Biologics and Beyond: Clinical Perspectives on Managing Complex Airway Inflammation

Over the last decade, the landscape of respiratory care has undergone a dramatic transformation, driven by advances in the understanding of asthma and chronic obstructive pulmonary disease (COPD) pathophysiology and the emergence of targeted biologic therapies. Where treatment once centered largely on inhaled corticosteroids and bronchodilators, the field has entered a new era defined by phenotypic precision, biomarker-driven strategies, and earlier, more tailored intervention. For clinicians and patients alike, this progress has shifted expectations for disease control and long-term outcomes, particularly in populations that previously had few effective options.

In asthma, the approvals of biologics like dupilumab (Dupixent), benralizumab (Fasenra), and most recently tezepelumab (Tezspire) have allowed treatment to move beyond allergen or eosinophil-based models toward broader and more inclusive criteria. Tezepelumab’s 2021 FDA approval, in particular, marked a turning point as the first biologic approved for severe asthma regardless of baseline eosinophil count.1 These developments have redefined what “uncontrolled” asthma means and raised the bar for treatment goals—including reduced exacerbation rates, improved lung function, and steroid-sparing potential. As a result, allergists and pulmonologists are increasingly aligned in a shared, multidisciplinary approach to asthma management, focused on identifying the right therapy for the right patient as early as possible.

COPD, historically considered less amenable to targeted therapy, has begun to follow a similar trajectory. In 2024, dupilumab became the first biologic approved for eosinophilic COPD in the US, signaling new therapeutic possibilities in a field where treatment had long stagnated.2 At the same time, a growing understanding of COPD endotypes and inflammatory mechanisms is prompting a reevaluation of how the disease is diagnosed and managed. These changes are leading to greater overlap in how clinicians think about asthma and COPD care and are presenting new challenges in integrating advanced therapeutics into real-world workflows.

To explore these evolving questions and clinical implications, HCPLive convened a clinical forum event featuring expert perspectives from pulmonologists and allergists at the forefront of respiratory care, led by Igor Barjaktarevic, MD, PhD, Director of Bedside ultrasound and Medical Director of Liver-transplant Intensive Care Units at Ronald Reagan Medical Center, and Medical Director of COPD at the David Geffen School of Medicine at University of California – Los Angeles (UCLA).

The panelists discussed how asthma is now widely accepted as a heterogeneous disease, with type 2 inflammation (especially eosinophilic) being the most actionable phenotype for biologic intervention. They touched on biomarkers such as eosinophils, IgE, and FENO as being essential, though imperfect, tools for guiding therapy. They also emphasized increasing interest in personalized combinations or early biologic use in difficult-to-treat asthma.

“If you pick the right biomarker, it's not just a number. It's actually a target and something that you can follow over time to ascertain if the disease state is improving. So, I think a couple of points there I would kind of solidify is that we now know that asthma is heterogeneous. You see a lot of patients with shortness of breath, chest tightness, wheezing, and cough. If you zoom in, they do not have the same inflammatory state, and if you're able to find a biomarker to hone in on which kind of inflammation is going on, you can just identify that patient and find a target,” Lorraine Anderson, MD, allergist-immunologist at UCLA said.

Moving on to COPD, they acknowledged that it is even more heterogeneous than asthma and is now recognized to include a significant subset of patients with eosinophilic inflammation who benefit from therapies traditionally used in asthma. Dupilumab and mepolizumab both show efficacy in patients with ≥300 eosinophils/μL, but their relative positioning and long-term roles are still debated. Biomarker development remains a challenge, with limited predictive reliability and interference from factors like smoking.

“Asthma is in young population. COPD is usually in the older population. So that's a big difference in terms of inflammation. They're far gone. So, then you feel the rush to reverse, which sometimes is not reversible. Asthma, you want to prevent chronic steroid use because they're in a young age. So, I think inflammation is very different in the 2 diseases,” participants said.

They also touched on bronchiectasis, asthma-COPD overlap, and fixed obstruction in non-smokers, and looked forward to upcoming research into biologics' potential in these settings.

“We’re seeing more bronchiectasis because it's being identified. These people were being labeled as chronic bronchitis before COPD. And so, and there is one phenotype of COPD in bronchiectasis, right? There is the COPD patient with bronchiectasis, that's one of the many potential etiologies of bronchiectasis, right? But yes, it's a hot topic right now because we're going to finally have a targeted drug specifically for bronchiectasis,” participants said.

Overall, the participants emphasized that biologics and personalized medicine, especially biomarker-guided approaches, are growing in importance across conditions, although the field must keep in mind the limits of current trial designs and the gap between real-world patients and study populations.

REFERENCES

1. FDA Approves Tezspire™ (Tezepelumab-ekko) in the U.S. for Severe Asthma. News release. Amgen. December 17, 2021. https://www.amgen.com/newsroom/press-releases/2021/12/fda-approves-tezspire-tezepelumabekko-in-the-us-for-severe-asthma

2. Dupixent® (dupilumab) Approved in the U.S. as the First-ever Biologic Medicine for Patients with COPD. Regeneron Pharmaceuticals, Inc. September 27, 2024. https://www.globenewswire.com/news-release/2024/09/27/2954552/0/en/Dupixent-dupilumab-Approved-in-the-U-S-as-the-First-ever-Biologic-Medicine-for-Patients-with-COPD.html.