ERS Congress 2024: highlights from the Airway Diseases Assembly

Abstract

This article presents highlights from #ERSCongress 2024 from Assembly 5 (airway diseases, asthma, COPD and chronic cough) https://bit.ly/4070nNw.

FIGURE 1

Schematic of the four main themes of remission in COPD and asthma. In COPD, the major focus of disease remission was identified to be the attainment of low disease activity. That meant obtaining minimal or non-worsening symptoms through therapeutic strategies, maintaining a low disease activity state through routine follow-up, and early identification and treatment of individuals at risk of COPD through public health outreach programmes. This “target-to-treat” approach was also highlighted as an important strategy to achieve clinical remission in asthma. That meant identifying and treating individuals with “treatable traits” such as high type 2 inflammation and preventing airway remodelling; achieving a well-controlled disease activity state without exacerbations and without the need for oral corticosteroid (OCS) use; and stabilisation of lung function. AI: artificial intelligence; Th2: T-helper cell type 2; IL: interleukin; FEV₁: forced expiratory volume in 1 s; SABA: short-acting β₂-agonist. Figure created with BioRender.com.

FIGURE 2

Schematic depicting the interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) alarmin pathways and how they are modulated by cigarette smoke. Tissue or cell damage from viral, helminth or bacterial infection, or from environmental agents such as cigarette smoke, or exposure to allergens, lead to the release of alarmins IL-33 and TSLP. Full-length bioactive IL-33 (IL-33_FL) is released, which binds to its receptor, ST2 (suppression of tumorigenicity 2), on ST2-expressing cells. This leads to MYD88 (myeloid differentiation primary response 88) activation of NF-κB and MAPK (mitogen-activated protein kinase) signalling pathways. ST2 also exists as a soluble isoform, which binds free active IL-33, and functions to negatively regulate downstream IL-33 signalling. TSLP binds its receptor (TSLPR) and mediates signalling by forming a heteromeric complex involving TSLPR and IL-7Rα, which activates JAK-STAT (janus kinase and signal transducer of activation) signalling pathways. The binding of IL-33 and TSLP alarmins to their receptors results in release of cytokines and inflammatory cascades, including recruitment and activation of inflammatory immune cells, B-cell class switching, release of immunoglobulin E, mast cell degranulation, release of neutrophil extracellular traps, and activation and priming of T-cell responses. These inflammatory cascades contribute to airway remodelling in asthma and COPD, ultimately leading to airway obstruction, emphysema and an impaired lung function. Paradoxically, current cigarette smoking also leads to the reduction of basal cell IL-33 and TSLP levels, possibly due to the loss of basal cells caused by current smoking. Additionally, cigarette smoking promotes the conversion of IL-33 into an oxidised, inactive form (IL-33^ox) through the formation of disulfide bridges and structural conformational change that prevents IL-33 from binding to ST2. IL-33^ox forms a complex with RAGE (receptor for advanced glycation end-products) and EGFR (epidermal growth factor receptor) and the activation of this ST2-independent pathway has been shown to lead to goblet cell metaplasia and mucus hypersecretion. IRAK: interleukin 1 receptor associated kinase; ILC2: group 2 innate lymphoid cells; Th: T-helper cell; NK: natural killer; IFN: interferon; TNF: tumour necrosis factor; GM-CSF: granulocyte–macrophage colony-stimulating factor; TGF: transforming growth factor; NETosis: neutrophil extracellular trap formation.