Rationale: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are both genetic diseases of mucociliary clearance resulting in progressive lung disease with onset in early life. PCD is often considered to be milder in childhood than CF, based on minimal evidence. Similar to CF, genotype-phenotype associations exist in PCD: pathogenic variants in CCDC39 and CCDC40, causing inner dynein arm/microtubular defects (IDA/MTD) are associated with more severe disease.
Objectives: To compare longitudinal outcomes in matched children with PCD and CF. We hypothesized that children with PCD with IDA/MTD defects would have lower lung function but better nutritional indices than matched children with CF with minimal function genotypes (i.e., those associated with pancreatic insufficiency).
Methods: Children with PCD enrolled in a prospective, multicenter, observational study were matched with CF patients from the CF Foundation Patient Registry by birth cohort, age, sex, race/ethnicity and year of study visit. The association of disease group overall and by severity class (PCD-IDA/MTD versus all other defects and CF-minimal versus residual function) with longitudinal outcomes up to age 17 was evaluated with cubic spline mixed effects models.
Measurement and main results: Groups included 136 children with PCD (40 IDA/MTD, 96 other) and 476 with CF (446 minimal function, 30 residual function). Below age 14, the PCD group had similar or lower estimated mean FEV1 % predicted compared to CF (e.g., at age 10, -5.4 % predicted lower (95% CI: -7.7, -3.1)). Compared to the CF-minimal function (pancreatic insufficient) group, the PCD-IDA/MTD group had similar BMI; estimated mean FEV1 % predicted was significantly lower by age 10 (mean difference -10.6% (95% CI: -14.7, -6.4), increasing to -15.7% (95% CI: -20.3, -11.2) at age 14. The CF cohort had increased prevalence of Pseudomonas aeruginosa cultured on one or more occasions compared to children with PCD (67% vs 27%, p<0.001); there was no difference in prevalence of P. aeruginosa between children with PCD-IDA/MTD and PCD-other.
Conclusions: In childhood, average lung function abnormalities in PCD are not milder than CF, particularly for those with IDA/MTD ciliary defects. New guidelines and treatments to improve outcomes in PCD are urgently needed.