Abstract
Background: Modulating excessive airway neutrophilia might have beneficial effects in neutrophilic airway diseases. In humans the effects of CXCR2 antagonism are well characterized in peripheral blood and sputum, but there are no data on human bronchial mucosa.
Methods: We conducted an exploratory, single centre, open-label, non-controlled, pilot study with oral twice daily (BD) administration of 45 mg AZD5069 (90 mg/day) over 4 weeks in patients with moderate persistent neutrophilic asthma. Co-primary endpoints were neutrophil cell counts in bronchial mucosa obtained via bronchoscopic biopsy, induced sputum, and blood. Secondary endpoints included ligands of CXCR2 (IL-8, GRO-α) in sputum supernatant and serum (ClinicalTrials.gov Identifier:NCT01890148).
Results: 5 patients (mean age 47 years, 4 male patients; mean FEV1 83% pred., 65% neutrophils in sputum) were enrolled and 4 patients completed the study. There was a numeric decrease in neutrophil counts in mucosa, sputum and blood with a consecutive increase of IL-8 and GRO-α levels in sputum and serum. There was a total of 11 adverse events (AEs) of mild to moderate intensity with one AE being related to study treatment (low blood neutrophil counts resulting in withdrawal of the patient from study treatment). No serious AE occurred.
Conclusion: CXCR2-antagonism seems to simultaneously reduce the number of neutrophils in all investigated compartments, which suggests that the reduction of sputum neutrophilia is due to a reduced entry of neutrophils to the lung rather than a retention in the mucosa.
- Copyright ©the authors 2016
