key: cord-1032783-nx81z31p
authors: Lipworth, Brian; Chan, Rory; Kuo, Chris
title: Inhaled corticosteroids and angiotensin-converting enzyme-2 in COPD
date: 2020-12-30
journal: J Allergy Clin Immunol
DOI: 10.1016/j.jaci.2020.11.018
sha: dbd5fbe2bbf9894fdc72ad9208670a29bb0812ad
doc_id: 1032783
cord_uid: nx81z31p

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Inhaled corticosteroids and angiotensinconverting enzyme-2 in COPD To the Editor:

Finney et al 1 elegantly showed in mice that inhaled corticosteroid (ICS) down-regulated the severe acute respiratory syndrome coronavirus-2 entry receptor angiotensin-converting enzyme 2 (ACE2) via suppression of type 1 interferon. It was also found that in 36 patients with chronic obstructive pulmonary disease (COPD), the use of ICS was associated with reduced expression of ACE2 compared with non-ICS users, whereas ACE2 expression is increased in cultured bronchial epithelial cells from patients with COPD and in turn suppressed by fluticasone propionate. They go on to postulate that this effect might therefore reduce susceptibility of patients with COPD to coronavirus disease 2019 (COVID-19).

The OpenSAFELY cohort showed that among 105,249 patients with COPD taking ICS combination therapy compared with 43,308 patients taking long-acting beta-agonist and long-acting muscarinic antagonist (LABA/LAMA) combination, the adjusted hazard ratio for mortality from COVID-19 was 1.39 (95% CI, 1.10-1.76). 2 The risk of death was more pronounced in those patients prescribed triple therapy with ICS/LABA/LAMA than those patients prescribed dual therapy with ICS/LABA, with hazard ratios (vs LABA/LAMA) of 1.43 (95% CI, 1.12-1.83) and 1.29 (95% CI, 0.96-1.74), respectively. Hence, reduced expression of ACE2 associated with ICS use does not appear to be associated with a commensurate reduction in COVID-19related deaths per se. However, the risk of mortality not related to COVID-19 was also observed to be higher in patients with COPD taking ICS-containing therapy versus LABA/LAMA, with an adjusted hazard ratio of 1.23 (95% CI, 1.08-1.40). This in turn perhaps suggests that other factors such as local immunosuppression due to ICS in the presence of impaired mucociliary clearance and altered microbiome 3 may have contributed to increased deaths in patients with COPD, or possibly that patients taking ICS had more severe disease. 

Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon

Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform

Long-term impact of inhaled corticosteroid use in asthma and chronic obstructive pulmonary disease (COPD): review of mechanisms that underlie risks