Chemical determinants of occupational hypersensitivity pneumonitis

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 categorised 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 mechanistic chemistry for a qualitative prediction of protein cross-linking potential and determination of lipophilicity (log Kow). 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 < 0.005). Nine of ten HP causing chemicals were predicted to be protein cross-linkers compared to 24/92 controls (p<0.0001). The distributions of log Kow indicated higher values for the HP list (median 3.47) compared to controls (median 0.81) (p < 0.05). Conclusion: 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. Key words: hypersensitivity pneumonitis, occupational chemicals, occupational respiratory disease, toxic inhalatio