PT  - JOURNAL ARTICLE
AU  - Perea, Lidia
AU  - Bottier, Mathieu
AU  - Cant, Erin
AU  - Richardson, Hollian
AU  - Dicker, Alison J.
AU  - Shuttleworth, Morven
AU  - Giam, Yan Hui
AU  - Abo-Leyah, Hani
AU  - Finch, Simon
AU  - Huang, Jeffrey T-J.
AU  - Shteinberg, Michal
AU  - Goeminne, Pieter C.
AU  - Polverino, Eva
AU  - Altenburg, Josje
AU  - Blasi, Francesco
AU  - Welte, Tobias
AU  - Aliberti, Stefano
AU  - Sibila, Oriol
AU  - Chalmers, James D.
AU  - Shoemark, Amelia
TI  - Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis
AID  - 10.1183/13993003.01966-2023
DP  - 2024 Aug 01
TA  - European Respiratory Journal
PG  - 2301966
VI  - 64
IP  - 2
4099  - http://erj.ersjournals.com/content/64/2/2301966.short
4100  - http://erj.ersjournals.com/content/64/2/2301966.full
SO  - Eur Respir J2024 Aug 01; 64
AB  - Rationale The inflammasome is a key regulatory complex of the inflammatory response leading to interleukin-1β (IL-1β) release and activation. IL-1β amplifies inflammatory responses and induces mucus secretion and hyperconcentration in other diseases. The role of IL-1β in bronchiectasis has not been investigated.Objectives To characterise the role of airway IL-1β in bronchiectasis, including the association with mucus properties, ciliary function, airway inflammation, microbiome and disease severity.Methods Stable bronchiectasis patients were enrolled in an international cohort study (n=269). IL-1β was measured in sputum supernatant. A validation cohort also had sputum rheology and hydration measured (n=53). For analysis, patients were stratified according to the median value of IL-1β in the population (high versus low) to compare disease severity, airway infection, microbiome (16S rRNA sequencing), inflammation and caspase-1 activity. Primary human nasal epithelial cells grown in air–liquid interface culture were used to study the effect of IL-1β on cilia function.Results Patients with high sputum IL-1β had more severe disease, increased caspase-1 activity and an increased T-helper type 1, T-helper type 2 and neutrophil inflammatory response compared with patients with low IL-1β. The active-dominant form of IL-1β was associated with increased disease severity. High IL-1β was related to higher relative abundance of Proteobacteria in the microbiome and increased mucus solid content and viscoelastic properties. Chronic IL-1β treatment reduced the functionality of cilia and tight junctions of epithelial cells in vitro.Conclusions A subset of stable bronchiectasis patients show increased airway IL-1β, suggesting pulmonary inflammasome activation is linked with more severe disease, airway infection, mucus dehydration and epithelial dysfunction.Airway IL-1β is a marker of severe disease, mucus hyperconcentration, Proteobacteria-dominant microbiome and Th1, Th2 and neutrophilic inflammation in bronchiectasis patients. In vitro, IL-1β directly impairs cilia function and epithelial integrity. https://bit.ly/4aeooF7