INTRODUCTION: Respiratory pathogens are frequently isolated from airway samples in primary ciliary dyskinesia (PCD) patients. Few studies have investigated associations between these pathogens and lung function, with current management based on evidence from cystic fibrosis. We investigated the association between commonly isolated respiratory pathogens and lung function in PCD patients. METHODS: Using a cross-sectional design, we prospectively collected clinical and concurrent microbiology data from 408 participants with probable or confirmed PCD, aged ≥5 years, from 12 countries. We used Global Lung Function Initiative 2012 references to calculate forced expiratory volume in 1 s (FEV1) z-scores. For 351 patients (86%) with complete data, we assessed the association of the four most frequently isolated pathogens with lung function by fitting multilevel linear models with country as random intercept, adjusted for age at diagnosis, age at lung function, use of antibiotic prophylaxis and body mass index z-scores. RESULTS: Individuals with Pseudomonas aeruginosa growth in culture had significantly lower FEV1 z-scores (β= -0.87, 95% CI -1.40- -0.34), adjusted for presence of Haemophilus influenzae, methicillin-sensitive Staphylococcus aureus and Streptococcus pneumoniae, and for covariates. When stratified by age, associations remained strong for adults but not for children. Results were similar when ciliary defects by transmission electron microscopy were included in the models and when restricting analysis to only confirmed PCD cases. CONCLUSIONS: We found that P. aeruginosa was associated with worse lung function in individuals with PCD, particularly adults. These findings suggest that it is prudent to aim for P. aeruginosa eradication in the first instance, and to treat exacerbations promptly in colonised patients.

AP HP Sorbonne Université Unité d'Exploration Fonctionnelle Respiratoire Hôpital Armand Trousseau and Sorbonne Université INSERM U938 Paris France

Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer Florence Italy

Children's Hospital and Research Institute Marienhospital Wesel Wesel Germany

Clinical and Experimental Sciences University of Southampton Faculty of Medicine Southampton UK

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

Danish PCD Centre Danish Paediatric Pulmonary Service Department of Paediatrics and Adolescent Medicine Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of CHROMETA Laboratory for Respiratory Diseases and Thoracic Surgery KU Leuven Leuven Belgium

Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark

Department of General Pediatrics University Hospital Muenster Muenster Germany

Department of Paediatric Pulmonology University Children's Hospital Ruhr University Bochum Katholisches Klinikum Bochum Bochum Germany

Department of Paediatrics Charles University 2nd Faculty of Medicine University Hospital in Motol Prague Czech Republic

Department of Pediatric Pulmonology Hacettepe University Faculty of Medicine Ankara Turkey

Department of Pediatric Pulmonology Marmara Universitesi Istanbul Turkey

Department of Pediatrics Division of Pediatric Pulmonology Ankara City Hospital Ankara Turkey

Department of Pediatrics Hospital de Santa Maria Centro Hospitalar Universitário Lisboa Norte and Faculty of Medicine University of Lisbon Lisbon Portugal

Department of Pediatrics University Hospital Leuven Leuven Belgium

Department of Respiratory Diseases University Hospitals Leuven Leuven Belgium

Department of Translational Medical Sciences Pediatric Pulmonology Federico 2 University Naples Italy

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

Faculty of Medicine Dentistry and Health Sciences Paediatrics University of Melbourne Melbourne Australia

FE Pediatría y Neumología Infantil Unidad de Neumología Infantil y Fibrosis Quística Hospital Clínico de Valencia Valencia Spain

Hospital Vall d'Hebron Neumología Infantil Barcelona Spain

Institute of Social and Preventive Medicine University of Bern Bern Switzerland

Medical School University of Cyprus Nicosia Cyprus

Primary Ciliary Dyskinesia Centre University Hospital Southampton NHS Foundation Trust Southampton UK

Respiratory and Cystic Fibrosis Unit Academic Pediatric Department Bambino Gesù Children Hospital IRCCS Rome Italy

Royal Brompton and Harefield NHS Foundation Trust Department of Paediatrics Primary Ciliary Dyskinesia Centre London UK

Royal Children's Hospital Respiratory Medicine Melbourne Australia

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