Long-Term Lung Function and Pseudomonas aeruginosa Infection in Genotyped Primary Ciliary Dyskinesia

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Rationale Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by progressive lung disease. Pseudomonas aeruginosa is a major pathogen in this disease and is known to impact lung function. Previous genotype–phenotype studies have been limited by cross-sectional designs, isolated adult or pediatric populations, small numbers, or short follow-up durations. Objectives We aimed to explore long-term lung function in PCD grouped by genotypes and ultrastructural defects, considering the influence of P. aeruginosa. Methods In this retrospective observational study, we analyzed 43 years of spirometry and 20 years of microbiology data. Using linear mixed-effects models, we estimated forced expiratory volume in 1 second z-score trends and compared them at ages 10, 25, and 50 years, whereas generalized estimating equations were used to assess P. aeruginosa prevalence between groups. In a secondary analysis, we matched spirometry and microbiology samples to evaluate the influence of P. aeruginosa on lung function. Results We included 127 genotyped patients, 6,691 spirometry measurements, and 10,082 microbiology samples. CCDC39 and CCDC40 variants showed early-onset and sustained decline in lung function, whereas DNAH11 and HYDIN variants demonstrated relative stability. Lung function in the proximity of positive P. aeruginosa cultures was on average 0.06 z-score lower. Despite this, differences between groups remained largely unaffected by P. aeruginosa. Conclusions Long-term lung function in PCD follows discrete genotype-specific profiles and appears independent of P. aeruginosa infection. 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.