Comparison of Longitudinal Outcomes in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis.

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 than CF in childhood, 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 patients with CF from the Cystic Fibrosis 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 vs. all other defects and CF-minimal vs. residual function) with longitudinal outcomes up to age 17 was evaluated with cubic spline mixed effects models.

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 forced expiratory volume in 1 second percent predicted compared with CF (e.g., at age 10, -5.4% predicted lower; 95% confidence interval [CI], -7.7, -3.1). Compared with the CF-minimal function (pancreatic insufficient) group, the PCD-IDA/MTD group had similar body mass index; estimated mean forced expiratory volume in 1 second percent predicted was significantly lower by age 10 (mean difference, -10.6%; 95% CI, -14.7, -6.4), increasing at age 14 (mean difference, -15.7%; 95% CI, -20.3, -11.2). The CF cohort had increased prevalence of Pseudomonas aeruginosa cultured on one or more occasions compared with children with PCD (67% vs. 27%; P < 0.001); there was no difference in the 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.