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Wando Mount Pleasant Library
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The effects of inhaled corticosteroids on healthy airways.
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- Author(s): Marchi, Emanuele; Hinks, Timothy S. C.; Richardson, Matthew; Khalfaoui, Latifa; Symon, Fiona A.; Rajasekar, Poojitha; Clifford, Rachel; Hargadon, Beverley; Austin, Cary D.; MacIsaac, Julia L.; Kobor, Michael S.; Siddiqui, Salman; Mar, Jordan S.; Arron, Joseph R.; Choy, David F.; Bradding, Peter
- Source:
Allergy; Jul2024, Vol. 79 Issue 7, p1831-1843, 13p- Subject Terms:
- Source:
- Additional Information
- Abstract: Background: The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. Objectives: To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease‐related genes and disease‐related alterations in ICS responsiveness. Methods: Randomized open‐label bronchoscopy study of high‐dose ICS therapy in 30 healthy adult volunteers randomized 2:1 to (i) fluticasone propionate 500 mcg bd daily or (ii) no treatment, for 4 weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics. Results: ICS induced small between‐group differences in blood and lamina propria eosinophil numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV1, microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type‐2 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell‐mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA‐DQB2, CD96, PTPN7), B‐cell immunity (CD20, immunoglobulin heavy and light chains) and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL‐17‐dependent gene signature was not upregulated by ICS. Conclusions: In healthy airways, 4‐week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type‐2 inflammation. This implies that homeostasis in health involves tonic type‐2 signalling in the airway mucosa, which is exquisitely sensitive to ICS. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Allergy is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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