1.Risk of non-cancer respiratory diseases attributed to humidifier disinfectant exposure in Koreans: age-period-cohort and differences-in-difference analyses
Jaiyong KIM ; Kyoung Sook JEONG ; Seungyeon HEO ; Younghee KIM ; Jungyun LIM ; Sol YU ; Suejin KIM ; Sun-Kyoung SHIN ; Hae-Kwan CHEONG ; Mina HA ;
Epidemiology and Health 2025;47(1):e2025006-
		                        		
		                        			 OBJECTIVES:
		                        			Humidifier disinfectants (HDs) were sold in Korea from 1994 until their recall in 2011. We examined the incidence patterns of 8 respiratory diseases before and after the HD recall and estimated the attributable risk in the Korean population. 
		                        		
		                        			METHODS:
		                        			Using National Health Insurance data from 2002 to 2019, we performed age–cohort–period and differences-in-diffference analyses (comparing periods before vs. after the recall) to estimate the population-attributable fraction and the excess number of episodes. The database comprised 51 million individuals (99% of the Korean population). The incidence of 8 diseases—acute upper respiratory infection (AURI), acute lower respiratory infection (ALRI), asthma, pneumonia, chronic sinusitis (CS), interstitial lung disease (ILD), bronchiectasis, and chronic obstructive pulmonary disease (COPD)—was defined by constructing episodes of care based on patterns of medical care and the clinical characteristics of each disease. 
		                        		
		                        			RESULTS:
		                        			The relative risks (RRs) for AURI, ALRI, asthma, pneumonia, CS, and ILD were elevated among younger individuals (with an RR as high as 82.18 for AURI in males), whereas chronic conditions such as bronchiectasis, COPD, and ILD showed higher RRs in older individuals. During the HD exposure period, the population-attributable risk percentage ranged from 4.6% for bronchiectasis to 25.1% for pneumonia, with the excess number of episodes ranging from 6,218 for ILD to 3,058,861 for CS. Notably, females of reproductive age (19-44 years) experienced 1.1-9.2 times more excess episodes than males. 
		                        		
		                        			CONCLUSIONS
		                        			This study provides epidemiological evidence that inhalation exposure to HDs affects the entire respiratory tract and identifies vulnerable groups. 
		                        		
		                        		
		                        		
		                        	
3.Risk of non-cancer respiratory diseases attributed to humidifier disinfectant exposure in Koreans: age-period-cohort and differences-in-difference analyses
Jaiyong KIM ; Kyoung Sook JEONG ; Seungyeon HEO ; Younghee KIM ; Jungyun LIM ; Sol YU ; Suejin KIM ; Sun-Kyoung SHIN ; Hae-Kwan CHEONG ; Mina HA ;
Epidemiology and Health 2025;47(1):e2025006-
		                        		
		                        			 OBJECTIVES:
		                        			Humidifier disinfectants (HDs) were sold in Korea from 1994 until their recall in 2011. We examined the incidence patterns of 8 respiratory diseases before and after the HD recall and estimated the attributable risk in the Korean population. 
		                        		
		                        			METHODS:
		                        			Using National Health Insurance data from 2002 to 2019, we performed age–cohort–period and differences-in-diffference analyses (comparing periods before vs. after the recall) to estimate the population-attributable fraction and the excess number of episodes. The database comprised 51 million individuals (99% of the Korean population). The incidence of 8 diseases—acute upper respiratory infection (AURI), acute lower respiratory infection (ALRI), asthma, pneumonia, chronic sinusitis (CS), interstitial lung disease (ILD), bronchiectasis, and chronic obstructive pulmonary disease (COPD)—was defined by constructing episodes of care based on patterns of medical care and the clinical characteristics of each disease. 
		                        		
		                        			RESULTS:
		                        			The relative risks (RRs) for AURI, ALRI, asthma, pneumonia, CS, and ILD were elevated among younger individuals (with an RR as high as 82.18 for AURI in males), whereas chronic conditions such as bronchiectasis, COPD, and ILD showed higher RRs in older individuals. During the HD exposure period, the population-attributable risk percentage ranged from 4.6% for bronchiectasis to 25.1% for pneumonia, with the excess number of episodes ranging from 6,218 for ILD to 3,058,861 for CS. Notably, females of reproductive age (19-44 years) experienced 1.1-9.2 times more excess episodes than males. 
		                        		
		                        			CONCLUSIONS
		                        			This study provides epidemiological evidence that inhalation exposure to HDs affects the entire respiratory tract and identifies vulnerable groups. 
		                        		
		                        		
		                        		
		                        	
4.Risk of non-cancer respiratory diseases attributed to humidifier disinfectant exposure in Koreans: age-period-cohort and differences-in-difference analyses
Jaiyong KIM ; Kyoung Sook JEONG ; Seungyeon HEO ; Younghee KIM ; Jungyun LIM ; Sol YU ; Suejin KIM ; Sun-Kyoung SHIN ; Hae-Kwan CHEONG ; Mina HA ;
Epidemiology and Health 2025;47(1):e2025006-
		                        		
		                        			 OBJECTIVES:
		                        			Humidifier disinfectants (HDs) were sold in Korea from 1994 until their recall in 2011. We examined the incidence patterns of 8 respiratory diseases before and after the HD recall and estimated the attributable risk in the Korean population. 
		                        		
		                        			METHODS:
		                        			Using National Health Insurance data from 2002 to 2019, we performed age–cohort–period and differences-in-diffference analyses (comparing periods before vs. after the recall) to estimate the population-attributable fraction and the excess number of episodes. The database comprised 51 million individuals (99% of the Korean population). The incidence of 8 diseases—acute upper respiratory infection (AURI), acute lower respiratory infection (ALRI), asthma, pneumonia, chronic sinusitis (CS), interstitial lung disease (ILD), bronchiectasis, and chronic obstructive pulmonary disease (COPD)—was defined by constructing episodes of care based on patterns of medical care and the clinical characteristics of each disease. 
		                        		
		                        			RESULTS:
		                        			The relative risks (RRs) for AURI, ALRI, asthma, pneumonia, CS, and ILD were elevated among younger individuals (with an RR as high as 82.18 for AURI in males), whereas chronic conditions such as bronchiectasis, COPD, and ILD showed higher RRs in older individuals. During the HD exposure period, the population-attributable risk percentage ranged from 4.6% for bronchiectasis to 25.1% for pneumonia, with the excess number of episodes ranging from 6,218 for ILD to 3,058,861 for CS. Notably, females of reproductive age (19-44 years) experienced 1.1-9.2 times more excess episodes than males. 
		                        		
		                        			CONCLUSIONS
		                        			This study provides epidemiological evidence that inhalation exposure to HDs affects the entire respiratory tract and identifies vulnerable groups. 
		                        		
		                        		
		                        		
		                        	
6.Risk of non-cancer respiratory diseases attributed to humidifier disinfectant exposure in Koreans: age-period-cohort and differences-in-difference analyses
Jaiyong KIM ; Kyoung Sook JEONG ; Seungyeon HEO ; Younghee KIM ; Jungyun LIM ; Sol YU ; Suejin KIM ; Sun-Kyoung SHIN ; Hae-Kwan CHEONG ; Mina HA ;
Epidemiology and Health 2025;47(1):e2025006-
		                        		
		                        			 OBJECTIVES:
		                        			Humidifier disinfectants (HDs) were sold in Korea from 1994 until their recall in 2011. We examined the incidence patterns of 8 respiratory diseases before and after the HD recall and estimated the attributable risk in the Korean population. 
		                        		
		                        			METHODS:
		                        			Using National Health Insurance data from 2002 to 2019, we performed age–cohort–period and differences-in-diffference analyses (comparing periods before vs. after the recall) to estimate the population-attributable fraction and the excess number of episodes. The database comprised 51 million individuals (99% of the Korean population). The incidence of 8 diseases—acute upper respiratory infection (AURI), acute lower respiratory infection (ALRI), asthma, pneumonia, chronic sinusitis (CS), interstitial lung disease (ILD), bronchiectasis, and chronic obstructive pulmonary disease (COPD)—was defined by constructing episodes of care based on patterns of medical care and the clinical characteristics of each disease. 
		                        		
		                        			RESULTS:
		                        			The relative risks (RRs) for AURI, ALRI, asthma, pneumonia, CS, and ILD were elevated among younger individuals (with an RR as high as 82.18 for AURI in males), whereas chronic conditions such as bronchiectasis, COPD, and ILD showed higher RRs in older individuals. During the HD exposure period, the population-attributable risk percentage ranged from 4.6% for bronchiectasis to 25.1% for pneumonia, with the excess number of episodes ranging from 6,218 for ILD to 3,058,861 for CS. Notably, females of reproductive age (19-44 years) experienced 1.1-9.2 times more excess episodes than males. 
		                        		
		                        			CONCLUSIONS
		                        			This study provides epidemiological evidence that inhalation exposure to HDs affects the entire respiratory tract and identifies vulnerable groups. 
		                        		
		                        		
		                        		
		                        	
8.Toxicological evidence integration to confirm the biological plausibility of the association between humidifier disinfectant exposure and respiratory diseases using the AEP-AOP framework
Ha Ryong KIM ; Jun Woo KIM ; Jong-Hyeon LEE ; Younghee KIM ; Jungyun LIM ; Yong-Wook BAEK ; Sunkyoung SHIN ; Mina HA ; Hae-Kwan CHEONG ; Kyu Hyuck CHUNG ;
Epidemiology and Health 2024;46(1):e2024060-
		                        		
		                        			 OBJECTIVES:
		                        			Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. 
		                        		
		                        			METHODS:
		                        			We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. 
		                        		
		                        			RESULTS:
		                        			By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. 
		                        		
		                        			CONCLUSIONS
		                        			The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions. 
		                        		
		                        		
		                        		
		                        	
9.Compression Neuropathy Caused by Pelvic Lymphocele after Laparoscopic Surgical Staging
Dong Jin CHAE ; Jong Bum PARK ; Mi Jin HONG ; Jungyun KIM ; Cho E. SIM ; Seung-Eun KIM ; Yung Jin LEE
Journal of Electrodiagnosis and Neuromuscular Diseases 2024;26(2):29-34
		                        		
		                        			
		                        			 Lymphocele is a complication of pelvic surgery that infrequently leads to compressive neuropathy. We present a case of compressive obturator neuropathy resulting from lymphocele development after pelvic surgery. Electrodiagnostic studies revealed severe axonal disruption in the left obturator nerve, which is associated with poor functional recovery. This case underscores the role of electrodiagnostic testing in the diagnosis and rehabilitation of patients experiencing lower limb weakness following gynecological pelvic surgery. 
		                        		
		                        		
		                        		
		                        	
10.Toxicological evidence integration to confirm the biological plausibility of the association between humidifier disinfectant exposure and respiratory diseases using the AEP-AOP framework
Ha Ryong KIM ; Jun Woo KIM ; Jong-Hyeon LEE ; Younghee KIM ; Jungyun LIM ; Yong-Wook BAEK ; Sunkyoung SHIN ; Mina HA ; Hae-Kwan CHEONG ; Kyu Hyuck CHUNG ;
Epidemiology and Health 2024;46(1):e2024060-
		                        		
		                        			 OBJECTIVES:
		                        			Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease. 
		                        		
		                        			METHODS:
		                        			We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases. 
		                        		
		                        			RESULTS:
		                        			By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases. 
		                        		
		                        			CONCLUSIONS
		                        			The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions. 
		                        		
		                        		
		                        		
		                        	
            
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