Thorax doi:10.1136/thoraxjnl-2012-202538
  • Cystic fibrosis
  • Original Article

Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation

  1. Eric WFW Alton1,3
  1. 1UK Cystic Fibrosis Gene Therapy Consortium, London, UK
  2. 2University of Manchester and Manchester Adult Cystic Fibrosis Centre, University Hospitals South Manchester, Manchester, UK
  3. 3Department of Gene Therapy, National Heart and Lung Institute, Imperial College, London, UK
  4. 4MRC/University of Edinburgh Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK
  5. 5Royal Hospital for Sick Children, Edinburgh, UK
  6. 6Department of Radiology, Royal Brompton Hospital, London, UK
  7. 7Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  8. 8Imperial Clinical Trials Unit, School of Public Health, Imperial College, London, UK
  9. 9Scottish Adult Cystic Fibrosis Service, Western General Hospital, Edinburgh, UK
  10. 10Nuffield Division of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
  1. Correspondence to Dr Christopher Boyd, Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Institute of Genetics & Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK; Chris.Boyd{at}; Dr Uta Griesenbach, Department of Gene Therapy, National Heart and Lung Institute, Imperial College, London, Manresa Road, London SW3 6LR, UK; u.griesenbach{at}
  • Received 6 August 2012
  • Revised 11 January 2013
  • Accepted 16 January 2013
  • Published Online First 9 February 2013


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.

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