Absolute Blood Eosinophil Counts to Guide Inhaled Corticosteroids Therapy Among Patients with COPD: Systematic Review and Meta-analysis

Author(s): Olorunfemi A. Oshagbemi, Jephthah O. Odiba, Abraham Daniel, Ismaeel Yunusa*

Journal Name: Current Drug Targets

Volume 20 , Issue 16 , 2019

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Graphical Abstract:


Introduction: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 recommends the use of absolute blood eosinophil count as a guide for the escalation and de-escalation of inhaled corticosteroids (ICS) in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). We evaluated the risk of moderate or severe exacerbations among patients escalating and de-escalating ICS therapy by absolute blood eosinophil thresholds in this systematic review.

Methods: Through a comprehensive literature search of Pubmed/MEDLINE, EMBASE, and clinical trial sites up to April 2019, we identified relevant studies. We used generic inverse variance method with fixed-effects estimates to compare the risk of moderate or severe exacerbations among COPD patients with elevated blood eosinophil counts exposed to inhaled corticosteroids (ICS) versus non-ICS treatments groups expressed as risk ratios.

Results: Ten studies (8 randomised control trials and 2 observational studies) were included, with a total of 85,059 COPD patients. In our pooled analysis, we found an overall reduction in risk of moderate or severe exacerbations in patients with absolute blood eosinophil thresholds ranging from ≥ 100 to ≥ 340 cells/µL among patients escalating ICS (RR, 0.77, 95% CI, 0.73-0.81). For studies evaluating the effects of de-escalation of ICS on moderate to severe exacerbations using blood eosinophil thresholds of ≥ 300 to ≥ 340 cells/µL had an increased risk of moderate or severe exacerbations following the de-escalation of ICS (RR, 1.66, 95% CI, 1.31-2.10).

Conclusion: This study confirms the validity of the recommended absolute blood eosinophil count thresholds for the escalation and de-escalation of ICS among COPD patients. However, this recommendation is for COPD patients with prior exacerbations rather than among newly diagnosed COPD patients as observed in this study. COPD patients with current or past history of asthma represent a unique phenotypic group which should be further evaluated.

Keywords: Chronic obstructive pulmonary disease, blood eosinophils, exacerbations, inhaled corticosteroids, eosinophil, pharmacological.

Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. gold executive summary. Am J Respir Crit Care Med 2017; 195: 557-82.
Franssen FME, Spruit MA, Wouters EFM. Determinants of polypharmacy and compliance with GOLD guidelines in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2011; 6: 493-501.
Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet 2007; 370: 786-96.
Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2014; 3CD010115
Hubbard RB, Smith CJP, Smeeth L, Harrison TW, Tattersfield AE. Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med 2002; 166: 1563-6.
GOLD. Global strategy for the prevention, diagnosis and treatment of chronic obstructive pulmonary disease (2019 Report) 2018.
Bafadhel M, McKenna S, Terry S, et al. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: A randomized placebo-controlled trial. Am J Respir Crit Care Med 2012; 186: 48-55.
Pascoe S, Locantore N, Dransfield MT, Barnes NC, Pavord I. Blood eosinophil counts as markers of response to inhaled corticosteroids in COPD? -Authors’ reply. Lancet Respir Med 2015; 3e27
Oshagbemi OA, Burden AM, Braeken DCW, et al. Stability of blood eosinophils in patients with chronic obstructive pulmonary disease and in control subjects, and the impact of sex, age, smoking, and baseline counts. Am J Respir Crit Care Med 2017; 195(10): 1402-4.
Siddiqui SH, Guasconi A, Vestbo J, et al. Blood eosinophils: a biomarker of response to extrafine beclomethasone/formoterol in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2015; 192: 523-5.
Han MK. GOLD 2019: a new way forward. Lancet Respir Med 2018; (18): 30498-.
Higgins P, Green S. Cochrane Handbook for Systematic Reviews of Interventions 2011.
Bafadhel M, Peterson S, De Blas MA, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med 2018; 6(2): 117-26.
Lipson DA, Barnhart F, Brealey N, et al. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med 2018; 378(18): 1671-80.
Papi A, Vestbo J, Fabbri L, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet 2018; 391(10125): 1076-84.
Roche N, Chapman KR, Vogelmeier CF, et al. Blood Eosinophils and Response to Maintenance COPD Treatment: Data from the FLAME Trial. Am J Respir Crit Care Med 2017; 195: 1189-97.
Chapman KR, Hurst JR, Frent S-M, et al. Long-term triple therapy de-escalation to indacaterol/ glycopyrronium in patients with chronic obstructive pulmonary disease (sunset): a randomized, double-blind, triple-dummy clinical trial. Am J Respir Crit Care Med 2018; 198: 329-39.
Watz H, Tetzlaff K, Wouters EFM, et al. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: A post-hoc analysis of the WISDOM trial. Lancet Respir Med 2016; 4: 390-8.
[http://dx.doi.org/10.1016/ S2213-2600(16)00100-4]
Oshagbemi OA, Franssen FME, Braeken DCW, et al. Blood eosinophilia, use of inhaled corticosteroids, and risk of COPD exacerbations and mortality. Pharmacoepidemiol Drug Saf 2018; 27: 1191-9.
Suissa S, Dell’Aniello S, Ernst P. Comparative effectiveness of LABA-ICS versus LAMA as initial treatment in COPD targeted by blood eosinophils: a population-based cohort study. Lancet Respir Med 2018; 6(11): 855-62.
Calverley PMA, Tetzlaff K, Vogelmeier C, Fabbri LM, Magnussen H, Wouters EFM, et al. Eosinophilia, Frequent Exacerbations, and Steroid Response in Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2017; 196(9): 1219-21.
Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol 2013; 131: 636-45.
Vestbo J, Anderson W, Coxson HO, et al. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE). Eur Respir J 2008; 31: 869-73.
Barnes PJ. Asthma-COPD Overlap. Chest 2016; 149: 7-8.
Suzuki M, Makita H, Konno S, et al. Asthma-like features and clinical course of chronic obstructive pulmonary disease. an analysis from the hokkaido copd cohort study. Am J Respir Crit Care Med 2016; 194: 1358-65.
Saha S, Brightling CE. Eosinophilic airway inflammation in COPD. Int J Chron Obstruct Pulmon Dis 2006; 1: 39-47.
Shrimanker R, Thulborn SJ, Mistry V, et al. The peripheral blood eosinophil count as a biomarker of eosinophilic airway inflammation in patients with asthma and COPD.Experience from a Single Centre. A33. Clin. Stud. Obstr. LUNG Dis., American Thoracic Society 2017; A1343-A1343.
[http://dx.doi.org/doi:doi:10.1164/ajrccmconference. 2017.195.1_ MeetingAbstracts.A1343]
Negewo N, McDonald V, Baines K, et al. Can blood eosinophils predict sputum eosinophils in stable COPD? Eur Respir J 2015; 46PA3967
Hastie AT, Martinez FJ, Curtis JL, et al. Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort. Lancet Respir Med 2017; 5: 956-67.
Balkissoon R. COPD association and repeatability of blood biomarkers in the ECLIPSE cohort. COPD J Chronic Obstr Pulm Dis 2012; 9: 84.
Landis SH, Suruki R, Hilton E, Compton C, Galwey NW. Stability of blood eosinophil count in patients with copd in the uk clinical practice research datalink. COPD J Chronic Obstr Pulm Dis 2017; 14: 382-8.
Barnes NC, Sharma R, Lettis S, Calverley PMA. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur Respir J 2016; 1374-82.
Pavord ID, Lettis S, Locantore N, et al. Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD. Thorax 2016; 71: 118-25.
Zysman M, Burgel PR, Paillasseur JL, et al. Relationship between blood eosinophil count (Eos), clinical characteristics and mortality of patients with COPD. Eur Respir J 2016. 48: PA 4614.
Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163-96.
Vedel-Krogh S, Nielsen SF, Lange P, Vestbo J, Nordestgaard BG. Blood Eosinophils and Exacerbations in Chronic Obstructive Pulmonary Disease. The Copenhagen General Population Study. Am J Respir Crit Care Med 2016; 193: 965-74.
Zeiger RS, Tran TN, Butler RK, et al. Relationship of Blood Eosinophil Count to Exacerbations in Chronic Obstructive Pulmonary Disease. J Allergy Clin Immunol Pract 2018; 6: 944-954.e5.
Yun JH, Lamb A, Chase R, et al. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol 2018; 141: 2037-2047.e10.
Morjaria JB, Rigby A, Morice AH. Inhaled Corticosteroid use and the Risk of Pneumonia and COPD Exacerbations in the UPLIFT Study. Lung 2017; 195: 281-8.
de Melo MN, Ernst P, Suissa S. Inhaled corticosteroids and the risk of a first exacerbation in COPD patients. Eur Respir J 2004; 23: 692-7.
Suh D-C, Lau H, La H-O, Choi I-S, Geba GP. Association between incidence of acute exacerbation and medication therapy in patients with COPD. Curr Med Res Opin 2010; 26: 297-306.
Funk MJ, Landi SN. Misclassification in administrative claims data: quantifying the impact on treatment effect estimates. Curr Epidemiol Rep 2014; 1: 175-85.

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Article Details

Year: 2019
Published on: 13 November, 2019
Page: [1670 - 1679]
Pages: 10
DOI: 10.2174/1389450120666190808141625
Price: $65

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