Unrecognized Bomb Hidden in the Babies' Room: Fatal Pulmonary Damage Related with Use of Biocide in Humidifiers

Korea Centers for Disease Control and Prevention recently suggested that prolonged inhalation of water aerosol containing biocide in humidifiers can bring about rapidly progressive respiratory fibrosis, which killed more than nine people, including four pregnant women in Korea, based on epidemiologic and toxicological studies [1-4]. It also ordered banning of six consumer products containing three responsible chemicals, oligo [2-(2-ethoxy) ethoxyethyl] guanidium chloride (PGH, Akacid) and polyhexamethyleneguanidine phosphate (PHMG phosphate, Skybio1125) or hydrochloride (PHMG HCl, Akacid plus). It suggested that extensive use of a humidifier in a poorly ventilated room with these biocides dissolved in the water could trigger development of fatal pulmonary syndrome, which has never been reported before. Using a humidifier is especially common during the winter season or in households with a respiratory infection patient or a pregnant woman. Biocide for the humidifiers first entered the market at 1994 in Korea and now more than 20 consumer products containing various biocides are available on the market. Considering widespread usage of biocide in humidifiers in this country [5], it is suggested that the total number of the victims by biocide in humidifiers could far exceed the current estimation. While it has been used so widely, what has prevented us from recognizing its hazardous effects so far? The natural course of the pulmonary syndrome, relatively minor respiratory symptoms until it reaches terminal stage with the absence of systemic involvement [2], may have played a role in its delayed reporting. A review of the pathologic findings shows that the main lesion of the damage begins in the terminal bronchiole, from which bronchiolar epithelial necrosis begins and the inflammatory lesion expands to the adjacent interstitial tissues, while alveolar space is relatively well preserved until extensive fibrosis deteriorates the respiratory functional reserve [2]. However, because of its sporadic nature related with lag time elapsed until the accumulation of toxic damage of the lung, its relationship with humidifier use was rarely suspected either by patients or clinicians. Reports of a cluster of severe respiratory failure cases among pregnant women by a pulmonologist initiated an epidemiologic survey on this unknown disease cluster [3]. Up to now, two types of health problem were reported in relation with the use of a humidifier. Humidifier fever, a relatively common respiratory disorder, is a type of hypersensitivity pneumonitis, which develops by inhalation of endotoxin produced by bacteria growing in the water of the humidifier [6]. Respiratory disorder related with inhalation of white dust develops from the mineral components of the water used in the humidifier [7]. These respiratory disorders may be disturbing, but are mostly reversible and rarely fatal or cause disability. However, the clinical syndrome of concern in this case, which is designated as a rapidly progressive respiratory fibrosis syndrome, is different because of the dose-dependent manner that shows more incidents occurring according to longer cumulative exposure over months, absence of involvement of other organ systems, high case fatality rate reaching up to 37%, and high number of victims among pregnant women and younger children [2]. Radiologically, it is characterized by bilateral diffuse peribronchial consolidation with ground glass opacity complicated by pneumothorax or pneumomediastinum in the late stage. Pathologically, it is characterized by subacute destructive and obliterative bronchiolitis and subsequent massive fibrosis. Combined with poor prognosis, it distinguishes itself from known respiratory diseases [2]. More than half of the Korean population lives in