Albert Rizzo, M.D.

Insights Into the Role of Mucus Plugging in Asthma

In recent research, mucus plugging has been shown to play a key role in severe cases of 

 and to be the most common driver of fatal events related to asthma. This role, enhanced by thoracic CT imaging studies of large airways, was explored in new research on the molecular characteristics of the airway epithelium in the peripheral lung.

This study is being led by Stephen Schworer, MD, PhD, an assistant professor of medicine at the University of North Carolina at Chapel Hill School of Medicine. Schworer spoke in the second issue of 

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

The team hypothesized that asthmatic small airways would exhibit mucus plugging with high expression of MUC5AC, the secreted mucin which is known to be upregulated in the large airway among those with asthma.

To test this hypothesis, we characterized small airways in tissues from fatal asthma cases and biopsies from steroid-resistant severe asthmatics. Using AB-PAS staining, we showed that there is a high mucus plug burden in bronchioles in both cohorts.

“We expand on previous fatal asthma morphology studies by adding the study of biopsies of severe, steroid-resistant asthmatics, and using innovative technologies including spatial transcriptomics and multiplex immunostaining to define the small airway molecular asthmatic phenotype,” Schworer said. “We hypothesized that asthmatic small airways would have mucus plugging with high expression of the MUC5AC, the secreted mucin known to be upregulated in the large airway and asthma. To test this hypothesis, we characterize small airways and tissues from fatal asthma cases and biopsies from steroid resistant severe asthmatics.”

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

Small Airway Mucus Plugging in Severe Asthma: Insights and Implications

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This interview in the latest issue of The Respiratory Report features Stephen Schworer, Md, PhD, discussing the role of mucus plugging in severe asthma.

Repurposing Medications for the Treatment of Patients with COPD

chronic obstructive pulmonary disease (COPD)

 is apparent to pulmonologists. Given the essential role of the stem-like alveolar epithelial type 2 (AT2) cells in repairing the lungs’ injured alveoli and maintaining alveoli number and lumen size, treatments designed to treat COPD should ideally either address AT2 cell biology and/or lead to AT2 cells number increases.

Joselyn Rojas-Quintero, MD, an instructor in medicine at Baylor College of Medicine, maintains a focus in her research to improve the world’s understanding of the pathophysiology of diseases such as COPD. In the second issue of 

 powered by the American Lung Association Research Institute, Rojas-Quintero spoke on her team’s current research in the COPD treatment space.

“Metformin has been known for over 55 years,” Rojas-Quintero said. “It's one of the safest drugs we have. It has all the pharmacovigilance you can find, and…has a multifactorial aspect of its mechanism of action. It can impact not just the liver, but the gut, the muscles, and the brain. It's not just the metabolic aspect, but also the aging aspect. So back in 2019, I was talking to my PI, back in Harvard and we started talking about how we can reverse the aging effect that we see in COPD…We thought, what if metformin really helps just to prevent the aging aspect of of the alveolar epithelial cells we see.”

Rojas-Quintero highlighted that metformin, a biguanide which can inhibit mitochondrial-complex-I, is a pleiotropic drug which has the capability to improve patients’ mitochondrial health. It does this through the use of AMPK activation, reducing oxidative stress and exerting anti-aging and anti-cancer results among patients.

Given the array of such effects, Rojas-Quintero and her team began by testing their theory that metformin may protect mice from cigarette smoke-induced emphysema through a pilot study.

“Quite impressively, we found that the telomeres of lungs were actually prevented from losing their length,” Rojas-Quintero said. “We thought there is more to this than just the metabolic aspect of it. We chose to analyze the kidneys and and the muscles of these mice, and we found the same thing. Then we thought ‘If this is in the animals, how can we translate that into humans? Is there anything we can try to map out from patients who have COPD and happen to have diabetes and are taking this medication?’...So we did a quantification of emphysema progression and patients who have COPD and also take metformin for their diabetes, they have slower emphysema progression. In fact, there is data out there now that says that patients who take this drug and have COPD, they actually do better.”

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

Metabolic Reprograming in Alveolar Epithelial Cells Type 2: Repurposing Old Drugs for Emphysema Treatment

Joselyn Rojas-Quintero, MD, speaks about her team's current research into COPD treatment on this issue of The Respiratory Report.

Duloxetine for Patients with COPD Suffering from Comorbid Depression

 who also suffer from comorbid depression may be 3 times more likely to be admitted to a hospital compared to non-depressed individuals with COPD. Given that over 15 million people suffer from physician-diagnosed COPD and given the likelihood of such comorbidities, addressing depression has become a significant concern for some in the world of health care providers.

Abebaw Yohannes, MSc, PhD, a professor of physical therapy at the University of Alabama at Birmingham School of Health Professions, is working with a team of investigators on a study assessing the feasibility of duloxetine as a treatment for depression among patients suffering from COPD. Yohannes spoke in the latest issue of 

, the quarterly pulmonology research newsletter powered by the American Lung Association Research Foundation, about his team’s work.

“We may ask why this study is needed,” Yohannes said. “We know from the literature that pharmacological interventions have been employed with the comorbidity of depression for moderate to severe COPD. However, they have been inconclusive. We're especially looking at using…selective norepinephrine reuptake inhibitors, sNRIs, as the first line of treatment for major depression in the general population, because of their efficacy and their safety, compared to tricyclic antidepressants.”

Yohannes highlighted the pilot study’s examination of duloxetine as a newer sNRI and its potential for patients with depression and COPD.

“The overall aim, for one, is to examine attitudes, perceptions, and beliefs of patients…living with depression,” Yohannes said. “So we are hoping to conduct a semi-structured qualitative interview. Patients will be recruited from the outpatient clinic here at the University of Alabama healthcare system as well as Baylor College of Medicine. We’ll try, first, to elucidate the acceptability and attitudes of patients about antidepressant drug therapy, and also probe any fears and misconceptions as well as barriers and facilitators about the treatment.”

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

Exploring Duloxetine for Depression in COPD: A Pilot Study

Abebaw Yohannes, MSc, PhD, speaks about his team’s pilot study designed to assess the use of duloxetine for patients with COPD and comorbid depression.

Enhancing Standards for Ethical Responsibilities within Clinical Research

A set of challenges have been identified in clinical research within the United States given inefficiencies in different processes, slow participant enrollment, and high costs. In an interview featured in the second issue of 

, the quarterly pulmonology research newsletter powered by the American Lung Association Research Foundation, Denise Kent, PhD, APRN, discussed her team’s research in this area.

Kent serves as an assistant professor for the department of biobehavioral nursing science at the University of Illinois at Chicago. Kent spoke in the latest issue of The Respiratory Report about the Returning Computed tomography rEsults to actIVE Lung Health Cohort participants (RECEIVE) study and its aims.

“The received study is an ancillary study embedded within the Lung Health Cohort study, also referred to as the LHC,” Kent said. “The LHC is funded by the National Heart, Lung, and Blood Institute, and is a study of 4000 healthy individuals between the ages of 25 and 35 years. It is the first ever study to focus on millennials. The overarching objective of the LHC is to establish a cohort of young adults for the purpose of defining lung health and developing targets to intercept chronic lung disease at its earliest stages.”

Kent went on to describe additional details regarding the RECEIVE study’s objectives and the implications of her team’s work.

“The overall objective of the received study is to develop a tool to support the return of chest CT results within the LHC,” Kent said. “The long term goal is to establish a process by which the return of individual research results is standardized for participants. Hopefully, our approach will inform how other studies return individual research results across a range of diseases and conditions across multiple studies.”

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

Ethical Excellence: Returning Computed tomography rEsults to actIVE Lung Health Cohort participants (RECEIVE)

This summarizes the latest in our pulmonology research quarterly newsletter powered by the American Lung Association Research Institute.

Albert Rizzo, M.D.

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