| Title: | Use of the Wnt/β-catenin Activator Lithium Is Associated with Less Emphysema |
| Journal: | Annals of the American Thoracic Society |
| Published: | 29 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42371758/ |
| DOI: | https://doi.org/10.1093/annalsats/aaoag167 |
Publication 20687
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Abstract
RATIONALE: 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.</p>
OBJECTIVES: To investigate whether lithium use is associated with less emphysema compared to users of other neuropsychiatric medications.</p>
METHODS: 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.</p>
MEASUREMENTS AND MAIN RESULTS: 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.</p>
CONCLUSIONS: 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.</p>
12 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 60327 | Role of Caspase 12 in respiratory diseases among people of African decent |
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