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Publications

Journal Article Research Support, Non-U.S. Gov't Epublish 12 citations

PubMed: 36396675 DOI: 10.1038/s41598-022-24406-z

Identification and characterization of lysophosphatidylcholine 14:0 as a biomarker for drug-induced lung disease.

Sci Rep 12(1):19819

Authors: Kosuke Saito, Akihiko Gemma, Koichiro Tatsumi, Noboru Hattori, Atsuhito Ushiki, Kenji Tsushima, Yoshinobu Saito, Mitsuhiro Abe, Yasushi Horimasu, Takeru Kashiwada, Kazuhiko Mori, Motonobu Sato, Takayoshi Nishiya, Kazuhiko Takamatsu, Yuchen Sun, Noriaki Arakawa, Takashi Izumi, Yasuo Ohno, Yoshiro Saito, Masayuki Hanaoka

Affiliations

  • Division of Medical Safety Science, National Institute of Health Sciences, Kawasaki, 210-9501, Japan.
  • Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, 113-8603, Japan.
  • Department of Respirology (B2), Graduate School of Medicine, Chiba University, Chiba, 260-8677, Japan.
  • Department of Respiratory Medicine, Hiroshima University Hospital, Hiroshima, 734-8551, Japan.
  • First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan.
  • School of Medicine, International University of Health and Welfare, Narita, 286-8686, Japan.
  • Daiichi Sankyo RD Novare Co. Ltd. Tokyo, 134-8630, Japan.
  • Astellas Pharma Inc. Tsukuba, 305-8585, Japan.
  • Kihara Memorial Foundation, Yokohama, 230-0045, Japan.
  • Division of Medical Safety Science, National Institute of Health Sciences, Kawasaki, 210-9501, Japan.

Abstract

Drug-induced interstitial lung disease (DILD) occurs when drug exposure causes inflammation of the lung interstitium. DILD can be caused by different types of drugs, and some DILD patterns results in a high mortality rate; hence, DILD poses a serious problem in clinical practice as well as drug development, and strategies to diagnose and distinguish DILD from other lung diseases are necessary. We aimed to identify novel biomarkers for DILD by performing lipidomics analysis on plasma samples from patients with acute and recovery phase DILD. Having identified lysophosphatidylcholines (LPCs) as candidate biomarkers for DILD, we determined their concentrations using validated liquid chromatography/mass spectrometry biomarker assays. In addition, we evaluated the ability of LPCs to discriminate patients with acute phase DILD from those with recovery phase DILD, DILD-tolerant, or other lung diseases, and characterized their association with clinical characteristics. Lipidomics analysis revealed a clear decrease in LPC concentrations in the plasma of patients with acute phase DILD. In particular, LPC(14:0) had the highest discriminative index against recovery phase and DILD-tolerant patients. LPC(14:0) displayed no clear association with causal drugs, or subjects' backgrounds, but was associated with disease severity. Furthermore, LPC(14:0) was able to discriminate between patients with DILD and other lung diseases, including idiopathic interstitial pneumonia and lung disease associated with connective tissue disease. LPC(14:0) is a promising biomarker for DILD that could improve the diagnosis of DILD and help to differentiate DILD from other lung diseases, such as idiopathic interstitial pneumonia and connective tissue disease.

MeSH

Lysophosphatidylcholines, Pharmaceutical Preparations, Recycling, Connective Tissue Diseases, Biomarkers, Pneumonia, Idiopathic Interstitial Pneumonias, Diagnosis, Natural Science Disciplines, Lung Diseases, Tissues, Plasma, Liquid Chromatography-Mass Spectrometry

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