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 99m Tc-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.