The lungs were on fire: a pilot study of 18F-FDG PET/CT in idiopathic-inflammatory-myopathy-related interstitial lung disease
28 Apr 2021-Arthritis Research & Therapy (Springer Science and Business Media LLC)-Vol. 23, Iss: 1, pp 198
TL;DR: Elevated bilateral lung SUVmean and abnormal mediastinal lymph node were associated with RP-ILD in IIM-ILD patients and the “DLM” model was valuable in predictingRP-ILD and demanded further evaluation.
Abstract: Background Interstitial lung disease (ILD) and its rapid progression (RP) are the main contributors to unfavourable outcomes of patients with idiopathic inflammatory myopathy (IIM). This study aimed to identify the clinical value of PET/CT scans in IIM-ILD patients and to construct a predictive model for RP-ILD. Methods Adult IIM-ILD patients who were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU), from 1 January 2017 to 31 December 2020 were reviewed. PET/CT scans and other characteristics of patients who met the inclusion and exclusion criteria were collected and analysed. Results A total of 61 IIM-ILD patients were enrolled in this study. Twenty-one patients (34.4%) developed RP-ILD, and 24 patients (39.3%) died during follow-up. After false discovery rate (FDR) correction, the percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.014), bilateral lung mean standard uptake value (SUVmean, P = 0.014) and abnormal mediastinal lymph node (P = 0.045) were significantly different between the RP-ILD and non-RP-ILD groups. The subsequent univariate and multivariate logistic regression analyses verified our findings. A "DLM" model was established by including the above three values to predict RP-ILD with a cut-off value of ≥ 2 and an area under the curve (AUC) of 0.905. Higher bilateral lung SUVmean (P = 0.019) and spleen SUVmean (P = 0.011) were observed in IIM-ILD patients who died within 3 months, and a moderate correlation was recognized between the two values. Conclusions Elevated bilateral lung SUVmean, abnormal mediastinal lymph nodes and decreased DLCO% were significantly associated with RP-ILD in IIM-ILD patients. The "DLM" model was valuable in predicting RP-ILD and requires further validation.
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TL;DR: In this paper, the authors investigated the 18F-Fluorodeoxyglucose (FDG) PET/CT characteristics and its prognostic value in anti-melanoma differentiation associated protein 5 antibody positive (anti-MDA5+) dermatomyositis (DM) patients.
Abstract: Objective. To elucidate the 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) characteristics and its prognostic value in anti-melanoma differentiation associated protein 5 antibody positive (anti-MDA5+) dermatomyositis (DM) patients. Methods. This retrospective cross-sectional study included 26 anti-MDA5+ DM patients and 43 anti-MDA5 negative (anti-MDA5-) idiopathic inflammatory myopathy (IIM) patients who were examined by 18F-FDG PET/CT from January 1st 2017 to December 31st 2020. The maximum standardized uptake value (SUVmax) of multiple organs and other clinical characteristics of patients were measured and analyzed. Results. Compared with the anti-MDA5- group, patients in the anti-MDA5+ group showed higher bilateral lung SUVmax (p=0.029), higher SUVmax of spleen (p=0.011) and bone marrow (p=0.048). Significant correlations between the spleen SUVmax and serum ferritin levels (r = 0.398, p <0.001), ESR (r = 0.274, p= 0.023), platelet count (r= − 0.265, p= 0.028), myositis disease activity assessment score (r = 0.332, p = 0.005), bone marrow SUVmax (r=0.564, p<0.001) and bilateral lung SUVmax (r=0.393, p<0.001) were as well observed. Conclusion. 18F-FDG PET/CT was found valuable in quantifying the pulmonary focal inflammation and potentially unveil the distinctive characteristics and pathophysiological mechanisms in anti-MDA5+ DM patients.
6 citations
TL;DR: 18F-FDG PET/CT is useful for assessing disease activity in patients with IIM-ILD and the combination of PET score, HRCT score, and anti-MDA5 antibody can be used to identify patients at increased risk of RP-ild and with poor prognoses.
4 citations
01 Jun 2022
TL;DR: In this paper , the use of nuclear magnetic resonance imaging (MRI), ultrasound (US), and positron emission tomography (PET) may have the most clinical utility in myositis.
Abstract: Imaging is an important tool in the evaluation of idiopathic inflammatory myopathies. It plays a role in diagnosis, assessment of disease activity and follow-up, and as a non-invasive biomarker. Among the different modalities, nuclear magnetic resonance imaging (MRI), ultrasound (US), and positron emission tomography (PET) may have the most clinical utility in myositis. MRI is currently the best modality to evaluate skeletal muscle and provides excellent characterization of muscle edema and fat replacement through the use of T1-weighted and T2-weighted fat suppressed/STIR sequences. Although MRI can be read qualitatively for the presence of abnormalities, a more quantitative approach using Dixon sequences and the generation of water T2 parametric maps would be preferable for follow-up. Newer protocols such as diffusion-weighted imaging, functional imaging measures, and spectroscopy may be of interest to provide further insights into myositis. Despite the advantages of MRI, image acquisition is relatively time-consuming, expensive, and not accessible to all patients. The use of US to evaluate skeletal muscle in myositis is gaining interest, especially in chronic disease, where fat replacement and fibrosis are detected readily by this modality. Although easily deployed at the bedside, it is heavily dependent on operator experience to recognize disease states. Further, systematic characterization of muscle edema by US is still needed. PET provides valuable information on muscle function at a cellular level. Fluorodeoxyglucose (FDG-PET) has been the most common application in myositis to detect pathologic uptake indicative of inflammation. The use of neurodegenerative markers is now also being utilized for inclusion body myositis. These different modalities may prove to be complementary methods for myositis evaluation.
3 citations
TL;DR: Visual interpretation and [18F]FDG-PET/CT indices have a good overall performance to detect muscle activity but objective, robust and standardized interpretation criteria are currently lacking and may be a promising tool to detect inflammatory lung activity and to early identify patients with rapidly progressive lung disease.
Abstract: Idiopathic inflammatory myopathies (IIM) are considered systemic diseases involving different organs and some subtypes are associated with increased cancer risk. In this review, we provide a comprehensive summary of the current use and potential applications of (semi-)quantitative [18F]FDG-PET/CT indices in patients with IIM focusing on dermatomyositis and polymyositis. Visual interpretation and (semi-)quantitative [18F]FDG-PET indices have a good overall performance to detect muscle activity but objective, robust and standardized interpretation criteria are currently lacking. [18F]FDG-PET/CT is a suitable modality to screen for malignancy in patients with myositis and may be a promising tool to detect inflammatory lung activity and to early identify patients with rapidly progressive lung disease. The latter remains to be determined in large, prospective comparative trials.
3 citations
TL;DR: In this article , a review of pre-clinical and clinical studies on molecular imaging with PET and single photon emission computed tomography (SPECT) in IPF and CTD-ILD is presented.
3 citations
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Karolinska University Hospital1, Karolinska Institutet2, Hospital of the University of Pennsylvania3, Great Ormond Street Hospital4, Brigham and Women's Hospital5, University of Kansas6, Mayo Clinic7, University of Alabama8, University of Pittsburgh9, Central Manchester University Hospitals NHS Foundation Trust10, University of Liverpool11, University of Debrecen12, University of Toronto13, University of Guadalajara14, University of Cambridge15, University of Tsukuba16, United States Department of Health and Human Services17, Tokyo Medical and Dental University18, Oregon State University19, Dalhousie University20, Peking University21, Duke University22, Oslo University Hospital23, New Generation University College24, Charles University in Prague25, National Institutes of Health26
TL;DR: New classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups, and have been partially validated and generally perform better than existing criteria.
Abstract: Objective To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. Results Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) ‘probable IIM’, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to ‘definite IIM’. A probability of Conclusions The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of ‘definite’, ‘probable’ and ‘possible’ IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.
754 citations
TL;DR: The integration of the spleen in the regulation of immune responses locally and in the whole body is discussed and the relevance of findings for the understanding of inflammatory and degenerative diseases and their treatments is presented.
669 citations
TL;DR: The data support the novel concept of glycolytic reprogramming in the pathogenesis of lung fibrosis and provide proof-of-concept that targeting this pathway may be efficacious in treating fibrotic disorders, such as idiopathic pulmonary fibrosis.
Abstract: Rationale: Dysregulation of cellular metabolism has been shown to participate in several pathologic processes. However, the role of metabolic reprogramming is not well appreciated in the pathogenesis of organ fibrosis.Objectives: To determine if glycolytic reprogramming participates in the pathogenesis of lung fibrosis and assess the therapeutic potential of glycolytic inhibition in treating lung fibrosis.Methods: A cell metabolism assay was performed to determine glycolytic flux and mitochondrial respiration. Lactate levels were measured to assess glycolysis in fibroblasts and lungs. Glycolytic inhibition by genetic and pharmacologic approaches was used to demonstrate the critical role of glycolysis in lung fibrosis.Measurements and Main Results: Augmentation of glycolysis is an early and sustained event during myofibroblast differentiation, which is dependent on the increased expression of critical glycolytic enzymes, in particular, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Augment...
297 citations
TL;DR: In this article, high-parameter imaging mass cytometry was used to investigate the cellular composition and spatial architecture of acute lung injury in humans, including injuries derived from SARS-CoV-2 infection at single-cell resolution.
Abstract: Recent studies have provided insights into the pathology of and immune response to COVID-191–8 However, a thorough investigation of the interplay between infected cells and the immune system at sites of infection has been lacking Here we use high-parameter imaging mass cytometry9 that targets the expression of 36 proteins to investigate the cellular composition and spatial architecture of acute lung injury in humans (including injuries derived from SARS-CoV-2 infection) at single-cell resolution These spatially resolved single-cell data unravel the disordered structure of the infected and injured lung, alongside the distribution of extensive immune infiltration Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia and COVID-19, respectively We provide evidence that SARS-CoV-2 infects predominantly alveolar epithelial cells and induces a localized hyperinflammatory cell state that is associated with lung damage We leverage the temporal range of fatal outcomes of COVID-19 in relation to the onset of symptoms, which reveals increased macrophage extravasation and increased numbers of mesenchymal cells and fibroblasts concomitant with increased proximity between these cell types as the disease progresses—possibly as a result of attempts to repair the damaged lung tissue Our data enable us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint We use this landscape to characterize the pathophysiology of the human lung from its macroscopic presentation to the single-cell level, which provides an important basis for understanding COVID-19 and lung pathology in general Imaging mass cytometry of the human lung reveals the cellular composition and spatial architecture during COVID-19 and other acute injuries, enabling the characterization of lung pathophysiology from structural, immunological and clinical perspectives
186 citations
TL;DR: The role of the innate and adaptive immune system in the initiation and perpetuation of IPF pathobiology is focused on and how immune responses are influenced by current anti-fibrotic treatments, such as pirfenidone and nintedanib are discussed.
173 citations