Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease.
Sphingolipid (SL) metabolites have been suggested to be important inflammatory mediators in airway inflammation and asthma. However, little is known about SL metabolites in aspirin-exacerbated respiratory disease (AERD). We aimed to explore the potential AERD biomarkers by conducting lipidomics targeting SL metabolites. The levels of SL metabolites in serum and urine samples from 45 AERD patients and 45 aspirin-tolerant asthma (ATA) patients were quantified through mass spectrometry. During the lysine-aspirin bronchoprovocation test (ASA-BPT), the levels of serum sphingomyelin (SM) were significantly decreased in AERD (P < 0.05) but not in ATA. The serum SM levels were positively correlated with airway responsiveness to methacholine. At the basal status before the ASA-BPT, the levels of serum sphingosine-1-phosphate (S1P) and urine sphingosine were significantly higher in the AERD patients compared with that of ATA patients (P < 0.001) and were positively correlated with a greater decrease in FEV1(%) values following the ASA-BPT test (P < 0.001 for each), and with serum periostin level (P < 0.05 for each). This study is the first to evaluate serum S1P and urine sphingosine as potential biomarkers of AERD as well as to examine the metabolic disturbance of SL in AERD patients.
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
Hoang Kim Tu
HK
Trinh
Translational Research Laboratory for Inflammatory Disease, Clinical Trial Center, Ajou University Medical Center, Suwon, South Korea.
Su-Chin
SC
Kim
Department of Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Kumsun
K
Cho
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Su-Jung
SJ
Kim
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
Ga-Young
GY
Ban
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Hyun-Ju
HJ
Yoo
Department of Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Joo-Youn
JY
Cho
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
Hae-Sim
HS
Park
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.|Translational Research Laboratory for Inflammatory Disease, Clinical Trial Center, Ajou University Medical Center, Suwon, South Korea.
Seung-Hyun
SH
Kim
D000293:Adolescent; D000328:Adult; D000368:Aged; D055963:Asthma, Aspirin-Induced / Q000097:blood* / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine*
D015415:Biomarkers; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine