PMID- 35710744 OWN - NLM STAT- MEDLINE DCOM- 20230222 LR - 20230404 IS - 1468-3296 (Electronic) IS - 0040-6376 (Linking) VI - 78 IP - 3 DP - 2023 Mar TI - Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: a multicentre study. PG - 225-232 LID - 10.1136/thoraxjnl-2021-218396 [doi] AB - BACKGROUND: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. METHODS: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM(2.5)) and PM(2.5)-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. FINDINGS: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM(2.5) and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nepsilon-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM(2.5) exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. INTERPRETATION: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity. CI - (c) Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Wu, Chao-Chien AU - Wu CC AD - Department of Internal Medicine, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan. FAU - Wang, Chin-Chou AU - Wang CC AD - Department of Internal Medicine, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan. AD - Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Chung, Wen-Yu AU - Chung WY AD - Department of Computer Science and Information Engineering, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan. FAU - Sheu, Chau-Chyun AU - Sheu CC AUID- ORCID: 0000-0002-7979-3749 AD - Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Yang, Yi-Hsin AU - Yang YH AD - National Institute of Cancer Research, National Health Research Institutes, Maioli, Taiwan. FAU - Cheng, Ming-Yen AU - Cheng MY AD - Hong Kong Baptist University, Hong Kong, Hong Kong. FAU - Lai, Ruay-Sheng AU - Lai RS AD - Division of Chest Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. FAU - Leung, Sum-Yee AU - Leung SY AD - Department of Internal Medicine, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan. FAU - Lin, Chi-Cheng AU - Lin CC AD - Department of Internal Medicine, Antai Medical Care Corp Antai Tian Sheng Memorial Hospital, Pingtung, Taiwan. FAU - Wei, Yu-Feng AU - Wei YF AD - Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan. FAU - Lin, Ching-Hsiung AU - Lin CH AD - Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan. AD - Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan. AD - Department of Recreation and Holistic Wellness, MingDao University, Changhua, Taiwan. FAU - Lin, Sheng-Hao AU - Lin SH AD - Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan. AD - Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan. AD - Department of Recreation and Holistic Wellness, MingDao University, Changhua, Taiwan. FAU - Hsu, Jeng-Yuan AU - Hsu JY AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Huang, Wei-Chang AU - Huang WC AD - Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. AD - Department of Medical Technology, Jen-Teh Junior College of Medicine Nursing and Management, Miaoli, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan. FAU - Tseng, Chia-Cheng AU - Tseng CC AD - Department of Internal Medicine, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan. FAU - Lai, Yung-Fa AU - Lai YF AD - Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan. FAU - Cheng, Meng-Hsuan AU - Cheng MH AD - Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. AD - Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Chen, Huang-Chi AU - Chen HC AD - Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan. FAU - Yang, Chih-Jen AU - Yang CJ AD - Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Hsu, Shih-Chang AU - Hsu SC AD - Emergency Department, Taipei Municipal Wan-Fang Hospital, Taipei, Taiwan. AD - Department of Emergency, Taipei Medical University School of Medicine, Taipei, Taiwan. FAU - Su, Chian-Heng AU - Su CH AD - Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Wang, Chien-Jen AU - Wang CJ AD - National Institute of Environmental Health Sciences, National Health Research Institutes, Maioli, Taiwan. FAU - Liu, Huei-Ju AU - Liu HJ AD - National Institute of Environmental Health Sciences, National Health Research Institutes, Maioli, Taiwan. FAU - Chen, Hua-Ling AU - Chen HL AUID- ORCID: 0000-0001-7406-5702 AD - National Institute of Environmental Health Sciences, National Health Research Institutes, Maioli, Taiwan. FAU - Hsu, Yuan-Ting AU - Hsu YT AD - National Institute of Environmental Health Sciences, National Health Research Institutes, Maioli, Taiwan. FAU - Hung, Chih-Hsing AU - Hung CH AD - Department of Pediatrics, Kaohsiung Medical University, Kaohsiung, Taiwan skhuang@nhri.edu.tw ed110209@edah.org.tw a0780047@g-mail.nsysu.edu.tw pedhung@gmail.com. AD - Department of Pediatrics, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan. FAU - Lee, Chon-Lin AU - Lee CL AD - Department of Marine Environment and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan skhuang@nhri.edu.tw ed110209@edah.org.tw a0780047@g-mail.nsysu.edu.tw pedhung@gmail.com. FAU - Huang, Ming-Shyan AU - Huang MS AD - Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan skhuang@nhri.edu.tw ed110209@edah.org.tw a0780047@g-mail.nsysu.edu.tw pedhung@gmail.com. AD - Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Huang, Shau-Ku AU - Huang SK AD - National Institute of Environmental Health Sciences, National Health Research Institutes, Maioli, Taiwan skhuang@nhri.edu.tw ed110209@edah.org.tw a0780047@g-mail.nsysu.edu.tw pedhung@gmail.com. AD - Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20220616 PL - England TA - Thorax JT - Thorax JID - 0417353 RN - 0 (Air Pollutants) RN - 0 (Sphingolipids) RN - 0 (Particulate Matter) RN - 0 (Polycyclic Aromatic Hydrocarbons) SB - IM CIN - Thorax. 2023 Mar;78(3):222. PMID: 36368893 MH - Adult MH - Humans MH - *Air Pollutants/toxicity/analysis MH - Sphingolipids MH - *Diabetes Mellitus, Type 2 MH - *Air Pollution/adverse effects/analysis MH - *Asthma MH - Particulate Matter/toxicity/analysis MH - *Polycyclic Aromatic Hydrocarbons/analysis MH - Environmental Monitoring/methods OTO - NOTNLM OT - Asthma COIS- Competing interests: None declared. EDAT- 2022/06/18 06:00 MHDA- 2023/02/22 06:00 CRDT- 2022/06/17 00:08 PHST- 2021/10/22 00:00 [received] PHST- 2022/05/12 00:00 [accepted] PHST- 2022/06/18 06:00 [pubmed] PHST- 2023/02/22 06:00 [medline] PHST- 2022/06/17 00:08 [entrez] AID - thoraxjnl-2021-218396 [pii] AID - 10.1136/thoraxjnl-2021-218396 [doi] PST - ppublish SO - Thorax. 2023 Mar;78(3):225-232. doi: 10.1136/thoraxjnl-2021-218396. Epub 2022 Jun 16.