Genetic background and pulmonary exacerbations in patients with primary ciliary dyskinesia

Résumé fourni par la source

Primary ciliary dyskinesia (PCD) is a rare genetic disorder causing motile cilia dysfunction. Patients with PCD experience often pulmonary exacerbations (PEx). Certain genotypes have been associated to worse clinical course1, but it is unknown whether the genetic background is a risk factor for PEx. This study aims to investigate the effect of the genetic background on PEx frequency. Patients from 11 centers (n=328) were monthly interviewed for ≥12 months. Information on genetics was retrieved by the ERN-LUNG international PCD registry. Those with genetic diagnosis were separated in Group 1 (mutations in genes associated with normal cilia ultrastructure) and Group 2 (mutations in genes associated with abnormal cilia ultrastructure: outer dynein arm ± inner dynein arm defects, microtubular disorganisation)1. Three PEx definitions were used (Def-1, based on a consensus statement2; Def-2, based on antibiotics use; self-reports). The Mann-Whitney test was used for between-groups comparisons. Participants with genetic confirmation of PCD (n=248) had significantly higher PEx frequency compared to those without (n=80) in self-reports (p<0.01), in Def-1 (p=0.02) and Def-2 (p=0.03). PEx frequency did not differ between Group 1 (n=73) and Group 2 (n=175) but was significantly higher in participants with microtubular disorganisation (CCDC39, CCDC40) by Def-2 (p<0.05). Our study highlights the importance of the genetic confirmation of PCD when using registry data. Although a direct effect of the genetic background on PEx frequency was not seen, participants with CCDC39 and CCDC40 mutations use more often antibiotics for PEx, compared to other genotypes. 1Raidt et al, ERJ 2024 2Lucas et al, ERJ Open Res 2019

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