Search Results (10)

Humidifier disinfectants (HDs), also known toxic indoor chemicals, have been linked to adverse health outcomes in children. However, their association with ADHD development remains largely unexplored. This study aimed to investigate the incidence of ADHD among HD claimants and assess the association between HD exposure and ADHD risk. A cohort of HD damage claimants born between 2002 and 2011 was established. ADHD cases and controls were identified using matched National Health Insurance Service claim data, with follow-ups required until age 10. ADHD incidence was calculated, and exposure characteristics—including the use of PHMG/PGH, humidifier distance and location, and cumulative and annual exposure duration—were analyzed. Cox proportional hazards analysis was performed, adjusting for sociodemographic factors and comorbidities. Among 1597 subjects, 84 were diagnosed with ADHD, resulting in an incidence density of 4.782 per 1000 person–years. Higher cumulative exposure duration and hours significantly increased the hazard ratio (HR) for ADHD. Additionally, exposure during the first three years after birth was associated with a higher HR for ADHD. These findings suggest that ADHD incidence is elevated in HD claimants and that HD exposure, particularly prolonged or early-life exposure, is associated with increased ADHD risk. Further research is required to confirm these findings in exposed cohorts and to elucidate the mechanisms underlying HD-related ADHD. Full article

Polyhexamethylene guanidine phosphate (PHMG-p) is a common biocidal disinfectant that is widely used in industry and household products. However, PHMG-p was misused as a humidifier disinfectant (HD) in South Korea, which had fatal health effects. Various health problems including cardiovascular diseases were observed in HD-exposed groups. However, the potential underlying mechanism of HD-associated cardiovascular diseases is poorly understood. Here, we examined the procoagulant activity of platelets caused by PHMG-p and clarified the underlying mechanism. PHMG-p enhanced phosphatidylserine (PS) exposure through alteration of phospholipid transporters, scramblase, and flippase. Intracellular calcium elevation, intracellular ATP depletion, and caspase-3 activation appeared to underlie phospholipid transporter dysregulation caused by PHMG-p, which was mediated by oxidative stress and mitochondrial dysfunction. Notably, antioxidant enzyme catalase and calcium chelator EGTA reversed PHMG-p-induced PS exposure and thrombin generation, confirming the contributive role of oxidative stress and intracellular calcium in the procoagulant effects of PHMG-p. These series of events led to procoagulant activation of platelets, which was revealed as enhanced thrombin generation. Collectively, PHMG-p triggered procoagulant activation of platelets, which may promote prothrombotic risks and cardiovascular diseases. These findings improve our understanding of HD-associated cardiovascular diseases. Full article

Around nine million people have been exposed to toxic humidifier disinfectants (HDs) in Korea. HD exposure may lead to HD-associated lung injuries (HDLI). However, many people who have claimed that they experienced HD exposure were not diagnosed with HDLI but still felt discomfort, possibly due to the unknown effects of HD. Therefore, this study examined HD-exposed subjects with normal-appearing lungs, as well as unexposed subjects, in clusters (subgroups) with distinct characteristics, classified by deep-learning-derived computed-tomography (CT)-based tissue pattern latent traits. Among the major clusters, cluster 0 (C0) and cluster 5 (C5) were dominated by HD-exposed and unexposed subjects, respectively. C0 was characterized by features attributable to lung inflammation or fibrosis in contrast with C5. The computational fluid and particle dynamics (CFPD) analysis suggested that the smaller airway sizes observed in the C0 subjects led to greater airway resistance and particle deposition in the airways. Accordingly, women appeared more vulnerable to HD-associated lung abnormalities than men. Full article

(1) Background: Humidifier disinfectant (HD) is a biocidal chemical to keep the water tank inside a humidifier clean. Thousands of Koreans have experienced HD-related lung injuries. Of them, 6.9% were exposed to HD in hospitals. (2) Methods: This study investigated changes of diseases in patients (or caregivers) who experienced HD exposures during hospitalization and also investigated characteristics of hospital exposure using data from all HD-related lung injury enrollment in Korea. (3) Results: Of a total of 162 subjects, 139 subjects were hospitalized for non-lung diseases, and 23 people were hospitalized for lung diseases at the time of hospitalization. During hospital exposure, 99 (71.2%) of those hospitalized with non-lung disease experienced a new-onset of lung disease, and 15 (65.2%) of those hospitalized with lung diseases experienced exacerbation of their existing lung diseases. When we compared their exposure characteristics, those exposed in hospitals (vs. non-hospital, mostly home) were exposed for shorter periods, at closer distances, at higher HD indoor concentrations, constantly all day, and directly in the facial direction. (4) Conclusion: In conclusion, HD exposures in hospital with a high intensity even for a short term were associated with new-onset or exacerbation of lung diseases. Our findings suggest that acute exposures to HD can cause lung diseases. Full article

The inhalation of humidifier disinfectants (HDs) is linked to HD-associated lung injury (HDLI). Polyhexamethylene guanidine (PHMG) is significantly involved in HDLI, but the correlation between chloromethylisothiazolinone (CMIT) and HDLI remains ambiguous. Additionally, the differences in the molecular responses to PHMG and CMIT are poorly understood. In this study, RNA sequencing (RNA-seq) data showed that the expression levels of metallothionein-1 (MT1) isoforms, including MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, and MT1X, were increased in human pulmonary alveolar epithelial cells (HPAEpiCs) that were treated with PHMG but not in those treated with CMIT. Moreover, upregulation of MT1B, MT1F, MT1G, and MT1H was observed only in PHMG-treated HPAEpiCs. The protein expression level of metal regulatory transcription factor 1 (MTF1), which binds to the promoters of MT1 isoforms, was increased in PHMG-treated HPAEpiCs but not in CMIT-treated HPAEpiCs. However, the expression of early growth response 1 (EGR1) and nuclear receptor superfamily 3, group C, member 1 (NR3C1), other transcriptional regulators involved in MT1 isomers, were increased regardless of treatment with PHMG or CMIT. These results suggest that MTF1 is an essential transcription factor for the induction of MT1B, MT1F, MT1G, and MT1H by PHMG but not by CMIT. Full article

(1) Background: Household humidifier disinfectant (HD) brands containing polyhexamethylene guanidine (PHMG) have been found to cause the most HD-associated lung injuries (HDLIs) in the Republic of Korea. Nevertheless, no study has attempted to characterize the potential association of the health effects, including HDLI, with the physicochemical properties of PHMG dissolved in different HD brands. This study aimed to characterize the molecular weight (MW) distribution, the number-average molecular weight (M_n), the weight-average molecular weight (M_w), and the structural types of PHMG used in HD products. (2) Methods: Quantitative measurements were made using matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS). The M_n, M_w, and MW distributions were compared among various HD products. (3) Results: The mean M_n and M_w were 542.4 g/mol (range: 403.0–692.2 g/mol) and 560.7 g/mol (range: 424.0–714.70 g/mol), respectively. The degree of PHMG oligomerization ranged from 3 to 7. The MW distribution of PHMG indicated oligomeric compounds regardless of the HD brands. (4) Conclusions: Based on the molecular weight distribution, the average molecular weight of PHMG, and the degree of polymerization, the PHMG collected from HDLI victims could be regarded as an oligomer. PHMG, as used in household humidifiers, should not be exempted from toxic chemical registration as a polymer. Further study is necessary to examine the association of PHMG oligomeric compounds and respiratory health effects, including HDLI. Full article

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. Full article

Polyhexamethylene guanidine (PHMG), a major component of humidifier disinfectants (HDs), is responsible for the outbreak of pulmonary diseases in pregnant women and children in South Korea. This study aims to characterize the developmental toxicity and thyroid endocrine disruption of Vegetable Home Cleanup HD and its main component, PHMG-hydrochloride (PHMG-H), in zebrafish embryo/larvae after a 7-d exposure. Acute lethality, development, whole-body thyroid hormones, and transcription of genes related to the hypothalamus-pituitary-thyroid axis were investigated. Zebrafish embryos exposed to the actual-use concentration (0.6%) of HD exhibited significant embryo coagulation and larval mortality. The concentration of triiodothyronine (T3) was significantly high in fish exposed to 0.4 mg/L PHMG-H, accompanied by the downregulation of the tshβ gene. These results suggest a feedback mechanism for the regulation of increased T3 levels. Significant decrease of thyroxine (T4) concentration, increase of T3/T4 ratio, and upregulation of the deio2 gene in fish exposed to PHMG-H suggested that there was an increase in the active T3 due to the catalysis of outer ring deiodination. Future research is required to determine the factors that contribute to the differences in toxicity between the two counter ions of PHMG. Full article

This study aimed to quantify both chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) dissolved in different product brands and to characterize the exposure to these chemicals among humidifier disinfectant-associated lung injury (HDLI) patients. Both CMIT and MIT dissolved in different humidifier disinfectant (HD) products were quantified using gas chromatography–mass spectrometry. The inhalation level of CMIT and MIT was estimated based on HD-associated factors as reported by HDLI patients. A total of eleven HD products marketed until the end of 2011 were found to contain CMIT and/or MIT. The level of combined CMIT and/or MIT dissolved in these HD products ranged from 12 to 353 ppm. The level varied among HD products and the year of manufacture. The average inhalation levels were estimated to be 7.5, 4.1, and 3.2 μg/m³ for the definite, probable, and possible groups, respectively. If probable and possible groups were collapsed together, the inhalation level of the collapsed group was significantly different from that of the definite group (p < 0.001). All HDLI patients responded as having used HD not only while sleeping, but also as having a humidifier treated with HD within close proximity every day in insufficiently ventilated spaces. These HD use characteristics of patients may be directly/indirectly linked to the HDLI development. Full article

The use of humidifier disinfectant (HD) has been determined to be associated with lung injuries (HDLI) in Korea. Although HD brands containing polyhexamethylene guanidine (PHMG) oligomers have been found to cause more HDLI compared to brands containing other disinfectants, the physicochemical properties of PHMG have been poorly defined. We aimed to quantify the PHMG dissolved in HD brands, characterize the number-average (M_n) and weight-average (M_w) molecular masses, and identify the polymerization degree of PHMG. Analysis of the PHMG oligomers was performed using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) operated in positive-ion reflectron mode. Eight brands of HD containing PHMG were identified. The PHMG concentrations in these brands ranged from 160 to 37,200 ppm (mean = 3100.9 ppm). Concentration was a significant variable among and within HD brands. The degree of PHMG oligomerization fell within the range of two to four. The averages of M_n and M_w were 517.2 g/mol (range: 422–613 g/mol) and 537.3 g/mol (range: 441.0–678.0 g/mol), respectively. Based on the average molecular weight and the degree of polymerization, the PHMG examined here could be regarded as oligomers, which may be associated with the highest proportion of HDLI being caused by PHMG. Full article