Dysregulation of prostaglandins, leukotrienes and lipoxin A₄ in bronchiectasis

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.

The aim of our study was to characterise the lipids obtained from serum and airways in patients with bronchiectasis in the stable state.

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).

In the stable state, in serum there were significantly higher levels of prostaglandin E₂ (PGE₂), 15-hydroxyeicosatetranoic acid (15-HETE) and leukotriene B₄ (LTB₄) in patients with moderate-severe disease compared with healthy volunteers. There was a significantly lower level of lipoxin A₄ (LXA₄) in severe bronchiectasis.In BALF, there were significantly higher levels of PGE₂, 5-HETE, 15-HETE, 9-hydroxyoctadecadienoic acid and LTB₄ in moderate-severe patients compared with healthy volunteers.In the stable state, there was a negative correlation of PGE₂ and LTB₄ with % predicted forced expiratory volume in 1 s and a positive correlation with antibiotic courses.LXA₄ improved blood and airway neutrophil phagocytosis and bacterial killing in patients with bronchiectasis. Additionally LXA₄ reduced neutrophil activation and degranulation.

There is a dysregulation of lipid mediators in bronchiectasis with excess proinflammatory lipids. LXA₄ improves the function of reprogrammed neutrophils. The therapeutic efficacy of LXA₄ in bronchiectasis warrants further studies.