Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

Investigators, COPDGene

doi:10.1016/j.jaci.2018.04.010

Cited by 163 publications

(168 citation statements)

References 60 publications

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“…There is evidence that eosinophilic COPD patients and those with a history of prior asthma have more frequent exacerbations, but this has not been confirmed in other studies in which increased blood eosinophil counts were not related to the frequency of severe exacerbations . In the Copenhagen General Population Study there was an increase in exacerbations when blood eosinophils were >340/μL, and this was also seen in the large COPDGene and ECLIPSE cohorts …”

Section: Eosinophilic Copdmentioning

confidence: 87%

Inflammatory endotypes in COPD

Barnes

2019

Allergy

180

155

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Chronic obstructive pulmonary disease (COPD) is a major global health problem that is poorly treated by current therapies as it has proved difficult to treat the underlying inflammation, which is largely corticosteroid-resistant in most patients. Although rare genetic endotypes of COPD have been recognized, despite the clinical heterogeneity of COPD, it has proved difficult to identify distinct inflammatory endotypes.Most patients have increased neutrophils and macrophages in sputum, reflecting the increased secretion of neutrophil and monocyte chemotactic mediators in the lungs.However, some patients also have increased eosinophils in sputum and this may be reflected by increased blood eosinophils. Increased blood and sputum eosinophils are associated with more frequent exacerbations and predict a good response to corticosteroids in reducing and treating acute exacerbations. Eosinophilic COPD may represent an overlap with asthma but the mechanism of eosinophilia is uncertain as, although an increase in sputum IL-5 has been detected, anti-IL-5 therapies are not effective in preventing exacerbations. More research is needed to link inflammatory endotypes to clinical manifestations and outcomes in COPD and in particular to predict response to precision medicines. K E Y W O R D Sasthma-COPD overlap, eosinophil, exacerbations, interleukin-5, macrophage, neutrophil

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Section: Eosinophilic Copdmentioning

confidence: 87%

Inflammatory endotypes in COPD

Barnes

2019

Allergy

180

155

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“…In the same study, multivariable logistic regression models using different eosinophil count cut-offs found that a threshold of 0.3×10 9 cells/L was associated with the greatest sensitivity (72.6 %) and specificity (66.0%) for identifying a risk of self-reported exacerbation of at least one event. 101 The Copenhagen Lung Study showed an increase in exacerbations when blood eosinophilia count was above 0.34×10 9 cells/l 94 . Overall, blood eosinophils represent a continuous biomarker and a threshold with perfect performance characteristics is very unlikely to be found.…”

Section: Exacerbations Characterised By Enhanced Eosinophilic Inflammmentioning

confidence: 99%

Acute exacerbations of chronic obstructive pulmonary disease: in search of diagnostic biomarkers and treatable traits

Mathioudakis

Janssens

Sivapalan

et al. 2020

Thorax

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Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden. Their diagnosis, assessment and management remain suboptimal and unchanged for decades. Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically. This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes. This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations.

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“…4,5 As many as 40% of patients with stable COPD may have eosinophilic inflammation, which is associated with an increased risk of exacerbations as well as glucocorticoid responsiveness. 6,7 Some studies have shown that elevated blood eosinophil counts are associated with an increased risk of exacerbations and that inhaled glucocorticoids are efficacious in preventing exacerbations in this population. [7][8][9][10][11] Targeted treatments to deplete blood eosinophils may also reduce the risk of COPD exacerbations.…”

mentioning

confidence: 99%

“…6,7 Some studies have shown that elevated blood eosinophil counts are associated with an increased risk of exacerbations and that inhaled glucocorticoids are efficacious in preventing exacerbations in this population. [7][8][9][10][11] Targeted treatments to deplete blood eosinophils may also reduce the risk of COPD exacerbations. 12,13 Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that induces direct, rapid, and substantial eosinophil depletion by means of antibody-dependent cellular cytotoxic activity.…”

mentioning

confidence: 99%

Benralizumab for the Prevention of COPD Exacerbations

et al. 2019

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T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med nejm.org 1 The authors' full names, academic degrees, and affiliations are listed in the Appendix. Address reprint requests to Dr. BACKGROUNDThe efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known. METHODSIn the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment. Patients were randomly assigned to receive benralizumab (30 or 100 mg in GALATHEA; 10, 30, or 100 mg in TERRANOVA) every 8 weeks (every 4 weeks for the first three doses) or placebo. The primary end point was the treatment effect of benralizumab, measured as the annualized COPD exacerbation rate ratio (benralizumab vs. placebo) at week 56 in patients with baseline blood eosinophil counts of 220 per cubic millimeter or greater. Safety was also assessed. RESULTSIn GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo. CONCLUSIONSAdd-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.)A BS TR AC T

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Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

Abstract: Patients with moderate-to-severe COPD and blood eosinophil counts of 300 cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

Cited by 163 publications

References 60 publications

Inflammatory endotypes in COPD

Inflammatory endotypes in COPD

Acute exacerbations of chronic obstructive pulmonary disease: in search of diagnostic biomarkers and treatable traits

Benralizumab for the Prevention of COPD Exacerbations

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