M) in the lungs, has been reported to be an independent indicator of pulmonary function decline as well as other clinically relevant measures, re-affirming previous histological studies^[@CR22]--[@CR24]^. In addition, McDonough and colleagues have shown pathologically in human core lung specimens imaged by micro-CT that small airways disease may in fact serve as a precursor to emphysema^[@CR25]^. This highlights the potential importance of the independent and non-invasive evaluation of fSAD through PRM^[@CR26]^. Although the spatial information of fSAD is retained as a 3D PRM classification binary map, studies have primarily focused on the use of a whole-lung measure of fSAD, presented as a relative lung volume, which serves as the extent of this COPD component within the patient. As observed with emphysema, the spatial distribution of fSAD may aid treating physicians by providing them unique diagnostics that serve as a surrogate of clinically meaningful outcomes.

The present study demonstrates an extension of the PRM approach that extracts local topological features from PRM-derived disease classifications maps (Fig. [1](#Fig1){ref-type="fig"}). Using CT scans from COPD patients assessed as GOLD stage 1--4 accrued as part of a well-controlled multi-center clinical trial^[@CR27]^, we found that disease pattern (i.e. topological features) is correlated with COPD severity independent of disease extent (i.e. relative volume). Through micro-CT analysis of explanted lung cores from a lung transplant recipient with bronchiolitis obliterans syndrome, an obstructive lung disease‚ and longitudinal CT data acquired from a COPD subject, we provide anecdotal evidence that PRM-derived topological features are associated with structural differences and may also reveal trends in progressing obstructive disease. This work demonstrates for the first time that spatial features extracted from PRM^fSAD^ maps, specifically the surface area (S^fSAD^), provide independent predictors of clinical outcome measures, as well as provide 