ABSTRACT
Rationale: Quantifying functional small airways disease (fSAD) requires additional expiratory computed tomography (CT) scan, limiting clinical applicability. Artificial intelligence (AI) could enable fSAD quantification from chest CT scan at total lung capacity (TLC) alone (fSAD TLC ). Objectives: To evaluate an AI model for estimating fSAD TLC and study its clinical associations in chronic obstructive pulmonary disease (COPD). Methods: We analyzed 2513 participants from the SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS). Using a subset ( n = 1055), we developed a generative model to produce virtual expiratory CTs for estimating fSAD TLC in the remaining 1458 SPIROMICS participants. We compared fSAD TLC with dual volume, parametric response mapping fSAD PRM . We investigated univariate and multivariable associations of fSAD TLC with FEV 1 , FEV 1 /FVC, six-minute walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ), and FEV 1 decline. The results were validated in a subset ( n = 458) from COPDGene study. Multivariable models were adjusted for age, race, sex, BMI, baseline FEV 1 , smoking pack years, smoking status, and percent emphysema. Measurements and Main Results: Inspiratory fSAD TLC was highly correlated with fSAD PRM in SPIROMICS (Pearson's R = 0.895) and COPDGene (R = 0.897) cohorts. In SPIROMICS, fSAD TLC was associated with FEV 1 (L) (adj.ß = -0.034, P < 0.001), FEV 1 /FVC (adj.ß = -0.008, P < 0.001), SGRQ (adj.ß = 0.243, P < 0.001), and FEV 1 decline (mL / year) (adj.ß = -1.156, P < 0.001). fSAD TLC was also associated with FEV 1 (L) (adj.ß = -0.032, P < 0.001), FEV 1 /FVC (adj.ß = -0.007, P < 0.001), SGRQ (adj.ß = 0.190, P = 0.02), and FEV 1 decline (mL / year) (adj.ß = - 0.866, P = 0.001) in COPDGene. We found fSAD TLC to be more repeatable than fSAD PRM with intraclass correlation of 0.99 (95% CI: 0.98, 0.99) vs. 0.83 (95% CI: 0.76, 0.88). Conclusions: Inspiratory fSAD TLC captures small airways disease as reliably as fSAD PRM and is associated with FEV 1 decline. Funding Source: This work was supported by NHLBI grants R01 HL142625, U01 HL089897 and U01 HL089856, by NIH contract 75N92023D00011, and by a grant from The Roy J. Carver Charitable Trust (19-5154). The COPDGene study ( NCT00608764 ) has also been supported by the COPD Foundation through contributions made to an Industry Advisory Committee that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion.
ABSTRACT
RATIONAL: Ground glass opacities (GGO) in the absence of interstitial lung disease are understudied. OBJECTIVE: To assess the association of GGO with white blood cells (WBCs) and progression of quantified chest CT emphysema. METHODS: We analyzed data of participants in the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). Chest radiologists and pulmonologists labeled regions of the lung as GGO and adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGO (%GGOAMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGOAMFM with WBC, changes in %emphysema, and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Among 2,714 participants, 1,680 had COPD and 1,034 had normal spirometry. Among COPD participants, based on the multivariable analysis, current smoking and chronic productive cough was associated with higher %GGOAMFM. Higher %GGOAMFM was cross-sectionally associated with higher WBCs and neutrophils levels. Higher %GGOAMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at one-year follow visit by 11.7% (Relative increase; 95%CI 7.5-16.1%;P<0.001). We found no association between %GGOAMFM and one-year FEV1 decline but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up time of 1,544 days (Interquartile Interval=1,118-2,059). Among normal spirometry participants, we found similar results except that %GGOAMFM was associated with progression to COPD at one-year follow-up. CONCLUSIONS: Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.