A systematic review of blood eosinophils and continued treatment with inhaled corticosteroids in patients with COPD - 07/06/22

Doi : 10.1016/j.rmed.2022.106880

Dagmar Abelone Dalin ^a,^⁎,^{^{1
Shared first authorship.}} , Anders Løkke ^b,^c,^{^{1
Shared first authorship.}}, Pernille Kristiansen ^d, Charlotte Jensen ^e, Kirsten Birkefoss ^f,^g, Hanne Rolighed Christensen ^a, Nina Skavlan Godtfredsen ^h,ⁱ, Ole Hilberg ^b,^c, Jeanett Friis Rohde ^f,^j, Anja Ussing ^f, Charlotte Vermehren ^a,^k, Mina Nicole Händel ^f,^j
^a Bispebjerg and Frederiksberg Hospital, Department of Clinical Pharmacology, Bispebjerg Bakke 23, 2400, Copenhagen NV, DK, Denmark
^b Little Belt Hospital, Department of Medicine, Beriderbakken 4, 7100, Vejle, DK, Denmark
^c University of Southern Denmark, Department of Regional Health Research, Campusvej 55, 5230, Odense, DK, Denmark
^d Nordsjællands Hospital, Department of Lung- and Infectious Diseases, Dyrehavevej 29, 3400, Hillerod, DK, Denmark
^e General Practice, Lægerne I Gothersgade, Gothersgade 137, 4 Tv, 1123, Copenhagen C, DK, Denmark
^f Danish Health Authority, Evidence-based Medicine, Islands Brygge 67, 2300, Copenhagen S, DK, Denmark
^g Freelance: StepChange, Sommervej 41, 3520 Farum, DK, Denmark
^h Hvidovre Hospital, Department of Respiratory Diseases, Kettegård Alle 30, 2650, Hvidovre, DK, Denmark
ⁱ University of Copenhagen, Institute of Clinical Medicine, Blegdamsvej 3B, 2200, Copenhagen N, DK, Denmark
^j Bispebjerg and Frederiksberg Hospital, The Parker Institute, Nordre Fasanvej 57, 2000, Frederiksberg, DK, Denmark
^k University of Copenhagen School of Pharmaceutical Sciences, Department of Drug Design and Pharmacology, Universitetsparken 2, 2100, Copenhagen, DK, Denmark

^∗Corresponding author.

Abstract

Inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD) has been debated for 20 years. In our systematic literature review and meta-analysis, we addressed the following: Should patients with COPD and a blood eosinophil count (EOS) of, respectively, a) < 150 cells/μl, b) 150–300 cells/μl, and c) > 300 cells/μl continue treatment with ICS? Protocol registered in PROSPERO (CRD42020178110) and funded by the Danish Health Authority.

We searched Medline, Embase, CINAHL and Cochrane Central on 22^nd July 2020 for randomized controlled trials (RCT) of ICS treatment in patients with COPD (≥40 years, no current asthma), which analyzed outcomes by EOS count and where >50% of patients used ICS prior. We used the GRADE method. Meta-analyzes for the outcomes were divided into EOS subgroups and analyzed for differences.

We identified 11 RCTs with a total of 29,654 patients. A significant difference (p < 0.00001) between the three subgroups’ reduction of risk of moderate to severe exacerbation was found. Rate ratios for EOS counts: <150 cells/μL was 0.88 (95%CI: 0.83, 0.94); 150–300 cells/μL was 0.80 (95%CI: 0.69, 0.94); >300 cells/μL was 0.57 (95%CI: 0.49, 0.66). Overall, the certainty of the effect estimates was low to very low due to risk of bias, unexplained heterogeneity, few RCTs, and wide confidence intervals.

A clear correlation was demonstrated between effect of continued ICS treatment (number of exacerbations, lung function, and quality of life) and increasing EOS count. Our meta-analyses suggested that treatment with ICS seemed beneficial for everyone except patients with EOS count below 150 cells/μl.

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Highlights

•	In COPD patients exists a correlation between effect of ICS and eosinophil.
•	ICS might not be beneficial for COPD patients with eosinophil count <150 cells/μl.
•	Exacerbation risk increased in patients with high eosinophil count when stopping ICS.

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Keywords : Inhaled corticosteroid, Chronic obstructive pulmonary disease, Blood eosinophils, Eosinophil

Abbreviations : AMSTAR, CI, COPD, EOS, FEV1, GOLD, GRADE, Assessment, ICS, LABA, LAMA, MD, PICO, PRISMA, PROSPERO, RCT, WHO