INTRODUCTION
METHODS
Fig. 1
Prisma flow chart for the systematic review of humidifier disinfectant.
![jkms-37-e257-g001](/upload/SynapseXML/0063jkms/thumb/jkms-37-e257-g001.jpg)
Table 1
Definition of groups for systematic review of included studies
![jkms-37-e257-i001](/upload/SynapseXML/0063jkms/thumb/jkms-37-e257-i001.jpg)
RESULTS
Human studies
Table 2
Published human epidemiological studies regarding humidifier disinfectant and its health effects (N = 49)
![jkms-37-e257-i002](/upload/SynapseXML/0063jkms/thumb/jkms-37-e257-i002.jpg)
Author/Reference | Journal | Language | Study design | Participant number | Main outcome |
---|---|---|---|---|---|
Kim et al. (2014)1 | Thorax | English | Case-control study | Case: 18 Control: 121 | HDLI |
Ryu et al. (2019)2 | Indoor Air | English | Descriptive survey | 1,153 | HDLI |
Koo et al. (2017)3 | Eur Radiol | English | Retrospective study | 59 | HDLI |
Park et al. (2014)4 | Environ Health | English | Case series | 38 | Lung injury cases |
Park et al. (2015)5 | Indoor Air | English | Case-control study | Case: 374 Control: 303 | Exposure site |
Lee et al. (2020)6 | J Environ Health Sci | Korean | Cross-sectional study | 1,555 | Exposure site |
Hong et al. (2014)7 | Thorax | English | Case series | 17 | HDLI |
Paek et al. (2015)9 | Ann Am Thorac Soc | English | Retrospective study | 374 | HDLI |
Lee et al. (2019)10 | J Environ Health Sci | Korean | Descriptive survey | 4,482 | Exposure assessment methodology |
Ryu et al. (2021)11 | BMC Public Health | English | Descriptive survey | 5,245 | Exposure assessment methodology |
Kim et al. (2020)12 | J Environ Health Sci | Korean | Descriptive survey | 3,445 | Exposure assessment methodology |
Ryu et al. (2019)13 | J Environ Health Sci | Korean | Descriptive survey | 5,245 | Exposure assessment methodology |
Ju et al. (2021)14 | Epidemiol Health | English | Descriptive survey | 1,413 | Non-specific death |
Lamichhane et al. (2019)17 | PLoS One | English | Case-control study | Case: 244 Control: 244 | IIP |
Kim et al. (2021)19 | Ann Occup Environ Med | English | Descriptive survey | 200 | HD effect evaluation |
Park et al. (2020)20 | J Environ Health Sci | Korean | Descriptive survey | 201 | HD monitoring program |
Yang et al. (2013)21 | PLoS One | English | Case-control study | Case: 16 Control: 47 | chILD |
Lee et al. (2013)22 | J Korean Med Sci | English | Case series | 16 | chILD |
Cho et al. (2017)23 | PLoS One | English | Cross-sectional study | 24 | Peripheral airway dysfunction |
Kim et al. (2017)24 | Respirology | English | Retrospective study | 40 | Pulmonary function in HD-exposed people |
Cho et al. (2019)25 | BMC Pulm Med | English | Case-control study | Case: 81 Control: 122 | DLCO in HD-exposed people |
Lee et al. (2018)26 | J Korean Med Sci | English | Case series | 2 | CMIT/MIT alone HDLI |
Li et al. (2019)27 | Drug Chem Toxicol | English | Case report | 1 | MIT and ARDS |
Jo et al. (2020)28 | J Environ Health Sci | Korean | Descriptive survey | Exposure to NaDCC | |
Yoon et al. (2021)29 | Int J Environ Res Public Health | English | Ecological study | HDLI | |
Park et al. (2020)30 | J Environ Health Sci | Korean | Ecological study | HDLI (annual trends) | |
Park et al. (2016)31 | J Environ Health Sci | Korean | Descriptive survey | 699 | HDLI |
Cho (2019)32 | J Environ Health Sci | Korean | Cross-sectional study | 1,598 | Bronchiolitis, allergic rhinitis |
Koh et al. (2020)33 | Ann Occup Environ Med | English | Cross-sectional study | 1,540 | Allergic rhinitis |
Lee et al. (2021)34 | Ann Am Thorac Soc | English | Cross-sectional study | 846 | Asthma |
Leem et al. (2020)35 | Int J Occup Med Environ Health | English | Case series | 24 | HD-related respiratory syndrome |
Lee et al. (2020)36 | Ann Occup Environ Med | English | Case report | 1 | Mental health |
Kim et al. (2021)37 | BMC Pediatr | English | Panel study (PSKC) | 1,113 | Neuropsychiatric outcomes |
Ko et al. (2021)38 | Int J Environ Res Public Health | English | Cross-sectional study | 456 | Psychological symptoms |
Park et al. (2016)39 | PLoS One | English | Case-control study | Case: 16 Control: 60 | HDLI |
Kang et al. (2018)40 | J Environ Health Sci | Korean | Descriptive survey | 42 | HD manufacturing worker |
Park et al. (2015)41 | PLoS One | English | Case-control study | Case: 169 Control: 303 | HDLI |
Park et al. (2018)42 | Sci Total Environ | English | Case-control study | Case: 214 Control: 123 | HDLI |
Nam et al. (2020)43 | Ann Occup Environ Med | English | Case report | 2 | HDLI (resolved) |
Lim et al. (2020)44 | J Korean Med Sci | English | Case series | 43 | HDLI |
Kim et al. (2014)45 | Am J Respir Crit Care Med | English | Descriptive survey | 138 | chILD |
Yoon et al. (2016)46 | Eur Radiol | English | Retrospective study | 47 | chILD |
Kim et al. (2016)47 | Pediatr Pulmonol | English | Retrospective study | 17 | chILD |
Park et al. (2017)48 | Sci Total Environ | English | Descriptive survey | 221 | HDLI |
Yoon et al. (2017)49 | Environ Res | English | Descriptive survey | 1,577 | Usage rate of HD |
Lee et al. (2019)50 | J Environ Health Sci | Korean | Descriptive survey | 4,030 | Usage rate of HD |
Byeon et al. (2020)51 | J Environ Health Sci | Korean | Descriptive survey | 15,472 | Usage rate of HD |
Han et al. (2020)52 | J Environ Health Sci | Korean | Descriptive survey | Exposure site | |
Han et al. (2019)53 | J Environ Health Sci | Korean | Descriptive survey | 301 | Exposure site |
Animal studies and in vitro studies
Table 3
Published toxicological animal or in-vitro studies regarding humidifier disinfectant and its health effects (N = 48)
![jkms-37-e257-i003](/upload/SynapseXML/0063jkms/thumb/jkms-37-e257-i003.jpg)
Author/Reference | Journal | Language | Study design | Results (keywords) |
---|---|---|---|---|
Song et al. (2021)16 | Toxicology | English | Animal study (BALB/c mice) | PHMG-P, asthma, irritant-induced airway inflammation |
Jung et al. (2014)39 | Toxicol In Vitro | English | In vitro study (A549 cell) | PHMG, cellular toxicity, alteration of gene expression |
Song et al. (2014)40 | Food Chem Toxicol | English | Animal study (C57BL/6 mice) | PHMG-P, pulmonary inflammation, fibrosis, thymic atrophy |
Kim et al. (2017)41 | Toxicol Lett | English | Animal study (SD rats) | PHMG-P, genomic changes in lungs |
Kim et al. (2017)42 | J Environ Health Sci | Korean | Animal study (C57BL/6 mice) | CMIT/MIT, death, pulmonary fibrosis |
Kang et al. (2018)43 | J Environ Health Sci | Korean | Animal study (ICR mice) | CMIT/MIT, stillbirth in pregnant mice |
Do et al. (2021)44 | Arch Toxicol | English | In vitro (vascular smooth muscles cells in SD rats) | CMIT/MIT, cytosolic Zn2+, ROS |
Lee and Yu (2017)60 | Toxicol Ind Health | English | Experimental characterization (PHMG) | Not sufficient to PHMG lung disease |
Park et al. (2021)61 | Molecules | English | Experimental characterization (PHMG) | PHMG as a polymer |
Kim et al. (2020)62 | Environ Res | English | Experimental characterization (PHMG) | Hydrodynamic properties of PHMG sprayed in the air |
Park et al. (2020)63 | Molecules | English | Experimental characterization (CMIT/MIT) | CMIT/MIT varied from 12 to 353 ppm |
Song et al. (2021)64 | Toxics | English | Animal study (C57BL/6 mice) | PHMG-P not reversed even after long-term recovery |
Park et al. (2019)65 | Inhal Toxicol | English | In vitro study (A549 cells) | PHMG-P, PHMB, PGH, fibrosis, EMT |
Shin et al. (2018)66 | Toxicol Lett | English | In vitro study (A549 cells) | PHMG-P-induced fibrosis |
Jeong et al. (2019)67 | Toxicol Appl Pharmacol | English |
Animal study (C57BL/6 mice) In vitro study (A549 cells) |
PHMG-P, EMT |
Oh et al. (2018)68 | Zebrafish | English | Animal study (Zebrafish) | PHMG-P, respiratory-specific molecular markers |
Kim et al. (2019)69 | Molecules | English | Animal study (C57BL/6 mice) | CG-745, EMT regulation |
Seo et al. (2019)70 | Metabolomics | English | Animal study (C57BL/6 mice) | PHMG, NADPH oxidase signaling, fibrosis |
Kwon et al. (2021)71 | Toxicol Appl Pharmacol | English | In vitro study (BEAS-2B cells) | CMIT/MIT, mechanical stress |
Jeong et al. (2021)72 | Toxics | English | In vitro study (HPAEpiCs) | PHMG, MT1 isomers |
Song et al. (2020)73 | Molecules | English | Animal study (C57BL/6 mice) | Kathon, fibrotic lung injury, Th2-dependent, fibrosis |
Park and Seong (2020)74 | Toxicol In Vitro | English | In vitro study (BEAS-2B cells) | MIT, apoptosis, MMPs |
Park et al. (2020)75 | Environ Toxicol | English |
In vitro study (BEAS-2B cells) Animal study (ICR mice) |
Eosinophilia-mediated disease, pulmonary surfactants |
Kim et al. (2016)76 | Arch Toxicol | English |
Animal study (SD rats) In vitro study (Calu-3, THP-1, HMC-1) |
PHMG-P, ROS, cytokines, pulmonary fibrosis |
Song et al. (2019)77 | Inhal Toxicol | English | Animal study (C57BL/6 mice) | Gene expression, PHMG-P |
Lee et al. (2020)78 | Arch Toxicol | English | Animal study (Wistar rats) | Arg1, Lcn2, PHMG-P |
Choi et al. (2022)79 | Ecotoxicol Environ Saf | English | In vitro (BEAS-2B, A549, human H9 ES cells) | Lung fibrosis, PHMG-P, viral infection. |
Li et al. (2021)80 | J Hazard Mater | English | Animal study (C57BL/6 mice) | PHMG, pulmonary fibrosis, surfactants |
Lim et al. (2018)81 | J Hazard Mater | English | Experimental characterization (PHMG) | PHMG, hydrophilic group of lipid |
Park et al. (2018)82 | Toxicol Lett | English | In vitro study (BEAS-2B cells) | PHMG-P, apoptosis |
Park et al. (2019)83 | J Toxicol Sci | English | In vitro study (A549 cells) | PHMG-P, G1/S arrest, apoptosis, ROS/ATM/p53 pathway |
Song et al. (2018)84 | Toxicol Appl Pharmacol | English | Animal study (C57BL/6 mice) | PHMG-P, pulmonary inflammation, fibrosis |
Kim and Choi (2019)85 | Toxicol Appl Pharmacol | English | Animal study (C.elegans) | CMIT/MIT, O-linked N-acetylglucosamine transferase |
Seo and Jo (2021)86 | Sci Rep | English | Animal study (F344 rats) | NaDCC, nasal cavity, larynx NOAEL 0.8 mg/m3 |
Lee et al. (2021)87 | Allergy Asthma Immunol Res | English | Animal study (BALB/c mice) | PHMG, allergic responses, CCL11, SERPINF1 |
Go et al. (2020)88 | Sci Rep | English | Animal study (BALB/c mice) | CMIT/MIT, Th2/Th17, atopic dermatitis |
Shim et al. (2018)89 | Chemosphere | English | Animal study (SD rats) | PHMG, Radioactive indium, liver |
Kim et al. (2022)90 | Biomol Ther | English | Animal study (C57BL/6 mice) | PHMG-P, IRAK3, GSTp1, GSTp2, liver fibrosis |
Song et al. (2020)91 | Toxics | English | Animal study (Zebrafish) | PHMG-P, cardiotoxic, transcriptome changes |
Chatterjee et al. (2021)92 | Environ Pollut | English | Animal study (Zebrafish) | CMIT/MIT, heart rates, hypermethylation, locomotion behavior |
Cho and Kim (2020)93 | Korean J. Environ. Biol. | Korean |
Animal study (Zebra fish) In vitro study (Human dermal cells) |
PHMG, PGH, CMIT/MIT, dermal cell toxicity, brain toxicity |
Lee et al. (2021)94 | J Hazard Mater | English | Animal study (SD rats) | PHMG, growth retardation fetus |
Lee et al. (2019)95 | Regul Toxicol Pharmacol | English | Animal study (SD rats) | NOAELs of PHMG-P: 40 mg/kg/day |
Lee and Seo (2020)96 | J Toxicol Pathol | English | Animal study (F344 rats) | NOAEL for PHMG·HCl below 1 mg/m3 |
Lee et al. (2022)97 | Chemosphere | English | Animal study (SD rats) | Prenatal PHMG-P exposure offspring's future health |
Kim and Ji (2019)98 | Ecotoxicol Environ Saf | English | Animal study (Zebrafish) | PHMG-P, oxidative stress, thyroid hormone |
Park et al. (2019)99 | Environ Health Toxicol | English | In vitro study (EpiOcular) | Not meet the criteria for serious eye damage or irritation |
Lee et al. (2021)100 | Environ Anal Health Toxicol | English | In vitro study (SIRC cells) | PHMG, eye, fibrosis |
Technical reports, presentation abstracts, and dissertations
Table 4
Technical reports of temporal projects conducted by governmental agencies (N = 22)
![jkms-37-e257-i004](/upload/SynapseXML/0063jkms/thumb/jkms-37-e257-i004.jpg)
Author | Year | Classification | Agency | Study design | Main results |
---|---|---|---|---|---|
Kim et al.101 | 2016 | Relief | SICSD | Descriptive survey | Necessity of relief system |
Leem et al.102 | 2017 | Relief | NIER | Report | Asthma |
Leem et al.103 | 2017 | Relief | NIER | Report | Interstitial pneumonia, pneumonia, toxic hepatitis |
Hong et al.104 | 2017 | Toxicology | NIER | In vitro study (serum) | Biomarkers specific to exposure |
Yang et al.105 | 2017 | Relief | NIER | Report | Big data analysis from NHI, asthma |
Park et al.106 | 2018 | Toxicology | SICSD | Experimental characterization (all) | Exposure doses |
Lee et al.107 | 2018 | Toxicology | NIER | Animal study (Wistar rats) | Combined use of humidifier disinfectant |
Choi et al.108 | 2018 | Toxicology | MOE |
Animal study (SD rats) In vitro study (BEAS-2B, A549, THP-1, MRC5) |
Lung fibrosis, skin, eye irritation, CMIT/MIT |
Kim et al.109 | 2018 | Epidemiology | NIER | Ecological study | Almost all respiratory diseases, NHI data, extrapulmonary diseases |
Jeong et al.110 | 2019 | Toxicology | KEITI | Animal study (Wistar rats, BALB/c mice, C57BL/6 mice) | Asthma induction and exacerbation |
Choi et al.111 | 2019 | Epidemiology | SICSD | Descriptive survey | Exposure in multi-use facilities |
Lee et al.112 | 2019 | Relief | SICSD | Descriptive survey | Exposure in medical institutions |
Kim et al.113 | 2019 | Toxicology | SICSD | Case-series (animal) | Unknown respiratory illnesses in companion animals |
Leem et al.114 | 2019 | Relief | NIER | Report | HDRS, COPD, toxic hepatitis |
Paek et al.116 | 2019 | Epidemiology | NIER | Report | Upper and lower respiratory diseases in CMIT/MIT alone user |
Jeong et al.117 | 2019 | Epidemiology | NIER | Self-controlled case series study | Pneumonia, adult interstitial lung disease |
Hong et al.118 | 2019 | Toxicology | NIER | In vitro study (serum) | Biomarkers of 26 proteins for HDLI |
Jeong et al.119 | 2019 | Toxicology | MOE |
Animal study (Wistar rats) In vitro study (BEAS-2B, A549, RAW264.7) |
Asthma, pulmonary fibrosis, liver disease, vascular disease, eye toxicity |
Kim120 | 2019 | Toxicology | NIER | Animal study (SD rats) | NaDCC, acute and subchronic respiratory effects, reversible |
Jeong et al.121 | 2019 | Epidemiology | NIER | Case-control study | Asthma, incubation period of up to 10 years, COPD |
Lee et al.122 | 2019 | Toxicology | KEITI |
Animal study (SD rats, C57BL/6 mice) In vitro study (A549 cells, serum) |
Fetal effects of exposure during pregnancy |
Kim et al.123 | 2020 | Epidemiology | SICSD | Descriptive survey | Estimation: 6.27 million users, 670,000 experienced health damage |
Table 5
Published short reports, narrative reviews, or grey literatures including conference materials, thesis, dissertation, etc. (N = 77)
![jkms-37-e257-i005](/upload/SynapseXML/0063jkms/thumb/jkms-37-e257-i005.jpg)
Report type | Number |
---|---|
Short communication | 9 |
Thesis or dissertation | 18 |
Conference abstract | 19 |
Narrative review | 16 |
Qualitative research | 2 |
Monitoring center report | 13 |
Total | 77 |