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

Abstract

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.

Keywords: cystic fibrosis; lung function; primary ciliary dyskinesia.

Figure 1.

Flowchart of cohort constitution. Children with primary ciliary dyskinesia (PCD) were matched 1:4 with children with cystic fibrosis (CF) from the U.S. Cystic Fibrosis Foundation National Patient Registry (17) by year of birth, sex, race, ethnicity, and presence of at least one encounter during the year in which the matched PCD patient had a study visit. *Definite PCD defined as abnormal ciliary ultrastructure by transmission electron microscopy and/or identification of two pathogenic variants in a PCD-associated gene along with compatible clinical features (9). ^†Cystic Fibrosis Foundation (CFF) National Patient Registry (18). ^‡Four children with PCD did not successfully match, all of Asian race, which is very rare in cystic fibrosis.

Figure 2.

Mean estimated spirometric indices and growth parameters by age and specific indices at representative ages (2, 6, 10, and 14 yr), stratified by disease group (primary ciliary dyskinesia [PCD] vs. cystic fibrosis [CF]). (A) Forced expiratory volume in 1 second (FEV₁) percent predicted. (B) Forced expiratory flow, midexpiratory phase (FEF_25–75), percent predicted. (C) Body mass index (BMI) percentile by age, stratified by disease cohort (PCD vs. CF).

Figure 3.

Mean estimated spirometric indices and growth parameters by age and specific indices at representative ages (2, 6, 10, and 14 yr), stratified by disease group (primary ciliary dyskinesia [PCD] inner dynein arm/microtubular defects [IDA/MTD], PCD-other, cystic fibrosis [CF]-minimal function, CF-residual function). (A) Forced expiratory volume in 1 second (FEV₁) percent predicted. (B) Forced expiratory flow, midexpiratory phase (FEF_25–75), percent predicted. (C) Body mass index (BMI) percentile.

Figure 4.

Prevalence of respiratory bacterial pathogens by age, stratified by disease group (primary ciliary dyskinesia [PCD] inner dynein arm/microtubular defects [IDA/MTD], PCD-other, cystic fibrosis [CF]-minimal function, CF-residual function). Respiratory data was collected at least once during the follow-up period in 135 (99%) children with PCD and 478 (100%) children with CF. Nontuberculous mycobacterium (NTM) data were available for 307 (69%) children with CF-Minimal, 14 (47%) children with CF-Residual, 36 (90%) children with PCD-IDA/MTD, and 78 (81%) children with PCD-other.