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

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.

Citations

Citations to this article as recorded by

Multi-omics study to elucidate molecular mechanism of polyhexamethylene guanidine phosphate (PHMG-p)-induced pulmonary damage in mice
Jung Dae Lee, Hyang Yeon Kim, Jueng-Eun Im, Handule Lee, Juyoung Park, Kwangsik Park, Keunsoo Kang, Hye Gwang Jeong, Sehyun Chae, Daehee Hwang, Beom Seok Han, Wan-Seob Cho, Suhkmann Kim, Kyu-Bong Kim
Archives of Toxicology.2026; 100(10): 4591. CrossRef

Original Article

Regional disparities in major cancer incidence in Korea, 1999-2018: Eun Hye Park, Mee Joo Kang, Kyu-Won Jung, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Hyun-Joo Kong, Chang Kyun Choi, Jeong-Soo Im, Hong Gwan Seo, The Community of Population-Based Regional Cancer Registries; Epidemiol Health. 2023;45:e2023089. Published online October 12, 2023; DOI: https://doi.org/10.4178/epih.e2023089

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Abstract Summary PDF Supplementary Material

Abstract

OBJECTIVES
This study investigated regional disparities in the incidence of 8 major cancers at the municipal level in Korea during 1999-2018 and evaluated the presence or absence of hot spots of cancer clusters during 2014-2018.

METHODS

The Korea National Cancer Incidence Database was used. Age-standardized incidence rates were calculated by gender and region at the municipal level for 4 periods of 5 years and 8 cancer types. Regional disparities were calculated as both absolute and relative measures. The possibility of clusters was examined using global Moran’s I with a spatial weight matrix based on adjacency or distance.

RESULTS

Regional disparities varied depending on cancer type and gender during the 20-year study period. For men, the regional disparities of stomach, colon and rectum, lung, and liver cancer declined, and those of thyroid and prostate cancer recently decreased, despite an overall increasing incidence. For women, regional disparities in stomach, colon and rectum, lung, liver, and cervical cancer declined, that of thyroid cancer recently decreased, despite an overall increasing incidence, and that of breast cancer steadily increased. In 2014-2018, breast cancer (I, 0.61; 95% confidence interval [CI], 0.53 to 0.70) showed a high probability of cancer clusters in women, and liver cancer (I, 0.48; 95% CI, 0.40 to 0.56) showed a high probability of cancer clusters in men.

CONCLUSIONS

Disparities in cancer incidence that were not seen at the national level were discovered at the municipal level. These results could provide important directions for planning and implementing local cancer policies.

Summary

Korean summary
이 연구는 한국 시군구 단위에서 지난 20년(1999-2018)간 주요 8개 암 발생률의 지역 간 격차를 조사하고, 최근 5년(2014-2018)의 암 발생 군집 가능성을 평가했습니다. 지역 간 격차는 여성에서 갑상선암, 남성에서는 폐암이 가장 큰 격차를 보였습니다. 군집 가능성은 여성의 경우 유방암, 남성의 경우 간암에서 가장 높았습니다. 전국 단위에서는 볼 수 없었던 지역 간 격차 및 군집 발생 가능성이 시군구 단위에서 발견되었고, 이러한 결과는 지역에 맞는 암 정책을 기획하고 실행하는 데 중요한 방향을 제시할 수 있을 것입니다.

Key Message
This study investigated regional disparities in the incidence of eight major cancers in Korea at the municipal level during 1999-2018 and assessed the possibility of cancer clusters during 2014-2018. Thyroid cancer in women and lung cancer in men showed the most significant regional disparities. Breast cancer in women and liver cancer in men displayed the highest possibility of clustering. Regional disparities and cancer clusters were identified locally, which were not detected nationally. These findings could provide valuable guidance for developing and implementing cancer policies that are tailored to local needs.

Citations

Citations to this article as recorded by

The impact of social inequalities on cancer incidence and mortality in a Brazilian City: Data from the population-based cancer registry
Andrea Paula Bruno von Zuben, Maria do Carmo Ferreira, Marilisa Berti de Azevedo Barros, Juliana Nativo, M. Elvira P. Correa, Carmino Antônio de Souza
Cancer Epidemiology.2026; 103: 103102. CrossRef
Inequalities in breast cancer incidence and mortality in women with and without disabilities in South Korea: A population-based cohort study
Hee-Yeon Kang, Eunjung Park, Thi Tra Bui, Byungmi Kim, Jin-Kyoung Oh
Preventive Medicine Reports.2025; 59: 103242. CrossRef
Medical travel patterns for hepatocellular carcinoma treatment in South Korea: National Health Insurance data from 2013 to 2021
Sungmin Kim, Naeun Kim, Hyung-Sik Lee, Mina Kim, Hoseob Kim, Youngmin Choi
World Journal of Gastrointestinal Oncology.2025;[Epub] CrossRef
Hormone Replacement Therapy and Risks of Various Cancers in Postmenopausal Women with De Novo or a History of Endometriosis
Hee Joong Lee, Banghyun Lee, Hangseok Choi, Minkyung Lee, Kyungjin Lee, Tae Kyoung Lee, Sung Ook Hwang, Yong Beom Kim
Cancers.2024; 16(4): 809. CrossRef
What is the relationship between the local population change and cancer incidence in patients with dyslipidemia: Evidence of the impact of local extinction in Korea
Wonjeong Jeong, Dong‐Woo Choi, Woorim Kim, Kyu‐Tae Han
Cancer Medicine.2024;[Epub] CrossRef

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