Quantitative CT of Normal Lung Parenchyma and Small Airways Disease Topologies are Associated With COPD Severity and Progression.

Objectives: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients, and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline.
Materials and Methods: PRM metrics of normal lung (PRM ^Norm ) and functional SAD (PRM ^fSAD ) were generated from CT scans collected as part of the COPDGene study (n=8956). Volume density (V) and Euler-Poincaré Characteristic (χ) image maps, measures of the extent and coalescence of pocket formations (i.e., topologies), respectively, were determined for both PRM ^Norm and PRM ^fSAD . Association with COPD severity, emphysema, and spirometric measures were assessed via multivariable regression models. Readouts were evaluated as inputs for predicting FEV ₁ decline using a machine learning model.
Results: Multivariable cross-sectional analysis of COPD subjects showed that V and χ measures for PRM ^fSAD and PRM ^Norm were independently associated with the amount of emphysema. Readouts χ ^fSAD (β of 0.106, p<0.001) and V ^fSAD (β of 0.065, p=0.004) were also independently associated with FEV ₁ % predicted. The machine learning model using PRM topologies as inputs predicted FEV ₁ decline over five years with an AUC of 0.69.
Conclusions: We demonstrated that V and χ of fSAD and Norm have independent value when associated with lung function and emphysema. In addition, we demonstrated that these readouts are predictive of spirometric decline when used as inputs in a ML model. Our topological PRM approach using PRM ^fSAD and PRM ^Norm may show promise as an early indicator of emphysema onset and COPD progression.
Competing Interests: Conflicts of Interest: Wassim W. Labaki reports personal fees from Continuing Education Alliance. Benjamin A. Hoff and Craig J. Galban are co-inventors and patent holders of tPRM, which the University of Michigan has licensed to Imbio, LLC. Craig J. Galban is co-inventor and patent holder of PRM, which the University of Michigan has licensed to Imbio, LLC. Benjamin A. Hoff and Craig J. Galban have financial interest in Imbio, LLC. Charles R. Hatt is employed by Imbio, LLC. David A. Lynch reports funds paid to the institution from NIH and personal payments from Boehringer Ingelheim. MeiLan K. Han reports personal fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, Novartis, Pulmonx, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, Regeneron, Amgen, UpToDate, Altesa Biopharma, Medscape, NACE, MDBriefcase and Integrity. She has received either in kind research support or funds paid to the institution from the NIH, Novartis, Sunovion, Nuvaira, Sanofi, AstraZeneca, Boehringer Ingelheim, Gala Therapeutics, Biodesix, the COPD Foundation and the American Lung Association. She has participated in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution. She has received stock options from Meissa Vaccines and Altesa Biopharma. For the remaining authors none were declared.