Role of infection in exacerbations of COPD

printing supported by . Visit Chiesi at Stand D.30 MONDAY, SEPTEMBER 26TH 2011 E-COPD significantly impact outcomes and costs. Less than one fourth of patients discharged after an E-COPD will undergo a PFT during two years, although its cost is extremely lower than the hospital stay. P3011 Safety and pharmacokinetics of multiple-dose ciprofloxacin dry powder for inhalation in patients with moderate or severe COPD Heino Stass1, Philipp Badorrek2, Jens Hohlfeld2,3 , Norbert Krug2, Johannes Nagelschmitz1, Tobias Welte3. 1Clinical Pharmacology, Bayer Schering Pharma AG, Wuppertal, Germany; 2Klinische Atemwegsforschung, Fraunhofer Institute for Toxicology and Experimental Science, Hannover, Germany; 3Klinik fuer Pneumologie, Medizinische Hochschule Hannover, Hannover, Germany Introduction: Many patients with COPD are chronically colonized with bacteria and could benefit from long-term antibacterial therapy. Ciprofloxacin dry powder for inhalation (DPI) is an investigational PulmoSphereTM formulation for pulmonary delivery of ciprofloxacin. Aim: To investigate the safety, tolerability and PK of ciprofloxacin DPI in patients with COPD. Methods: In a randomized, phase I, single-blind, parallel-group study, adults with GOLD stage II or III COPD received 32.5 mg or 48.75 mg ciprofloxacin (50 mg, 75 mg ciprofloxacin DPI, respectively) or matching placebo as a single dose on Day 0 and 12 and bid on Days 2–11. Results: Patients received 32.5 mg (n=6) or 48.75 mg (n=9 including 3 who replaced drop-outs) ciprofloxacin, or placebo (n=4). There were no severe or serious AEs; most AEs were mild in severity. There were treatment-related AEs in 4, 8 and 1 patients in the 32.5 mg and 48.75 mg ciprofloxacin and placebo groups, respectively. Three patients discontinued (48.75 mg ciprofloxacin) due to AEs: moderate treatment-related dyspnoea (n=1); infectious diseases (n=2). Day 0 geometric mean plasma ciprofloxacin AUC was 0.532 mg*h/l and 0.727 mg*h/l, and AUC0–last in induced sputum was 1190 mg*h/l and 2010 mg*h/l, for the 32.5 mg and 48.75 mg groups, respectively. Ciprofloxacin sputum concentrations were highly variable; geometric mean induced sputum Cmax:plasma Cmax ratios ranged 1650–10,600. Conclusions: Ciprofloxacin DPI was well tolerated over 12 days’ treatment in patients with moderate or severe COPD. High sputum concentrations contrasted with low systemic exposure. P3012 Does presence of multiple viruses in the stable state predispose COPD patients to exacerbations? Marijke Vanspauwen1, Frits Franssen2, Cathrien Bruggeman1, Emiel Wouters2,3 , Catharina Linssen1. 1Medical Microbiology, Maastricht University Medical Centre, Caphri School, Maastricht, Netherlands; 2Ciro+, Centre of Expertise for Chronic Organ Failure, Horn, Netherlands; 3Respiratory Medicine, Maastricht University Medical Centre, Maastricht, Netherlands Introduction: Respiratory viruses are associated with acute exacerbations (AE) in patients with COPD, but may also lead to asymptomatic carriership. This study investigates whether co-detection of viruses in the stable state predisposes for AEs in patients with COPD. Since it is known that many viruses circulate during the year we included the most important respiratory viruses in our study. Material and methods: From March 2009 until August 2010 sputum samples of COPD patients clinically rehabilitating at the centre of expertise for chronic organ failure (CIRO), were included. Sputum samples were collected during the stable state and during an AE. Real-time polymerase chain reaction for rhinovirus, hMPV, RSV, influenza A and B and parainfluenza 1-4, was performed. Results: A total of 498 sputum samples (218 patients) were included. Viruses were detected in 208 samples (42%) of which 106 (51%) were collected during the stable state. In 11% of the samples multiple viruses were found, of which the combination of rhinovirus and hMPV was the most frequent (58%). Patients with multiple viruses in the stable sample did not experience more AEs in the first weeks after stable sample collection than patients with a single virus or without a virus in the stable sample. Conclusion: In 11% of sputum samples of COPD patients multiple respiratory viruses were found. The presence of multiple viruses does not predispose these patients to the short-term occurrence of an AE. P3013 The relationship between PBMC secretion of IFN-alpha following TLR7 and TLR9 activation and lung function in COPD Vijay Mistry, Mona Bafadhel, Sue McKenna, Sarah Terry, Christopher Brightling. Infection, Immunity and Inflammation, University of Leicester, Leicester, United