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Keywords:

  • aspirin-exacerbated respiratory disease;
  • CysLT;
  • eosinophil;
  • proteomics

Summary

Background

Eosinophil activation is the key feature of upper and lower airway inflammation in aspirin-exacerbated respiratory disease (AERD).

Objective

To investigate the mechanism of eosinophil activation and identify novel inflammatory mediators using proteomics.

Methods

Thirty-two asthmatic subjects were enrolled: 18 AERD patients who showed positive responses to the lysine-aspirin nasal provocation test (L-ASA NPT) and 14 aspirin-tolerant asthma (ATA) patients who showed negative responses to the L-ASA NPT (control group). Nasal lavage fluid (NLF) was collected before (baseline), at 10, 30 and 60 min (early response), and at 3 h (late response) after the L-ASA NPT. Eosinophil cationic protein (ECP) and cysteinyl leucotriene (CysLT) levels were measured using an ImmunoCAP system and ELISA respectively. To identify proteins involved in AERD, comparative proteomics was applied using NLFs collected before and after L-ASA NPTs in AERD patients. The clinical relevance of identified novel proteins was evaluated by ELISA using NLFs from the AERD and ATA groups.

Results

Eosinophil cationic protein and CysLT levels both increased significantly during the early response in AERD. ECP levels increased until the late response in AERD, while CysLT levels were not significantly increased during the late response. Proteomic analysis showed up-regulation of apolipoprotein A1 (ApoA1), α2-macroglobulin (α2M) and ceruloplasmin (CP), with significant increases in NLF of AERD patients, which was significantly higher in AERD patients with chronic rhinosinusitis. Significant correlations were noted between ECP and CysLT, ApoA1, α2M and CP levels during the early response in AERD patients.

Conclusion

Eosinophil activation occurred in early and late responses after L-ASA NPT in upper airway mucosa of AERD patients, where ApoA1, α2M and CP as well as CysLT may be involved in eosinophilic inflammation.