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

Area of Science:

• Pulmonary Medicine
• Pharmacology
• Wnt/β-catenin Signaling

Background:

• Emphysema involves alveolar destruction and impaired repair, with Wnt/β-catenin signaling playing a key role.
• Preclinical studies suggest lithium, a Wnt/β-catenin activator, may mitigate emphysema, but human data are lacking.

Purpose of the Study:

• To investigate if lithium use for neuropsychiatric conditions is associated with reduced emphysema susceptibility.
• To compare emphysema prevalence and severity in lithium users versus users of other neuropsychiatric medications.

Main Methods:

• Cross-sectional analysis of over 800 oral lithium users from the UK Biobank and COPDGene cohorts.
• Comparison with individuals using other neuropsychiatric medications, adjusting for demographics, smoking, and psychiatric diagnoses.
• Outcomes included spirometry, physician-diagnosed emphysema, and CT-based emphysema quantification.

Main Results:

• Lithium users showed higher FEV1 and FVC, and approximately 50% lower odds of diagnosed emphysema in the UK Biobank.
• In COPDGene, lithium users had improved lung function (FEV1, FVC, FEV1/FVC) and reduced CT-measured emphysema.
• These associations remained significant after multivariable adjustments and sensitivity analyses.

Conclusions:

• Lithium use is linked to reduced emphysema in two independent cohorts.
• Findings support Wnt/β-catenin activation as a protective mechanism against emphysema.
• Further research into lithium and related compounds as emphysema therapies is warranted.