Purpose of review
Isocyanates, reactive chemicals used to generate polyurethane, are a leading cause of occupational asthma worldwide. Workplace exposure is the best-recognized risk factor for disease development, but is challenging to monitor. Clinical diagnosis and differentiation of isocyanates as the cause of asthma can be difficult. The gold-standard test, specific inhalation challenge, is technically and economically demanding, and is thus only available in a few specialized centers in the world. With the increasing use of isocyanates, efficient laboratory tests for isocyanate asthma and exposure are urgently needed.
The review focuses on literature published in 2005 and 2006. Over 150 articles, identified by searching PubMed using keywords ‘diphenylmethane’, ‘toluene’ or ‘hexamethylene diisocyanate’, were screened for relevance to isocyanate asthma diagnostics. New advances in understanding isocyanate asthma pathogenesis are described, which help improve conventional radioallergosorbent and enzyme-linked immunosorbent assay approaches for measuring isocyanate-specific IgE and IgG. Newer immunoassays, based on cellular responses and discovery science readouts are also in development.
Contemporary laboratory tests that measure isocyanate-specific human IgE and IgG are of utility in diagnosing a subset of workers with isocyanate asthma, and may serve as a biomarker of exposure in a larger proportion of occupationally exposed workers.
Diisocyanates (toluene diisocyanate, TDI; hexamethylene diisocyanate, HDI; and diphenylmethane diisocyanate, MDI) or functionally similar polymeric isocyanates are the obligate cross-linking agent for the commercial production of polyurethane, a polymer upon which modern society has become dependent. Millions of tons of isocyanate are produced and consumed annually throughout the world in a wide variety of end-use work environments [1,2–5,6•,7•]. Workplace exposure remains the best-recognized risk factor for isocyanate asthma, but is complicated to quantitate, involving mixtures of isomers and ‘prepolymers’ diluted in solvents, in aerosol and vapor phases. In certain occupational settings, exposure can cause isocyanate asthma and long-lasting bronchial hyperreactivity [1,8,9,10•,11•]. Early recognition of isocyanate asthma and prompt removal from isocyanate exposure improves the long-term prognosis for sensitive individuals . There thus exists the need for practical screening/diagnostic tests for isocyanate asthma as well as tests that can monitor personal exposure.
The clinical presentation of isocyanate asthma is strikingly similar to common environmental asthma, prompting the hypothesis that the disease has an immunological basis, although subtle differences have been noted [9,10•,12•]. Animal models support this hypothesis, and are beginning to dissect the potential role of individual genes with transgenic strains [13••,14••,15,16••,17,18]. Allergists and immunologists have overcome substantial challenges working with reactive isocyanates to develop serology assays for isocyanate-specific antibodies [19–21]. Such assays have provided evidence to support allergic asthma to isocyanate in a small percentage of workers, but cannot detect isocyanate-specific IgE in the majority of sensitive individuals. These results have left great uncertainty in the field. Does isocyanate asthma involve mechanisms of pathogenesis (e.g. non-IgE) distinct from those in common atopic asthma or are specific IgE antibodies present, but our detection assay for them is flawed? Are we using the wrong antigenic form of isocyanate in our serology tests, or testing workers at the wrong time (after removal from exposure)? Does isocyanate asthma, as presently defined, possibly represent a spectrum of diseases, which only in some cases is associated with an antibody response [3,9,10•]?
The present review summarizes the rationale and use of clinical laboratory tests for immune responses that reflect isocyanate exposure and asthma, with emphasis on data generated within the past year. The potential utility of ‘isocyanate-specific’ serum IgE and IgG as biomarkers and the isocyanate antigen recognized by these immunoglobulins are described [22••,23]. Clinical usage and limits of contemporary assays for isocyanate asthma and exposure are discussed along with promising future assays [20,24,25••].
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The Irish Army Air Corps has dismissed a number of previously fit personnel as suffering from asthma. It has never carried out a health study of personnel exposed long term and without protection to Isocyanates and has never carried out adequate risk specific health surveillance. Neither has the Air Corps ever carried out risk specific health surveillance for personnel who suffered long term exposure to jet fuel & jet exhaust gasses.
Bizarrely serving and former Air Corps personnel have been “reassured” by Air Corps medical personnel that their asthma does not have a workplace related cause despite no evidence of any testing for them to form a conclusion either way.
Considering what is now known about the extremely poor chemical health & safety environment in the Irish Air Corps any doctor, dismissing without appropriate testing, any possibility of a workplace casual link is surely opening himself or herself up to accusations of professional misconduct.