Nicola Hanania, MD, MS

Hanania explains how IL-33 inhibitors including itepekimab and astegolimab may uniquely benefit COPD exacerbation.

Prospecting the IL-33 Pathway for COPD Care, with Nicola Hanania, MD, MS

Mepolizumab (Nucala) and dupilumab (Dupixent) made history as the first biologic therapies indicated to treat eligible patients with 

 The recency of those pharmaceutical breakthroughs highlights not only the previous dearth of treatment advancement for patients with obstructive lung disease — it also showed how much more clinicians must uncover about the pathophysiology of COPD.

As one leading expert explains, similar pathway-targeting agents may be on the horizon for an even wider population of patients with COPD.

Chronic Obstructive Lung Disease (GOLD) International COPD Conference

 in Philadelphia, PA, Nicola Hanania, MD, MS, professor of medicine and director of the Asthma Clinical Research Center at Baylor College of Medicine, discussed the potential of IL-33 inhibitors to treat patients with COPD.

COPD is driven by 3 epithelial cytokines, Hanania explained: interleukin 33, 25 (IL-33; IL-25), and thymic stromal lymphopoietin (TSLP). IL-33 is released when the epithelium is harmed.

“And we know COPD patients [suffer] exposure to smoke, exposure to microbes and pollution, and all these can trigger injury to the epithelium,” Hanania said. “And thus, IL-33 has been shown to be expressed at a higher level in COPD and actually correlates with increased risk of exacerbation.”

IL-33 is associated with the trigger of type 1, 2, and 3 inflammation in patients with COPD. Whereas the IL-4 and IL-13-targeting dupilumab solely benefits exacerbations in patients with type 2 inflammation, an IL-33 inhibitor hypothetically may positively impact most patients with COPD.

Early clinical trials assessing 3 different IL-33 inhibitors — including itepekimab, tozorakimab and the ST2 receptor inhibitor astegolimab — suggest this approach may particularly benefit COPD exacerbations in patients who previously smoked.

“I think the jury is still out regarding blocking IL-33, but certainly it's a plausible pathway,” Hanania said. “I think there's been lots of discussion here and excitement that we're looking outside the box now for COPD. Certainly, type 2 pathway [targeting]…is very important, but blocking other inflammatory pathways is also very plausible.”

Johnson V, Iapoce C. FDA Approves Mepolizumab for Eosinophilic COPD. 

. Published online May 22, 2025. https://www.hcplive.com/view/fda-approves-mepolizumab-for-eosinophilic-copd

Smith T. FDA Approves Dupilumab (Dupixent) for Treatment of COPD. 

. Published online September 27, 2024. https://www.hcplive.com/view/fda-approves-dupilumab-dupixent-for-treatment-of-copd

Rabe KF, Martinez FJ, Bhatt SP, et al. AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD. ERJ Open Res. 2024;10(5):00718-2023. Published 2024 Sep 23. doi:10.1183/23120541.00718-2023

Singh D, Guller P, Reid F, et al. A phase 2a trial of the IL-33 monoclonal antibody tozorakimab in patients with COPD: FRONTIER-4. Eur Respir J. 2025;66(1):2402231. Published 2025 Jul 14. doi:10.1183/13993003.02231-2024

Greening N, Brightling C, Tal-Singer R, et alS1 Randomised, placebo-controlled trial of astegolimab for COPD with frequent exacerbations: ALIENTOThorax 2025;80:A7.

Videos

American College of CHEST Physicians (CHEST) 2025 Annual Meeting

 in Chicago, IL, this month was hallmarked by a monumental milestone: it was the 90th anniversary of the global conference of leading pulmonary experts. As described in the agenda, the meeting served to celebrate the history of CHEST as much as did to "look ahead to the next decade of medicine."

When CHEST convenes for its 100th anniversary in 2035, it will possibly feel like the last 10 years of innovation equaled to that achieved in the previous 90. Targeted, precision medicine has increasingly become standard in 

chronic obstructive pulmonary disease (COPD)

, and research into disease pathology and severity, as well as treatment response, has better informed our treatment initiation strategies.

 Nicola A. Hanania, MD, MS, professor of medicine and director of the Asthma Clinical Research Center at Baylor College of Medicine, discussed some of the sessions and data presentations from CHEST 2025 that speak to these latest innovations in asthma and COPD. Along with recapping the annual meeting's biggest takeaways, Hanania talked about the evolving role of biomarkers in determining treatment strategy and the importance of initiating care with the patient's priorities clearly defined.

What stood out to you as an acknowledgement of major change in pulmonary care during CHEST 2025?

We can start with asthma. There had been several sessions during the meeting focusing on targeted therapies in asthma, biologics specifically. The questions that clinicians are always intrigued about include when do I start biologic, how do I select the right biologic, what are the patient populations that I should consider biologics? We had some sessions where we discussed some clinical trial data about the efficacy of some of the new biologics. For example, we had a session where several speakers including myself discussed the selection of biologics — what are some patient characteristics where a specific biologic is chosen for a patient compared to others? As you know, in asthma, we have 6 biologics approved. More and more data with real-world scenarios are coming out to the point where it's really hard to pinpoint which one as a clinician. So there's been some discussion about using biomarkers to choose the right biologic, using patient characteristics and comorbidities as one of the pointers where you pick one biologic versus the other.

I had the chance to discuss remission, which is another unique term in asthma. When patients on biologics have minimal symptoms, their lung function stabilizes. When they have no exacerbation, no need for oral steroids, the question comes up of, "Can I stop or taper the biologic? Is that remission?" And so, I had the session where I gave a talk on defining clinical remission. So, right now, there's lots of potential definitions. Most people agree that when it comes to asthma, clinical remission includes absence of exacerbation, stabilizing lung function, normalizing symptoms, and no need for oral steroids. So, I reviewed the data about clinical remission that is out there with the different biologics, but also alluded to what's next. If a patient achieves clinical remission, does that mean I can stop their controller therapy? Does that mean I can taper down their biologics and give it less frequently? All these are questions that need to be studied. We don't know. Currently, we think that that last question is probably not applicable, because we don't have a cure for asthma yet. But I think cutting down the controller therapy in patients who achieve clinical remission on biologics may be a feasible thing to do, and there's some few studies out there that suggest that may be an option.

I also left the audience with several questions about clinical remission that needs to be explored in future studies: coming up with a universal definition, looking at other biomarkers including imaging to decide on clinical remission, not just symptoms and lung function. This field is very rich, and with more questions than answer, to be honest. But it's exciting because we are in the Precision Medicine Era now, and we're trying to not approach this disease as a one-size fits-all.

What is the state of COPD care, post-CHEST?

We're still a bit behind asthma. As you know, we have now a couple of biologics that have been approved for specific groups of patients with COPD — those with high eosinophil counts, or what we call type 2 COPD. And I had 3 presentations on specific topics in COPD intervention.

One was regarding data from the MATINEE study, which is a study that looked at mepolizumab in COPD patients who have recurrent exacerbations.

 We were interested to look at the cumulative dose of oral steroids during the two-year study. This was post hoc analysis of the large trial that was published in the New England Journal of Medicine. And we showed that being on a biologic can allow patients to need less oral steroids.

I also presented some data on patient-reported outcomes in COPD. As we know, symptoms are very important in these patients. Of course, exacerbations are also very important. We have done a study with dupilumab, another biologic approved for patients, and we looked specifically at a secondary endpoint of patients' symptoms, using standard questionnaires like SGRQ. We showed that dupilumab over the one year of the trial significantly improved symptoms in addition to reduction of exacerbation, which was the main outcome of the study in 2 trials, the NOTUS and the BOREAS study.

And then lastly, I presented data on another novel agent — which is not a biologic, but nebulized phosphodiesterase (PDE) 3 and 4 inhibitor ensifentrine. We showed in the clinical trials that we can improve lung function, reduce exacerbation, and improve symptoms — dyspnea, particularly. In the post hoc analysis that I presented, we looked at patients who did not have any exacerbation during the 6 months of the study, and we specifically looked at reduction in symptoms, mainly dyspnea.

 And we showed that this drug, on top of standard of care, reduced dyspnea in these patients, even if they didn't have an exacerbation. And you know, exacerbation and symptoms sometimes go hand in hand, but they don't have to both be there. You know, some patients have more dyspnea than they have exacerbations.

You talked a bit about blood-based biomarkers and the role they're playing in prescribing strategy, especially for targeted therapies, across asthma and COPD. We also saw some head-to-head trial data, for the first time, in some of these patients receiving biologics.

 And through all these new data, we seem to keep finding that we need to be testing for biomarkers. 

What do you think about our frequency and priority of blood-based and otherwise testing before initiating targeted severe airway disorder care?

We don't have many biomarkers available, as opposed to other fields of medicine. Currently, in both asthma and COPD, we certainly appreciate the usefulness of blood eosinophil count as a biomarker. It's very important in the subgroup of asthmatics — a large subgroup, but a smaller subgroup in COPD. High blood eosinophil in this population can serve both as a good, predictive biomarker, and it could be a pharmacodynamic biomarker. Most studies in asthma and COPD now show that the higher the blood eosinophils, the higher risk of exacerbation. GOLD in COPD has now endorsed that blood eosinophils are predictive of exacerbations, lung function decline, and even readmission to the hospital. But also, blood eosinophil can predict response to inhaled corticosteroids in COPD, and we know that is true in asthma as well.

And in asthma, there is a growing field of interest in what we call composite biomarker: using more than one. We had some data presented at CHEST but also other conferences, looking at the role of FeNO — which is not a blood-based biomarker but an exhaled biomarker. And when you look at both blood eosinophil and FeNO together, you have a better prognostic indicator. So, that leads us to think maybe in the future, one biomarker may not do it, and more than one may be needed.

In COPD, the role of FeNO is emerging but not yet endorsed yet by by everybody, because there is some fluctuation to levels. Smoking can affect FeNO levels as well. But blood eosinophil particularly has been a very important biomarker. People have looked at others. There were not too many papers at CHEST presenting on the role of other biomarkers, but I can tell you that there's some interest to look at other biomarkers that may be of prognostic value.

Another area of biomarker that is emerging is the utility of CT imaging biomarkers. They're not blood tests, and certainly more costly, but imaging can be actually a good tool if done properly to subdivide these patients and try to have a more precise approach to treatment. So, I think we have to wait and see. They're not ready for prime-time use in the clinic, but have been studied in several research papers and studies.

You also mentioned treating the subjective response to care: patient-reported outcomes and their own interpretation of clinical benefit.

 How does that conversation inform our next ventures or priorities in research?

We always have to keep patients in perspective. In fact, that's one of the things that, especially when it comes to expensive, targeted therapies that need long-term commitment, patient buy-in is very important. We advocate for, and almost every guideline suggests that we practice shared decision-making with the patient when it comes to choice of special treatments, including biologics. I think we have to keep that in mind, but we also have to look at what the patient's expectation of care is. As clinicians, we sometimes jump on prescribing the most expensive medicine that we think is is going to work best for the patient. That's good in a way, to think about the best for the patient, but we need to also get the patient's input. And that's something that I do personally in my clinic, and we advocate to do it.

First of all, patients may have different priorities as to what they're expecting from you. They also may have questions, and unless you address them, you're not going to get their adherence. And sometimes in COPD we get their caregiver involved, because they may have some other cognitive function issues. It also includes using inhalers. We have 4 platforms of inhaled delivery systems, and we cannot assume that they're all going to be working the same way for patients. So, choosing the right inhaler is a very important factor when it comes to managing COPD and asthma.

And last but not the least, patient outcomes are important. It's not just enough to look at numbers like lung function. It's important, but it's not the only thing. We want to see how a patient feels, that they're able to do things. We use questionnaires in our clinic like asthma control tests and COPD assessment tests. Those tell us subjectively how the patient is doing. Additionally, we shouldn't be stuck to FEV1 only. FEV

 is the hallmark of physiologic measure that suggests airway obstruction if it's low. But it doesn't tell the whole story. People are more interested now to look at small airway function as well. We had a session at CHESTdiscussing the role of small airway function and small airway disease in asthma and COPD — how is it important? How can we test for it? There are specific tests that can be done to assess small airway function. And why is that? Because current therapies don't address it. There are certain delivery systems that can deliver aerosol to the small airways, systemic treatments like biologics can address small airways, but we don't think about it as clinicians. We're stuck to FEV

. So ,all this is all new and quite interesting, at least making us think outside the box when it comes to patients and their outcomes.

Is there anything else you want to add or highlight from CHEST?

I've been in this field for 31 years, and every time we think, "Okay, that's it, we're done," it's wrong. There's lots of more work to be done. I think in both asthma and COPD, we are definitely thinking outside the box. I think we are embracing this precision medicine approach and no longer have this tunnel vision to these diseases. We're looking at the different phenotypes, endotypes, mechanisms, and biomarkers that drive the disease — and importantly, we're incorporating patient outcomes that we never really thought we would in the past.

Sciurba FC, Criner GJ, Christenson SA, et al. Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype. N Engl J Med. 2025;392(17):1710-1720. doi:10.1056/NEJMoa2413181

Kunzmann K. Dupilumab Lessens COPD Exacerbation Impact, with Nicola Hanania, MD, MS. HCPLive. Published online October 21, 2025. https://www.hcplive.com/view/dupilumab-lessens-copd-exacerbation-impact-nicola-hanania

Anzueto A, Barjaktarevic IZ, Siler TM, et al. Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase III Trials (the ENHANCE Trials). Am J Respir Crit Care Med. 2023;208(4):406-416. doi:10.1164/rccm.202306-0944OC

Kunzmann K. Dupilumab Bests Omalizumab in Airway Improvement for Patients with CRSwNP and Asthma. HCPLive. Published online October 22, 2025. https://www.hcplive.com/view/dupilumab-bests-omalizumab-airway-improvement-patients-crswnp-asthma

Kunzmann K. Clinical and Patient Definitions of Acute COPD Exacerbation Recovery Differ Greatly. HCPLive. Published online October 20, 2025. https://www.hcplive.com/view/clinical-patient-definitions-acute-copd-exacerbation-recovery-differ-greatly

Articles

The 2025 CHEST Annual Meeting marked its 90th anniversary, focusing on advancements in pulmonary care, particularly in asthma and COPD. Precision medicine and targeted therapies, including biologics, are becoming standard, with biomarkers playing a crucial role in treatment strategies. Discussions highlighted the potential for clinical remission in asthma and the evolving landscape of COPD care, including new biologics and patient-reported outcomes. The importance of shared decision-making and patient priorities in treatment was emphasized, alongside the need for further research into biomarkers and personalized approaches to pulmonary diseases.

Following CHEST 2025, Hanania discusses the progress being made toward more tailored, patient-oriented care in airway disorders.

The Asthma and COPD Precision Medicine Era, with Nicola A. Hanania, MD, MS

Hanania discusses the pooled BOREAS and NOTUS post hoc data showing dupilumab protects lung function before and after COPD exacerbations. 

Dupilumab Lessens COPD Exacerbation Impact, with Nicola Hanania, MD, MS

Dupilumab (Dupixent) reduced not only the rate of exacerbations, but their impact on lung function in treated patients with 

, according to late-breaking data presented at the 

American College of Chest Physicians (CHEST) 2025 Annual Meeting

Post hoc pooled data from the phase 3, randomized, placebo-controlled BOREAS and NOTUS trials showed subcutaneous 300 mg add-on dupilumab with triple inhaler therapy resulted in an approximate 6.1 percentage-point reduction in moderate-to-severe COPD exacerbation risk versus placebo. The biologic therapy regimen also was linked to a numerically less impaired change in mean post-bronchodilator percent predicted forced expiratory volume in 1 second (ppFEV

The US Food and Drug Administration (FDA) approved dupilumab for the treatment of patients with COPD based on the findings from BOREAS and NOTUS in September 2024.

"I think clinicians who see COPD patients need to understand that there's more to COPD...there are non-pharmacologic approaches, which we need to keep in mind. We want to get them stop smoking. We want them to exercise. We want to make sure they get vaccinated. When it comes to pharmacologic treatment, we have several options. Certainly, inhalers and bronchodilators are important, but in a subset of patients who continue to exacerbate, who have the biomarker profile like high eosinophils their blood, there are options now—and also to think outside the box when it comes to these options."

The new findings, presented by Nicola A. Hanania, MD, MS, professor of medicine and director of the Asthma Clinical Research Center at Baylor College of Medicine, suggest that dupilumab may protect lung function in patients with COPD who experience ≥1 moderate or severe exacerbation during their treatment with the biologic therapy.

 If investigators can find further evidence that patient lung function is preserved or improved through dupilumab, COPD exacerbations may not indicate treatment failure.

 at CHEST 2025, Hanania emphasized the impact of these new findings. Approximately one-fourth of all patients with COPD who experience an exacerbation never fully recover lung function back to baseline health. Dupilumab may help prevent the permanent dip in lung function — before, during, and even after an exacerbation.

“In addition to the fact that dupilumab can reduce exacerbation in this population, it may actually have a protective effect…on lung function during the attack,” Hanania said.

An interleukin-4 and -13 (IL-4; IL-13) pathway inhibitor, dupilumab targets the cytokines that propagate inflammation. This observed clinical effect on exacerbation impact helps elucidate the physiology of COPD — a condition without any prospects for curation. As Hanania explained, the biologic drug class including dupilumab has only recently provided clinicians more ability to personalize their targeted treatment approach for patients.

“About 50% of patients on standard-of-care therapy continue to exacerbate, so there is still a big, unmet need,” Hanania said. If the biologic drug class can mitigate the frequency and harms of exacerbations, then future treatment regimens may afford patients with COPD a state of disease stability.

“Maybe in the future we will [get closer to a cure], but we at least want to get them to a level where the lung function will not decline as quickly as it would without these drugs — that they would not get exacerbations, because with every exacerbation, there's a big hit,” Hanania said.

Hanania's disclosures include Sanofi, Genzyme, Regeneron, GSK, AstraZeneca, Regeneron, Genentech, and Merck.

Hanania NA, Brightling C, Puggioni F, Bhatt SP, et al. COPD Exacerbations Have Less Impact on Lung Function During Dupilumab Treatment: Pooled Analysis from BOREAS and NOTUS. Poster presented at: CHEST Annual Meeting 2025. Chicago, IL. October 19 – 22, 2025.

. Published September 27, 2024. https://www.hcplive.com/view/fda-approves-dupilumab-dupixent-for-treatment-of-copd

Early Lung Function Gains With Dupilumab Linked to Long-Term Asthma Outcomes, With Nicola Hanania, MD, MS

The treatment landscape for chronic obstructive pulmonary disease (COPD) has long centered on preventing exacerbations and slowing the relentless progression of lung function decline. While current inhaled therapies and biologics have improved patient outcomes, clinicians remain challenged by the variability of disease expression and the difficulty of predicting long-term benefit from new treatments. Recent data with dupilumab, an IL-4/IL-13 pathway–targeting biologic, offer important insight into how early improvements in lung function may translate into sustained outcomes, including reduced exacerbation rates and improved quality of life.

In a new post hoc analysis of the phase 3 NOTUS and BOREAS trials presented at the European Respiratory Society (ERS) Congress 2025, held September 27 to October 1 in Amsterdam, Netherlands, investigators examined whether lung function gains seen as early as 4 weeks after treatment initiation could predict reductions in exacerbations over 1 year, as well as improvements in patient-reported outcomes. 

 spoke with Nicola A. Hanania, MD, MS, professor of medicine and director of the Asthma Clinical Research Center at Baylor College of Medicine, who has been at the forefront of research into dupilumab’s role in COPD management and served as study investigator on the trials. The findings showed that early lung function improvement was modestly but significantly correlated with both reduced exacerbation risk and enhanced quality-of-life scores, offering a potential new tool for clinicians in monitoring treatment response.

For physicians, this analysis highlights an important shift. COPD management has often relied on retrospective markers, such as exacerbation history, to guide therapy escalation. If early, objective measures like forced expiratory volume can serve as reliable indicators of long-term benefit, clinicians may be better equipped to identify responders sooner, optimize biologic use, and personalize treatment strategies. In this interview, Hanania discussed the rationale for investigating early lung function improvements, the implications for clinical practice, and what these findings may mean for the broader goal of improving outcomes in COPD.

"Post hoc analyses have to always be looked at with a grain of salt, but it's an important addition to what we know. It also reinforces the knowledge that lung function improvement is an important thing to to work for to improve in the management of COPD... we sometimes say these patients have fixed airway obstruction. We can't move the needle. That's not true. We can improve lung function, and indeed, in our analysis, it sounds like those who have improvement lung function as early as 4 weeks had also reduction exacerbation and improvement in symptoms," Hanania said.

Media Update: ERS: new data across Sanofi’s immunology pipeline reinforce leadership in respiratory diseases. News release. Sanofi. September 4, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-09-04-05-30-00-3144180

Hanania discussed the rationale and findings of the BOREAS and NOTUS studies.