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Biologics and airway remodeling in asthma: early, late, and potential preventive effects
G Varricchi1,2,3,4, R Poto1,2,3, M Lommatzsch5
1Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Abstract:
Although airway remodeling in severe and/or fatal asthma is still considered irreversible, its individual components as a cause of clinical symptoms and/or lung function changes remain largely unknown. While inhaled glucocorticoids have not consistently been shown to affect airway remodeling, biologics targeting specific pathways of airway inflammation have been shown to improve lung function, mucus plugging, and airway structural changes that can exceed those seen with glucocorticoids. This superiority of biologic treatment, which cannot be solely explained by insufficient doses or limited durations of glucocorticoid therapies, needs to be further explored. For this field of research, we propose a novel classification of the potential effects of biologics on airway remodeling into three temporal effects: early effects (days to weeks, primarily modulating inflammatory processes), late effects (months to years, predominantly affecting structural changes), and potential preventive effects (outcomes of early treatment with biologics). For the identification of potential preventive effects of biologics, we call for studies exploring the impact of early biological treatment on airway remodeling in patients with moderate-to-severe asthma, which should be accompanied by a long-term evaluation of clinical parameters, biomarkers, treatment burden, and socioeconomic implications.
Insights
Biologics may reverse airway remodeling in severe asthma, unlike glucocorticoids. Further research is needed to understand early, late, and preventive effects of biologic treatments on asthma.
Area of Science:
- Pulmonology
- Immunology
- Pharmacology
Background:
- Airway remodeling in severe asthma is often considered irreversible, with unclear contributions to symptoms and lung function decline.
- Inhaled glucocorticoids show limited efficacy in reversing airway remodeling.
- Biologics targeting specific inflammatory pathways demonstrate superior improvements in lung function and airway structure compared to glucocorticoids.
Purpose of the Study:
- To propose a novel classification of biologic effects on airway remodeling based on temporal effects: early, late, and preventive.
- To highlight the need for further exploration of biologic treatment superiority over glucocorticoids.
- To call for studies investigating the long-term preventive effects of early biologic intervention in moderate-to-severe asthma.
Main Methods:
- Literature review and synthesis of existing data on airway remodeling and biologic therapies.
- Proposal of a temporal classification framework for biologic effects (early, late, preventive).
- Conceptualization of future research designs for evaluating preventive effects.
Main Results:
- Biologics show potential to improve lung function, mucus plugging, and airway structural changes beyond glucocorticoid effects.
- A three-tiered temporal classification (early, late, preventive) is proposed for understanding biologic impacts.
- Early biologic treatment may offer preventive effects on airway remodeling.
Conclusions:
- Biologics represent a promising therapeutic strategy for addressing airway remodeling in severe asthma.
- Further research is essential to elucidate the mechanisms and long-term benefits of biologics, particularly their preventive potential.
- Long-term studies evaluating clinical, biomarker, and socioeconomic outcomes are crucial for optimizing biologic therapy.
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