Introduction: Primary ciliary dyskinesia (PCD) is a rare, chronic, genetic disorder characterized by severe progressive lung disease. Pseudomonas aeruginosa is a major pathogen in this disease, known to impact lung function. Previous genotype-phenotype studies have been limited by either cross-sectional designs, isolated adult or paediatric populations, small numbers, or short follow-up.

Aims and objectives: We explored long-term lung function trends among genotypes and ultrastructural defect groups at key age milestones, while considering the influence of P. aeruginosa.

Methods: In this observational, retrospective study, we included 43 years of spirometry data and 20 years of microbiology samples. FEV1 z-score trends were estimated using linear mixed-effects models and compared among groups at ages 10, 25, and 50 years. In a secondary analysis, measurements were matched to microbiology samples including P. aeruginosa.

Results: We included 127 genotyped individuals with PCD, 6,691 spirometry measurements and 10,082 microbiology samples. CCDC39 and CCDC40 were associated with a persistent reduction in lung function with early onset. Conversely, DNAH11 and HYDIN mutations were associated with a better maintained lung function. P. aeruginosa had an annual prevalence of 28%, were found in 72% of subjects, and showed an average impact on lung function of -0.06 z-score with a non-significant age-related effect.

Conclusion: We highlight a diverse lung function among genotypes independent of P. aeruginosa presence. We confirm and extend previous findings of CCDC39 and CCDC40 as variants associated with early onset severe lung function impairment persisting in the long term.