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Chronic Lung Allograft Dysfunction: Review of CT and Pathologic Findings.

ABSTRACT: Chronic lung allograft dysfunction (CLAD) is the most common cause of mortality in lung transplant recipients after the 1st year of transplantation. CLAD has traditionally been classified into two distinct obstructive and restrictive forms: bronchiolitis obliterans syndrome and restrictive allograft syndrome. However, CLAD may manifest with a spectrum of imaging and pathologic findings and a combination of obstructive and restrictive physiologic abnormalities. Although the initial CT manifestations of CLAD may be nonspecific, the progression of findings at follow-up should signal the possibility of CLAD and may be present on imaging studies prior to the development of functional abnormalities of the lung allograft. This review encompasses the evolution of CT findings in CLAD, with emphasis on the underlying pathogenesis and pathologic condition, to enhance understanding of imaging findings. The purpose of this article is to familiarize the radiologist with the initial and follow-up CT findings of the obstructive, restrictive, and mixed forms of CLAD, for which early diagnosis and treatment may result in improved survival. Supplemental material is available for this article. © RSNA, 2021.

SUBMITTER: Byrne D

PROVIDER: S-EPMC7978021 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Chronic Lung Allograft Dysfunction: Review of CT and Pathologic Findings.

Byrne Danielle D Nador Roland G RG English John C JC Yee John J Levy Robert R Bergeron Celine C Swiston John R JR Mets Onno M OM Muller Nestor L NL Bilawich Ana-Maria AM

Radiology. Cardiothoracic imaging 20210211 1

Chronic lung allograft dysfunction (CLAD) is the most common cause of mortality in lung transplant recipients after the 1st year of transplantation. CLAD has traditionally been classified into two distinct obstructive and restrictive forms: bronchiolitis obliterans syndrome and restrictive allograft syndrome. However, CLAD may manifest with a spectrum of imaging and pathologic findings and a combination of obstructive and restrictive physiologic abnormalities. Although the initial CT manifestati ...[more]

PMID: 33778654

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Project description:IntroductionChronic lung allograft dysfunction (CLAD) can take two forms: bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). The aim was to determine if chest-CT abnormalities after lung transplantation (LTx) could predict CLAD before respiratory functional deterioration.Materials and methodsThis monocentric retrospective study analyzed consecutive patients who underwent LTx from January 2015 to December 2018. Initial CT post-LTx (CTi) and a follow-up CT at least 9 months post-LTx (CTf) were reviewed. CLAD was defined as a persistent respiratory functional decline (> 20% of basal FEV1) outside acute episode. A Cox regression was performed in univariate, then in multivariate analysis (including features with p < 0.01 in univariate or of clinical importance) to determine risk factors for CLAD. Subgroup analyses were made for BOS, RAS, and death.ResultsAmong 118 LTx patients (median (min-max) 47 (18-68) years), 25 developed CLAD during follow-up (19 BOS). The median time to CLAD since LTx was 570 days [150-1770]. Moderate pulmonary artery stenosis (30-50%) was associated with the occurrence of CLAD on CTi (hazard ratio HR = 4.6, CI [1.6-13.2]) and consolidations and pleural effusion on CTf (HR = 2.6, CI [1.3-4.9] and HR = 4.5, CI [1.5-13.6] respectively). The presence of mosaic attenuation (HR = 4.1, CI [1.4-12.5]), consolidations (HR = 2.6, CI [1.3-5.4]), and pleural effusions (p = 0.01, HR = 5.7, CI [1.4-22.3]) were risk factors for BOS on CTf. The consolidations (p = 0.029) and pleural effusions (p = 0.001) were risk factors for death on CTf.ConclusionsCTi and CTf in the monitoring of LTx patients could predict CLAD. Moderate pulmonary artery stenosis, mosaic pattern, parenchyma condensations, and pleural effusions were risk factors for CLAD.Critical relevance statementThere is a potential predictive role of chest CT in the follow-up of LTx patients for chronic lung allograft dysfunction (CLAD). Early chest CT should focus on pulmonary artery stenosis (risk factor for CLAD in this study). During the follow-up (at least 9 months post-LTx), parenchymal consolidations and pleural effusions were shown to be risk factors for CLAD, and death in subgroup analyses.Key points• Pulmonary artery stenosis (30-50%) on initial chest-CT following lung transplantation predicts CLAD HR = 4.5; CI [1.6-13.2]. • Pleural effusion and consolidations 1 year after lung transplantation predict CLAD and death. • Early evaluation of lung transplanted patients should evaluate pulmonary artery anastomosis.

Project description:BackgroundChronic lung allograft dysfunction (CLAD) is the leading cause of poor long-term survival after lung transplantation (LT). Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) aimed to predict CLAD.MethodsTo predict CLAD, we investigated the clinicome of patients with LT; the exposome through assessment of airway microbiota in bronchoalveolar lavage cells and air pollution studies; the immunome with works on activation of dendritic cells, the role of T cells to promote the secretion of matrix metalloproteinase-9, and subpopulations of T and B cells; genome polymorphisms; blood transcriptome; plasma proteome studies and assessment of MSK1 expression.ResultsClinicome: the best multivariate logistic regression analysis model for early-onset CLAD in 422 LT eligible patients generated a ROC curve with an area under the curve of 0.77. Exposome: chronic exposure to air pollutants appears deleterious on lung function levels in LT recipients (LTRs), might be modified by macrolides, and increases mortality. Our findings established a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant. Immunome: a decreased expression of CLEC1A in human lung transplants is predictive of the development of chronic rejection and associated with a higher level of interleukin 17A; Immune cells support airway remodeling through the production of plasma MMP-9 levels, a potential predictive biomarker of CLAD. Blood CD9-expressing B cells appear to favor the maintenance of long-term stable graft function and are a potential new predictive biomarker of BOS-free survival. An early increase of blood CD4 + CD57 + ILT2+ T cells after LT may be associated with CLAD onset. Genome: Donor Club cell secretory protein G38A polymorphism is associated with a decreased risk of severe primary graft dysfunction after LT. Transcriptome: blood POU class 2 associating factor 1, T-cell leukemia/lymphoma domain, and B cell lymphocytes, were validated as predictive biomarkers of CLAD phenotypes more than 6 months before diagnosis. Proteome: blood A2MG is an independent predictor of CLAD, and MSK1 kinase overexpression is either a marker or a potential therapeutic target in CLAD.ConclusionSystems prediction of Chronic Lung Allograft Dysfunction generated multiple fingerprints that enabled the development of predictors of CLAD. These results open the way to the integration of these fingerprints into a predictive handprint.

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Chronic Lung Allograft Dysfunction: Review of CT and Pathologic Findings.

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Chronic Lung Allograft Dysfunction: Review of CT and Pathologic Findings.

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