• Journal of Environmental Health Sciences
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• v.44 no.2
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• pp.107-114
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• 2018

Objectives: The objectives of this study are to describe strategy for exposure assessment of humidifier disinfectant (HD) used in the national program to associate the use of HD with lung injury. Methods: Strategy and method employed to evaluate HD use characteristics were developed to associate health effects including HD associated with lung injury (HDLI). We developed HD-specific questionnaire to assess potential HD exposure, which was consistently used in the national program. Trained environmental health scientists visited the residences of registered subjects and investigated HD use characteristics. Results: Major HD exposure related variables were type of HD brand/s used; HD volume added to the humidifier, frequency of HD addition, and time spent in room/s with the humidifier; duration of HD use in the household in average months/year, weeks/month, and days/week; average sleeping hours in a room with an operating humidifier containing a disinfectant; number of HD brands used and type of HD; average distance of the bed from the humidifier in meters. Conclusions: We concluded that estimated airborne HD concentration was significantly associated with the risk of HDLI.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.14.1-14.4
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• 2016

A total of 221 patients were evaluated to be humidifier disinfectant associated with lung injury (HDLI) through two rounds of programs through April 2015. The humidifier disinfectant (HD) brands most often associated with HDLI were found to be Oxy (n=151, 68 %) and Cefu (n=26, 17 %). Polyhexamethylene guanidine used for disinfectant for four types of HD brands including Oxy was found to be associated with the highest number of HDLI cases (n=188). Further programs are operating to identify various health effects including lung injury which may be associated with the use of HD. Not only national agencies, but also pertinent environmental health societies should cooperate in the necessary investigations so that this tragedy can be properly addressed and future incidents concerning chemicals and chemical-containing products can be prevented.

• Journal of Environmental Health Sciences
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• v.42 no.6
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• pp.365-374
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• 2016

Objectives: Studies are needed to examine the characteristics of health effects reported by people who used humidifier disinfectant (HD), including the distribution of victims. Methods: We analyzed the distribution of health effects including lung injury that were asserted by a total of 699 individuals who registered with the first through third national programs to determine health effects associated with the use of HD. Results: We found that HD-associated lung injury (HDLI) occurred every year from 2002 through 2011, and in 2011 for 37.2% (n=96) of the total of 258 clinically evaluated HDLI victims. More than half of the victims responded that they were victimized between 2010 and 2011. This was consistent among all classifications by sex, age, HD brand and HD chemical ingredient. Conclusion: This study assumed that the major reason for the outbreak of the health effect between 2010 and 2011 could be the variations in concentrations and physical properties related to polyhexamethylene guanidine (PHMG). Further studies are necessary to examine if some factors related to the chemical disinfectants contained in HD brands may have caused the massive outbreak of health effects including HDLI.

• Journal of Environmental Health Sciences
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• v.46 no.3
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• pp.312-323
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• 2020

Objective: This study aimed to summarize the physiochemical properties, toxicity, and legal regulation of chloromethylisothiazolinone (CMIT) and/or methylisothiazolinone (MIT), review the health effects caused by exposure to CMIT/MIT, and evaluate the individual association of lung injury with the use of humidifier disinfectants (HD) containing a mixture of CMIT and MIT. Method: A literature review was conducted by searching keywords such as CMIT, MIT, health effect, dermatitis, asthma, and lung injury, either singly or combined. Results: Both CMIT and/or MIT were found to be associated with the development of several types of adverse health effects. In particular, respiratory diseases including asthma, nasal symptoms, cough, and rhinitis were caused by the use of products including CMIT or/and MIT. The mixture of CMIT/MIT has been banned in cosmetics. As of the end of 2017, nine patients who were confirmed to have HD associated lung injury (HDLI) were found to have used only an HD brand containing CMIT and MIT. Their responses regarding the name of the HD used could be trustworthy based on the short duration of HD use (less than six months) before the onset of HDLI and frequent use of HD per day. Conclusion: According to the toxicity and HDLI cases, the use of HD containing CMIT and /or MIT can cause fatal lung injury. Further study with manufacturers' assistance is necessary in order to obtain more clear evidence on the causal relationship since HDLI cases are being reported continuously.

• Journal of Environmental Health Sciences
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• v.46 no.2
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• pp.128-135
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• 2020

Objective: The objectives of this study are to report the number of humidifier disinfectant (HD) associated health problems, including HD associated lung injury (HDLI), by year. This data was analyzed by the type of HD and HD brand. Methods: A total of 530 patients registered with the national program on HD through its third round were distributed based on the year when they developed their first health problem including HDLI (N=221). The distribution of health problems at diagnosis was clinically evaluated in order to examine the association between their lung injury and the use of HD. Results: The number of HD associated victims and HDLI patients was found to rise sharply from 2008 to 2011, with a peak in 2011. This trend was found not only for HD brands containing polyhexamethylene guanidine phosphate (PHMG), but also chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT). The number of patients who responded as developing health problems in the specific year was 35 for 2008, 51 for 2009, 108 for 2010 and 182 for 2011. Other types of HD brands and HD chemicals did not follow the trend of abrupt increase in HD associated patients since 2008. Conclusion: This study found the number of HD associated victims and HDLI patients who used HD brands containing PHMG sharply increased starting in 2008. A significant change in the process of manufacturing PHMG can be suspected with the abrupt rise in HD associated patients in specific years.

• Tuberculosis and Respiratory Diseases
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• v.80 no.4
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• pp.351-357
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• 2017

In 2011, a cluster of peripartum patients were admitted to the intensive care unit of a tertiary hospital in Seoul with signs and symptoms of severe respiratory distress of unknown etiology. Subsequent epidemiological and animal studies suggested that humidifier disinfectant (HD) might represent the source of this pathology. Epidemiological studies, animal studies, and dose-response analysis demonstrated a strong association between HD use and lung injuries. The diagnostic criteria for HD-associated lung injury (HDALI) was defined on the basis of the clinical, pathological, and radiological attributes of the patients. The clinical spectrum of HDALI appears to range from asymptomatic to full-blown acute respiratory failure, and some patients have required actual lung transplantation for survival. The overall mortality of the exposed population was not significant, although peripartum patients and children who were admitted to the intensive care unit did show high mortality rates. Persistent clinical findings such as diffuse ill-defined centrilobular nodules and restrictive lung dysfunction were observed in some of the survivors. The findings of this review emphasize the importance of assessment of the level of toxicity of chemical inhalants utilized in a home setting, as well as the need to identify and monitor afflicted individuals after inhalational injury.

• Journal of Environmental Health Sciences
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• v.47 no.6
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• pp.513-520
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• 2021

Background: Benzalkonium chloride (BKC) has been extensively used as a preservative in industrial products and in hygiene, medical, and cosmetic applications. Humidifier disinfectant (HD) products containing BKC have been used in South Korea. Objectives: This study was aimed to review types of products containing BKC, to summarize the regulations in the US, EU, Japan, and South Korea, and to review the health effects associated with the use of HD. Methods: We reviewed and summarized documents which were searched through PubMed and Google Scholar with the key words: BKC and asthma/contact dermatitis, humidifier disinfectant-associated lung injury (HDLI), and more. Results: Regulations in most countries including South Korea do not allow its use as disinfectants in spray-type of products for medicine, cosmetics, and household products. Two types of HD containing BKC (800~1,270 ppm) were marketed in South Korea from 1996~2003. Health effects reported from people who used products containing BKC were allergic contact dermatitis, erythema, and respiratory disease, including asthma. Two people who responded as HD users containing BKC only were confirmed to have developed asthma. HD-associated lung injury (HDLI) was reported by consumers who used both HD containing polyhexamethylene guanidine (PHMG) and HD containing BKC. Conclusions: In conclusion, the use of BKC as a biocide has to be controlled considering the route and pattern of exposure. Products containing BKC as preservatives were reviewed with exposure routes and sites in the human body such as skin, eyes, and the respiratory tract. HD containing BKC was clinically evaluated to be associated with asthma.

• Journal of Environmental Health Sciences
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• v.47 no.3
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• pp.193-204
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• 2021

Objectives: In January 2021, the former heads of the manufacturer SK Chemical and the vendor Aekyung were acquitted for manufacturing and selling humidifier disinfectant (HD) containing 5-chloro-2-methylisothiazol-3(2H)-one/2-methylisothiazol-3(2H)-one (CMIT/MIT). In this article, we analyzed the rationale used in this judgement in the light of scientific consideration. Methods: The sentencing document for the judgements was obtained from the Korea Supreme Court Service. In particular, the judgements made by the court related to the toxicological and individual association with HD perspectives were discussed based on scientific evidence. Results: The ruling stated that the necessary conditions for causality between CMIT/MIT and such diseases were not met based on the fact that asthma and lung damage were not found in the inhalation exposure animal experiments. The judgment overlooked the inevitable limitations of using animal experiments for verifying health effects in humans, which are often inconsistent with the observations in animals. Among 11 governmentaffirmed lung injury cases with CMIT/MIT usage, three patients' humidifier disinfectant-associated lung injury (HDLI) pathology proved that CMIT/MIT could cause lung injury similar to that caused by PHMG and PGH. In addition, five children showed decreased lung function related to damage caused by humidifier disinfectant exposure. Conclusions: We conclude that there is sufficient evidence supporting the assertion that HDs containing CMIT/MIT cause lung injuries, including asthma, contrary to the court's decision.

• Journal of Environmental Health Sciences
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• v.46 no.2
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• pp.224-231
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• 2020

Objective: The objectives of this study are to update the information on the characteristics of humidifier disinfectant (HD) usage with HD associated health problems and to discuss the role of HD exposure assessment in the national program to monitor health problems in patients with HD associated diseases. Method: A total of 201 HD associated patients who registered to undergo clinical examination at Kangbuk Samsung Hospital was interviewed to acquire their responses regarding several HD use characteristics, including type of HD brands used, HD use duration, average daily HD use hours, and the volume of the room in which HD was used. The responses of the HD associated patients to HD use-related questions were compared between responses in the lung injury investigation and this study. Results: The responses of HD associated patients in this study were found to be different from those in the lunginjury investigation. In particular, some of the patients who had not answered in the lung-injury investigation were able to answer thanks to assistance from the investigator in this study. For their responses regarding the name of the most commonly used HD brand, the number of patients who did not answer (N=11) was reduced to eight in this study. Significant changes in the responses of study subjects to questions related to HD use were achieved through the interview in this study. Conclusion: This study found significant changes in the responses regarding HD use characteristics. HD exposure assessment should be included in the program in order to allow surveillance of HD associated health problems.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.