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 g 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 g 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.

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Exacerbations of chronic obstuctive pulmonary disease (COPD) are associated with worse health status. The Inhaled Steroids in Obstructive Lung Disease in Europe (ISOLDE) study showed that treatment with fluticasone propionate (FP) reduced exacerbation frequency and the rate of deterioration in health status as compared with placebo. The present study analysed these data to test whether the effect of FP on health status was attributable to its effect on exacerbations.Rates of deterioration in St George9s Respiratory Questionnaire (SGRQ) total score were obtained for 613 patients with moderate to severe COPD followed for a maximum of 3 yrs. Exacerbation rates were skewed and could not be normalised, therefore, patients were stratified into three exacerbation groups: none, infrequent (v1.65 exacerbations?yr -1 ) and frequent (w1.65 exacerbations?yr -1 ). There were 91 patients with no exacerbations, 285 with infrequent exacerbations and 235 with frequent exacerbations. Frequent exacerbations were independently associated with a worse baseline SGRQ score (pv0.0001) and a more rapid rate of deterioration in health status (p=0.0003). Exacerbation frequency and rate of decline in forced expiratory volume in one second were independently related to the rate of deterioration in SGRQ score.Statistical modelling showed the beneficial effect of fluticasone propionate on deterioration in health status to be largely due to its effect on exacerbation frequency. The current analysis was supported by a grant from GlaxoSmithKline, UK.Chronic obstructive pulmonary disease (COPD) is a complex disease characterised by incompletely reversible airways obstruction, progressive loss of lung function, recurrent exacerbations and poor health. The relationship between health status and exacerbations is well established; poor health is associated with a higher frequency of exacerbations [1,2], an increased likelihood of hospitalisation [3] and increased mortality [4]. Recent meta-analyses have reported that inhaled corticosteroids (ICS) have a minimal or no effect on the rate of decline in forced expiratory volume in one second (FEV1) [5,6], but they do reduce the severity [7] and frequency of exacerbations [8], and reduce the rate of deterioration in health status [8,9]. A number of recent studies have also shown that inhaled therapy can reduce exacerbations and improve health status over 1 yr [10][11][12]. While there appears to be an association between exacerbations and health status, the mechanism has not yet been established. Furthermore, there is no direct evidence that reducing exacerbation frequency can improve health. The aim of the present study was to re-analyse data from the 3-yr Inhaled Steroids in Obstructive Pulmonary Lung Disease in Europe (ISOLDE) study of fluticasone propionate (FP) in COPD [8], using statistical models, to test whether there is evidence of a direct association between exacerbation frequency and deterioration in health status, and whether the effect of FP on health status is attributable to its ...

An accelerated decline of FEV 1 is well-documented in patients with chronic obstructive pulmonary disease (COPD). Although FEV 1 is a useful measure for diagnosis and prognosis, it is neither a good predictor of the symptomatic response to treatment in COPD (1) nor of the likelihood of hospitalization (2). This has led to the use of generic and disease-specific questionnaires to measure the impact of COPD on health status. Crosssectional studies have shown that patient populations with a lower FEV 1 have worse health-related quality of life (3). However, to our knowledge there are no data concerning the rate of change in health status within patients over time.We hypothesized that decline in health status would be detectable in a population of patients in whom COPD was the principal pathology and that this would be amenable to treatment. All components of the disease-specific St George's Respiratory Questionnaire (SGRQ) have shown sensitivity to impaired health in COPD (4). The physical function components of the generic Short-Form 36 (SF-36) have demonstrated sensitivity to change in COPD and to treatment with fluticasone in severe asthma (5, 6) so we expected these components of the SGRQ and SF-36 to show the greatest sensitivity to change in our study. Because it is known that smoking has an effect on rate of decline in FEV 1 , we also hypothesized that smoking status would influence health status and its rate of deterioration. We used data collected as part of the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) study of fluticasone in COPD. The intention-to-treat analyses of the principal outcomes of this trial are reported elsewhere (7). For this analysis, health status was measured using a generic instrument, the SF-36 and a disease-specific instrument, the SGRQ. METHODS PatientsFull details of the study methodology, patient selection, and spirometric procedures are presented elsewhere (7). Seven hundred fifty-one patients (560 men) with a diagnosis of COPD consistent with American Thoracic Society (ATS) recommendations (8) were recruited from 18 centers throughout the United Kingdom. All were current or exsmokers age 40 to 75 yr with a postbronchodilator FEV 1 of at least 0.8 L, but less than 85% predicted. The FEV 1 /FVC ratio was less than 70%. Exclusion criteria were: an FEV 1 response to 400 g salbutamol of Ͼ 10% predicted; use of ␤ -adrenergic blockers; use of nontrial inhaled corticosteroids or regular oral corticosteroid; a life expectancy of less than 5 yr from non-COPD diseases. At baseline values, postbronchodilator FEV 1 expressed as percent of predicted normal was 50 Ϯ 15 (SD)%. The mean FEV 1 response to salbutamol was 4.4% predicted (0.13 L). During the study, patients requiring long-term treatment with oral corticosteroids or more than two short courses of treatment in any 3-mo period were withdrawn. Ethical committee approval was obtained in each participating center and informed consent was obtained before entry to the study.

Background: The magnitude and time course of effect of an acute exacerbation of chronic bronchitis (AECB) on health status are not known. Data from the GLOBE study, a randomised double blind trial of antibiotic therapy, were used to investigate these effects. Methods: 438 patients with AECB received either gemifloxacin 320 mg once daily for 5 days (214 patients) or clarithromycin 500 mg twice daily for 7 days (224 patients) and were followed up for 26 weeks. St George's Respiratory Questionnaire (SGRQ) scores were obtained at baseline and after 4, 12, and 26 weeks. Results: At presentation during an exacerbation SGRQ scores were worse (Total score difference 5.4 units, 95% CI 1.9 to 8.8, p=0.002) in patients who had a subsequent exacerbation during follow up. The greatest improvement in SGRQ score occurred within the first 4 weeks (mean 8.9 units, 95% CI 6.5 to 11.5, p<0.0001). Subsequently, scores improved more rapidly in patients with no further exacerbations. At 26 weeks the difference between the two groups was 9.6 units (95% CI 5.7 to 13.4, p<0.0001). In patients with no further exacerbations the SGRQ score improved between 4 and 12 weeks by a further 4.1 units (95% CI 2.2 to 5.9, p<0.0001). Conclusions: A single infective AECB has a sustained effect on health status. The recovery period is long even in patients who have no further exacerbations. A second episode within 6 months limits recovery markedly. Treatments that reduce exacerbation frequency could have a significant impact on health status.

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Background Manipulation under anaesthesia and arthroscopic capsular release are costly and invasive treatments for frozen shoulder, but their effectiveness remains uncertain. We compared these two surgical interventions with early structured physiotherapy plus steroid injection. MethodsIn this multicentre, pragmatic, three-arm, superiority randomised trial, patients referred to secondary care for treatment of primary frozen shoulder were recruited from 35 hospital sites in the UK. Participants were adults (≥18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation (≥50%) in the affected shoulder. Participants were randomly assigned (2:2:1) to receive manipulation under anaesthesia, arthroscopic capsular release, or early structured physiotherapy. In manipulation under anaesthesia, the surgeon manipulated the affected shoulder to stretch and tear the tight capsule while the participant was under general anaesthesia, supplemented by a steroid injection. Arthroscopic capsular release, also done under general anaesthesia, involved surgically dividing the contracted anterior capsule in the rotator interval, followed by manipulation, with optional steroid injection. Both forms of surgery were followed by postprocedural physiotherapy. Early structured physiotherapy involved mobilisation techniques and a graduated home exercise programme supplemented by a steroid injection. Both early structured physiotherapy and postprocedural physiotherapy involved 12 sessions during up to 12 weeks. The primary outcome was the Oxford Shoulder Score (OSS; 0-48) at 12 months after randomisation, analysed by initial randomisation group. We sought a target difference of 5 OSS points between physiotherapy and either form of surgery, or 4 points between manipulation and capsular release. The trial registration is ISRCTN48804508.

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