicine Charles University Prague and University Hospital Motol Prague Czech Republic

Paediatric Dept of Allergy and Lung Diseases Oslo University Hospital Oslo Norway

Pediatric Pulmonology Dept APHP Hôpital Trousseau Sorbonne Université Centre de Recherche Saint Antoine Inserm UMR_S938 Paris France

Pediatric Pulmonology Unit and Cystic fibrosis Center Hadassah Medical Center and Faculty of Medicine Hebrew University of Jerusalem Jerusalem Israel

Primary Ciliary Dyskinesia Centre NIHR Respiratory Biomedical Research Centre University of Southampton and University Hospital Southampton UK

The PCD Israeli Consortium

These authors contributed equally to the manuscript

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