Background: Globally, ?5% of patients have severe asthma. Despite new treatments, many remain symptomatic (ACQ>1.5) with low levels of Type-2 inflammation (T2-low: FeNO<20ppb & Blood Eosinophil count [BEC]<0.15x109cells/L).
Aims: To profile urinary eicosanoids in ?T2-low? severe asthma.
Methods: Urine samples were analysed, from T2-low patients, by liquid-chromatography/mass-spectrometry, during a multi-centre, 48-week RCT enabling corticosteroid optimisation.
Results: Urinary concentrations of isoprostanes, thromboxane and PGD2 metabolites are elevated in ?symptom-high? [SH: uncontrolled] v ?symptom-low? [SL: controlled], T2-low patients (Table 1) and are associated with a reduced FEV1 (71.7% v 88.5%, P<0.0001). After adjusting for obesity, thromboxane 2,3-dinor-TXB2 (0.32 v 0.16ng/mL, P=0.0337) and isoprostane 8,12-iso-iPF2a-VI (3.73 v 2.10ng/mL, P=0.0234) remain elevated in ?SH? v ?SL?, T2-low patients and are associated with a reduced FEV1(88.0% v 70.6%, P=0.002).
Conclusion: Elevated urinary eicosanoids in ?SH/T2-low? patients are in part due to obesity, however, some thromboxane and prostaglandin metabolites are independently associated with persistent symptoms.
Table 1: Lung-function, eicosanoids & biomarkers in ?SH? v ?SL?, T2-low patients
| Controlled(ACQ7?1.5)[n=30] | Uncontrolled(ACQ7>1.5)[n=61] | |
| ACQ7 | 0.8(0.4) | 2.6(0.8)** |
| %FEV1 | 88.5(17.0) | 71.7(18.6)** |
| BEC(109cells/L) | 0.11(0.07,0.12) | 0.08(0.04,0.11)* |
| FeNO(ppb) | 14(12,18) | 13(10,16) |
| 11-dehydroTXB2(ng/mL) | 0.48(0.22,0.67) | 0.76(0.42,1.16)* |
| 2,3-dinor-TXB2(ng/mL) | 0.16(0.10,0.33) | 0.32(0.18,0.52)* |
| 8,12-iso-iPF2a-VI(ng/mL) | 2.32(1.80,3.33) | 3.66(2.79,5.21)* |
| TetranorPGDM(ng/mL) | 1.93(1.01,2.94) | 2.93(1.85,3.96 )* |
| 5-iPF2a-VI(ng/mL) | 0.80(0.53,1.56) | 1.40(1.09,1.94)* |
*P <0.05; **P <0.0001