Search PubMed⌕ Search

Biomedical subjects

P S Burge

Publications and source records attributed to P S Burge.

At least 19 recordsLinked to original sources

Prednisolone response in patients with chronic obstructive pulmonary disease: results from the ISOLDE study.

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.

Administration, Oral↗

Bronchodilator reversibility testing in chronic obstructive pulmonary disease.

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.

Adult↗

Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with worse health and increased healthcare utilisation. The Inhaled Steroids in Obstructive Lung Disease in Europe (ISOLDE) study in COPD showed a 26% reduction in the yearly rate of exacerbations in patients treated with fluticasone propionate (FP) compared to placebo, but did not indicate which patients showed greatest benefit. In this study the patients were stratified into mild and moderate-to-severe COPD using the American Thoracic Society criterion of forced expiratory volume in one second (FEV1) 50% predicted, and the total number of exacerbations and those requiring treatment with oral corticosteroids were examined. There were 391 (195 FP) patients with mild COPD and 359 (180 FP) patients with moderate-to-severe disease. The exacerbation rate was highly skewed in mild disease, but more normally distributed in moderate-to-severe disease. FP reduced the overall exacerbation rate in moderate-to-severe disease (FP median rate 1.47 yr(-1), placebo 1.75 yr(-1)), but not in mild disease (FP 0.67 yr(-1), placebo 0.92 yr(-1)). FP use was associated with fewer patients with > or = 1 exacerbation x yr(-1) being treated with oral corticosteroids (mild: FP 8%, placebo 16%; moderate-to-severe: FP 17%, placebo 30%). Effects of fluticasone propionate on exacerbations were seen predominantly in patients with a postbronchodilator forced expiratory volume in one second <50% predicted. These data support recommendations in the Global Initiative for Chronic Obstructive Disease treatment guidelines that inhaled corticosteroids should be considered in patients with moderate-to-severe chronic obstructive pulmonary disease who experience recurrent exacerbations.

Administration, Inhalation↗

Guidance on standards of health for clinical health care workers.

Judgements about the health of clinical health care workers in relation to fitness to practice are made by a variety of doctors. These guidelines have been written to assist with such judgements and to facilitate equitable decision making in matters of employment.

Delivery of Health Care↗

Interpretation of occupational peak flow records: level of agreement between expert clinicians and Oasys-2.

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.

Asthma↗

Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants.

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.

Asthma↗

Occupational asthma caused by chloramines in indoor swimming-pool air.

The first series of three workers who developed occupational asthma following exposure to airborne chloramines in indoor chlorinated swimming pools is reported. Health problems of swimmers in indoor pools have traditionally been attributed to the chlorine in the water. Chlorine reacts with bodily proteins to form chloramines; the most volatile and prevalent in the air above swimming pools is nitrogen trichloride. Two lifeguards and one swimming teacher with symptoms suggestive of occupational asthma kept 2-hourly measurements of peak expiratory flow at home and at work, analysed using the occupational asthma system (OASYS) plotter, and/or had specific bronchial challenge testing to nitrogen trichloride, or a workplace challenge. Air measurement in one of the pools showed the nitrogen trichloride levels to be 0.1-0.57 mg x m(-3), which was similar to other studies. Two workers had peak expiratory flow measurements showing occupational asthma (OASYS-2 scores 2.88 and 3.8), both had a positive specific challenge to nitrogen trichloride at 0.5 mg x m(-3) with negative challenges to chlorine released from sodium hypochlorite. The third worker had a positive workplace challenge. Swimming-pool asthma due to airborne nitrogen trichloride can occur in workers who do not enter the water because of this chloramine. The air above indoor swimming pools therefore needs to be assessed and managed as carefully as the water.

Adult↗

Sensitisation to natural rubber latex: an epidemiological study of workers exposed during tapping and glove manufacture in Thailand.

OBJECTIVES: To estimate the prevalence of sensitisation to natural rubber latex in latex tappers and latex glove factory workers, and to relate this to airborne exposure to latex. METHODS: Five hundred workers employed in three latex glove factories, 314 tappers, and 144 college students (control group) were studied. The workers in the glove factories were classified into three exposure groups; high, moderate, and low. Personal exposures to natural rubber latex aeroallergens were measured by immunoassay. Symptom questionnaires and skin prick tests with latex allergens (Stallergènes 1:200 w/v) and other common environmental allergens were performed. The criterion for positivity was a wheal reaction at least 3 mm in diameter greater than that to a diluent control. RESULTS: The geometric mean (GM) concentration of latex in air was 15.4 microg/m(3) for those employed in glove stripping, glove inspections, and packing of powdered gloves. The moderate exposure glove manufacturing group and the tappers had GM concentrations of 2.3 and 2.4 microg/m(3) respectively, compared with United Kingdom users of latex powdered gloves,who had GM concentrations of 0.5 microg/m(3). The prevalence of sensitisation to latex in the tappers and latex glove factory workers was 1.3% and 1.7% respectively. No positive cases were found among the college students. Workers who showed a positive skin prick test to latex were more likely to be atopic. Work related respiratory and dermatological symptoms were found in about 20% of each population studied, but were not related to the presence of positive latex prick tests. CONCLUSIONS: This study suggests that in the Thai latex industries, latex sensitisation is rare despite high concentrations of airborne exposure and is less prevalent than in the healthcare sector in Europe where skin exposure is greater.

Adult↗

OASYS-3: improved analysis of serial peak expiratory flow in suspected occupational asthma.

Serial peak expiratory flow (PEF) records are useful for the screening and diagnosis of patients with occupational asthma. We have presented work on a method based on linear discriminant analysis (OASYS-2) and have now tried to improve on this technique and investigate the repeatabilities of expert interpretation. 268 serial PEF records made by workers with possible occupational asthma were divided into four sets. The first two were development sets; development set 1 was used to develop a discriminant analysis to match the human expert, who scored each complex (a sequence of work days, then rest days, then work days, or its counterpart: rest-work-rest) for its likelihood of having a work-related effect. This was modelled using 729 new measurements from each complex, together with the 50 measurements originally used in the development of OASYS-2. Linear discriminant analysis is a statistical technique which can refine from a large number of indices a narrower range that best predict a known outcome. Combinations of these indices are weighted and used to assign outcomes for novel cases. Models were produced containing a combination of measurements that generated scores best matching the expert. Development set 2 was used to test the model. Sets 3 and 4 were "gold standard" sets where the diagnosis had been made independently of the PEF record. Set 3 was used to set the cut-off for an occupational effect, the sensitivity and specificity for the combined model was determined from the fourth (gold standard) set. The fourth set was also used to determine the sensitivity and specificity of the human expert. The repeatability of the human expert re-scoring the same complexes had a weighted kappa score of 0.71. OASYS-3 was 100% repeatable. Comparing the scores awarded to whole records by the new (OASYS-3) and OASYS-2 analysis methods with the scores awarded by the human expert revealed mean (95% CI) differences of -0.28 (0.30, -0.26) and -0.34 (-0.37, -0.31) respectively. Hence both OASYS-3 and OASYS-2 tended to score records less positively for work-related changes in PEF than the expert. OASYS-3 scored complexes marginally better than OASYS-2. The sensitivity of OASYS-3 was better than OASYA-2 (82% and 75% respectively) for an equivalent specificity (94%). The sensitivity of the human expert was 100% with a specificity of 93%. OASYS-3 provides an objective method of interpreting serial peak flow records with a sensitivity and specificity approaching that of a human expert and is a modest improvement on OASYS-2.

Adult↗

Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.

OBJECTIVES: To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease. DESIGN: Double blind, placebo controlled study. SETTING: Eighteen UK hospitals. PARTICIPANTS: 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV(1)) 50% of predicted normal. INTERVENTIONS: Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo. MAIN OUTCOME MEASURES: Efficacy measures: rate of decline in FEV(1) after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events. RESULTS: There was no significant difference in the annual rate of decline in FEV(1 )(P=0.16). Mean FEV(1) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034). CONCLUSIONS: Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.

Administration, Inhalation↗

Natural rubber latex aeroallergen exposure in rubber plantation workers and glove manufacturers in Thailand and health care workers in a UK hospital.

OBJECTIVES: To estimate personal airborne natural rubber latex (NRL) concentrations for three occupational exposure groups; rubber plantation workers and NRL glove manufacturers in Thailand and health care workers in the UK. To utilise these data to classify the populations into appropriate exposure groups for the exposure-response analysis in the epidemiological study on latex allergy. METHODS: Two rubber plantations (110 workers), three NRL glove manufacturing factories (583 workers) in Thailand and one UK hospital (490 workers) were selected for the study. A preliminary workplace survey was carried out at each workplace in order to assign job titles subjectively in to high, moderate or low exposure groups for the purpose of sample selection. Between 5 and 20% of workers from each group for the three populations were then selected randomly for personal measurement of latex airborne allergens. Personal sampling was conducted using a 25 mm PTFE filter loaded in to an IOM sampling head at 2 l. min(-1). NRL aeroallergens were measured by an inhibition assay with NRL-specific IgE antibodies from NRL-sensitised people. RESULTS: A total of twenty-two personal samples were collected from plantation workers, sixty-one samples from the glove manufacturer employees and twenty seven from health care workers. The highest geometric mean (GM) NRL aeroallergen concentration was found in the glove manufacturing factories (7.3 microg m(-3)), followed by the rubber plantations (2.4 microg m(-3)) and the UK hospital (0.46 microg m(-3)). Amongst the NRL glove factories, the NRL aeroallergen concentrations were highest for those conducting the following tasks; glove stripping, glove inspections and packing of powdered gloves. The GM NRL aeroallergen for these tasks were in the range of 12.9 to 17.8 microg m(-3). CONCLUSIONS: In the process from tapping and manufacture of latex gloves through to their use the highest exposure to NRL aeroallergens is likely to occur in the manufacturing factories. Exposure to aeroallergens for the plantation workers was considered to be moderate and that of health care workers to be low.

Agriculture↗

An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease. ISOLDE Study Group.

Withdrawal of inhaled corticosteroids is known to worsen disease control in bronchial asthma but similar data are lacking in chronic obstructive pulmonary disease (COPD). We hypothesized that clinical exacerbations requiring treatment would occur more often in patients whose inhaled corticosteroids were stopped than in other patients not treated with these agents. We studied 272 patients in mean age 65 (SD 0.8) years, mean FEV1 42.8 (SD 12.6)% predicted, entering the run-in phase of the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) trial. All had been clinically stable for at least 6 weeks and there were no differences in the degree of bronchodilator reversibility, baseline lung function or pack-years of smoking between the 160 patients receiving inhaled corticosteroids and those not so treated. Inhaled corticosteroids were withdrawn in the first week of the study and during the remaining 7 weeks of the study 38% of those previously treated with these drugs had an exacerbation compared to 6% of the chronically untreated group. Patients receiving inhaled corticosteroids reported a longer duration of symptoms but neither this or any other recorded variable predicted the risk of exacerbation. These data suggest that abrupt withdrawal of inhaled corticosteroids should be monitored carefully even in patients with apparently irreversible COPD.

Administration, Inhalation↗

Glutaraldehyde: an occupational hazard in the hospital setting.

BACKGROUND: We report a series of 24 health-care workers with respiratory symptoms suggestive of occupational asthma due to glutaraldehyde exposure. METHODS: The history of asthmatic symptoms was investigated with peak expiratory flow rate (PEFR) monitoring, and in eight of the subjects, the specific bronchial provocation test (SBPT) was applied as reference standard for diagnosis of occupational asthma. Levels of glutaraldehyde were monitored in the challenge chamber during the SBPT. Work environmental levels of glutaraldehyde were measured from air samples collected at least once during the PEFR monitoring of endoscopy and theatre nurses. Specific IgE antibodies to glutaraldehyde were measured with a series of glutaraldehyde modified proteins. RESULTS: In the eight workers who underwent SBPT, the diagnosis of occupational asthma was confirmed by a positive reaction (late and dual reaction in five and in three subjects, respectively). The mean level of glutaraldehyde observed during the challenge tests was 0.075 mg/m3 (range 0.065-0.084 mg/m3). In 13 out of the 16 remaining workers, the serial PEFR monitoring showed a work-related effect. In three workers, there was no physiological confirmation of occupational asthma. Levels of glutaraldehyde from the air samples collected in the workplace were as follows: personal short-term samples (mean 0.208 mg/m3; median 0.14 mg/m3; range 0.06-0.84 mg/m3), personal long-term samples (mean 0.071 mg/m3; median 0.07 mg/m3; range 0.003-0.28 mg/m3). Measurements of specific IgE antibodies to glutaraldehyde-modified proteins were positive in seven patients (29.1%) according to a cutoff value of 0.88% RAST binding. The presence of atopy to common environmental allergens and smoking was not associated with specific IgE positivity (P>0.05; Fisher's exact test). CONCLUSIONS: Our report indicates the importance of glutaraldehyde as an occupational hazard among exposed health-care workers. Intervention in the workplace, training of personnel handling this chemical, and accurate health surveillance may reduce the risk of developing occupational asthma due to glutaraldehyde.

Adult↗