Occupational Asthma Reference

Seed MJ, Enoch SJ, Agius RM, Chemical determinants of occupational hypersensitivity pneumonitis, Occup Med, 2015;65:673-681,10.1093/occmed/kqv143

Keywords: UK, hypersensitivity pneumonitis, EAA, prediction, QSAR

Known Authors

Raymond Agius, Centre for Occupational and Environmental Health, Manchester University Raymond Agius

Martin Seed, Manchester University Martin Seed

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Abstract

Background
Workplace inhalational exposures to low molecular weight (LMW) chemicals cause hypersensitivity pneumonitis (HP) as well as the more common manifestation of respiratory hypersensitivity, occupational asthma (OA).

Aims
To explore whether chemical causation of HP is associated with different structural and physico-chemical determinants from OA.

Methods
Chemical causes of human cases of HP and OA were identified from searches of peer-reviewed literature up to the end of 2011. Each chemical was categorized according to whether or not it had been the attributed cause of at least one case of HP. The predicted asthma hazard was determined for each chemical using a previously developed quantitative structure–activity relationship (QSAR) model. The chemicals in both sets were independently and ‘blindly’ analysed by an expert in mech anistic chemistry for a qualitative prediction of protein cross-linking potential and determination of lipophilicity (log K ow).

Results
Ten HP-causing chemicals were identified and had a higher median QSAR predicted asthma hazard than the control group of 101 OA-causing chemicals (P < 0.01). Nine of 10 HP-causing chemicals were predicted to be protein cross-linkers compared with 24/92 controls (P < 0.001). The distributions of log K ow indicated higher values for the HP list (median 3.47) compared with controls (median 0.81) (P < 0.05).

Conclusions
These findings suggest that chemicals capable of causing HP tend to have higher predicted asthma hazard, are more lipophilic and are more likely to be protein cross-linkers than those causing OA.

Plain text: Background Workplace inhalational exposures to low molecular weight (LMW) chemicals cause hypersensitivity pneumonitis (HP) as well as the more common manifestation of respiratory hypersensitivity, occupational asthma (OA). Aims To explore whether chemical causation of HP is associated with different structural and physico-chemical determinants from OA. Methods Chemical causes of human cases of HP and OA were identified from searches of peer-reviewed literature up to the end of 2011. Each chemical was categorized according to whether or not it had been the attributed cause of at least one case of HP. The predicted asthma hazard was determined for each chemical using a previously developed quantitative structure-activity relationship (QSAR) model. The chemicals in both sets were independently and 'blindly' analysed by an expert in mech anistic chemistry for a qualitative prediction of protein cross-linking potential and determination of lipophilicity (log K ow). Results Ten HP-causing chemicals were identified and had a higher median QSAR predicted asthma hazard than the control group of 101 OA-causing chemicals (P < 0.01). Nine of 10 HP-causing chemicals were predicted to be protein cross-linkers compared with 24/92 controls (P < 0.001). The distributions of log K ow indicated higher values for the HP list (median 3.47) compared with controls (median 0.81) (P < 0.05). Conclusions These findings suggest that chemicals capable of causing HP tend to have higher predicted asthma hazard, are more lipophilic and are more likely to be protein cross-linkers than those causing OA.

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Comments

First attempt at a predictive model for low MW causes of HP. Chemicals capable of causing HP tend to have higher predicted asthma hazard index, are more lipophilic and are more likely to be protein cross-linkers than those causing OA.
11/23/2015

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