Respiratory symptoms in insect breeders.

BACKGROUND: A number of specialist food suppliers in the UK breed and distribute insects and insect larvae as food for exotic pets, such as reptiles, amphibians and invertebrates. AIMS: To investigate the extent of work-related (WR) symptoms and workplace-specific serum IgE in workers potentially exposed to a variety of biological contaminants, including insect and insect larvae allergens, endotoxin and cereal allergens at a UK specialist insect breeding facility. METHODS: We undertook a study of respiratory symptoms and exposures at the facility, with subsequent detailed clinical assessment of one worker. All 32 workers were assessed clinically using a respiratory questionnaire and lung function. Eighteen workers consented to provide serum for determination of specific IgE to workplace allergens. RESULTS: Thirty-four per cent (11/32) of insect workers reported WR respiratory symptoms. Sensitization, as judged by specific IgE, was found in 29% (4/14) of currently exposed workers. Total inhalable dust levels ranged from 1.2 to 17.9 mg/m(3) [mean 4.3 mg/m(3) (SD 4.4 mg/m(3)), median 2.0 mg/m(3)] and endotoxin levels of up to 29435 EU/m(3) were recorded. CONCLUSIONS: Exposure to organic dusts below the levels for which there are UK workplace exposure limits can result in respiratory symptoms and sensitization. The results should alert those responsible for the health of similarly exposed workers to the potential for respiratory ill-health and the need to provide a suitable health surveillance programme.

Approaches to the diagnosis and management of occupational asthma amongst UK respiratory physicians.

This study aimed to assess the approach to the diagnosis and management of occupational asthma amongst general (non-specialist) respiratory consultants in the UK. A random sample of 100 UK general respiratory physicians were invited to participate, and asked to provide information on their diagnostic approach to a case scenario of a patient with possible occupational asthma relating to flour exposure. Participation rates were 42% for the main part of the study. Less than half of consultants specifically reported they would ask whether symptoms improved away from work, and just over a third mentioned examining the patient. All of those interviewed recommended a chest X-ray, and 98% simple spirometry. Eighty-six per cent suggested measurement of serial peak flows, recorded for between 2 and 8 weeks, with measurements taken half-twelve hourly. Less than half advocated a specific flour allergy test, and almost one-quarter (23%) would not perform any immunological test at all. Once a diagnosis of occupational asthma was confirmed, less than two-thirds of those interviewed commented they would recommend some form of exposure reduction, and only 28% specifically stated they would offer compensation advice. The diagnosis of occupational asthma by general respiratory physicians within the UK lacks standardisation, and in some cases falls short of evidence-based best practise.

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.

Dust related risks of clinically relevant lung functional deficits.

AIM: To quantify the risks of clinically important deficits of FEV1 in coal miners in relation to cumulative and average concentrations of respirable dust. METHODS: Data were studied from over 7000 men who had been surveyed in the late 1970s. Linear regression equations for the association between FEV1 and self-reported breathlessness on mild exertion were used to define clinically important levels of FEV1 deficit, and the probabilities that individuals with different dust exposures would experience these deficits were calculated. RESULTS: Levels of FEV1 were lower among breathless men than among others, with a large overlap of the distributions. The relations between standardised FEV1 and breathlessness were constant over all age and smoking groups. A decrease of 100 ml in FEV1 was associated with an increase of 1.12 in the odds of reporting breathlessness. FEV1 deficits of -0.367, -0.627, and -0.993 l (designated as "small", "medium", and "large" deficits) were, on average, associated with proportional increases of risks of breathlessness by factors of 1.5, 2.0, and 3.0 respectively. Cumulative respirable dust exposure ranged up to 726 gh/m3, mean 136 gh/m3 (British Medical Research Council measurement convention). An increase of 50 gh/m3 was associated with an increase of about 2% in the proportion of men with small deficits in FEV1. For medium deficits the increases ranged from 1.5% to 2%, depending on age. A similar pattern was seen for large deficits, but with smaller increases. CONCLUSIONS: In the unlikely event of continuous exposure at the proposed new maximum respirable dust limit for British mines of 3 mg/m3 (ISO-CEN measurement convention) for a working lifetime, the risk of a medium deficit of FEV1 for a non-smoker at age 60 would be estimated to be 34%, compared with 25% for zero dust exposure; for smokers, about 54% compared with 44%.

Quantifying the advantages and disadvantages of pre-placement genetic screening.

BACKGROUND: Tests of genotype may enable workers at unusual risk of future ill-health to be identified. Using them to select for employment, however, entails gains and losses to employers and employees. Ensuring a fair balance between the rights and obligations of each group requires a value judgement, but the advantages and disadvantages to interested parties must first be quantified in a meaningful way. METHOD AND RESULTS: The purposes of pre-employment screening are reviewed, and several simple measures relevant to the separate interests of employers and job applicants proposed-number screened to prevent a single adverse outcome; number excluded to prevent a case; expected incidence of the adverse outcome in those excluded; and preventable fraction. The derivation of these measures is illustrated, and the factors that influence them (the prevalence of the prognostic trait, the relative risk that it carries for an adverse outcome, and the overall incidence of disease) are related algebraically and graphically, to aid judgement on the utility of screening under different circumstances. CONCLUSIONS: In sensitive areas such as genetic testing the onus should be on the employer to justify plans for pre-placement screening. Several quantitative measures can be used to inform the ethical and economic debate about screening and to evaluate alternative strategies for prevention.

Prevalence of sensitisation to cellulase and xylanase in bakery workers.

AIMS: To assess the prevalence of sensitisation to a range of exogenous fungal enzymes used in bakeries, and determine the relation between sensitisation and work related symptoms. METHODS: Serum samples (n = 135) from a previous cross sectional study investigating the prevalence of respiratory symptoms and sensitisation to dust components, were reanalysed for specific IgE to the mixed enzymes cellulase, hemicellulase, and xylanase. RESULTS: Eight (6%) of sera tested had detectable specific IgE to mixed enzymes (excluding fungal alpha-amylase) and 16 (12%) to fungal alpha-amylase. A significant increase (p = 0.03) in nasal symptoms was found in those workers sensitised to enzymes (including alpha-amylase and the mixed enzymes, but with or without sensitisation to wheat flour) when compared to those sensitised to wheat flour alone. Both groups had significantly greater levels of nasal symptoms in comparison to those with no evidence of sensitisation. CONCLUSIONS: The association between specific IgE to mixed enzymes, and an increased prevalence of nasal symptoms in individuals sensitised to enzymes, highlights the importance of measuring sensitisation to the full range of exogenous enzymes used in the baking industry, as well as to wheat flour.

Monocyte CD14 response following endotoxin exposure in cotton spinners and office workers.

BACKGROUND: Monocyte cell surface CD14 acts as the major lipopolysaccharide (LPS) binding structure, and as such is of interest in the etiology of LPS induced disease. METHODS: The objective was to assess change in monocyte cell surface CD14 and CD4+ CD25+ lymphocytes in a group of cotton workers exposed to LPS over a working week, and to compare this to changes in office workers. Twenty-five cotton workers and nine office workers were studied. Monocyte CD14 fluorescence was measured by flow cytometry, on samples taken pre-shift on a Monday morning (baseline/pre-exposure), and subsequently after 6 and 72 hr. The majority of cotton workers were exposed to at least 1 EU/m(3) of endotoxin over a working shift, and some highly exposed (between 100 and 400 EU/m(3)). RESULTS: After 6 hr of work in the mill, cotton workers developed a significant upregulation in CD14 in comparison to office workers (P = 0.016), whereas CD14 expression had returned to levels not significantly differing from the office workers at 72 hr after first work exposure (P = 0.426). CONCLUSIONS: We propose that CD14 expression on monocytes may help to determine the mechanism of action of lipopolysaccharide in producing respiratory ill health, and may ultimately play a role in monitoring the health effect associated with LPS exposure in the workplace.

Evidence for the activation of organophosphate pesticides by cytochromes P450 3A4 and 2D6 in human liver microsomes.

The role of specific cytochrome P450 isoforms in catalysing the oxidative biotransformation of the organophosphorothioate pesticides parathion, chlorpyrifos and diazinon into structures that inhibit cholinesterase has been investigated in human liver microsomes using chemical inhibitors. Pesticides were incubated with human liver microsomes and production of the anticholinergic oxon metabolite was investigated by the inhibition of human serum cholinesterase. Quinidine and ketoconazole at 10 micromol/l inhibited oxidative biotransformation. Compared to control incubations (no inhibitor) where cholinesterase activity was inhibited to between 1 and 4% of control levels, incorporation of the CYP2D6 inhibitor quinidine into the microsomal incubation resulted in cholinesterase activity of 50% for parathion, 38% for diazinon and 30% for chlorpyrifos. Addition of the CYP3A4 inhibitor ketoconazole to microsomal incubations resulted in 66% cholinesterase activity with diazinon, 20% with parathion and 5% with chlorpyrifos. The unexpected finding that CYP2D6, as well as CYP3A4, catalysed oxidative biotransformation was confirmed for chlorpyrifos and parathion using microsomes prepared from a human lymphoblastoid cell line expressing CYP2D6. While parathion has been investigated only as a model compound, chlorpyrifos and diazinon are both very important, widely used pesticides and CYP2D6 appears to be an important enzyme in their bioactivation pathway. CYP2D6 is polymorphic and hence may influence individual susceptibility to exposure to chlorpyrifos and diazinon as well as other structurally similar pesticides.

Rates of spontaneous reactivation and aging of acetylcholinesterase in human erythrocytes after inhibition by organophosphorus pesticides.

The in vitro rates of spontaneous reactivation and aging in human erythrocyte acetylcholinesterase were studied after inhibition by a dimethoxy (R1R2) and diethoxy substituted (R1R2) organophosphate pesticide (OP) of general structure R1R2P(O)X. These have been compared with data for human plasma cholinesterase previously reported using a similar methodology. A significantly slower rate of aging for erythrocyte acetylcholinesterase was found compared to plasma cholinesterase, whether inhibited by dimethoxy or diethoxy substituted OPs. For diethoxy OPs the rate of spontaneous reactivation of the inhibited plasma enzyme was significantly slower than for the inhibited red cell enzyme. This acetylcholinesterase, and previously published plasma cholinesterase, data suggest that in practise a blood sample taken 30-40 h after significant acute OP exposure will still show inhibition in either plasma or erythrocyte cholinesterase when analysed, but that any inhibited plasma enzyme is more likely to be in the aged form. In contrast a substantial proportion of the erythrocyte acetylcholinesterase is found unaged and therefore sensitive to reactivation by oximes. Samples from an occupational exposure where depressions in plasma or erythrocyte cholinesterase activity from baseline measurements were reactivated ex vivo using the oxime 2-PAM support this hypothesis. These data also confirm that the plasma enzyme is a more sensitive than erythrocyte acetylcholinesterase as an indicator of OP exposure and thus the potential value of ex vivo oxime reactivation of erythrocyte acetylcholinesterase in a blood sample to indicate subclinical OP exposure may be limited. However, this study is too small to draw conclusions on the sensitivity of ex vivo oxime reactivation of acetylcholinesterase as a novel biomarker of excessive OP absorption. Given that there is a better relationship between anticholinergic symptoms and red cell acetylcholinesterase inhibition, and that the slower resynthesis rate of any aged or inhibited red cell enzyme may be interpretatively useful when venepuncture is delayed, it is suggested that red cell acetylcholinesterase activity does have a place in monitoring potential OP exposure.

Observations from six years' experience of a health and safety research ethics committee.

The work of the Health and Safety Executive Research Ethics Committee is presented in the light of 100 studies submitted for consideration over its first six years of operation. Ethical issues which have arisen in the context of this non-therapeutic research, and which are considered by the committee to be of particular importance are highlighted and exemplified by specific case studies.

Future impact of genetic screening in occupational and environmental medicine.

New genetic technologies open up the possibility of predictive screening, both for individual genetic risk factors for susceptibility to workplace hazards and for late onset (both single gene and multifactorial) hereditary disease. Although the initiative for testing may lie with employers and employees there are many potential stakeholders--from family members and workplace colleagues to insurers and society in general. The role of the occupational health professional will not only involve the contextual interpretation of genetic test results but also the myriad of associated ethical and moral questions. This paper considers a range of ethical issues with which the occupational health professional may be confronted as genetic technology advances.

The measurement of 'environmental tobacco smoke' particulates.

An analysis of sidestream smoke particulates in a wide range of study conditions, utilizing a variety of methods of measurement, was undertaken. The conclusion is that the term 'total particulate matter', as defined for mainstream smoke, has little or no meaning in the context of environmental tobacco smoke. Light-scattering instruments offer, in terms of portability and short sampling times, the best option for ambient particulate measurement. However, any quantitative interpretation of the results is dependent upon the initial calibration.

Switching to low tar cigarettes: are the tar league tables relevant?

Representative samples of smokers of regular middle tar and regular low tar cigarettes responded to a questionnaire concerning their smoking habits and participated in a blind product test, returning 24 hour butt collections from the smoking of both middle tar and low tar cigarettes. An estimate of the mouth intake of tar derived from a measurement of filter nicotine confirmed partial compensation by the low tar smokers relative to the middle tar smokers, resulting in 32% lower tar delivery rather than the 46% expected from the standard machine values. Most middle tar smokers (98%) achieved an estimated tar delivery within or below that of the league table middle tar band when smoking middle tar cigarettes, while 70% of low tar smokers had a mouth intake of 10 X 49 mg or below within the low tar band when smoking low tar cigarettes. These results support the current tar league tables as a guide to the smoker in selecting a lower delivery cigarette.

Respiratory impairment induced by smoking in children in secondary schools.

A longitudinal study was carried out from 1975 to 1979 in a cohort of 405 secondary school children. At yearly intervals they underwent a series of tests of pulmonary function designed to monitor lung development; some of these tests are relatively sensitive indicators of early abnormalities. A self administered questionnaire provided details of smoking habits and respiratory symptoms. The prevalence of smoking increased with age; most of those smoking at 16 had already been smoking, at least experimentally, at 13. Taking up smoking was clearly associated with the early onset of cough, production of phlegm, and shortness of breath on exertion. After two years of smoking more than a few cigarettes a day the children who smoked appeared considerably less healthy than their non-smoking peers and showed some evidence of early obstruction of the airways.

Patterns of smoking: measurement and variability in asymptomatic smokers.

Measurements of patterns of puffing (cigarette-holder pneumotachograph) and ventilation (plethysmography) were made in ten asymptomatic smokers during the smoking of a cigarette, on four separate occasions. There were marked individual differences and these were consistent over 3-5 weeks. In itself, the pattern of smoking could be responsible for a threefold variation in smoke intake. Puffing but not inhalation became less intense as a cigarette was smoked. It was not possible to predict indices of absorption from smoking patterns. Certain smoking patterns, e.g. small puff volume, low puff frequency, short duration of inhalation and expulsion of volume between puff and inhalation, may be less harmful than others and this may explain why some individuals remain healthy despite a lifetime of smoking.

Cigarette smoking among secondary schoolchildren 1975-79.

A questionnaire relating to smoking habits, respiratory symptoms, and health attitude was administered to schoolchildren aged between 11 and 17 throughout a defined geographical area in both 1975 and 1979, with a valid response from 10498 and 12002 young people respectively. Each cohort was almost entirely different. The results suggest that although the prevalence of regular smoking has decreased in boys from 16 to 13% it has increased in girls from 13 to 14% and that at all ages more girls smoke more than boys. However despite the fall in the prevalence of regular smoking in boys there has been an overall increase in cigarette consumption. Young people who are regular smokers predominantly smoke middle tar cigarettes while among experimental smokers there is a high incidence of low tar smoking, which might suggest that such cigarettes facilitate the taking up of the habit in children. The previously described relationships between smoking and respiratory symptoms was confirmed. During the 4-year study period young people's knowledge of the associated links between smoking and heart disease and stroke has increased appreciably. It is suggested that specific health education during the years 1975-79 has not been successful, and there is the need for research.