Abstract
Background
Approximately 5–10% of patients with asthma have severe disease. A proportion remain symptomatic despite suppression of T2-related inflammation but what drives persistent symptoms remains unclear. Eicosanoids exert a functional role in pulmonary inflammation. We explored the relationship between urinary eicosanoids, asthma symptoms, obesity and T2-biomarker status.
Methods
Urine was sampled during a randomized controlled trial assessing corticosteroid optimization using T2-biomarker directed care at scheduled study visits (n=728) and at exacerbation (n=103). Urine eicosanoid concentrations were measured by mass spectrometry, then log2-transformed, z-scored and concatenated by biosynthetic pathway generating six pathway scores. Results were stratified by T2-status (T2-Low: fractional-exhaled nitric-oxide [FeNO]<20 ppb and blood eosinophil count [BEC]<0.15×109cells·L−1) versus T2-high: (FeNO ≥20 ppb and BEC ≥0.15×109cells·L−1), symptoms (symptom-low: Asthma Control Questionnaire-7 [ACQ-7<1.5)] versus symptom-high: ACQ-7≥1.5), and obesity.
Results
Isoprostane (pathway score p=0.02) and thromboxane (pathway score p=0.04) levels were higher in symptom-high versus symptom-low, T2-low participants. Isoprostane levels were greater in symptom-high versus symptom-low participants, irrespective of T2-status (pathway score p=0.01). Cysteinyl-leukotriene E4 levels (LTE4) were elevated in T2-high versus T2-low participants (pathway score p=0.0007), irrespective of symptoms. Corticosteroid exposure, obesity and exacerbations were not associated with increased eicosanoid levels (p≥0.05).
Conclusion
Raised urinary eicosanoid levels of isoprostanes and thromboxanes were associated with increased symptoms in T2-low severe asthma. Elevated excretion of these metabolites, in T2-low participants, could reflect increased thromboxane-receptor (TP) activation, which may be promoting increased asthma severity and bronchoconstriction. Further research and interventions are needed to explore the role of TP-modulation in T2-low severe asthma.
Approximately 5–10% of patients with asthma have severe disease. A proportion remain symptomatic despite suppression of T2-related inflammation but what drives persistent symptoms remains unclear. Eicosanoids exert a functional role in pulmonary inflammation. We explored the relationship between urinary eicosanoids, asthma symptoms, obesity and T2-biomarker status.
Methods
Urine was sampled during a randomized controlled trial assessing corticosteroid optimization using T2-biomarker directed care at scheduled study visits (n=728) and at exacerbation (n=103). Urine eicosanoid concentrations were measured by mass spectrometry, then log2-transformed, z-scored and concatenated by biosynthetic pathway generating six pathway scores. Results were stratified by T2-status (T2-Low: fractional-exhaled nitric-oxide [FeNO]<20 ppb and blood eosinophil count [BEC]<0.15×109cells·L−1) versus T2-high: (FeNO ≥20 ppb and BEC ≥0.15×109cells·L−1), symptoms (symptom-low: Asthma Control Questionnaire-7 [ACQ-7<1.5)] versus symptom-high: ACQ-7≥1.5), and obesity.
Results
Isoprostane (pathway score p=0.02) and thromboxane (pathway score p=0.04) levels were higher in symptom-high versus symptom-low, T2-low participants. Isoprostane levels were greater in symptom-high versus symptom-low participants, irrespective of T2-status (pathway score p=0.01). Cysteinyl-leukotriene E4 levels (LTE4) were elevated in T2-high versus T2-low participants (pathway score p=0.0007), irrespective of symptoms. Corticosteroid exposure, obesity and exacerbations were not associated with increased eicosanoid levels (p≥0.05).
Conclusion
Raised urinary eicosanoid levels of isoprostanes and thromboxanes were associated with increased symptoms in T2-low severe asthma. Elevated excretion of these metabolites, in T2-low participants, could reflect increased thromboxane-receptor (TP) activation, which may be promoting increased asthma severity and bronchoconstriction. Further research and interventions are needed to explore the role of TP-modulation in T2-low severe asthma.
| Original language | English |
|---|---|
| Journal | ERJ Open Research |
| Early online date | 27 Feb 2025 |
| DOIs | |
| Publication status | Early online date - 27 Feb 2025 |
Keywords
- Urinary thromboxane
- isoprostane levels
- symptom-high
- asthma
