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1.  Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant 
Thorax  2007;62(11):981-990.
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.
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.
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.
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.
PMCID: PMC2117138  PMID: 17504818
2.  Immune response to flour and dust mites in a United Kingdom bakery. 
In a study of 279 United Kingdom bakery workers a high prevalence of immunological response to storage mites was found. To determine whether this was the consequence of exposure to storage mites in bakery work, a population of salt packing workers was examined as a comparison group not at occupational risk of exposure to storage mites. Forty two per cent of both groups were atopic (had a positive skin prick response greater than negative controls to D pteronyssinus, grass pollen, or cat fur by 2 mm or more) and 33% had an immediate skin prick test response to at least one of four storage mites (L destructor, G domesticus, T putrescentiae, A Siro). A higher percentage of the salt packing workers than the bakery workers had a positive radioallergosorbent test (RAST) (greater than or equal to 0.35 PRU) to D pteronyssinus and to the four storage mites. Logistic regression analysis identified atopy as the most significant variable for a positive skin test and RAST response to storage mites in both groups of workers. RAST inhibition was used to analyse extracted area and personal air samples. Analysis of static area samples for aeroallergen showed immunological identity with flour but L destructor was found in only one of seven exposed filters. The concentration of airborne flour was related to exposure rank of perceived dustiness and gravimetric measurement of total dust. Nineteen out of 32 filters from workers in jobs with higher dust exposure (rank >/=6) had a level of > 10 microgram/m(3) flour whereas this concentrations was exceeded in only one of 23 filters from workers in low dust exposure (< rank 6). It is concluded that storage mites are not of special significance in allergic responses in bakery workers. The development of immunological (and airway) responsiveness to inhaled flour dust is increased in those exposed to higher concentrations of airborne allergen, which appears to be predominantly flour and not storage mites.
PMCID: PMC1039292  PMID: 1515350
3.  Factors relating to the development of respiratory symptoms in coffee process workers. 
After several cases of occupational asthma had been reported in a coffee processing factory in England, 197 coffee workers representing 80% of the production workforce were studied to determine the factors affecting the development of work related respiratory symptoms of wheeze, cough, and dyspnoea. Two computer administered questionnaires concerning the presence of respiratory symptoms and the occurrence of work related respiratory symptoms were used. Workers underwent skin prick testing to green coffee bean extract (GCB) and 11 common inhalant allergen extracts and bronchial provocation testing with methacholine. The presence of specific immunoglobulin E (IgE) antibodies to GCB and castor bean extract (CAB) were determined by a radioallergosorbent test (RAST). The prevalence of work related respiratory symptoms was 12.7%, bronchial hyperresponsiveness 30%, atopy 54%, positive GCB skin prick test 14.7%, positive GCB RAST 14%, and positive CAB RAST 14.7%. None of the workers was sensitised to fungi present in the factory and the numbers of certain species of fungi, despite being greater than may be found out of doors or in an uncontaminated indoor environment, were fewer than are generally associated with the presence of work related respiratory symptoms among agricultural workers. Storage mites were not isolated. Green coffee bean extract and CAB RAST were significantly correlated using the McNemar test but there was limited allergenic cross reactivity in RAST inhibition studies of the two extracts. The only factors that were significantly and independently associated with work related symptoms were CAB RAST and duration of employment. Bronchial hyperresponsiveness was not independently associated with work related respiratory symptoms. The significant independent associations of bronchial hyperresponsiveness included GCB RAST, duration of employment, and resting forced expiratory volume in one second. Exposure to CAB, a highly potent antigen, may be overriding the effects of other factors such a GCB, atopy, bronchial hyperresponsiveness, and smoking. This study suggests that CAB contamination remains a potential problem in the coffee processing industry and all efforts to eliminate it from the working environment should continue.
PMCID: PMC1012039  PMID: 2039743
4.  Respiratory symptoms, lung function, and sensitisation to flour in a British bakery. 
A survey of dust exposure, respiratory symptoms, lung function, and response to skin prick tests was conducted in a modern British bakery. Of the 318 bakery employees, 279 (88%) took part. Jobs were ranked from 0 to 10 by perceived dustiness and this ranking correlated well with total dust concentration measured in 79 personal dust samples. Nine samples had concentrations greater than 10 mg/m3, the exposure limit for nuisance dust. All participants completed a self administered questionnaire on symptoms and their relation to work. FEV1 and FVC were measured by a dry wedge spirometer and bronchial reactivity to methacholine was estimated. Skin prick tests were performed with three common allergens and with 11 allergens likely to be found in bakery dust, including mites and moulds. Of the participants in the main exposure group, 35% reported chest symptoms which in 13% were work related. The corresponding figures for nasal symptoms were 38% and 19%. Symptoms, lung function, bronchial reactivity, and response to skin prick tests were related to current or past exposure to dust using logistic or linear regression analysis as appropriate. Exposure rank was significantly associated with most of the response variables studied. The study shows that respiratory symptoms and sensitisation are common, even in a modern bakery.
PMCID: PMC1009839  PMID: 2789967
5.  Diagnosis of coronary artery disease by estimation of coronary sinus lactate. 
British Heart Journal  1978;40(9):979-983.
In an attempt to assess the value of coronary sinus lactate estimation before and during atrial pacing for the diagnosis of obstructive coronary artery disease, 70 patients with angina were investigated in this way and by selective coronary arteriography. Thirty-five had radiologically normal coronary arteries and 35 had coronary artery disease. When the change in coronary arteriovenous lactate difference was less than 0.09 mmol/l (0.8 mg/100 ml) between the control and the peak atrial pacing sample, the coronary arteries were normal except in one patient who had distal disease of a single vessel. When the change was greater than 0.22 mmol/l (2.0 mg/100 ml) coronary artery disease was always found, and when the change was greater than 0.39 mmol/l (3.5 mg/100 ml) there was always disease of two or three vessels. Unfortunately, the presence or absence of coronary artery disease could not be predicted when the change fell between 0.09 and 0.22 mmol/l (0.8 and 2.0 mg/100 ml). Estimation of coronary sinus lactate before and during atrial pacing can thus frequently distinguish patients with normal coronary arteries from those with coronary artery disease.
PMCID: PMC483520  PMID: 708539
6.  Letter from...Holland. Pastures new for cardiac surgery. 
British Medical Journal  1978;1(6106):159-160.
PMCID: PMC1602822  PMID: 620237
7.  Clinical electrophysiological effects of atenolol--a new cardioselective beta-blocking agent. 
British Heart Journal  1978;40(1):14-21.
Atenolol, a cardioselective beta-blocking agent, at dose levels of 0.03, 0.06, and 0.12 mg/kg intravenously, produced prolongation of atrioventricular nodal conduction in 22 patients with suspected coronary artery disease. In a dose of 0.12 mg/kg body weight atenolol produced significant prolongation of sinus cycle length, sinus node recovery time, atrioventricular node conduction, and the effective and functional refractory periods of the atrium and the atrioventricular node. No significant effects were observed on the His Purkinje system or the effective refractory periods of the ventricle. In these actions atenolol closely resembles propranolol. However, because in contrast to propranolol it increases atrial refractoriness, it may have advantages in the treatment of atrial arrhythmias.
PMCID: PMC481968  PMID: 341927
8.  Indirect measurement of sinoatrial conduction time in patients with sinoatrial disease and in controls. 
British Heart Journal  1977;39(7):771-777.
Clinical recognition of sinoatrial disease currently depends on the presence of transient sinus bradycardia, sinoatrial block, or supraventricular tachyarrhythmias. The value of clinical electrophysiological assessment in these patients is not clear. Using intracardiac electrophysiological recordings and programmed stimulation we have examined 14 patients with sinoatrial disease and 11 control patients undergoing investigation for chest pain. Intracardiac conduction times were normal in all patients. There was no significant difference of sinus node recovery times between the sinoatrial disease and control groups. Sinoatrial conduction times were measured by the indirect method and two populations were identified. However, the mean values of 128 +/- 27 ms in patients and 112 +/- 30 ms in controls were not significantly different and major overlap rendered this measurement clinically valueless. It is concluded that no current electrophysiological measurement has diagnostic value in patients with sinoatrial disease.
PMCID: PMC483315  PMID: 884027
10.  Mycotic aneurysms of coronary arteries. 
British Heart Journal  1973;35(1):107-109.
PMCID: PMC458573  PMID: 4739316

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