Dysregulation of prostaglandins, leukotrienes and lipoxin A<sub>4</sub>in bronchiectasis
Pallavi Bedi, Kerstin Ziegler, Phil Whitfield, Donald J. Davidson, Adriano G. Rossi, Adam T. Hill
Abstract
Introduction Bronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. Further characterisation of these lipids and understanding the interplay of anti-inflammatory and proinflammatory lipid mediators could lead to the development of novel anti-inflammatory therapies for bronchiectasis. Aim The aim of our study was to characterise the lipids obtained from serum and airways in patients with bronchiectasis in the stable state. Methods Six healthy volunteers, 10 patients with mild bronchiectasis, 15 with moderate bronchiectasis and 9 with severe bronchiectasis were recruited. All participants had 60 mL of blood taken and underwent a bronchoscopy while in the stable state. Lipidomics was done on serum and bronchoalveolar lavage fluid (BALF). Results In the stable state, in serum there were significantly higher levels of prostaglandin E 2 (PGE 2 ), 15-hydroxyeicosatetranoic acid (15-HETE) and leukotriene B 4 (LTB 4 ) in patients with moderate–severe disease compared with healthy volunteers. There was a significantly lower level of lipoxin A 4 (LXA 4 ) in severe bronchiectasis. In BALF, there were significantly higher levels of PGE 2 , 5-HETE, 15-HETE, 9-hydroxyoctadecadienoic acid and LTB 4 in moderate–severe patients compared with healthy volunteers. In the stable state, there was a negative correlation of PGE 2 and LTB 4 with % predicted forced expiratory volume in 1 s and a positive correlation with antibiotic courses. LXA 4 improved blood and airway neutrophil phagocytosis and bacterial killing in patients with bronchiectasis. Additionally LXA 4 reduced neutrophil activation and degranulation. Conclusion There is a dysregulation of lipid mediators in bronchiectasis with excess proinflammatory lipids. LXA 4 improves the function of reprogrammed neutrophils. The therapeutic efficacy of LXA 4 in bronchiectasis warrants further studies.