title: Nationwide Study of Humidifier Disinfectant Lung Injury in South Korea, 1994-2011. Incidence and Dose-Response Relationships.
abstract: BACKGROUND
  Humidifier disinfectant lung injury is an acute lung disease attributed to recurrent inhalation of certain disinfectant aerosols emitted from room humidifiers. An outbreak of this toxic lung injury occurred in South Korea from 1995 until all humidifier disinfectant products were recalled from the consumer market by the government in 2011.
  
  
  OBJECTIVE
  A nationwide study was conducted to ascertain and classify all potential cases of humidifier disinfectant lung injury in Korea and to assess dose-response relationships.
  
  
  METHODS
  By several mechanisms, clinicians and the general public were invited to report all suspected cases of humidifier disinfectant lung injury to public health officials in South Korea. A committee was convened to define diagnostic criteria based on pathologic, radiologic, and clinical findings for index cases, combined with assessment of environmental exposure to humidifier disinfectants. Clinical review and environmental assessments were performed and later combined to determine overall likelihood of disease for each study participant, classified as definite, probable, possible, or unlikely. Survival time from exposure to onset of symptoms was analyzed to assess dose-response relationships. Three broad categories of risk factors were examined: (1) biological susceptibility, (2) temporal cycle of exposure and recovery, and (3) spatial conditions and density of disinfectant.
  
  
  RESULTS
  Of 374 possible cases identified and reviewed, 329 were unanimously classified by the diagnostic committee, as follows: 117 definite, 34 probable, 38 possible and 140 unlikely cases. A total of 62 individuals with definite or probable disease died. Risk factors examined for polyhexamethyleneguanidine phosphate exposure that were found to be significant in shortening survival included age 4 years or younger at onset, use of disinfectant for 7 days per week, airborne density of 800 μg/m(3) or more of disinfectant, and daily exposure 11 or more hours in duration.
  
  
  CONCLUSIONS
  Dose-response analysis indicated that development of humidifier disinfectant lung injury and death were associated strongly with recurrent, intense, acute exposure without sufficient recovery time between exposures, more so than long-term cumulative exposure. These findings may explain some reversible or clinically unapparent cases among coexposed family members.
authors.affiliation: 1 School of Public Health, Seoul National University, Seoul, Korea.
authors.forename: Domyung
authors.initials: D
authors.lastname: Paek
authors.affiliation: 2 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Younsuck
authors.initials: Y
authors.lastname: Koh
authors.affiliation: 3 Korea National Open University, Seoul, Korea.
authors.forename: Dong-Uk
authors.initials: DU
authors.lastname: Park
authors.affiliation: 4 School of Medicine and.
authors.forename: Hae-Kwan
authors.initials: HK
authors.lastname: Cheong
authors.affiliation: 2 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Do
authors.affiliation: 2 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Chae-Man
authors.initials: CM
authors.lastname: Lim
authors.affiliation: 2 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Soo-Jong
authors.initials: SJ
authors.lastname: Hong
authors.affiliation: 5 Korea Institute of Toxicology, Daejeon, Korea.
authors.forename: Yong-Hwa
authors.initials: YH
authors.lastname: Kim
authors.affiliation: 6 Inha University Hospital, Incheon, Korea.
authors.forename: Jong-Han
authors.initials: JH
authors.lastname: Leem
authors.affiliation: 7 School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors.forename: Kyu Hyuck
authors.initials: KH
authors.lastname: Chung
authors.affiliation: 8 Asian Citizen's Center for Environment and Health, Seoul, Korea.
authors.forename: Ye-Yong
authors.initials: YY
authors.lastname: Choi
authors.affiliation: 9 Institute of Environmental Safety and Protection, NeoEnBiz Company, Bucheon, Korea.
authors.forename: Jong-Hyeon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: 10 College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Sin-Ye
authors.initials: SY
authors.lastname: Lim
authors.affiliation: 11 National Medical Center, Seoul, Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Chung
authors.affiliation: 2 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Cho
authors.affiliation: 2 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Chae
authors.affiliation: 11 National Medical Center, Seoul, Korea.
authors.forename: Joon-Sung
authors.initials: JS
authors.lastname: Joh
authors.affiliation: 11 National Medical Center, Seoul, Korea.
authors.forename: Yup
authors.initials: Y
authors.lastname: Yoon
authors.affiliation: 12 Korea Institute of Toxicology, Jeongup, Korea.
authors.forename: Kyu-Hong
authors.initials: KH
authors.lastname: Lee
authors.affiliation: 13 College of Medicine, Hanyang University, Seoul, Korea; and.
authors.forename: Bo Youl
authors.initials: BY
authors.lastname: Choi
authors.affiliation: 14 Korea Centers for Disease Control and Prevention, Cheongju, Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Gwack
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004202:Disinfectants / Q000009:adverse effects*; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005427:Flocculation; D005544:Forecasting; D006146:Guanidines / Q000009:adverse effects; D006801:Humans; D000068998:Humidifiers; D015994:Incidence; D007223:Infant; D019570:Inhalation Exposure / Q000009:adverse effects*; D055370:Lung Injury / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D009330:Nebulizers and Vaporizers; D011159:Population Surveillance; D011379:Prognosis; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D055815:Young Adult
chemical_list: D004202:Disinfectants; D006146:Guanidines; C060540:polyhexamethyleneguanidine
keywords: humidifier biocide; methylisothiazolinone; minimum acute exposure; oligo(2-(2-ethoxy)ethoxyethylguanidinium chloride; polyhexamethyleneguanidine phosphate