Sputum prostaglandin E2 levels linked to asthma severity
MedWire News: Sputum concentrations of prostaglandin (PG)E2 increase with increasing asthma severity, indicating a bronchoprotective and anti-inflammatory role for the biomarker in patients with more severe asthma, say researchers.
“Inflammation of the airways in asthma is associated with the production of cysteinyl leukotrienes (cysLT), PGE2, 8-isoprostane, nitric oxide, and other mediators,” explain Neil Misso and team from the University of Western Australia in Perth.
However, they add that “the relationship between asthma severity or eosinophilic inflammation and the concentrations of mediators in sputum is unclear.”
To investigate, the team assessed sputum levels of PGE2, cysLT, 8-isoprostane and nitrates, as well as urinary leukotriene (LT)E4 and 9α,11β-prostaglandin (PG)F2 concentrations in 12 patients with mild, 14 with moderate, and 12 with severe, persistent asthma. Levels of these markers were also assessed in 13 controls without the respiratory condition.
Participants with asthma were also categorized according to whether they had eosinophilic or non-eosinophilic airway inflammation.
The researchers found that sputum PGE2 concentrations were significantly higher in patients with moderate and severe asthma (1710 and 1590 pg/ml, respectively), compared with controls (827 pg/ml).
The difference in the median sputum cysLT concentrations between controls (313 pg/ml) and all asthmatic patients (466 pg/ml) did not reach statistical significance. However, cysLT concentrations were significantly greater in patients with moderate asthma (565 pg/ml) compared with both controls and patients with severe asthma (324 pg/ml).
Among participants with asthma, sputum PGE2 concentrations were lower in patients with eosinophilic inflammation (1180 pg/ml) than in those with non-eosinophilic inflammation (2520 pg/ml). In contrast, sputum cysLT and urinary LTE4 concentrations were higher in patients with eosinophilic inflammation than in those with non-eosinophilic inflammation.
The team also found that FEV1 was inversely associated with sputum eosinophil counts in all patients with asthma. There were no significant differences in sputum 8-isoprostane or nitrate concentrations between any of the groups studied.
Misso and team conclude in the journal Clinical and Experimental Allergy: “Increased airway concentrations of PGE2 are consistent with the hypothesis that PGE2 has a bronchoprotective and anti-inflammatory role in patients with more severe asthma.
“A reduced PGE2 to cysLT ratio in the airways may adversely affect lung function and contribute to persistence of symptoms and airway remodeling in patients with eosinophilic airway inflammation.”
They add: “Measurement of these sputum eicosanoids therefore not only provides insights into underlying pathophysiological mechanisms but, with further validation, may also facilitate the clinical assessment of differences in asthma phenotype, monitoring of airway inflammation and optimization of therapeutic strategies.”
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By Mark Cowen