Quantifying Pulmonary Inflammation in Cystic Fibrosis with Positron Emission Tomography

Chen, Delphine L.; Ferkol, Thomas; Mintun, Mark A.; Pittman, Jessica E.; Rosenbluth, Daniel; Schuster, Daniel P.

doi:10.1164/rccm.200506-934oc

Cited by 91 publications

(76 citation statements)

References 38 publications

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“…Animal studies have shown that neutrophils are primary effectors of ''atelectrauma,'' (9, 32) and, in the setting of pulmonary inflammation, PET is a sensitive tool to detect the activation of these cells. Microautoradiography studies conducted both in animals (2,5,19,33) and in humans (20,21,34) suggest that uptake of 18 FDG occurs primarily by neutrophils. Furthermore, neutrophil depletion profoundly blunts the injury induced by mechanical ventilation (35) and the uptake of 18 FDG, albeit without abolishing it (3,36).…”

Section: Discussionmentioning

confidence: 99%

Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

Bellani¹,

Guerra²,

Musch³

et al. 2011

Am J Respir Crit Care Med

190

159

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Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an estimate of the intensity of inflammation, metabolic activity can be measured by positron emission tomography imaging of [ 18 F]fluoro-2-deoxy-D-glucose. Objectives: To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI. Methods: In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolic activity was measured from the [ 18 F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment-derecruitment, and normally aerated. Measurements and Main Results: Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H 2 O, and with regional VT normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. Conclusions: In patients with ALI managed with relatively high endexpiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional VT normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment-derecruitment and increased metabolic activity.Keywords: acute lung injury; respiration, artificial; tomography, X-ray computed; positron emission tomographyWe reported (1) that positron emission tomography (PET) with [ 18 F]fluoro-2-deoxy-D-glucose ( 18 FDG) shows diffuse increase in metabolic activity in the lungs of patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).In keeping with previous evidence, we interpreted the increased metabolic activity as indicating the presence of an inflammatory process (2-5). The cross-registration of dynamic PET images with computed tomography (CT) scans allowed us to show that the increased metabolic activity was not confined to regions with abnormal density but also involved normally aerated regions (1, 6).Mechanical ventilation can be a powerful inflammatory stimulus and ventilator-induced lung injury (VILI) has been the object of extensive research. Two main mechanisms have been advocated for VILI, the first being the cyclic recruitment and derecruitment of alveolar units (sometimes referred to as ''atelectrauma'') (7, 8) and the second being the (over)distension of aerated alveolar units (9, 10). Most of the data on VILI derive from animal ...

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Section: Discussionmentioning

confidence: 99%

Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

Bellani¹,

Guerra²,

Musch³

et al. 2011

Am J Respir Crit Care Med

190

159

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“…In humans, PET has been shown to demonstrate pulmonary inflammation in infective pneumonia (38) and cystic fibrosis (39). Recently, there have been 2 small studies using 18 F-FDG PET (without CT) in IPF (40,41).…”

Section: Discussionmentioning

confidence: 99%

Idiopathic Pulmonary Fibrosis and Diffuse Parenchymal Lung Disease: Implications from Initial Experience with¹⁸F-FDG PET/CT

Groves¹,

Win²,

Screaton³

et al. 2009

J Nucl Med

142

126

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The purpose of this study was to evaluate integrated 18 F-FDG PET/CT in patients with idiopathic pulmonary fibrosis (IPF) and diffuse parenchymal lung disease (DPLD). Methods: Thirty-six consecutive patients (31 men and 5 women; mean age 6 SD, 68.7 6 9.4 y) with IPF (n 5 18) or other forms of DPLD (n 5 18) were recruited for PET/CT and high-resolution CT (HRCT), acquired on the same instrument. The maximal pulmonary 18 F-FDG metabolism was measured as a standardized uptake value (SUV max ). At this site, the predominant lung parenchyma HRCT pattern was defined for each patient: ground-glass or reticulation/honeycombing. Patients underwent a global health assessment and pulmonary function tests. Results: Raised pulmonary 18 F-FDG metabolism in 36 of 36 patients was observed. The parenchymal pattern on HRCT at the site of maximal 18 F-FDG metabolism was predominantly ground-glass (7/36), reticulation/ honeycombing (26/36), and mixed (3/36). The mean SUV max in patients with ground-glass and mixed patterns was 2.0 6 0.4, and in reticulation/honeycombing it was 3.0 6 1.0 (MannWhitney U test, P 5 0.007). The mean SUV max in patients with IPF was 2.9 6 1.1, and in other DPLD it was 2.7 6 0.9 (MannWhitney U test, P 5 0.862). The mean mediastinal lymph node SUV max (2.7 6 1.3) correlated with pulmonary SUV max (r 5 0.63, P , 0.001). Pulmonary 18 F-FDG uptake correlated with the global health score (r 5 0.50, P 5 0.004), forced vital capacity (r 5 0.41, P 5 0.014), and transfer factor (r 5 0.37, P 5 0.042). Conclusion: Increased pulmonary 18 F-FDG metabolism in all patients with IPF and other forms of DPLD was observed. Pulmonary 18 F-FDG uptake predicts measurements of health and lung physiology in these patients. 18 F-FDG metabolism was higher when the site of maximal uptake corresponded to areas of reticulation/honeycomb on HRCT than to those with ground-glass patterns.

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“…Even though pulmonary insufficiency remains the leading cause of morbidity and mortality in CF, the causes and manifestations of chronic airway inflammation appear to differ between CF patients (31)(32)(33)(34)(35). This interpatient variability could result from unique underlying CFTR defects, differences in microbial infection, the associated immune responses, environmental influences, and disease-modifying genes (36,37).…”

Section: Introductionmentioning

confidence: 99%

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

Skopelja¹,

Hamilton²,

Jones³

et al. 2016

JCI Insight

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Quantifying Pulmonary Inflammation in Cystic Fibrosis with Positron Emission Tomography

Cited by 91 publications

References 38 publications

Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

Idiopathic Pulmonary Fibrosis and Diffuse Parenchymal Lung Disease: Implications from Initial Experience with¹⁸F-FDG PET/CT

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

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Quantifying Pulmonary Inflammation in Cystic Fibrosis with Positron Emission Tomography

Cited by 91 publications

References 38 publications

Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

Idiopathic Pulmonary Fibrosis and Diffuse Parenchymal Lung Disease: Implications from Initial Experience with18F-FDG PET/CT

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

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Idiopathic Pulmonary Fibrosis and Diffuse Parenchymal Lung Disease: Implications from Initial Experience with¹⁸F-FDG PET/CT