Q&A: Mucus Plugging, Multimorbidity, and GOLD 2027, With Gerard Criner, MD

Mucus plugging is drawing attention as a measurable treatment target in COPD. In a COPDGene analysis of 4363 participants published in JAMA, investigators tracked all-cause mortality over a median follow-up of 9.5 years.¹

Mortality reached 34.0% among patients without plugs, 46.7% among those with plugs in 1 to 2 lung segments, and 54.1% among those with plugs in 3 or more segments.¹ Adjusted hazard ratios for death were 1.15 and 1.24 for the 2 plugging categories, respectively, compared with no plugging.¹

Therapeutic data are beginning to follow. An integrated analysis of the phase 3 OBERON and TITANIA trials, presented at the 2026 European Respiratory Society Congress, compared the anti-IL-33 monoclonal antibody tozorakimab with placebo.² Among 704 patients with paired CT scans, tozorakimab 300 mg every 4 weeks reduced segmental mucus plug score at the 52-week mark (mean difference, −0.959; P = .0005), a 25% relative reduction from baseline vs 3% with placebo.²

Exacerbation burden also extends well beyond the airways. In the EXACOS-CV US retrospective cohort study, a moderate exacerbation was associated with higher 30-day risks of acute cardiovascular events (HR, 1.23; 95% CI, 1.12-1.35) and death (HR, 1.22; 95% CI, 1.04-1.43).³ Risks remained elevated for 1 to 2 years following moderate and severe exacerbations.³

Gerard Criner, MD, chair and professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University and director of the Temple Lung Center, moderated sessions on clinician education and mucus plugging. In the following interview, Criner spoke with the team at HCPLive during the GOLD 2026 COPD International Conference in Philadelphia about those sessions, multimorbidity, the weight of a single moderate exacerbation, and his expectations for the 2027 GOLD Report:

HCPLive: What did yesterday’s sessions you moderated cover for clinicians?

Gerard Criner, MD: Some of the things we talked about in yesterday’s session were really at the level of the provider, talking about things they see in everyday practice, such as reviewing patients’ inhaler use, common mistakes with inhalers, and the differences between types of inhalers. We were trying to drill down, for people who provide care to patients as a nurse practitioner or a physician assistant, on how the GOLD guidelines can be interpreted for clinical practice for the diagnosis and assessment of patients, and on following the recommendations for treatment based on the patient’s characteristics or phenotype.

We also talked about how oxygen, noninvasive ventilation, and high-flow nasal therapy can be provided and used in patients in both the acute and the chronic setting. So, in the hospital and at home, what are the differences between them? What do you treat? How can you use combination therapy, and how can you best use those devices?

Then, in the evening, we used the current information to do case scenarios with live actors simulating patient care. We looked at the patient history and how you can take the history and distill the most important features of a patient, so you can guide further pharmacologic and non-pharmacologic therapy.

HCPLive: You also moderated a plenary session on mucus plugs. What was covered?

Gerard Criner, MD: With the mucus plugs, we spent a plenary session talking about what mucus plugs are, what they’re composed of, and what they mean to the patient with COPD in terms of worsened exacerbations, worse quality of life, worsened lung function, and really an increased risk for mortality. Then we talked about various agents shown to decrease the presence of mucus plugging, one of those being tozorakimab, and then some studies looking at targeting type 2 inflammation in patients with asthma, and some now being done in patients with COPD.

HCPLive: Is there any new or practice-shifting COPD data clinicians should know about right now?

Gerard Criner, MD: I think the most important things currently being talked about here are, first, the assessment of patients’ comorbid states and the multimorbidity they have. We want to make people aware of the importance of being more global in their perspective on how COPD affects the patient, rather than just the lung, and how to incorporate that into their practice of taking care of patients.

Another is the problem of just one moderate exacerbation. It’s important because it’s an important pathophysiologic process that can have long-term effects on patients’ lung health in terms of…lung function, but also their need for hospitalization, their morbidity or mortality, and major acute cardiac events.

We also talked about the importance of looking at patients with COPD and not just focusing on an exacerbation, but trying to capture the overall health, activity, and stability of the patient’s condition. That should be our goal for therapy.

HCPLive: What are you most looking forward to in the 2027 GOLD Report?

Gerard Criner, MD: Well, I think most of what I said is going to be incorporated into the report. Those would be the things we would focus on the most: trying to take the findings from this meeting and from the current literature and distill them into clinical guidance for people who take care of patients.

Editor’s Note: This Q&A transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. Diaz AA, Orejas JL, Grumley S, et al. Airway-occluding mucus plugs and mortality in patients with chronic obstructive pulmonary disease. JAMA. 2023;329(21):1832-1839. doi:10.1001/jama.2023.2065.

2. Washko G, et al. Tozorakimab reduces the number of lung segments with mucus plugs in patients with COPD at high risk of exacerbations: integrated analysis of the replicate OBERON and TITANIA phase 3 studies. Presented at: European Respiratory Society Congress 2026; September 5-9, 2026; Barcelona, Spain. Eur Respir J. 2026;68(suppl 70):PA2522. doi:10.1183/13993003.congress-2026.PA2522.

3. Daniels K, Lanes S, Tave A, et al. Risk of death and cardiovascular events following an exacerbation of COPD: the EXACOS-CV US study. Int J Chron Obstruct Pulmon Dis. 2024;19:225-241. doi:10.2147/COPD.S438893.