Abstract Rationale Primary Ciliary Dyskinesia (PCD) is a rare motile ciliopathy characterized by chronic airway infection, mucus retention, and progressive bronchiectasis. In Puerto Rico, a founder variant in RSPH4A (c. 921 + 3₆delAAGT) is the most common cause of genetically confirmed PCD. Despite its prevalence, longitudinal data integrating structural and functional changes remain limited. Advanced three-dimensional (3D) imaging may provide quantitative biomarkers for disease progression and regional lung involvement. Methods Six patients (ages 13-62 years; 3 males, 3 females) with biallelic RSPH4A founder variants underwent high-resolution computed tomography (HRCT), spirometry, and 3D reconstruction using the Slicer Lung CT Analyzer. Lung parenchyma was segmented into inflated, infiltrated, collapsed, and emphysematous compartments based on Hounsfield unit thresholds. Volumetric data were correlated with forced expiratory volume in one second (FEV₁, % predicted). Airway trees were extracted to assess proximal and distal dilation, and coronal HRCT overlays were used to visualize the spatial distribution of bronchiectasis and parenchymal involvement. Results Inflated lung volume increased from 2. 3 L at age 13 to 4. 7 L at age 48, reflecting compensatory hyperinflation, followed by a sharp decline to 1. 4 L by age 62 as fibrosis and collapse predominated. Infiltrated and collapsed volumes progressively rose from 0. 6 L to 1. 3 L, consistent with mucus plugging and chronic consolidation. FEV₁ declined from 45% to 30% predicted across age groups (r ≈ -0. 9 with infiltrated volume). 3D airway models demonstrated progressive proximal bronchial dilation, loss of distal branching, and asymmetric volume loss, particularly in lower lobes. HRCT segmentation revealed an early inflammatory-obstructive phase in younger patients transitioning to a fibrotic-collapsing phase in older adults. Airflow-volume loops exhibited increasing expiratory flow limitation with age, confirming fixed severe obstruction. Conclusion Quantitative 3D CT segmentation offers a robust imaging biomarker for tracking disease severity and progression in RSPH4A-related PCD. The observed biphasic pattern—from hyperinflation to parenchymal collapse—illustrates a continuum from reversible inflammation to irreversible structural remodeling. Coupling 3D imaging with functional testing enables precise monitoring of rare bronchiectatic lung disease and supports future therapeutic trials targeting early intervention in the Puerto Rican PCD population. This abstract is funded by: None
Roman et al. (Fri,) studied this question.
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