Use of the Wnt/β-catenin Activator Lithium Is Associated with Less Emphysema

Divay Chandra; Kassandra Allbright; Gregory L Kinney; Yisha Li; Russell Bowler; Karina Serban; Seyed Mehdi Nouraie; Toru Nyunoya; Puja Dutta; Stephen Rennard; Frank Sciurba; Melanie Königshoff

doi:10.1093/annalsats/aaoag167

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Use of the Wnt/β-catenin Activator Lithium Is Associated with Less Emphysema

Journal article

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Use of the Wnt/β-catenin Activator Lithium Is Associated with Less Emphysema

Divay Chandra, Kassandra Allbright, Gregory L Kinney, Yisha Li, Russell Bowler, Karina Serban, Seyed Mehdi Nouraie, Toru Nyunoya, Puja Dutta, Stephen Rennard, …

Annals of the American Thoracic Society

06/29/2026

DOI: 10.1093/annalsats/aaoag167

PMID: 42371758

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Abstract

Emphysema is defined by progressive alveolar destruction and impaired tissue repair, with diminished Wnt/β-catenin signaling implicated in its pathogenesis. Preclinical studies suggest that lithium, a pharmacologic activator of Wnt/β-catenin signaling, may attenuate emphysema. However, its effects in humans remain unknown. To investigate whether lithium use is associated with less emphysema compared to users of other neuropsychiatric medications. We analyzed cross-sectional data from two large cohorts-the U.K. Biobank and COPDGene-comprising over 800 individuals using oral lithium. Lithium users were compared to individuals using other neuropsychiatric medications. In the U.K. Biobank, outcomes included spirometry and self-reported physician-diagnosed emphysema. In COPDGene, outcomes included spirometry and quantitative CT measures of emphysema. Multivariable regression and propensity score matching accounted for demographics, smoking history, and psychiatric diagnoses. In the U.K. Biobank, lithium use was associated with higher FEV1 and FVC (% predicted) and ∼50% lower adjusted odds of emphysema diagnosis. In COPDGene, lithium users exhibited significantly higher FEV1, FVC, and FEV1/FVC ratios, lower CT-measured emphysema (LAA %F950), and higher lung density. These associations persisted after multivariable adjustment and across sensitivity analyses. Lithium use is associated with less emphysema in two independent cohorts. These findings align with preclinical evidence supporting Wnt/β-catenin activation as a protective mechanism and warrant further investigation of lithium as a potential therapy for emphysema.

Pulmonary Emphysema

Lithium Compounds/pharmacology

Wnt Signaling Pathway

COPD

Details

Title: Subtitle: Use of the Wnt/β-catenin Activator Lithium Is Associated with Less Emphysema
Creators: Divay Chandra - University of Pittsburgh
Kassandra Allbright - University of Pittsburgh
Gregory L Kinney - University of Colorado Denver
Yisha Li - Department of Epidemiology, University of Colorado, Denver, CO
Russell Bowler - National Jewish Health
Karina Serban - University of Florida
Seyed Mehdi Nouraie - University of Pittsburgh
Toru Nyunoya - University of Pittsburgh
Puja Dutta - University of Pittsburgh
Stephen Rennard - University of Michigan
Frank Sciurba - University of Pittsburgh
Melanie Königshoff - University of Pittsburgh
Resource Type: Journal article
Publication Details: Annals of the American Thoracic Society
DOI: 10.1093/annalsats/aaoag167
PMID: 42371758
ISSN: 2325-6621
eISSN: 2325-6621
Publisher: Oxford University Press
Grant note: I01 BX006096 / BLRD VA
Language: English
Electronic publication date: 06/29/2026
Academic Unit: Psychiatry; Internal Medicine
Record Identifier: 9985217040502771

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