Abstract
BackgroundBlood 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.MethodsWe 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.ResultsSixteen 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.ConclusionThis 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.
Highlights
Inhaled corticosteroid (ICS) therapy has been reported to be associated with a reduction in the risk of moderate and severe exacerbations in a subgroup of patients with chronic obstructive pulmonary disease (COPD) [1]
Relevant data published from two post-hoc analyses of four Randomised controlled trial (RCT) were not presented in a form that could be incorporated in this review [5, 40]
At the 2% blood eosinophil threshold we have presented the results of the pooled analysis of all studies and the further analysis of those studies which show the independent effect of inhaled corticosteroid (ICS)
Summary
Inhaled corticosteroid (ICS) therapy has been reported to be associated with a reduction in the risk of moderate and severe exacerbations in a subgroup of patients with chronic obstructive pulmonary disease (COPD) [1] Those COPD patients with predominantly eosinophilic airways inflammation [2] may derive the most benefit from ICS use [3,4,5,6,7]. In one stable state COPD population 37.4% of patients had a blood eosinophil count of ≥2% [11] This threshold may predict response to ICS treatment with respect to modification of exacerbation risk in COPD patients [12]. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined
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