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.

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.

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.

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.

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.

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.

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.

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.

OBJECTIVES: Inhalation exposure to humidifier disinfectants has resulted to various types of health damages in Korea. To determine the epidemiological correlation necessary for presuming the legal causation, we aimed to develop a method to synthesize the entire evidence. METHODS: Epidemiological and toxicological studies are systematically reviewed. Target health problems are selected by criteria such as frequent complaints of claimants. Relevant epidemiologic studies are reviewed and the risk of bias and confidence level of the total evidence are evaluated. Toxicological literature reviews are conducted on three lines of evidence including hazard information, animal studies, and mechanistic studies, considering the source-to-exposure-to-outcome continuum. The confidence level of the body of evidence is then translated into the toxicological evidence levels for the causality between humidifier disinfectant exposure and health effects. Finally, the levels of epidemiological and toxicological evidence are synthesized. RESULTS: Under the Special Act revised in 2020, if the history of exposure and the disease occurred/worsened after exposure were approved, and the epidemiological correlation between the exposure and disease was verified, the legal causation is presumed unless the company proves the evidence against it. The epidemiological correlation can be verified through epidemiological investigations, health monitoring, cohort investigations and/or toxicological studies. It is not simply as statistical association as understood in judicial precedents, but a general causation established by the evidence as a whole, i.e., through weight-of-the-evidence approach. CONCLUSIONS The weight-of-the-evidence approach differs from the conclusive single study approach and this systematic evidence integration can be used in presumption of causation.

To provide a nationwide representative dataset for the study on health impact of air pollution, we combined the data from the Korea National Health and Nutrition Examination Survey with the daily air quality and weather data by matching the date of examination and the residential address of the participants. The database of meteorological factors and air quality as sources of exposure data were estimated using the Community Multiscale Air Quality model. The linkage dataset was merged by three ways; administrative district, si-gun-gu (city, county, and district), and geocode (in latitude and longitude coordinate units) based on the participants’ residential address, respectively. During the study period, the exposure dataset of 85,018 individuals (38,306 men and 46,712 women) whose examination dates were recorded were obtained. According to the definition of exposure period, the dataset was combined with the data on short-term, mid-term, and long-term exposure to air pollutants and the meteorological indices. Calculation of the daily merged dataset’s average air pollution linked by si-gun-gu and geocode units showed similar results. This study generated a daily average of meteorological indices and air pollution exposure dataset for all regions including rural and remote areas in Korea for 11 years. It is expected to provide a platform for the researchers studying the health impact of air pollution and climate change on the representative population and area, which may facilitate the establishment of local health care plans by understanding the residents’ health status at the local as well as national level.