Long-term pathologic consequences of acute irritant-induced asthma.
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.


CONCLUSIONS
This study provides evidence of a significant eosinophilic and neutrophilic inflammation as well as remodeling in IrIa many years after an inhalational accident.
Takeda
Naoya
N
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Maghni
Karim
K
Daigle
Sylvie
S
L'Archevêque
Jocelyne
J
Castellanos
Lucero
L
Al-Ramli
Wisam
W
Malo
Jean-Luc
JL
Hamid
Qutayba
Q
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002908:Chronic Disease; D047150:Eosinophil Cationic Protein / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D007509:Irritants / Q000633:toxicity*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011795:Surveys and Questionnaires; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism
D016209:Interleukin-8; D007509:Irritants; D053773:Transforming Growth Factor beta1; D005346:Fibroblast Growth Factors; D047150:Eosinophil Cationic Protein; D020781:Matrix Metalloproteinase 1