RT Journal Article SR Electronic T1 Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation JF Thorax JO Thorax FD BMJ Publishing Group Ltd and British Thoracic Society SP 532 OP 539 DO 10.1136/thoraxjnl-2012-202538 VO 68 IS 6 A1 Alex R Horsley A1 Jane C Davies A1 Robert D Gray A1 Kenneth A Macleod A1 Jackie Donovan A1 Zelena A Aziz A1 Nicholas J Bell A1 Margaret Rainer A1 Shahrul Mt-Isa A1 Nia Voase A1 Maria H Dewar A1 Clare Saunders A1 James S Gibson A1 Javier Parra-Leiton A1 Mia D Larsen A1 Sarah Jeswiet A1 Samia Soussi A1 Yusura Bakar A1 Mark G Meister A1 Philippa Tyler A1 Ann Doherty A1 David M Hansell A1 Deborah Ashby A1 Stephen C Hyde A1 Deborah R Gill A1 Andrew P Greening A1 David J Porteous A1 J Alastair Innes A1 A Christopher Boyd A1 Uta Griesenbach A1 Steve Cunningham A1 Eric WFW Alton YR 2013 UL http://thorax.bmj.com/content/68/6/532.abstract AB Background Clinical trials in cystic fibrosis (CF) have been hindered by the paucity of well characterised and clinically relevant outcome measures. Aim To evaluate a range of conventional and novel biomarkers of CF lung disease in a multicentre setting as a contributing study in selecting outcome assays for a clinical trial of CFTR gene therapy. Methods A multicentre observational study of adult and paediatric patients with CF (>10 years) treated for a physician-defined exacerbation of CF pulmonary symptoms. Measurements were performed at commencement and immediately after a course of intravenous antibiotics. Disease activity was assessed using 46 assays across five key domains: symptoms, lung physiology, structural changes on CT, pulmonary and systemic inflammatory markers. Results Statistically significant improvements were seen in forced expiratory volume in 1 s (p<0.001, n=32), lung clearance index (p<0.01, n=32), symptoms (p<0.0001, n=37), CT scores for airway wall thickness (p<0.01, n=31), air trapping (p<0.01, n=30) and large mucus plugs (p=0.0001, n=31), serum C-reactive protein (p<0.0001, n=34), serum interleukin-6 (p<0.0001, n=33) and serum calprotectin (p<0.0001, n=31). Discussion We identify the key biomarkers of inflammation, imaging and physiology that alter alongside symptomatic improvement following treatment of an acute CF exacerbation. These data, in parallel with our study of biomarkers in patients with stable CF, provide important guidance in choosing optimal biomarkers for novel therapies. Further, they highlight that such acute therapy predominantly improves large airway parameters and systemic inflammation, but has less effect on airway inflammation.