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Exploratory CT-Based Assessment of Emphysema Burden in Smokers with Bipolar Disorder Receiving Lithium Treatment

Year: 2026

Type: article

Abstract: Purpose: Experimental studies suggest that lithium may modulate emphysema-related tissue injury through activation of the WNT/β-catenin signaling pathway. However, clinical data examining the relationship between lithium exposure and emphysema burden remain limited. This study aimed to investigate the association between long-term lithium use and CT-derived emphysema burden in smokers with bipolar disorder. Patients and Methods: This retrospective observational study included 67 smokers with bipolar disorder who had received lithium treatment for at least 5 years and 71 matched controls with similar demographic and smoking characteristics. Quantitative emphysema measurements were obtained from thoracic computed tomography using low attenuation area percentage (LAA%). Multivariable linear regression analyses were performed adjusting for age, sex, BMI, and smoking exposure. Results: Right, left, and total lung LAA% values were lower in the lithium-treated group than in controls (7.53% vs 10.11%, p=0.009; 7.73% vs 10.02%, p=0.019; and 7.64% vs 10.07%, p=0.011, respectively). In multivariable analysis, lithium treatment remained independently associated with lower total LAA% after adjustment for age, sex, body mass index, and smoking exposure (B = -2.636, standardized β = -0.236, 95% CI -4.537 to -0.736; p = 0.007). Weak inverse correlations between serum lithium concentrations and emphysema measurements were observed in unadjusted analyses but were no longer significant after multivariable adjustment. Conclusion: Long-term lithium exposure was associated with lower CT-derived emphysema burden in smokers with bipolar disorder. Given the observational design and potential influence of inspiratory effort during CT acquisition, these findings should be considered hypothesis-generating rather than evidence of a protective effect. Prospective longitudinal and mechanistic studies are warranted to clarify the relationship between lithium exposure and smoking-related parenchymal lung injury.

Source: International Journal of COPD

DOI: 10.2147/copd.s626791