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Use of the Wnt/β-catenin Activator Lithium Is Associated with Less Emphysema
Divay Chandra1, Kassandra Allbright1, Gregory L Kinney2
1Department of Medicine, University of Pittsburgh, Pittsburgh, PA.
Annals of the American Thoracic Society
|June 29, 2026
Summary
Lithium use is linked to reduced emphysema severity in human studies, suggesting potential therapeutic benefits for this lung disease. Further research is warranted to explore lithium
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Wnt/β-catenin Signaling
Background:
- Emphysema involves alveolar destruction and impaired repair, with Wnt/β-catenin signaling dysfunction playing a role.
- Preclinical data suggest lithium, a Wnt/β-catenin activator, may mitigate emphysema.
- Human data on lithium's effects on emphysema are currently lacking.
Purpose of the Study:
- To determine if lithium use correlates with reduced emphysema prevalence and severity.
- To compare emphysema outcomes in lithium users versus users of other neuropsychiatric medications.
Main Methods:
- Analysis of cross-sectional data from the U.K. Biobank and COPDGene cohorts.
- Comparison of over 800 oral lithium users with individuals on other neuropsychiatric drugs.
- Outcomes included spirometry, physician-diagnosed emphysema, and CT-based emphysema measures, with adjustments for confounders.
Main Results:
- Lithium users showed higher FEV1 and FVC (% predicted) in the U.K. Biobank, with ~50% lower odds of emphysema diagnosis.
- In COPDGene, lithium users had improved spirometry (FEV1, FVC, FEV1/FVC) and lower CT-defined emphysema (LAA %F950).
- Associations remained significant after multivariable adjustment and sensitivity analyses.
Conclusions:
- Lithium use is associated with less emphysema in two independent human cohorts.
- Findings support preclinical evidence of Wnt/β-catenin activation's protective role in emphysema.
- Further investigation of lithium as a potential emphysema therapy is warranted.
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