Integrative multi-omics approach for mechanism of humidifier disinfectant-associated lung injury.
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ABSTRACT:
SUBMITTER: Kim JH
PROVIDER: S-EPMC8567041 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Integrative multi-omics approach for mechanism of humidifier disinfectant-associated lung injury.
Kim Jeong-Hyun JH Kim Kwoneel K Yeom Jeonghun J Lee Eun E Kang Mi-Jin MJ Lee Seung-Hwa SH Kim Kyunggon K Lee So-Yeon SY Hong Sang-Bum SB Oh Dong Kyu DK Lee Kyuhong K Choi Seong-Jin SJ Yang Mi-Jin MJ Kim Jiyeon J Hong Soo-Jong SJ
Clinical and translational medicine 20211101 11
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Project description:This SuperSeries is composed of the SubSeries listed below.
2021-07-06 | GSE179447 | GEO
Project description:Inhalation of toxic chemicals, including recent e-cigarettes, often cause life-threatening lung injury. Although exposure to polyhexamethylene guanidine (PHMG)-containing humidifier disinfectant (HD) has been identified as a cause of fatal lung injury, the mechanism underlying HD-associated lung injury (HDLI) is unknown. The present study evaluated global changes in gene expression in lung tissues from patients with PHMG-induced HDLI, and compared gene expression changes in PHMG-induced rat lung tissues. Significantly different expressions in lung tissues between patients with HDLI and unaffected controls were observed. Furthermore, several fibrosis-associated overlapping genes (such as MMP2 and COL1A2) shared between humans with HDLI and rats exposed to PHMG were identified. Interactome network analysis predicted different pathways between children and adults with HDLI: the TGFβ/SMAD signaling pathway was central in adults, whereas other pathways, including integrin signaling, were associated with HDLI in children. Further interactome network analysis revealed that Rap1 and CCKR signaling pathways were significantly enriched in HDLI compared with idiopathic pulmonary fibrosis as well as their recapitulation in the lung tissues of rats exposed to PHMG. Our results suggest that MMP2-mediated different mechanisms between children and adults may be associated with PHMG-induced HDLI development, and Rap1 and CCKR pathways appear to be crucial.
2021-07-06 | GSE179446 | GEO
Project description:Inhalation of toxic chemicals, including recent e-cigarettes, often cause life-threatening lung injury. Although exposure to polyhexamethylene guanidine (PHMG)-containing humidifier disinfectant (HD) has been identified as a cause of fatal lung injury, the mechanism underlying HD-associated lung injury (HDLI) is unknown. The present study evaluated global changes in gene expression in lung tissues from patients with PHMG-induced HDLI, and compared gene expression changes in PHMG-induced rat lung tissues. Significantly different expressions in lung tissues between patients with HDLI and unaffected controls were observed. Furthermore, several fibrosis-associated overlapping genes (such as MMP2 and COL1A2) shared between humans with HDLI and rats exposed to PHMG were identified. Interactome network analysis predicted different pathways between children and adults with HDLI: the TGFβ/SMAD signaling pathway was central in adults, whereas other pathways, including integrin signaling, were associated with HDLI in children. Further interactome network analysis revealed that Rap1 and CCKR signaling pathways were significantly enriched in HDLI compared with idiopathic pulmonary fibrosis as well as their recapitulation in the lung tissues of rats exposed to PHMG. Our results suggest that MMP2-mediated different mechanisms between children and adults may be associated with PHMG-induced HDLI development, and Rap1 and CCKR pathways appear to be crucial.
2021-07-06 | GSE179445 | GEO
Project description:Integrative multi-omics approach for mechanism of humidifier disinfectant-associated lung injury
| PRJNA743863 | ENA
Project description:Integrative multi-omics approach for mechanism of humidifier disinfectant-associated lung injury [human]
| PRJNA743868 | ENA
Project description:Integrative multi-omics approach for mechanism of humidifier disinfectant-associated lung injury [rat]
| PRJNA743869 | ENA
Project description:Humidifier disinfectant (HD) is a household biocidal product used in humidifier water tanks to prevent the growth of microorganisms. In 2011, a series of lung injury cases of unknown causes emerged in children and pregnant women who had used HD in Korea. This study investigated changes in the nationwide number of cases of humidifier disinfectant-associated lung injury (HDLI) in concordance with nationwide HD consumption using data covering the entire Korean population. More than 25 kinds of HD products were sold between 1994 and 2011. The number of diagnosed HDLI, assessed by S27.3 (other injuries of lungs) of the Korea National Health Insurance Service (NHIS) data, sharply increased by 2005, subsequently decreased after 2005, and almost disappeared after 2011 in concordance with the annual number of HD sales. The number of self-reported HDLIs, assessed using data from all suspected HDLI cases registered in the Korea Ministry of Environment, changed with the annual number of HD sales, with a delay pattern, potentially induced by the late awareness of lung injury diseases. The present study suggests that changes in the nationwide annual consumption of HD products were consistent with changes in the annual number of HDLI cases in Korea.
| S-EPMC8201190 | biostudies-literature
Project description:BackgroundHumidifier disinfectant-associated children's interstitial lung disease has an unpredictable clinical course with a high morbidity and mortality.ObjectivesTo evaluate the differences in clinical findings between survivors and non-survivors of humidifier disinfectant-associated children's interstitial lung disease. To evaluate dynamic changes in serum cytokines related to inflammation and fibrosis in lung injury, and to determine whether these changes are predictive of survival in this disease.MethodsWe evaluated 17 children with humidifier disinfectant-associated children's interstitial lung disease, from whom serum samples were obtained weekly during hospitalization. The severity of chest tomographic and lung pathologic findings was scored. Levels of several cytokines were measured in the serial serum samples.ResultsSeven of the 17 children were survivors. Compared to survivors, non-survivors had greater ground-glass attenuation on follow-up chest tomography, higher admission neutrophil counts, and more macrophages on pathologic findings. Transforming growth factor-beta 1 persisted at an elevated level (1,000-1,500 pg/ml) in survivors, whereas it decreased abruptly in non-survivors. At the time of this decrease, non-survivors had clinical worsening of their respiratory failure. Transforming growth factor-beta 1 was positively correlated with PaO2 /FiO2 (r = 0.481, P < 0.0001).ConclusionsNon-survivors exhibited more inflammatory clinical findings than survivors. Transforming growth factor-beta 1 remained elevated in survivors, suggesting that it affected the clinical course of humidifier disinfectant-associated children's interstitial lung disease. The prognosis of this lung disease may depend more on controlling excessive inflammation and repairing damaged lung than on fibrosis, and transforming growth factor-beta 1 may play a key role in this process.
| S-EPMC7167780 | biostudies-literature
Project description:An outbreak of fatal humidifier disinfectant lung injuries (HDLI) occurred in Korea. Human studies on mechanisms underlying HDLI have yet to be conducted. This study aimed to investigate methylation changes and their potential role in HDLI after exposure to HDs containing polyhexamethylene guanidine-phosphate. DNA methylation analysis was performed in blood samples from 10 children with HDLI and 10 healthy children using Infinium Human MethylationEPIC BeadChip. Transcriptome analysis was performed using lung tissues from 5 children with HDLI and 5 controls. Compared to healthy controls, 92 hypo-methylated and 79 hyper-methylated CpG sites were identified in children with HDLI at the statistical significance level of |Δβ|>0.2 and p<0.05. NOTCH1 was identified as a candidate network hub gene in cases. NOTCH1 transcripts significantly increased in lung tissues from HDLI cases compared to unexposed controls (p=0.05). NOTCH1 may play an important role in pulmonary fibrosis of HDLI.
| S-EPMC6992453 | biostudies-literature
Project description:Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.
| S-SCDT-10_1038-S44320-024-00072-3 | biostudies-other