PT  - JOURNAL ARTICLE
AU  - Alex R Horsley
AU  - Jane C Davies
AU  - Robert D Gray
AU  - Kenneth A Macleod
AU  - Jackie Donovan
AU  - Zelena A Aziz
AU  - Nicholas J Bell
AU  - Margaret Rainer
AU  - Shahrul Mt-Isa
AU  - Nia Voase
AU  - Maria H Dewar
AU  - Clare Saunders
AU  - James S Gibson
AU  - Javier Parra-Leiton
AU  - Mia D Larsen
AU  - Sarah Jeswiet
AU  - Samia Soussi
AU  - Yusura Bakar
AU  - Mark G Meister
AU  - Philippa Tyler
AU  - Ann Doherty
AU  - David M Hansell
AU  - Deborah Ashby
AU  - Stephen C Hyde
AU  - Deborah R Gill
AU  - Andrew P Greening
AU  - David J Porteous
AU  - J Alastair Innes
AU  - A Christopher Boyd
AU  - Uta Griesenbach
AU  - Steve Cunningham
AU  - Eric WFW Alton
TI  - Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation
AID  - 10.1136/thoraxjnl-2012-202538
DP  - 2013 Jun 01
TA  - Thorax
PG  - 532--539
VI  - 68
IP  - 6
4099  - http://thorax.bmj.com/content/68/6/532.short
4100  - http://thorax.bmj.com/content/68/6/532.full
SO  - Thorax2013 Jun 01; 68
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.