What have recent advances in therapy taught us about severe asthma disease mechanisms?

ABSTRACT

Introduction: Severe asthma still represents a worldwide challenge. The need for further treatment options has stimulated basic and pharmacological research to focus on the immune and inflammatory background of asthma. The new biologic drugs express the considerable advances in the field and besides providing a revolutionary treatment option for severe asthma, contribute themselves to better understand the pathophysiologic mechanisms they address, paving the way to new potential targets.

Areas covered: A selective search on PubMed and Medline was performed, including the evidence on immunology of severe asthma published up to May 2019 by focusing on the immunological effects of biologic drugs underlying their clinical outcomes.

Expert opinion: The recent pharmacological research in the field of biologics has represented an exceptional opportunity for exploring severe asthma mechanisms. However, some points deserve to be addressed by further investigation. Although in the absence of safety warnings so far, interfering with the immune system may raise some safety concerns, especially in the long-term use. Particularly when interacting with epithelial and innate immunity the selection of candidates probably deserves special caution. Also, whether biologics exert a true disease-modifying effect is not completely clear. As a direct practical implication, the optimal treatment duration is still controversial.

KEYWORDS:

• Severe asthma
• dupilumab
• omalizumab
• reslizumab
• mepolizumab
• benralizumab
• tezepelumab
• immunology of severe asthma

Article highlights

• The recent pharmacological research in the field of biologics has represented an exceptional opportunity for exploring severe asthma mechanisms.

• Blocking IgE antibodies revealed different and more complex inflammatory patterns they are involved in, and that viruses, pollutants and other environmental factors beyond atopy could trigger them.

• The innate immunity players are able to directly orchestrate an eosinophilic-impaired response before the activation of adaptive immunity.

• Epithelium itself actively contributes to the immune response, not only as a physical barrier, but also through a complex cross-talking with innate and adaptive immunity, providing a therapeutic target, still partially unexplored in terms of clinical potentialities.

• The disease-modifying effect of biologics is not yet completely clear, as a consequence the optimal treatment duration is still controversial.

• Long-term safety, especially when interacting with epithelial and innate immunity should be carefully evaluated.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.