Imperial College London
Alternate

ProfessorEricAlton

Faculty of Medicine, National Heart & Lung Institute

Chair in Gene Therapy
 
 
 
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Contact

 

+44 (0)20 7594 7929e.alton

 
 
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Assistant

 

Miss Samia Soussi +44 (0)20 7594 7980

 
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Location

 

Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Horsley:2013:10.1136/thoraxjnl-2012-202538,
author = {Horsley, AR and Davies, JC and Gray, RD and Macleod, KA and Donovan, J and Aziz, ZA and Bell, NJ and Rainer, M and Mt-Isa, S and Voase, N and Dewar, MH and Saunders, C and Gibson, JS and Parra-Leiton, J and Larsen, MD and Jeswiet, S and Soussi, S and Bakar, Y and Meister, MG and Tyler, P and Doherty, A and Hansell, DM and Ashby, D and Hyde, SC and Gill, DR and Greening, AP and Porteous, DJ and Innes, JA and Boyd, AC and Griesenbach, U and Cunningham, S and Alton, EWFW},
doi = {10.1136/thoraxjnl-2012-202538},
journal = {Thorax},
pages = {532--539},
title = {Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation},
url = {http://dx.doi.org/10.1136/thoraxjnl-2012-202538},
volume = {68},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
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 (>10years) 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 1s (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.
AU  - Horsley,AR
AU  - Davies,JC
AU  - Gray,RD
AU  - Macleod,KA
AU  - Donovan,J
AU  - Aziz,ZA
AU  - Bell,NJ
AU  - Rainer,M
AU  - Mt-Isa,S
AU  - Voase,N
AU  - Dewar,MH
AU  - Saunders,C
AU  - Gibson,JS
AU  - Parra-Leiton,J
AU  - Larsen,MD
AU  - Jeswiet,S
AU  - Soussi,S
AU  - Bakar,Y
AU  - Meister,MG
AU  - Tyler,P
AU  - Doherty,A
AU  - Hansell,DM
AU  - Ashby,D
AU  - Hyde,SC
AU  - Gill,DR
AU  - Greening,AP
AU  - Porteous,DJ
AU  - Innes,JA
AU  - Boyd,AC
AU  - Griesenbach,U
AU  - Cunningham,S
AU  - Alton,EWFW
DO  - 10.1136/thoraxjnl-2012-202538
EP  - 539
PY  - 2013///
SN  - 1468-3296
SP  - 532
TI  - Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation
T2  - Thorax
UR  - http://dx.doi.org/10.1136/thoraxjnl-2012-202538
UR  - http://hdl.handle.net/10044/1/23495
VL  - 68
ER  -
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