Epidemiology and Health

Systematic Review

Integrated evidence supports a causal association between PHMG-P exposure and pneumonitis: Yong Joo Park, Hye-Jin Kim, Youngmee Lee, Haewon Kim, Ha Ryong Kim, Jaiyong Kim, Hae-Kwan Cheong, Mina Ha, Kyu Hyuck Chung; Epidemiol Health. 2025;47:e2025073. Published online December 14, 2025; DOI: https://doi.org/10.4178/epih.e2025073

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Abstract Summary PDF Supplementary Material: Abstract
Polyhexamethylene guanidine phosphate (PHMG-P) is a guanidine-based disinfectant previously used in household humidifiers in Korea. This study evaluated whether PHMG-P exposure is causally linked to pneumonitis by integrating epidemiological, toxicological, and mechanistic evidence. We prespecified an evidence-integration framework aligned with the Office of Health Assessment and Translation/Grading of Recommendations Assessment, Development and Evaluation approaches, and applied the Organisation for Economic Cooperation and Development adverse outcome pathway (AOP) guidance to organize mechanistic evidence. We systematically identified studies and synthesized findings across 3 domains: epidemiology (age-period-cohort [APC], difference-in-differences [DID], and interrupted time-series [ITS] analyses), toxicology (animal and in vitro studies), and mechanism (mapping key events to an AOP). We assessed internal and external validity, coherence, and strength of evidence within and across domains. Epidemiological analyses showed that pneumonitis incidence rose during humidifier disinfectant use and declined after the 2011-2012 withdrawal, with higher risks in children and reproductive-age females. APC, DID, and ITS, including PHMG-P–specific time-series analysis, indicated increased pneumonitis incidence and mortality during exposure periods. Toxicological studies demonstrated that PHMG-P exposure resulted in epithelial injury, inflammation, fibrosis, and impaired lung function consistent with chemical pneumonitis. Mechanistic evidence linked PHMG-P exposure to epithelial damage, oxidative stress, macrophage polarization, and fibrotic changes. Multiple lines of evidence support a causal link between PHMG-P exposure and pneumonitis, underscoring the value of integrating epidemiology and toxicology to strengthen risk assessment and inform policy.; Summary

Korean summary
인구집단 기반 역학 연구와 독성발현경로(AOP) 기반 기전 독성학적 증거를 통합 분석한 결과, 폴리헥사메틸렌구아니딘 인산염(PHMG-P) 노출과 화학성 폐렴 간의 인과관계가 과학적으로 입증되었다.

Key Message
Population-based epidemiological analyses, including age–period–cohort, difference-in-differences, and interrupted time series approaches, demonstrated increases in pneumonia diagnoses during periods of PHMG-P use and subsequent declines following its market withdrawal. Toxicological evidence, structured through adverse outcome pathway mapping, provided mechanistic support for PHMG-P–induced chemical pneumonitis, collectively establishing a causal association between PHMG-P exposure and chemical pneumonitis.

Original Article

Association between humidifier disinfectant use duration and lung cancer development in Korea: Sungchan Kang, Jeong-In Hwang, Su Hwan Kim, Hyungryul Lim, Dong-wook Lee, Woojoo Lee, Jong Hun Kim, Sol Yu, Jungyun Lim, Younghee Kim, Kyoung-Nam Kim; Epidemiol Health. 2025;47:e2025023. Published online May 2, 2025; DOI: https://doi.org/10.4178/epih.e2025023

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Abstract Summary PDF Supplementary Material: Abstract
OBJECTIVES
This study was conducted to assess the association between the duration of humidifier disinfectant use and lung cancer development.
METHODS
We analyzed data from 3,605 applicants registered for compensation from the Korean government due to health conditions related to humidifier disinfectant exposure. Among these individuals, 121 were diagnosed with lung cancer at least 4 years after their initial exposure (through December 2021). Hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence were estimated according to the duration of disinfectant use using Cox proportional hazards models.
RESULTS
Compared with <5 months of use, the HRs for lung cancer were 1.81 (95% CI, 0.41 to 7.97) for 5-14 months, 2.45 (95% CI, 0.58 to 10.41) for 15-29 months, and 4.61 (95% CI, 1.12 to 18.91) for ≥30 months. Using never smokers with <15 months of use as the reference category, the HRs were 2.97 (95% CI, 1.34 to 6.56) for never smokers with ≥15 months of use, 2.73 (95% CI, 0.94 to 7.95) for current or former smokers with <15 months of use, and 4.74 (95% CI, 1.94 to 11.61) for current or former smokers with ≥15 months of use.
CONCLUSIONS
Our study provides some of the first robust epidemiological evidence that prolonged humidifier disinfectant use contributes to lung cancer development. Future studies—particularly those including unexposed populations—are needed to confirm these findings.; Summary

Korean summary
* 장기간의 가습기 살균제 사용과 폐암 발생의 위험 간에는 정량적 연관성을 발견할 수 있었습니다. * 가습기살균제를 30개월 이상 사용했다고 응답한 사람들은, 가습기살균제를 5개월 미만 사용했다고 응답한 사람들과 비교하여 폐암 발생 위험이 4배 높았습니다.

Key Message
* There is a quantitative association between prolonged humidifier disinfectants use and the risk of lung cancer incidence. * Individuals reported they used humidifier disinfectants for more than 30 months had more than four times higher risk of lung cancer than those of individuals who reported they used humidifier disinfectants for less than five months.

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