BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by dysfunction of motile cilia. Symptoms include recurrent and chronic airway infections which can lead to deteriorating lung function and inflammatory destructive lung disease in the form of persistent atelectasis and bronchiectasis. Routine blood testing may be used as a tool for disease monitoring and management. However, currently there are no consensus-based guidelines within the field of PCD. BEAT-PCD together with the ERN-LUNG PCD-Clinical Trial Network aimed to develop an international expert consensus statement on which routine blood tests should be conducted in patients with PCD. METHODS: An international panel of 33 PCD experts from 17 countries was established to generate consensus on routine blood testing in PCD. A modified Delphi technique with three e-survey rounds was used to reach consensus, which was defined as ≥80% agreement for each statement. Two patient representatives were included in the consensus process. RESULTS: The expert panel reached consensus on 51 out of 101 statements (50%) on routine blood testing in children and adults with PCD to be performed at diagnosis, annually and on exacerbation. The statements include biomarkers for inflammation, haemoglobin, iron status, vitamin D, immune function, inhalant allergies, liver and kidney function, and allergic bronchopulmonary aspergillosis. CONCLUSIONS: This is the first international consensus on routine blood testing in PCD. It highlights blood tests that may be relevant to perform at diagnosis, annually and on exacerbation in people with PCD. Further research on the clinical usefulness of routine blood testing in PCD is needed.

Association Dyskinésie Ciliaire Primitive St Etienne France

Berlin Institute of Health at Charité Universitätsmedizin Berlin Berlin Germany

Centre de Référence des Maladies Respiratoires Rares de l'Enfant Service de Pneumologie Pédiatrique Hospices Civils de Lyon Lyon France

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

Danish PCD Centre Copenhagen Department of Infectious Diseases Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

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

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Development and Regeneration Woman and Child Unit KU Leuven Leuven Belgium

Department of General Paediatrics University Children's Hospital Muenster Muenster Germany

Department of Paediatric Pneumology University Children's Hospital Bochum Bochum Germany

Department of Paediatrics Division of Paediatric Pulmonology Allergology and Endocrinology Medical University of Vienna Vienna Austria

Department of Pediatric Pulmonology Hacettepe University Medical Faculty Ankara Turkiye

Department of Pediatric Respiratory Medicine Immunology and Critical Care Medicine Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin Berlin Germany

Department of Pediatrics Pediatric Pulmonology University Hospital Leuven Belgium

Department of Pediatrics University Hospital of Pisa Pisa Italy

Department of Pneumonology and Cystic Fibrosis National Tuberculosis and Lung Diseases Institute Rabka Zdrój Poland

Department of Pulmonary Medicine Amsterdam University Medical Centre location AMC University of Amsterdam Amsterdam The Netherlands

Department of Respiratory Medicine and Infectious Diseases Hannover Medical School and Biomedical Research in End Stage and Obstructive Lung Disease Hannover German Center for Lung Research Hannover Germany

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

Division of Pediatric Pulmonology Marmara University Istanbul Turkey

European Reference Network on Rare and Complex Respiratory Diseases Frankfurt Germany

German Center for Lung Research associated partner site Berlin Germany

Leeds Institute of Medical Research University of Leeds Leeds UK

Macquarie University Hospital Sydney Australia

Medical School University of Cyprus Nicosia Cyprus

North of England PCD Management Service Leeds Teaching Hospitals NHS Trust Leeds UK

Paediatric Department of Allergy and Lung Diseases Oslo University Hospital Rikshospitalet Oslo Norway

Pediatric Pulmonology Hospital Clinico de Valencia Valencia Spain

Pediatric Pulmonology Pediatric Department 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Pediatric Pulmonology Unit Hospital Archbishop Makarios 3 Nicosia Cyprus

Pneumology and Cystic Fibrosis Unit Bambino Gesù Children's Hospital IRCCS Rome Italy

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

Queen Silvias Children's Hospital Sahlgrenska University Hospital Gothenburg Sweden

Respiratory Medicine Royal Children's Hospital and University of Melbourne Melbourne Australia

Royal Brompton Hospital and Imperial College London London UK

Royal Brompton Hospital and National Heart and Lung Institute Imperial College London London UK

Service de Pneumologie Centre Hospitalier Intercommunal de Créteil Unité de Pneumologie GH Mondor AP HP Créteil France

Service de Pneumologie Pédiatrique Hôpital Trousseau AP HP Sorbonne Université INSERM Centre de Recherche Saint Antoine CRSA Paris France

UMR 5558 Equipe EMET Université Claude Bernard Lyon 1 Villeurbanne France

University Hospital Llandough Cardiff and Vale University Health Board Cardiff UK

See more in PubMed

Wallmeier J, Nielsen KG, Kuehni CE, et al. Motile ciliopathies. Nat Rev Dis Primers 2020; 6: 77. doi: 10.1038/s41572-020-0209-6 PubMed DOI

Goutaki M, Meier AB, Halbeisen FS, et al. Clinical manifestations in primary ciliary dyskinesia: systematic review and meta-analysis. Eur Respir J 2016; 48: 1081–1095. doi: 10.1183/13993003.00736-2016 PubMed DOI

Lucas JS, Davis SD, Omran H, et al. Primary ciliary dyskinesia in the genomics age. Lancet Respir Med 2020; 8: 202–206. doi: 10.1016/S2213-2600(19)30374-1 PubMed DOI

Nielsen KG, Holgersen MG, Crowley S, et al. Chronic airway disease in primary ciliary dyskinesia – spiced with geno-phenotype associations. Am J Med Genet C Semin Med Genet 2022; 190: 20–35. doi: 10.1002/ajmg.c.31967 PubMed DOI PMC

Davis SD, Rosenfeld M, Lee HS, et al. Primary ciliary dyskinesia: longitudinal study of lung disease by ultrastructure defect and genotype. Am J Respir Crit Care Med 2019; 199: 190–198. doi: 10.1164/rccm.201803-0548OC PubMed DOI PMC

Loges NT, Marthin JK, Raidt J, et al. A range of 30–62% of functioning multiciliated airway cells is sufficient to maintain ciliary airway clearance. Eur Respir J 2024; 64: 2301441. doi: 10.1183/13993003.01441-2023 PubMed DOI PMC

Hannah WB, Seifert BA, Truty R, et al. The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis. Lancet Respir Med 2022; 10: 459–468. doi: 10.1016/S2213-2600(21)00453-7 PubMed DOI PMC

Kuehni CE, Goutaki M, Rubbo B, et al. Management of primary ciliary dyskinesia: current practice and future perspectives. DOI

Lucas JS, Alanin MC, Collins S, et al. Clinical care of children with primary ciliary dyskinesia. Expert Rev Respir Med 2017; 11: 779–790. doi: 10.1080/17476348.2017.1360770 PubMed DOI

Kobbernagel HE, Buchvald FF, Haarman EG, et al. Efficacy and safety of azithromycin maintenance therapy in primary ciliary dyskinesia (BESTCILIA): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med 2020; 8: 493–505. doi: 10.1016/S2213-2600(20)30058-8 PubMed DOI

Ringshausen FC, Shapiro AJ, Nielsen KG, et al. Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial. Lancet Respir Med 2023; 12: 21–33. doi: 10.1016/S2213-2600(23)00226-6 PubMed DOI

Castellani C, Duff AJA, Bell SC, et al. ECFS best practice guidelines: the 2018 revision. J Cyst Fibros 2018; 17: 153–178. doi: 10.1016/j.jcf.2018.02.006 PubMed DOI

National Guideline Alliance (UK) . Cystic Fibrosis: Diagnosis and Management. London, National Institute for Health and Care Excellence, 2017. PubMed

Lahiri T, Hempstead SE, Brady C, et al. Clinical practice guidelines from the cystic fibrosis foundation for preschoolers with cystic fibrosis. Pediatrics 2016; 137: e20151784. doi: 10.1542/peds.2015-1784 PubMed DOI

Yankaskas JR, Marshall BC, Sufian B, et al. Cystic fibrosis adult care: consensus conference report. Chest 2004; 125: Suppl. 1, 1S–39S. doi: 10.1378/chest.125.1_suppl.1S PubMed DOI

Jaffé A, Buchdahl R, Bush A, et al. Are annual blood tests in preschool cystic fibrosis patients worthwhile? Arch Dis Child 2002; 87: 518–520. doi: 10.1136/adc.87.6.518 PubMed DOI PMC

Shapiro AJ, Zariwala MA, Ferkol T, et al. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD Foundation consensus recommendations based on state of the art review. Pediatr Pulmonol 2016; 51: 115–132. doi: 10.1002/ppul.23304 PubMed DOI PMC

Chang AB, Fortescue R, Grimwood K, et al. European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis. Eur Respir J 2021; 58: 2002990. doi: 10.1183/13993003.02990-2020 PubMed DOI

Polverino E, Goeminne PC, McDonnell MJ, et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J 2017; 50: 1700629. doi: 10.1183/13993003.00629-2017 PubMed DOI

Goutaki M, Crowley S, Dehlink E, et al. The BEAT-PCD (Better Experimental Approaches to Treat Primary Ciliary Dyskinesia) Clinical Research Collaboration. Eur Respir J 2021; 57: 2004601. doi: 10.1183/13993003.04601-2020 PubMed DOI

Raidt J, Maitre B, Pennekamp P, et al. The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN. ERJ Open Res 2022; 8: 00139-2022. doi: 10.1183/23120541.00139-2022 PubMed DOI PMC

Powell C. The Delphi technique: myths and realities. J Adv Nurs 2003; 41: 376–382. doi: 10.1046/j.1365-2648.2003.02537.x PubMed DOI

Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs 2000; 32: 1008–1015. doi: 10.1046/j.1365-2648.2000.t01-1-01567.x PubMed DOI

Niederberger M, Köberich S. Coming to consensus: the Delphi technique. Eur J Cardiovasc Nurs 2021; 20: 692–695. doi: 10.1093/eurjcn/zvab059 PubMed DOI

Coban H, Gungen AC. Is there a correlation between new scoring systems and systemic inflammation in stable bronchiectasis? Can Respir J 2017; 2017: 9874068. doi: 10.1155/2017/9874068 PubMed DOI PMC

Marino LV, Harris A, Johnstone C, et al. Characterising the nutritional status of children with primary ciliary dyskinesia. Clin Nutr 2019; 38: 2127–2135. doi: 10.1016/j.clnu.2018.08.034 PubMed DOI

Thomas MR, Storey RF. The role of platelets in inflammation. Thromb Haemost 2015; 114: 449–458. doi: 10.1160/TH14-12-1067 PubMed DOI

Chen Y, Zhong H, Zhao Y, et al. Role of platelet biomarkers in inflammatory response. Biomark Res 2020; 8: 28. doi: 10.1186/s40364-020-00207-2 PubMed DOI PMC

Aliberti S, Sotgiu G, Gramegna A, et al. Thrombocytosis during stable state predicts mortality in bronchiectasis. Ann Am Thorac Soc 2021; 18: 1316–1325. doi: 10.1513/AnnalsATS.202002-094OC PubMed DOI

Mattiello V, Schmugge M, Hengartner H, et al. Diagnosis and management of iron deficiency in children with or without anemia: consensus recommendations of the SPOG Pediatric Hematology Working Group. Eur J Pediatr 2020; 179: 527–545. doi: 10.1007/s00431-020-03597-5 PubMed DOI

Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med 2020; 287: 153–170. doi: 10.1111/joim.13004 PubMed DOI

Li L, Li Z, Bi J, et al. The association between serum albumin/prealbumin level and disease severity in non-CF bronchiectasis. Clin Exp Pharmacol Physiol 2020; 47: 1537–1544. doi: 10.1111/1440-1681.13331 PubMed DOI

Lee SJ, Kim HJ, Kim JY, et al. Serum albumin and disease severity of non-cystic fibrosis bronchiectasis. Respir Care 2018; 62: 1075–1084. PubMed

Aranow C. Vitamin D and the immune system. J Investig Med 2011; 59: 881–886. doi: 10.2310/JIM.0b013e31821b8755 PubMed DOI PMC

Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 2017; 18: 153–165. doi: 10.1007/s11154-017-9424-1 PubMed DOI

Mirra V, Caffarelli C, Maglione M, et al. Hypovitaminosis D: a novel finding in primary ciliary dyskinesia. Ital J Pediatr 2015; 41: 14. doi: 10.1186/s13052-015-0119-5 PubMed DOI PMC

Shypailo RJ, Wong WW. Fat and fat-free mass index references in children and young adults: assessments along racial and ethnic lines. Am J Clin Nutr 2020; 112: 566–575. doi: 10.1093/ajcn/nqaa128 PubMed DOI

Chalmers JD, McHugh BJ, Docherty C, et al. Vitamin-D deficiency is associated with chronic bacterial colonisation and disease severity in bronchiectasis. Thorax 2013; 68: 39–47. doi: 10.1136/thoraxjnl-2012-202125 PubMed DOI

Marcinowska-Suchowierska E, Kupisz-Urbanska M, Lukaszkiewicz J, et al. Vitamin D toxicity – a clinical perspective. Front Endocrinol 2018; 9: 550. doi: 10.3389/fendo.2018.00550 PubMed DOI PMC

Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy 2013; 43: 850–873. doi: 10.1111/cea.12141 PubMed DOI

Li BCM, Huh SM, Prieto MD, et al. Biomarkers for the diagnosis of allergic bronchopulmonary aspergillosis in cystic fibrosis: a systematic review and meta-analysis. J Allergy Clin Immunol Pract 2021; 9: 1909–1930. doi: 10.1016/j.jaip.2020.12.064 PubMed DOI

Sharma B, Sharma M, Bondi E, et al. Kartagener's syndrome associated with allergic bronchopulmonary aspergillosis. MedGenMed 2005; 7: 25. PubMed PMC

Sehgal IS, Dhooria S, Bal A, et al. Allergic bronchopulmonary aspergillosis in an adult with Kartagener syndrome. BMJ Case Rep 2015; 2015: bcr2015211493. doi: 10.1136/bcr-2015-211493 PubMed DOI PMC

Allaer L, Lejeune S, Mordacq C, et al. Primary ciliary dyskinesia and fungal infections: two cases of allergic bronchopulmonary aspergillosis in children. Pediatr Pulmonol 2022; 57: 1809–1813 doi: 10.1002/ppul.25945 PubMed DOI

Sunman B, Ademhan Tural D, Ozsezen B, et al. Current approach in the diagnosis and management of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. Front Pediatr 2020; 8: 582964. doi: 10.3389/fped.2020.582964 PubMed DOI PMC

Stevens DA, Moss RB, Kurup VP, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis – state of the art: cystic fibrosis foundation consensus conference. Clin Infect Dis 2003; 37: Suppl. 3, S225–S264. doi: 10.1086/376525 PubMed DOI

Boon M, De Boeck K, Jorissen M, et al. Primary ciliary dyskinesia and humoral immunodeficiency – is there a missing link? Respir Med 2014; 108: 931–934. doi: 10.1016/j.rmed.2014.03.009 PubMed DOI

Nur Husna SM, Tan HTT, Md Shukri N, et al. Allergic rhinitis: a clinical and pathophysiological overview. Front Med 2022; 9: 874114. doi: 10.3389/fmed.2022.874114 PubMed DOI PMC

Scadding GK, Smith PK, Blaiss M, et al. Allergic rhinitis in childhood and the new EUFOREA algorithm. Front Allergy 2021; 2: 706589. doi: 10.3389/falgy.2021.706589 PubMed DOI PMC

Saad A, Young MR, Studtmann AE, et al. Incidence of nephrotoxicity with prolonged aminoglycoside exposure in patients with cystic fibrosis. Pediatr Pulmonol 2020; 55: 3384–3390. doi: 10.1002/ppul.25066 PubMed DOI

Novel-Catin E, Pelletier S, Reynaud Q, et al. Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients. Nephrol Dial Transplantat 2019; 34: 118–122. doi: 10.1093/ndt/gfy084 PubMed DOI

Hannah WB, DeBrosse S, Kinghorn BA, et al. The expanding phenotype of PubMed DOI PMC

Bukowy-Bieryllo Z, Rabiasz A, Dabrowski M, et al. Truncating mutations in exons 20 and 21 of PubMed DOI

Martinez MA, Vuppalanchi R, Fontana RJ, et al. Clinical and histologic features of azithromycin-induced liver injury. Clin Gastroenterol Hepatol 2015; 13: 369–376. doi: 10.1016/j.cgh.2014.07.054 PubMed DOI PMC

Goutaki M, Papon JF, Boon M, et al. Standardised clinical data from patients with primary ciliary dyskinesia: FOLLOW-PCD. ERJ Open Res 2020; 6: 00237-2019. doi: 10.1183/23120541.00237-2019 PubMed DOI PMC

Kos R, Goutaki M, Kobbernagel HE, et al. A BEAT-PCD consensus statement: a core outcome set for pulmonary disease interventions in primary ciliary dyskinesia. ERJ Open Res 2023; 10: 00115-2023. doi: 10.1183/23120541.00115-2023 PubMed DOI PMC