Episode #50 The Quest to Intercept Lung Disease with Drs. Ravi Kalhan, Amy Olson & George Washko

Dr. Albert Rizzo: Welcome back to LC, the monthly respiratory health podcast series from the American Lung Association and medical news site HCP Live. I’m your host, Dr. Albert Rizzo, chief medical officer of the American Lung Association. Before we introduce our guests today, just a reminder that Lancast is available on all your favorite streaming platforms. Subscribe to Lancast on YouTube to get new and archived episodes, as well as interview segments and episode highlights as they come out. A link to the show page, as well as the American Lung Association and HCP Live homepages for Lancast, can be found in each episode description.

For those of you who prefer a podcast, you can subscribe to Lungcast on Spotify, Apple Podcasts, and your favorite listening platforms. You can also register for more respiratory news and insights at both Lung.org and HCP Live.com.

Over the last few decades, the development of biomarkers in lung disease—both serum and imaging—has allowed more precise, targeted therapies to slow or stabilize diseases such as asthma, COPD, and lung cancer. Pursuing the same method, the American Lung Association Lung Health Cohort is trying to identify biomarkers and lifestyle patterns that may accurately identify disease processes before the disease becomes clinically evident. This approach may allow for earlier intervention and potential avoidance of certain diseases.

Today's discussion includes our guests:

• Dr. Robbie Cowan: Professor of Medicine and Preventive Medicine, Director of Asthma and COPD Programs, and Associate Chief for Clinical and Translational Research in the Division of Pulmonary and Critical Care at Northwestern.

• Dr. George Wasko: Physician at Brigham and Women’s Hospital, Professor of Medicine at Harvard Medical School.

They are both PIs in the American Lung Association’s Lung Health Cohort study. They are joined today by:

• Dr. Amy Olsson: Executive Director of Medical Affairs for Interstitial Lung Disease and Respiratory at Boehringer Ingelheim.

Dr. Rizzo: I want to thank you all for being here today.

Dr. Olsson: Thank you.

Dr. Cowan: Thanks for having me.

Dr. Rizzo: The Lung Health Cohort study leverages the national infrastructure of the American Lung Association’s Airways Clinical Research Centers (ACRC), which is 35 sites across the country, to engage diverse communities and ensure widespread participation. The ACRC network is the largest nonprofit clinical network dedicated to asthma and COPD research, and its infrastructure has been supported by the American Lung Association since 1999.

As the first large-scale lung health study to be embarked on, the Lung Health Cohort aims to track 4,000 healthy adults between the ages of 25 and 35 at the time of enrollment over their life course to understand how and why lung disease develops. We’re going to take the liberty of quoting Dr. Cowan, who has stated: by identifying early markers of lung disease, including environmental influences and genetic predispositions, the goal is to intercept disease progression before it becomes clinically evident. The Lung Health Cohort represents a paradigm shift toward enhancing lung health versus reacting to lung disease.

This proactive approach mirrors preventive measures in cardiovascular health, offering the potential to significantly reduce the burden of lung disease and improve public health. I would like to have Dr. Cowan and Dr. Wasko start the discussion by explaining the enrollment experience once participants are identified as candidates in this cohort, including questionnaires, tests, procedures, and planned visits over the course of the study.

Dr. Cowan: Sure, well thanks, Al. It’s really great to be with you again to talk about the Lung Health Cohort. As you mentioned, we seek participation from 25- to 35-year-olds who do not have chronic respiratory disease. We want to understand what we define as peak respiratory health. Lung function peaks in young adulthood, and this is as good as it’s going to get for a young, healthy person. We’re really interested in the determinants of peak respiratory health across the life course.

After participants provide informed consent, they answer a variety of questionnaires. Key questions relate to gestational age at birth, as premature birth can influence lung function across the life course. We also ask about residence at key points in life—birth, kindergarten, high school—to generate an exposure history using satellite models of outdoor air pollution estimates and model social determinants of health.

In addition to questionnaires about behaviors, fitness, vaping, and smoking, we perform physiologic testing, including spirometry in the clinic and follow-up home spirometry—generously supported by Boehringer Ingelheim. We also perform CT scans, collect blood biomarkers, nasal epithelial fluid, and urine for future biological ascertainment. We maintain regular contact with participants over the course of the study, including interim home testing and questionnaires to track exposures and behaviors over time.

Dr. Rizzo: That’s a great summary. I know the study plans to follow these individuals for many years, if not their lifetime. Some answers will take time to find, such as what you often call the “cholesterol of lung disease.” Can you also comment on some early learnings, such as portable spirometry experience or ancillary studies included in the cohort? Dr. Wasko, do you want to take this?

Dr. Wasko: Yeah, absolutely. Some chronic conditions take a life course of susceptibility and exposures to understand. We’re using data from other cohorts to build an artificial life course in silico. We look at early echoes of advanced disease in younger, otherwise healthy individuals. Symptomatology such as cough and sputum production is highly prognostic and related to impaired respiratory health.

We’re also conducting ancillary studies, including the Deep Lung Phenotyping Study, which uses advanced physiologic testing and imaging to assess small airway structure and function and relate it to symptoms. This helps us understand structural bases for respiratory symptoms earlier than previously possible.

Dr. Cowan: Sometimes, the respiratory community has a “learned helplessness” about waiting for disease to develop. But we don’t need to wait to understand ideal respiratory health. We don’t yet fully understand the determinants of maximum respiratory health. Even early biomarkers, like proteomic biomarkers, are being explored to identify unfavorable lung trajectories before disease onset. The goal is to preserve respiratory health at its peak.

Dr. Rizzo: Great perspective, Robbie. The study is supported by the American Lung Association and the National Heart, Lung, and Blood Institute. Funding has also come from pharmaceutical partners, including Boehringer Ingelheim, who joined in 2021 through a scientific advancement grant to support recruitment, retention, site infrastructure, and home spirometry. Dr. Olsson, why does your company see this study as so important?

Dr. Olsson: Boehringer Ingelheim has a long-standing commitment to respiratory health. The Lung Health Cohort aligns with our mission to improve patient outcomes through innovative research. Investing in this study helps us understand early stages of lung health and how it evolves. This knowledge informs treatment development and strategies to prevent disease before it begins. Our hope is that this study brings meaningful insights that support patient-centric R&D efforts.

Dr. Rizzo: Dr. Wasko, you’ve been involved in several cohort studies. Can you give more details about the CT imaging for presumed healthy participants?

Dr. Wasko: There’s a tremendous amount of structural and functional information in chest CT scans. Radiation doses have been reduced to preserve quality. Initially, CT scans characterized advanced lung disease, but now we can observe pre-COPD characteristics, small airway disease, and broader population-based findings. In younger participants, we’re using low-dose CT scans to safely assess structural and functional respiratory health, creating a foundation to predict future lung trajectories.

Dr. Rizzo: Dr. Cowan, enrollment is currently around 2,000 participants, halfway to the goal. Recruitment of healthy participants is challenging. Can you describe the strategies and struggles for recruiting a representative population?

Dr. Cowan: Recruiting healthy individuals is hard because they don’t gain immediate benefit. We initially used a volunteer sample, but that creates bias. In partnership with the ALA, we’ve employed broad marketing strategies, including targeted social media ads, influencers, and direct invitations to people based on demographic data. Our messaging emphasizes contributing to science and understanding respiratory health as part of a larger solution. Qualitative interviews showed participants are motivated by contributing to something bigger than themselves.

Dr. Rizzo: Before we conclude, I’d like closing comments. Dr. Olsson?

Dr. Olsson: Thank you for the opportunity. This study is a crucial step forward in understanding respiratory health. By focusing on healthy lungs, we can address lung diseases before they begin. Our hope is this research leads to targeted therapies and early intervention strategies, potentially impacting millions of lives.

Dr. Rizzo: Dr. Cowan and Dr. Wasko?

Dr. Cowan: This is a great opportunity to shift focus from disease treatment to prevention. We hope participants engage in the broader agenda, pharmaceutical companies continue involvement, and the scientific community generates ideas to study this unique 25-35-year-old cohort.

Dr. Wasko: We’re excited about the potential to prevent chronic respiratory disease. We’re grateful to sponsors and participants who contribute to this vision, helping change how we approach chronic conditions.

Dr. Rizzo: Thank you all for your time and expertise. To our listeners, for more on respiratory health, lung cancer screening, and CT scans, check our archives. Subscribe and rate Lungcast on your preferred platform, and visit Lung.org and HCP.com for more news and resources. Until next time, I’m Dr. Albert Rizzo, reminding you: if you can’t breathe, nothing else matters.