Inhaled corticosteroid-containing medications reduce the frequency of COPD exacerbations (mainly infectious in origin) while paradoxically increasing the risk of other respiratory infections The aim was to determine the effects of inhaled corticosteroids on airway microbial load in COPD patients and evaluate the influence of the underlying inflammatory profile on airway colonisation and microbiome.This is a proof-of-concept prospective, randomised, open-label, blinded endpoint study. Sixty patients with stable moderate COPD were randomised to receive one inhalation twice daily of either a combination of salmeterol 50 μg plus fluticasone propionate 500 μg or salmeterol 50 μg for 12 months. The primary outcome was the change of sputum bacterial loads over the course of treatment.Compared with salmeterol, 1-year treatment with salmeterol plus fluticasone was associated with a significant increase in sputum bacterial load (p=0.005), modification of sputum microbial composition and increased airway load of potentially pathogenic bacteria. The increased bacterial load was observed only in inhaled corticosteroid-treated patients with lower baseline sputum or blood eosinophil (≤2%) levels but not in patients with higher baseline eosinophils.Long-term inhaled corticosteroid treatment affects bacterial load in stable COPD. Lower eosinophil counts are associated with increased airway bacterial load.
Background Asthma and bronchiectasis are different conditions that frequently coexist. The prevalence of bronchiectasis rises considerably in subjects with severe asthma (25%–51%). Objective We evaluated the clinical and biological efficacy of mepolizumab on our pilot population of severe uncontrolled asthmatics with bronchiectasis not related to other pathologies. Patients and methods Four patients with severe uncontrolled asthma and diagnosed as bronchiectasis were recruited and started biological treatment with mepolizumab. Standard investigations were performed in all four patients at baseline (T0), after 3 months (T1) and after 1 year (T2) of treatment. Results After 1 year (T2) of therapy with mepolizumab, patients showed a significant increment of asthma control test value (12±1.1 vs 24.5±0.3, P <0.01), a reduction of the number of exacerbations/year (5±0.7 vs 0.75±0.75, P <0.01), an increase of pre-bronchodilator FEV 1 (1,680±500 vs 1,860±550 mL, P <0.01) and a reduction of eosinophils in blood (0.75±0.14 vs 0.12±0.02 cells/µL, P <0.01), in the sputum (9.6%±2.1% vs 5.6%±2.7%, P <0.05) and in nasal cytology (++ vs +). Conclusion The efficacy of mepolizumab in terms of reduction of inflammation and increase of control that we observed in our patients might suggest that targeting the IL-5 in severe eosinophilic asthma with bronchiectasis may be a good therapeutic strategy.
Summary The human airway epithelium is a pseudostratified heterogenous layer comprised of ciliated, secretory, intermediate and basal cells. As the stem/progenitor population of the airway epithelium, airway basal cells differentiate into ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. Transcriptome analysis of airway basal cells revealed high expression of vascular endothelial growth factor A (VEGFA), a gene not typically associated with the function of this cell type. Using cultures of primary human airway basal cells, we demonstrate that basal cells express all of the 3 major isoforms of VEGFA (121, 165 and 189) but lack functional expression of the classical VEGFA receptors VEGFR1 and VEGFR2. The VEGFA is actively secreted by basal cells and while it appears to have no direct autocrine function on basal cell growth and proliferation, it functions in a paracrine manner to activate MAPK signaling cascades in endothelium via VEGFR2 dependent signaling pathways. Using a cytokine- and serum-free co-culture system of primary human airway basal cells and human endothelial cells revealed that basal cell secreted VEGFA activated endothelium to express mediators that, in turn, stimulate and support basal cell proliferation and growth. These data demonstrate novel VEGFA mediated cross-talk between airway basal cells and endothelium, the purpose of which is to modulate endothelial activation and in turn stimulate and sustain basal cell growth.
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