Autoimmune Connective Tissue Disease Following Carbon Monoxide Poisoning: A Nationwide Population-Based Cohort Study

Chien-Cheng Huang,1– 3 Chung-Han Ho,4,5 Yi-Chen Chen,4 Chien-Chin Hsu,1,6 Hung-Jung Lin,1,7 Jhi-Joung Wang,4,8 How-Ran Guo2,9,10 1Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Senior Services, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 4Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 5Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 6Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 7Department of Emergency Medicine, Taipei Medical University, Taipei, Taiwan; 8Allied AI Biomed Center, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 9Department of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 10Occupational Safety, Health and Medicine Research Center, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: How-Ran GuoDepartment of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 1 Daxue Road, East District, Tainan City 701, TaiwanTel +886-6-235-3535Fax +886-6-275-2484Email hrguo@mail.ncku.edu.twBackground: In addition to hypoxia, oxidative stress and inflammation due to carbon monoxide (CO) poisoning cause adverse health effects. These mechanisms are related to the occurrence of autoimmune connective tissue disease, but studies on the association between CO poisoning and autoimmune connective tissue disease are limited. We conducted a study to evaluate the occurrence of autoimmune connective tissue disease following CO poisoning.Methods: We identified participants with CO poisoning diagnosed between 1999 and 2012 from the Nationwide Poisoning Database and selected participants without CO poisoning from the Taiwan National Health Insurance Research Database with matching age and index dates at a 1:3 ratio. Sex, underlying comorbidities, and monthly income were also included in the analyses. We followed up the participants until 2013 and made comparison of the risk of autoimmune connective tissue disease between participants with and without CO poisoning.Results: The 23,877 participants with CO poisoning had a higher risk for autoimmune connective tissue disease than the 71,631 participants without CO poisoning (adjusted hazard ratio [AHR], 3.5; 95% confidence interval [CI], 3.1– 3.9) after adjustment for sex, diabetes, Lyme disease, herpes zoster, infectious mononucleosis, hepatitis, HIV infection, liver disease, renal disease, non-CO poisoning or drug abuse, malignancy, hypertension, hyperlipidemia, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and monthly income. An increased risk was observed even after 4 years of follow-up (AHR, 3.6; 95% CI, 3.0– 4.4).Conclusion: The risk of autoimmune connective tissue disease increased following CO poisoning. Close follow-up of the patients with CO poisoning for the development of connective tissue disease is recommended, and further investigation of the detailed mechanisms is warranted.Keywords: autoimmune, carbon monoxide poisoning, connective tissue disease, hypoxia, inflammation, oxidative stress