Is Lung Function Decline Always Severe in Primary Ciliary Dyskinesia Due to Mutations in CCNO Gene?

Primary Ciliary Dyskinesia (PCD) is a rare and genetically heterogeneous disease, in which some of the clinical variability is attributed to the different responsible genes (E1). A subgroup of PCD includes the reduced generation of multiple motile cilia (RGMC) caused by biallelic mutations in CCNO [1-3]. This genotype is considered to be associated with a more severe phenotype and a more rapid decline in lung function. However, only a small number of patients with CCNO pathogenetic mutations have been reported [1-3], so that knowledge of its clinical manifestations is based on very few observations and the decline in lung function has been inferred from cross-sectional measurements [1-3]. Hence a longitudinal assessment of lung function in this group of patients has not previously been performed. The aim of our exploratory longitudinal study was to verify for the first time in our small series of patients with CCNO mutations whether long-term evolution of lung function is significantly worse than in other genotypes of PCD (CCDC39 and CCDC40, severe mutations; and DNAH5, DNAH11, mild mutations), and if a rapid lung function decline in these patients is associated with chronic lower airways Pseudomonas aeruginosa (P. a.) infection or worse lung structural changes on High-Resolution Computed Tomography (HRCT).