Abstract Rationale Airway mucus plugging is an early manifestation of cystic fibrosis (CF) lung disease that obstructs airflow and facilitates local inflammation and infection, leading to permanent lung damage. Computed tomography (CT) is the gold-standard for assessing pulmonary structural abnormalities including mucus plugging; however, current lobe-based CT scoring systems often miss subtle changes typical of mild CF1. We hypothesize that a novel scoring system that quantifies mucus plugging by bronchopulmonary segment and generation will more precisely quantify the underlying pathophysiology of CF and will correlate well with clinical metrics like forced expiratory volume (FEV1) and ventilation defect percent (VDP) from Xe-MRI. Methods Xe-MRI and retrospective review of clinically-obtained CTs were performed with IRB approval. Xe-MRI was analyzed using standard software to calculate VDP. Individual mucus plugs were identified and assigned to bronchopulmonary segment and generation. These data were used to calculate 3 CT mucus scores: total number of plugs (Nplugs), total number of segments with any plug (Nseg), and percent lung volume obstructed by mucus (%Volobs), using each plug’s subtended volume percentage of total lung volume. Group differences were analyzed using Wilcoxon tests and relationships by Spearman correlation Results CT scans from 21 CF patients were analyzed (mean age 11.8±4.4 yrs). 19 had FEV1 obtained within two months of CT (FEV1=93±13%), and 11 had MRI-derived VDP data within three months (VDP=14.1±7.6). Mucus score averages for all patients were as follows: Nplugs=38±50; Nseg=7.0±4.5 and %Volobs=9.0±6.9%. Patients with high %Volobs (defined as %Volobs8.5, mean %Volobs) had significantly lower FEV1 scores (median=85.0) compared with the low mucus group (median=102.0; p = 0.03). %Volobs also correlated with FEV1 (ρ= -0.597, p = 0.007). All mucus scores demonstrated strong positive associations with Xe VDP: %Volobs (ρ = 0.845, p = 0.002), Nplugs (ρ = 0.736, p = 0.01), and Nseg (ρ = 0.648, p = 0.03). Importantly, %Volobs in mild patients (defined as FEV1 80,) also showed significant correlation with VDP (ρ = 0.833, p = 0.008; n = 9) and FEV1 (ρ=-0.497, p = 0.04; n = 17). Conclusion Precise mucus scores are significantly associated with lung function and regional ventilation defects in CF. While prior studies have linked mucus scores (Nseg and Nplugs) to clinical outcomes in pulmonary diseases such as asthma2, this work extends these scores to CF and introduces %Volobs as a more precise metric. These findings suggest that CT-based mucus scoring could provide clinically meaningful quantification of disease burden in CF, and %Volobs may offer a transferable framework for assessing airway obstruction across pulmonary diseases. References 1.Thia et al. Thorax(2014). 2.Dunican et al. JCI(2018). This abstract is funded by: CF Foundation and NIH
Georgiades et al. (Fri,) studied this question.