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Review
. 2023 Jul 3;220(7):e20221212.
doi: 10.1084/jem.20221212. Epub 2023 Jun 2.

Type 2 inflammation and biological therapies in asthma: Targeted medicine taking flight

Imran Howell  1 , Aleksandra Howell  1 , Ian D Pavord  1
Affiliations
Review

Type 2 inflammation and biological therapies in asthma: Targeted medicine taking flight

Imran Howell et al. J Exp Med. .

Abstract

The field of asthma has undergone a dramatic change in recent years. Advances in our understanding of type 2 airway inflammation have driven the discovery of monoclonal antibodies targeting specific aspects of the immune pathway. In landmark trials, these drugs have shown efficacy in reducing asthma attacks and exposure to oral corticosteroids, important causes of morbidity in people with asthma. Our review explores the key features of type 2 inflammation in asthma and summarizes the clinical trial evidence of the novel monoclonal antibody treatments and future avenues for treatment.

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Conflict of interest statement

Disclosures: I.D. Pavord reported having, over the last 5 years, received speaker’s honoraria for speaking at sponsored meetings from Astra Zeneca, Boehringer Inglehiem, Aerocrine, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini, and GSK, as well as payments for organizing educational events from Astra Zeneca, GSK, Sanofi/Regeneron, and Teva. He has also received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, Astra Zeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi, and Knopp, as well as payments to support FDA approval meetings from GSK; receiving sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, Astra Zeneca, Teva, and Chiesi; and has received a grant from Chiesi to support a phase 2 clinical trial in Oxford. No other disclosures were reported.

Figures

Figure 1.
Figure 1.
Type 2 inflammation in asthma and targets for monoclonal antibody treatment. Type 2-high inflammation is the predominant treatable trait in asthma. It is present in both childhood-onset allergic asthma and adult-onset eosinophilic asthma. Different people have different pathways that predominate, and our understanding of why these develop and how to best characterize their activity is developing. In allergen-sensitized people, DCs present inhaled aeroallergens to tissue-resident CD4+ type 2 helper T lymphocytes (Th2 lymphocytes). These produce a large amount of type 2 cytokines (IL-4, IL-5, IL-13, and IL-9). In parallel, alarmins also stimulate the Th2 lymphocyte pathway, as well as ILC2, to produce type 2 cytokines. IL-4 and IL-13 stimulate B cells to mature into plasma cells and secrete IgE. IgE binds to the high-affinity FcεRI on mast cells, leading them to release PGD2 and histamine amongst other cytokines causing bronchoconstriction. Additionally, IL-13 induces the production of nitric oxide via the iNOS enzyme. This process can be measured by FeNO. IL-13 also stimulates mucous hypersecretion and smooth muscle contraction, and both IL-4 and IL-13 facilitate the recruitment of eosinophils from circulation to the airway mucosa. IL-5 enhances the proliferation and activation of eosinophils which degranulate causing tissue damage and producing mucous plugs through the formation of CLCs, eosinophil granules, and eosinophil extracellular traps.
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