Albert Rizzo, M.D.

This interview in the latest issue of The Respiratory Report features Jamie Hook, MD, discussing research into targeting the lung and not the virus to treat influenza.

Bolstering Alveolar Defense to Treat Complicated Influenza

Influenza is a major cause of global mortality and a frequent cause of pandemics, with death often resulting from secondary pneumonia by inhaled 

 (SA), especially in children. New research is uncovering how influenza infection disrupts lung defenses and opens the door to deadly bacterial co-infections with SA.

Jaime Hook, MD, Assistant Professor, Division of Pulmonary, Critical Care, and Sleep Medicine, Departments of Medicine and Microbiology, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, and her team are studying new therapeutic approaches for influenza lung infection that protect against fatal SA coinfection. 

Hook spoke in the third issue of The Respiratory Report, a quarterly newsletter from 

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

Her team found that influenza impairs alveolar defense by blocking CFTR-dependent liquid secretion and activating ENaC-driven absorption, creating an absorptive environment that allows inhaled 

 to cause fatal lung injury and were able to rescue alveolar wall liquid secretion and protect against SA-induced lung injury with the CFTR potentiator drug ivacaftor.

"These findings support CFTR potentiator therapy as a new treatment strategy for flu, SA coinfection, and they also inform the design of new CFTR potentiating therapies that might have more precise alveolar sites of action,  better drug efficacy, fewer side effects, and perhaps resilience in the face of new pandemic viruses and new viral and bacterial mutations that threaten the efficacy of existing drugs," Hook said.

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

Developing new treatments for influenza that target the lung – not the virus

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This interview in the latest issue of The Respiratory Report features Jamie Hook, MD, discussing research into targeting the lung and not the virus to treat influenza.


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

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.



This interview in the latest issue of The Respiratory Report features William Zhang, MD, discussing AM iron accumulation, which may contribute to the well-known phenomenon of AM dysfunction in COPD6.

Investigating COPD Pathogenesis: Abnormal Iron Homeostasis in Alveolar Macrophages

Disruptions in iron metabolism within alveolar macrophages may play a key role in the progression and exacerbation of chronic obstructive pulmonary disease (COPD), according to ongoing research led by William Zhang, MD, Assistant Professor of Medicine at Weill Cornell Medicine. His research aims to better understand the biological mechanisms underlying COPD and address gaps that currently limit the development of targeted therapies.

Zhang and his team used murine models of cigarette smoke exposure and single-cell RNA sequencing to investigate how dysregulated iron metabolism in alveolar macrophages contributes to COPD pathogenesis and exacerbation risk. He found that cigarette smoke induces iron loading in these immune cells, impairing their function, and that disrupting iron regulation may reduce emphysema development but could also weaken infection response. He also discussed proof-of-concept studies in humans the team is conducting.

"To get rid of an important protein that breaks down ferritin and allows the cell to retrieve iron when it needs to, especially when macrophages are fighting infection, I think probably also hampers them to some extent in this infection model. So, I think that the biology behind this is is more complex than we initially hypothesized and not so straightforward," Zhang said.

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

Abnormal Iron Homeostasis in Alveolar Macrophages: Implications for COPD Pathogenesis

This interview in the latest issue of The Respiratory Report features Peter Miller, MD, PhD, discussing the potential role of CH in developing COPD.

Uncovering the Link Between Clonal Hematopoiesis and COPD

Recent research has uncovered a potential link between clonal hematopoiesis and an increased risk of chronic obstructive pulmonary disease (COPD). This association was further explored in new research led by Peter Miller, MD, PhD, Assistant Professor of Medicine at Massachusetts General Hospital and Harvard Medical School.

In a cohort study of 50,000 individuals, his team found that people with CH were more likely to develop COPD, even after adjusting for age and smoking history. Interestingly, cigarette smoke not only increases COPD risk but also appears to drive the development of CH, creating a potential feedback loop: smoke exposure promotes CH, which in turn heightens inflammatory responses that may exacerbate or even trigger COPD. This hypothesis was further supported by mouse model studies in Miller's lab which found that mice with CH mutations exposed to cigarette smoke developed more emphysema than controls.

"What we're trying to do is really refine the association in the human genetics of how these risk factors play together, and potentially take advantage of different variations in DNA amongst that are different between different people to understand what other factors may be playing a role in these in these risks," Miller said.

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

Uncovering the Link Between Clonal Hematopoiesis and Chronic Obstructive Pulmonary Disease

This interview in the latest issue of The Respiratory Report features Peter Miller, MD, PhD, discussing the potential role of CH in developing COPD.



Albert Rizzo, M.D.

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