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Competing Interests: Competing interests: None declared.

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 >or=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 >or=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.

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.

Background: In occupational asthma continued workplace exposure to the causative agent is associated with a poor prognosis. However, there is little information available on how rapidly lung function declines in those who continue to be exposed, nor how removal from exposure affects lung function., Methods: Forced expiratory volume in 1 second (FEV1) was studied in 156 consecutive subjects with occupational asthma (87% due to low molecular weight agents) using simple regression analyses to provide estimates of the decline in FEV1 before and after removal from exposure., Results: In 90 subjects in whom FEV1 measurements had been performed for at least 1 year before removal from exposure (median 2.9 years), the mean (SE) rate of decline in FEV1 was 100.9 (17.7) ml/year. One year after removal from exposure FEV1 had improved by a mean (SE) of 12.3 (31.6) ml. The mean (SE) decline in FEV1 was 26.6 (18.0) ml/year in 86 subjects in whom measurements were made for at least 1 year (median 2.6 years) following removal from exposure. The decline in FEV1 was not significantly worse in current smokers than in never smokers, nor was it affected by the use of inhaled corticosteroids., Conclusion: FEV1 declines rapidly in exposed workers with occupational asthma. Following removal from exposure, FEV1 continued to decline but at a slower rate, similar to the rate of decline in healthy adults.

Background: Clinical studies suggest that inhaled corticosteroids reduce exacerbations and improve health status in chronic obstructive pulmonary disease (COPD). However, their effect on mortality is unknown., Methods: A pooled analysis, based on intention to treat, of individual patient data from seven randomised trials (involving 5085 patients) was performed in which the effects of inhaled corticosteroids and placebo were compared over at least 12 months in patients with stable COPD. The end point was all-cause mortality., Results: Overall, 4% of the participants died during a mean follow up period of 26 months. Inhaled corticosteroids reduced all-cause mortality by about 25% relative to placebo. Stratification by individual trials and adjustments for age, sex, baseline post-bronchodilator percentage predicted forced expiratory volume in 1 second, smoking status, and body mass index did not materially change the results (adjusted hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.55 to 0.96). Although there was considerable overlap between subgroups in terms of effect sizes, the beneficial effect was especially noticeable in women (adjusted HR 0.46; 95% CI 0.24 to 0.91) and former smokers (adjusted HR 0.60; 95% CI 0.39 to 0.93)., Conclusions: Inhaled corticosteroids reduce all-cause mortality in COPD. Further studies are required to determine whether the survival benefits persist beyond 2-3 years.

Background: A trial of corticosteroids has been recommended for all patients with chronic obstructive pulmonary disease (COPD), with the subsequent "response" determining the treatment selected. This approach assumes that patients can be reliably divided into responder and non-responder groups. We have assessed whether such a separation is statistically valid, which factors influence the change in forced expiratory volume in 1 second (FEV(1)) after prednisolone, and whether the prednisolone response predicts 3 year changes in FEV(1), health status, or number of exacerbations during placebo or fluticasone propionate treatment., Methods: Oral prednisolone 0.6 mg/kg was given for 14 days to 524 patients with COPD before randomised treatment for 3 years with fluticasone propionate or placebo. Factors relating to change in FEV(1) after prednisolone were investigated using multiple regression. The response to prednisolone was entered into separate mixed effects models of decline in FEV(1) and health status during the 3 years of the study., Results: The post-bronchodilator FEV(1) increased by a mean 60 ml (CI 46 to 74) after prednisolone with a wide unimodal distribution. Current smoking was the factor most strongly associated with the change in FEV(1) after prednisolone, with an increase of 35 ml in current smokers and 74 ml in confirmed ex-smokers (p<0.001). There was no relationship between the change in FEV(1) after prednisolone and the response to inhaled bronchodilators, baseline FEV(1), atopic status, age, or sex. The response to prednisolone, however expressed, was unrelated to the subsequent change in FEV(1) over the following 3 years on either placebo or fluticasone propionate. Regression to the mean effects explained much of the apparent prednisolone response. The significant effect of treatment on decline in health status was not predicted by the prednisolone response., Conclusion: Patients with COPD cannot be separated into discrete groups of corticosteroid responders and non-responders. Current smoking reduces the FEV(1) response to prednisolone. Prednisolone testing is an unreliable predictor of the benefit from inhaled fluticasone propionate in individual patients.

Background: A limited or absent bronchodilator response is used to classify chronic obstructive pulmonary disease (COPD) and can determine the treatment offered. The reliability of the recommended response criteria and their relationship to disease progression has not been established., Methods: 660 patients meeting European Respiratory Society (ERS) diagnostic criteria for irreversible COPD were studied. Spirometric parameters were measured on three occasions before and after salbutamol and ipratropium bromide sequentially or in combination over 2 months. Responses were classified using the American Thoracic Society/GOLD (ATS) and ERS criteria. Patients were followed for 3 years with post-bronchodilator FEV(1) and exacerbation history recorded 3 monthly and health status 6 monthly., Results: FEV(1) increased significantly with each bronchodilator, a response that was normally distributed. Mean post-bronchodilator FEV(1) was reproducible between visits (intraclass correlation 0.93). The absolute change in FEV(1) was independent of the pre-bronchodilator value but the percentage change correlated with pre-bronchodilator FEV(1) (r=-0.44; p<0.0001). Using ATS criteria, 52.1% of patients changed responder status between visits compared with 38.2% using ERS criteria. Smoking status, atopy, and withdrawing inhaled corticosteroids were unrelated to bronchodilator response, as was the rate of decline in FEV(1), decline in health status, and exacerbation rate., Conclusion: In moderate to severe COPD bronchodilator responsiveness is a continuous variable. Classifying patients as "responders" and "non-responders" can be misleading and does not predict disease progression.

Background: Oasys-2 is a validated diagnostic aid for occupational asthma that interprets peak expiratory flow (PEF) records as well as generating summary plots. The system removes inconsistency in interpretation, which is important if there is limited agreement between experts. A study was undertaken to assess the level of agreement between expert clinicians interpreting serial PEF measurements in relation to work exposure and to compare the responses given by Oasys-2., Method: 35 PEF records from workers under investigation for suspected occupational asthma were available for review. Records included details of nature of work, intercurrent illness, drug therapy, predicted PEF, rest periods, and holidays. Simple plots of PEF and the Oasys-2 generated plots were available. Experts were advised that approximately 1 hour was available to review the records. They were asked to score each work-rest-work (WRW) period and each rest-work-rest (RWR) period for evidence of occupational effect. At the end of each record scores of 0-100% were given for evidence of "asthma" and "occupational effect" for the whole record. Kappa values were calculated for each scored period and for the opinions on the whole record. The scores were converted into four groups (0-25%, 26-50%, 51-75%, 76-100%) and two groups (0-50% and 51-100%) for analysis. This is relevant to scores produced by Oasys-2. Agreement between Oasys-2 scores and each expert was calculated., Results: 24 of 35 records were analysed by seven experts in the allotted time. For whole record occupational effect, median kappa values were 0.83 (range 0.56-0.94) for two groups and 0.62 (0.11-0.83) for four groups. For asthma, median kappa values were 0.58 (0-0.67) and 0.42 (0.15-0.70) for two and four groups respectively. For all WRW and RWR periods kappa values were 0.84 (0.42-0.94) and 0.70 (0.46-0.87) respectively. Agreement between Oasys-2 and individual experts showed a median kappa value of 0.75 (0.50-0.92) for two groups and 0.50 (0.39-0.70) for four groups. Kappa values for the median expert score v Oasys-2 were 0.75 for two groups and 0.67 for four groups. Agreement was poor for records with intermediate probability, as defined by Oasys-2., Conclusion: Considerable variation in agreement was seen in expert interpretation of occupational PEF records which may lead to inconsistencies in diagnosis of occupational asthma. There is a need for an objective scoring system which removes human variability, such as that provided by Oasys-2.

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 microg v 1401 microg, 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 FEV(1). 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.

Background: The number of peak expiratory flow (PEF) readings required per day to assess diurnal variation accurately is not known; published studies have used between two and seven PEF readings per day. This study compares the diurnal variation calculated using 2-10 PEF readings per day., Methods: All days with 10 readings were selected from a database of PEF records. For each day, diurnal variations calculated using 2-9 of the readings available were compared with that calculated using the full 10 PEF readings. Diurnal variation calculated using all 10 readings was taken as the true diurnal variation. When less than 10 readings were used the readings were evenly spaced over waking hours. Diurnal variation was calculated as maximum--minimum/predicted., Results: Two hundred and 25 days with 10 readings per day were selected from PEF records provided by 63 individuals. When only two PEF readings per day were used, the limits of agreement suggested a possible underestimate of true diurnal variation, calculated using all 10 readings, of 1.23-15.10%. The possible underestimate fell to 0.27-3.96% when calculated using four evenly spaced readings. Analysis of the timing of the highest PEF reading of the day was undertaken for rest and work days. This showed a mean (SD) timing of 13:56 (4:56 hours) for rest days and 11:47 (5:59 hours) for work days., Conclusions: Clinically significant underestimates of true diurnal variation may be seen when only small numbers of PEF readings per day are used in its calculation. At and above four readings the results suggest that the underestimate becomes increasingly insignificant in terms of the diagnosis and treatment of asthma. Analysis of the timing of the highest PEF reading of the day showed a wide variation, precluding the ability to capture the true diurnal variation with just two or three carefully timed PEF readings per day. The authors suggests that at least four readings per day should be performed, evenly spaced during waking hours, to obtain an accurate assessment of diurnal variation in PEF.

Background: Exposure to chromium during electroplating is a recognised though poorly characterised cause of occupational asthma. The first series of such patients referred to a specialist occupational lung disease clinic is reported., Methods: The diagnosis of occupational asthma was made from a history of asthma with rest day improvement and confirmed by specific bronchial provocation testing with potassium dichromate and nickel chloride., Results: Seven workers had been exposed to chrome and nickel fumes from electroplating for eight months to six years before asthma developed. One subject, although exposed for 11 years without symptoms, developed asthma after a single severe exposure during a ventilation failure. This was the only subject who had never smoked. The diagnosis was confirmed by specific bronchial challenges. Two workers had isolated immediate reactions, one a late asthmatic reaction, and four a dual response following exposure to nebulised potassium dichromate at 1-10 mg/ml. Two of the four subjects were also challenged with nebulised nickel chloride at 0.1-10 mg/ml. Two showed isolated late asthmatic reactions, in one at 0.1 mg/ml, where nickel was probably the primary sensitising agent. Four workers carried out two hourly measurements of peak expiratory flow over days at and away from work. All were scored as having occupational asthma using OASYS-2. Breathing zone air monitoring was carried out in 60 workers from four decorative and two hard chrome plating shops from workers with similar jobs to those sensitised. No measurement exceeded the current occupational exposure standard for chromate or nickel, the mean levels of chromate exposure for jobs similar to those of the affected workers were 9-15 micrograms/m3., Conclusion: Chrome used in electroplating is a potential cause of occupational asthma. Sensitivity to chrome in electroplaters may occur in situations where exposure levels are likely to be within the current exposure standards. There may be cross reactivity with nickel. Inhalation challenge with nebulised potassium dichromate solution is helpful in making the specific diagnosis where doubt exists.

Background: Serial peak expiratory flow (PEF) measurement is usually the most appropriate first step in the confirmation of occupational asthma. Visual assessment of the plotted record is more sensitive and specific than statistical methods so far reported. The use of visual analysis is limited by lack of widespread expertise in the methods. A computer assisted diagnostic aid (OASYS-2) has been developed which is based on a scoring system developed from visual analysis. This removes the requirement for an experienced interpreter and should lead to the more widespread use of the technique., Methods: PEF records were collected from workers attending an occupational lung disease clinic for investigation of suspected occupational asthma and from workers participating in a study of respiratory symptoms in a postal sorting office. PEF records were divided into two development sets and two gold standard sets. The latter consisted of records from workers in which a final diagnosis had been reached by a method other than PEF recording. An experienced observer scored individual work and rest periods for the two development set PEF records; linear discriminant analysis was used to compare measurements taken from development set 1 records with visual scores. Two equations were produced which allowed prediction of scores for individual work or rest periods. The development set 2 was used to determine how these scores should be used to produce a whole record score. The first gold standard set was used to determine the whole record score which best separated those with and without occupational asthma. The second set determined the sensitivity and specificity of the chosen score., Results: Two hundred and sixty eight PEF records were collected from 169 workers and divided into two development sets (81 and 60 records) and two gold standard sets (60 and 67 records). Linear discriminant analysis produced equations predicting the score for work periods incorporating five indices of PEF change and one for rest periods using seven indices. These equations correctly predicted the score for development set 1 work and rest periods on 61% of occasions (kappa = 0.47). The whole record score for development set 2 records, after weighting for definite or definitely no occupational effect, correlated with the visual score (correlation coefficient 0.86). Comparison with gold standard set 1 identified a cut off which proved to have a sensitivity of 75% and a specificity of 94% for an independent diagnosis of occupational asthma when applied to gold standard set 2., Conclusions: These results suggest that the sensitivity and specificity of analysing PEF records for occupational asthma using OASYS-2 approaches that of visual analysis, but it should be absolutely reproducible. The performance of OASYS-2 is more specific and approaches the sensitivity of other statistical methods of analysis. The evaluation of a large number of PEF records from workers exposed to different sensitising agents suggests that these results should be robust and should be repeatable in clinical practice.

Background: Glutaraldehyde is the best disinfectant for fibreoptic endoscopes. It is also used in the processing of x ray films. A number of studies have reported eye, nose, and respiratory symptoms in exposed workers. Three individual case reports of occupational asthma in endoscopy workers and a radiographer have also been published. We describe a further seven cases of occupational asthma due to glutaraldehyde in endoscopy and x ray departments, together with exposure levels measured during the challenge tests and in 19 endoscopy and x ray departments in the region., Methods: Eight workers were referred for investigation of suspected occupational asthma following direct or indirect exposure to glutaraldehyde at work. They were investigated by serial measurements of peak expiratory flow (PEF) and specific bronchial provocation tests. Glutaraldehyde levels were measured using personal and static short and longer term air samples during the challenge tests and in 13 endoscopy units and six x ray darkrooms in the region where concern about glutaraldehyde exposure had been expressed. Three of the workers investigated with occupational asthma came from departments where glutaraldehyde air measurements had been made; the others came from other hospitals or departments., Results: The diagnosis of occupational asthma was confirmed in seven workers, all of whom had PEF records suggestive of occupational asthma and positive specific bronchial challenge tests to glutaraldehyde. Bronchial provocation testing was negative in one worker who was no longer exposed and who had a less clearcut history of occupational asthma. Three workers also had a positive specific bronchial challenge to formaldehyde. The mean level of glutaraldehyde in air during the challenge tests was 0.068 mg/m3, about one tenth of the short term occupational exposure standard of 0.7 mg/m3. The levels obtained in the challenge chamber were similar to those measured in 13 endoscopy suites and six x ray darkrooms where median short term levels were 0.16 mg/m3 during decantation in endoscopy suites and < 0.009 mg/m3 in darkrooms., Conclusions: Glutaraldehyde can cause occupational asthma. The exposure levels measured in the workplace suggest that sensitisation may occur at levels below the current occupational exposure standard.

The case is described of a 44 year old pharmacist who developed severe occupational asthma threatening his continued employment, confirmed by serial measurement of peak expiratory flow at home and work. The cause was found to be the cleaning agent used in his office when it was unoccupied. Bronchial challenge testing identified the specific agent to which he was sensitised as lauryl dimethyl benzyl ammonium chloride, a constituent of the floor cleaner. Substitution of this floor cleaner by a simple detergent cleaner led to a substantial improvement in his asthma, confirmed by repeated serial peak flow measurements.

Objective: To study the general and specific incidence of occupational asthma within a defined geographic area; to audit the diagnosis of occupational asthma; to determine proposed mechanisms of asthma; and to determine the employment state of workers at diagnosis., Design: A surveillance scheme of physicians likely to see cases of occupational asthma., Setting: The West Midlands Region of the United Kingdom., Subjects: Workers with occupational asthma diagnosed within the boundaries of the West Midlands Region., Main Measures: Demographic data, employer, agent to which exposed, date of diagnosis, method of diagnosis, proposed mechanism of asthma, and employment state., Results: A recognised incidence of 43 (95% confidence interval CI 35-52) new cases per million general workers per year was detected. Specific occupational incidences varied from 1833 (95% CI 511-2990) per million paint sprayers to eight per million clerks. Specific incidence by District Health Authority varied from 103 in Solihull to 14 per million general workers in South Warwickshire. Agents to which workers were exposed at the time of diagnosis were generally well recognised (isocyanates 20.4%, flour 8.5%, colophony 8.3%). The most commonly used method of diagnosis was serial peak expiratory flow (PEF) measurement. Its use varied (specialist unit 72%, general chest physicians 50%, compensation board 48%). Workers were still exposed and therefore could have usefully performed PEF readings in 4% of cases where they were omitted from the specialist centre, 16% seen by chest physicians, and 2% seen by the Compensation Board. Other methods of diagnosis were used only infrequently outside the specialist unit. Fifty six per cent of reporting physicians considered that the mechanism of asthma was allergy compared with 18% who believed that it was irritation. Twenty eight per cent of workers were exposed to the suspected causative agent at the time of diagnosis, 38% were either on long term sickness absence, had retired, or had become unemployed. More workers (38%) who were exposed to agents recognised for statutory compensation before the 1991 changes seen at the specialist centre reach compensation and were reported to the scheme by the Compensation Board than those seen by chest physicians (9%)., Conclusions: These recognised incidences are likely to be an underestimate of the true incidence. They highlight at risk occupations and suggest underdiagnosis in some District Health Authorities. They suggest that diagnostic methods are underused outside specialist centres and that the mechanism of asthma is generally considered to be allergic.

Background: High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma. Although effective, they may cause systemic side effects. Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses., Methods: Fluticasone propionate, 1.5 mg per day, was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate. The study was multicentre, double blind and of a parallel design. For the first three months patients attended the clinic every four weeks and completed daily diary cards. For the next nine months they were only seen at three monthly intervals in the clinic., Results: During the first three months diary card peak expiratory flow (PEF) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate (difference in morning PEF 15 l/min (95% CI 6 to 25)), and these differences were apparent at the end of the first week. The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8% compared with those receiving beclomethasone dipropionate. No significant differences between the two groups were observed in morning plasma cortisol levels, urinary free cortisol levels, or response to synthetic ACTH stimulation. In addition, both the rates of withdrawal and of adverse events were low, and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate., Conclusions: This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate, with no increase in systemic or other side effects.

Objective: To study the health, employment, and financial outcome of occupational asthma., Design: A follow study of workers with confirmed occupational asthma., Setting: A specialist occupational lung disease clinic., Subjects: All workers had a diagnosis of occupational asthma made at least one year earlier. Diagnosis was confirmed by serial peak expiratory flow measurement, specific bronchial provocation testing, or specific immunology., Main Outcome Measures: Respiratory symptoms, medication, pulmonary function, employment state, and financial position., Results: 112 of a total of 140 eligible workers were followed up. 32% of patients remained exposed to the causative agent. These workers had more symptoms at follow up than those removed and a greater number were taking inhaled steroids. Continued exposure was also associated with a fall in % predicted forced expiratory volume in one second (FEV1) of 3% compared with that at presentation. Their median loss of annual income due to occupational asthma was 35%. Those removed from exposure were worse off financially (median loss 54% of annual income), had fewer respiratory symptoms than the group who remained exposed, and their % predicted FEV1 had improved by 4.6%. Statutory compensation and that obtained by common law suits did not match the loss of earnings due to the development of occupational asthma. Of the workers removed from exposure, those who no longer complained of breathlessness had been diagnosed significantly earlier after the onset of their first symptom (48 v 66 months, p = 0.001) and had a significantly higher FEV1 at presentation (90% v 73% predicted, p = 0.008) compared with those who were still breathless. They had developed symptoms earlier after first exposure (48 v 66 months, p > 0.05) and had been removed from exposure sooner (eight v 12 months, p > 0.05)., Conclusion: Removal from exposure after diagnosis of occupational asthma is beneficial in terms of symptoms and lung function, but is associated with a loss of income. Early diagnosis is important for symptomatic improvement after removal from exposure. Inadequate compensation may contribute to the workers' decision to remain exposed after diagnosis.

Background: The effect of treatment with inhaled corticosteroids in patients with non-asthmatic chronic airflow obstruction is still disputed. Whether any physiological improvements seen are accompanied by changes in bronchial responsiveness and symptoms and quality of life is also still unclear., Methods: A sequential placebo controlled, blinded parallel group study investigating the effect of three weeks of treatment with inhaled beclomethasone dipropionate (BDP), 750 micrograms or 1500 micrograms twice daily, and oral prednisolone, 40 mg per day, was carried out in 105 patients with severe non-asthmatic chronic airflow obstruction (mean age 66 years, mean forced expiratory volume in one second (FEV1) 1.05 litres [40% predicted], geometric mean PD20 0.52 mumol). End points assessed were FEV1, forced vital capacity (FVC), and peak expiratory flow (PEF), bronchial responsiveness to inhaled histamine, and quality of life as measured by a formal quality of life questionnaire., Results: Both doses of BDP produced equivalent, small, but significant improvements in FEV1 (mean 48 ml), FVC (mean 120 ml), and PEF (mean 12.4 l/min). The addition of oral prednisolone to the treatment regime in two thirds of the patients did not produce any further improvement in these parameters. Inhaled BDP produced a treatment response in individual patients (defined as an improvement in FEV1, FVC, or mean PEF of at least 20% compared with baseline values) more commonly than placebo (34% v 15%). The two doses of BDP were equally effective in this respect and again no further benefit of treatment with oral prednisolone was noted. Treatment with BDP for up to six weeks did not affect bronchial responsiveness to histamine. Small but significant improvements were seen in dyspnoea during daily activities, and the feeling of mastery over the disease., Conclusions: High dose inhaled BDP is an effective treatment for patients with chronic airflow obstruction not caused by asthma. Both objective and subjective measures show improvement. Unlike asthma, no improvement in bronchial responsiveness was detected after six weeks of treatment.

Occupational asthma due to the pyrolysis products of polyvinyl chloride (PVC) produced by shrink wrapping processes has previously been reported. The first case of occupational asthma in a shrink wrap worker using a different plastic, polyethylene, is reported; the association was confirmed by specific bronchial provocation testing.

The results from the first year of a notification scheme for occupational asthma in the West Midlands Region are presented. The scheme includes recognised new and old cases of occupational asthma. Thirty new cases were recognised per million general working population in the first year. Cases recognised in different occupational groups ranged from 154 per million painters and assembly workers to three per million clerical staff. Analysis of the agents to which workers with recognised occupational asthma were exposed identified commonly recognised agents such as isocyanates, colophony, and flour and generally less well recognised ones such as oil mists. The distribution of new and old reported cases, including those receiving compensation from the Department of Social Security, were calculated by health authority using estimated working population as the denominator. The number of reported cases varied from 303 per million in a semi-urban health authority that has a respiratory physician with a special interest in occupational asthma to less than 30 cases per million in eight health authorities. The most likely cause for these differences is lack of ascertainment.

One hundred and twenty one patients considered on clinical grounds to have non-asthmatic chronic airflow obstruction completed a double blind, crossover trial comparing oral prednisolone 40 mg per day with inhaled beclomethasone dipropionate 500 micrograms thrice daily, each given for 14 days, with a 14 day washout period between treatments. The time course of response was analysed for the 57 occasions where there was a significant increase in mean daily peak expiratory flow (PEF) over the treatment period. Mean daily PEF was still rising at day 14 on 12 occasions. After withdrawal of treatment mean daily PEF remained above pretreatments levels for more than two weeks in half the responses analysed. The peak response occurred earlier with inhaled beclomethasone (median 9.5 (range 3-14) days) than with oral prednisolone (median 12 (range 1-14) days), though both treatments produced a response that was sustained for a similar period. The results suggest that a trial of treatment with corticosteroids in this group of patients should last more than 14 days, and that in a study with a crossover design the washout period should be longer than two weeks.

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.

An outbreak of occupational asthma, of unknown cause and extent, was detected in a steel coating plant. In 1979 a cross-sectional study which defined occupational asthma in terms of respiratory symptoms detected 21 people with suggestive symptoms among the 221 studied. They all worked in the coating shop, but the plastic coatings used at the plant contained many potential sensitising agents that might have caused the asthma. All 21 developed their symptoms after 1971, and it was found that in this year a supplier had modified a coating allowing, at the temperatures used in the process, toluene di-isocyanate to be liberated. Two of the symptomatic subjects were tested by inhalation of the isocyanate and showed asthmatic reactions and other subjects were found to have asthma related to periods spent at work by records of peak expiratory flow rate. Over half the 21 had a symptom free latent period after first exposure of three years or less, a pattern not seen in other subjects with respiratory symptoms. After the isocyanate had been removed from the process 17 of these subjects became asymptomatic or improved, a greater proportion than in other subjects with respiratory symptoms.

Peak expiratory flow rate (PEFR) has been measured hourly from waking to sleeping in 29 workers with respiratory symptoms exposed to the fumes of soft soldering fluxes containing colophony (pine resin). Thirty-nine records of mean length 33 days have been analysed, and the results compared with the occupational history and bronchial provocation testing in the same workers. From plots of daily mean, maximum, and minimum PEFR, recurring physiological patterns of asthma emerge. The most common pattern is for asthma to increase with each successive working day. Some workers have an equivalent deterioration each working day. Regular recovery patterns taking one, two, and three days are described. The combination of a three-day recovery pattern and a late asthmatic reaction on Monday results in Monday being the best day of each week. Assessment of these records has shown them to be specific and sensitive, provided the worker was not taking corticosteroids or sodium cromoglycate during the period of the record and that bronchodilator usage was kept constant on days at home and at work. The results of the PEFR records correlate well with bronchial provocation testing, and provide a suitable alternative to this for the diagnosis of mild to moderate occupational asthma. The records are of particular use for screening symptomatic workers whose symptoms appear unlikely to be related to work.

Twenty five patients who were exposed to oil mists at their place of work were investigated for possible work related asthma. Serial peak expiratory flow recordings showed 13 to have definite work related asthma, seven equivocal work related asthma, and three asthma unrelated to work; two had normal recordings. Subjects with work related asthma often produced different patterns of peak flow response during the working week; patterns also varied between patients. Six of these patients had bronchial tests with oil from their place of work. Three had asthma induced by exposure to unused (clean) soluble oil and one reacted to used but not to clean oil. The challenge tests in the remaining two gave inconclusive results. It is concluded that occupational asthma due to oil mists is common, the peak flow response is heterogeneous, and the provoking agent within the oil may vary from worker to worker.

Two cases of occupational asthma due to soft corrosive soldering fluxes used in metal jointing are described in which the diagnosis was based on work related deterioration in daily peak expiratory flow rate and positive responses in bronchial provocation tests. Both fluxes contained ammonium chloride and zinc chloride. Occupational asthma provoked by these agents has not previously been reported.

Thirty-nine electronics workers were investigated by bronchial provocation testing to soldering fluxes containing colophony and were followed up one to four years later. At presentation and on follow-up each worker had nonspecific bronchial reactivity measured with inhaled histamine, and also had detailed measurements of lung function and estimation of total immunoglobulin levels. They completed a questionnaire designed to detect residual disability. The workers were divided into three groups. Twenty had left work after their initial diagnosis, eight had been moved to alternative work within their original factories, and 11 were thought to have asthma unrelated to colophony exposure as they failed to react to colophony at presentation. Histamine reactivity had returned to normal in half the workers who had left their original factories, but in only one worker who had moved within her original factory. This suggested that the nonspecific bronchial reactivity to histamine was the result rather than the cause of the occupational asthma, and that indirect exposure at work was sufficient to delay recovery of histamine reactivity. However, only two of the 20 affected workers who had left their original factories were symptom free on follow-up, and most had a considerable reduction in their quality of life by continuing asthma, which was particularly provoked by exercise, respiratory infections, and nonspecific irritants. Continuing symptoms may have been caused by domestic sources of colophony, or possibly the failure to eliminate colophony from the lungs.

Thirty five printers who had work related wheeze, chest tightness, or breathlessness kept two hourly records of their peak expiratory flow for at least two weeks. They all worked in a factory supplied by air from contaminated humidifiers. The peak flow records showed consistent work related deterioration in 15 workers, nine of whom had a diurnal variation in peak flow exceeding 20%. Ten workers kept further records after the humidifiers had been cleaned, other work practices remaining unchanged. There was substantial improvement in all 10 workers, implying that material from the contaminated humidifier was the cause of the work related changes in peak flow. The patterns of work related changes in peak flow fell into four groups: falls maximal on the first work day, falls maximal midweek, falls equivalent each work day, and falls progressive throughout the working week. Three quarters of this last group had immediate prick test responses to humidifier antigen, which were negative in all the others with work related changes in peak flow. This suggests that the progressive daily deterioration pattern alone is due to an IgE mediated response to humidifier antigens. A large range of microorganisms was identified in the humidifiers. No single microorganism appeared to be the antigen responsible for the precipitating antibody seen in 75% of the study population.

Three workers developed classical extrinsic allergic alveolitis while working in a printing works that had a contaminated cold water humidifier. All had nodular shadows on their chest radiographs, reduced gas transfer measurements, and lung biopsy specimens that showed an alveolitis with giant cells and cholesterol clefts. In two subjects bronchoalveolar lavage was performed and the lavage fluid contained more than 70% lymphocytes in each case. Bronchial provocation tests with the humidifier antigen in these two workers reproduced their symptoms. Unlike previously reported cases, where exposure was to humidifiers working at generally higher temperatures, challenge with thermophilic actinomycetes in our two patients produced no reaction. Tests for precipitins to the humidifier antigen gave strongly positive reactions in the three workers but no single organism isolated from the humidifier produced a significantly positive reaction.

Occupationally related asthma developing in three patients due specifically to exposure to 1,5-naphthylene di-isocyanate (NDI), a hot curing agent used in manufacturing rubber, has been confirmed for the first time using bronchial provocation testing. This substance has been thought to be safer than toluene di-isocyanate (TDI) and diphenylmethane di-isocyanate (MDI) because of its relatively high melting point (120 degrees C). Each patient worked in the same factory and the circumstances of exposure were similar. Provocation testing was also performed with TDI in concentrations up to 0.018 parts per million (ppm) and MDI in concentrations up to 0.02 ppm, to which the patients had been exposed in the past, but no reactions were elicited. None of the patients had increased bronchial reactivity judged by histamine lability and exercise testing. Each patient was advised to give up his job, but two of the three could not find alternative employment and remained exposed. Three-year follow-up shows that airways narrowing has persisted in those who have remained exposed.

A toolsetter developed occupational asthma due to the oil mist generated by his lathe on which it was used as a coolant. The diagnosis was confirmed by serial measurements of peak expiratory flow at home and work, including a prolonged period away from work. Occupational type bronchial provocation tests were performed using the whole emulsified oil and its components separately. He reacted specifically to the whole emulsified oil and to the reodorant, a pine oil preparation. He also reacted to colophony, a constituent of the emulsifier.

Records of peak expiratory flow rate (PEFR), commonly used in hospital in the management of asthma, have not been evaluated as a method of identifying cases of asthma in population surveys. Four observers were asked to report on whether asthma was present or absent in 61 graphs of PEFR recorded two hourly for four weeks during surveys of working population. Agreement within individual observers was measured using a subset of 29 graphs which had been copied and distributed at random among the set of 61; agreement was good, from 90% in one observer to 100% in two. Agreement between observers was measured on the basis of all 61 graphs. Agreement occurred between all four observers in 69% of graphs, between at least three out of four in 97%, and, when pairs of observers were examined, between 72% and 93% of graphs. Graphs assessed as showing asthma demonstrated more within day PEFR variability (expressed as the number of days in which the difference between maximum and minimum readings was at least 15%) than graphs assessed as not showing asthma. Some graphs with little within day variability were assessed as showing asthma, apparently because they demonstrated between day PEFR variability.

Eighty nine adults with asthma who were receiving inhaled corticosteroid and bronchodilator treatment took part in a double blind, randomised, placebo controlled trial of nedocromil sodium, 4 mg four times daily by inhalation. During a run in period of two to four weeks corticosteroid treatment was reduced when possible to produce a comparable level of symptoms across the trial population. The test treatment was then taken for four weeks, with the severity of asthma recorded daily by patients and assessed at two weekly hospital visits. There was an improvement in symptoms in the patients taking nedocromil sodium by comparison with those having the placebo, the differences being significant for diary card PEF readings, asthma symptom scores, and bronchodilator usage at night. The mean difference between the two groups was 18 l/min for PEF, 0.42 for daytime asthma score, and 1.73 puffs in 24 hours for bronchodilator usage. These results suggest that asthmatic patients who require inhaled steroids show better control of their asthma with the addition of nedocromil sodium than of placebo over a four week period after reduction of the dosage of their inhaled steroids.

The prevalence of work-related wheeze and breathlessness was measured in factory employees manufacturing flux-cored solder. The flux contained colophony which was heated in the production process, exposing the workers to colophony fumes. Measurement of colophony in the breathing zone defined three grades of exposure with median levels of 1.92 mg/m3 (six subjects), 0.02 mg/m3 (14 subjects), and less than 0.01 mg/m3 (68 subjects). All but two workers in the first two groups, and 90% of a random sample of the last group, were studied. Occupational asthma was present in 21% of the higher two exposure groups and 4% of the lowest exposure group. Mean values of FEV1 and FVC fell with increasing exposure. The prevalence of upper and lower respiratory symptoms was only one-third to a half that found in a previous study of shop floor electronics workers, whose work raised the flux to a higher temperature and produced higher concentrations of colophony fume. Total IgM levels were higher in the solder manufacturers than in unexposed controls, and were higher still in the electronics workers. The solder manufacturers were exposed to colophony fumes at 140 degrees C, below the temperature at which the resin acids decompose, supporting the hypothesis that it is the whole resin acids rather than decomposition products which cause occupational asthma. The threshold limit value should be based on the resin acid content of the fume, and not the aldehyde content as at present. The survey suggests that sensitisation will not be prevented unless exposure is kept well below the present threshold limit value.

Peak expiratory flow rate (PEFR) has been recorded hourly or two-hourly from waking to sleeping in workers with respiratory symptoms who were exposed to isocyanate fumes at work. Twenty-three recordings averaging 33 days duration were recorded in 20 workers. Each worker was also admitted for bronchial provocation testing to toluene di-isocyanate (TDI) or diphenylmethane di-isocyanate (MDI) fumes or both. A final assessment of work-related asthma made from subsequent work exposure was compared with the results of bronchial provocation testing and a subjective assessment of the peak flow records. Both techniques were specific and sensitive. Physiological patterns of occupational asthma were defined from the records of PEFR. The most striking finding was the slow recovery from work-induced asthma. This commonly took several days to start and in one worker took 70 days to complete after leaving work. Several workers developed a pattern resembling fixed airways obstruction after repeated exposure at work. The consequences of these findings for the recording of symptoms of occupational asthma are discussed and recommendations are made for the recording of PEFR in workers in general.

Patients in clinical practice often falsely report their smoking status. To see if this was so in occupational surveys we have validated smoking histories (using a serum thiocyanate assay) in 206 randomly sampled office workers who completed a smoking questionnaire administered by a doctor. Past and present cigarette consumption was determined with an assessment of exposure to passive cigarette smoke at home and at work in the non-smokers. Serum thiocyanate concentrations were measured by the ferric nitrate method. All smoking groups showed mean thiocyanate concentrations greater than non-smokers except those smoking five or fewer cigarettes a day. There was a significant increase in plasma thiocyanate with increasing smoking (p less than 0.01). Non-smokers with and without exposure to passive smoke could not be separated by thiocyanate concentration. In our hands serum thiocyanate concentrations identified moderate and heavy smokers but could not distinguish between non-smokers, light smokers, and passive smokers. Fourteen non-smokers had serum thiocyanate concentrations higher than 70 mumol/l which were still raised on a repeat sample. On a further questionnaire two admitted to smoking. To help confirm non-smoking status, expired carbon monoxide levels were also checked in this group. One person had a level of 22 ppm and subsequently admitted to smoking. In the others the levels were less than or equal to 10 ppm. Using a combination of serum thiocyanate assay and exhaled breath carbon monoxide levels, non-smoking was confirmed in 98% of those stating that they were non-smokers. In non-smokers exposure to passive cigarette smoke was much more likely to occur at work than at home.

Five patients had asthma provoked by cyanoacrylates and one by methyl methacrylate, possibly because of the development of a specific hypersensitivity response. Acrylates have wide domestic as well as industrial uses, and inhalation of vapour emitted during their use can cause asthma.

Workers in a modern electronics factory were surveyed by questionnaire and lung function testing to see if there was evidence of widespread work-related respiratory symptoms. Of the responding workers exposed to solder flux fumes on the shop floor, 22% had work-related breathlessness or wheeze or both. Exposed workers had a lower FEV1 and FVC than unexposed workers. Work-related rhinitis was also present in 22% of exposed workers. The most likely cause for these results is sensitivity to colophony fumes, released from solder flux during soldering. Levels of solder flux fume were below the threshold limit value in this factory during the survey.