Airway Disease in Children with Primary Ciliary Dyskinesia: Impact of Ciliary Ultrastructure Defect and Genotype.

<bold>Rationale: </bold>Primary ciliary dyskinesia (PCD) is characterized by impaired mucociliary clearance, recurrent respiratory infections, and progressive airway damage and obstructive lung disease. While the association of ciliary ultrastructure defect/genotype with severity of airflow obstruction has been well characterized, their association with airway abnormalities on chest computed tomography (CT) has been minimally evaluated.<bold>Objectives: </bold>We sought to delineate the association of ciliary defect class/genotype with chest CT scores in children with PCD.<bold>Methods: </bold>Cross-sectional analysis of children with PCD (N=146) enrolled in a prospective multicenter observational study, stratified by defect type: ODA (outer dynein arm), ODA/IDA (outer and inner dynein arm), IDA/MTD (inner dynein arm and microtubular disorganization), and Normal/Near Normal ultrastructure with associated genotypes. CTs were scored utilizing the Melbourne-Rotterdam Annotated Grid Morphometric Analysis for PCD (MERAGMA-PCD), evaluating airway abnormalities in a hierarchical order: atelectasis, bronchiectasis, bronchial wall thickening, mucus plugging/tree in bud opacities. Volume fraction of each component was expressed as % of total lung volume. %Disease was computed as the sum of all components. Regression analyses were utilized to describe the association between clinical predictors and CT scores.<bold>Results: </bold>Acceptable chest CTs were obtained in 141 children (71 male): 57 ODA, 20 ODA/IDA, 40 IDA/MTD, 24 Normal/Near Normal. Mean (SD) age was 8.5 (4.6) years, forced expiratory volume in 1 second (FEV1) % predicted was 82.4 (19.5), and %Disease was 4.6 (3.5). Children with IDA/MTD defects had higher %Disease compared to children with ODA defects (2.71% higher (95%CI: 1.37-4.06, p<0.001)), driven by higher %Mucus plugging (2.35% higher (1.43-3.26, p<0.001)). Increasing age, lower BMI, and lower FEV1 were associated with higher %Disease (0.23%, 95%CI: 0.11-0.35, p<0.001; 0.03%, 95%CI: 0.01-0.04, p=0.008; and 0.05%, 95%CI: 0.01-0.08, p=0.011, respectively).<bold>Conclusions: </bold>Children with IDA/MTD defects had significantly greater airway disease on CT, primarily mucus plugging, compared to children with ODA defects. [ABSTRACT FROM AUTHOR]