Association of "Emptying Emphysema" with Clinical and Radiographic Features in People with Smoking History

Spyridon Fortis; Sarah E Gerard; Matthew Strand; Amin Motahari; Surya P Bhatt; Meilan K Han; James D Crapo; Edwin K Silverman; Joseph M Reinhardt; Eric A Hoffman; Alejandro P Comellas

doi:10.1093/annalsats/aaoag151

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Association of "Emptying Emphysema" with Clinical and Radiographic Features in People with Smoking History

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Association of "Emptying Emphysema" with Clinical and Radiographic Features in People with Smoking History

Spyridon Fortis, Sarah E Gerard, Matthew Strand, Amin Motahari, Surya P Bhatt, Meilan K Han, James D Crapo, Edwin K Silverman, Joseph M Reinhardt, Eric A Hoffman, …

Annals of the American Thoracic Society

06/08/2026

DOI: 10.1093/annalsats/aaoag151

PMID: 42261268

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Abstract

Emphysema is a hallmark of chronic obstructive pulmonary disease (COPD), yet its presumed coexistence with small airway disease remains debated. To investigate the clinical significance of a novel CT-feature, "emptying emphysema," characterized by preserved expiratory density despite inspiratory attenuation consistent with emphysematous changes. We analyzed data from 8,171 COPDGene participants with paired inspiratory-expiratory CT scans. Emptying emphysema was quantified using Parametric Response Mapping (%PRMEE) as the percentage of lung voxels with attenuation < -950 HU on inspiration and ≥ -856 HU on expiration. Multivariable models assessed associations between %PRMEE and clinical, functional, and radiographic outcomes. Each one standard deviation (SD) higher in baseline %PRMEE was independently associated with less dyspnea (OR = 0.89; 95%CI: 0.94 to 0.95; P < .001) and impaired quality of life (OR = 0.87; 95%CI 0.83 to 0.93; P < .001). Each SD higher in %PRMEE was associated with a 11.2-meter increase in 6-minute walk distance (95%CI 8.7 to 13.6; P < .001). Higher %PRMEE was associated with lower FRC/TLC. Given the correlation between %PRMEE and traditional emphysema, we performed stratified analyses. Within each traditional emphysema quartile, higher %PRMEE was generally associated with higher FEV1% predicted and FEV1/FVC. Longitudinally, higher baseline %PRMEE was associated with attenuated lung density decline, and reduced mortality (HR = 0.90 per SD increase; 95%CI 0.86 to 0.95; P < .001). Emptying emphysema represents a CT-defined feature associated with preserved lung function and favorable clinical outcomes. Although it remains unclear whether this reflects a true pathological entity, these findings raise the possibility that emptying emphysema reflects alveolar-predominant changes occurring without significant airway disease, warranting further investigation.

Pulmonary Disease

Death

Chronic Obstructive

disease progression

Emphysema

Smoking

UIOWA OA Agreement

Details

Title: Subtitle: Association of "Emptying Emphysema" with Clinical and Radiographic Features in People with Smoking History
Creators: Spyridon Fortis - University of Iowa
Sarah E Gerard - University of Iowa
Matthew Strand - National Jewish Health
Amin Motahari - University of Iowa, Radiology
Surya P Bhatt - University of Alabama at Birmingham
Meilan K Han - Michigan Medicine
James D Crapo - National Jewish Health
Edwin K Silverman - Brigham and Women's Hospital
Joseph M Reinhardt - University of Iowa
Eric A Hoffman - University of Iowa, Radiology
Alejandro P Comellas - University of Iowa
Resource Type: Journal article
Publication Details: Annals of the American Thoracic Society
DOI: 10.1093/annalsats/aaoag151
PMID: 42261268
NLM abbreviation: Ann Am Thorac Soc
ISSN: 2325-6621
eISSN: 2325-6621
Publisher: Oxford University Press
Language: English
Electronic publication date: 06/08/2026
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
Record Identifier: 9985174611602771

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