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Owing to the size of the data set, these missing values were imputed, but the results did not appreciably change in sensitivity analyses where values were not imputed. Other limitations to cluster analysis include that the algorithm cannot adjust for multiple comparisons, which could yield spurious Selleck CP673451 results. We were unable to externally validate the clusters defined by eosinophils and smoking history using the SFC versus SAL data because baseline eosinophil levels were not collected in the SFC versus SAL studies. This is an important limitation in light of the fact that the findings from the previous cluster analysis of SFC versus SAL were not able to be externally validated within the present analysis. Eosinophil levels are becoming established as a clinically relevant biomarker of oral corticosteroid and ICS response in COPD16�C23 and also in asthma.24�C26 Earlier work focused on sputum eosinophils, but blood eosinophils are now being accepted as an alternative measurement that is more practical to use in a clinical setting.27 Azastene 28 The clinical relevance of the 2.4% cut-off in blood eosinophil levels requires additional exploration; however, it lies between the 3% value commonly used to define sputum eosinophilia8 22 29 and the 2% value that was identified as a relevant cut-off point in selleckchem patients with COPD based on an analysis of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End points (ECLIPSE) cohort.30 No minimal clinically important difference has yet been defined for eosinophilia in COPD,29 but clinically meaningful differences have been found in other studies and analyses based on either a 2% or 2.5% cut-off.3 16 20 23 In particular, this work complements the post hoc subgroup analysis of the same clinical trials of FF/VI versus VI that was conducted by Pascoe et al23 That analysis found that patients with COPD with blood eosinophils ��2% at baseline experienced a reduction in exacerbation rates of 29% (p
