Evaluating Metabolic Signatures in the Serum of South Korean Patients with Humidifier Disinfectant–Associated Lung Injury Identified through Untargeted Metabolomics

Abstract

BACKGROUND: The South Korean humidifier disinfectant–associated lung injury case was one of the worst disasters involving household chemical products, resulting in over 5,800 casualties. Despite the strong association between lung injury and humidifier disinfectants, the underlying pathogenic mechanisms remain unclear. OBJECTIVES: We investigated patients with humidifier disinfectant–associated lung injury to identify key metabolic signatures, aiming to gain insights into the underlying pathogenic mechanisms based on the characteristics of these metabolites. METHODS: We employed untargeted metabolomics to assess the differential enrichment of plasma metabolites in 80 South Korean children with lung injuries caused by exposure to humidifier disinfectant containing polyhexamethylene guanidine. The key metabolites identified were subsequently validated in an independent cohort of 132 South Korean adults. RESULTS: In the plasma of patients with humidifier disinfectant–associated lung injuries, we observed significantly higher levels of oxidized lipids in comparison with healthy controls, with these levels negatively correlating with lung function. These metabolic signatures differentiated humidifier disinfectant–associated lung injury from other respiratory diseases in children, such as asthma and bronchiolitis obliterans. The 47 key metabolites identified in children were validated in an independent adult cohort. Furthermore, the classification performance of these metabolic signatures for humidifier disinfectant–associated lung injury achieved an accuracy of 0.97, a precision of 0.95, an F1 score of 0.97, and a recall of 1.00. DISCUSSION: These findings suggest a connection between humidifier disinfectant–associated lung injury and oxidative stress-induced lipid peroxidation. The oxidative stress signatures provide valuable insights into the underlying pathogenesis of humidifier disinfectant–associated lung injury and may serve as potential targets for biomarker development.