title: The effect of aspirin desensitization on novel biomarkers in aspirin-exacerbated respiratory diseases.
abstract: BACKGROUND
  Patients with aspirin-exacerbated respiratory disease have been shown to benefit clinically from aspirin desensitization followed by chronic high-dose aspirin therapy. However, the mechanism of this phenomenon is still unclear.
  
  
  OBJECTIVE
  The aim of this study was to characterize the airway inflammatory response to aspirin desensitization and after treatment with high-dose aspirin for 6 months.
  
  
  METHODS
  Twenty-one adult patients with asthma, chronic polypoid sinusitis, and a convincing history of acute respiratory reaction to the ingestion of aspirin or nonsteroidal anti-inflammatory drugs were selected. These patients underwent an oral desensitization to aspirin over a 2-day period, followed by daily ingestion of aspirin 650 mg twice daily. Induced sputum samples and exhaled nitric oxide measurements were taken before the procedure, during the second day of the procedure, and after 6 months of treatment.
  
  
  RESULTS
  There was a significant elevation in both the exhaled nitric oxide level (P = .03) and sputum tryptase level (P = .05) during the desensitization process. After 6 months of aspirin treatment, sputum IL-4 (P = .0007) and matrix metalloproteinase 9 (MMP-9; P = .05) decreased significantly compared with baseline. Predesensitization to postdesensitization changes in MMP-9 and tissue inhibitors of metalloproteinases 1 were highly correlated (r = 0.79; P = .0003). Immediately after the desensitization, MMP-9 and tryptase were correlated (r = 0.82; P = .001), whereas IL-4 was inversely related with FMS-like tyrosine kinase 3 ligand (FLT3-L) (r = -0.79; P = .0008). There was a significant decrease in the average symptom score at 6 months.
  
  
  CONCLUSIONS
  Consistent with previous reports, acute aspirin desensitization in patients with aspirin-exacerbated respiratory disease involves mast cell degranulation. In contrast, long-term treatment with aspirin involves suppression of IL-4 as well as downregulation of proinflammatory MMP-9 while T(H)1 marker FLT3-L increases.
authors: Division of Allergy and Immunology, National Jewish Health, Denver, CO 80206, USA. katialr@njhealth.org
authors: Rohit K
authors: RK
authors: Katial
authors: Matthew
authors: M
authors: Strand
authors: Theerapol
authors: T
authors: Prasertsuntarasai
authors: Roxanne
authors: R
authors: Leung
authors: Weihong
authors: W
authors: Zheng
authors: Rafeul
authors: R
authors: Alam
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000150:complications / Q000188:drug therapy; D015415:Biomarkers / Q000032:analysis*; D002908:Chronic Disease; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D012852:Sinusitis / Q000150:complications / Q000188:drug therapy; D013183:Sputum / Q000737:chemistry* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D008565:Membrane Proteins; C084881:flt3 ligand protein; D015847:Interleukin-4; D020780:Matrix Metalloproteinase 9; D001241:Aspirin