A urine biomarker for severe obstructive sleep apnoea patients: lipocalin-type prostaglandin D synthase

Eur Respir J. 2013 Dec;42(6):1563-74. doi: 10.1183/09031936.00133512. Epub 2012 Dec 6.

Abstract

Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of prostaglandin D2, has been reported to have a close connection with cardiovascular disease and sleep regulation. This study aimed to test the hypothesis that the L-PGDS level is a useful marker to identify patients with obstructive sleep apnoea. 64 subjects were enrolled in this prospective study. Urinary concentrations of L-PGDS were measured in the morning. Measurements were made every 4 h in 25 of the 64 patients. Endothelial function was assessed by the reactive hyperaemia peripheral arterial tone index. Circadian variations in L-PGDS concentrations had a significant time-dependent fluctuation (p = 0.0002). L-PGDS was higher in the subjects with severe obstructive sleep apnoea (median 784.7 ng per mg of creatinine, n = 23) than in control subjects (262.1 ng per mg of creatinine, n = 16; p = 0.004) and in those with moderate obstructive sleep apnoea (371.7 ng per mg of creatinine, n = 25; p = 0.0008). After 2 days of continuous positive airway pressure treatment, L-PGDS concentrations in severe obstructive sleep apnoea subjects (n = 12) decreased significantly (p = 0.02) to levels present in control subjects whereas endothelial function did not change significantly. Morning urinary L-PGDS concentrations had significant correlations with the apnoea/hypopnoea index (R2 = 13.9%) and serum high-density lipoprotein cholesterol (R2 = 6.2%), but not with sleepiness. Urinary L-PGDS might be a moderately useful marker to identify patients with severe obstructive sleep apnoea.

Trial registration: ClinicalTrials.gov NCT01096433.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / urine*
  • Cholesterol, HDL / blood
  • Circadian Rhythm
  • Continuous Positive Airway Pressure
  • Creatinine / analysis
  • Female
  • Humans
  • Intramolecular Oxidoreductases / blood*
  • Intramolecular Oxidoreductases / urine*
  • Lipocalins / blood*
  • Lipocalins / urine*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polysomnography
  • Prospective Studies
  • ROC Curve
  • Sleep Apnea, Obstructive / diagnosis*
  • Sleep Apnea, Obstructive / urine*
  • Young Adult

Substances

  • Biomarkers
  • Cholesterol, HDL
  • Lipocalins
  • Creatinine
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase

Associated data

  • ClinicalTrials.gov/NCT01096433