Patients with Chronic Obstructive Pulmonary Disease and Evidence of Eosinophilic Inflammation Experience Exacerbations Despite Receiving Maximal Inhaled Maintenance Therapy

Background: Some patients with chronic obstructive pulmonary disease (COPD) experience frequent exacerbations despite maximal inhaled therapy ("triple therapy"), possibly leading to high health care resource utilization (HCRU).Aim: Describe characteristics, future HCRU, and mortality of patients with COPD who experience frequent exacerbations despite triple therapy; characterize individuals who may be candidates for biologic therapies.Methods: This descriptive observational study used primary care data of patients aged >40 years in the United Kingdom receiving maintenance therapy for COPD who had >1 year of data prior to index date and >1 year of follow-up data. We described these patients' clinical and demographic characteristics, including blood eosinophil counts (BEC), pattern of exacerbations, hospitalizations, and corticosteroid exposure, as well as future exacerbations, hospitalizations, and death.Results: Of 43,753 patients with maintenance-treated COPD, 6480 experienced exacerbations despite >3 months of triple therapy. Of these, 5669 had available BEC: 1287 (22.7%) had BEC >250 cells/mu L and >3 exacerbations in the year prior to the index date; 471 (36.6%) received >4 acute courses of oral corticosteroids. Patients with a pattern of high disease burden continued to have high disease burden: 51.1% experienced >3 exacerbations and 2.6% experienced >3 hospitalizations. Patients who experienced exacerbations despite triple therapy had a significantly higher risk of COPD-related death than other maintenance-treated patients (5.8% vs 2.1%). Conclusion: Nearly one-quarter of patients receiving triple therapy for COPD who experienced frequent exacerbations had elevated BEC and >3 exacerbations, suggesting a potential mechanism of persistent eosinophilic inflammation that could be a target for eosinophil-depleting biologic therapy.