Divay Chandra, MD, MSc

This interview in the latest issue of The Respiratory Report features Divay Chandra, MD, MSc, discussing lithium's potential enhancement of alveolar repair after injury.

Exploring Lithium: A Potential Disease-Modifying Therapy for Emphysema

While chronic obstructive pulmonary disease (COPD) remains a leading cause of death worldwide, there is still no treatment that reverses or halts its progression.  Recent research is exploring the potential of lithium, a drug commonly used for bipolar disorder, as a candidate to repair lung damage by targeting a key regenerative signaling pathway in the lung.

This study is being led by Divay Chandra, MD, MSc, an associate professor in the Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, at University of Pittsburgh in Pennsylvania. Chandra spoke in the third issue of 

 that is powered by the American Lung Association Research Institute, on his team’s current research in this area.

Chandra and his team analyzed data from large population cohorts to assess whether individuals taking lithium for other conditions had less lung disease and then measured environmental lithium exposure in people not on the drug. They found that both therapeutic and naturally occurring lithium levels were associated with reduced COPD severity, supporting its potential as a disease-modifying agent. The next step in Chandra's research is scaling up their studies to look at longitudinal progression and is enabled by an American Lung Association grant.

"Despite decades of research and multiple clinical trials, as yet, we have not been able to identify a disease modifying agent in COPD. And that is really the frustrating part. We have drugs that can treat symptoms. You know, we have drugs which can treat eosinophilia, which can reduce exacerbations, but we have no drug that can get at the fundamental disease process that drives this lung disease. That is exactly where lithium could play a role," Chandra said.

To learn more about Chandra's research, view the interview above or read his contribution to the third issue of The Respiratory Report here:

Exploring Lithium as a Potential Disease-Modifying Therapy for Emphysema

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This interview in the latest issue of The Respiratory Report features Divay Chandra, MD, MSc, discussing lithium's potential enhancement of alveolar repair after injury.



Chronic obstructive pulmonary disease (COPD) remains the fourth leading cause of death among adults in the United States.

 Despite its prevalence and significant burden on healthcare, no disease-modifying therapies exist. While tobacco smoking is a primary risk factor, it accounts for only ~50% of attributable risk, highlighting the need for further research into environmental and biological contributors.

 Lithium, a naturally occurring element, has recently emerged as a potential therapeutic candidate for emphysema due to its ability to activate WNT/β-catenin signaling—a pathway critical for lung development and repair.

Lithium and WNT/β-Catenin Signaling in COPD

WNT/β-catenin signaling is indispensable for alveolar repair after injury.

 Our preliminary work indicates that lithium may enhance this reparative mechanism. Intra-peritoneal lithium administration in mice activated WNT/β-catenin signaling and reduced experimental emphysema.

 Individuals using lithium for mood stabilization exhibited lower emphysema severity in independent cohorts. Ex vivo studies of human lung tissue demonstrated that lithium-induced reparative processes were proportional to the degree of airflow obstruction.

Given these promising preliminary findings, our study aims to assess whether higher circulating lithium levels are associated with emphysema in a new study. Using data from 200 COPDGene participants, we will measure lithium levels via inductively coupled plasma mass spectrometry (ICP-MS) and correlate them with radiographic emphysema. Additionally, we seek to determine the relationship between circulating and lung tissue lithium levels. By utilizing plasma and lung tissue samples from 35 organ donors and transplant recipients, we will compare lithium levels to establish whether systemic lithium levels reflect pulmonary lithium concentrations.

Our findings could pave the way for a paradigm shift in COPD treatment. Unlike conventional therapies that primarily target symptoms, lithium offers a potential disease-modifying approach. Lithium at levels found in the environment or available as over-the-counter supplements has demonstrated neuroprotective and anti-inflammatory benefits with minimal toxicity. Given lithium’s established pharmacokinetics and widespread availability, transitioning from observational studies to interventional trials is highly feasible.

Lithium's ability to activate WNT/β-catenin signaling and promote alveolar repair presents a compelling case for its role as a novel COPD therapy. Our ongoing studies seek to provide robust evidence supporting lithium’s protective effects, ultimately laying the groundwork for clinical trials. If successful, lithium supplementation could offer a cost-effective, widely accessible intervention for emphysema—challenging the current paradigm that COPD is an irreversible disease.

Chandra has no relevant disclosures to report.

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Articles

Chronic obstructive pulmonary disease (COPD) is a leading cause of death, with no current disease-modifying therapies. While smoking is a major risk factor, it accounts for only half of the cases, necessitating further research into other contributors. Lithium has emerged as a potential therapeutic candidate due to its ability to activate WNT/β-catenin signaling, crucial for lung repair. Preliminary studies suggest lithium may reduce emphysema severity. Ongoing research aims to correlate lithium levels with emphysema, potentially paving the way for lithium as a novel, cost-effective COPD treatment.

Divay Chandra, MD, MSc, University of Pittsburgh, is evaluating whether higher circulating lithium levels are associated with emphysema in a new study.