Inhaled Steroids, Circulating Eosinophils, Chronic Airway Infection, and Pneumonia Risk in Chronic Obstructive Pulmonary Disease A Network Analysis

Rationale: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids (ICS) is controversial, because it can reduce the risk of future exacerbations of the disease at the expense of increasing the risk of pneumonia. Objectives: To assess the relationship between the presence of chronic bronchial infection (CBI), reduced number of circulating eosinophils, ICS treatment, and the risk of pneumonia in patients with COPD. Methods: This was a post hoc long-term observational study of an historical cohort of 201 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease H-IV) who were carefully characterized (including airway microbiology) and followed for a median of 84 months. Results were analyzed by multivariate Cox regression and network analysis. Measurements and Main Results: Mean age was 70.3 years, 90.5% of patients were male, mean FEV1 was 49%, 71.6% of patients were treated with ICS, 57.2% of them had bronchiectasis, and 20.9% had <100 blood eosinophils/mu l. Pathogenic microorganisms were isolated in 42.3% of patients, and 22.4% of patients fulfilled the definition of CBI. During follow-up, 38.8% of patients suffered one or more episodes of pneumonia, with CBI (hazard ratio [HR], 1.635) and <100 eosinophils/pd (HR, 1.975) being independently associated with the risk of pneumonia, particularly when both coexist (HR, 3.126). ICS treatment increased the risk of pneumonia in those patients with <100 eosinophils/mu l and CBI (HR, 2.925). Conclusions: Less than 100 circulating eosinophils/mu l combined with the presence of CBI increase the risk of pneumonia in patients with COPD treated with ICS.