Cystic Fibrosis: Detecting Changes in Airway Inflammation with FDG PET/CT

Amin, Reshma; Charron, Martin; Grinblat, Leonard; Shammas, Amer; Grasemann, Hartmut; Graniel, Karla; Ciet, Pierluigi; Tiddens, Harm A.W.M.; Ratjen, Félix

doi:10.1148/radiol.12111873

Cited by 41 publications

(30 citation statements)

References 41 publications

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“…Previous computed tomography studies have demonstrated that all of these factors can improve with treatment of a pulmonary exacerbation, but that the predominant component may vary between patients [12,13]. Recent studies would suggest that mucus plugging, and specifically large-airway mucus plugging changes more than other aspects of CF lung disease with antibiotic therapy [12,41]. In contrast, LCI is affected by heterogeneities at all levels of the airway tree, including peripheral airway disease, and changes in bronchomotor tone do not affect the measurement as much as FEV1, as demonstrated by studying LCI before and after administration of bronchodilators [42][43][44].…”

Section: Discussionmentioning

confidence: 99%

Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations

et al. 2015

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Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response.A systematic literature search was performed to identify prospective observational studies. Factors predicting the relative change in LCI and spirometry were evaluated while adjusting for within-study clustering.Six previously reported studies and one unpublished study, which included 176 pulmonary exacerbations in both paediatric and adult patients, were included. Overall, LCI significantly decreased by 0.40 units (95% CI −0.60-−0.19, p=0.004) or 2.5% following treatment. The relative change in LCI was significantly correlated with the relative change in forced expiratory volume in 1 s (FEV1), but results were discordant in 42.5% of subjects (80 out of 188). Higher (worse) baseline LCI was associated with a greater improvement in LCI (slope: −0.9%, 95% CI −1.0-−0.4%).LCI response to therapy for pulmonary exacerbations is heterogeneous in CF patients; the overall effect size is small and results are often discordant with FEV1. @ERSpublications Lung clearance index response to therapy for pulmonary exacerbations is heterogeneous in cystic fibrosis patients http://ow.ly/Mnvtd

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Section: Discussionmentioning

confidence: 99%

Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations

et al. 2015

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“…Normalizing it for the air fraction will likely improve its accuracy as a reflection of lung cell metabolic activity (38). Normalization for blood (such as the tissue-toblood ratio, as explored in a dog model of ARDS (46)) may further improve the accuracy of V B ; however, whether this approach is comparable to correcting for V B as measured by kinetic analysis or other imaging (such as 15 O-CO scans) remains to be seen.…”

Section: Analysis Methods and Their Applications In Lung Diseases Quamentioning

confidence: 99%

“…Inflammation characterizes several lung diseases, including pneumonia, cystic fibrosis, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), asthma, and interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF), among others (7,8,10,11,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Because ARDS, COPD, and IPF can cause significant variability in the amounts of air, blood, and water in the lungs (Fig.…”

Section: Clinical Applications Investigated With 18 F-fdg Pet Imagingmentioning

confidence: 99%

Quantification of Lung PET Images: Challenges and Opportunities

et al. 2017

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“…Also, the combination of CT and PET scan in fusion images using fluorodeoxyglucose (FD) PET/CT is a useful tool for detecting inflammatory changes resulting from treatment for pulmonary exacerbations in pediatric patients with CF. These changes correlated with lung function, sputum neutrophil counts, and CF-CT scores, quantified by using standardized uptake values (SUVs) [12].…”

Section: Outcomes In Trials For Rare Pulmonary Diseasesmentioning

confidence: 99%

Innovations in Outcomes and Designs of Clinical Trials for Respiratory Drug Development

Lins¹

2017

J Clin Respir Dis Care

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Clinical trials for the development of respiratory drugs have for years been reliant upon measurements of physiologic tests, combined with the use of questionnaires. New drugs were mostly administered by inhalation and increasingly in fixed combinations. However, these lung function tests have a lack of sensitivity for patient-relevant clinical outcomes. Moreover, new insights in phenotypes and endotypes of these diseases in the basic mechanisms and the discovery of new targets for therapy, have led to the need for a more personalized patient-centered approach and precision medicine.In recent years, a great number of techniques have been proposed but some need further validation. These include fractional exhaled nitric oxide, health-related quality of life and the use of biomarkers like blood and sputum eosinophils and neutrophils, IgE, sIgE, periostin, copeptin and specific cytokines. Additionally, exhaled breath condensate and lung deposition studies by functional residual imaging and by local bronchial pharmacokinetics can be used. In rare diseases like cystic fibrosis, Lung Clearance Index and CT and PET scan fusion images seem to be valuable outcome measurements. Lastly leverage of lung function tests can be done by using body plethysmography, measuring respiratory impedance, variability and the use of modeling and simulation.The need for a patient-centric approach through all stages of clinical development is becoming mandatory. So, an evolution from classical randomized clinical trials (RCTs) to more efficient and patient-relevant designs will be seen more in the future. RCTs will remain necessary for regulatory submission but more efficient and adaptive designs with lower heterogeneity and the use of pragmatic trials are needed. This evolution from undefined targets to a more targeted approach will lead us closer to precision medicine.In this overview, the unmet medical need for better outcomes and study designs in the development of treatments for respiratory diseases, are discussed.

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Cystic Fibrosis: Detecting Changes in Airway Inflammation with FDG PET/CT

Cited by 41 publications

References 41 publications

Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations

Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations

Quantification of Lung PET Images: Challenges and Opportunities

Innovations in Outcomes and Designs of Clinical Trials for Respiratory Drug Development

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