Patients with severe asthma benefit most from biologic therapies when treatment begins before permanent structural damage develops in the airways, with early intervention potentially preventing irreversible lung function decline and airway remodeling.
- Window of opportunity: Biologic therapies are most effective when started early, before substantial airway remodeling and structural changes occur
- Key biomarkers: Advanced imaging (CT scans and MRI), mucus plugging detection, and connected health technologies help identify disease progression and optimal treatment timing
- AI role: Machine learning and digital biomarkers support earlier treatment decisions and predict patient-specific disease trajectories
Patients with severe asthma may benefit more from biologic therapies when treatment is initiated before permanent structural damage develops in the lungs. That’s according to a new scientific review examining airway remodeling, emerging biomarkers and the role of artificial intelligence (AI) in asthma care.
The paper, “Targeting Airway Remodeling in Severe Asthma: Is There a Window of Opportunity for Biologic Therapy Predicting Effects Using Causal Artificial Intelligence?” explores whether a critical “window of opportunity” exists to best alter the long-term course of severe asthma by preventing or slowing airway remodeling, the structural changes that contribute to declining lung function and fixed airflow limitation. The paper, which was published in Allergy, also addresses the use of imaging-based remodeling measures, objective adherence monitoring and standardized digital biomarkers to determine timing.
Biologic therapies have already transformed treatment for severe asthma by reducing exacerbations and lowering reliance on oral corticosteroids. However, the authors said, questions remain about whether these treatments can do more than control symptoms and acute attacks. Their research suggests that the next frontier is to determine if biologics can modify the disease itself when administered during a time-sensitive period.
Investigators said introducing biologics early in the disease course offers a crucial therapeutic advantage, arguing that initiating treatment before substantial airway remodeling occurs could help preserve lung architecture and prevent irreversible airflow obstruction. Once structural changes become permanent, they noted, biologics may still reduce exacerbations but are unlikely to restore lost lung function.
The paper identifies airway remodeling as a key driver of asthma progression. Remodeling includes epithelial damage, fibrosis, airway smooth muscle growth, mucus abnormalities, angiogenesis and changes in airway nerves, investigators noted. These structural alterations can continue even when traditional signs of inflammation are controlled, making them a critical but often overlooked component of severe asthma, they wrote.
Airway remodeling is not a consequence of chronic inflammation, investigators said. Rather, structural cells and mechanical forces within the airways actively contribute to disease progression, creating self-sustaining pathways that can eventually lead to fixed airflow limitation.
To further determine the window of opportunity for biologic therapy, investigators also noted the benefits of advances in imaging technology and certain biomarkers. Imaging helps track structural changes more precisely, they said. For example, computed tomography (CT) scans can quantify airway wall abnormalities and mucus plugging, while specialized MRI techniques can reveal persistent ventilation defects that correlate with disease severity.
Mucus plugging is an important biomarker to observe, the researchers wrote. Studies have shown that mucus plugs are strongly associated with severe disease, eosinophilic inflammation, reduced lung function and persistent airflow obstruction. Unlike temporary symptoms, these plugs often remain stable over time, making them valuable indicators of long-term disease progression, they said.
Additionally, researchers said connected health technologies, such as smart inhalers, remote monitoring systems, wearable devices and smartphone-based cough tracking, are creating new opportunities to continuously monitor patients outside the clinic. Such technologies, they said, can identify periods when patients are at highest risk of progression and most likely to benefit from targeted intervention.
Researchers also noted the benefits of AI in identifying when biologic therapies should begin. They indicated that tools like machine learning, causal inference methods, digital biomarkers and future “digital twin” technologies that model patient-specific disease trajectories support an earlier versus delayed treatment approach.
In reviewing the effectiveness of current biologic therapies designed to measure symptom control and exacerbation reduction, investigators said emerging evidence indicates some of these treatments may affect structural features of asthma. They cited studies that have reported reductions in extracellular matrix deposition, tissue eosinophils, mucus burden and ventilation defects among patients receiving certain biologic therapies. Their analysis documented findings involving anti-IgE and anti-IL-5 therapies, including reductions in remodeling-associated tissue markers and improvements in imaging-based measures of airway obstruction.
