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Quantitative 18F-FDG PET/CT to assess pulmonary inflammation in chronic obstructive pulmonary disease

Laurence Vass, Marie Fisk, Joseph Cheriyan, Divya Mohan, Julia Forman, Adelola Oseni, Anand Devaraj, Kaisa M. Mäki-Petäjä, Carmel M McEniery, Jonathan Fuld, Nicholas S. Hopkinson, David A. Lomas, John R. Cockcroft, Ruth Tal-Singer, Michael I. Polkey, Ian B. Wilkinson
ERJ Open Research 2021; DOI: 10.1183/23120541.00699-2020
Laurence Vass
1Division of Experimental Medicine and Immunotherapeutics, University of Cambridge
10Joint first authors
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Marie Fisk
1Division of Experimental Medicine and Immunotherapeutics, University of Cambridge
10Joint first authors
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  • For correspondence: mf503@medschl.cam.ac.uk
Joseph Cheriyan
1Division of Experimental Medicine and Immunotherapeutics, University of Cambridge
2Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Divya Mohan
3GSK RD, Collegeville, Pennsylvania, USA
9Former employees of GSK, were employed during the study
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  • ORCID record for Divya Mohan
Julia Forman
2Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Adelola Oseni
4Department of Radiology, St Georges Hospital NHS Trust, London, UK
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Anand Devaraj
5National Heart and Lung Institute, Imperial College, London, UK
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Kaisa M. Mäki-Petäjä
1Division of Experimental Medicine and Immunotherapeutics, University of Cambridge
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Carmel M McEniery
1Division of Experimental Medicine and Immunotherapeutics, University of Cambridge
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Jonathan Fuld
6Division of Respiratory Medicine, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Nicholas S. Hopkinson
5National Heart and Lung Institute, Imperial College, London, UK
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David A. Lomas
7UCL Respiratory, Division of Medicine, Rayne Building, University College London, UK
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John R. Cockcroft
8Department of Cardiology, Wales Heart Research Institute, Cardiff University, Cardiff, UK
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Ruth Tal-Singer
3GSK RD, Collegeville, Pennsylvania, USA
9Former employees of GSK, were employed during the study
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Michael I. Polkey
5National Heart and Lung Institute, Imperial College, London, UK
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Ian B. Wilkinson
1Division of Experimental Medicine and Immunotherapeutics, University of Cambridge
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Abstract

Ationale Chronic obstructive pulmonary disease (COPD) and smoking are characterised by pulmonary inflammation. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker.

Objectives To evaluate pulmonary inflammation, assessed by FDG uptake in whole and regional lung in ‘usual’ (smoking-related)-COPD patients, alpha-1 antitrypsin deficiency (α1ATD)-COPD patients, smokers without COPD and never smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients.

Methods Data from two imaging studies were evaluated. Pulmonary FDG uptake was measured by Patlak graphical analysis in four subject groups: 84 COPD, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKi and systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKi values at baseline and 4-months follow up.

Results COPD, α1ATD patients and smokers had increased whole lung FDG uptake (nKi) compared to never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001 versus 0.0028±0.001 ml·cm−3/min−1 respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi, (β=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory lung volume in 1 s % predicted, systemic neutrophils and C reactive protein levels. Mean percentage difference in nKi between the baseline and follow-up was 3.2%; and the within subject coefficient of variability was 7.7%.

Conclusions FDG PET/CT has potential as a non-invasive tool to enable whole lung and regional quantification of FDG to assess smoking and COPD-related pulmonary inflammation.

Footnotes

This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.

Conflict of interest: L. Vass reports a PhD studentship grant from GlaxoSmithKline during the conduct of the study.

Conflict of interest: Fisk has nothing to disclose.

Conflict of interest: J. Cheriyan reports grants from GlaxoSmithKline (GSK) during the conduct of the study and is a Cambridge University Hospital National Health Service (NHS) Trust employee who is obligated to spend 50% of his NHS time to do clinical trial work for GSK. However ,he receives no employee benefits from GSK. The payment for this time is made directly by GSK to Cambridge University Hospitals NHS Trust.

Conflict of interest: D. Mohan is an employee of and shareholder in GSK.

Conflict of interest: Forman has nothing to disclose.

Conflict of interest: Oseni has nothing to disclose.

Conflict of interest: Devaraj has nothing to disclose.

Conflict of interest: Mäki-Petäjä has nothing to disclose.

Conflict of interest: McEniery has nothing to disclose.

Conflict of interest: Dr. Fuld has nothing to disclose.

Conflict of interest: Hopkinson has nothing to disclose.

Conflict of interest: Dr. Lomas reports grants from GlaxoSmithKline, personal fees from GlaxoSmithKline, non-financial support from GlaxoSmithKline, during the conduct of the study; personal fees from GlaxoSmithKline, personal fees from GlaxoSmithKline, grants from GlaxoSmithKline, personal fees from Griffols, outside the submitted work.

Conflict of interest: Cockcroft received grant from GSK outside this submitted work.

Conflict of interest: Ruth Tal-Singer

Conflict of interest: M.I. Polkey reports personal fees for an advisory board on this topic from GSK and grants from Innovate UK paid to his institution to conduct this work, during the conduct of the study.

Conflict of interest: Professor Wilkinson received a grant from Innovate UK and an educational imaging award from GSK during the conduct of the study.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received September 29, 2020.
  • Accepted April 12, 2021.
  • Copyright ©The authors 2021
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

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Quantitative 18F-FDG PET/CT to assess pulmonary inflammation in chronic obstructive pulmonary disease
Laurence Vass, Marie Fisk, Joseph Cheriyan, Divya Mohan, Julia Forman, Adelola Oseni, Anand Devaraj, Kaisa M. Mäki-Petäjä, Carmel M McEniery, Jonathan Fuld, Nicholas S. Hopkinson, David A. Lomas, John R. Cockcroft, Ruth Tal-Singer, Michael I. Polkey, Ian B. Wilkinson
ERJ Open Research Jan 2021, 00699-2020; DOI: 10.1183/23120541.00699-2020

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Quantitative 18F-FDG PET/CT to assess pulmonary inflammation in chronic obstructive pulmonary disease
Laurence Vass, Marie Fisk, Joseph Cheriyan, Divya Mohan, Julia Forman, Adelola Oseni, Anand Devaraj, Kaisa M. Mäki-Petäjä, Carmel M McEniery, Jonathan Fuld, Nicholas S. Hopkinson, David A. Lomas, John R. Cockcroft, Ruth Tal-Singer, Michael I. Polkey, Ian B. Wilkinson
ERJ Open Research Jan 2021, 00699-2020; DOI: 10.1183/23120541.00699-2020
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