Cobalt asthma in metalworkers from an automotive engine valve manufacturer

Transcription

1 Occupational Medicine 2014;64: Advance Access publication 11 April 2014 doi: /occmed/kqu043 Cobalt asthma in metalworkers from an automotive engine valve manufacturer G. I. Walters, A. S. Robertson, V. C. Moore and P. S. Burge Occupational Lung Disease Unit, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK. Correspondence to: G. I. Walters, Occupational Lung Disease Unit, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK. Tel: +44 (0) ; fax: +44 (0) ; Background Cobalt asthma has previously been described in cobalt production workers, diamond polishers and glassware manufacturers. Aims Methods Results To describe a case series of occupational asthma (OA) due to cobalt, identified at the Birmingham Heartlands Occupational Lung Disease Unit, West Midlands, UK. Cases of cobalt asthma from a West Midlands manufacturer of automotive engine valves, diagnosed between 1996 and 2005, were identified from the SHIELD database of OA. Case note data on demographics, employment status, asthma symptoms and diagnostic tests, including spirometry, peak expiratory flow (PEF) measurements, skin prick testing (SPT) and specific inhalational challenge (SIC) tests to cobalt chloride, were gathered, and descriptive statistics used to illustrate the data. The natural history of presentations has been described in detail, as well as a case study of one of the affected workers. Fourteen metalworkers (86% male; mean age 44.9 years) were diagnosed with cobalt asthma between 1996 and Workers were principally stellite grinders, stellite welders or machine setter-operators. All workers had positive Occupational Asthma SYStem analyses of serial PEF measurements, and sensitization to cobalt chloride was demonstrated in nine workers, by SPT or SIC. Conclusions We have described a series of 14 workers with cobalt asthma from the automotive manufacturing industry, with objective evidence for sensitization. Health care workers should remain vigilant for cobalt asthma in the automotive manufacturing industry. Key words Introduction Cobalt; hard metal; metalworking fluid; occupational allergy; occupational asthma; occupational respiratory disease. Occupational cobalt exposure confers an increased risk of sensitizer-induced asthma [1 6] as well as allergic dermatitis and hard metal lung disease [7 9]. Cobalt asthma has been reported in diamond polishers [10 14], cobalt and hard metal production workers [4,5,15,16] and a glassware factory worker [17] but is rarely described in metalworkers [18] or welders. We describe a case series of cobalt asthma in metalworkers from an engine valve manufacturing company encountered at the Birmingham Heartlands Occupational Lung Disease Unit between 1996 and Methods Cases of cobalt asthma from a manufacturer of stellitetipped steel engine valves, confirmed between 1996 and 2005, were identified from the Midland Thoracic Society s Rare Respiratory Disease Registry Surveillance Scheme of Occupational Asthma (SHIELD) database, a voluntary reporting scheme for occupational asthma (OA) in the West Midlands, UK [19]. For each worker, case note data regarding demographics (age, gender, ethnicity, co-morbidity, atopy, smoking status), employment duration, asthma symptoms at diagnosis and work effect were gathered, along with details of diagnostic tests: (i) skin prick testing (SPT) to common aeroallergens and to 1 10 mg/ml cobalt chloride, (ii) urinary cobalt concentration (μg/l), (iii) two hourly peak expiratory flow (PEF) measurements analysed using Occupational Asthma SYStem (OASYS) [20], (iv) non-specific bronchial responsiveness (NSBR) to methacholine challenge tested using the Yan method [21], (v) spirometry measured according to European Respiratory Society/ The Author Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please journals.permissions@oup.com

2 G. I. WALTERS ET AL.: COBALT ASTHMA IN METALWORKERS 359 American Thoracic Society standards using European Community for Coal and Steel predicted values [22] and (vi) specific inhalational challenge (SIC) tests to controls and to 1 10 mg/ml cobalt chloride. Parametric data were displayed using means and standard deviation, non-parametric data using medians and interquartile range (IQR) and categorical data using percentages. Workers were admitted to Birmingham Heartlands Hospital for SIC to a nebulized control substance, and then to 1 10 mg/ml of nebulized cobalt chloride for between 3 and 20 min, on a subsequent day. Serial measurements of forced expiratory volume in 1 s (FEV 1 ) were performed for up to 24 h after each SIC. SIC was considered positive if the FEV 1 fell >15% from baseline on >1 measurement (within min for immediate asthmatic reactions) or fell below the lower 95% confidence limit for the mean FEV 1 from 3 days without occupational exposure immediately before SIC (dual or late asthmatic reactions only) [23]. NSBR to methacholine was measured immediately prior to the control challenge, and again 24 h after the positive challenge. Affected workers were employees of a mediumsized automotive engineering firm, manufacturing steel engine valves. Valve seats and tips were welded with stellite, an alloy containing 30 65% cobalt, and finished by grinding and polishing with metalworking fluid (MWF) lubrication. Shortly before the first cases emerged, all machines using synthetic MWF had been connected to a common sump, with cleaning, ph control and biocide addition done in a central plant room outside the main factory. This allowed the return MWF from the machines grinding the stellite, to mix with the MWF from machines grinding uncoated steel, and distribution of any dissolved cobalt to all machines connected to the common sump. Machines were separated from offices, the development room and the foundry by internal brick walls and from the stores by a chickenwire mesh with no air filtering properties. Machines using mineral oil were enclosed and had local exhaust ventilation (LEV) but there was initially no LEV for those using synthetic MWFs. The index case was seen in 1996 in a stellite welder, and this was controlled by enclosing the auto welding machine. Changing to a low-cobalt-solubility MWF and enclosing other machines allowed eventual control of cobalt exposure. This was only possible after an accurate diagnosis of the affected workers. Later cases were associated with increased exposure due to ventilation systems being turned off throughout night shifts, as a result of the noise impact on local residents. Ethical approval for the study was granted by the North of Scotland-2 National Research Ethics Service Committee (REC reference: 13/NS/0097). The worker used as an illustrative case provided written informed consent for publication. Results Illustrative case: Worker 2 A 39-year-old worker was referred by the company occupational health service, with an 18 month history of chest tightness, breathlessness on exertion, wheeze, blocked nose and runny nose. His symptoms became progressively worse throughout the working week and were better away from work on holiday. He had no past medical history. There was no family history or prior history of asthma, hay fever or cat allergy and he had never smoked cigarettes regularly. He used a 100 μg salbutamol metered-dose inhaler infrequently for asthma symptoms. The worker had been employed at the company for 4 years on day shifts as a machine setter-operator, which included grinding and polishing of stellite valve seats. Clinical examination and chest radiograph were normal. Spirometry revealed FEV 1 /forced vital capacity (FVC) = 78%, FEV 1 = 3.41 l (78% predicted) and FVC = 4.38 l (82% predicted) with normal gas transfer measurement (diffusing capacity = ml CO/ min/mmhg; 98% predicted). He was moderately hyperreactive to methacholine while still exposed at work (PD 20 = 713 μg). SPTs revealed a 6 mm wheal to histamine control, 6 mm to dermatophagoides pteronyssinus and 4 mm to cat dander. Analysis of two hourly PEF monitoring revealed definite OA, with an OASYS score of 4.0 (Figure 1). Total serum immunoglobulin E (IgE) measured 932 ku/l (reference range ku/l), urine cobalt concentration was 3 μg/l suggesting occupational exposure (UK population reference range μg/l) [24], white blood cell count was /l (normal range /l) and eosinophil count /l (normal range /l). The worker underwent SIC to nebulized 1 mg/ml cobalt chloride solution in a buffered solution to ph 6.8 (three active challenges totalling 5 min). At 11 h post-challenge, he experienced wheeze and chest tightness, resembling his symptoms at work, and a late fall in FEV 1 from 4.00 l, by 20%, to 3.21 l (Figure 2). FEV 1 continued to drop to 3.17 l/min ( 21%) at 12 h post-challenge. The worker underwent three control exposures to nebulized 0.9% saline, lasting 5 min in total, with an immediate but non-sustained fall in FEV 1 of 11.6% accompanied by a brief episode of light headedness, but no asthma symptoms, and then no change in FEV 1 over 12 h following the challenge. Additionally, he experienced a 3-fold increase in NSBR from a baseline PD 20 of >4800 μg to 1500 μg 24 h postchallenge to cobalt chloride. The worker was diagnosed with OA due to sensitization to cobalt and was moved to quality control inspection. However, his bench was situated within 10 m of stellite grinding machines, and serial PEF monitoring and urine cobalt measurements at 12 months after diagnosis indicated ongoing exposure. The worker was granted ill-health retirement and found alternative work as a postman.

3 360 OCCUPATIONAL MEDICINE Figure 1. Serial PEF measurements from Worker 2 were analysed using OASYS. The plot showed OA and OASYS score was 4.0. The top part of the chart shows the diurnal variation (DV) for each day. The middle of the chart shows the maximum, mean and minimum peak flow for each day. Workdays are shaded (diagonal slash bars are afternoon shifts, diagonal backslash bars are morning shifts) and the rest days are blank. The horizontal lines containing numbers in this part of the chart are scores for the work rest work and rest work rest complexes (seven complexes in total in this record). The bottom of the record shows the days, dates and number of readings per day for the record. Figure 2. SIC to nebulized 1 mg/ml cobalt chloride from Worker 2. The FEV 1 fell by 20%, from a baseline of 4.1 l to 3.21 l at 11 h post-challenge. After control challenge with nebulized 0.9% saline solution, FEV 1 remained within 15% of baseline.

4 G. I. WALTERS ET AL.: COBALT ASTHMA IN METALWORKERS 361 Case series Fourteen workers were diagnosed with OA due to cobalt, including the illustrative case. One further worker had OA with a positive SIC to used MWF but negative SIC to cobalt chloride 1 10 mg/ml. The demographics and diagnostic characteristics of the 14 workers with cobalt asthma are shown in Table 1. Twelve employees worked directly with stellite (six machine setter-operators, five stellite grinders, one stellite welder) and two indirectly (one packer and one electrician). All cases were diagnosed between 1996 and 2005, with a peak incidence of five cases diagnosed in 1999 (see Figure 3). The median duration of employment prior to onset of symptoms was 8 years (IQR = ) and median symptom latency prior to diagnosis was 30 months (IQR = 24 48). Cough (93%) and wheeze (93%) were the most commonly reported symptoms and 43% of workers had work-related rhinitis symptoms at diagnosis. All 14 workers reported Table 1. Characteristics of cobalt-exposed workers with OA, at diagnosis Workers, n 14 Gender; male, n (%) 12 (86) Ethnicity; white, British, n (%) 14 (100) Age at diagnosis, mean years (range) 44.9 (31 62) Smoking Never smokers, n (%) 8 (57) Ex-smokers, n (%) 5 (36) Active smokers, n (%) 1 (7) Atopic status History of prior or childhood asthma, n (%) 1 (7) Positive SPT to one or more 9 (64) common allergen, n (%) Positive SPT to cobalt chloride, 6/8 (75) n/total done (%) Presenting symptoms Any respiratory symptom, n (%) 14 (100) Cough, n (%) 13 (93) Wheeze, n (%) 13 (93) Breathlessness, n (%) 12 (86) Chest tightness, n (%) 12 (86) Nasal symptoms, n (%) 6 (43) Sputum, n (%) 4 (29) Sore throat, n (%) 4 (29) Eye symptoms, n (%) 3 (21) Dermatitis, n (%) 3 (21) Chest pain, n (%) 0 (0) Respiratory symptoms improve on days 14 (100) away from work or on holiday, n (%) NSBR (exposed at work) Bronchial hyper-responsiveness, n (%) 6 (43) Serial PEF measurements Work effect demonstrated, n (%) 14 (100) Spirometry FEV 1 /FVC, mean % (SD) 72.6 (11) FEV 1, mean % predicted; (SD) 87.1 (17) SIC to 1 10 mg/ml cobalt chloride Positive test, n/total done (%) 7/7 (100) respiratory symptoms that were better away from work at the weekend or on holiday. Seven out of 10 (70%) workers tested in clinic had urine cobalt concentration >2 μg/l, the level associated with occupational exposure (median = 2.6 μg/l; IQR = ). OASYS analysis of serial PEF readings from all 14 workers demonstrated OA (OASYS score range ). Nine workers had evidence of sensitization to cobalt, either by positive SPT to 1 10 mg/ml cobalt chloride (n = 6) or positive SIC to nebulized cobalt chloride 1 10 mg/ml (n = 7), or both. The details of positive SICs are shown in Table 2; there were three immediate, three dual and one late asthmatic reactions to cobalt chloride. The remaining five workers were diagnosed with cobalt asthma on the balance of probability, based on positive PEF records, clinical presentation and exposure patterns. Following diagnosis, eight cobalt workers were relocated within the company (three of whom remained exposed), two were retired, two made redundant and two remained exposed in the same job. Discussion Fourteen metalworkers from a single manufacturing company were diagnosed with OA due to cobalt between 1996 and Principally, workers were stellite grinders, stellite welders or machine setter-operators. All workers experienced asthma symptoms that were better away from work, either on days off or on holiday, and many showed features of occupational rhinitis (43%). All workers had positive OASYS analyses of serial PEF measurements, and sensitization to cobalt chloride was demonstrated in nine of those workers by SPT or SIC. Since 1989, new cases of OA in the West Midlands, UK, have been prospectively reported to the Midland Thoracic Society s SHIELD voluntary surveillance scheme, by regional respiratory and occupational physicians. Thus, the strength of this study is that we were able to identify all cases of cobalt asthma from a single employer. SHIELD receives notifications when OA is more likely than not, and no specific tests are required before notification. Acute irritant-induced asthma and work-exacerbated asthma are excluded, but no particular mechanism is required, provided that there is latency and regular deterioration related to occupational exposure. Our series is limited by the fact that five workers did not undertake cobalt-specific testing; the attribution of cobalt as the cause of the OA was made on the balance of probability, based on these workers having similar exposure patterns to workers with confirmed cobalt asthma. One additional worker (machine setter-operator) had a negative SIC to cobalt chloride and positive challenge to contaminated MWF, so there is the potential for attributing asthma to the incorrect agent. We have provided evidence for a sensitization mechanism in nine workers, with positive SICs and SPTs

5 362 OCCUPATIONAL MEDICINE Figure 3. Timeline of incident cases of cobalt asthma, by occupation. The index case was diagnosed with cobalt asthma in 1996, nine further cases were identified between 1998 and 2001, along with a case of contaminated MWF-related OA, and four further cases of cobalt asthma were diagnosed between 2003 and Grey-shaded boxes represent night-shift workers, unshaded boxes represent day-shift workers. Table 2. Characteristics of all SIC tests undertaken Worker Pre-SIC PD 20 (μg) Post-SIC PD 20 (μg) Nebulized control challenge Active nebulized challenge MWF (1% solution); 15 min Cobalt chloride 10 mg/ml; 3 min 2 > % saline; 5 min Cobalt chloride 1 mg/ml; 5 min 3 >4800 >4800 Aluminium chloride Cobalt chloride 10 mg/ml; 5 min 10 mg/ml; 5 min 4 >4800 >4800 Clean MWF (1% Cobalt chloride solution); 15 min 1 mg/ml; 10 min % saline; 20 min Cobalt chloride 5 mg/ml; 20 min Aluminium chloride Cobalt chloride 5 mg/ml; 12 min 5 mg/ml; 17 min Clean MWF (1% Cobalt chloride solution); 5 min 10 mg/ml; 5 min Other worker >4800 >4800 Cobalt chloride Used MWF (2% 10 mg/ml; 5 min solution) for 10 min PD 20, provocative dose that decreases FEV 1 by 20%, methacholine reactivity by the Yan method [21]. a Within 1 h post-challenge. b Greater than 1 h and up to 12 h post-challenge. % Max immediate reaction a % Max late reaction b to cobalt chloride, accompanied by a mean latency of exposure of 8 years (IQR = ) prior to symptom onset. This is consistent with documented reports of sensitization to cobalt in asthma [1 6] and dermatitis [25,26] in occupational settings. Both IgEdependent [15] and non-ige-dependent mechanisms have been implicated [16]. The workers in our series were predominantly atopic (64%), with positive SPTs to cobalt chloride (75%), and six of seven positive SICs to cobalt chloride were immediate (including dual) asthmatic reactions. This is suggestive of a predominant IgE-mediated response, although the measurement of serum-specific IgE to cobalt would have been helpful in this regard.

6 G. I. WALTERS ET AL.: COBALT ASTHMA IN METALWORKERS 363 Although we have previously reported a single case of cobalt asthma from the automotive manufacturing industry [18], this is the first case series in metalworkers described in detail. Cobalt asthma has been reported in cobalt production workers [7 9], diamond polishers [10 14] and a glassware factory worker [17]. Cobalt production workers have higher exposures [4,16] compared with other cobalt industries [27], and exposure from production work confers a 5-fold risk of asthma over non-exposed workers [5]. Our workers showed modest increases in urinary cobalt concentration (median = 2.6 μg/l) in keeping with non-production work exposures. We postulated that workers cobalt exposure increased significantly, firstly when a common sump for used MWF was installed, widely distributing cobalt-contaminated oil mist, and secondly when ventilation systems were switched off overnight to decrease noise. 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7 364 OCCUPATIONAL MEDICINE of 13 elements in blood and urine of a United Kingdom population. Sci Total Environ 1998;216: Dooms-Goossens A, Ceuterick A, Vanmaele N, Degreef H. Follow-up study of patients with contact dermatitis caused by chromates, nickel, and cobalt. Dermatologica 1980;160: Shum KW, Gawkrodger DJ. Occupational cobalt sensitivity in 2 hard-metal press operators. Contact Dermatitis 2002;47: Linnainmaa M, Kiilunen M. Urinary cobalt as a measure of exposure in the wet sharpening of hard metal and stellite blades. Int Arch Occup Environ Health 1997;69: Neurological memories One of my pleasures in reading journals is the stirring of memories, as when I read Dr Sealy s informative paper on the management of dizziness [1]. It started with a pithy quote from Dr WB Mathews book, Practical Neurology, published in How well I remember it! At that time, as a young medical registrar, I was attracted to a career in neurology and obtained a post that gave me a great deal of practical experience of the subject. Indeed, there was rather more than I would have wished for, as my consultant s main interest was in his private practice and he expected me to do his clinics with the help of the house physician. I was familiar with the standard large textbooks of neurology but quickly found they were deficient in practical advice on management. Dr Mathews book was a lifesaver, as it dealt with presenting symptoms rather than anatomical syndromes headache, dizziness, blackouts, etc. I quickly became an adequate substitute for my boss. Why did I not become a neurologist? It would certainly have become progressively easier as modern diagnostic techniques displaced carotid and vertebral angiograms, air encephalograms and frequent lumbar punctures, but it was not to be. I finally lost patience with my boss when he refused to come to his clinic to help me when my wife ran into difficulties in labour and I got my revenge by starting my outpatient letters with I saw your patient in the unexpected absence of Dr X. It worked he got a curt message from the professor of medicine, but I was instructed to change the format of my letters and when I refused he said: Don t ever ask me for a reference, Seaton! So I went into cardiology then chest medicine and doi: /occmed/kqu059 later added occupational medicine. In contrast, the house physician decided that medicine was not for him and became a knighted president of a surgical Royal College. In my day one didn t train formally in medicine. It was necessary every year or so to apply for the jobs one thought appropriate, while in one s spare time (before study leave) one wrote papers, passed exams, tried to do research and taught medical students, activities which in that very competitive world increased one s chances of obtaining the jobs one wanted. My knowledge of cardiology led me to propose a hypothesis to explain the cardiac effects of air pollution and to delve into the effects of inhaled nanoparticles. My experience of chest medicine led me to propose an explanation for the increase in asthma in relation to maternal diet during pregnancy. My interest in neurology led me to studies of neurological effects of chemicals and to propose that significant exposures to solvents may have diverse effects on the nervous system depending on the genetic susceptibilities of the individual. And Dr Mathews book inspired me to write with my colleagues a similar book for trainee occupational physicians, Practical Occupational Medicine. I hope you have a copy. Anthony Seaton Reference a.seaton@abdn.ac.uk 1. Sealy A. Vestibular assessment: a practical approach. Occup Med (Lond) 2014;64:78 86.