Prostaglandin E 2 decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin

Allergy. 2019 May;74(5):922-932. doi: 10.1111/all.13671. Epub 2018 Dec 5.

Abstract

Background: A special regulatory role for prostaglandin E2 (PGE2 ) has been postulated in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD).

Objective: To investigate the effect of systemic aspirin (acetylsalicylic acid) administration on airway PGE2 biosynthesis in induced sputum supernatant (ISS) among subjects with NERD or aspirin-tolerant asthma with chronic rhinosinusitis with nasal polyposis (ATA-CRSwNP), as well as healthy controls (HC).

Methods: Induced sputum (IS) was collected from patients with NERD (n = 26), ATA-CRSwNP (n = 17), and HC (n = 21) at baseline and after aspirin challenge. Sputum differential cell count and IS supernatant (ISS) levels of prostanoids, PGE2 , 8-iso-PGE2 , tetranor-PGE-M, 8-iso-PGF2 α, and leukotriene C4 , D4 , and E4 , were determined using mass spectrometry. Urinary excretion of LTE4 was measured by ELISA.

Results: NERD subjects had elevated sputum eosinophilic count as compared to ATA-CRSwNP and HC (median NERD 9.1%, ATA-CRSwNP 2.1%, and HC 0.4%; P < 0.01). Baseline ISS levels of PGE2 were higher in asthmatics as compared to HC at baseline (NERD vs HC P = 0.04, ATA-CRSwNP vs HC P < 0.05). Post-challenge ISS levels of PGE2 compared to baseline significantly decreased in NERD and HC (P < 0.01 and P = 0.01), but not in ATA-CRSwNP. In NERD, a similar decrease in PGE2 as in HC resulted from 2.8 times lower dose of aspirin.

Conclusion: Aspirin-precipitated bronchoconstriction is associated with a decrease in airway PGE2 biosynthesis. These results support the mechanism of PGE2 biosynthesis inhibition as a trigger for bronchoconstriction in NERD.

Keywords: eicosanoids; induced sputum; nonsteroidal anti-inflammatory drug-exacerbated respiratory disease; oral aspirin challenge; prostaglandins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Aspirin / metabolism*
  • Asthma / diagnosis
  • Asthma / etiology*
  • Asthma / metabolism*
  • Asthma, Aspirin-Induced / diagnosis*
  • Asthma, Aspirin-Induced / metabolism*
  • Asthma, Aspirin-Induced / urine
  • Biomarkers
  • Dinoprostone / metabolism*
  • Disease Susceptibility
  • Female
  • Humans
  • Leukotriene E4 / urine
  • Male
  • Middle Aged
  • Phenotype
  • Respiratory Function Tests
  • Sputum / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Leukotriene E4
  • Dinoprostone
  • Aspirin