Abstract Primary Ciliary Dyskinesia (PCD) is a rare, genetically heterogenous disorder of motile cilia, leading to impaired mucociliary clearance and chronic respiratory disease. Its clinical presentation often overlaps with common conditions, including obstructive pulmonary diseases, contributing to diagnostic delays. Mutations in the DNAH11 gene are associated with PCD, but patients frequently lack the classic ultrastructural ciliary defects. We present a case which highlights the importance of considering rare ciliopathies in patients with refractory respiratory symptoms and the evolving role of genetic testing in diagnosis. A 44-year-old woman with early onset asthma was referred for evaluation of recurrent pneumonias, occurring biannually in recent years. She had been affected by respiratory disease since childhood. Despite aggressive asthma management, including long-term mepolizumab, she reported frequent pneumonias and persistent respiratory symptoms. Pulmonary function tests demonstrated obstructive physiology with bronchodilator responsiveness. Chest CT revealed diffuse cylindrical bronchiectasis, small airway disease, and a tree-in-bud pattern. Initial genetic testing identified heterozygous variants in DNAH11 and AP3D1. Whole genome sequencing later revealed a maternally inherited, likely pathogenic, DNAH11 variant and a paternally inherited variant of uncertain significance (VUS), suggesting a compound heterozygous state. Although not definitively diagnostic, this genetic profile, combined with lifelong respiratory symptoms, and imaging findings, raised strong clinical suspicion for PCD. She was treated targeting both asthma and PCD. Her regimen included a combination inhaler of fluticasone, umeclidinium, and vilanterol, as-needed albuterol, mepolizumab, and the addition of airway clearance focused techniques, including nebulized hypertonic saline, flutter valves, and chest physiotherapy. She demonstrated significant symptomatic improvement and a dramatic reduction in pneumonias or exacerbations. This case underscores the diagnostic complexity of chronic respiratory disease in young adults. PCD should be considered in patients with early-onset, persistent respiratory symptoms and recurrent infections, particularly when standard asthma therapies fail. DNAH11 mutations are known to cause PCD, often without detectable ciliary ultrastructural abnormalities, making diagnosis reliant on clinical features, nasal nitric oxide levels, high-speed video microscopy, and genetic testing. Compound heterozygosity involving a pathogenic variant and a VUS, as seen in this case, is not definitively diagnostic per current ATS/ERS guidelines, but may support a clinical diagnosis when aligned with phenotype and imaging findings. This case illustrates the importance of a multidisciplinary approach, including pulmonology, allergy, genetics, and immunology, in evaluating complex respiratory presentations. Early recognition and tailored therapy, including airway clearance and infection prevention, are critical to improving patient outcomes and quality of life in patients with suspected PCD. This abstract is funded by: None
Mainra et al. (Fri,) studied this question.