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Inhaled corticosteroids, blood eosinophils, and FEV1 decline in patients with COPD in a large UK primary health care setting

Authors Whittaker HR, Müllerova H, Jarvis D, Barnes NC, Jones PW, Compton CH, Kiddle SJ, Quint JK

Received 9 January 2019

Accepted for publication 1 April 2019

Published 23 May 2019 Volume 2019:14 Pages 1063—1073


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Richard Russell

Hannah R Whittaker,1 Hana Müllerova,2 Deborah Jarvis,1 Neil C Barnes,2 Paul W Jones,2 Chris H Compton,2 Steven J Kiddle,3 Jennifer K Quint1

1National Heart and Lung Institute, Imperial College London, London, UK; 2Respiratory Epidemiology, GlaxoSmithKline R&D, Uxbridge, UK; 3MRC Biostatistics Unit, University of Cambridge, Cambridge, UK

Background: Inhaled corticosteroid (ICS)-containing medications slow rate of decline of FEV1. Blood eosinophil (EOS) levels are associated with the degree of exacerbation reduction with ICS.
Purpose: We investigated whether FEV1 decline differs between patients with and without ICS, stratified by blood EOS level.
Patients and methods: The UK Clinical Practice Research Datalink (primary care records) and Hospital Episode Statistics (hospital records) were used to identify COPD patients aged 35 years or older, who were current or ex-smokers with ≥2 FEV1 measurements ≥6 months apart. Prevalent ICS use and the nearest EOS count to start of follow-up were identified. Patients were classified at baseline as higher stratum EOS (≥150 cell/μL) on ICS; higher stratum EOS not on ICS; lower stratum EOS (<150 cells/μL) on ICS; and lower stratum EOS not on ICS. In addition, an incident ICS cohort was used to investigate the rate of FEV1 change by EOS and incident ICS use. Mixed-effects linear regression was used to compare rates of FEV1 change in mL/year.
Results: A total of 26,675 COPD patients met our inclusion criteria (median age 69, 46% female). The median duration of follow up was 4.2 years. The rate of FEV1 change in prevalent ICS users was slower than non-ICS users (−12.6 mL/year vs −21.1 mL/year; P =0.001). The rate of FEV1 change was not significantly different when stratified by EOS level. The rate of FEV1 change in incident ICS users increased (+4.2 mL/year) vs −21.2 mL/year loss in non-ICS users; P<0.001. In patients with high EOS, incident ICS patients showed an increase in FEV1 (+12 mL/year) compared to non-ICS users whose FEV1 decreased (−20.8 mL/year); P<0.001. No statistical difference was seen in low EOS patients. Incident ICS use is associated with an improvement in FEV1 change, however, over time this association is lost.
Conclusion: Regardless of blood EOS level, prevalent ICS use is associated with slower rates of FEV1 decline in COPD.

Keywords: COPD, lung function, eosinophil, inhaled corticosteroids

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