Effect of once-daily fluticasone furoate/vilanterol versus vilanterol alone on bone mineral density in patients with COPD: a randomized, controlled trial.

BACKGROUND: The relationship between inhaled corticosteroids and bone mineral density (BMD) remains uncertain despite extensive research. METHODS: This was an international, multicenter, randomized, double-blind, parallel-group, 3-year noninferiority study. Patients with chronic obstructive pulmonary disease (COPD) (⩾40 years of age; smoking history ⩾10 pack years) and at least one native hip evaluable for BMD were enrolled and randomized 1:1, stratified by sex, to treatment with vilanterol (VI) 25 µg or fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg. BMD measurements were taken via dual-energy X-ray absorptiometry every 6 months. The primary endpoint was assessment of the noninferiority of change from baseline in total hip BMD per year at the -1% noninferiority level. Change from baseline in BMD at the lumbar spine and BMD measurements by sex were secondary endpoints. Incidences of COPD exacerbations and bone fractures throughout the study were also recorded. RESULTS: Of 283 randomized patients, 170 (60%) completed the study. Noninferiority was demonstrated for FF/VI versus VI with regards to change from baseline in total hip BMD per year, with changes of -0.27% and 0.18%, respectively, and a treatment difference of -0.46% per year [95% confidence interval (CI) -0.97 to 0.06]. The treatment difference for FF/VI versus VI regarding lumbar spine BMD was -0.51% per year (95% CI -1.11 to 0.10). COPD exacerbations and bone fracture rates were similar between treatment groups. CONCLUSION: FF/VI showed noninferiority to VI for change from baseline in total hip BMD per year, when assessed at the -1% noninferiority margin in a combined sample of men and women with COPD.The reviews of this paper are available via the supplemental material section.

ERS Congress highlight: educational forum on continuing professional development.

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A new class of bronchodilator improves lung function in COPD: a trial with GSK961081.

GSK961081 is a bifunctional molecule demonstrating both muscarinic antagonist and ß-agonist activities. This was a 4-week, multicentre, randomised, double-blind, double-dummy, placebo and salmeterol controlled parallel group study. Doses ranging across three twice-daily doses and three once-daily doses were assessed in moderate and severe chronic obstructive pulmonary disease (COPD) patients. Trough forced expiratory volume in 1 s (FEV1) at day 29 was the primary end-point. At days 1 and 28, 12-h FEV1 spirometry was performed in all patients. A subset of patients underwent complete 24-h spirometry at day 28. The study recruited 436 patients. GSK961081 showed statistically and clinically significant differences from placebo in all doses and regimens for trough FEV1 on day 29 (155-277 mL). The optimal total daily dose was 400 µg, either as 400 µg once daily or as 200 µg twice daily, with an improvement in day 29 trough FEV1 of 215 mL and 249 mL, respectively. Other efficacy end-points also showed improvement. No effects were observed on glucose, potassium, heart rate, blood pressure and no dose-response effect was seen on corrected QT elongation. This study showed that GSK961081 is an effective bronchodilator in COPD and appeared to be safe and well tolerated.

Increased systemic inflammation is a risk factor for COPD exacerbations.

BACKGROUND: COPD is characterized by episodic increases in respiratory symptoms, so-called exacerbations. COPD exacerbations are associated with an increase in local and systemic inflammation. Data of a previously published study in a well-characterized COPD cohort were analyzed to define predictive factors of acute exacerbations, particularly focusing on systemic inflammation. OBJECTIVE: To determine if an elevated systemic inflammatory status measured at baseline is related to the occurrence of acute exacerbations in patients with COPD. METHODS: The occurrence of moderate (requiring oral prednisolone) and severe exacerbations (requiring hospitalization) was prospectively recorded over 1 year. At the beginning of the study, lung function values (FEV1, FVC, functional residual capacity, and diffusion capacity of the lung for carbon monoxide [Dlco]) and serum levels of C-reactive protein, fibrinogen, lipopolysaccharide binding protein, tumor necrosis factor (TNF)-alpha, and its soluble receptors (soluble TNF receptors 55 and 75) as markers of systemic inflammation were determined. RESULTS: Two hundred seventy-seven person-years of follow-up were analyzed in the total group of 314 patients: 186 patients were responsible for 411 exacerbations (374 moderate and 37 severe). Multivariate analyses showed that a higher initial fibrinogen level and a lower FEV1 predicted a higher rate of both moderate and severe exacerbations. Additional independent predictors of a severe exacerbation were a higher number of prestudy severe exacerbations and lower Dlco. A higher number of prestudy moderate exacerbations was the only additional independent risk factor for the rate of moderate exacerbations. CONCLUSION: This study demonstrates that besides lung function impairment systemic inflammation manifested by elevated fibrinogen levels is an independent risk factor for exacerbations of COPD. Attenuation of systemic inflammation may offer new perspectives in the management of COPD patients to reduce the burden of exacerbations.

Efficacy of formoterol Turbuhaler in the emergency treatment of patients with obstructive airway diseases.

Dry powder devices are rarely used in the emergency room (ER) treatment of acute and severe bronchoconstriction due to hesitations with respect to clinical efficacy. This study investigated the effects of two inhalers with formoterol in patients visiting the ER Department for acute and severe dyspnoea, mainly exacerbations of chronic obstructive pulmonary disease. Two doses of 12mug formoterol were given at enrolment, either via Turbuhaler or via pressurised metered dose inhaler, connected to a spacer device (pMDI+S) in a double-blind way and parallel design. Another two doses of 12 microg formoterol were given after 30 min. Forced expiratory volume in the 1s (FEV(1)) and Borg dyspnoea score were assessed until 60 min. The study was designed to test non-inferiority in effects on FEV(1). Seventy-seven patients were enrolled with a mean age of 66 years and a FEV(1) of 1.03 L (39% of predicted). The effects of the two treatments were almost identical. The mean improvement in FEV(1) at 60 min after formoterol Turbuhaler was 94% of the improvement after formoterol pMDI+S. A statistically significant non-inferiority was shown (p=0.037) at 60 min (primary endpoint) as well as at 5 and 30 min (secondary endpoints, p=0.0043 and 0.013, respectively). Improvements in the Borg dyspnoea score and other lung-function parameters did not differ significantly between the two devices. In conclusion, formoterol Turbuhaler was equally effective as formoterol pMDI+S in the treatment of acute bronchoconstriction within the ER.

Surgical mediastinal staging in daily practice.

STUDY OBJECTIVES: An adequately staged mediastinum remains obligatory in patients with NSCLC prior to surgery. In this study, we investigated the accuracy of preoperative surgical mediastinal staging procedures in four hospitals. SETTING: Non-university teaching hospital and three surrounding community hospitals in Eindhoven, The Netherlands. PATIENTS, MEASUREMENTS AND RESULTS: Patients with NSCLC who underwent mediastinoscopy and/or thoracotomy, between 1993 and 1999. Adherence to guidelines for indicating and performing mediastinoscopy were investigated and compared in four hospitals. Guidelines for indicating mediastinoscopy were adequately followed in two-thirds of cases. Mediastinoscopy was performed according to gold standards in 40% of cases. The hospital with the smallest number of evaluated patients scored the worst. Postoperatively, 17% of patients appeared to have "unforeseen N2-3 disease". In approximately 18% of these "upstaged" patients, thoracotomy could have been prevented, if guidelines had been followed adequately. CONCLUSIONS: In clinical practice the adherence to staging guidelines with respect to mediastinoscopy is insufficient in one-third of patients. Furthermore, mediastinoscopy was performed according to gold standards in 40% of patients.