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Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis

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Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. / Harries, Timothy Hugh; Rowland, Victoria Mary; Corrigan, Christopher John; Marshall, Iain James; Prasad, Vibhore; McDonnell, Lucy Mary; Schofield, Peter; Armstrong, David; White, Patrick Thomas.

In: RESPIRATORY RESEARCH, Vol. 21, No. 1, 3, 03.01.2020.

Research output: Contribution to journalReview article

Harvard

Harries, TH, Rowland, VM, Corrigan, CJ, Marshall, IJ, Prasad, V, McDonnell, LM, Schofield, P, Armstrong, D & White, PT 2020, 'Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis', RESPIRATORY RESEARCH, vol. 21, no. 1, 3. https://doi.org/10.1186/s12931-019-1268-7

APA

Harries, T. H., Rowland, V. M., Corrigan, C. J., Marshall, I. J., Prasad, V., McDonnell, L. M., Schofield, P., Armstrong, D., & White, P. T. (2020). Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. RESPIRATORY RESEARCH, 21(1), [3]. https://doi.org/10.1186/s12931-019-1268-7

Vancouver

Harries TH, Rowland VM, Corrigan CJ, Marshall IJ, Prasad V, McDonnell LM et al. Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. RESPIRATORY RESEARCH. 2020 Jan 3;21(1). 3. https://doi.org/10.1186/s12931-019-1268-7

Author

Harries, Timothy Hugh ; Rowland, Victoria Mary ; Corrigan, Christopher John ; Marshall, Iain James ; Prasad, Vibhore ; McDonnell, Lucy Mary ; Schofield, Peter ; Armstrong, David ; White, Patrick Thomas. / Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. In: RESPIRATORY RESEARCH. 2020 ; Vol. 21, No. 1.

Bibtex Download

@article{5f830646d4cf4c228ed1d35746121178,
title = "Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis",
abstract = "BACKGROUND: Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD. An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed. Doubt has been cast on the role by observational studies. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined. METHODS: We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS. Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used. Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL. Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out. Initial analysis included all studies of ICS vs. any non-ICS regimen. Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators. RESULTS: Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients. Eleven studies (25,881 patients) were post-hoc analyses of RCTs. Five studies (109,704 patients) were retrospective observational studies. The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44-0.78). No association was found in four out of five observational studies. CONCLUSION: This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds. Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed. The lack of association found in the observational studies questions the relevance of these observations to a {"}real world{"} COPD population. To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies.",
keywords = "Eosinophils, Inhaled corticosteroids, Observational studies, Pulmonary disease, chronic obstructive, Randomised controlled trials",
author = "Harries, {Timothy Hugh} and Rowland, {Victoria Mary} and Corrigan, {Christopher John} and Marshall, {Iain James} and Vibhore Prasad and McDonnell, {Lucy Mary} and Peter Schofield and David Armstrong and White, {Patrick Thomas}",
year = "2020",
month = jan,
day = "3",
doi = "https://doi.org/10.1186/s12931-019-1268-7",
language = "English",
volume = "21",
journal = "RESPIRATORY RESEARCH",
issn = "1465-9921",
publisher = "BioMed Central",
number = "1",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis

AU - Harries, Timothy Hugh

AU - Rowland, Victoria Mary

AU - Corrigan, Christopher John

AU - Marshall, Iain James

AU - Prasad, Vibhore

AU - McDonnell, Lucy Mary

AU - Schofield, Peter

AU - Armstrong, David

AU - White, Patrick Thomas

PY - 2020/1/3

Y1 - 2020/1/3

N2 - BACKGROUND: Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD. An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed. Doubt has been cast on the role by observational studies. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined. METHODS: We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS. Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used. Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL. Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out. Initial analysis included all studies of ICS vs. any non-ICS regimen. Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators. RESULTS: Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients. Eleven studies (25,881 patients) were post-hoc analyses of RCTs. Five studies (109,704 patients) were retrospective observational studies. The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44-0.78). No association was found in four out of five observational studies. CONCLUSION: This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds. Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed. The lack of association found in the observational studies questions the relevance of these observations to a "real world" COPD population. To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies.

AB - BACKGROUND: Blood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD. An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed. Doubt has been cast on the role by observational studies. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined. METHODS: We conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS. Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used. Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL. Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out. Initial analysis included all studies of ICS vs. any non-ICS regimen. Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators. RESULTS: Sixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients. Eleven studies (25,881 patients) were post-hoc analyses of RCTs. Five studies (109,704 patients) were retrospective observational studies. The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44-0.78). No association was found in four out of five observational studies. CONCLUSION: This is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds. Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed. The lack of association found in the observational studies questions the relevance of these observations to a "real world" COPD population. To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies.

KW - Eosinophils

KW - Inhaled corticosteroids

KW - Observational studies

KW - Pulmonary disease, chronic obstructive

KW - Randomised controlled trials

UR - http://www.scopus.com/inward/record.url?scp=85077480226&partnerID=8YFLogxK

U2 - https://doi.org/10.1186/s12931-019-1268-7

DO - https://doi.org/10.1186/s12931-019-1268-7

M3 - Review article

VL - 21

JO - RESPIRATORY RESEARCH

JF - RESPIRATORY RESEARCH

SN - 1465-9921

IS - 1

M1 - 3

ER -

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