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European Radiology

, Volume 27, Issue 1, pp 203–211 | Cite as

Humidifier disinfectant-associated lung injury in adults: Prognostic factors in predicting short-term outcome

  • Hyun Jung Koo
  • Kyung-Hyun DoEmail author
  • Eun Jin Chae
  • Hwa Jung Kim
  • Joon Seon Song
  • Se Jin Jang
  • Sang-Bum Hong
  • Jin Won Huh
  • En Lee
  • Soo-Jong Hong
Chest

Abstract

Objectives

To identify clinical and radiologic findings that affect disease severity and short-term prognosis of humidifier disinfectant-associated lung injury in adults and to compare computed tomography (CT) findings between the patients with and without death or lung transplantation.

Methods

Fifty-nine adults (mean age, 34 years; M/F = 12:47) were enrolled in this retrospective study. Medical records and prospective surveillance data were used to assess clinical and radiological factors associated with a poor clinical outcome. Multivariate generalized estimating equation models were used to analyse serial CT findings. Overall cumulative major events including lung transplantation and mortality were assessed using the Kaplan–Meier method.

Results

Almost half needed ICU admission (47.5 %) and 17 died (28.8 %). Young age, peripartum and low O2 saturation were factors associated with ICU admission. On initial chest radiographs, consolidation (P < 0.001) and ground-glass opacity (P = 0.01) were significantly noted in patients who required ICU admission. CT findings including consolidation (odds ratio (OR), 1.02), pneumomediastinum (OR, 1.66) and pulmonary interstitial emphysema (OR, 1.61) were the risk factors for lung transplantation and mortality.

Conclusion

Clinical and radiologic findings are related to the risks of lung transplantation and mortality of humidifier disinfectant-associated lung injury. Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings.

Key Points

Young age, peripartum and low O 2 saturation were associated with ICU admission.

Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings.

Consolidation and ground-glass opacity disappeared within 3 months and replaced by centrilobular nodules.

Radiologic findings are related to the outcome of humidifier disinfectant-associated lung injury.

Keywords

Adult Interstitial lung disease Environmental chemicals Computed tomography Prognosis 

Abbreviations

ARDS

acute respiratory distress syndrome

COP

cryptogenic organizing pneumonia

CT

computed tomography

ICU

intensive care unit

OR

odds ratio

Notes

Acknowledgements

The authors would like to thank all of the patients who participated in this study. We also thank the members of Humidifier Disinfectant Interstitial Lung Disease Surveillance and Research Team including the pulmonologists, pathologists and radiologists in our institution for their valuable help.

The scientific guarantor of this publication is Kyung-Hyun Do. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. This research was supported by the Environmental Health Center for Hazardous Chemical Exposure funded by the Ministry of Environment (2015-0510), Republic of Korea. One of the authors (Hwa Jung Kim) has significant statistical expertise. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study.

Seventeen patients from this were previously described (Hong S.B. et al. Thorax 69(8):694–702, 2014), as mentioned in the “Materials and methods” of this manuscript. Methodology: retrospective, observational, multicentre study.

Supplementary material

330_2016_4367_Fig6_ESM.gif (59 kb)
Supplementary Figure 1

Pathologic findings in patients with four phases of lung injury from humidifier disinfectant use. (A) Acute phase: a transbronchial lung biopsy specimen showing organizing pneumonia pattern with proliferation of intra-alveolar fibroblastic polyps (hematoxylin and eosin, original magnification ×100). Wedge-resected specimens indicate the subacute phase (B), early chronic phase (C), and late chronic phase (D) (original magnifications ×40). The specimen showed a spectrum of fibro-inflammatory processes (arrows) with centrilobular distribution. Interestingly, the subpleural space was well preserved, even in the late chronic phase (arrowheads). (GIF 59 kb)

330_2016_4367_Fig7_ESM.gif (73 kb)
Supplementary Figure 1

Pathologic findings in patients with four phases of lung injury from humidifier disinfectant use. (A) Acute phase: a transbronchial lung biopsy specimen showing organizing pneumonia pattern with proliferation of intra-alveolar fibroblastic polyps (hematoxylin and eosin, original magnification ×100). Wedge-resected specimens indicate the subacute phase (B), early chronic phase (C), and late chronic phase (D) (original magnifications ×40). The specimen showed a spectrum of fibro-inflammatory processes (arrows) with centrilobular distribution. Interestingly, the subpleural space was well preserved, even in the late chronic phase (arrowheads). (GIF 59 kb)

330_2016_4367_Fig8_ESM.gif (69 kb)
Supplementary Figure 1

Pathologic findings in patients with four phases of lung injury from humidifier disinfectant use. (A) Acute phase: a transbronchial lung biopsy specimen showing organizing pneumonia pattern with proliferation of intra-alveolar fibroblastic polyps (hematoxylin and eosin, original magnification ×100). Wedge-resected specimens indicate the subacute phase (B), early chronic phase (C), and late chronic phase (D) (original magnifications ×40). The specimen showed a spectrum of fibro-inflammatory processes (arrows) with centrilobular distribution. Interestingly, the subpleural space was well preserved, even in the late chronic phase (arrowheads). (GIF 59 kb)

330_2016_4367_Fig10_ESM.gif (70 kb)
Supplementary Figure 1

Pathologic findings in patients with four phases of lung injury from humidifier disinfectant use. (A) Acute phase: a transbronchial lung biopsy specimen showing organizing pneumonia pattern with proliferation of intra-alveolar fibroblastic polyps (hematoxylin and eosin, original magnification ×100). Wedge-resected specimens indicate the subacute phase (B), early chronic phase (C), and late chronic phase (D) (original magnifications ×40). The specimen showed a spectrum of fibro-inflammatory processes (arrows) with centrilobular distribution. Interestingly, the subpleural space was well preserved, even in the late chronic phase (arrowheads). (GIF 59 kb)

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330_2016_4367_Fig11_ESM.gif (70 kb)
Supplementary Figure 2

Pathologic findings in the late chronic phase in patients who did not require intensive care (A and B) and who required intensive care (C and D). Both cases showed the typical pathologic findings of lung injury associated with humidifier disinfectant use. The fibro-inflammatory process showed a centrilobular distribution (arrow, A and C, original magnification ×40). Notably, the subpleural space was not involved, even in the end stage (arrowhead, A and C). Variable degrees of fibroblastic proliferation resulted in bronchiolar obliteration and peribronchiolar fibrosis (B, arrow, original magnification ×100). (D) In the case of the intensive care patient, the infiltration of numerous interstitial lymphoplasma cells in the background of pulmonary edema accompanied by bronchiolar obliteration could be identified (arrow, original magnification ×100). (GIF 70 kb)

330_2016_4367_Fig12_ESM.gif (79 kb)
Supplementary Figure 2

Pathologic findings in the late chronic phase in patients who did not require intensive care (A and B) and who required intensive care (C and D). Both cases showed the typical pathologic findings of lung injury associated with humidifier disinfectant use. The fibro-inflammatory process showed a centrilobular distribution (arrow, A and C, original magnification ×40). Notably, the subpleural space was not involved, even in the end stage (arrowhead, A and C). Variable degrees of fibroblastic proliferation resulted in bronchiolar obliteration and peribronchiolar fibrosis (B, arrow, original magnification ×100). (D) In the case of the intensive care patient, the infiltration of numerous interstitial lymphoplasma cells in the background of pulmonary edema accompanied by bronchiolar obliteration could be identified (arrow, original magnification ×100). (GIF 70 kb)

330_2016_4367_Fig13_ESM.gif (81 kb)
Supplementary Figure 2

Pathologic findings in the late chronic phase in patients who did not require intensive care (A and B) and who required intensive care (C and D). Both cases showed the typical pathologic findings of lung injury associated with humidifier disinfectant use. The fibro-inflammatory process showed a centrilobular distribution (arrow, A and C, original magnification ×40). Notably, the subpleural space was not involved, even in the end stage (arrowhead, A and C). Variable degrees of fibroblastic proliferation resulted in bronchiolar obliteration and peribronchiolar fibrosis (B, arrow, original magnification ×100). (D) In the case of the intensive care patient, the infiltration of numerous interstitial lymphoplasma cells in the background of pulmonary edema accompanied by bronchiolar obliteration could be identified (arrow, original magnification ×100). (GIF 70 kb)

330_2016_4367_Fig14_ESM.gif (86 kb)
Supplementary Figure 2

Pathologic findings in the late chronic phase in patients who did not require intensive care (A and B) and who required intensive care (C and D). Both cases showed the typical pathologic findings of lung injury associated with humidifier disinfectant use. The fibro-inflammatory process showed a centrilobular distribution (arrow, A and C, original magnification ×40). Notably, the subpleural space was not involved, even in the end stage (arrowhead, A and C). Variable degrees of fibroblastic proliferation resulted in bronchiolar obliteration and peribronchiolar fibrosis (B, arrow, original magnification ×100). (D) In the case of the intensive care patient, the infiltration of numerous interstitial lymphoplasma cells in the background of pulmonary edema accompanied by bronchiolar obliteration could be identified (arrow, original magnification ×100). (GIF 70 kb)

330_2016_4367_MOESM5_ESM.tif (5.5 mb)
High Resolution Image (TIF 5663 kb)
330_2016_4367_MOESM6_ESM.tif (5.5 mb)
High Resolution Image (TIF 5663 kb)
330_2016_4367_MOESM7_ESM.tif (5.5 mb)
High Resolution Image (TIF 5663 kb)
330_2016_4367_MOESM8_ESM.tif (5.5 mb)
High Resolution Image (TIF 5663 kb)
330_2016_4367_MOESM9_ESM.docx (19 kb)
Supplementary Table 1 (DOCX 18 kb)
330_2016_4367_MOESM10_ESM.docx (19 kb)
Supplementary Table 2 (DOCX 19 kb)
330_2016_4367_MOESM11_ESM.docx (20 kb)
Supplementary Table 3 (DOCX 20 kb)
330_2016_4367_MOESM12_ESM.docx (21 kb)
Supplementary Table 4 (DOCX 21 kb)

References

  1. 1.
    Cheon CK, Jin HS, Kang EK et al (2008) Epidemic acute interstitial pneumonia in children occurred during the early 2006s. Kor J Pediatr 51:383–390Google Scholar
  2. 2.
    Kim BJ, Kim HA, Song YH et al (2009) Nationwide surveillance of acute interstitial pneumonia in korea. Kor J Pediatr 52:324–329Google Scholar
  3. 3.
    Lee E, Seo JH, Kim HY et al (2013) Toxic inhalational injury-associated interstitial lung disease in children. J Korean Med Sci 28:915–923CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lee JH, Kim YH, Kwon JH (2012) Fatal misuse of humidifier disinfectants in Korea: importance of screening risk assessment and implications for management of chemicals in consumer products. Environ Sci Technol 46:2498–2500Google Scholar
  5. 5.
    Ohnuma A, Yoshida T, Tajima H et al (2010) Didecyldimethylammonium chloride induces pulmonary inflammation and fibrosis in mice. Exp Toxicol Pathol 62:643–651Google Scholar
  6. 6.
    Korea Centers for Disease Control and Prevention (2011) Interim report of epidemiological investigation on lung injury with unknown cause in Korea. Public Health Wkly Rep 4:817–825Google Scholar
  7. 7.
    Yang HJ, Kim HJ, Yu J et al (2013) Inhalation toxicity of humidifier disinfectants as a risk factor of children's interstitial lung disease in Korea: a case-control study. PLoS ONE 8, e64430CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lee E, Seo JH, Kim HY et al (2012) Two series of familial cases with unclassified interstitial pneumonia with fibrosis. Allergy, Asthma Immunol Res 4:240–244CrossRefGoogle Scholar
  9. 9.
    Nemery B, Hoet PH (2015) Humidifier disinfectant-associated interstitial lung disease and the Ardystil syndrome. Am J Respir Crit Care Med 191:116–117CrossRefPubMedGoogle Scholar
  10. 10.
    Yoon HM, Lee E, Lee JS et al (2016) Humidifier disinfectant-associated children's interstitial lung disease: computed tomographic features, histopathologic correlation and comparison between survivors and non-survivors. Eur Radiol 26:235–243CrossRefPubMedGoogle Scholar
  11. 11.
    Kim KW, Ahn K, Yang HJ et al (2014) Humidifier disinfectant-associated children's interstitial lung disease. Am J Respir Crit Care Med 189:48–56PubMedGoogle Scholar
  12. 12.
    Hong SB, Kim HJ, Huh JW et al (2014) A cluster of lung injury associated with home humidifier use: clinical, radiological and pathological description of a new syndrome. Thorax 69:694–702CrossRefPubMedGoogle Scholar
  13. 13.
    Park D, Leem J, Lee K et al (2014) Exposure characteristics of familial cases of lung injury associated with the use of humidifier disinfectants. Environ Health 13:70CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J (2008) Fleischner Society: glossary of terms for thoracic imaging. Radiology 246:697–722CrossRefPubMedGoogle Scholar
  15. 15.
    Jeon BH, Park YJ (2012) Frequency of humidifier and humidifier disinfectant usage in gyeonggi provine. Environ Health Toxicol 27, e2012002CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chang MH, Park H, Ha M, Kim Y, Hong YC, Ha EH (2012) Characteristics of humidifier use in Korean pregnant women: the Mothers and Children's Environmental Health (MOCEH) Study. Environ Health Toxicol 27, e2012003CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ohnuma A, Yoshida T, Horiuchi H et al (2011) Altered pulmonary defense system in lung injury induced by didecyldimethylammonium chloride in mice. Inhal Toxicol 23:476–485CrossRefPubMedGoogle Scholar
  18. 18.
    Park S, Lee K, Lee EJ et al (2014) Humidifier disinfectant-associated interstitial lung disease in an animal model induced by polyhexamethylene guanidine aerosol. Am J Respir Crit Care Med 190:706–708CrossRefPubMedGoogle Scholar
  19. 19.
    Song JA, Park HJ, Yang MJ et al (2014) Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy. Food Chem Toxicol 69:267–275CrossRefPubMedGoogle Scholar
  20. 20.
    Primack SL, Hartman TE, Ikezoe J, Akira M, Sakatani M, Muller NL (1993) Acute interstitial pneumonia: radiographic and CT findings in nine patients. Radiology 188:817–820CrossRefPubMedGoogle Scholar
  21. 21.
    Gattinoni L, Caironi P, Pelosi P, Goodman LR (2001) What has computed tomography taught us about the acute respiratory distress syndrome? Am J Respir Crit Care Med 164:1701–1711CrossRefPubMedGoogle Scholar
  22. 22.
    Ichikado K, Suga M, Muller NL et al (2002) Acute interstitial pneumonia: comparison of high-resolution computed tomography findings between survivors and nonsurvivors. Am J Respir Crit Care Med 165:1551–1556CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2016

Authors and Affiliations

  • Hyun Jung Koo
    • 1
  • Kyung-Hyun Do
    • 1
    Email author
  • Eun Jin Chae
    • 1
  • Hwa Jung Kim
    • 2
  • Joon Seon Song
    • 3
  • Se Jin Jang
    • 3
  • Sang-Bum Hong
    • 4
  • Jin Won Huh
    • 4
  • En Lee
    • 5
  • Soo-Jong Hong
    • 6
  1. 1.Department of Radiology and Research Institute of Radiology, Asan Medical CenterUniversity of Ulsan College of MedicineSongpa-guSouth Korea
  2. 2.Department of Clinical Epidemiology and Biostatistics, Asan Medical CenterUniversity of Ulsan College of Medicine, Cancer CenterSeoulKorea
  3. 3.Department of Pathology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  4. 4.Department of Pulmonary and Critical Care Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  5. 5.Department of PediatricsInje University Haundae Paik HospitalBusanKorea
  6. 6.Department of Pediatrics, Childhood Asthma and Atopy Center, Environmental Health Center, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea

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