Therapies Used by Children With Primary Ciliary Dyskinesia: A Natural History Study

Robert A Gardner; Thomas W Ferkol; Stephanie D Davis; Margaret Rosenfeld; Scott D Sagel; Sharon D Dell; Carlos E Milla; Lang Li; Feng-Chang Lin; Kelli M Sullivan; Maimoona A Zariwala; Michael R Knowles; Margaret W Leigh; Genetic Disorders of Mucociliary Clearance Consortium

doi:10.1002/ppul.27412

Therapies Used by Children With Primary Ciliary Dyskinesia: A Natural History Study

Pediatr Pulmonol. 2024 Nov 22:e27412. doi: 10.1002/ppul.27412. Online ahead of print.

Authors

Affiliations

¹ Department of Pediatrics, Levine Children's Hospital, Wake Forest University School of Medicine, Charlotte, North Carolina, USA.
² Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
³ Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁴ Department of Pediatrics, University of Washington, Seattle, Washington State, USA.
⁵ Department of Pediatrics, University of Colorado, Aurora, Colorado, USA.
⁶ Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
⁷ Department of Pediatrics, Stanford University, Palo Alto, California, USA.
⁸ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

PMID: 39575633
DOI: 10.1002/ppul.27412

Abstract

Introduction: Primary ciliary dyskinesia (PCD) management has not been systematically evaluated and is largely empirical.

Methods: Pediatric participants with PCD were enrolled in a prospective, longitudinal, multicenter, observational study. Therapies were recorded at annual visits and categorized by type. Age-related trends in prevalence of therapies were described by serial cross-sectional analyses. Generalized estimating equations analyzed covariates affecting prevalence of certain therapies and whether these covariates impacted oral antibiotic courses.

Results: A total of 137 participants completed 897 visits over 13 years. All but one received ≥ 1 antibiotic courses during study participation, most often cephalosporins (74%) or amoxicillin-clavulanate (73%). Thirty-one percent reported chronic azithromycin use. Per participant, there was an average of 2.3 (SD = 2.2) oral antibiotic courses annually. The rate of reported antibiotic courses at the 6 United States sites was 2.6 times higher compared to the Canadian site (p < 0.001). As patients got older, they were more likely to report use of amoxicillin-clavulanate (p < 0.001), chronic azithromycin (p < 0.001), fluroquinolones (p < 0.001), inhaled steroids with long-acting beta-agonists (p = 0.010), and hypertonic saline (p < 0.001). Compared to outer dynein arm defects, those with inner dynein arm/microtubular disorganization defects reported increased use of chronic azithromycin (p = 0.011) and inhaled steroids (p = 0.015).

Discussion: Older participants and those with inner dynein arm/microtubular disorganization defects reported more therapies likely due to disease progression and more severe phenotypes, respectively. We report that a wide range of therapies are used in PCD without disease-specific studies defining benefits and risks.

Keywords: natural history; primary ciliary dyskinesia; therapy.

Grants and funding

Funding support for research was provided by US NIH/ORDR/NCATS/NHLBI grant U54HL096458; NIH/NCATS Colorado CTSA Grant UM1TR004399; US NIH/NHLBI grant R01HL071798. The Genetic Disorders of Mucociliary Clearance Consortium (U54HL096458) is part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) and supported by the RDCRN Data Management and Coordinating Center (DMCC) (U2CTR002818). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR) funded through a collaboration between NCATS and National Heart, Lung, and Blood Institute (NHLBI).