Treatment of Lung Disease in Primary Ciliary Dyskinesia: A Review of Current and Emerging Interventions.

Primary ciliary dyskinesia (PCD) is a rare genetic disease caused by impaired function of motile cilia. There have been few clinical trials conducted in people with PCD, and current management strategies are extrapolated from expert consensus and evidence-based approaches for cystic fibrosis and non-cystic fibrosis bronchiectasis. Clinical guidelines for PCD have focused on symptom management, primarily a combination of antibiotics and airway clearance techniques, but many people are treated with bronchodilators, inhaled corticosteroids, and inhaled mucolytic agents, despite the lack of evidence to support these interventions. Several, more disease-specific therapies are under investigation, with some currently being tested in clinical trials. Novel anti-infective approaches include new inhaled antibiotics, antibodies and vaccines targeting Pseudomonas aeruginosa, and inhaled immunoglobulin G. Anti-inflammatory therapies, such as dipeptidyl peptidase 1 and neutrophil elastase inhibitors, have shown clinical benefit in adolescents and adults with bronchiectasis. Similar therapeutic effects are expected in patients with PCD. Advances in genetic therapies, specifically inhaled lipid nanoparticle (LNP)-encapsulated mRNA products, have been tested pre-clinically and are currently in clinical trials involving healthy volunteers and adults with DNAI1 defects. In addition to newer agents focusing on the unique pathophysiology of PCD, future progress in research will require animal models and the development of validated, reliable outcome measures. This review summarizes current management, highlights emerging therapies, and discusses optimizing treatment of lung disease for people with PCD.