Sputum biomarkers during aspirin desensitization in nonsteroidal anti-inflammatory drugs exacerbated respiratory disease

Respir Med. 2019 Jun;152:51-59. doi: 10.1016/j.rmed.2019.04.021. Epub 2019 Apr 30.

Abstract

Background: Aspirin desensitization (AD) is an effective and safe therapeutic option for patients with nonsteroidal anti-inflammatory drugs (NSAIDs)-exacerbated respiratory disease (N-ERD). The mechanisms driving its beneficial effects remain poorly understood.

Objective: To investigate the effect of long-term AD on clinical, biochemical and radiological changes in N-ERD patients.

Methods: The study group consisted of twenty-three individuals with N-ERD who underwent AD, followed by ingestion of 325 mg aspirin twice daily. Twenty patients completed the 52 weeks of AD. The following evaluations were conducted at baseline and in the 52nd week of AD: (i) clinical: asthma exacerbations, Asthma Control Test (ACT), Visual Analogue Scale (VAS) for the assessment of nasal symptoms; (ii) blood and induced sputum supernatant (ISS) periostin, (iii) phenotypes based on induced sputum (IS) cells, (iiii) ISS and nasal lavage (NL) concentration of prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), tetranor-PGD-M, tetranor-PGE-M, 8-iso-PGE2, leukotriene B4 (LTB4), LTC4, LTD4 and LTE4, and urine LTE4.

Results: A significant improvement was observed in ACT (P = 0.02) and VAS score (P = 0.008) in the 52nd week of AD. ISS periostin and IS eosinophil count decreased significantly in the 52nd week of AD (P = 0.04 and P = 0.01, respectively). ISS and NL eicosanoid concentrations did not change following long-term AD.

Conclusion: and Clinical Relevance: AD is associated with a decrease in sputum periostin biosynthesis, which may prevent the recruitment of eosinophils into respiratory tissue and be one of explanation of the clinical benefits of AD. Long-term aspirin administration does not lead to an imbalance between pro- and anti-inflammatory ISS eicosanoids.

Keywords: Aspirin desensitization; Eicosanoids; Induced sputum; Nasal lavage; Nonsteroidal anti-inflammatory drugs exacerbated respiratory disease; Periostin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspirin / administration & dosage
  • Aspirin / adverse effects*
  • Aspirin / therapeutic use
  • Asthma / chemically induced
  • Asthma / metabolism
  • Asthma / physiopathology
  • Biomarkers / blood
  • Biomarkers / urine
  • Carrier Proteins / metabolism
  • Cell Adhesion Molecules / blood
  • Cell Adhesion Molecules / drug effects
  • Desensitization, Immunologic / methods*
  • Eicosanoids / metabolism
  • Eosinophils / drug effects
  • Female
  • Humans
  • Lipoproteins / metabolism
  • Male
  • Middle Aged
  • Nasal Lavage Fluid / immunology
  • Prospective Studies
  • Respiration Disorders / chemically induced
  • Respiration Disorders / immunology*
  • Sputum / metabolism*
  • Symptom Flare Up
  • Trans-Activators / metabolism
  • Visual Analog Scale

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Eicosanoids
  • Lipoproteins
  • POSTN protein, human
  • SEC14L2 protein, human
  • Trans-Activators
  • Aspirin