The Use of Computed Tomography Densitometry for the Assessment of Emphysema in Clinical Trials: A Position Paper from the Fleischner Society
Emphysema's significant morbidity and mortality underscore the need for reliable outcome metrics in clinical trials. However, commonly accepted chronic obstructive pulmonary disease outcome measures do not adequately capture emphysema severity or progression. Computed tomography (CT) metrics have been validated as accurate indicators of pathological emphysema and predictors of chronic obstructive pulmonary disease progression, exacerbations, and mortality. This position paper reviews the evidence supporting CT densitometry as a biomarker for emphysema, establishes implementation standards, and highlights areas for future research. A systematic literature review addressed three key questions: whether CT densitometry can be used as a diagnostic biomarker of emphysema, whether CT densitometry can be used as a prognostic biomarker, and whether longitudinal change in densitometry can be used as a disease progression monitoring biomarker. Emphysema metrics, such as the percentage of low attenuation areas below -950 Hounsfield units, are validated, highly reproducible diagnostic and prognostic biomarkers. Volume-adjusted lung density is recommended for disease monitoring. Both metrics demonstrate a scan-rescan intraclass correlation coefficient of 0.99 with proper technique. The paper also discusses relevant CT physics, techniques, and sources of variation, including technical factors, physiological changes, and software analysis. Key recommendations for clinical trials include using standardized CT techniques, proper subject selection, and longitudinal evaluation with volume-adjusted lung density.
Authors
- Raúl San Jośe Estépar (ORCID: https://orcid.org/0000-0002-3677-1996)
- Joon Beom Seo (ORCID: https://orcid.org/0000-0003-0271-7884)
- Charlie Strange (ORCID: https://orcid.org/0000-0002-8109-8067)
- Eric A. Hoffman (ORCID: https://orcid.org/0000-0001-8456-9437)
- John D. Newell (ORCID: https://orcid.org/0000-0002-7337-5001)
- Sean B. Fain (ORCID: https://orcid.org/0000-0001-5461-0646)
- David A. Lynch (ORCID: https://orcid.org/0000-0002-6329-2325)
- Martine Rémy‐Jardin (ORCID: https://orcid.org/0000-0003-1944-4288)
- Samuel Y. Ash (ORCID: https://orcid.org/0000-0003-0224-6939)
- Philippe Greniér (ORCID: https://orcid.org/0000-0003-3745-0032)
- Christopher J. Ryerson (ORCID: https://orcid.org/0000-0003-1049-393X)
- Liz Kellermeyer (ORCID: https://orcid.org/0000-0001-6115-4343)
- Edwin K. Silverman (ORCID: https://orcid.org/0000-0002-3641-3822)
- Ruth Tal‐Singer (ORCID: https://orcid.org/0000-0002-5275-8062)
- Mathias Prokop (ORCID: https://orcid.org/0000-0001-8157-8055)
- R. Graham Barr
- Jonathan Goldin (ORCID: https://orcid.org/0000-0003-3007-9947)
- Bruce E. Miller (ORCID: https://orcid.org/0000-0003-3904-3182)
- James D. Crapo (ORCID: https://orcid.org/0000-0002-1262-5230)
- Yoshiharu Ohno (ORCID: https://orcid.org/0000-0002-4431-1084)
- George R. Washko (ORCID: https://orcid.org/0000-0002-2712-0569)
- Lars H. Nordenmark (ORCID: https://orcid.org/0000-0002-7139-8816)
- Miranda Kirby (ORCID: https://orcid.org/0000-0003-2951-784X)
- Cynthia H. McCollough (ORCID: https://orcid.org/0000-0002-5346-332X)
- Stephen M. Humphries (ORCID: https://orcid.org/0000-0002-5113-4530)
- Nancy A. Obuchowski (ORCID: https://orcid.org/0000-0003-1891-7477)
- Meilan Han
- Alexander A. Bankier (ORCID: https://orcid.org/0009-0006-1113-7821)
Institutions
- Ulsan College (KR)
- University of Iowa (US)
- Brigham and Women's Hospital (US)
- Cleveland Clinic (US)
- Mayo Clinic (US)
- Harvard University (US)
- University of British Columbia (CA)
- Fujita Health University (JP)
- Radboud University Nijmegen (NL)
- Medical University of South Carolina (US)
- University of California, Los Angeles (US)
- University of Massachusetts Chan Medical School (US)
- Université de Lille (FR)
- University of Michigan (US)
- Columbia University Irving Medical Center (US)
- Asan Medical Center (KR)
- Radboud University Medical Center (NL)
- National Jewish Health (US)
- University of Ulsan (KR)
- Association of Research Libraries (US)
- Memorial Medical Center (US)
- South Shore Hospital (US)
- Michigan United (US)
- Michigan Medicine (US)
- COPD Foundation (US)
- AstraZeneca (Sweden) (SE)
- St. Paul's Hospital (CA)
- AstraZeneca (Spain) (ES)
- Hôpital Foch (FR)
- UMass Memorial Medical Center (US)
- Toronto Metropolitan University (CA)
- Columbia University (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- American Journal of Respiratory and Critical Care Medicine
- Published
- 2025-03-24
- DOI
- https://doi.org/10.1164/rccm.202410-2012so
- Citations
- 12
- Primary Topic
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Type
- article
- Field-Weighted Citation Impact
- 18.22
Funders
- American Thoracic Society
- COPD Foundation
- National Heart, Lung, and Blood Institute