Pulmonary Radioaerosol Mucociliary Clearance Parameters as Potential Outcomes in Primary Ciliary Dyskinesia Trials

ABSTRACT Background: Pulmonary Radioaerosol Mucociliary Clearance (PRMC) is an in vivo whole lung ciliary function test reliable for assessing mucociliary clearance for diagnostic purposes in individuals suspected of primary ciliary dyskinesia (PCD). We aimed to evaluate expanded use of PRMC by providing advantages and limitations for its potential use in providing outcome parameters in future trials aiming to restore ciliary activity. Material and Methods: In this retrospective study, PRMC tests performed over a period of 24 years (1999-2022) were meticulously re-analyzed. Patients with genetically verified PCD and non-PCD controls were included. Originally, nebulized 99mTc-albumin colloid was inhaled, and static and dynamic imaging acquired for 60 and 120 minutes, and 24 hours. For the purpose of the present study 3 PRMC parameters were defined: 1 hour lung retention (LR1), tracheobronchial velocity (TBV), and cough clearance. Results: Sixty-nine patients were included from the Danish PCD cohort. PRMC was overall completely absent regardless of PCD genotypes. In one patient with CCDC103 mutation, residual ciliary function and normal nasal NO, we found normal PRMC LR1 and measurable, however low, TBV. Voluntary cough significantly increased clearance with a median (IQR) of 11 (4;24) %. Conclusion: Absolute absence of PRMC would be the expected baseline result in by far the majority of patients with PCD regardless of genotype before introducing ciliary protein correctors in a clinical trial. Measurable PRMC TBV and normal LR1 in one patient with residual ciliary function, indicated that PRMC parameters could potentially improve if ciliary function was to be restored during a clinical trial. Involuntary cough and peripheral radioaerosol deposition were the main challenges of the PRMC method. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The source data are openly available from The Danish PCD Registry at Rigshospitalet, Copenhagen I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors