Search Results (26)

In South Korea, issues have been raised regarding exposure to humidifier disinfectant products containing certain chemicals postulated to induce lung diseases in consumers. Several rodent studies utilizing whole-body inhalation, which comprises freely moving animals breathing through the nares, and intranasal instillation involving restraint, were conducted by various Korean Governmental Agencies on these products to investigate whether there is a causal relationship between these products and the development of lung diseases. In particular, the humidifier disinfectant product Kathon, containing chloromethylisothiazolinone and methylisothiazolinone (CMIT and MIT), when directly introduced into inhalation chambers at varying concentrations for up to 13 weeks, produced no significant histopathological alterations and no marked changes in pulmonary function parameters. Further, there was no evidence of cytotoxicity; total and differential cell counts did not differ from control. In addition, the levels of cytokine markers of inflammation were not markedly altered. In contrast to published papers utilizing intratracheal and intranasal instillation, where the animal is anesthetized and chemical bypasses the defense mechanisms in the respiratory tract, then reaches the pulmonary region, ignoring recommended dose levels was found to initiate fibrotic responses in mice and rats. However, the usefulness of experimental results to extrapolate to humans obtained following intratracheal and intranasal instillation studies is of limited value because the data generated did not use a realistic design and appropriate dosimetry. Therefore, these findings have significant drawbacks in their use to characterize an inhalation risk for pulmonary fibrosis in humans and cannot be used for the extrapolation of such risk to humans. It is thus evident that the inhalation data generated by the Korean Regulatory Agencies are more realistic and show that exposure to CMIT and MIT does not initiate pulmonary fibrosis. Although inhalation studies still do not fully replicate real-world human exposure scenarios and have limitations for direct extrapolation to humans, they are nevertheless more appropriate than intratracheal or intranasal instillation models. Full article

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

This study aims to investigate the association between exposure to toxic indoor chemicals, specifically polyhexamethylene guanidine (PHMG) and oligo(2-(2-ethoxy) ethoxyethyl guanidinium) chloride (PGH), used in humidifier disinfectants, and gestational diabetes mellitus (GDM). We confirmed pregnancy from 2003 to 2017 and identified GDM by linking a cohort of claimants who reported exposure to PHMG/PGH with National Health Insurance Service data. The GDM incidence was calculated, and PHMG/PGH exposure characteristics—exposure status, the humidifier’s distance/location, and exposure duration/hours—were investigated. Logistic regression and mediation analysis were applied using asthma, frequently treated with steroids, as a mediator. Among 521 pregnancies, 38 were identified as GDM, with 2.4% before exposure and 8.9% after exposure. Pregnancies after exposure had a higher odds ratio (OR) for GDM (OR 2.968, 95% CI: 1.004–12.725). A trend of increased GDM risk was observed with longer exposure duration/hours. Additionally, pregnancies after exposure demonstrated total and direct effects on GDM (β = 0.0435, p = 0.036, β = 0.0432, p = 0.030) independent of the indirect effects by asthma. The incidence of GDM was higher after PHMG/PGH exposure compared to before. PHMG/PGH exposure was associated with GDM, independent of asthma. Further research is warranted to confirm these findings in exposed cohorts and to explore the underlying mechanisms. Full article

Polyhexamethylene guanidine phosphate (PHMG-p), a major ingredient of humidifier disinfectants, is known to induce inflammation, interstitial pneumonitis, and fibrosis in the lungs. While its histopathologic toxicities have been studied in rodents, research on pulmonary function test (PFT) changes following PHMG-p exposure is limited. This study aimed to investigate the acute and chronic effects, as well as the dose and time response, of PHMG-p on the lungs in mice using PFT and histopathologic examinations. In the single instillation model, mice received PHMG-p and were sacrificed at 2, 4, and 8 weeks. In the five-time instillation model, PHMG-p was administered five times at one-week intervals, and mice were sacrificed 10 weeks after the first instillation. Results showed that PHMG-p exposure reduced lung volume, increased resistance, and decreased compliance, indicating a restrictive ventilation defect. Histopathologic examination showed increases in lung inflammation and fibrosis scores. Changes in several lung volume and compliance parameters, as well as histopathology, were dose-dependent. Lung resistance and compliance parameters had significant correlations with lung inflammation and fibrosis scores. PHMG-p exposure in mice resulted in a restrictive ventilation defect with altered lung resistance and compliance, along with histopathologic lung inflammation and fibrosis. Full article

Two sporadic cases of legionellosis occurring in consecutive years were confirmed by positive antigenuria to Legionella pneumophila serogroup 1 in individuals with limited mobility who were confined to their homes. Both cases had a history of using ultrasonic humidifiers and of low exposure to other possible sources of infection. This study was conducted through an expanded epidemiological survey and home inspection. Samples were collected from domestic hot water and humidifiers. Environmental isolates were characterised by immunoagglutination and immunofluorescence. The Dresden panel is employed for the determination of groups and subgroups of serogroup 1. The amoebae were isolated by water filtration and subsequent cultivation of the filters. Identification of the isolates was conducted through the sequencing of PCR products. In both cases, epidemiological studies identified the ultrasonic humidifiers as the probable source of infection. The presence of Legionella pneumophila was confirmed in the sanitary water installation and in the humidifiers, where high values of Legionella pneumophila serogroup 1 counts were also obtained. The isolates were characterised as Olda Oxford and Olda OLDA. Furthermore, in addition to the Legionella isolates, the presence of Vermamoeba vermiformis was also identified in samples obtained from domestic hot water and humidifiers in one of the residential addresses under investigation. It has been demonstrated that humidifiers can act as an amplification mechanism for pathogenic microorganisms when they are not cleaned and maintained correctly. This can pose a health danger, especially to people with previous respiratory pathologies, the immunosuppressed, and the elderly. Therefore, it is of the utmost importance that professionals who recommend the therapeutic use of this equipment should issue warnings regarding the importance of its correct use, cleaning, and disinfection. Finally, humidifiers should be considered in epidemiological surveys and in the study of sporadic cases. 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

This study aimed to examine group differences in the survivors of humidifier damage and the effect of individual psychotherapy on the psychological symptoms of the survivor groups, using the single group pre–post study design. A series of Wilcoxon–Mann–Whitney tests were conducted to investigate the level of psychological problems before and after psychotherapy, as well as the main and interaction effects of demographic characteristics and adaptive functioning on the treatment effects in 69 humidifier disinfectant survivors. The results demonstrated significant differences in problems with socioeconomic status (SES), life functioning, friendships, family relationships, and job adjustment in the survivor groups. Groups with high SES, low life functioning, and poor friend relationships had more problem behaviors than other groups. Problem behaviors related to friendship levels were different before and after psychotherapy. After psychotherapy, individuals with limited social connections exhibited a greater decrease in problem behaviors compared to those with strong friendships. This paper extends the international literature on the long-term consequences of environmental health hazards and the importance of tailored mental health interventions. Full article

Biocides are widely used in everyday life, and accordingly, human exposure to them is inevitable. Especially, the inhalational exposure of humans to biocides and resultant respiratory toxicity are gaining public interest due to the recent catastrophe associated with humidifier disinfectants. Aerosolized chemicals are subject to gravitational deposition and chemical degradation. Therefore, the characterization of the disposition of aerosols is essential to estimate the inhalational exposure to biocides. Here, we compared the disposition of aerosols of one of the commonly used biocide classes, isothiazolinone-based biocides, BIT, MIT, and OIT. An acrylic chamber (40 cm × 40 cm × 50 cm) was created to simulate the indoor environment, and a vacuum pump was used to create airflow (1 LPM). Biocides were sprayed from a vertical nebulizer placed on the ceiling of the chamber, and the distribution of particle sizes and volume was measured using the Optical Particle Sizer (OPS) 3330 device. During and after the aerosol spraying, airborne biocides and those deposited on the surface of the chamber were sampled to measure the deposition using LC-MS/MS. As a result, the broad particle size distribution was observed ranging from 0.3 to 8 μm during the nebulization. The inhalable particle faction (>2 μm) of the isothiazolinones was 32–67.9% in number but 1.2 to 6.4% in volume. Most of the aerosolized biocides were deposited on the chamber’s surface while only a minimal portion was airborne (<1%) after the nebulization. More importantly, significant amounts of MIT and OIT were degraded during aerosolization, resulting in poor total recovery compared to BIT (31%, 71% vs. 97% BIT). This result suggests that some isothiazolinones may become unstable during nebulization, affecting their disposition and human exposure significantly. Full article

Polyhexamethylene guanidine phosphate (PHMG-p), the main ingredient of humidifier disinfectants, circulates systemically through the lungs; however, its toxicological assessment has been primarily limited to pulmonary disease. Herein, we investigated the possible abnormalities in hematopoietic function 20 weeks after intratracheal instillation of PHMG-p in a rat model. Notable abnormalities were found out in the peripheral blood cell count and bone marrow (BM) biopsy, while RNA sequencing of BM tissue revealed markedly altered gene expression. Furthermore, signaling involved in hematopoietic dysfunction was predicted by analyzing candidate genes through Ingenuity Pathway Analysis (IPA) program. Respiratory PHMG-p exposure significantly decreased monocyte and platelet (PLT) counts and total protein, while significantly increasing hemoglobin and hematocrit levels in peripheral blood. Histopathological analysis of the BM revealed a reduced number of megakaryocytes, with no significant differences in spleen and liver weight to body weight. Moreover, PHMG-p exposure significantly activated estrogen receptor signaling and RHOA signaling, and inhibited RHOGDI signaling. In IPA analysis, candidate genes were found to be strongly related to ‘hematological system development and function’ and ‘hematological disease.’ Accordingly, our results suggest that PHMG-p could affect hematopoiesis, which participates in monocyte differentiation and PLT production, and may induce hematologic diseases via the respiratory tract. 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

In this study, humidified air dielectric barrier discharge (DBD) plasma was used to inactivate Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and bacteriophages in biofilms containing DNA, NaCl, carbohydrates, and proteins. The humidified DBD plasma was very effective in the inactivation of microbes in the (≤1.0 μm) biofilms. The number of surviving E. coli, S. aureus, and bacteriophages in the biofilms was strongly dependent on the constituent and thickness of the biofilms and was greatly reduced when the plasma treatment time increased from 5 s to 150 s. Our analysis shows that the UV irradiation was not responsible for the inactivation of microbes in biofilms. The short-lived RONS generated in the humidified air DBD plasma were not directly involved in the inactivation process; however, they recombined or reacted with other species to generate the long-lived RONS. Long-lived RONS diffused into the biofilms to generate very active species, such as ONOOH and OH. This study indicates that the geminated NO₂ and OH pair formed due to the homolysis of ONOOH can cause the synergistic oxidation of various organic molecules in the aqueous solution. Proteins in the biofilm were highly resistant to the inactivation of microbes in biofilms, which is presumably due to the existence of the unstable functional groups in the proteins. The unsaturated fatty acids, cysteine-rich proteins, and sulfur–methyl thioether groups in the proteins were easily oxidized by the geminated NO₂ and OH pair. Full article

This study aimed to compare the psychological symptoms of humidifier disinfectant survivors to the general population and explore socio-demographic factors influencing survivors’ psychological symptoms. A one-way Multivariate Analysis of Covariance (MANCOVA) and a series of two-way MANCOVA were conducted with a sample of 228 humidifier disinfectant survivors and 228 controls. The results demonstrated that the survivor group displayed higher anxious/depressed symptoms, withdrawn symptoms, somatic complaints, thought problems, attention problems, aggressive behavior and rule-breaking behavior than the general group. Moreover, among the socio-demographic factors, the two-way interaction effects of group × family economic status and group × number of friends were found to be statistically significant. The limitations and implications of this study are discussed. Full article

Polyhexamethyleneguanidine phosphate (PHMG-P) is one of the causative agents of humidifier disinfectant-induced lung injury. Direct exposure of the lungs to PHMG-P causes interstitial pneumonia with fibrosis. Epidemiological studies showed that patients with humidifier disinfectant-associated lung injuries have suffered from restrictive lung function five years after the onset of the lung injuries. We investigated whether lung damage was sustained after repeated exposure to PHMG-P followed by a long-term recovery and evaluated the adverse effects of PHMG-P on mice lungs. Mice were intranasally instilled with 0.3 mg/kg PHMG-P six times at two weeks intervals, followed by a recovery period of 292 days. Histopathological examination of the lungs showed the infiltration of inflammatory cells, the accumulation of extracellular matrix in the lung parenchyma, proteinaceous substances in the alveoli and bronchiolar–alveolar hyperplasia. From RNA-seq, the gene expression levels associated with the inflammatory response, leukocyte chemotaxis and fibrosis were significantly upregulated, whereas genes associated with epithelial/endothelial cells development, angiogenesis and smooth muscle contraction were markedly decreased. These results imply that persistent inflammation and fibrotic changes caused by repeated exposure to PHMG-P led to the downregulation of muscle and vascular development and lung dysfunction. Most importantly, this pathological structural remodeling induced by PHMG-P was not reversed even after long-term recovery. 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