Abstract Rationale The SPIROMICS Study of Early COPD Progression (SOURCE) was designed to investigate early disease mechanisms by defining biological and imaging correlates of COPD in younger individuals with a smoking history. We applied a deep learning algorithm to baseline CT scans in the SOURCE cohort to evaluate the relationship between mucus plugging, lung function, and exacerbations. Methods SOURCE (ClinicalTrials.gov Identifier: NCT05033990) is an observational cohort of participants aged 30–55 years with a ≥ 10 pack-year smoking history. Using a two-stage deep learning pipeline, which combined a 3D nnU-Net airway segmentation model trained on n = 279 inspiratory CT scans from the Airway Tree Modeling (ATM’22) dataset with a lightweight three-layer encoder CNN, we identified regions connecting disjoint airway endpoints as mucus plug obstructions. Quantitative CT metrics included emphysema and functional small airways disease (fSAD). We used telephone follow-up to assess “breathing problems” as a marker of acute respiratory events. Associations between mucus plug burden (number of mucus plugs), quantitative CT metrics, and clinical outcomes were evaluated using linear and negative binomial regression analyses. Results Among n = 657 participants with available imaging data, mucus plug counts ranged from 0–11, with 93% showing no plugs and 7% demonstrating one or more. Most plugs were in the lower lobes, with 30.2% in the left lower lobe (LLL) and 30.2% in the right lower lobe (RLL) vs. 20.6% in the left upper lobe (LUL), 8.7% in the right upper lobe (RUL), and 10.3% in the right middle lobe (RML) (Figure 1). In both lower lobes, plug presence was significantly associated with emphysema (RLL, p 0.05; LLL, p 0.001) and CT-defined fSAD (RLL, p = 0.01; LLL, p 0.001). In negative binomial regression, higher mucus plug burden was significantly associated with increased total exacerbations requiring treatment in the 12 months before baseline (p = 0.05) and the six months following baseline (p 0.05). The strongest relationship was seen between mucus plug count and exacerbations requiring hospitalization between baseline and 6 months (p 0.001). Conclusion In the SOURCE early COPD cohort, approximately 7% of participants exhibited mucus plugging, predominantly in the lower lobes. Mucus plugs were associated with increased emphysema and fSAD and more frequent exacerbations, supporting their potential as an early imaging biomarker of small airway dysfunction and disease activity. This abstract is funded by: This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) Grants R01 HL139690 (to CJG) and R01 HL150023 (to MKH, CJG, and CRH), and R01 HL144718 (to JLC, MKH, and FJM), which support the SOURCE and SPIROMICS study.
Ram et al. (Fri,) studied this question.