Abstract
Our aim was to correlate chest CT and pathologic findings of polyhexamethylene guanidine phosphate (PHMG)-induced lung injuries in a rat model, to determine whether PHMG exposure causes lung tumors, and to explore genetic alterations according to PHMG exposure under the guidance of CT. A PHMG solution was intratracheally administrated to 40 male rats. Chest CT was carried out in all rats and both lungs were collected for histopathologic evaluation. At 4- and 8-weeks post-instillation, one lobe of the right lung from 3 rats was subjected to RNA sequencing. At least one abnormal CT finding was found in all rats at all weeks. The major CT findings were inflammation, fibrosis, and tumors in the pathologic analysis, where significant changes were observed over time. The lung lesions remained persistent after 8 weeks of PHMG exposure. In the pathologic analysis, the extent/severity of inflammation did not show statistically significant changes over time, whereas the extent/severity of fibrosis increased continuously up to 6 weeks after PHMG exposure and then decreased significantly at 8 weeks. Bronchiolar-alveolar adenomas which have malignant potential were found in 50% of rats at 6 and 8 weeks after PHMG exposure. Also, several genes associated with lung cancer, acute lung injury, and pulmonary fibrosis were detected. Our study revealed that PHMG-induced lung injury and its changes according to the number of weeks after exposure were demonstrated using chest CT and pathologic evaluation. In addition, we showed that PHMG exposure caused lung tumors and genetic alterations according to PHMG exposure under the guidance of CT.
Highlights
Our aim was to correlate chest CT and pathologic findings of polyhexamethylene guanidine phosphate (PHMG)-induced lung injuries in a rat model, to determine whether PHMG exposure causes lung tumors, and to explore genetic alterations according to PHMG exposure under the guidance of CT
The purposes of this study were to correlate chest CT and pathologic findings of PHMG-induced lung injury in a rat model, to determine whether PHMG exposure causes lung tumors, and to explore genetic alterations according to PHMG exposure under the guidance of CT
We evaluated PHMG-induced lung injury and its changes according to the number of weeks after exposure in a rat model using chest CT and pathologic evaluation
Summary
Our aim was to correlate chest CT and pathologic findings of polyhexamethylene guanidine phosphate (PHMG)-induced lung injuries in a rat model, to determine whether PHMG exposure causes lung tumors, and to explore genetic alterations according to PHMG exposure under the guidance of CT. Our study revealed that PHMG-induced lung injury and its changes according to the number of weeks after exposure were demonstrated using chest CT and pathologic evaluation. Polyhexamethylene guanidine phosphate (PHMG) is a member of the polymeric guanidine family which is widely used as a biocide in the medicine, agriculture, and food industries because of its broad-spectrum antibacterial, antifungal, and antiviral activities in addition to its relatively low toxicity for h umans[1] This compound was used as humidifier disinfectants, and several epidemiological and experimental studies revealed a causal association between PHMG exposure through humidifiers and severe lung injuries[2,3]. Chest CT analysis and pathologic correlations of humidifier disinfectant-associated lung disease were performed in both children and a dults[4,5] In these studies, only patients who had rapidly progressive respiratory distress for several days or weeks were included. Since PHMG is known to cause cell cycle arrest and apoptosis in lung epithelial cells[6], we hypothesized that exposure of PHMG may be related to tumorigenesis
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