Nationwide study of humidifier disinfectant lung injury in South Korea, 1994-2011 incidence and dose-response relationships

Rationale: 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. Objectives: 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. Measurements and Main 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 mg/m3 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 longterm cumulative exposure. These findings may explain some reversible or clinically unapparent cases among coexposed family members.