Population based epidemiology and prognosis of mesothelioma in Leeds, UK.

INTRODUCTION: Malignant mesothelioma is a fatal neoplasm, which is rapidly increasing in incidence throughout Western Europe. To date there have been no studies reporting on the natural history and interventional practices on a comprehensive unselected population, as opposed to reports from referral institutions or compensation claimants. We present a population based study capturing data on all patients with mesothelioma presenting within a defined geographical area over a 4 year period in the UK. METHOD: Data of all cases occurring in Leeds with a population of 750 000 were collected retrospectively from 2002 to 2003 and prospectively from 2004 to 2005. All patients' hospital records and the Trust histology database were reviewed, as well as coroner's reports on all patients with a post mortem diagnosis of mesothelioma. RESULTS: Over the 4 year study period, there were a total of 146 cases in Leeds; 77% were male. Median age was 74 years (range 36-93). Median survival from diagnosis was 8.9 months. 92% and 8% had histological or cytological confirmation, respectively. 85% had documented evidence of definite or probable exposure to asbestos. 110/146 (75%) had symptomatic pleural effusions at presentation. Twice the number of patients (42 vs 17) were managed with surgical rather than bedside pleurodesis and these had a lower recurrence rate (14% vs 47%; p = 0.02). 122 patients had video assisted thoracoscopic surgery/cutting CT biopsies or chest drains. 73/122 (60%) had prophylactic radiotherapy to these sites. There were seven cases (5%) of tract invasion by tumour and six of these had received prophylactic radiotherapy. Median time to seeding was 174 days. 92/146 (63%) had a performance status of 2 or better at diagnosis but only 54/146 were considered fit for chemotherapy. Of these, 28 (52%) declined chemotherapy; the overall uptake of chemotherapy or entry into a trial was 18%. No patient had radical surgery. CONCLUSION: This comprehensive population based audit has shown that the median age at presentation of malignant mesothelioma is increasing and baseline performance status and survival is worse than in selected series. 37% of patients were considered suitable for palliative chemotherapy but less than 20% accepted this offer. Thorascopic pleurodesis appears to be associated with fewer recurrences. The role of prophylactic radiotherapy to chest drain and biopsy sites needs reappraisal.

Do elderly people with lung cancer benefit from palliative radiotherapy?

The median age at diagnosis of patients with lung cancer is currently around 70 and is rising, yet the trials on which treatment is based included few elderly people. We conducted a prospective observational cohort study of 83 elderly patients (aged 75 and above) being treated with palliative radiotherapy for lung cancer, with a comparison group of 49 younger patients (aged 65 and under). Response to treatment was evaluated by patient-assessed symptom and quality of life scores using the EORTC QLQ-C30 and its companion lung module LC17. This is to date the largest prospective study of elderly lung cancer patients in routine practice. We found no significant differences in response or toxicity between the two groups. Elderly people with lung cancer should be offered palliative radiotherapy the same as younger patients, with the same expectation of benefit.

Understanding alpha-globin gene regulation: Aiming to improve the management of thalassemia.

Over the past 50 years, many advances in our understanding of the general principles controlling gene expression during hematopoiesis have come from studying the synthesis of hemoglobin. Discovering how the alpha- and beta-globin genes are normally regulated and documenting the effects of inherited mutations that cause thalassemia have played a major role in establishing our current understanding of how genes are switched on or off in hematopoietic cells. Previously, nearly all mutations causing thalassemia have been found in or around the globin loci, but rare inherited and acquired trans-acting mutations are being found more often. Such mutations have demonstrated new mechanisms underlying human genetic disease. Furthermore, they are revealing new pathways in the regulation of globin gene expression that, in turn, may open up new avenues for improving the management of patients with common types of thalassemia.

Effect of regular use of high-dose nebulized beta2-agonists on resting energy expenditure, weight, and handgrip strength in patients with chronic airflow limitation.

STUDY OBJECTIVES: A proportion of patients with chronic airflow limitation (CAL) have a raised resting energy expenditure (REE). The mechanism underlying this is not known. The question of whether the increased REE seen in some patients with CAL is due to beta2-agonist therapy has arisen, and the aim of this study was to examine REE, body composition, and peripheral muscle strength in patients before and after the use of regular high-dose beta2-agonists administered by nebulizer. DESIGN: Prospective observational study. SETTING: Respiratory outpatient clinic. PARTICIPANTS: Twenty outpatients with CAL being considered for a home nebulizer prescription. INTERVENTIONS: REE was measured by indirect calorimetry. Fat-free mass and handgrip strength were measured. Quality of life was assessed by the St. George's Hospital Respiratory Questionnaire. All subjects were assessed independently of this study for provision of a home nebulizer using a standard protocol. Based on the assessment, either standard-dose salbutamol therapy was continued or a nebulizer was provided with a prescription for high-dose salbutamol (5 mg qd). A mean of 8.1 months later (range, 3 to 16 months), 16 patients were restudied. MEASUREMENTS AND RESULTS: Eight patients had been taking regular high-dose nebulized salbutamol, and eight had continued taking standard-dose salbutamol by metered dose inhaler. There was no difference in baseline measures between the group who were later prescribed high-dose salbutamol and the group who were not. There were no changes in REE, anthropometric measures, or handgrip strength over time in either of the groups. CONCLUSIONS: The long-term use of high-dose nebulized beta2-agonists in patients with chronic airflow limitation has no effect on baseline REE, handgrip strength, weight, or body composition.

Modified ice study: a phase II study of an intensive, modified ICE regimen (ifosfamide, carboplatin and etoposide) in patients with better prognosis, small cell lung cancer.

A total of 30 with good prognosis small cell lung cancer were treated with a modified 'ICE' (ifosfamide, carboplatin and etoposide) chemotherapy regimen in an attempt to achieve a high response rate with less toxicity than is seen with the full 'ICE' regimen. This was given every 4 weeks for a maximum of six cycles. In total 25 patients (83%, 95% CI (70-97%)) experienced a partial or complete response at some stage of their treatment. Of these patients, 12 (40%, 95% CI (22-58%)) showed a complete response. A total of 19 patients (63%) had to have their dose reduced and/or delayed at some point due to toxicity. Nadir blood counts showed that 19 patients (63%, 95% CI (46-81%)) had WHO grade 3 or 4 thrombocytopenia, and 24 (86%, 95% CI (73-99%)) had grade 3 or 4 neutropenia. A total of 17 patients (53%) completed six cycles of chemotherapy. In total 3 patients died during treatment all due to treatment-related complications. Median survival was 12.6 months (95% CI (11.6, 14.7 months)). Nausea, vomiting, dysphagia, activity, mood and overall condition, as recorded using daily diary cards, were worse at the beginning of each chemotherapy cycle. Both response rates and survival were clinically acceptable. However, neutropenia and thrombocytopenia, although reduced from rates reported with the full ICE regimen, were still high. A prospective randomised controlled trial is now needed to assess this regimen in more detail.

Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common diseases of the airways and lungs that have a major impact on the health of the population. The mainstay of treatment is by inhalation of medication to the site of the disease process. This can be achieved by a number of different device types, which have wide variations in costs to the health service. A number of different inhalation devices are available. The pressurised metered-dose inhaler (pMDI) is the most commonly used and cheapest device, which may also be used in conjunction with a spacer device. Newer chlorofluorocarbons (CFC)-free inhaler devices using hydrofluoroalkanes (HFAs) have also been developed. The drug is dissolved or suspended in the propellant under pressure. When activated, a valve system releases a metered volume of drug and propellant. Other devices include breath-actuated pMDIs (BA-pMDI), such as Autohaler and Easi-Breathe. They incorporate a mechanism activated during inhalation that triggers the metered-dose inhaler. Dry powder inhalers (DPI), such as Turbohaler, Diskhaler, Accuhaler and Rotahaler, are activated by inspiration by the patient. The powdered drug is dispersed into particles by the inspiration. With nebulisers oxygen, compressed air, or ultrasonic power is used to break up solutions or suspensions of medication into droplets for inhalation. The aerosol is administered by mask or by a mouthpiece. There has been no previous systematic review of the evidence of clinical effectiveness and cost-effectiveness of these different inhaler devices. OBJECTIVES: To review systematically the clinical effectiveness and cost-effectiveness of inhaler devices in asthma and COPD. METHODS: The different aspects of inhaler devices were separated into the most clinically relevant comparisons. Methods involved systematic searching of electronic databases and bibliographies for randomised controlled trials (RCTs) and systematic reviews. Pharmaceutical companies and experts in the field were contacted for further information. Trials that met the inclusion criteria were appraised and data extraction was under-taken by one reviewer and checked by a second reviewer, with any discrepancies being resolved through agreement. RESULTS--IN VITRO CHARACTERISTICS VERSUS IN VIVO TESTING AND CLINICAL RESPONSE: There is evidence that when comparative testing is performed on inhaler devices using the same methods, there is some correlation between particle size measurements and clinical response. However, the measurements are dependent upon the methods used, and a single measure of a device in isolation is of limited value. Also, there is little data on comparing devices of different types. There is currently insufficient data to verify the ability of in vitro assessments to predict inhaler performance in vivo. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF CORTICOSTEROIDS IN ASTHMA: The review of three trials in children and 21 trials in adults demonstrated no evidence to suggest clinical benefits of any other inhaler device over a pMDI in corticosteroid delivery. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF BETA-AGONISTS IN STABLE ASTHMA: In children, 11 studies were reviewed, of which seven compared the Turbohaler with the pMDI. One study found a significant treatment difference in peak expiratory flow rate, although there were differences in the patients' baseline characteristics. In adults, a review of 70 studies found no demonstrable difference in the clinical bronchodilator effect of short-acting b2-agonists delivered by the standard pMDI compared with that produced by any other DPI, HFA-pMDI or the Autohaler device. The finding that HFA-pMDIs may reduce treatment failure and oral steroid requirement in beta-agonist delivery needs further confirmatory research in adequately randomised clinical trials. RESULTS--EFFECTIVENESS OF NEBULISERS VERSUS METERED-DOSE INHALERS FOR THE DELIVERY OF BRONCHODILATORS IN STABLE ASTHMA: In children, three included trials compared different devices with a nebuliser and demonstrated no evidence of clinical superiority of nebulisers over inhaler devices in bronchodilator delivery. A total of 23 studies in adults found no equivalence for the main pulmonary outcomes and no evidence of difference in other outcomes. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF BETA-AGONISTS IN COPD: Only two studies were included in this review. No evidence of clinical difference was found in beta-agonist delivery. RESULTS--EFFECTIVENESS OF NEBULISERS VERSUS METERED-DOSE INHALERS FOR THE DELIVERY OF BRONCHODILATORS IN COPD: Evidence from 14 trials demonstrated equivalence for the main outcomes of pulmonary function. For other outcomes there was no evidence of treatment difference in bronchodilator delivery. RESULTS--PATIENTS' ABILITY TO USE METERED-DOSE INHALERS: Differences among studies and the heterogeneity of the results make it difficult to draw conclusions about inhaler technique differences between device types. The review of technique after teaching the correct technique suggests that there is no difference in patients' ability to use DPI or pMDIs. RESULTS--ECONOMIC ANALYSIS: The total number of NHS prescriptions for inhaler therapy for asthma in 1998 was over 31 million, with a net ingredient cost in excess of 392 million GB pounds. This economic assessment uses decision analysis to estimate the relative cost-effectiveness of inhaler devices for the delivery of bronchodilator and corticosteroid inhaled therapy. Overall, there were no differences in patient outcomes among the devices. On the assumption that the devices were clinically equivalent, pMDIs were the most cost-effective devices for asthma treatment. CONCLUSIONS: This systematic review examined the evidence from clinical trials evaluating the clinical effectiveness of different inhaler devices in the delivery of inhaled corticosteroids and beta2-bronchodilators for patients with asthma and COPD. The evidence from the published clinical literature demonstrates no difference in clinical effectiveness between nebulisers and alternative inhaler devices compared to standard pMDI with or without a spacer device. The cost-effectiveness evidence therefore favours pMDIs (or the cheapest inhaler device) as first-line treatment in all patients with stable asthma unless other specific reasons are identified. Patients can use pMDIs as effectively as other inhaler devices as long as the correct inhalation technique is taught. CONCLUSIONS--RECOMMENDATIONS FOR RESEARCH: Further clinical trials are required to demonstrate any differences in the clinical effectiveness and cost-effectiveness of inhaler devices and nebulisers compared with pMDIs. These should be of sufficient statistical power and methodological rigour to demonstrate any clinical benefit. Trials should be undertaken in community settings to ensure the generalisability of results. Outcome measures should be more patient-centred and report adverse effects more completely. Reporting of data from trials should be improved.

Lung cancer: district active treatment rates affect survival.

STUDY OBJECTIVE: This study investigates variation in management and treatment of lung cancer patients and determines the impact of any variation in treatment on survival. DESIGN: A retrospective study of population based data held by the Northern & Yorkshire Cancer Registry and Information Service (NYCRIS), comparing active treatment rates for lung cancer with survival by districts. SETTING The then 17 districts in Yorkshire and South Humber, England. PATIENTS: 22 654 patients registered with lung cancer between 1986 and 1994 and followed up until end of 1996. RESULTS: The overall rates of active treatment (surgery, radiotherapy, and chemotherapy) varied between districts from 37% to 56%. One year survival (with 95% CI) was significantly better in the districts with highest rates of active treatment 23% (22% to 24%) compared with 19% (17% to 20%) for those with lowest treatment rates. Non-small cell lung cancer patients (55%) in the districts with highest active treatment rates had an age adjusted relative risk of death during the follow up period, relative to risk of death in the districts with the lower treatment rates of 0.88 (0.83 to 0.92). Clinically diagnosed patients (34%) had an age adjusted RR of 0.92 (0.86 to 0.96). RR in small cell cancer (11%) was not significant. CONCLUSION: This study has shown wide variations in the rates of active treatment for lung cancer patients within districts across one large region of England. Active treatment was strongly associated with improved survival, especially in non-small cell lung cancer.

A simple radiographic scoring method for monitoring pulmonary sarcoidosis: relations between radiographic scores, dyspnoea grade and respiratory function in the British Thoracic Society Study of Long-Term Corticosteroid Treatment.

BACKGROUND: We used a simple semi-quantitative radiographic scoring system for a controlled prospective study of long term corticosteroids in pulmonary sarcoidosis, conducted by the British Thoracic Society. METHODS: Radiographic opacities were described in 4 categories: reticulo-nodular shadows [R], mass opacities [M], confluence [C], and shadows associated with possible pulmonary fibrosis [F]. The extent of each type was scored on a 0-4 scale by quartiles, and profusion by a 0-4 scale as absent, minimal (just perceptible), mild moderate or gross. Combined scores for each film were derived by multiplying the extent and profusion for each type of opacity. In the study 149 patients were examined at entry and periodically over a 5-year period. Using the whole study population we examined the relationship between the radiographic scores for extent and profusion, how predominant types change with time and how the scores correlated with other indices of disease severity. RESULTS: R was the predominant abnormality throughout the study with a strong correlation between extent and profusion. Significant correlations in the expected directions were demonstrated between the R and F scores and a dyspnoea score, spirometry and TLCO, both at study entry, after 6 months and after 5 years. Similarly, there were significant relations between changes in spirometry and TLCO over five years and changes in R and F Scores. CONCLUSION: This scoring system would seem to be suitable, perhaps after further validation work, for other prospective clinical studies.

The incidence of airflow obstruction in bronchial carcinoma, its relation to breathlessness, and response to bronchodilator therapy.

Breathlessness is a common symptom in patients with primary bronchial carcinoma and is often not well-controlled. Most patients are ex- or current smokers, and therefore are at high risk for co-existing chronic obstructive pulmonary disease (COPD). The incidence of airflow obstruction in patients with bronchial carcinoma, its relation to breathlessness, and response to bronchodilator therapy was examined prospectively. Fifty-seven consecutive patients attending our outpatient clinic with bronchial carcinoma diagnosed in the preceding 12 months were studied (22 female, 35 male, mean age 68.4 years). Spirometry was performed and breathlessness rated. Those with airflow obstruction (FEV1:FVC < 65% and FEV1 < 70% predicted) and who judged themselves to have moderate or severe breathlessness, were offered a trial of bronchodilator therapy. The response to regular inhaled fenoterol and ipratropium bromide by metered dose inhaler (MDI) and large volume spacer, and to regular nebulized salbutamol and ipratropium bromide was assessed by home peak flow recordings, spirometry and two subjective scores: (a) rating of breathlessness on a simple four-point scale, and (b) activity score of the St George's Respiratory Questionnaire. There was very strong association between airflow obstruction and breathlessness. Twenty-eight patients (49%) had airflow obstruction, and we had breathlessness ratings on 26 of these patients of whom 18 (69%) had rated it as moderate or severe. Only four of the patients with airflow obstruction and breathlessness were using bronchodilator therapy. There was no significant difference in the mean age, time from diagnosis, tumour site, or smoking history between the groups with, and without, airflow obstruction. There was no association between cell type and the presence of airflow obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Simplifying the assessment of patients with chronic airflow limitation for home nebulizer therapy.

One-hundred nebulizer trials were performed in 98 adult patients with chronic airflow limitation who had remained symptomatic despite regular use of bronchodilators by metered dose or dry powder inhalation. Mean baseline FEV1 was 0.9 (SD = 0.41) 1, FVC -2.0 (0.74) 1 and PEFR 169 (77) 1 min-1. After laboratory measurements of reversibility to inhaled salbutamol (5 mg) and ipratropium bromide (0.5 mg), patients were supplied with a compressor and a peak flow meter to make twice daily measurements at home for 3 weeks. They nebulized normal saline, salbutamol (5 mg) and salbutamol (5 mg) ipratropium (0.5 mg) mixture 6-hourly, each for 1 week. A positive nebulizer trial was defined as a 15% increase in mean PEFR over a week on an active treatment compared to the week on saline. Twenty-eight patients had positive trials based on these criteria. Of these nine responded to both active treatments and 16 to the salbutamol/ipratropium mixture. Although no laboratory measurements predicted a positive domiciliary trial, the patients' subjective assessment of benefit had a 93% sensitivity and 87% negative predictive value. We conclude that an appropriate protocol for assessing the value of long-term nebulized bronchodilators is for patients to measure their PEFR during a week of nebulized saline and a week of nebulized beta-agonist/ipratropium mixture. Those with an increase of 15% in mean PEFR in the week on active treatment and who experienced subjective benefit should be supplied with a compressor. Had we conducted our 100 trials in this way we would have started 25 of our 98 patients on long-term home nebulized bronchodilators.

Local anaesthesia for fibreoptic bronchoscopy: comparison between intratracheal cocaine and lignocaine.

In a double-blind study of 60 patients undergoing fibreoptic bronchoscopy we have compared the local anaesthetic effects of intratracheal injections of cocaine (4 ml, 2.5%) and lignocaine (4 ml, 4%). The two local anaesthetics were equally effective in terms of cough suppression, requirement for extra local anaesthetic, patient discomfort and operator acceptability.

Response to nebulized ipratropium bromide and terbutaline in acute severe asthma.

Outpatient studies on asthmatics have shown that inhaled anti-cholinergic agents decrease in efficacy as FEV1 falls. To determine whether there are changes in response to inhaled anti-cholinergics during acute bronchoconstriction we have examined the effects of nebulized ipratropium and terbutaline in nine hospitalized patients recovering from acute severe asthma. At 6 a.m. each day throughout the admission, baseline PEFR was recorded. Ipratropium bromide, 1 mg, was nebulized and PEFR measured again 1 h later. Following this, terbutaline, 5 mg, was nebulized with further measurement of PEFR 15 min after nebulization. Results were analysed by paired t-tests. Mean baseline PEFR rose from 157 l m-1 on patients worst day to 300 l m-1 on their best day (P less than 0.01). Ipratropium improved mean PEFR by 55 l m-1 and 42 l m-1 on patients worst and best days respectively (P less than 0.01). Subsequent terbutaline improved mean PEFR on patients worst day by 23 l m-1 (P less than 0.01) but only by a non-significant 4 l m-1 on their best day (P = 0.09). Hence, ipratropium produced 96% of total bronchodilatation when baseline was highest, but achieved only 71% of total response when baseline was lowest, a highly significant change in response (P less than 0.01). We conclude that in acute severe asthma as baseline PEFR rises response to inhaled ipratropium improves, compared with total response to combined ipratropium followed by terbutaline.

Reversibility tests in chronic obstructive airways disease: their predictive value with reference to benefit from domiciliary nebuliser therapy.

The role of short-term tests of reversibility in selecting patients with COAD for long-term nebuliser therapy is uncertain. In a double-blind placebo-controlled crossover study we have examined the correlation between short-term reversibility and response to a home nebuliser. We studied 20 patients with severe COAD (mean age 66, mean FEV1 0.81 l) and little reversibility (less than 20% increase in FEV1 post-inhaled salbutamol 200 micrograms and less than 25% increase in peak expiratory flow rate, PEFR, on oral steroids). PEFR, spirometry, lung volumes and airways conductance were recorded before and 1 h after a mixture of nebulised ipratropium 0.5 mg and fenoterol 1.25 mg. Patients then recorded twice-daily PEFR at home while they received nebulised ipratropium plus fenoterol, or saline placebo, four times a day for three week blocks using a double-blind cross over protocol. Mean PEFR on home nebuliser rose from 164 l m-1 (placebo) to 196 l m-1 (ipratropium plus fenoterol), paired t-test P = 0.0001. Correlation coefficients between short-term response for PEFR, spirometry and lung volumes, and improvement in home PEFR on nebulised ipratropium plus fenoterol, were all poor (R = -0.37-0.35, P = 0.83-0.11). We conclude that in severe COAD, reversibility tests of PEFR, spirometry and lung volumes do not correlate with response to a home nebuliser. Home measurements of PEFR are probably the best objective method of assessing response to a home nebuliser in such patients.

Living with severe COPD. A qualitative exploration of the experience of patients in Leeds.

A sample of 37 patients with severe chronic obstructive pulmonary disease (COPD) drawn from a larger group of 64 patients being studied in a randomized trial of nebulizer versus high-dose inhaler therapy, and similar in age and gender mix, was interviewed in depth, with a view to illuminating standardized outcome measures and improving the understanding of these patients' needs. Three patients are described in detail. The interview material was analysed using non-computerized methods. Quality of life was seen as depending mainly on family relationships, opportunities afforded locally for neighbourliness and freedom from fear, mobility and independence in the activities of daily living, and the absence or successful mitigation of symptoms of concomitant disease. Disease-specific, symptom-oriented outcome measures may miss these. Additionally, the near and repeatedly threatening approach of death recommended extension of a palliative approach to endstage COPD.

Assessment and provision of home nebulizers for chronic obstructive pulmonary disease (COPD) in the Yorkshire region of the U.K.

A survey was undertaken to determine the current practice in the Yorkshire Health Region for the assessment and provision of home nebulizers for adults with chronic obstructive pulmonary disease (COPD). A detailed postal questionnaire on assessment methods was sent to each of the 22 consultant physicians in respiratory medicine. The 17 consultants who also organized the adult home nebulizer service for their health district were asked about the services offered and funding for the service. Replies were received from all consultants. All physicians use objective measurement for assessing patients for home nebulizer therapy, but there is a variable emphasis on laboratory studies, walking distance and home trials with peak flow measurements. The majority (86%) incorporate a home trial into their assessment. Many physicians also take into account subjective response to nebulized bronchodilators. There is considerable variation in the provision and funding of home nebulizer services. Those districts with a coordinated service appear to offer a more comprehensive service. A consensus on nebulizer provision, with recommendations for minimum levels of provision in each health district, should result in a more uniform delivery of service.

Pressurised metered-dose inhalers versus all other hand-held inhalers devices to deliver bronchodilators for chronic obstructive pulmonary disease.

BACKGROUND: Bronchodilator therapy for COPD may be delivered by a number of different inhaler devices. OBJECTIVES: To determine the efficacy of pressurised metered dose inhalers (pMDI) compared to any other handheld inhaler device for the delivery of bronchodilators in non-acute COPD. SEARCH STRATEGY: The Cochrane Collaboration, Asthma and Wheeze Randomised Controlled Clinical Trials register was searched for studies. The UK pharmaceutical companies who manufacture inhaled COPD medication were also contacted. SELECTION CRITERIA: Two reviewers independently reviewed the results of computerised search and any potentially relevant articles were obtained in full. DATA COLLECTION AND ANALYSIS: One reviewer extracted details of each trial and a second reviewer checked all extracted data. Dichotomous outcomes such as exacerbation rate were assessed using relative risk, with 95% confidence interval (CI). MAIN RESULTS: Fourteen studies appeared potentially relevant but only three studies (61 patients) met the entry criteria. Two studies compared a dry powder device (Turbuhaler or Rotahaler) with a pMDI for beta2-agonist delivery, and one (36 patients cross-over design) the Respimat (soft mist device for ipratropium) vs a pMDI. For the Turbuhaler and Rotahaler, none of the reported outcome measures were significantly different. The Rotahaler study used a high and low dose of medication with or without large volume spacer. The study using the Respimat showed significant increases in FEV1 when compared to a pMDI (difference in change from base line 70 ml, 95% CI 10, 130 ml). The effect on change in FVC was of similar size. There were no differences between these two devices for any other reported outcomes. Although none of the included studies required prior patient ability to use any of the inhalers (and no study mentioned device training), it was assumed that all patients randomised into the study would have undergone training in use of the study inhalers and were capable of using those devices. REVIEWER'S CONCLUSIONS: In patients with stable COPD, pMDI produced similar outcomes to a dry powder device for delivering beta2-agonists, but the very small number of studies and included patients does not permit firm conclusions to be drawn. The soft mist device for ipratropium was more effective than a pMDI, but the data come from one small study. There need to be further well designed randomised controlled trials to define the role of inhaler devices using bronchodilators in stable COPD.