Assessment of pulmonary neutrophilic inflammation in emphysema by quantitative positron emission tomography

Deepak R Subramanian; Lee Jenkins; Ross Edgar; Mohammed Nabil Quraishi; Robert A Stockley; David G Parr

doi:10.1164/rccm.201201-0051OC

Assessment of pulmonary neutrophilic inflammation in emphysema by quantitative positron emission tomography

Deepak R Subramanian, Lee Jenkins, Ross Edgar, Mohammed Nabil Quraishi, Robert A Stockley, David G Parr

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

Abstract

RATIONALE: Neutrophilic inflammation is understood to be of pathogenetic importance in chronic obstructive pulmonary disease (COPD) and may be quantified using 18-fluorodeoxyglucose positron emission tomography-computed tomography ((18)FDG PET-CT) as a noninvasive, spatially informative biomarker.

OBJECTIVES: To assess the potential usefulness of (18)FDG PET-CT as a surrogate measure of pulmonary neutrophilic inflammation in patients with usual COPD and α(1)-antitrypsin deficiency (AATD).

METHODS: (18)FDG PET-CT imaging was performed in 10 patients with usual COPD, 10 patients with AATD, and 10 healthy control subjects. Pulmonary (18)FDG uptake was estimated by three-dimensional Patlak graphical analysis as an indicator of pulmonary neutrophilic glycolytic activity. Patients with AATD were treated with 12 weekly intravenous infusions of AAT augmentation therapy before repeat imaging. (18)FDG uptake, lung physiology, lung density, and systemic markers of inflammation were compared for all groups at baseline and, in patients with AATD, at baseline and on treatment.

MEASUREMENTS AND MAIN RESULTS: (18)FDG uptake in the upper lung of patients with usual COPD was greater compared with the healthy control group (P = 0.009) and correlated with measures of disease severity (FEV(1)% predicted, r = -0.848, P = 0.001; FEV(1)/FVC, r = -0.918, P < 0.001; Kco% predicted, r = -0.624, P = 0.027; 15th percentile point, r = -0.709, P = 0.011). No significant difference was observed between measurements at baseline and on treatment in patients with AATD.

CONCLUSIONS: Quantitative (18)FDG PET-CT has a potential role as an imaging biomarker in mechanistic and interventional studies in patients with usual COPD. The data support previous evidence of distinct functional characteristics of neutrophils in COPD. Clinical trial registered with https://eudract.ema.europa.eu/index.html (EudraCT 2007-004869-18).

Original language	English
Pages (from-to)	1125-32
Number of pages	8
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	186
Issue number	11
DOIs	https://doi.org/10.1164/rccm.201201-0051OC
Publication status	Published - 1 Dec 2012

Keywords

Aged
Bronchitis/diagnostic imaging
Cohort Studies
Cross-Sectional Studies
Female
Fluorodeoxyglucose F18
Forced Expiratory Volume
Humans
Inflammation Mediators/analysis
Male
Middle Aged
Multimodal Imaging/methods
Neutrophil Activation
Positron-Emission Tomography
Pulmonary Disease, Chronic Obstructive/diagnostic imaging
Reference Values
Respiratory Function Tests
Sensitivity and Specificity
Severity of Illness Index
Statistics, Nonparametric
Tomography, X-Ray Computed
United Kingdom
alpha 1-Antitrypsin Deficiency/diagnostic imaging

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10.1164/rccm.201201-0051OC

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title = "Assessment of pulmonary neutrophilic inflammation in emphysema by quantitative positron emission tomography",

abstract = "RATIONALE: Neutrophilic inflammation is understood to be of pathogenetic importance in chronic obstructive pulmonary disease (COPD) and may be quantified using 18-fluorodeoxyglucose positron emission tomography-computed tomography ((18)FDG PET-CT) as a noninvasive, spatially informative biomarker.OBJECTIVES: To assess the potential usefulness of (18)FDG PET-CT as a surrogate measure of pulmonary neutrophilic inflammation in patients with usual COPD and α(1)-antitrypsin deficiency (AATD).METHODS: (18)FDG PET-CT imaging was performed in 10 patients with usual COPD, 10 patients with AATD, and 10 healthy control subjects. Pulmonary (18)FDG uptake was estimated by three-dimensional Patlak graphical analysis as an indicator of pulmonary neutrophilic glycolytic activity. Patients with AATD were treated with 12 weekly intravenous infusions of AAT augmentation therapy before repeat imaging. (18)FDG uptake, lung physiology, lung density, and systemic markers of inflammation were compared for all groups at baseline and, in patients with AATD, at baseline and on treatment.MEASUREMENTS AND MAIN RESULTS: (18)FDG uptake in the upper lung of patients with usual COPD was greater compared with the healthy control group (P = 0.009) and correlated with measures of disease severity (FEV(1)% predicted, r = -0.848, P = 0.001; FEV(1)/FVC, r = -0.918, P < 0.001; Kco% predicted, r = -0.624, P = 0.027; 15th percentile point, r = -0.709, P = 0.011). No significant difference was observed between measurements at baseline and on treatment in patients with AATD.CONCLUSIONS: Quantitative (18)FDG PET-CT has a potential role as an imaging biomarker in mechanistic and interventional studies in patients with usual COPD. The data support previous evidence of distinct functional characteristics of neutrophils in COPD. Clinical trial registered with https://eudract.ema.europa.eu/index.html (EudraCT 2007-004869-18).",

keywords = "Aged, Bronchitis/diagnostic imaging, Cohort Studies, Cross-Sectional Studies, Female, Fluorodeoxyglucose F18, Forced Expiratory Volume, Humans, Inflammation Mediators/analysis, Male, Middle Aged, Multimodal Imaging/methods, Neutrophil Activation, Positron-Emission Tomography, Pulmonary Disease, Chronic Obstructive/diagnostic imaging, Reference Values, Respiratory Function Tests, Sensitivity and Specificity, Severity of Illness Index, Statistics, Nonparametric, Tomography, X-Ray Computed, United Kingdom, alpha 1-Antitrypsin Deficiency/diagnostic imaging",

author = "Subramanian, {Deepak R} and Lee Jenkins and Ross Edgar and Quraishi, {Mohammed Nabil} and Stockley, {Robert A} and Parr, {David G}",

year = "2012",

month = dec,

day = "1",

doi = "10.1164/rccm.201201-0051OC",

language = "English",

volume = "186",

pages = "1125--32",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "11",

}

TY - JOUR

T1 - Assessment of pulmonary neutrophilic inflammation in emphysema by quantitative positron emission tomography

AU - Subramanian, Deepak R

AU - Jenkins, Lee

AU - Edgar, Ross

AU - Quraishi, Mohammed Nabil

AU - Stockley, Robert A

AU - Parr, David G

PY - 2012/12/1

Y1 - 2012/12/1

N2 - RATIONALE: Neutrophilic inflammation is understood to be of pathogenetic importance in chronic obstructive pulmonary disease (COPD) and may be quantified using 18-fluorodeoxyglucose positron emission tomography-computed tomography ((18)FDG PET-CT) as a noninvasive, spatially informative biomarker.OBJECTIVES: To assess the potential usefulness of (18)FDG PET-CT as a surrogate measure of pulmonary neutrophilic inflammation in patients with usual COPD and α(1)-antitrypsin deficiency (AATD).METHODS: (18)FDG PET-CT imaging was performed in 10 patients with usual COPD, 10 patients with AATD, and 10 healthy control subjects. Pulmonary (18)FDG uptake was estimated by three-dimensional Patlak graphical analysis as an indicator of pulmonary neutrophilic glycolytic activity. Patients with AATD were treated with 12 weekly intravenous infusions of AAT augmentation therapy before repeat imaging. (18)FDG uptake, lung physiology, lung density, and systemic markers of inflammation were compared for all groups at baseline and, in patients with AATD, at baseline and on treatment.MEASUREMENTS AND MAIN RESULTS: (18)FDG uptake in the upper lung of patients with usual COPD was greater compared with the healthy control group (P = 0.009) and correlated with measures of disease severity (FEV(1)% predicted, r = -0.848, P = 0.001; FEV(1)/FVC, r = -0.918, P < 0.001; Kco% predicted, r = -0.624, P = 0.027; 15th percentile point, r = -0.709, P = 0.011). No significant difference was observed between measurements at baseline and on treatment in patients with AATD.CONCLUSIONS: Quantitative (18)FDG PET-CT has a potential role as an imaging biomarker in mechanistic and interventional studies in patients with usual COPD. The data support previous evidence of distinct functional characteristics of neutrophils in COPD. Clinical trial registered with https://eudract.ema.europa.eu/index.html (EudraCT 2007-004869-18).

AB - RATIONALE: Neutrophilic inflammation is understood to be of pathogenetic importance in chronic obstructive pulmonary disease (COPD) and may be quantified using 18-fluorodeoxyglucose positron emission tomography-computed tomography ((18)FDG PET-CT) as a noninvasive, spatially informative biomarker.OBJECTIVES: To assess the potential usefulness of (18)FDG PET-CT as a surrogate measure of pulmonary neutrophilic inflammation in patients with usual COPD and α(1)-antitrypsin deficiency (AATD).METHODS: (18)FDG PET-CT imaging was performed in 10 patients with usual COPD, 10 patients with AATD, and 10 healthy control subjects. Pulmonary (18)FDG uptake was estimated by three-dimensional Patlak graphical analysis as an indicator of pulmonary neutrophilic glycolytic activity. Patients with AATD were treated with 12 weekly intravenous infusions of AAT augmentation therapy before repeat imaging. (18)FDG uptake, lung physiology, lung density, and systemic markers of inflammation were compared for all groups at baseline and, in patients with AATD, at baseline and on treatment.MEASUREMENTS AND MAIN RESULTS: (18)FDG uptake in the upper lung of patients with usual COPD was greater compared with the healthy control group (P = 0.009) and correlated with measures of disease severity (FEV(1)% predicted, r = -0.848, P = 0.001; FEV(1)/FVC, r = -0.918, P < 0.001; Kco% predicted, r = -0.624, P = 0.027; 15th percentile point, r = -0.709, P = 0.011). No significant difference was observed between measurements at baseline and on treatment in patients with AATD.CONCLUSIONS: Quantitative (18)FDG PET-CT has a potential role as an imaging biomarker in mechanistic and interventional studies in patients with usual COPD. The data support previous evidence of distinct functional characteristics of neutrophils in COPD. Clinical trial registered with https://eudract.ema.europa.eu/index.html (EudraCT 2007-004869-18).

KW - Aged

KW - Bronchitis/diagnostic imaging

KW - Cohort Studies

KW - Cross-Sectional Studies

KW - Female

KW - Fluorodeoxyglucose F18

KW - Forced Expiratory Volume

KW - Humans

KW - Inflammation Mediators/analysis

KW - Male

KW - Middle Aged

KW - Multimodal Imaging/methods

KW - Neutrophil Activation

KW - Positron-Emission Tomography

KW - Pulmonary Disease, Chronic Obstructive/diagnostic imaging

KW - Reference Values

KW - Respiratory Function Tests

KW - Sensitivity and Specificity

KW - Severity of Illness Index

KW - Statistics, Nonparametric

KW - Tomography, X-Ray Computed

KW - United Kingdom

KW - alpha 1-Antitrypsin Deficiency/diagnostic imaging

U2 - 10.1164/rccm.201201-0051OC

DO - 10.1164/rccm.201201-0051OC

M3 - Article

C2 - 22837375

SN - 1073-449X

VL - 186

SP - 1125

EP - 1132

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 11

ER -

Assessment of pulmonary neutrophilic inflammation in emphysema by quantitative positron emission tomography

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