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2 "Sol Yu"
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Original article
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
Epidemiol Health. 2025;e2025006.   Published online February 22, 2025
DOI: https://doi.org/10.4178/epih.e2025006    [Accepted]
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AbstractAbstract PDF
Abstract
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 difference-in-differences analyses (comparing periods before versus 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, women of reproductive age (19–44 years) experienced 1.1-9.2 times more excess episodes than men.
CONCLUSIONS
This study provides epidemiological evidence that inhalation exposure to HDs affects the entire respiratory tract and identifies vulnerable groups.
Summary
Special Article
Evidence integration on health damage for humidifier disinfectant exposure and legal presumption of causation
Mina Ha, Taehyun Park, Jong-Hyun Lee, Younghee Kim, Jungyun Lim, Yong-Wook Baek, Sol Yu, Hyen-Mi Chung, Kyu Hyuck Chung, Hae-Kwan Cheong, Review Committee for the Epidemiological Correlations between Humidifier Disinfectants Exposure and Health Effects
Epidemiol Health. 2023;45:e2023095.   Published online October 24, 2023
DOI: https://doi.org/10.4178/epih.e2023095
  • 5,987 View
  • 167 Download
  • 2 Web of Science
  • 3 Crossref
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
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.
Summary
Korean summary
저자들은 가습기살균제 노출로 인한 건강피해의 법적 인과관계 추정요건인 역학적 상관관계를 확인하기 위한 과정으로서 체계적 문헌고찰과 역학과 독성학의 전체 과학적 근거를 체계적으로 종합하는 방법을 제시하였다. 이것은 법적 증거 방법에서 개별 연구가 가지는 제한점이나 불확실성을 이유로 배척하지 않고, 전체 증거의 부분으로서 종합적으로 접근하는 것을 통해 사실 관계에 도달하는 방법이다. 이 전체증거접근법은 향후 인과관계 추정에서 전범(model)이 될 수 있다.
Key Message
We establish a systematic method for integrating a body of scientific evidence of epidemiology and toxicology to verify the epidemiological correlation, which is essential for presuming legal causation of health damages due to exposure to humidifier disinfectants. In terms of a legal proof, this method does not exclude individual studies due to their limitations or uncertainty but integrates them as part of a body of evidence to arrive at a conclusion that better reflects the truth of the evidence. This weight-of-the-evidence approach can be a model for future causal inference.

Citations

Citations to this article as recorded by  
  • Prenatal and Childhood Exposure to Humidifier Disinfectants and Attention-Deficit/Hyperactivity Disorder (ADHD): Insights from a Retrospective Cohort Design
    Hyowon Choi, Hunju Lee, Yeon-Soon Ahn
    Toxics.2025; 13(2): 78.     CrossRef
  • A systematic review and BMD modeling approach to develop an AOP for humidifier disinfectant-induced pulmonary fibrosis and cell death
    Donghyun Kim, Yusun Shin, Jong-In Park, Donghyeon Lim, Hyunjoon Choi, Seongwon Choi, Yong-Wook Baek, Jungyun Lim, Younghee Kim, Ha Ryong Kim, Kyu Hyuck Chung, Ok-Nam Bae
    Chemosphere.2024; 364: 143010.     CrossRef
  • 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: e2024060.     CrossRef

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