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Review
. 2022 Dec;77(12):3538-3552.
doi: 10.1111/all.15473. Epub 2022 Aug 23.

Biologics and airway remodeling in severe asthma

Gilda Varricchi  1   2   3   4 , Sebastian Ferri  5 , Jack Pepys  6 , Remo Poto  1   2   3 , Giuseppe Spadaro  1   2   3 , Emanuele Nappi  5   6 , Giovanni Paoletti  5   6 , Johann Christian Virchow  7 , Enrico Heffler  5   6 , Walter G Canonica  5   6
Affiliations
Review

Biologics and airway remodeling in severe asthma

Gilda Varricchi et al. Allergy. 2022 Dec.

Abstract

Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a "fixed" airflow obstruction due to structural changes unresponsive to current therapies, from a "reversible" one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert "fixed" remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.

Keywords: airway remodeling; biologics; biomarkers; immunotherapies; severe asthma.

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Conflict of interest statement

G.V., S.F., J.P., R.P., and G.S. have not potential conflicts of interest to declare. J.C.V. is a full time employee of the University of Rostock as a full time professor and chair of the Departments of Pneumology and Intensive Care Medicine has given independent advice, lectured for and received honoraria from AstraZeneca, Avontec, Bayer, Bencard, Bionorica, Boehringer‐Ingelheim, Chiesi, Essex/Schering‐Plough, GSK, Janssen‐Cilag, Leti, MEDA, Merck, MSD, Mundipharma, Novartis, Nycomed/Altana, Pfizer, Revotar, Sandoz‐Hexal, Stallergens, TEVA, UCB/Schwarz‐Pharma, Zydus/Cadila, has participated in advisory boards for Avontec, Boehringer‐Ingelheim, Chiesi, Essex/Schering‐Plough, GSK, Janssen‐Cilag, MEDA, MSD, Mundipharma, Novartis, Regeneron, Revotar, Roche, Sanofi‐Aventis, Sandoz‐Hexal, TEVA, UCB/Schwarz‐Pharma and has received research grants from the Deutsche Forschungsgesellschaft, Land Mecklenburg‐Vorpommern, GSK, MSD. E.H. received grants and personal fees from AstraZeneca, Sanofi, Regeneron, Novartis, GSK, Circassia, Nestlè Purina, Stallergenes‐Greer outside the submitted work. G.W.C. received honoraria for lectures, presentations, speakers from AstraZeneca, GSK, Novartis, Sanofi, Stallergenes, Greer, Hal Allergy, Menarini, Chiesi, Mylan, Valeas, Faes.

Figures

FIGURE 1
FIGURE 1
Monoclonal antibodies (mAbs) effective in the treatment of patients with severe asthma are listed, and their known immunological mechanisms are summarized. The _targets of approved add‐on biologic treatments of severe asthma include IgE (omalizumab), IL‐5 (mepolizumab and reslizumab), IL‐5 receptor (benralizumab), IL‐4/IL‐13 receptor complex (dupilumab), and TSLP (tezepelumab).
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