Cedd Burge

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.

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.

An outbreak of occupational asthma due to chromium and cobalt

BACKGROUND Five metal turners employed by an aerospace manufacturer presented to the Birmingham Chest Clinic occupational lung disease unit. Four cases of occupational asthma (OA) due to chromium salt (3) and cobalt (1) were diagnosed by serial peak-expiratory flow measurements and specific inhalation challenge testing. AIMS To measure the extent of the outbreak and to provide epidemiological data to ascertain the aetiology. METHODS Participants answered a detailed, self-administered questionnaire, designed to detect occupational lung disease. Urine chromium and cobalt excretion, spirometry and exhaled nitric oxide measurements were taken. Those with possible, probable or definite non-OA or OA, after questionnaire, were invited to undertake two-hourly peak flow measurements and received specialist follow-up. RESULTS A total of 62 workers (95% of workforce) participated. Sixty-one per cent of employees were working in higher metalworking fluid (MWF) exposure areas. Ninety per cent of workers had urinary chromium excretion indicating occupational exposure. Sixty-six per cent of workers reported active respiratory symptoms, although there were no significant differences between exposure groups. Two further workers with probable OA were identified and had significantly higher urinary chromium and cobalt concentration than asymptomatic controls. Eighteen cases of occupational rhinitis (OR) were identified, with significantly raised urinary chromium concentration compared with asymptomatic controls. CONCLUSIONS Chromium salt and cobalt can be responsible for OA and OR in workers exposed to MWF aerosols. Onset of symptoms in those with positive specific challenges followed change in MWF brand. Workers with OA had increased urinary concentrations of chromium and cobalt, and those with OR had increased urinary concentrations of chromium.

PEF analysis requiring shorter records for occupational asthma diagnosis

BACKGROUND The Oasys programme plots serial peak expiratory flow (PEF) measurements and produces scores of the likelihood that the recordings demonstrate occupational asthma. We have previously shown that the area between the mean workday and rest day PEF curves [the area between the curves (ABC) score] has a sensitivity of 69% and specificity of 100% when plotted from waking time using a cut-off score of 15 l/min/h. AIMS To investigate the minimum data requirements to maintain the sensitivity and specificity of the ABC score. METHODS A total of 196 sets of measurements from workers with occupational asthma confirmed by methods other than serial PEFs and 206 records from occupational and non-occupational asthmatics who were not at work at the time of PEF monitoring were analysed according to their mean number of readings per day. Measurements from work and rest days were sequentially removed separately and the ABC score calculated at each reduction. The sensitivity and specificity of the ABC score (using a cut-off of 15 l/min/h) was calculated for each duration. RESULTS Two-hourly measurements (approximately 8 readings per day) with eight workdays and three rest days had 68% sensitivity and 91% specificity for occupational asthma diagnosis. As readings decreased to <or=4 readings per day, >or=15 workdays were required to provide a specificity above 90%. CONCLUSIONS To be sensitive and specific in the diagnosis of occupational asthma, the ABC score requires 2-hourly PEF measurements on eight workdays and three rest days. This is a short assessment period that should improve patient compliance.

Serial PEF measurement is superior to cross-shift change in diagnosing occupational asthma

Cross-shift measurements of peak expiratory flow (PEF) are commonly employed in the diagnosis of occupational asthma, although evidence for this approach is lacking. The current paper presents an evaluation of the technique. Mean changes in PEF across morning/day shifts were compared between workers with occupational asthma, confirmed using specific challenge testing, and non-working asthmatics. Individuals were divided into a development set, used to identify the optimum cross-shift change for diagnosing occupational asthma, and an evaluation set, used to test the sensitivity and specificity of this value. Comparative analysis of serial PEF records was performed using the Oasys-2 computerised system. A cross-shift decrease in PEF of 5 L·min−1 achieved acceptable specificity in the development set. Applied to the evaluation set, this cut-off had a specificity of 90.9% and a sensitivity of 50%. Sensitivity could not be improved without unacceptable compromise to specificity. Analysis of serial PEF records using linear discriminant analysis identified occupational asthma with a sensitivity of 83.3% and a specificity of 90.9%. Serial analysis using mean work/rest day PEF comparison had a sensitivity of 66.7% and a specificity of 100%. Cross-shift changes in PEF in morning/day-shift workers have poor sensitivity in diagnosing occupational asthma, and are inferior to serial techniques.

Serial lung function variability using four portable logging meters.

Objective. Portable lung function logging meters that allow measurement of peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) are useful for the diagnosis and exclusion of asthma. The aim of this study was to investigate the within and between-session variability of PEF and FEV1 for four logging meters and to determine the sensitivity of meters to detect FEV1 and PEF diurnal changes. Methods. Thirteen assessors (all hospital staff members) were asked to record 1 week of 2-hour PEF and FEV1 measurements using four portable lung function meters. Within-session variability of PEF and FEV1 were compared for each meter using a coefficient of variation (COV). Between-session variability was quantified using parameter estimates from a cosinor analysis which modeled diurnal change for both lung function measures and also allowed for variation between days for individual sessions. Results. The mean within-session COV for FEV1 was consistently lower than that for PEF (p < 0.001). PEF showed a higher but not significantly different (p = 0.068) sensitivity for detecting diurnal variation than FEV1. PEF was also slightly more variable between days, but not significantly different than FEV1 (p = 0.409). PEF and FEV1 diurnal variability did not differ between the 4 meters (p = 0.154 and 0.882 respectively), but within-session FEV1 COV differed between meters (p = 0.009). Conclusion. PEF was marginally more sensitive to within-day variability than FEV1 but was less repeatable. Overall, differences between the 4 meters were small, suggesting that all meters are clinically useful.

Two variants of occupational asthma separable by exhaled breath nitric oxide level

UNLABELLED Exhaled nitric oxide (FE(NO)) has been used as a marker of asthmatic inflammation in non-occupational asthma, but some asthmatics have a normal FE(NO). In this study we investigated whether, normal FE(NO) variants have less reactivity in methacholine challenge and smaller peak expiratory flow (PEF) responses than high FE(NO) variants in a group of occupational asthmatics. METHODS We measured FE(NO) and PD(20) in methacholine challenge in 60 workers currently exposed to occupational agents, who were referred consecutively to a specialist occupational lung disease clinic and whose serial PEF records confirmed occupational asthma. Bronchial responsiveness (PD(20) in methacholine challenge) and the degree of PEF change to occupational exposures, (measured by calculating diurnal variation and the area between curves score of the serial PEF record in Oasys), were compared between those with normal and raised FE(NO). Potential confounding factors such as smoking, atopy and inhaled corticosteroid use were adjusted for. RESULTS There was a significant correlation between FE(NO) and bronchial hyper-responsiveness in methacholine challenge (p = 0.011), after controlling for confounders. Reactivity to methacholine was significantly lower in the normal FE(NO) group compared to the raised FE(NO) group (p = 0.035). The two FE(NO) variants did not differ significantly according to the causal agent, the magnitude of the response in PEF to the asthmagen at work, or diurnal variation. CONCLUSIONS Occupational asthma patients present as two different variants based on FE(NO). The group with normal FE(NO) have less reactivity in methacholine challenge, while the PEF changes in relation to work are similar.

Shift work effects on serial PEF measurements for occupational asthma

BACKGROUND Diurnal variation (DV) affects lung function but the changes are thought to be related to sleep patterns rather than time of day. When diagnosing occupational asthma (OA), serial peak expiratory flow (PEF) measurements are the recommended first line investigation, but could be confounded by shift work. AIMS The aim of the study was to investigate the effects of shift work on PEF measurements used for diagnosing OA. METHODS PEF records containing more than one shift pattern with ≥ 4 days per shift were identified. OA diagnosis was based on an Oasys-2 score ≥ 2.51 and non-OA on having an alternative clinical diagnosis and Oasys-2 score <2.51. The mean area between curves (ABC) score, mean PEF DV and cross-shift PEF changes were calculated for each shift. RESULTS Records from 123 workers with OA and 69 without OA satisfied inclusion criteria. In the OA group, PEF declined more on afternoon and night shifts than days (P < 0.001). The ABC score was lower in the OA group on night (P < 0.05) and afternoon shifts (P < 0.05) as compared with days, without significant differences in DV. Among those without OA, cross-shift PEF increased more on day shifts (mean + 25 l/min) than afternoon or night shifts (+1 l/min) (P < 0.001). The sensitivity for the ABC score and DV were good and similar across shifts, but specificity was reduced using DV (DV mean 39%; ABC 98%). CONCLUSIONS PEF responses between work and rest show small differences according to shift type. The ABC score has a high sensitivity and specificity for all shifts; differences in DV have lower specificity.

Can serial PEF measurements separate occupational asthma from allergic alveolitis

BACKGROUND Occupational asthma commonly results in work-related changes in serial peak expiratory flow (PEF) measurements. Whether alveolitis can result in similar changes is unknown. AIMS To identify differences and similarities of serial PEF between workers with occupational alveolitis and asthma seen during an outbreak investigation in a factory with metal-working fluid exposure. METHODS Workers with respiratory symptoms and rest-day improvement were identified by questionnaire. Each was asked to measure PEF 8 times daily for 4 weeks at home and work. Alveolitis was subsequently diagnosed from a validated scoring system including radiological changes, carbon monoxide diffusing capacity, bronchoalveolar lavage and biopsy results. Occupational asthma was confirmed with a positive Oasys score >2.5 and a mean rest-work PEF >16 l/min from serial 2-hourly PEF measurements. The Oasys PEF plotter calculated differences between rest and workdays for mean PEF, diurnal variation and the scores were used to confirm an occupational effect (Oasys, area between curve and time point). Records were compared between the alveolitis group and the group with occupational asthma without alveolitis. RESULTS Forty workers with occupational asthma and 16 with alveolitis had indistinguishable PEF changes on workdays in terms of magnitude (median reduction 18.5 and 16.1 l/min, respectively) and diurnal variation. Immediate reactions were more common with occupational asthma and late reactions more common with alveolitis. CONCLUSIONS PEF responses to metal-working fluid aerosols do not distinguish occupational asthma from alveolitis except in timing. They can be used to identify the workplace as the cause of asthma and also alveolitis.