Time-course of functional and pathological changes after a single high acute inhalation of chlorine in rats

Abstract

Reactive airways dysfunction syndrome (RADS) is an asthma-like condition that follows exposure to very high concentrations of an irritant material. We assessed the time-course of pathophysiological alterations in a model of RADS. Sprague-Dawley rats were exposed to 1,500 parts per million (ppm) of chlorine for 5 min. Lung resistance (RL), responsiveness to inhaled methacholine (MCh), the airway epithelium and bronchoalveolar lavage (BAL) were assessed over a 3 month period after exposure. RL increased significantly up to 3 days after exposure, reaching a maximal change of 110+/-16% from baseline. There was a significant decrease in the concentration of MCh required to increase RL by 0.20 cmH2O x mL(-1) x s from days 1-7 after exposure. In some rats, MCh hyperresponsiveness and RL changes persisted after exposure for as long as 1 and 3 months, respectively. Histological evaluation with morphometric evaluation revealed epithelial flattening, necrosis, increase in smooth muscle mass and evidence of epithelial regeneration. BAL showed an increased number of neutrophils. The timing of maximal abnormality in the appearance of the epithelium (days 1-3) corresponded to that of the maximal functional changes. Acute high chlorine exposure results in functional and pathological abnormalities that resolve in the majority of animals after a variable period; however, these changes can persist in some animals. Functional abnormalities in the initial stages may be related to airway epithelial damage.

Definitions and types of work-related asthma: a nosological approach

“…After the initial event, the reversibility of airway obstruction is not as constant and as marked in subjects with RADS as in those with OA or nonoccupational asthma. Moreover, the chronic pathological features point to more airway remodelling than for standard asthma [29,30]. That said, there is still sufficient clinical and functional evidence for accepting RADS as a category of asthma causally related to workplace exposure.…”

Occupational asthma: a review.

“…Development of appropriate animal models would be a major advance. Although considerable progress has been made with regard to models of HMW sensitizerinduced asthma, models of LMW sensitizerinduced asthma (79) and irritant-induced asthma following a single high-concentration exposure are still in a relatively early stage of development (80 …”

Histopathological Study of Short and Long-Term Pulmonary Effects of Nebulized Sodium Bicarbonate Treatment in Chlorine Gas Exposured Rats

“…Most of the recently reported chlorine gas exposures include exposures caused by the inhalation of toxic vapor arising from mixing of hypochlorite-containing household cleaning products with acid products. 1,8,12,16 Therefore, we obtained the chlorine gas by mixing bleach water and hydrochloric acid sold in the market. Pulmonary injury caused by chlorine gas inhalation depends on the dose and duration of inhalation.…”

“…No clinical regression has been reported in patients given nebulized sodium bicarbonate. 1,8,9 However, the use of nebulized sodium bicarbonate is yet controversial. 10 In chlorine gas exposure, rapid sodium bicarbonate administration has been suggested to neutralize the HCl arising from the reaction of chlorine gas with the water in the mucosal membranes of the respiratory tract.…”