Medline ® Abstracts for References 1,19,40
of 'Reactive airways dysfunction syndrome and irritant-induced asthma'
Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures.
Brooks SM, Weiss MA, Bernstein IL
Ten individuals developed an asthma-like illness after a single exposure to high levels of an irritating vapor, fume, or smoke. In most instances, the high level exposure was the result of an accident occurring in the workplace or a situation where there was poor ventilation and limited air exchange in the area. In all cases, symptoms developed within a few hours and often minutes after exposure. We have designated the illness as reactive airway dysfunction syndrome (RADS) because a consistent physiologic accompaniment was airways hyperreactivity. When tested, all subjects showed positive methacholine challenge tests. No documented preexisting respiratory illness was identified nor did subjects relate past respiratory complaints. In two subjects, atopy was documented, but in all others, no evidence of allergy was identified. In the majority of the cases, there was persistence of respiratory symptoms and continuation of airways hyperreactivity for more than one year and often several years after the incident. The incriminated etiologic agent varied, but all shared a common characteristic of being irritant in nature. In two cases, bronchial biopsy specimens were available, and an airways inflammatory response was noted. This investigation suggests acute high level, uncontrolled irritant exposures may cause an asthma-like syndrome in some individuals which is different from typical occupational asthma. It can lead to long-term sequelae and chronic airways disease. Nonimmunologic mechanisms seem operative in the pathogenesis of this syndrome.
Cross-sectional assessment of workers with repeated exposure to chlorine over a three year period.
Gautrin D, Leroyer C, L'Archevêque J, Dufour JG, Girard D, Malo JL
Eur Respir J. 1995;8(12):2046.
Airflow obstruction has been described in workers who experienced symptoms after acute exposure to chlorine. Persistent bronchial hyperresponsiveness has also been assessed, but mainly in case studies. In this cross-sectional study, we have assessed the relationship between inhalational accidents ("puffs") involving chlorine and persistent symptoms as well as hyperresponsiveness in 239 out of 255 at-risk workers (94%). No relationship was found between persistent symptoms and the exposure variables studied. Forced vital capacity (FVC) was higher in subjects who had had no symptoms after a "puff", compared with those who had experienced mild symptoms. Forced expiratory volume in one second (FEV1) and FVC were significantly lower in subjects who experienced more than 10 puffs with mild symptoms than in subjects who reported no symptomatic puff. The presence of bronchial hyperresponsiveness was not related to exposure, but the methacholine dose-response slope showed a tendency to increased bronchial responsiveness with increased exposure. A significant difference was shown in subjects who experienced more than 10 puffs with mild symptoms. In this group of workers, repeated exposure to chlorine with acute respiratory symptoms was associated with a slight but significant reduction in expiratory flow rates, together with an increase in bronchial responsiveness, without long-term symptoms.
Dept of Chest Medicine, Hôpital du Sacré-Coeur, Montreal, Canada.
Chlorine-induced injury to the airways in mice.
Martin JG, Campbell HR, Iijima H, Gautrin D, Malo JL, Eidelman DH, Hamid Q, Maghni K
Am J Respir Crit Care Med. 2003;168(5):568.
Exposure to chlorine gas (Cl2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice 24 hours after a 5-minute exposure to 100, 200, 400, or 800 ppm Cl2 and 2 and 7 days after inhalation of 400 ppm Cl2. Airway responsiveness was higher 24 hours after 400 and 800 ppm Cl2. Responsiveness after inhalation of 400 ppm Cl2 returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates, and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl2. Macrophages, granulocytes, epithelial cells, and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl2 stained for 3-nitrotyrosine residues. Inhibition of inducible nitric oxide synthase with 1400W (1 mg/kg) abrogated the Cl2-induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. Inducible nitric oxide synthase is involved in the induction of changes in responsiveness to methacholine.
Meakins-Christie Laboratories, 3626 St Urbain, Montreal, Province of Quebec, H2X 2P2 Canada. email@example.com