New approaches for identifying and testing potential new anti-asthma agents

ABSTRACT

Introduction: Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities.

Areas covered: The expanding knowledge on the pathogenetic mechanisms of asthma has allowed researchers to investigate a range of new treatment options matched to patient profiles. The aim of this review is to provide a comprehensive and updated overview of the currently available, new and developing approaches for identifying and testing potential treatment options for asthma management.

Expert opinion: Future therapeutic strategies for asthma require the identification of reliable biomarkers that can help with diagnosis and endotyping, in order to determine the most effective drug for the right patient phenotype. Furthermore, in addition to the identification of clinical and inflammatory phenotypes, it is expected that a better understanding of the mechanisms of airway remodeling will likely optimize asthma targeted treatment.

KEYWORDS:

• Asthma
• airway hyperresponsiveness
• airway remodeling
• T2-high inflammation
• T2-low inflammation
• omalizumab
• mepolizumab
• biological therapy

Article highlights

• Airway inflammation, airway hyperresponsiveness, and bronchial remodeling are the key pathophysiological features of asthma.

• Asthma pathogenesis is characterized by two major pathophysiological pathways: a T2-high featuring increased eosinophilic airway inflammation, and a non T2/T2-low with either neutrophilic or paucigranulocytic airway inflammation.

• Ongoing research on asthma, aimed to recognize distinct clinical phenotypes, molecular endotypes, and associated reliable biomarkers, has led to the development of new targeted treatment modalities.

• Most available biological therapies for severe asthma targets T2-high asthma, including omalizumab, mepolizumab, and reslizumab. These therapies demonstrated to improve asthma symptoms, exacerbation rates, and lung function parameters; a disease-modifying action has not been provided yet.

• Other biologics, as well as other targeted treatment options, are required for optimal asthma management but deserve further clinical development both in adults and children.

• In addition to clinical and inflammatory phenotypes, a better understanding of the mechanisms of remodeling is highly expected to optimize asthma targeted treatment.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.