Inhalation toxicity of humidifier disinfectants as a risk factor of children's interstitial lung disease in Korea: a case-control study

Abstract

Background: The occurrence of numerous cases of interstitial lung disease in children (chILD) every spring in Korea starting in 2006 raised suspicion about a causal relationship with the use of humidifier disinfectants (HDs). The aim of this study was to evaluate the association between HD use and the risk of chILD.

Methods: This retrospective, 1∶3 matched case-control study consisted of 16 cases of chILD that had developed between 2010 and 2011. The three groups of parallel controls (patients with acute lobar pneumonia, asthma, and healthy children) were matched by age, gender, and index date. Indoor/outdoor environmental risk factors, including HD use, were investigated by asking the guardians to complete a questionnaire.

Results: The median age of the affected children (43.8% male) was 26 months (18.25-36.25). The chILD group did not differ significantly from the control groups with respect to socio-demographic and clinical variables. Indoor and outdoor environmental factors were not associated with a risk of chILD. However, the previous use of HDs (OR; 2.73. 95% CI; 1.41-5.90, P = 0.00) were independently associated with an increased risk.

Conclusions: This study showed that HDs, which are widely used in South Korea in the winter season, independently increased the risk of chILD in spring. Therefore, continuous monitoring and, if needed, changes in policy are essential to prevent and control pediatric diseases caused by toxic chemicals.

Figure 1. Case ascertainment criteria.

(A) Chest radiography showing diffuse, ill-defined ground-glass opacities and several ill-defined small nodular opacities in both lungs (in the 4 weeks after respiratory symptoms started). (B) Chest computed tomography showing diffuse centrilobular nodules in both lungs, with ground-glass opacities suggestive of peribronchiolar fibrosis (in the 4 weeks after respiratory symptoms started). (C) The most striking histological feature, interstitial thickening and fibrosis with a centrilobular distribution and relative sparing of the subpleural parenchyma (upper one-third). Original magnification ×40. (D) Interstitial fibroblasts proliferating in a pale myxoid stroma (arrows) and collapsed alveolar spaces lined by activated pneumocytes (arrowhead). Original magnification ×200.