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Review
. 2023 Oct 18;32(170):230084.
doi: 10.1183/16000617.0084-2023. Print 2023 Dec 31.

How inhaled corticosteroids target inflammation in COPD

Simon Lea  1 , Andrew Higham  2 , Augusta Beech  2 , Dave Singh  2   3
Affiliations
Review

How inhaled corticosteroids target inflammation in COPD

Simon Lea et al. Eur Respir Rev. .

Abstract

Inhaled corticosteroids (ICS) are the most commonly used anti-inflammatory drugs for the treatment of COPD. COPD has been previously described as a "corticosteroid-resistant" condition, but current clinical trial evidence shows that selected COPD patients, namely those with increased exacerbation risk plus higher blood eosinophil count (BEC), can benefit from ICS treatment. This review describes the components of inflammation modulated by ICS in COPD and the reasons for the variation in response to ICS between individuals. There are corticosteroid-insensitive inflammatory pathways in COPD, such as bacteria-induced macrophage interleukin-8 production and resultant neutrophil recruitment, but also corticosteroid-sensitive pathways including the reduction of type 2 markers and mast cell numbers. The review also describes the mechanisms whereby ICS can skew the lung microbiome, with reduced diversity and increased relative abundance, towards an excess of proteobacteria. BEC is a biomarker used to enable the selective use of ICS in COPD, but the clinical outcome in an individual is decided by a complex interacting network involving the microbiome and airway inflammation.

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Conflict of interest statement

Conflict of interest: D. Singh has received sponsorship to attend and speak at international meetings or honoraria for lecturing or attending advisory boards from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Teva, Theravance and Verona. A. Beech, A. Higham and S. Lea have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Mechanisms by which inhaled corticosteroids (ICS) facilitate an environment more susceptible to bacterial colonisation. CD: cluster of differentiation; IFN: interferon; MERTK: Mer tyrosine kinase; SLPI: secretory leukoprotease inhibitor.
FIGURE 2
FIGURE 2
A summary of key corticosteroid-sensitive and -insensitive pathways and the effects of inhaled corticosteroids (ICS) on the microbiome. IL: interleukin; ILC2: type 2 innate lymphoid cells; TNF: tumour necrosis factor.
See this image and copyright information in PMC

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