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Abstract / Description of output
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 and pro-inflammatory 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 bronchiectasis patients in the stable state.
6 healthy volunteers, 10 patients with mild, 15 with moderate and 9 with severe bronchiectasis were recruited. All participants had 60mls of blood taken and underwent a bronchoscopy, whilst in the stable state. Lipidomics was done on serum and bronchoalveolar fluid (BALF).
In the stable state, in serum there were significantly higher levels of PGE2, 15-HETE and LTB4 in patients with moderate-severe disease compared to 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-HODE and LTB4 in moderate-severe patients compared to healthy volunteers.
In the stable state, there was a negative correlation of PGE2 and LTB4 with % predicted FEV1 and positive correlation with antibiotic courses.
LXA4 improved blood and airways neutrophil phagocytosis and bacterial killing in bronchiectasis patients. Additionally LXA4 reduced neutrophil activation and degranulation.
There is a dysregulation of lipid mediators in bronchiectasis with excess pro-inflammatory lipids. LXA4 improves the function of reprogrammed neutrophils. The therapeutic efficacy of LXA4 in bronchiectasis warrants further studies.
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- 3 Finished
The role of cyclin-dependent kinase-9 inhibition in promoting the resolution of chronic inflammation
1/05/13 → 30/10/19
1/04/11 → 31/03/17
Shonna Johnston (Manager), Fiona Rossi (Manager), Claire Cryer (Other) & Ailsa Laird (Other)Institute of Regeneration and Repair