Polyhexamethylene guanidine phosphate (PHMG-p) is a biocidal compound linked to respiratory toxicity following exposure to humidifier disinfectants, but long-term pulmonary outcomes after inhalation remain insufficiently characterized. This study evaluated the pulmonary carcinogenic effects of chronic PHMG-p inhalation in a rat model under environmentally relevant exposure conditions. Sprague-Dawley rats were exposed to aerosolized PHMG-p at concentrations of 0.01, 0.03, or 0.09 mg/m[3] via whole-body inhalation for approximately 90 days and were serially assessed at 26, 52, 78, and 96 weeks using noninvasive chest computed tomography and histopathological examination to evaluate pulmonary lesion development. Pulmonary lesions demonstrated clear dose- and time-dependent patterns, with no bronchioloalveolar hyperplasia or no malignant lung tumors observed in the control or low-dose groups throughout the study period. In contrast, medium- and high-dose exposure resulted in progressive increases in hyperplastic and neoplastic lesions over time, and bronchioloalveolar adenoma/epithelioma and malignant lung tumors appeared only after prolonged exposure, predominantly in the high-dose group at later follow-up periods in both sexes. Imaging findings closely corresponded with histopathological progression, indicating that chronic inhalation exposure to PHMG-p can induce progressive pulmonary neoplastic lesions in a dose- and time-dependent manner and providing experimental evidence for potential long-term respiratory hazards associated with inhaled PHMG-p.

Polyhexamethylene guanidine phosphate (PHMG-p), a cationic disinfectant previously used in humidifiers, has been linked to severe pulmonary diseases in Korea. This study aimed to elucidate the molecular mechanisms underlying PHMG-p-induced lung toxicity using an integrated multi-omics approach. BALB/c mice were intratracheally instilled with PHMG-p (0, 0.03, 0.1 mg/kg, twice weekly for 4 weeks). Histopathology revealed dose-dependent pulmonary lesions, including inflammatory infiltration, alveolar wall hyperplasia, and fibrosis. Transcriptomic profiling identified 213 and 1,506 differentially expressed genes (DEGs) in the low- and high-dose groups, respectively, with enriched pathways related to immune activation, cytokine signaling, and cellular stress responses. Proteomic analysis detected 148 and 1,168 differentially expressed proteins (DEPs), many of which overlapped with DEGs and were associated with chemokine signaling, protein refolding, and ion transport dysregulation. Metabolomic profiling of serum samples identified dose-responsive alterations in amino acid and energy metabolism, with notable increases in glutamate, leucine, serine, and related metabolites. Integrated omics analysis revealed consistent up-regulation of CDKN1A, HSP90AA1, HSPA1A, HSPA8, and HSPH1, and down-regulation of FPR1, suggesting their roles as potential biomarkers of PHMG-p-induced pulmonary injury. Pathway convergence indicated activation of inflammatory and fibrotic remodeling processes, as well as metabolic reprogramming involving glutamate and branched-chain amino acid pathways. These findings provide mechanistic insight into PHMG-p-induced lung toxicity and highlight multi-omics signatures that may serve as biomarkers for monitoring or predicting pulmonary damage caused by cationic polymer biocides.

A 3:1 disinfectant composed of 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and 2-methyl-4-isothiazolin-3-one (MIT) has been widely used in water-based household products such as detergents, toothpaste, and cosmetic applications. In the United States, it was classified as a pesticide in 1998 and designated as a Category 2 dermal-toxicity substance for cosmetics. Several studies in the Republic of Korea have reported that components of humidifier disinfectants (HDs) such as polyhexamethylene guanidine (PHMG), CMIT, and MIT cause chronic pulmonary conditions. However, its toxicity is still controversial because of the discrepant results between human cases and animal experiments. We recapitulate the in vivo characteristics of the pulmonary epithelial cells and introduce an air-liquid interface (ALI) system to replicate acute inhalation injury. To assess compound-specific toxicity in the human airway, NHBE cells were first differentiated under ALI conditions and then exposed to MIT under submerged conditions. In parallel, [AX]Barrier-on-Chip (AlveoliX AG) technology integrated with the Cloud α AX12 (Vitrocell Systems GmbH) allowed us to mimic human lung physiology more realistically. In this study, this inhalation platform was utilized to nebulize MIT onto primary cell-derived immortalized alveolar epithelial cells ([AX]iAECs) co-cultured with human lung microvascular endothelial cells (hLMVECs) seeded onto the AX12. Additionally, PHMG was used as a positive control to compare MIT toxicity levels. Using this approach, significant barrier disruption and cytotoxicity were observed when MIT was introduced into the alveolar lung-on-chip. Overall, we confirmed MIT-induced toxicity in both bronchial and alveolar epithelial models, highlighting the importance of multiscale in vitro systems for inhalation toxicology.

Trans-nasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) has emerged as a promising technique for prolonging safe apnea time while maintaining oxygenation during airway procedures. This case highlights the successful application of THRIVE as a respiratory support modality during interventional bronchoscopy. By ensuring adequate oxygenation, reducing airway trauma, and improving procedural conditions, THRIVE proves to be a valuable alternative to conventional ventilation techniques in select airway interventions.

BACKGROUND: Polyhexamethylene guanidine phosphate (PHMG-p), a commonly utilized ingredient in humidifier disinfectants, has emerged as a primary factor contributing to pulmonary damage, asthmatic conditions, and prenatal complications in South Korea. Nevertheless, the extended neurological impacts resulting from PHMG-p exposure have not been adequately investigated. Our objective was to examine the fundamental mechanisms underlying PHMG-p-triggered neurological dysfunction in a murine model after biocide exposure. METHODS: Adult mice aged eight weeks underwent intratracheal instillation (ITI) with either PHMG-p solution (0.9 mg/kg) or saline solution (serving as controls). After a four-week recuperation interval, we examined histopathological features including inflammatory responses and fibrotic alterations in lung tissue. Behavioral performance was assessed through open field testing, Y-maze evaluation, and Rotarod performance tests. Brain tissue molecular characteristics were investigated via RNA sequencing, RT-PCR analysis, and western blot techniques. Cellular composition in neural tissues was determined using immunofluorescence methods. RESULTS: Four weeks after the exposure, the brains of the mice displayed abnormal neuronal and astrocyte populations owing to activated neuronal death. Notably, exposure to PHMG-p impaired synaptic formation and altered behavioral patterns in the mice. The observed changes appeared to be associated with transfer RNA (tRNA)-mediated neuronal death and synaptic formation, as RNA sequencing-based gene ontology analysis revealed the downregulation of tRNA expression following PHMG-p exposure. CONCLUSION: These findings enhance our understanding of the pathophysiological mechanisms triggered by PHMG-p exposure.