Family-based case-control study of exposure to household humidifier disinfectants and risk of idiopathic interstitial pneumonia

Abstract

Background In Korea, several household humidifier disinfectants (HDs) were clinically confirmed to cause HD-associated lung injury (HDLI). Polyhexamethylene guanidine (PHMG) phosphate is the main ingredient of the HDs found to be associated with lung disease. However, the association of HDs with other interstitial lung disease including idiopathic interstitial pneumonia (IIP) is not clear. We examined the relationship between HD exposure and IIP in a family-based study. Methods This case-control study included 244 IIP cases and 244 family controls who lived with the IIP patients. The IIP cases were divided into two groups, HDLI and other IIP, and were matched to family controls based on age and gender. Information on exposure to HDs was obtained from a structured questionnaire and field investigations. Conditional logistic regression was used to estimate odds ratio (ORs) and their corresponding 95% confidence interval (CI), investigating the association of HD-related exposure characteristics with IIP risk. Results The risks of IIP increased two-fold or more in the highest compared with the lowest quartile of several HD use characteristics, including average total use hours per day, cumulative sleep hours, use of HD during sleep, and cumulative exposure level. In analyses separated by HDLI and other IIP, the risks of HDLI were associated with airborne HD concentrations (adjusted OR = 3.01, 95% CI = 1.34–6.76; Q 4 versus Q 1 ) and cumulative exposure level (adjusted OR = 3.57, 95% CI = 1.59–8.01; Q 4 versus Q 1 ), but this relationship was not significant in the patients with other IIP. In comparison between HDLI and other IIP, the odds ratios of average total use hours, cumulative use hours, and cumulative sleeps hours was higher for other IIP. Conclusion The use of household HDs is associated not only with HDLI but also with other IIP.

Humidifier Disinfectant Consumption and Humidifier Disinfectant-Associated Lung Injury in South Korea: A Nationwide Population-Based Study

“…Taken together, it seems plausible that HD-induced inflammation and mRNA expression of fibronectin might trigger a wound-healing response, causing epithelial cells to be stiff and thickened, eventually leading to pulmonary fibrosis, which is identical to the features of HDLI cases. Although a few small-scale studies of matched case-control design support the above experimental findings and suggest significant associations with HD exposure and an increased risk of HDLI, there were still limited large-scale epidemiological studies [ 13 , 14 , 15 ].…”

“…A growing body of evidence from in vitro [ 9 , 10 ] and in vivo [ 11 , 12 ] studies demonstrated that exposure to PHMG, CMIT/MIT, and PGH chemicals causes apoptosis, inflammation, and reactive oxygen stress in alveolar epithelial cells and induces airway barrier injuries, thereby leading to pulmonary inflammation and lung fibrosis. In addition, matched case-control studies (i.e., hospital-based, family-based, and community-based case-control studies) reported consistent findings of significant associations between the levels of HD exposure and the risk of a fatal lung injury called HD-associated lung injury (HDLI) [ 13 , 14 , 15 ]. Despite the potential role of PHMG, CMIT/MIT, and PGH in the pathogenesis of fatal lung injury as well as emerging evidence from case-control studies, the nationwide contribution of exposure to HD-related synthetic chemicals to the lung injury epidemic remains underappreciated.…”

MTF1 Is Essential for the Expression of MT1B, MT1F, MT1G, and MT1H Induced by PHMG, but Not CMIT, in the Human Pulmonary Alveolar Epithelial Cells

“…In human and animal studies, the inhalation of PHMG is strongly associated with lung injuries, including interstitial pneumonitis and lung fibrosis, which eventually lead to death owing to the loss of lung function [ 1 , 28 , 29 , 30 ]. Lung injuries occur in people exposed to PHMG, a representative HD substance; however, less severe lung damage has been reported in people exposed to CMIT [ 4 ].…”

New-Onset and Exacerbation of Lung Diseases after Short-Term Exposures to Humidifier Disinfectant during Hospitalization

“…A Toxics 2022, 10, 371 2 of 12 review of epidemiologic studies has reported a causal association between HD exposure and the risk of HD-related lung injury (HDLI) [11]. Furthermore, a study of lung injury cases suggested a higher risk of lung injury in people associated with HD use than those with insecticide uses, indoor molds, and only humidifier uses (without HD) at home [12], and a previous study suggested that HD exposure was associated with lung diseases, including idiopathic interstitial pneumonia [13].…”