Imbalance of anti-inflammatory (resolving D1) and pro-inflammatory (leukotrien B4) arachidonic acid products in exhaled breath condensate of severe refractory asthma

Abstract

Severe refractory asthma (SRA) is characterized by prominent airway inflammation and oxidative stress. Inadequate production of anti-inflammatory arachidonic acid product lipoxin was described in severe phenotype of asthma. Aims: We sought to investigate whether concentration of lipoxin A4 (LXA) and leukotrien B4 (LTB) in exhaled breath condensate differs in various phenotypes of SRA. Methods: We harvested EBC of 59 SRA patients and 38 healthy controls (HC) by standardized protocol (EcoScreen). LXA and LTB were compared between subgroups of eosinophilic (EA, n=29) and non-eosinophilic (NEA, n=30) phenotype defined by exhaled nitric oxide > 30ppb despite high dose of inhaled corticosteroid therapy. LXA and LTB in EBC were analyzed by liquid chromatography and mass spectrometry. Measured results were analyzed together with FEV1, FeNO50, PBE and subgroups statistically evaluated. Results: EA and NEA were comparable by FEV1, ACT, peripheral blood eosinophilia (all p>0.05). LXA and concentration in SRA were markedly lower than in HC (27.65 vs. 59.89 pg/ml, p Conclusion: We showed imbalance of anti-inflammatory and pro-inflammatory arachidonic acid products in SRA in comparison to HC. SRA is associated with decreased production of LXA4, which is significantly lower in non-eosinophilic asthma phenotype (NEA). NEA phenotype could be associated with prolonged resolving of airway inflammatory damage.