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

The 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 asthma and chronic obstructive pulmonary disease (COPD), and research into disease pathology and severity, as well as treatment response, has better informed our treatment initiation strategies.

In an interview with HCPLive, 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.1 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.2

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.3 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.4 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.5 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. FEV1 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 FEV1. 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.

References

1. 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
2. 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
3. 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
4. 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
5. 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