Abstract
There is an emerging role for blood eosinophil count (EOS) as a biomarker to guide inhaled corticosteroid (ICS) therapy in COPD. Since ICS administration could influence EOS, we hypothesised that change in EOS following treatment with ICS may predict outcomes of long-term therapy.
In a post hoc analysis of ISOLDE, a 3-year, double-blind trial comparing 500 µg fluticasone propionate twice daily with placebo in 751 patients with moderate-to-severe COPD, we evaluated whether the initial changes in EOS during ICS treatment were predictive of ICS treatment response.
EOS change within 1 year after the introduction of ICS was strongly predictive of treatment response. A suppressed EOS was associated with treatment effect. Characteristically, in patients with EOS suppression of ≥200 cells·μL−1, ICS use was associated with a decelerated rate of decline of forced expiratory volume in 1 s (FEV1), by 32 mL·year−1, and a 30% reduction in the exacerbation rate. In contrast, in patients experiencing an increase in EOS of ≥200 cells·μL−1, ICS use was associated with an accelerated rate of decline of FEV1, by 37 mL·year−1 and an 80% increase in the exacerbation rate (p<0.0001). EOS change was not predictive of clinical response with regards to health status evaluated using the St George's Respiratory Questionnaire.
These findings suggest that EOS change after ICS administration may predict clinical response to ICS therapy in patients with moderate-to-severe COPD at risk of exacerbations. ICS administration may be associated with more frequent exacerbations and an accelerated lung function decline in the 20% of patients in whom EOS increases after the administration of ICS. These hypothesis-generating observations will need validation in prospectively designed studies.
The ISOLDE trial was conducted before the ICJME recommended a prospective registration of RCT protocols.
Abstract
Blood eosinophil change in response to ICS may predict long-term response to ICS in COPD. A rise in eosinophils was observed in 20% of participants in ISOLDE and was associated with lack of clinical benefit and a potential risk of harm. http://bit.ly/3bPKLnD
Footnotes
This article has supplementary material available from erj.ersjournals.com
Author contributions: A.G. Mathioudakis and J. Vestbo contributed to the conception and design of the study. A.G. Mathioudakis conducted data analysis and drafted the manuscript with input from all authors. P. Foden provided statistical expertise. All authors contributed to data interpretation, discussion and critical revision of the paper for intellectual content.
Data availability: Data ownership lies with GlaxoSmithKline. Data sharing is possible via Clinical Study Data Request platform (www.clinicalstudydatarequest.com), after submission of a research proposal, which is reviewed by an independent research panel.
Conflict of interest: A.G. Mathioudakis reports grants from Boehringer Ingelheim, personal fees from Boehringer Ingelheim, personal fees from GlaxoSmithKline, outside the submitted work.
Conflict of interest: A. Bikov has nothing to disclose.
Conflict of interest: P. Foden has nothing to disclose.
Conflict of interest: L. Lahousse reports grants from AstraZeneca, grants from Chiesi, personal fees from Boehringer Ingelheim, personal fees from Novartis, outside the submitted work.
Conflict of interest: G. Brusselle reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from GlaxoSmithKline, personal fees from Novartis, personal fees from Teva, personal fees from Sanofi, outside the submitted work.
Conflict of interest: D. Singh reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Chiesi, personal fees from Cipla, personal fees from Genentech, grants and personal fees from GlaxoSmithKline, grants and personal fees from Glenmark, grants and personal fees from Menarini, grants and personal fees from Mundipharma, grants and personal fees from Novartis, personal fees from Peptinnovate, grants and personal fees from Pfizer, grants and personal fees from Pulmatrix, grants and personal fees from Therevance, grants and personal fees from Verona, outside the submitted work.
Conflict of interest: J. Vestbo reports personal fees from Chiesi Pharmaceuticals, personal fees from Boehringer-Ingelheim, personal fees from Novartis, personal fees from AstraZeneca, outside the submitted work.
Support statement: A.G. Mathioudakis is supported by an Academic Clinical Fellowship in Respiratory Medicine from the National Institute for Health Research (NIHR, UK). A.G. Mathioudakis, D. Singh, A. Bikov and J. Vestbo are supported by the National Institute of Health Research Manchester Biomedical Research Centre (NIHR Manchester BRC). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 30, 2019.
- Accepted February 17, 2020.
- Copyright ©ERS 2020
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