Tuberc Respir Dis.  2017 Oct;80(4):351-357. 10.4046/trd.2017.0048.

Humidifier Disinfectant-Associated Lung Injury: Six Years after the Tragic Event

• Kim WY
• Hong SB

• KMID: 2420577
• DOI: http://doi.org/10.4046/trd.2017.0048

Abstract

In 2011, a cluster of peripartum patients were admitted to the intensive care unit of a tertiary hospital in Seoul with signs and symptoms of severe respiratory distress of unknown etiology. Subsequent epidemiological and animal studies suggested that humidifier disinfectant (HD) might represent the source of this pathology. Epidemiological studies, animal studies, and dose-response analysis demonstrated a strong association between HD use and lung injuries. The diagnostic criteria for HD-associated lung injury (HDALI) was defined on the basis of the clinical, pathological, and radiological attributes of the patients. The clinical spectrum of HDALI appears to range from asymptomatic to full-blown acute respiratory failure, and some patients have required actual lung transplantation for survival. The overall mortality of the exposed population was not significant, although peripartum patients and children who were admitted to the intensive care unit did show high mortality rates. Persistent clinical findings such as diffuse ill-defined centrilobular nodules and restrictive lung dysfunction were observed in some of the survivors. The findings of this review emphasize the importance of assessment of the level of toxicity of chemical inhalants utilized in a home setting, as well as the need to identify and monitor afflicted individuals after inhalational injury.

Keyword

Humidifiers; Disinfectants; Lung Injury; Diagnosis; Prognosis; Review

MeSH Terms

Animals
Child
Diagnosis
Disinfectants
Epidemiologic Studies
Humans
Humidifiers*
Intensive Care Units
Lung Injury*
Lung Transplantation
Lung*
Mortality
Pathology
Peripartum Period
Prognosis
Respiratory Insufficiency
Seoul
Survivors
Tertiary Care Centers
Disinfectants

Figure

• 

  Figure 1 The three stages of humidifier disinfectant-associated lung injury in a 33-year-old woman. (A) Initial computed tomography (CT) scan shows diffuse centrilobular ground-glass opacity nodules with patchy multifocal consolidations. (B) CT examination performed on the day of admission to our hospital shows resolution of the consolidations, but diffuse ground-glass opacity nodules have become more distinct. (C) Follow-up CT scan obtained 2 weeks after admission shows persistence of diffuse ground-glass opacity nodules and pneumomediastinum.

• 

  Figure 2 Pathology of the explanted lungs. (A) The main pathology was that of a fibroinflammatory process, which predominantly involved the bronchioles and centrilobular lung parenchyma in the absence of notable granuloma formation. Subpleural and paraseptal airspaces were relatively preserved (H&E stain, ×40). (B) Parenchymal lesions showed histological patterns, which ranged from the early exudative phase to the extensive fibrosing phase (H&E stain, ×40).

• 

  Figure 3 Mean changes in lung function over time after humidifier disinfectant-associated lung injury. FVC: forced vital capacity; FEV1: forced expiratory volume in 1 second. ***p<0.001, *p<0.05 compared with the previous year, as assessed with repeated measures analysis of variance.

• 

  Figure 4 Frequency over time of patients whose lung function was normal of abnormal (A) or whose lung function improved (B) compared with previous years. Five patients who had normal lung function at onset were excluded from this analysis. It was considered to have improved but not normalized if the forced vital capacity % predicted (FVC%pred) increased but did not achieve ≥80%. The total number of patients in each group is shown above the bar.

Reference

1. Jeon BH, Park YJ. Frequency of humidifier and humidifier disinfectant usage in Gyeonggi provine. Environ Health Toxicol. 2012; 27:e2012002.

2. Hong SB, Kim HJ, Huh JW, Do KH, Jang SJ, Song JS, et al. A cluster of lung injury associated with home humidifier use: clinical, radiological and pathological description of a new syndrome. Thorax. 2014; 69:694–702.

3. Kim HJ, Lee MS, Hong SB, Huh JW, Do KH, Jang SJ, et al. A cluster of lung injury cases associated with home humidifier use: an epidemiological investigation. Thorax. 2014; 69:703–708.

4. Yang HJ, Kim HJ, Yu J, Lee E, Jung YH, Kim HY, et al. Inhalation toxicity of humidifier disinfectants as a risk factor of children's interstitial lung disease in Korea: a case-control study. PLoS One. 2013; 8:e64430.

5. Kim HR, Lee K, Park CW, Song JA, Shin DY, Park YJ, et al. Polyhexamethylene guanidine phosphate aerosol particles induce pulmonary inflammatory and fibrotic responses. Arch Toxicol. 2016; 90:617–632.

6. Korea Center for Disease Control and Prevention. Interim report of epidemiological investigation on lung injury with unknown cause in Korea [Internet]. Cheongju: Korea Center for Disease Control and Prevention;2011. cited 2017 Feb 9. Available from: http://cdc.go.kr/CDC/cms/content/mobile/00/12700_view.html.

7. Kim KW, Ahn K, Yang HJ, Lee S, Park JD, Kim WK, et al. Humidifier disinfectant-associated children's interstitial lung disease. Am J Respir Crit Care Med. 2014; 189:48–56.

8. Paek D, Koh Y, Park DU, Cheong HK, Do KH, Lim CM, et al. Nationwide study of humidifier disinfectant lung injury in South Korea, 1994-2011: incidence and dose-response relationships. Ann Am Thorac Soc. 2015; 12:1813–1821.

9. Park JH, Kim HJ, Kwon GY, Gwack J, Park YJ, Youn SK, et al. Humidifier disinfectants are a cause of lung injury among adults in South Korea: a community-based case-control study. PLoS One. 2016; 11:e0151849.

10. Lee JH, Kim YH, Kwon JH. Fatal misuse of humidifier disinfectants in Korea: importance of screening risk assessment and implications for management of chemicals in consumer products. Environ Sci Technol. 2012; 46:2498–2500.

11. Park S, Lee K, Lee EJ, Lee SY, In KH, Kim HK, et al. Humidifier disinfectant-associated interstitial lung disease in an animal model induced by polyhexamethylene guanidine aerosol. Am J Respir Crit Care Med. 2014; 190:706–708.

12. Park DU, Friesen MC, Roh HS, Choi YY, Ahn JJ, Lim HK, et al. Estimating retrospective exposure of household humidifier disinfectants. Indoor Air. 2015; 25:631–640.

13. Huh JW, Hong SB, Do KH, Koo HJ, Jang SJ, Lee MS, et al. Inhalation lung injury associated with humidifier disinfectants in adults. J Korean Med Sci. 2016; 31:1857–1862.

14. Chang MH, Park H, Ha M, Kim Y, Hong YC, Ha EH. Characteristics of humidifier use in Korean pregnant women: the Mothers and Children’s Environmental Health (MOCEH) study. Environ Health Toxicol. 2012; 27:e2012003.

15. Koo HJ, Do KH, Chae EJ, Kim HJ, Song JS, Jang SJ, et al. Humidifier disinfectant-associated lung injury in adults: Prognostic factors in predicting short-term outcome. Eur Radiol. 2017; 27:203–211.

16. Kim WY, Park S, Kim HJ, Chae EJ, Do KH, Huh JW, et al. Lung function in patients with lung injury due to household chemical inhalation: post hoc analysis of a prospective nationwide cohort. Respirology. 2017; 22:345–351.

17. Kim WY, Kim SW, Jo KW, Choi SH, Kim HR, Kim YH, et al. Lung transplantation for chronic humidifier disinfectant-associated lung injury. Korean J Crit Care Med. 2016; 31:146–151.

18. Cheon CK, Jin HS, Kang EK, Kim HB, Kim BJ, Yu J, et al. Epidemic acute interstitial pneumonia in children occurred during the early 2006s. Korean J Pediatr. 2008; 51:383–390.