Improving trends estimates for specific work-related ill-health conditions when excess zeros are present in a voluntary health reporting scheme.

BACKGROUND: Trends in occupational disease incidence are estimated in voluntary reporting schemes such as The Health and Occupational Reporting (THOR) Network in the UK. Voluntary reporting schemes request responses even if no cases are observed to reduce uncertainty in non-response. This may result in false zeros that bias trends estimates. Analysis using zero-inflated models is unsuitable for specific health outcomes due to overestimates of the excess zeros. Here, we attempt to account for excess zeros while investigating condition-specific trends. METHODS: Zero-inflated negative binomial (ZINB) models were fitted to three THOR work-related ill health surveillance schemes Occupational Skin Disease Surveillance (437 reporters between 1996 and 2019), Occupational Physicians Reporting Activity (1094 between 1996 and 2019) and Surveillance of Work-Related and Occupational Respiratory Disease (878 between 1999 and 2019). The probability associated with a response being a false zero was estimated and applied in weighted negative binomial (wgt-NB) models fitted to specific ill-heath conditions. Three ill-health conditions from the three THOR schemes were considered; contact dermatitis, musculoskeletal and asthma, respectively. RESULTS: Wgt-NB models approximately estimated the incidence rate ratios reported by the ZINB models (eg, EPIDERM; ZINB=0.969, NB=0.963, wgt-NB=0.968) for all health outcome annual trends. This was consistent for specific health outcomes which also tended towards the null (eg, contact dermatitis; NB=0.964, wgt-NB=0.969), indicating potentially overestimated downward trends. Though as the ratio of excess zeros to true zeros decreased in rarer health outcomes, the influence on trends also decreased. CONCLUSIONS: Through weighting, we were able to adjust for excess zeros in health outcome-specific trends estimates. Though uncertainty is still present in underlying reporter behaviour meaning caution should be applied with interpretation of any results.

Insufficient respiratory hazard identification in the safety data sheets for cleaning and disinfection products used in healthcare organisations across England and Wales.

BACKGROUND: Exposure to cleaning and disinfection products has been associated with respiratory disorders such as asthma in cleaning and healthcare workers. Safety data sheets (SDSs) provide information on hazardous chemicals that are present in products to help users with risk assessment and implement appropriate control measures. However, they have potential limitations in identifying respiratory hazards due to a lack of regulatory test methods for respiratory sensitisation and irritation of chemicals. METHODS: SDSs were first used to identify chemicals on the database as respiratory sensitisers and irritants. A quantitative structure-activity relationship (QSAR) model and an asthmagen list established by the Association of Occupational and Environmental Clinics (AOEC) were used to identify potential respiratory sensitisers and irritants (by the AOEC list only) in the cleaning and disinfection products. RESULTS: From a total of 459 cleaning and disinfection products used in healthcare organisations across England and Wales, 35 respiratory sensitisers not labelled as such on the SDS were identified by QSAR or AOEC. Only 2% of cleaning and disinfection products contained at least one respiratory sensitiser as identified by their SDSs; this was increased to 37.7% of products when the QSAR or the AOEC list was used. CONCLUSIONS: A significantly higher proportion of cleaning products contain respiratory hazardous chemicals, particularly respiratory sensitisers than would be expected from the information provided by SDSs alone. Cleaners and healthcare workers may, therefore, be insufficiently protected.

Occupational and work-related respiratory disease attributed to cleaning products.

OBJECTIVES: Exposure to cleaning products has been associated with adverse respiratory outcomes. This study aimed to investigate the medically reported incidence, trends in incidence and occupational determinants of work-related respiratory disorders attributed to cleaning agents and to explore the role of 'Quantitative Structure Activity Relationships' (QSAR) in corroborating the identification of chemical respiratory sensitisers. METHODS: Respiratory diagnoses attributed to cleaning agents were extracted from The Health and Occupation Research (THOR) surveillance network, 1989-2017. Incidence, trends in incidence and incidence rate ratios by occupation were investigated. Agents were classified by chemical type and QSAR hazard indices were determined for specific organic chemicals. RESULTS: Approximately 6% (779 cases) of the (non-asbestos) THOR respiratory cases were attributed to cleaning agents. Diagnoses were predominantly asthma (58%) and inhalation accidents (27%) with frequently reported chemical categories being aldehydes (30%) and chlorine/its releasers (26%). No significant trend in asthma incidence (1999-2017) was observed (annual average change of -1.1% (95% CI -4.4 to 2.4)). This contrasted with a statistically significant annual decline in asthma incidence (-6.8% (95% CI -8.0 to -5.6)) for non-cleaning agents. There was a large variation in risk between occupations. 7 of the 15 organic chemicals specifically identified had a QSAR generated hazard index consistent with being a respiratory sensitiser. CONCLUSION: Specific occupations appear to be at increased risk of adverse respiratory outcomes attributed to cleaning agents. While exposure to agents such as glutaraldehyde have been addressed, other exposures, such as to chlorine, remain important. Chemical features of the cleaning agents helped distinguish between sensitising and irritant agents.

Emerging trends in the UK incidence of occupational asthma: should we be worried?

While 15% of adult-onset asthma is estimated to have an occupational cause, there has been evidence of a downward trend in occupational asthma incidence in several European countries since the start of this millennium. However, recent data from The Health and Occupation Reporting network in the UK have suggested a possible reversal of this downward trend since 2014. We present these data and discuss possible explanations for this observed change in incidence trend. A high index of suspicion of occupational causation in new-onset asthma cases continues to be important, whether or not the recently observed increase in occupational asthma incidence in the UK is real or artefactual.

Progress with Structure-Activity Relationship modelling of occupational chemical respiratory sensitizers.

PURPOSE OF REVIEW: This appraises currently available computer-based ('in silico') models relating the molecular structure of low molecular weight compounds to their respiratory sensitization hazard. The present review places focus on the two main applications of such structure--activity relationship (SAR) models: hypotheses on disease mechanisms and toxicological prediction. RECENT FINDINGS: Analyses of the chemical structures of low molecular weight organic compounds known to have caused occupational asthma has led to the development of mechanistic alerts usually based on electrophilic reaction chemistry and protein cross-linking potential. Protein cross-linking potential has also been found to be a consistent feature of chemicals that have caused human cases of hypersensitivity pneumonitis. Stepwise iteration of quantitative SAR (QSAR) modelling has shown appreciable improvements in predictivity for occupational asthma hazard and useful prospects for practical application. A good case has also been made for the potential use of structural alert-based mechanistic SARs in predictive toxicology. SUMMARY: Further understanding of the molecular interactions between chemical respiratory sensitizers and components of human proteins have been obtained from in-vitro and in-silico techniques. There have been developments in both qualitative (mechanistic) SARs and QSARs, which offer potential for use in a predictive algorithm for the toxicological screening of industrial chemicals for respiratory sensitization potential.

Methods for the prediction of low-molecular-weight occupational respiratory sensitizers.

PURPOSE OF REVIEW: There is recognition that respiratory sensitization is an occupational hazard of high concern. Despite international regulatory requirements there is no established protocol for the efficient prospective identification of chemical respiratory sensitizers. We review the predictive behaviour of available methods and suggest a possible high-throughput protocol. RECENT FINDINGS: Animal or in-vitro tests specific to respiratory exposure and resulting in direct asthma-related outcomes have not been developed, although the use of a local lymph node assay originally designed for skin sensitization has been advocated in a respiratory context. Various methods have been used to develop quantitative structure-activity relationship models for prediction of low-molecular-weight organic chemical respiratory sensitizers. The estimated negative predictive value for all of the published models is 1, but their differences in positive predictive value can be exploited. SUMMARY: The most pragmatic as well as valid approach for screening large numbers of industrial chemicals for respiratory sensitization hazard is likely to consist of an algorithm starting with quantitative structure-activity relationship models. Further corroboration from animal or human data, however, may be required for chemicals with a positive result by quantitative structure-activity relationship.