LETTERS

A computer based asthmahazard prediction model andnew molecular weight agentsin occupational asthma

Given the high estimated prevalence andfinancial burden of occupational asthma(OA),1 2 prevention is a major concern.However, in the absence of a regulatoryscreening protocol, the respiratory sensi-tising potential of a chemical is usuallyonly apparent when it has caused ahuman case of OA.

The purpose of primary prevention isto detect hazardous agents before theoccurrence of the issue, in order to avoidexposure of workers.3

Agius et al4 have developed and vali-dated a computer based asthma hazardprediction model to predict the potentialof low molecular weight (LMW) organicagents to cause asthma due to sensitisa-tion.5 6 Based on the hazard index (HI)and using a cut-point of 0.5, the modelshowed good discriminative properties(sensitivity 79%, specificity 93%, negativepredictive value 91–100%).6

The aim of secondary prevention is theearly detection of symptomatic workersexposed to a sensitising agent.3 Secondaryprevention in OA therefore requiresknowledge of new sensitisers reported inthe literature.

More than 400 agents are known asrespiratory sensitisers able to cause OA.7

New agents are frequently reported in theliterature, as shown by Pralong et al8 in theirrecent review, 41 new LMW agents havingbeen reported between 2000 and 2010.We present in table 1 all the new

organic LMW agents published between2000 and 2012 and their HI. Metals,wood dusts and chemicals with a molecu-lar weight greater than 1000 Da areexcluded, due to the inability of themodel to calculate a HI for thesecategories.Thirteen of the compounds shown in

table 1 have their asthmagenic potentialcorroborated by a HI greater than 0.5.Among the five compounds with HI lessthan 0.5, peracetic acid showed a HI of0.03 but for the authors it is unclearwhether the mechanism inducing OA issensitisation or irritation.9 This Quantita-tive Structure-Activity Relationship model(QSAR) model is not applicable to OAdue to irritation, although the difficultiesin distinguishing clinically between irritantand sensitisation mechanisms haverecently been described.10 Moreover, spe-cific inhalation challenge (SIC) was con-ducted with a mixture of peracetic acidand hydrogen peroxide, so either couldhave been the cause of OA.In the four remaining compounds with

a HI<0.5 (namely sevoflurane, lasamideprecursor, eugenol and fluazinam), noprecise explanation can be postulated yet.However, these compounds could be

included in a future expansion of theQSAR learning set so as to furtherimprove the model by iteration.

We highlighted here the QSAR model’sability to correctly predict the asthmagenicpotential of new organic LMWagents.

Jacques André Pralong,1 Martin J Seed,2

Ranya Yasri,1 Raymond M Agius,2

André Cartier,1 Manon Labrecque1

1Department of Chest Medicine, Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal,Canada2Centre for Occupational and Environmental Health,University of Manchester, .Manchester, UK

Correspondence to Dr Manon Labrecque,Department of Chest Medicine, Hôpital du Sacré-Coeurde Montréal, 5400 Boulevard GouinOuest, MontrealH4J 1C5, Canada; manon.labrecque@umontreal.ca

Contributors JAP was involved in the conception anddesign of this study and were assisted by MJS andRAA. JAP assisted by RR carried out the analysis andinterpretation of data. JAP drafted the article. ML andAC revised and improved the content. ML, MD andMSC approved the final version of the manuscript.

Competing interests None.

Provenance and peer review Not commissioned;internally peer reviewed.

To cite Pralong JA, Seed MJ, Yasri R, et al. OccupEnviron Med 2013, 70, 70.

Received 14 September 2012Revised 14 September 2012Accepted 20 September 2012Published Online First 19 October 2012

Occup Environ Med 2013;70:70.doi:10.1136/oemed-2012-101189

REFERENCES1 Ayres JG, Boyd R, Cowie H, et al. Costs of

occupational asthma in the UK. Thorax2011;66:128–33.

2 Tarlo SM, Balmes J, Balkissoon R, , et al Diagnosisand management of work-related asthma: AmericanCollege Of Chest Physicians Consensus Statement.Chest 2008;134(3 Suppl):1S–41S.

3 Tarlo SM, Liss GM. Prevention of occupationalasthma. Curr Allergy Asthma Rep 2010;10:278–86.

4 Agius RM, Nee J, McGovern B, et al. Structureactivity hypotheses in occupational asthma caused bylow molecular weight substances. Ann Occup Hyg1991;35:129–37.

5 Jarvis J, Seed MJ, Elton R, et al. Relationshipbetween chemical structure and the occupationalasthma hazard of low molecular weight organiccompounds. Occup Environ Med 2005;62:243–50.

6 Seed M, Agius R. Further validation ofcomputer-based prediction of chemical asthmahazard. Occup Med (Lond) 2010;60:115–20.

7 Malo JL, Chan-Yeung M. Agents causingoccupational asthma. J Allergy Clin Immunol2009;123:545–50.

8 Pralong JA, Cartier A, Vandenplas O, et al.Occupational asthma: new low-molecular-weightcausal agents, 2000–2010. J Allergy (Cairo)2012;2012:597306.

9 Cristofari-Marquand E, Kacel M, Milhe F, et al.Asthma caused by peracetic acid-hydrogen peroxidemixture. J Occup Health 2007;49:155–8.

10 Burge PS, Moore VC, Robertson AS. Sensitizationand irritant-induced occupational asthma withlatency are clinically indistinguishable. Occup Med(Lond) 2012;62:129–33.

Table 1 Hazard indices generated by QSAR model: Quantitative Structure-ActivityRelationship for new low molecular weight agents, 2000–2012

Name of molecule |CASnumber

Number ofasthma cases

Hazardindex

7-aminocephalosporanic acid 957-68-6 1 1Thiamphenicol 15318-45-3 3 0.99Cefterampivoxil 82547-81-7 2 17-amino-3-thiomethyl-3-cephalosporanic acid (7-TACA) 37539-03-3 1 1Thiamine 59-43-8 2 0.95Lasamideprecursor (2,4-dichloro-5-chlorosulfonylbenzoic acid) 3740-18-9 3 0.33Sevoflurane 28523-86-6 1 0Mitoxantrone 65271-80-9 1 0.955-aminosalicylicacid 89-57-6 1 0.82Uroniumsalts TBTU 125700-67-6 1–4 0.96

Dodecanedioicacid 693-23-2 1 0.953-amino-5-mercapto-1,2,4-triazole 16691-43-3 1 0.71Tetramethrin 7696-12-0 1 0.97Eugenol 97-53-0 1 0.01Peracetic acid 79-21-0 2 0.03Ortho-phthalaldehyde 643-79-8 1 0.73Fluazinam 79622-59-6 1 0Chlorendic anhydride 115-27-5 1 0.86

CAS, Chemical Abstracts Service.

70 Occup Environ Med January 2013 Vol 70 No 1

PostScript

group.bmj.com on July 17, 2014 - Published by oem.bmj.comDownloaded from

doi: 10.1136/oemed-2012-1011892012

2013 70: 70 originally published online October 19,Occup Environ Med Jacques André Pralong, Martin J Seed, Ranya Yasri, et al. occupational asthmamodel and new molecular weight agents in A computer based asthma hazard prediction

http://oem.bmj.com/content/70/1/70.full.htmlUpdated information and services can be found at:

These include:

References http://oem.bmj.com/content/70/1/70.full.html#ref-list-1

This article cites 10 articles, 5 of which can be accessed free at:

serviceEmail alerting

the box at the top right corner of the online article.Receive free email alerts when new articles cite this article. Sign up in

Notes

http://group.bmj.com/group/rights-licensing/permissionsTo request permissions go to:

http://journals.bmj.com/cgi/reprintformTo order reprints go to:

http://group.bmj.com/subscribe/To subscribe to BMJ go to:

group.bmj.com on July 17, 2014 - Published by oem.bmj.comDownloaded from