Abstract
Background: CHF6001 is a selective inhaled PDE4i (NEXThaler®). The aim of this study was to assess the effects of CHF6001 on markers of inflammation in sputum and blood.
Methods: In this randomized, double-blind, 3-way crossover study, moderate-to-severe COPD subjects with chronic bronchitis (CB) received CHF6001 1600 or 3200µg daily or placebo for 32 days on top of ICS/LABA/LAMA therapy. CHF6001 concentrations and biomarkers of inflammation were analyzed in sputum supernatant and whole blood, plasma or serum. A post-hoc microarray gene expression analysis in blood and sputum cells was also carried out.
Results: 61 patients were randomized. CHF6001 sputum concentrations were ~2000-fold higher than in plasma. In sputum supernatant, both doses significantly (p<0.05) decreased leukotriene B4, interleukin 8, macrophage inflammatory protein 1β, matrix metalloproteinase 9, and tumor necrosis factor α compared to placebo. CHF6001 1600µg also significantly reduced monocyte chemotactic protein-1 and macrophage in sputum. In serum, both doses significantly decreased the level of surfactant protein D by ~20% compared to placebo. Both CHF6001 doses had no effect on gene expression in whole blood cells but strongly affected gene expression in sputum cells compared to placebo for cytokines and metalloproteases such as CCL3, CCL4, IL32, IL12B, MMP7, MMP12, MMP14, which were all significantly downregulated (pFDR<0.05).
Conclusion: Both doses of CHF6001 significantly decreased a number of key biomarkers of airway inflammation in COPD patients with CB. Moreover, these effects were essentially localized to the lung with inhaled delivery limiting systemic exposure
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA2044.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019