High-Dose Aspirin Increases Type 2 Inflammation in AERD

High-dose aspirin therapy paradoxically increases markers of type 2 inflammation in patients with aspirin-exacerbated respiratory disease (AERD) despite reducing nasal symptoms, but this effect is not observed in individuals with asthma who are aspirin tolerant, according to study results published in the American Journal of Respiratory and Critical Care Medicine.¹

Daily high-dose aspirin therapy is the only targeted therapy available for patients with AERD, but provides no benefit for patients with asthma who are aspirin tolerant.^2-4 While type 2 inflammation characterizes AERD, the mechanism by which daily aspirin provides therapeutic benefit in AERD and early biomarkers of clinical response are poorly understood.¹

Therefore, researchers sought to determine whether high-dose aspirin therapy would change biomarkers of type 2 inflammation in 42 patients with AERD compared with 15 patients with asthma who were aspirin tolerant. They found that 8 weeks of high-dose aspirin (1300 mg/d) decreased nasal symptoms and urinary prostaglandin (PG) E metabolite and increased urinary leukotriene E₄ levels in individuals with AERD, but not in individuals with aspirin-tolerant asthma. Urinary PGD₂ and thromboxane metabolites, however, decreased in both groups. In patients with AERD, exhaled nitric oxide, plasma tryptase, and blood eosinophil and basophil counts increased and plasma tryptase correlated with eosinophil on aspirin only.

However, after correction for eosinophil counts, aspirin-induced changes in blood granulocyte transcripts did not differ between groups. In addition, aspirin had no effect on platelet-leukocyte aggregates, platelet activation markers, or plasma cytokines in either group.

The researchers concluded that “these observations support [the theory] that the exquisite dependence on PGE₂ inhibition for mast cell activation and 5-lipooxygenase activity is a central defect in AERD and reveal that the therapeutic benefit of high-dose aspirin is independent of a global change in the PGE₂ pathway.”¹

References

1. Cahill KN, Cui J, Kothari P, et al. Unique effect of aspirin therapy on biomarkers in aspirin-exacerbated respiratory disease: a prospective trial [published online April 12, 2019]. Am J Respir Crit Care Med. doi:10.1164/rccm.201809-1755OC
2. Berges-Gimeno MP, Simon RA, Stevenson DD. Long-term treatment with aspirin desensitization in asthmatic patients with aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2003;111:180-186.
3. Stevenson DD, Hankammer MA, Mathison DA, Christiansen SC, Simon RA. Aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma: long-term outcomes. J Allergy Clin Immunol. 1996;98:751-758.
4. Swierczynska-Krepa M, Sanak M, Bochenek G, et al. Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma: a double-blind study. J Allergy Clin Immunol. 2014;134:883-890.