1. Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis.
- Author
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Perea L, Bottier M, Cant E, Richardson H, Dicker AJ, Shuttleworth M, Giam YH, Abo-Leyah H, Finch S, Huang JT, Shteinberg M, Goeminne PC, Polverino E, Altenburg J, Blasi F, Welte T, Aliberti S, Sibila O, Chalmers JD, and Shoemark A
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Inflammasomes metabolism, Mucus metabolism, Caspase 1 metabolism, Microbiota, Inflammation, Cohort Studies, RNA, Ribosomal, 16S genetics, Adult, Cilia metabolism, Interleukin-1beta metabolism, Bronchiectasis physiopathology, Bronchiectasis metabolism, Bronchiectasis microbiology, Sputum metabolism, Mucociliary Clearance, Severity of Illness Index
- Abstract
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., Competing Interests: Conflict of interest: M. Shteinberg reports consulting fees from GSK, Boehringer Ingelheim, Kamada and Zambon; payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, Boehringer Ingelheim, GSK, AstraZeneca, Teva, Novartis, Kamada and Sanofi; support for attending meetings and/or travel from Novartis, Actelion, Boehringer Ingelheim, GSK and Rafa; participation on a data safety monitoring board or advisory board for Bonus Therapeutics, Israel; leadership roles for EMBARC Management, Israel Pulmonology Society Board, Israel Society for TB and Mycobacterial Diseases; receipt of equipment, materials, drugs, medical writing, gifts or other services from Trudell Medical Int; and is an associate editor of the American Journal of Respiratory and Critical Care Medicine. P.C. Goeminne reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed, GSK and Chiesi; support for attending meetings and/or travel from Chiesi; and participation on a data safety monitoring board or advisory board for Boehringer, GSK and Pfizer. E. Polverino reports grants or contracts from Grifols; consulting fees from Insmed, Bayer, Chiesi and Zambon; payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Chiesi, Grifols, GSK, Insmed, Menarini and Zambon; and support for attending meetings and/or travel from Insmed, Pfizer and Moderna. F. Blasi reports grants or contracts from AstraZeneca, Chiesi and Insmed; consulting fees from Menarini; and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Chiesi, GSK, Guidotti, Grifols, Insmed, Menarini, Novartis, OM Pharma, Pfizer, Sanofi, Viatris, Vertex and Zambon. S. Aliberti reports grants or contracts from Insmed Incorporated, Chiesi, Fisher and Paykel and GSK; royalties or licences from McGraw Hill; consulting fees from Insmed Incorporated, Insmed Italy, Insmed Ireland Ltd, Zambon Spa, AstraZeneca UK Ltd, AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna, Chiesi, MCD Italis SrL, Brahms, Physioassist SAS and GSK SpA; payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK SpA, Thermofisher Scientific, Insmed Italy, Insmed Ireland, Zambon and Fondazione Internazionale Menarini; and participation on a data safety monitoring board or advisory board for Insmed Incorporated, Insmed Italy, AstraZeneca UK Ltd and MSD Italia SrL. J.D. Chalmers reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Genentech, Gilead Sciences, GSK, Grifols, Insmed, LifeArc and Novartis; and consulting fees from AstraZeneca, Chiesi, GSK, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon. A. Shoemark reports consulting fees from Spirovant and Translate Bio; payment or honoraria for lectures, presentations, manuscript writing or educational events from Translate Bio, Ethris and Insmed; and a leadership role in European Respiratory Society Clinical Research Collaborations (EMBARC, BEATPCD, AMR). The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)
- Published
- 2024
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