Single inhaler triple therapy in COPD – all that glitters is not gold

Dear Editor, The recent studies on combination triple therapy of inhaled corticosteroid, long acting beta2 agonist and long-acting muscarinic antagonist (ICS-LABA-LAMA) in COPD have consistently demonstrated an improvement in exacerbation frequency and/or improvement of lung function...

Macrolides in children: judicious use, avoiding resistance and reducing adverse effects

Macrolides, a group of antibiotics molecularly characterised by a macrocyclic ring, are among the most frequently prescribed antibiotics for children. Beyond their antibacterial action, macrolides exert immunomodulatory effects. Prophylactic use is increasing. Macrolides are usually well tolerated in children, and dosing schedules are convenient. Furthermore, increasing data suggests that their prophylactic usage reduces the exacerbation frequency in children with bronchiectasis. Yet, to preserve their antibacterial action, each macrolide prescription should be judiciously considered. For prophylactic use, the indication should be regularly reviewed, and usage longer than 6 months should be avoided to reduce antimicrobial resistance.

Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD

Background Lower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters. Methods Monocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR. Results Phagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs. 2.5 × 103 RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state. Conclusion Impaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.