Sastre et al described a case of occupational asthma caused by a novel low molecular weight (LMW) respiratory sensitiser, 5-aminosalicylic acid (5-ASA) [1]. They concluded that the mechanism was probably not IgE-mediated because of a negative skin prick test and a late response to bronchial challenge testing with 5-ASA. They remarked, as is the case with several other LMW asthmagens, that the mechanism by which 5-ASA caused asthma is unknown.

Such uncertainty, and likely heterogeneity in the pathophysiological mechanisms of asthma due to LMW chemicals, is one of the reasons why no single in vitro or in vivo testing method has been developed for the prediction of asthmagenic potential. One way round this problem has been to utilise an ‘in silico’ approach that makes no a priori assumptions about pathophysiological mechanism. The development of such a quantitative structure activity relationship (QSAR) model and its initial validation was published in a previous edition of Occupational and Environmental Medicine [2]. This assigns an asthma hazard index, which is a value between zero and one, and the most recent validation [3] has demonstrated that it has good global predictive value.

By entering the chemical structure of 5-ASA (fig 1) into this model, an ‘asthma hazard index’ of 0.82 was obtained indicating a high probability of asthmagenicity.





Novel LMW chemical causes of occupational asthma such as the one reported by Sastre et al appear only intermittently in the literature but respiratory physicians have used this QSAR model to provide corroborating evidence in the identification of a novel asthmagen [4]. This model may also be of use when a clinician has diagnosed occupational asthma where the cause could be one of several LMW (organic) chemicals none of which are recognized respiratory sensitisers. By ranking the possible causes according to the QSAR-generated asthma hazard index, it may be possible to prioritise the agent(s) with which to perform bronchial challenge testing. Further evaluation of the QSAR model for this purpose is planned and we would encourage respiratory and occupational physicians to utilise the model, which is freely available on the internet [5] for such purposes, and register their interest and observations by email with the undersigned.

Dr. Martin Seed, University of Manchester

Professor Raymond Agius, University of Manchester

Martin.seed@manchester.ac.uk

REFERENCES

1. Sastre J, del Potro MG, Aguado E, et al. Occupational asthma due to 5- aminosalicylic acid. Occup Environ Med 2010;67:798-9.

2. Jarvis J, Seed MJ, Elton RA, et al. Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds. Occup Environ Med 2005;62:243-50.

3. Seed MJ, Agius RM. Further validation of computer-based prediction of chemical asthma hazard. Occup Med 2010;60:115–20.

4. Moore VC, Manney S, Vellore AD, et al. Occupational asthma to gel flux containing dodecanedioic acid. Allergy 2009;64:1099-1107.

5. The University of Manchester. Centre for Occupational and Environmental Health. Mechanisms of Occupational Asthma; Occupational asthma hazard prediction programme. http://www.medicine.manchester.ac.uk/oeh/research/asthma/ (accessed November 2010).