Medline ® Abstracts for References 1,41,42
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.
Long-term pathologic consequences of acute irritant-induced asthma.
Takeda N, Maghni K, Daigle S, L'Archevêque J, Castellanos L, Al-Ramli W, Malo JL, Hamid Q
J Allergy Clin Immunol. 2009;124(5):975.
BACKGROUND: Acute irritant-induced asthma (IrIa) or reactive airways dysfunction syndrome is caused by exposure to a high concentration of an agent. The long-term pathologic consequences of IrIa remain thus far unknown.
OBJECTIVE: The aim of our study was to investigate the chronic airway inflammation and remodeling that occur in association with IrIa.
METHODS: Ten subjects with a history of IrIa (mean interval of 10.9 years, minimum of 4 years, since the inhalational accident) underwent bronchoscopy followed by bronchoalveolar lavage and bronchial biopsies. Immunologic and morphologic data from patients with IrIa were compared with those of patients with mild to moderate asthma as well as healthy controls.
RESULTS: Bronchoalveolar lavage fluid analysis showed increased eosinophil and neutrophil counts in 30% and 60% of subjects with IrIa, respectively. In the supernatant of bronchoalveolar lavage, we found a significant increase in the majority of mediators compared with healthy subjects and a significant increase in eosinophilic cationic protein, IL-8, basic fibroblast growth factor, and matrix metalloproteinase 1 compared with control patients with asthma. Evaluation of basement membrane thickness (subepithelial fibrosis) demonstrated a significant increase in patients with IrIa compared with healthy subjects and subjects with asthma. Basement membrane thickness also significantly correlated with the PC(20) value. The epithelial cell detachment showed an elevated although not significant trend compared with subjects with asthma and control subjects. Immunocytochemical analysis demonstrated increases in the number of eosinophil cationic protein and TGF-beta1-positive cells compared with healthy controls.
CONCLUSION: This study provides evidence of a significant eosinophilic and neutrophilic inflammation as well as remodeling in IrIa many years after an inhalational accident.
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Persistent asthma after repeated exposure to high concentrations of gases in pulpmills.
Chang-Yeung M, Lam S, Kennedy SM, Frew AJ
Am J Respir Crit Care Med. 1994;149(6):1676.
This is a clinicopathologic study of three subjects with irritant-induced asthma. They were pulpmill workers who had a history of multiple "gassing" episodes that occurred over a period of years. Persistent symptoms of asthma and nonspecific bronchial hyperresponsiveness and/or variable airflow obstruction occurred after at least one episode of "gassing," resulting in symptoms severe enough to require emergency room treatment. One of the three subjects had normal spirometry values before he entered the pulpmill. Bronchial biopsy done on these subjects showed changes compatible with asthma, including thickened basement membrane in two and cellular infiltration with activated eosinophils and mononuclear cells in all three. The results of immunohistology of bronchial mucosal biopsy of these subjects were compared with those of patients with allergic asthma and patients with Western red cedar-induced asthma. Subjects with irritant-induced asthma had a greater density of activated eosinophils and fewer T-lymphocytes, suggesting that cell-mediated immune mechanisms are not involved in the pathogenesis of this condition.
Department of Medicine, University of British Columbia, Vancouver General Hospital, Canada.