Abstract
BackgroundPatients with chronic obstructive pulmonary disease (COPD) have excess risk of developing pneumonia; however, no definitive biomarkers of risk have been established. We hypothesized that blood neutrophils would help predict pneumonia risk in COPD.MethodsA meta-analysis of randomized, double-blind clinical trials of COPD patients meeting the following criteria were selected from the GlaxoSmithKline trial registry: ≥1 inhaled corticosteroid-containing (ICS) arm (fluticasone propionate/salmeterol or fluticasone furoate/vilanterol), a control arm (non-ICS), pre-randomization blood neutrophil counts, ≥24-week duration. The number of patients with pneumonia events and time to first event (Kaplan–Meier analysis) were evaluated (post-hoc), stratified by baseline blood neutrophil count and ICS use. A Cox proportional hazards model was used to calculate hazard ratios (HR), split by median baseline blood neutrophils.ResultsTen studies (1998 to 2011) with 11,131 patients were identified. The ICS (n = 6735) and non-ICS (n = 4396) cohorts were well matched in neutrophil distributions and demographics. Increasing neutrophil count was associated with an increased proportion of patients with pneumonia events; patients below the median neutrophil count were at less risk of a pneumonia event (HR, 0.75 [95% confidence interval 0.61–0.92]), and had longer time to a first event, compared with those at/above the median. The increase in pneumonia risk by neutrophil count was similar between the two cohorts.ConclusionsIncreased blood neutrophils in COPD were associated with increased pneumonia risk, independent of ICS use. These data suggest blood neutrophils may be a useful marker in defining treatment pathways in COPD.
Highlights
Patients with chronic obstructive pulmonary disease (COPD) have excess risk of developing pneumonia; no definitive biomarkers of risk have been established
We hypothesized that blood neutrophil levels could be reflective of changes in the microbiome that are associated with the risk of developing pneumonia
In this post-hoc study, we examined patient data across 10 clinical trials to evaluate the association between circulating blood neutrophils and pneumonia risk in patients with COPD
Summary
Patients with chronic obstructive pulmonary disease (COPD) have excess risk of developing pneumonia; no definitive biomarkers of risk have been established. Patients with chronic obstructive pulmonary disease (COPD) are at a heightened risk of pneumonia compared with otherwise healthy individuals and often have worse clinical outcomes in terms of pneumonia severity [1]. We hypothesized that blood neutrophil levels could be reflective of changes in the microbiome that are associated with the risk of developing pneumonia. The demonstration of an association between blood neutrophil levels and pneumonia risk has potential to both inform on the biological basis for the increased risk of developing pneumonia in COPD and to provide a prospective biomarker for risk stratification
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