title: Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation.
abstract: BACKGROUND
  Clinical trials in cystic fibrosis (CF) have been hindered by the paucity of well characterised and clinically relevant outcome measures.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: UK Cystic Fibrosis Gene Therapy Consortium, London, UK.
authors: Alex R
authors: AR
authors: Horsley
authors: Jane C
authors: JC
authors: Davies
authors: Robert D
authors: RD
authors: Gray
authors: Kenneth A
authors: KA
authors: Macleod
authors: Jackie
authors: J
authors: Donovan
authors: Zelena A
authors: ZA
authors: Aziz
authors: Nicholas J
authors: NJ
authors: Bell
authors: Margaret
authors: M
authors: Rainer
authors: Shahrul
authors: S
authors: Mt-Isa
authors: Nia
authors: N
authors: Voase
authors: Maria H
authors: MH
authors: Dewar
authors: Clare
authors: C
authors: Saunders
authors: James S
authors: JS
authors: Gibson
authors: Javier
authors: J
authors: Parra-Leiton
authors: Mia D
authors: MD
authors: Larsen
authors: Sarah
authors: S
authors: Jeswiet
authors: Samia
authors: S
authors: Soussi
authors: Yusura
authors: Y
authors: Bakar
authors: Mark G
authors: MG
authors: Meister
authors: Philippa
authors: P
authors: Tyler
authors: Ann
authors: A
authors: Doherty
authors: David M
authors: DM
authors: Hansell
authors: Deborah
authors: D
authors: Ashby
authors: Stephen C
authors: SC
authors: Hyde
authors: Deborah R
authors: DR
authors: Gill
authors: Andrew P
authors: AP
authors: Greening
authors: David J
authors: DJ
authors: Porteous
authors: J Alastair
authors: JA
authors: Innes
authors: A Christopher
authors: AC
authors: Boyd
authors: Uta
authors: U
authors: Griesenbach
authors: Steve
authors: S
authors: Cunningham
authors: Eric W F W
authors: EW
authors: Alton
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology*; D006801:Humans; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood; D039841:Leukocyte L1 Antigen Complex / Q000097:blood; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008171:Lung Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D012008:Recurrence; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D015850:Interleukin-6; D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein
keywords: Cystic Fibrosis; Imaging/CT MRI etc; Lung Physiology