Recent developments in diisocyanate asthma.
OBJECTIVE
To summarize the latest experimental findings on diisocyanate asthma and discuss the impact of these data on our understanding of disease pathogenesis and diagnosis.


METHODS
The literature reviewed includes articles from PubMed (National Library of Medicine) published within the last 3 years (1999-2001). In addition, pertinent older references are discussed to provide a historical perspective and background.


METHODS
The data discussed were chosen to highlight key concepts relevant to diisocyanate asthma pathogenesis and are grouped accordingly.


RESULTS
In many ways, diisocyanate-induced asthma mirrors allergic asthma caused by other stimuli; however, the immune-mediated pathways believed to be central to the disease have been difficult to define. Recent studies on the human immune response to diisocyanates provide additional evidence supportive of an immune basis for pathogenesis but also highlight well-recognized differences between diisocyanate asthma and common atopic asthma. Studies on the antigenic form of diisocyanates and their interaction with epithelial tissues provide new insights that may help explain these apparent immunologic differences. Genetic factors that influence disease have begun to be identified but remain poorly characterized. Associations of particular major histocompatibility complex class II alleles with diisocyanate asthma further fuel the hypothesis that immune-dependent mechanisms underlie pathogenesis, whereas associations of glutathione S-transferase polymorphisms (in conjunction with recent studies defining the effects of diisocyanates on thiol-redox homeostasis) may implicate additional antigen-independent mechanisms. Long-term follow-up studies of diisocyanate asthma patients have confirmed the prognostic value of early removal of symptomatic patients from exposure and highlight the need for effective diagnostic tests of sensitivity and susceptibility.


CONCLUSIONS
Diisocyanate-induced asthma appears to be a multifactorial disease involving the immune system, airway epithelium, and genetic factors. The potential long-term adverse effects of diisocyanate exposure in sensitized patients underscore the need for further studies to elucidate the pathogenesis of this disease and identify biomarkers for sensitization and susceptibility.
Liu
Qing
Q
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Wisnewski
Adam V
AV
D001249:Asthma / Q000139:chemically induced* / Q000276:immunology; D003485:Cyanates / Q000009:adverse effects*; D004847:Epithelial Cells / Q000187:drug effects; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D017953:Isocyanates / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects; D009784:Occupational Diseases / Q000139:chemically induced* / Q000276:immunology; D016273:Occupational Exposure; D012867:Skin / Q000187:drug effects; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects*; D001559:Benzhydryl Compounds
D003485:Cyanates; D017953:Isocyanates; D014051:Toluene 2,4-Diisocyanate; C015262:1,6-hexamethylene diisocyanate; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds