Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lung Ultrasound to Phenotype Chronic Lung Allograft Dysfunction in Lung Transplant Recipients. A Prospective Observational Study.

ABSTRACT:

Background

Bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) are two distinct phenotypes of chronic lung allograft dysfunction (CLAD) in lung transplant (LTx) recipients. Contrary to BOS, RAS can radiologically present with a pleuroparenchymal fibroelastosis (PPFE) pattern. This study investigates lung ultrasound (LUS) to identify potential surrogate markers of PPFE in order to distinguish CLAD phenotype RAS from BOS.

Methods

A prospective cohort study performed at a National Lung Transplantation Center during June 2016 to December 2017. Patients were examined with LUS and high-resolution computed tomography of the thorax (HRCT).

Results

Twenty-five CLAD patients (72% males, median age of 54 years) were included, corresponding to 19/6 BOS/RAS patients. LUS-identified pleural thickening was more pronounced in RAS vs. BOS patients (5.6 vs. 2.9 mm) compatible with PPFE on HRCT. LUS-identified pleural thickening as an indicator of PPFE in RAS patients' upper lobes showed a sensitivity of 100% (95% CI; 54-100%), specificity of 100% (95% CI; 82-100%), PPV of 100% (95% CI; 54-100%), and NPV of 100% (95% CI; 82-100%).

Conclusion

Apical pleural thickening detected by LUS and compatible with PPFE on HRCT separates RAS from BOS in patients with CLAD. We propose LUS as a supplementary tool for initial CLAD phenotyping.

SUBMITTER: Davidsen JR

PROVIDER: S-EPMC7961975 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Increase of Th17 Cell Phenotype in Kidney Transplant Recipients with Chronic Allograft Dysfunction.

Project description:This study was performed to determine the association of Th17 cell phenotype with chronic allograft dysfunction in kidney transplant recipients (KTRs). We compared the expression of Th17 cell phenotype in KTRs with chronic allograft dysfunction group (CAD, n = 52) with four control groups (long-term stable KTRs (LTS, n = 67), early stable KTRs (ES, n = 28), end stage renal disease (ESRD, n = 45), and healthy control (HC, n = 26). We also performed in vitro study using human proximal renal tubular epithelial cell line (HPRTEpiC) to evaluate the effect of IL-17 on human renal tubular epithelial cells. The CAD group showed increased percentage of Th17 cells out of CD4+ T cells and also increased proportion of IL-17 producing cells out of effector memory T cells or out of CCR4+CCR6+/CD4+ T cells compared to the LTS group and other control groups. Also, the serum level of IL-17, IL-33, and RAGE, and the expression of IL-1beta, RAGE, and HMGB1 mRNA showed an increase in the CAD group compared to the LTS group. In vitro study revealed that IL-17 increased production of IL-6 and IL-8 and up-regulated profibrotic gene expression such as ACTA-2 and CTGF in HPRTEpiC in a dose-dependent manner, which suggests that IL-17 has a role in the development of renal tubular cell injury. The results of our study may suggest that increase of Th17 cell phenotype could be a marker for the chronic allograft injury; hence there is a need to develop diagnostic and therapeutic tools targeting the Th17 cells pathway.

| S-EPMC4696852 | biostudies-literature

Urinary microbiome associated with chronic allograft dysfunction in kidney transplant recipients.

Project description:BACKGROUND:We performed a study to identify differences in the urinary microbiome associated with chronic allograft dysfunction (CAD) and compared the urinary microbiome of male and female transplant recipients with CAD. METHODS:This case-control study enrolled 67 patients within the Deterioration of Kidney Allograft Function (DeKAF) Genomics cohort at two transplant centers. CAD was defined as a greater than 25% rise in serum creatinine relative to a 3 month post-transplant baseline. Urine samples from patients with and without CAD were analyzed using 16S V4 bacterial ribosomal DNA sequences. RESULTS:Corynebacterium was more prevalent in female and male patients with CAD compared to non-CAD female patients (P = 0.0005). A total 21 distinct Operational Taxonomic Unit (OTUs) were identified as significantly different when comparing CAD and non-CAD patients using Kruskal-Wallis (P < 0.01). A subset analysis of female patients with CAD compared to non-CAD females identified similar differentially abundant OTUs, including the genera Corynebacterium and Staphylococcus (Kruskal-Wallis; P = 0.01; P = 0.004, respectively). Male CAD vs female CAD analysis showed greater abundance of phylum Proteobacteria in males. CONCLUSION:There were differences in the urinary microbiome when comparing female and male CAD patients with their female non-CAD counterparts and these differences persisted in the subset analysis limited to female patients only.

| S-EPMC6984979 | biostudies-literature

Interstitial pneumonitis and the risk of chronic allograft rejection in lung transplant recipients.

Project description:The presence of interstitial pneumonitis (IP) on surveillance lung biopsy specimens in lung transplant recipients is poorly described, and its impact on posttransplant outcomes is not established. The following study assessed the association of posttransplant IP with the development of bronchiolitis obliterans syndrome (BOS).We examined all recipients of primary cadaveric lung transplants at our institution between January 1, 2000, and December 31, 2007 (N = 145). Patients had bronchoscopies with BAL, and transbronchial biopsies performed for surveillance during posttransplant months 1, 3, 6, and 12 as well as when clinically indicated. Patients were given a diagnosis of IP if, in the absence of active infection and organizing pneumonia, they showed evidence of interstitial inflammation and fibrosis on two or more biopsy specimens.IP was a significant predictor of BOS (OR, 7.84; 95% CI, 2.84-21.67; P < .0001) and was significantly associated with time to development of BOS (hazard ratio, 3.8; 95% CI, 1.93-7.39; P = .0001) within the first 6 years posttransplant. The presence of IP did not correlate with a significantly higher risk of mortality or time to death. There was no association between the presence of IP and the development of or time to acute rejection.The presence of IP on lung transplant biopsy specimens suggests an increased risk for BOS, which is independent of the presence of acute cellular rejection.

| S-EPMC3653348 | biostudies-other

Functional and histological improvement after everolimus rescue of chronic allograft dysfunction in renal transplant recipients.

Project description:BACKGROUND:We tested the strategy of mTOR inhibitors with calcineurin inhibitor minimization in renal transplant recipients with known chronic allograft dysfunction. METHODS:In this open-label, single-arm study, renal transplant patients were recruited after biopsy-confirmed chronic allograft dysfunction in the absence of acute rejection episode within 2 months, with proteinuria <0.8 g/day, and serum creatinine <220 ?mol/L or estimated glomerular filtration rate >40 mL/min/1.73 m(2). They were converted to everolimus (aiming for trough everolimus level 3-8 ng/mL) with cyclosporine minimization, to assess the effect on renal function, rate of glomerular filtration rate decline, and longitudinal transplant biopsy at 12 months. RESULTS:Seventeen Chinese patients (median transplant duration, 4.2 years) were recruited; no patients discontinued study medication. The mean slope of the glomerular filtration rate over time was -4.31±6.65 mL/min/1.73 m(2) per year in the year before everolimus, as compared with 1.29±5.84 mL/min/1.73 m(2) per year in the 12 months of everolimus therapy, a difference of 5.61 mL/min/1.73 m(2) per year (95% confidence interval [CI], 0.40-10.8) favoring everolimus therapy (P=0.036). Serial renal biopsy histology showed significant decrease of tubular atrophy (15.7%±11.3% versus 7.1%±7.3%, P=0.005) and interstitial fibrosis (14.8%±11.5% versus 7.2%±8.2%, P=0.013). Intrarenal expression of TGF-?1 mRNA showed a nonsignificant decrease after everolimus treatment. CONCLUSION:In renal transplant recipients with biopsy-confirmed chronic allograft dysfunction, we found a significant beneficial effect of everolimus rescue therapy and calcineurin inhibitor minimization strategy on the improvement of glomerular filtration rate decline rate. In secondary analysis, everolimus was shown to slow down the disease progression by reducing the tubular atrophy and interstitial fibrosis scoring.

| S-EPMC4445695 | biostudies-literature

Inflammation in the setting of chronic allograft dysfunction post-kidney transplant: phenotype and genotype.

Project description:BackgroundChronic allograft dysfunction (CGD) is a common outcome in kidney transplants, but its pathogenesis is unclear. We investigated the CGD phenotype and single-nucleotide polymorphisms (SNPs) associated with CGD.MethodThis prospective study enrolled 2336 transplants from seven transplant centers in North America. CGD was defined as a >25% rise in serum creatinine relative to a three-month post-transplant baseline, requiring a kidney biopsy. We genotyped 2724 SNPs in the initial 979 transplants, which form the test cohort.ResultsCGD occurred 11.2 times per 100 person-years at a median of 509 ± 387 days from the three-month baseline. CGD was independently associated with death-censored, allograft failure, in an adjusted analysis [HR=20.6 (11.8-35.8, p < 0.001)]. Among 366 transplant recipients with CGD, 91% had inflammation on biopsy scores. 94 (26%) had inflammatory changes consistent with a diagnosis of concomitant acute rejection. SNPs in FM06 and FM03, potential drug metabolism genes, were associated with CGD, after accounting for multiple testing.ConclusionCGD phenotype with concomitant inflammation is associated with increased risk of allograft failure. SNPs associated with CGD in novel drug metabolism and transport genes, will be validated in subsequent transplants.

| S-EPMC3647022 | biostudies-literature

Humoral immune responses mediate the development of a restrictive phenotype of chronic lung allograft dysfunction.

Project description:Understanding the distinct pathogenic mechanisms that culminate in allograft fibrosis and chronic graft failure is key in improving outcomes after solid organ transplantation. Here, we describe an F1 ? parent orthotopic lung transplant model of restrictive allograft syndrome (RAS), a particularly fulminant form of chronic lung allograft dysfunction (CLAD), and identify a requisite pathogenic role for humoral immune responses in development of RAS. B6D2F1/J (H2-b/d) donor lungs transplanted into the parent C57BL/6J (H2-b) recipients demonstrated a spectrum of histopathologic changes, ranging from lymphocytic infiltration, fibrinous exudates, and endothelialitis to peribronchial and pleuroparenchymal fibrosis, similar to those noted in the human RAS lungs. Gene expression profiling revealed differential humoral immune cell activation as a key feature of the RAS murine model, with significant B cell and plasma cell infiltration noted in the RAS lung allografts. B6D2F1/J lung allografts transplanted into ?Mt-/- (mature B cell deficient) or activation-induced cytidine deaminase (AID)/secretory ?-chain (?s) double-KO (AID-/-?s-/-) C57BL/6J mice demonstrated significantly decreased allograft fibrosis, indicating a key role for antibody secretion by B cells in mediating RAS pathology. Our study suggests that skewing of immune responses determines the diverse allograft remodeling patterns and highlights the need to develop targeted therapies for specific CLAD phenotypes.

| S-EPMC7714414 | biostudies-literature

Human neutrophil peptide in lung chronic allograft dysfunction.

Project description:Our previous case-control study identified human neutrophil peptide (HNP) as a potential biomarker for bronchiolitis obliterans syndrome (BOS) in lung transplant recipients.To prospectively validate HNP as a biomarker for BOS.HNP was measured by ELISA in bronchoalveolar lavage (BAL) fluid in lung transplant recipients.The first HNP measurement after reaching baseline pulmonary function was predictive of developing BOS ?2 (p?=?0.0419). HNP remained elevated in those that developed BOS. The effect of potential confounders did not significantly impact BOS-free survival time.HNP levels are elevated early and persistently in those that develop BOS.

| S-EPMC3222782 | biostudies-literature

Host-Pathogen Interactions and Chronic Lung Allograft Dysfunction.

Project description:Lung transplantation is now considered to be a therapeutic option for patients with advanced-stage lung diseases. Unfortunately, due to post-transplant complications, both infectious and noninfectious, it is only a treatment and not a cure. Infections (e.g., bacterial, viral, and fungal) in the immunosuppressed lung transplant recipient are a common cause of mortality post transplant. Infections have more recently been explored as factors contributing to the risk of chronic lung allograft dysfunction (CLAD). Each major class of infection-(1) bacterial (Staphylococcus aureus and Pseudomonas aeruginosa); (2) viral (cytomegalovirus and community-acquired respiratory viruses); and (3) fungal (Aspergillus)-has been associated with the development of CLAD. Mechanistically, the microbe seems to be interacting with the allograft cells, stimulating the induction of chemokines, which recruit recipient leukocytes to the graft. The recipient leukocyte interactions with the microbe further up-regulate chemokines, amplifying the influx of allograft-infiltrating mononuclear cells. These events can promote recipient leukocytes to interact with the allograft, triggering an alloresponse and graft dysfunction. Overall, interactions between the microbe-allograft-host immune system alters chemokine production, which, in part, plays a role in the pathobiology of CLAD and mortality due to CLAD.

| S-EPMC5711338 | biostudies-literature

Prospective Study on Sexual Dysfunction in Male Chinese Liver Transplant Recipients.

Project description:In patients with end-stage liver disease, hypogonadism and erectile dysfunction are often seen. This study was to determine the incidence of erectile dysfunction before and after liver transplantation (LT) with correlation to change in sex hormone levels from a Chinese cohort. This prospective longitudinal study was registered with The University of Hong Kong Clinical Trials Centre (HKUCTR-1563). The Institutional Review Board approval number is UW-12-273. The study period was from January 2012 to December 2016. Adult male patients with end-stage liver disease enlisted for LT were recruited on informed written consent. All recruited patients were to complete a cross-sectional cohort questionnaire-International Index of Erectile Function, version 5 (IIEF5)-and to receive serum sex hormone checks before and after LT. Twenty-eight patients who underwent LT were included in the analysis. The included patients had significantly reduced prolactin ( p < .001) and 17-beta-estradiol ( p = .024) after LT. There was also a significant drop of IIEF5 score at 1 month after LT, but the score returned to pre-LT level at 6 months. This study demonstrated that there was improvement in sex hormone levels after LT, namely, normalization of estradiol level and lowering of prolactin and progesterone levels. However, improvement in sex hormone levels did not translate into improvement of erectile dysfunction.

| S-EPMC6440053 | biostudies-literature

Symptomatic Respiratory Virus Infection and Chronic Lung Allograft Dysfunction.

Project description:BackgroundChronic lung allograft dysfunction (CLAD) is a major cause of allograft loss post-lung transplantation. Prior studies have examined the association between respiratory virus infection (RVI) and CLAD were limited by older diagnostic techniques, study design, and case numbers. We examined the association between symptomatic RVI and CLAD using modern diagnostic techniques in a large contemporary cohort of lung transplant recipients (LTRs).MethodsWe retrospectively assessed clinical variables including acute rejection, cytomegalovirus pneumonia, upper and lower RVI, and the primary endpoint of CLAD (determined by 2 independent reviewers) in 250 LTRs in a single university transplantation program. Univariate and multivariate Cox models were used to analyze the relationship between RVI and CLAD in a time-dependent manner, incorporating different periods of risk following RVI diagnosis.ResultsFifty patients (20%) were diagnosed with CLAD at a median of 95 weeks post-transplantation, and 79 (32%) had 114 episodes of RVI. In multivariate analysis, rejection and RVI were independently associated with CLAD (adjusted hazard ratio [95% confidence interval]) 2.2 (1.2-3.9), P = .01 and 1.9 (1.1-3.5), P = .03, respectively. The association of RVI with CLAD was stronger the more proximate the RVI episode: 4.8 (1.9-11.6), P < .01; 3.4 (1.5-7.5), P < .01; and 2.4 (1.2-5.0), P = .02 in multivariate analysis for 3, 6, and 12 months following RVI, respectively.ConclusionsSymptomatic RVI is independently associated with development of CLAD, with increased risk at shorter time periods following RVI. Prospective studies to characterize the virologic determinants of CLAD and define the underlying mechanisms are warranted.

| S-EPMC4706632 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data