Episode #57 Going for GOLD: Updated COPD Guidelines with Dr. Gerard Criner

Dr. Albert Rizzo: Welcome back to Lungcast, the monthly respiratory health podcast series from the American Lung Association and medical news site hcpive.com. I'm your host, Dr. Albert Rizzo, the chief medical officer of the American Lung Association.

Before we introduce our topic and our guest today, just a reminder that Lungcast is available on all your favorite streaming platforms. Subscribe to Lungcast 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 ALA and HCP live homepages for Lungcast, can be found in each episode description.

For those of you who prefer podcasts, 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 hcpive.com.

Today's discussion is on important updates in the diagnosis and management of COPD. As of 2024 in the United States, COPD affects more than 14 million adults, and there are likely many more people who have COPD that are not yet diagnosed.

Let me review a few other facts regarding COPD. It's currently the sixth leading cause of death in the United States and fourth globally. More than half of the people diagnosed with COPD in the United States are women. COPD rates are higher in rural areas than in urban areas. Tobacco smoking remains the major cause of COPD and accounts for over 70% of COPD cases in high-income countries. Household air pollution is a major risk factor for COPD in low- and middle-income countries, and 14% of COPD cases are occupational in nature, caused by exposure to vapors, gases, dusts, and fumes in the workplace.

Today's discussion is going to focus on the 2025 updates in the GOLD guidelines for COPD. The Global Initiative for Obstructive Lung Disease, or GOLD, was launched back in 1997 in collaboration with the National Heart, Lung, and Blood Institute, National Institutes of Health, and the World Health Organization. This collaboration determines management guidelines for COPD care, shaped by committees made up of leading experts from around the world.

We're fortunate to have one of those experts with us today. Dr. Gerard Criner is Chair and Professor of Thoracic Medicine and Surgery at the Lewis Katz School of Medicine and Director of the Temple Lung Center in Philadelphia. Dr. Criner is also on the GOLD Board of Directors and the GOLD Science Committee. He and the Temple Lung Center have been hosting a yearly meeting in Philadelphia that showcases the GOLD updates with faculty from around the world.

Many of our listeners may remember we hosted Dr. Criner back on Lungcast in 2022, and we thought it appropriate to have him back to discuss important updates that have occurred in COPD in the GOLD guidelines since that episode.

Thank you for being with us today, Dr. Criner.

Dr. Gerard Criner: Thanks, Albert. I appreciate it.

Dr. Albert Rizzo: So, the 2025 Global Initiative for Chronic Obstructive Lung Disease report introduced several updates. I would like your perspective on a few of them. Spirometry remains a key diagnostic tool in COPD, and there's a section in the guidelines that speaks to the trajectories of FEV1 over a lifetime and also talks about the synapsis. In the same section, terms such as early, mild, young, pre-COPD, and PRISM are used to identify patients. Please explain to our listeners what these terms are used for and what they mean.

Dr. Gerard Criner: Yeah, a lot of different terms. The goal for COPD during my career has been trying to change the trajectory of the disease, and that's very difficult when you only start to identify patients and diagnose them when they're older and they have fixed airway obstruction, with very little reversibility that you can induce.

The ID from some of the more recent studies over the last two decades shows that all patients with COPD are not the same. They don't all get to the point of airflow obstruction in the same way. Some have developmental abnormalities from early neonatal development. Some develop it in adolescence. Some have environmental or genetic predisposition. Not everyone comes at COPD at the same point in their life or for the same reason.

The idea is to capture the broader group of patients at a time in their life where they may have reversible elements that could be targets for treatment, avoidance of hazards, or identification prognostically of having a greater likelihood of developing COPD later in life so that you could intercede and avoid them ending up with fixed airflow obstruction at the age of 60 or 70.

Early means early in the biologic process, not just a clinical term. Mild refers to mild airflow obstruction. Young refers to people developing COPD or COPD risk at age 20 to 50, rather than 60 to 70. Pre-COPD captures patients who may have structural abnormalities or symptoms but do not yet have fixed airflow obstruction. For example, people coming in for lung cancer screening—25% may have symptoms like cough, mucus production, or shortness of breath, or structural evidence of emphysema, but FEV1/FVC is not less than 70%.

PRISM refers to people with FEV1 reduced to 80% of normal but no fixed airflow obstruction. These patients often have metabolic disorders—obesity, cardiovascular disease, diabetes, or hypertension—that drive morbidity and mortality, and they have a 10–30% likelihood of developing COPD later in life.

All of these terms attempt to encapsulate different forms or pathways leading to fixed airflow obstruction, so interventions can occur earlier in the disease process.

Dr. Albert Rizzo: Makes perfect sense. That's a broad net to gather all these individuals. The mainstay for initial therapy for COPD still remains bronchodilation. In previous guidelines, we moved away from the four ABCD quadrants of identifying patients based on symptoms and exacerbations to direct therapy and instead combined the C and D quadrants into the E group. Why was this felt to be important, and what are the implications for therapy?

Dr. Gerard Criner: The major goal of GOLD is to distill clinical trial information and epidemiologic evidence into something clinically relevant for practitioners. The ABCD classification was based on symptoms and exacerbations. In reality, very few patients with low symptoms had frequent or severe exacerbations, so the CR group became very small.

We thought it was more practical to focus on symptom grading, and patients with moderate or severe exacerbations, regardless of symptomatology, would be captured in the E group. This simplifies clinical application.

Dr. Albert Rizzo: Makes sense. Aside from bronchodilators and inhaled corticosteroids, there were pharmacologic updates, including ensentrine, a selective dual inhibitor of PDE3 and PDE4. Could you discuss this medication and its role in therapy?

Dr. Gerard Criner: Ensentrine is a phosphodiesterase 3 and 4 inhibitor. It functions as both a bronchodilator and an anti-inflammatory agent, reducing the risk of exacerbations. Two six-month studies showed improvements in lung function and exacerbation reduction, mainly compared to placebo or non-triple therapy.

It may be used as a bronchodilator in patients who cannot tolerate long-acting bronchodilators or as an alternative to inhaled corticosteroids. It's currently approved only in the US, and its role in patients who have failed triple therapy is unknown.

Dr. Albert Rizzo: So it's not an add-on for those already on triple therapy but can replace ICS or bronchodilators in certain individuals.

Dr. Gerard Criner: Correct.

Dr. Albert Rizzo: Another pharmacologic update is the evolving role of biologics in COPD treatment. Can you discuss their role in reducing exacerbations and the current and upcoming therapies?

Dr. Gerard Criner: Biologics target exacerbation-prone patients, especially those with type 2 inflammation. Early studies with benralizumab and mepolizumab were not initially successful. Post-hoc analyses identified patients with eosinophil counts ≥300 as likely to respond.

Recent dupilumab trials showed significant improvements in exacerbation reduction, FEV1, and quality of life. Mepolizumab and benralizumab trials targeting this subgroup are ongoing, and new biologics targeting the alarmin pathway (IL-33, TSLP) are in clinical trials. The future is personalized therapy based on patient endotype and phenotype.

Dr. Albert Rizzo: Exciting research. The guidelines also point out the frequent coexistence of cardiovascular disease in COPD patients. Could you comment on this recommendation?

Dr. Gerard Criner: Shared risk factors like age, smoking, and immobility contribute to a 25% incidence of coronary artery disease in COPD patients. Exacerbations increase the likelihood of acute cardiac events within 90 days. Pulmonary hypertension affects 30–40% of mild-to-moderate COPD patients, driven by lung damage, hyperinflation, hypoxemia, and inflammation.

Some patients with disproportionate pulmonary hypertension may benefit from therapies like prostaglandins or vasodilators, alongside oxygen, rehabilitation, and other interventions.

Dr. Albert Rizzo: Thank you. Despite gaps in diagnosis, spirometry screening has been controversial. Can you clarify the distinction between screening and case-finding and how spirometry should be used?

Dr. Gerard Criner: The USPSTF does not recommend general population screening. GOLD focuses on high-risk populations, such as those undergoing lung cancer screening (age ≥50, ≥20 pack-years). In these groups, airflow obstruction is common, often underdiagnosed, and associated with other comorbidities detectable on imaging.

Dr. Albert Rizzo: So if a scan shows emphysema, the physician should evaluate the patient more deeply for COPD risk.

Dr. Gerard Criner: Correct. About 8% of screened patients have interstitial lung abnormalities, some with early pulmonary fibrosis markers.

Dr. Albert Rizzo: Before closing, can you discuss the proposed taxonomy or endotypes of COPD?

Dr. Gerard Criner: This framework highlights different pathways to COPD. Early lung development issues (like dyskinesia in premature infants) or biomass exposure may affect drug responses. Lung cancer screening and COPD are intertwined, highlighting the need to treat the patient, not just the disease.

Dr. Albert Rizzo: Thank you. Can you comment on COPD research at the Temple Lung Center?

Dr. Gerard Criner: We’re studying biologics, triple therapy, chronic bronchitis, emphysema, and novel interventions like metered-dose nitrogen cryospray, pulsed electrical field ablation, targeted lung denervation, endobronchial valves, airway stabilizers, and thermal ablation. Several results will be released this year.

Dr. Albert Rizzo: Sounds like a busy place. Dr. Criner, thank you for your work and insights.

To our listeners, review the full 2025 GOLD report at goldcopd.org/2025. The Temple Lung Center will host an in-person COPD conference in Philadelphia on November 12–13. Subscribe and rate Lungcast, and visit lung.org and hcpive.com for more resources.

Until next time, I'm Dr. Albert Rizzo reminding you: if you can't breathe, nothing else matters.