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.

To date, no international surveys estimating the burden of chronic obstructive pulmonary disease (COPD) in the general population have been published. The Confronting COPD International Survey aimed to quantify morbidity and burden in COPD subjects in 2000.From a total of 201,921 households screened by random-digit dialling in the USA, Canada, France, Italy, Germany, the Netherlands, Spain and the UK, 3,265 subjects with a diagnosis of COPD, chronic bronchitis or emphysema, or with symptoms of chronic bronchitis, were identified.The mean age of the subjects was 63.3 yrs and 44.2% were female. Subjects with COPD in North America and Europe appear to underestimate their morbidity, as shown by the high proportion of subjects with limitations to their basic daily life activities, frequent work loss (45.3% of COPD subjects of v65 yrs reported work loss in the past year) and frequent use of health services (13.8% of subjects required emergency care in the last year), and may be undertreated. There was a significant disparity between subjects9 perception of disease severity and the degree of severity indicated by an objective breathlessness scale. Of those with the most severe breathlessness (too breathless to leave the house), 35.8% described their condition as mild or moderate, as did 60.3% of those with the next most severe degree of breathlessness (breathless after walking a few minutes on level ground).This international survey confirmed the great burden to society and high individual morbidity associated with chronic obstructive pulmonary disease in subjects in North America and Europe. Eur Respir J 2002; 20: 799-805.

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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 ...

Background: A study was undertaken to test the hypothesis that patients respond better to lung volume reduction surgery (LVRS) if their emphysema is confluent and predominantly located in the upper lobes. Methods: A density mask analysis was used to identify voxels inflated beyond 10.2 ml gas/g tissue (-910 HU) on preoperative and postoperative CT scans from patients receiving LVRS. These hyperinflated regions were considered to represent emphysematous lesions. A power law analysis was used to determine the relationship between the number (K) and size (A) of the emphysematous lesions in the whole lung and two anatomical regions using the power law equation Y=KA -D . Results: The analysis showed a positive correlation between the change in the power law exponent (D) and the change in exercise (Watts) after surgery (r=0.47, p=0.03). There was also a negative correlation between the power law exponent D in the upper region of the lung preoperatively and the change in exercise following surgery (r=-0.60, p<0.05). Conclusions: These results confirm that patients with large upper lobe lesions respond better to LVRS than patients with small uniformly distributed disease. Power law analysis of lung CT scans provides a quantitative method for determining the extent and location of emphysema within the lungs of patients with COPD.