Skin and respiratory ill-health attributed to occupational face mask use.

BACKGROUND: Face mask use in the workplace has become widespread since the onset of the Covid-19 pandemic and has been anecdotally linked to adverse health consequences. AIMS: To examine reports of adverse health consequences of occupational face mask use received by The Health and Occupation Research (THOR) network before and after the pandemic onset. METHODS: THOR databases were searched to identify all cases of ill-health attributed to 'face mask' or similar suspected causative agent between 1 January 2010 and 30 June 2021. RESULTS: Thirty two cases were identified in total, 18 reported by occupational physicians and 14 by dermatologists. Seventy-five per cent of cases were reported after the pandemic onset and 91% cases were in the health and social care sector. 25 of the 35 (71%) diagnoses were dermatological, the most frequent diagnoses being contact dermatitis (14 cases) and folliculitis/acne (6 cases). Of the seven respiratory diagnoses, four were exacerbation of pre-existing asthma. CONCLUSIONS: There is evidence of an abrupt increase in reports of predominantly dermatological ill-health attributed to occupational face mask use since the start of the pandemic. Respiratory presentations have also occurred.

Chemical determinants of occupational hypersensitivity pneumonitis.

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.

A refined QSAR model for prediction of chemical asthma hazard.

BACKGROUND: A previously developed quantitative structure-activity relationship (QSAR) model has been extern ally validated as a good predictor of chemical asthma hazard (sensitivity: 79-86%, specificity: 93-99%). AIMS: To develop and validate a second version of this model. METHODS: Learning dataset asthmagenic chemicals with molecular weight (MW) <1 kDa were identified from reports published in the peer-reviewed literature before the end of 2012. Control chemicals for which no reported case(s) of occupational asthma had been identified were selected at random from UK and US occupational exposure limit tables. MW banding was used in an attempt to categorically match the control group for MW distribution of the asthmagens. About 10% of chemicals in each MW category were excluded for use as an external validation set. An independent researcher utilized a logistic regression approach to compare the molecular descriptors present in asthmagens and controls. The resulting equation generated a hazard index (HI), with a value between zero and one, as an estimate of the probability that the chemical had asthmagenic potential. The HI was determined for each compound in the external validation set. RESULTS: The model development sets comprised 99 chemical asthmagens and 204 controls. The external validation showed that using a cut-point HI of 0.39, 9/10 asthmagenic (sensitivity: 90%) and 23/24 non-asthmagenic (specificity: 96%) compounds were correctly predicted. The new QSAR model showed a better receiver operating characteristic plot than the original. CONCLUSIONS: QSAR refinement by iteration has resulted in an improved model for the prediction of chemical asthma hazard.

Development of mechanism-based structural alerts for respiratory sensitization hazard identification.

This study outlines how mechanistic organic chemistry related to covalent bond formation can be used to rationalize the ability of low molecular weight chemicals to cause respiratory sensitization. The results of an analysis of 104 chemicals which have been reported to cause respiratory sensitization in humans showed that most of the sensitizing chemicals could be distinguished from 82 control chemicals for which no clinical reports of respiratory sensitization exist. This study resulted in the development of a set of mechanism-based structural alerts for chemicals with the potential to cause respiratory sensitization. Their potential for use in a predictive algorithm for this purpose alongside an externally validated quantitative structure-activity relationship model is discussed.

Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds.

AIMS: To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships. METHODS: A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model. RESULTS: Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%. CONCLUSIONS: Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard.

Anaphylaxis caused by neostigmine.

A patient developed anaphylaxis during anaesthesia, towards the end of surgery, 30 s after intravenous administration of neostigmine. Anaphylaxis to neostigmine was confirmed by demonstrating an elevated mast cell tryptase and a strongly/positive skin prick test, showing the presence of drug-specific IgE (skin prick tests to neostigmine were negative in normal subjects). This is a rare cause of anaphylaxis during anaesthesia.