Alastair Robertson

Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants

Background: Despite having a work related deterioration in peak expiratory flow (PEF), many workers with occupational asthma show a low degree of within day diurnal variability atypical of non-occupational asthma. It was hypothesised that these workers would have a neutrophilic rather than an eosinophilic airway inflammatory response. Methods: Thirty eight consecutive workers with occupational asthma induced by low molecular weight agents underwent sputum induction and assessment of airway physiology while still exposed at work. Results: Only 14 (36.8%) of the 38 workers had sputum eosinophilia (>2.2%). Both eosinophilic and non-eosinophilic groups had sputum neutrophilia (mean (SD) 59.5 (19.6)% and 55.1 (18.8)%, respectively). The diurnal variation and magnitude of fall in PEF during work periods was not significantly different between workers with and without sputum eosinophilia. Those with eosinophilia had a lower forced expiratory volume in 1 second (FEV1; 61.4% v 83% predicted, mean difference 21.6, 95% confidence interval (CI) 9.2 to 34.1, p=0.001) and greater methacholine reactivity (geometric mean PD20 253 μg v 1401 μg, p=0.007). They also had greater bronchodilator reversibility (397 ml v 161 ml, mean difference 236, 95% CI of difference 84 to 389, p=0.003) which was unrelated to differences in baseline FEV1. The presence of sputum eosinophilia did not relate to the causative agent, duration of exposure, atopy, or lack of treatment. Conclusions: Asthma caused by low molecular weight agents can be separated into eosinophilic and non-eosinophilic pathophysiological variants with the latter predominating. Both groups had evidence of sputum neutrophilia. Sputum eosinophilia was associated with more severe disease and greater bronchodilator reversibility but no difference in PEF response to work exposure.

Fifteen-year trends in occupational asthma: data from the Shield surveillance scheme

BACKGROUND Trends of occupational asthma (OA) differ between regions depending on local industries, provisions for health and safety at the workplace and the availability of a reporting scheme to help in data collection and interpretation. AIM To assess trends in OA in an industrialized part of the UK over a 15-year period. METHODS Occupational and chest physicians in the West Midlands were invited to submit details of newly diagnosed cases with OA. Data were then transferred to the regional centre for occupational lung diseases for analysis. RESULTS A total of 1461 cases were reported to the scheme. Sixty-eight per cent were males with mean (standard deviation) age of 44 (12) years. The annual incidence of OA was 42 per million of working population (95% CI = 37-45). OA was most frequently reported in welders (9%) and health care-related professions (9%) while < 1% of cases were reported in farmers. Isocyanates were the commonest offending agents responsible for 21% of reports followed by metal working fluids (MWFs) (11%), adhesives (7%), chrome (7%), latex (6%) and glutaraldehyde (6%). Flour was suspected in 5% of cases while laboratory animals only in 1%. CONCLUSIONS Our data confirm a high annual incidence of OA in this part of the UK. MWFs are an emerging problem, while isocyanates remain the commonest cause. Incidence remained at a fairly stable background level with many small and a few large epidemics superimposed. Schemes like Midland Thoracic Societys Rare Respiratory Disease Registry Surveillance Scheme of Occupational Asthma could help in identifying outbreaks by linking cases at the workplace.

Corticosteroid trials in non-asthmatic chronic airflow obstruction: a comparison of oral prednisolone and inhaled beclomethasone dipropionate.

One hundred and twenty seven adults considered on clinical grounds to have non-asthmatic chronic airflow obstruction entered a randomised, double blind, placebo controlled, crossover trial comparing the physiological response to inhaled beclomethasone dipropionate 500 micrograms thrice daily with oral prednisolone 40 mg a day, both given for two weeks. One hundred and seven patients completed the study. Response was assessed as change in FEV1 and FVC measured on the last treatment day, and as change in mean peak expiratory flow (PEF) over the final seven days of treatment from home PEF recordings performed five times daily. A full response to treatment was defined as an increase in FEV or FVC, or an increase in mean daily PEF over the final seven days of treatment, of at least 20% from baseline values. An improvement in one measurement of at least 15%, or of 10% in any two measurements, was defined as a partial treatment response. Response to placebo showed a significant order effect, suggesting a carry over effect of active treatment of at least three weeks. Response to active treatment was therefore related to initial baseline values, and compared with placebo by considering responses in the first treatment phase only. A full response to oral prednisolone (16/38) was significantly more common than to placebo (3/35). The number of full responses to inhaled beclomethasone (8/34) did not differ significantly from the number responding to oral prednisolone or placebo in the first treatment phase, though full and partial responses to inhaled beclomethasone (12/34) were significantly more common than those to placebo (4/35). When all three treatment phases were considered 44/107 patients showed a full response to one or both forms of corticosteroid treatment, a response to prednisolone (39) occurring more frequently than to inhaled beclomethasone (26). Only 21 of the 44 responders showed a response to both forms of treatment. Inhaled beclomethasone dipropionate 500 micrograms thrice daily was inferior to oral prednisolone 40 mg per day, but better than placebo, in producing improvement in physiological measurements in patients thought to have nonasthmatic chronic airflow obstruction. It was, however, an effective alternative in over half of those showing a response to prednisolone.

Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant

Background: Exposure to metal working fluid (MWF) has been associated with outbreaks of extrinsic allergic alveolitis (EAA) in the USA, with bacterial contamination of MWF being a possible cause, but is uncommon in the UK. Twelve workers developed EAA in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. The study had three aims: (1) to measure the extent of the outbreak by identifying other workers who may have developed EAA or other work-related respiratory diseases; (2) to provide case detection so that those affected could be treated; and (3) to provide epidemiological data to identify the cause of the outbreak. Methods: The outbreak was investigated in a three-phase cross-sectional survey of the workforce. In phase I a respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. In phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481 (94.4%) responded and 48/50 (96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). In phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. Results: 87 workers (10.4% of the workforce) met case definitions for occupational lung disease, comprising EAA (n = 19), occupational asthma (n = 74) and humidifier fever (n = 7). 12 workers had more than one diagnosis. The peak onset of work-related breathlessness was Spring 2003. The proportion of workers affected was higher for those using MWF from a large sump (27.3%) than for those working all over the manufacturing area (7.9%) (OR = 4.39, p<0.001). Two workers had positive specific provocation tests to the used but not the unused MWF solution. Conclusions: Extensive investigation of the outbreak of EAA detected a large number of affected workers, not only with EAA but also occupational asthma. This is the largest reported outbreak in Europe. Mist from used MWF is the likely cause. In workplaces using MWF there is a need to carry out risk assessments, to monitor and maintain fluid quality, to control mist and to carry out respiratory health surveillance.

Biologically relevant assessment of dermal exposure

Dermal uptake of hazardous substances is dependent on the concentration of the material on the surface of the skin rather than its mass. It is suggested that it would be appropriate to consider the integral of concentration, over the skin surface and throughout the exposure duration, as an appropriate index of dermal exposure. For a low volatility substance this exposure index would correspond to the product of concentration, area of skin exposed and the duration of exposure. For volatile materials the magnitude of the exposure index would additionally depend on the loss of the substance by evaporation. This dermal exposure index is more likely to reflect the contribution to the overall dose received from the skin than the previously used determinations of mass of hazardous substance on the skin. Suggestions are made for possible methods of making measurements using this index.

Sensitization and irritant-induced occupational asthma with latency are clinically indistinguishable

BACKGROUND Acute irritant exposures at work are well-recognized causes of asthma. In the occupational setting, low-dose exposure to the same agent does not provoke asthma. Occupational asthma (OA) with latency due to irritants is not widely accepted. AIMS To compare workers with OA with latency likely to be due to irritant exposures with workers with the more usual sensitization-induced OA. METHODS Following identification of a worker who fulfils all the criteria for irritant-induced OA with latency whose investigation documented lime dust as a cause for his OA, we searched the Shield reporting scheme database between 1989 and 2010 for entries where the OA was more likely to be due to irritant than allergic mechanisms and compared these with the remainder where allergic mechanisms were likely. Outcome measures were latent interval from first exposure to first work-related symptom, non-specific bronchial reactivity, smoking, atopy and the presence of pre-existing asthma. RESULTS A previously fit lecturer teaching bricklaying had irritant-induced OA with latency without unusual exposures with an immediate asthmatic reaction following exposure to a sand/lime mixture (pH 8). The Shield database identified 127 workers with likely irritant-induced asthma with latency and 1646 with hypersensitivity-induced OA. The two groups were indistinguishable in terms of pre-existing asthma, atopy, age, latent interval, non-specific reactivity and smoking. CONCLUSIONS Irritant exposure is a cause of OA with latency currently clinically indistinguishable from OA due to sensitization.

Standards of care for occupational asthma: an update

Background The British Thoracic Society (BTS) Standards of Care (SoC) Committee produced a standard of care for occupational asthma (OA) in 2008, based on a systematic evidence review performed in 2004 by the British Occupational Health Research Foundation (BOHRF). Methods BOHRF updated the evidence base from 2004–2009 in 2010. Results This article summarises the changes in evidence and is aimed at physicians, nurses and other healthcare professionals in primary and secondary care, occupational health and public health and at employers, workers and their health, safety and other representatives. Conclusions Various recommendations and evidence ratings have changed in the management of asthma that may have an occupational cause.

A New Diagnostic Score for Occupational Asthma: The Area Between the Curves (ABC Score) of Peak Expiratory Flow on Days at and Away From Work

BACKGROUND Evidence-based guidelines recommend serial measurements of peak expiratory flow (PEF) on days at and away from work as the first step in the objective confirmation of occupational asthma. The aim of this study was to improve the diagnostic value of computer-based PEF analysis by using the program Oasys-2 to calculate a score from the area between the curves (ABC) of PEF on days at and away from work. METHODS Mean 2-hourly PEFs were plotted separately for workdays and rest days for 109 workers with occupational asthma and 117 control asthmatics. A score based on the ABC was computed from records containing >or= 4 day shifts, >or= 4 rest days, and >or= 6 readings per day. Patients were randomly classified into two data sets (analysis and test sets). Receiver operator characteristic (ROC) curve analysis determined a cutoff point from set 1 that best identified those with occupational asthma, which was then tested in set 2. RESULTS Logistic regression analysis showed that all ABC PEF scores were significant predictors of occupational asthma, with the best being ABC per hour from waking (odds ratio, 11.9 per 10 L/h/min; 95% confidence interval, 10.8 to 13.1). ROC curve analysis showed that a difference of 15 L/min/h provided a high specificity without compromising sensitivity in diagnosing occupational asthma. Analysis of data set 2 confirmed a specificity of 100% and sensitivity of 72%. CONCLUSION The ABC PEF score is sensitive and specific for the diagnosis of occupational asthma and can be calculated from a shorter PEF surveillance than is needed for the current Oasys-2 work effect index.

Diagnosis of occupational asthma from time point differences in serial PEF measurements

Background: The diagnosis of occupational asthma requires objective confirmation. Analysis of serial measurements of peak expiratory flow (PEF) is usually the most convenient first step in the diagnostic process. A new method of analysis originally developed to detect late asthmatic reactions following specific inhalation testing is described. This was applied to serial PEF measurements made over many days in the workplace to supplement existing methods of PEF analysis. Methods: 236 records from workers with independently diagnosed occupational asthma and 320 records from controls with asthma were available. The pooled standard deviation for rest day measurements was obtained from an analysis of variance by time. Work day PEF measurements were meaned into matching 2-hourly time segments. Time points with mean work day PEF statistically lower (at the Bonferroni adjusted 5% level) than the rest days were counted after adjusting for the number of contributing measurements. Results: A minimum of four time point comparisons were needed. Records with ⩾2 time points significantly lower on work days had a sensitivity of 67% and a specificity of 99% for the diagnosis of occupational asthma against independent diagnoses. Reducing the requirements to ⩾1 non-waking time point difference increased sensitivity to 77% and reduced specificity to 93%. The analysis was only applicable to 43% of available records, mainly due to differences in waking times on work and rest days. Conclusion: Time point analysis complements other validated methods of PEF analysis for the diagnosis of occupational asthma. It requires shorter records than are required for the Oasys score and can identify smaller changes than other methods, but is dependent on low rest day PEF variance.

Perceptions of illness and their impact on sickness absence

BACKGROUND A patients perception of their illness can influence their coping ability, compliance with treatment and functional recovery. Psychological interventions to address negative beliefs may facilitate an earlier return to work. AIMS To compare perceptions of illness, fitness to return to work and time to return to work among employees with those of their occupational physicians (OPs). METHODS A cross-sectional study of employees off sick for >2 weeks, with the return to work date ascertained at 3 months. Employees and their OPs completed similar questionnaires that included the Brief Illness Perception Questionnaire. RESULTS Of total, 84 employees (76% response rate) and nine OPs participated. Employees reported a greater impact on their life (P < 0.01), a longer duration of illness (P < 0.01), more symptoms (P < 0.01), more concern about their illness (P < 0.01), more emotional impact of their illness (P < 0.01) and that their illness was more serious (P < 0.01) than did the OPs. They attributed their illness to work more often than their OPs (P < 0.05) and predicted more accurately when they would be fit to return to work (P < 0.01). Employees who returned to work believed that their illness was shorter lasting (P < 0.01), more treatable (P < 0.01), more controllable (P < 0.05), less serious (P < 0.01), had less emotional impact (P < 0.01), perceived fewer symptoms (P < 0.05) and had less concern (P < 0.05) than those who failed to return to work. CONCLUSIONS Employees had more negative perceptions about their illness than OPs. Positive perceptions were associated with an earlier return to work. Unhelpful negative beliefs about illness need to be addressed by OPs.