J Korean Med Sci.  2013 Jun;28(6):915-923. 10.3346/jkms.2013.28.6.915.

Toxic Inhalational Injury-Associated Interstitial Lung Disease in Children

• Lee E
• Seo JH
• Kim HY
• Yu J
• Jhang WK
• Park SJ
• Kwon JW
• Kim BJ
• Do KH
• Cho YA
• Kim SA
• Jang SJ
• Hong SJ

• KMID: 2158041
• DOI: http://doi.org/10.3346/jkms.2013.28.6.915

Abstract

Interstitial lung disease in children (chILD) is a group of disorders characterized by lung inflammation and interstitial fibrosis. In the past recent years, we noted an outbreak of child in Korea, which is possibly associated with inhalation toxicity. Here, we report a series of cases involving toxic inhalational injury-associated chILD with bronchiolitis obliterans pattern in Korean children. This study included 16 pediatric patients confirmed by lung biopsy and chest computed tomography, between February 2006 and May 2011 at Asan Medical Center Children's Hospital. The most common presenting symptoms were cough and dyspnea. The median age at presentation was 26 months (range: 12-47 months), with high mortality (44%). Histopathological analysis showed bronchiolar destruction and centrilobular distribution of alveolar destruction by inflammatory and fibroproliferative process with subpleural sparing. Chest computed tomography showed ground-glass opacities and consolidation in the early phase and diffuse centrilobular nodular opacity in the late phase. Air leak with severe respiratory difficulty was associated with poor prognosis. Although respiratory chemicals such as humidifier disinfectants were strongly considered as a cause of this disease, further studies are needed to understand the etiology and pathophysiology of the disease to improve the prognosis and allow early diagnosis and treatment.

Keyword

Lung Disease, Interstitial; Pulmonary Fibrosis; Bronchioles; Inhalation; Toxin, Biological

MeSH Terms

APACHE
Bronchi/pathology
Child, Preschool
Cough/etiology
Cyclophosphamide/therapeutic use
Disinfectants/*toxicity
Dyspnea/etiology
Enzyme Inhibitors/therapeutic use
Humans
Hydroxychloroquine/therapeutic use
Immunoglobulins/therapeutic use
Infant
Inhalation
Lung Diseases, Interstitial/chemically induced/drug therapy/*pathology
Prognosis
Retrospective Studies
Steroids/therapeutic use
Tomography, X-Ray Computed
Disinfectants
Enzyme Inhibitors
Immunoglobulins
Steroids
Hydroxychloroquine
Cyclophosphamide

Figure

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  Fig. 1 Lung histology in two patients with toxic inhalational lung injury associated with interstitial lung disease in children. (A) Air spaces are diffusely filled with edema fluid. Alveolar septa are focally infiltrated by lymphocytes (H&E, original magnification ×200). (B) A few bronchioles are disrupted and infiltrated by lymphocytes (arrows) (H&E, Original magnification ×400). (C) Alveolar septa are thickened by inflammatory infiltration. Hyaline membranes are deposited air-side of alveolar septa (arrow). Histiocytes with occasional foamy change fill alveolar spaces (H&E, original magnification ×400). (D) Low magnification of this example shows prominent centrilobular distribution of interstitial thickening and fibrosis (H&E, Original magnification ×40). (E) Bronchioles are destructed by inflammatory cells (arrow) and fibroblastic proliferation (asterisk) and epithelial cells are denuded. Peribronchiolar interstitial septa are severely thickened with infiltration of chronic inflammatory cells, fibroblasts and foamy histiocytes (left half) (H&E, Original magnification ×200). (F) Fibroblastic proliferation in pale myxoid stroma obliterates the bronchiolar space (asterisk). Collapsed alveolar spaces are lined by activated pneumocytes and filled with collection of foamy histiocytes (arrow) (H&E, original magnification ×200).

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  Fig. 2 Radiologic findings in a 41-month-old boy with toxic inhalational lung injury associated interstitial lung disease. (A) A high resolution computed tomography scan performed 2 weeks after symptom onset demonstrates focal patchy consolidation and ground-glass opacity in both lower lobes with subpleural sparing. (B) Chest CT scan of the patient 6 weeks after symptom onset shows progression of diffuse centrilobular nodules with ground-glass opacity, suggesting peribronchiolar fibrosis in both lungs. (C) One-year follow-up chest CT scan shows decreased density, but residual diffuse centrilobular ground-glass opacity involving both lungs.

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