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Record W4416215047 · doi:10.17615/6455-md85

Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans

2025· article· en· W4416215047 on OpenAlexfundno aff
Russell P. Bowler, Fernando J. Martínez, David Couper, Mark T. Dransfield, Martin R. Prince, Elsa D. Angelini, Andrew J. Swift, Jie Yang, John S. Kim, Wei Shen, Elizabeth C. Oelsner, João Pedroso Lima, Ani Manichaikul, Michael H. Cho, Nadia N. Hansel, Tuuli Lappalainen, Karol E. Watson, Edwin K. Silverman, Christine Kim Garcia, Robert Paine, David R. Jacobs, MeiLan K. Han, Andrew F. Laine, Stephen S. Rich, Prescott G. Woodruff, Benjamin M. Smith, Eugene R. Bleecker, Silva Kasela, John H. M. Austin, Victor E. Ortega, Pallavi Balte, Wendy S. Post, Eric A. Hoffman, Norrina B. Allen, R. Graham Barr, Daniel Malinsky, Christopher S. Cooper, Tess D. Pottinger, Emlyn Hughes, Joel D. Kaufman

Bibliographic record

VenueUNC Libraries · 2025
Typearticle
Languageen
FieldMedicine
TopicChronic Obstructive Pulmonary Disease (COPD) Research
Canadian institutionsnot available
FundersFonds de Recherche du Québec - SantéNational Institutes of HealthGenentechGrifolsRegeneron PharmaceuticalsMcGill University Health CentreMcGill UniversityTeva Pharmaceutical IndustriesCOPD FoundationGlaxoSmithKlineNational Heart, Lung, and Blood InstitutePfizerNovartis Pharmaceuticals CorporationAstraZenecaChiesi FarmaceuticiSanofiCanadian Institutes of Health ResearchSunovionAmerican Heart AssociationIkariaU.S. Environmental Protection Agency
KeywordsCOPDLungPulmonary emphysemaUnsupervised learningPulmonary diseaseRespiratory disease

Abstract

fetched live from OpenAlex

BACKGROUND: Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations. METHODS: New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined. RESULTS: The algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91-1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near <em>DRD1</em>, which is implicated in mucin hypersecretion (p=1.1 &times;10<sup>-8</sup>). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome. CONCLUSION: Large-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.284
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.257
Teacher spread0.244 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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