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

Abstract

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

Acknowledgments

This manuscript was funded by GlaxoSmithKline; study number 208602. This study has been previously presented as an abstract at the European Respiratory Society Conference in Paris, September 2018. Steven J Kiddle and Jennifer K Quint are joint last authors for this study.

Abbreviation list

ICS, Inhaled corticosteroids; EOS, eosinophils; FEV₁, Forced expiratory volume in 1 s; LAMA, Long-acting muscarinic antagonist; LABA, long active beta agonist; BMI, Body mass index; MI, Myocardial infarction; HF, Heart failure; GORD, Gastro-oesophageal reflux disease; WBC, White blood cell; AECOPD, Exacerbation of COPD; RCT, Randomized control trial.

Ethics approval

The protocol for this research was approved by the Independent Scientific Advisory Committee (ISAC) for MHRA Database Research (protocol number 17_229R) and the approved protocol was made available to the journal and reviewers during peer review. Generic ethical approval for observational research using the CPRD with approval from ISAC has been granted by a Health Research Authority (HRA) Research Ethics Committee (East Midlands – Derby, REC reference number 05/MRE04/87).

Author contributions

Hannah R Whittaker: data management, data analysis, data interpretation, writing, figures & tables. Hana Müllerova, Steven J Kiddle, Jennifer K Quint: data analysis, data interpretation, writing. Deborah Jarvis, Neil C Barnes, Paul W Jones, Chris H Compton: data interpretation, writing. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

Miss Whittaker reports grants from GlaxoSmithKline, during the conduct of the study; Dr Müllerova was employed by and reported personal fees from GlaxoSmithKline, during the conduct of the study; Dr Jarvis reports grants from European Union and Cystic Fibrosis Trust, outside the submitted work; she also reports grants from GlaxoSmithKline, during the conduct of the study. Dr Barnes is employed, holds shares and reports personal fees from GlaxoSmithKline, outside the submitted work; he also received grants from GlaxoSmithKline, during the conduct of the study. Dr Jones is employed by and reports personal fees from GlaxoSmithKline, during the conduct of the study; Dr Compton is employed, holds shares and reports personal fees from GlaxoSmithKline, during the conduct of the study; Dr Kiddle reports grants from MRC, during the conduct of the study; grants from Roche Diagnostics, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, National Institute for Health Research, Alzheimer’s Society, Eli Lily, and Jannsen, outside the submitted work; Dr Kiddle was supported by a MRC Career Development Award (MR/PO21573/1). Dr Quint reports grants from GlaxoSmithKline, during the conduct of the study; grants from The Health Foundation, MRC, Wellcome Trust, British Lung Foundation, Insmed, AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Teva, and GlaxoSmithKline, outside the submitted work. The authors report no other conflicts of interest in this work.