Unique Effect of Aspirin Therapy on Biomarkers in Aspirin-exacerbated Respiratory Disease. A Prospective Trial.

Abstract

Rationale: Daily high-dose aspirin therapy benefits many patients with aspirin-exacerbated respiratory disease but provides no benefit for aspirin-tolerant patients with asthma. Type 2 inflammation characterizes aspirin-exacerbated respiratory disease.Objectives: To determine whether high-dose aspirin therapy changes biomarkers of type 2 inflammation in aspirin-exacerbated respiratory disease.Methods: Forty-two subjects with aspirin-exacerbated respiratory disease underwent an aspirin desensitization and were placed on high-dose aspirin (1,300 mg daily). Fifteen aspirin-tolerant subjects with asthma were also placed on high-dose aspirin. Biologic specimens and clinical parameters were collected at baseline and after 8 weeks on aspirin. Urinary eicosanoids, plasma tryptase and cytokine levels, platelet-leukocyte aggregates, and granulocyte transcripts were assessed.Measurements and Main Results: Eight weeks of high-dose aspirin decreased nasal symptoms and urinary prostaglandin E metabolite (P < 0.05) and increased urinary leukotriene E4 (P < 0.01) levels in subjects with aspirin-exacerbated respiratory disease, but not in those with aspirin-tolerant asthma. Urinary prostaglandin D2 and thromboxane metabolites decreased in both groups. Only in subjects with aspirin-exacerbated respiratory disease, exhaled nitric oxide (P < 0.05), plasma tryptase (P < 0.01), and blood eosinophil (P < 0.01) and basophil (P < 0.01) counts increased and plasma tryptase correlated with eosinophil counts (Pearson r = 0.514; P < 0.01) on aspirin. After correction for eosinophil counts, aspirin-induced changes in blood granulocyte transcripts did not differ between groups. Aspirin had no effect on platelet-leukocyte aggregates, platelet activation markers, or plasma cytokines in either group.Conclusions: High-dose aspirin therapy for 8 weeks paradoxically increases markers of type 2 inflammation in subjects with aspirin-exacerbated respiratory disease, despite reducing nasal symptoms. This effect of aspirin is unique to aspirin-exacerbated respiratory disease and not observed in subjects with aspirin-tolerant asthma.

• Authors: Katherine N Cahill, Jing Cui, Parul Kothari, Katherine Murphy, Benjamin A Raby, Joseph Singer, Elliot Israel, Joshua A Boyce, Tanya M Laidlaw
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 200 Issue 6 Pg. 704-711 (09 15 2019) ISSN: 1535-4970 [Electronic] United States
• PMID: 30978291 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Biomarkers
• Receptors, Leukotriene
• Aspirin

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, therapeutic use)
• Aspirin (adverse effects, therapeutic use)
• Asthma, Aspirin-Induced (drug therapy)
• Biomarkers (urine)
• Drug Hypersensitivity (complications)
• Female
• Humans
• Male
• Middle Aged
• Prospective Studies
• Receptors, Leukotriene (analysis)
• Respiratory Tract Infections (chemically induced)