Yonsei Med J.  2020 Feb;61(2):186-191. 10.3349/ymj.2020.61.2.186.

NOTCH1 Pathway is Involved in Polyhexamethylene Guanidine-Induced Humidifier Disinfectant Lung Injuries

Affiliations
  • 1Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea.
  • 2Asan Medical Center, Asan Institute for Life Sciences, Environmental Health Center, Seoul, Korea.
  • 3Department of Medicine, University of Ulsan Collage of Medicine, Seoul, Korea.
  • 4Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. sjhong@amc.seoul.kr
  • 5Department of Pediatrics, International St. Mary's hospital, Catholic Kwandong University College of Medicine, Incheon, Korea.
  • 6Department of Pediatrics, Mediplex Hospital, Incheon, Korea.
  • 7Department of Pediatrics, Pusan National University Yangsan Hospital, Yangsan, Korea.
  • 8Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 9Department of Pulmonary and Critical Care Medicine, Asan Medical Center, Seoul, Korea.
  • 10Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

An outbreak of fatal humidifier disinfectant lung injuries (HDLI) occurred in Korea. Human studies on mechanisms underlying HDLI have yet to be conducted. This study aimed to investigate methylation changes and their potential role in HDLI after exposure to HDs containing polyhexamethylene guanidine-phosphate. DNA methylation analysis was performed in blood samples from 10 children with HDLI and 10 healthy children using Infinium Human MethylationEPIC BeadChip. Transcriptome analysis was performed using lung tissues from 5 children with HDLI and 5 controls. Compared to healthy controls, 92 hypo-methylated and 79 hyper-methylated CpG sites were identified in children with HDLI at the statistical significance level of |Δβ|>0.2 and p<0.05. NOTCH1 was identified as a candidate network hub gene in cases. NOTCH1 transcripts significantly increased in lung tissues from HDLI cases compared to unexposed controls (p=0.05). NOTCH1 may play an important role in pulmonary fibrosis of HDLI.

Keyword

Humidifier disinfectant; pulmonary fibrosis; NOTCH1; methylation; polyhexamethylene guanidine
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