Abstract

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