Pulmonary radioaerosol mucociliary clearance assessment: searching for genotype-specific differences and potential as an outcome measure in primary ciliary dyskinesia

June K Marthin; Mathias G Holgersen; Kim G Nielsen; Jann Mortensen

doi:10.1183/23120541.00685-2023

Pulmonary radioaerosol mucociliary clearance assessment: searching for genotype-specific differences and potential as an outcome measure in primary ciliary dyskinesia

ERJ Open Res. 2023 Dec 4;9(6):00685-2023. doi: 10.1183/23120541.00685-2023. eCollection 2023 Nov.

Authors

June K Marthin^{1

2}, Mathias G Holgersen^{1

2}, Kim G Nielsen^{1

3

4}, Jann Mortensen^{3

5

4}

Affiliations

¹ Danish PCD Centre, Danish Pediatric Pulmonary Service, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
² Joint first authors.
³ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁴ Joint senior authors.
⁵ Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Abstract

Background: Pulmonary radioaerosol mucociliary clearance (PRMC) is a reliable method for assessing in vivo whole lung mucociliary clearance and has been used at the Danish PCD Centre as a supplementary diagnostic test for primary ciliary dyskinesia (PCD) for more than two decades. This study aimed to investigate genotype-specific differences in PRMC measures and evaluate its potential as an outcome parameter.

Material and methods: The study was based on a retrospective analysis of PRMC tests performed over a 24-year period (1999-2022) in individuals referred for PCD work-up and included patients with genetically confirmed PCD and non-PCD controls. Patients inhaled nebulised technetium-albumin-colloid before static and dynamic imaging was obtained. Three parameters were evaluated: 1-h lung retention (LR1), tracheobronchial velocity (TBV) and cough clearance.

Results: The study included 69 patients from the Danish PCD cohort, representing 26 different PCD genotypes. Mucociliary clearance by PRMC was consistently absent in most PCD patients, regardless of genotype. However, a single patient with a CCDC103 mutation, preserved ciliary function and normal nasal nitric oxide levels exhibited normal LR1 and low TBV values. Voluntary cough significantly improved clearance, with a median improvement of 11% (interquartile range 4-24%).

Conclusion: Absent mucociliary clearance by PRMC should be expected in PCD regardless of genotype but residual ciliary function could result in measurable PRMC. This indicates a potential for PRMC to detect improvements in ciliary function if this can be restored. Addressing involuntary cough and peripheral deposition of radioaerosol is important if PRMC is to be used as an outcome measure in future clinical PCD trials.