case_images: PMC10866027_01
case_images: Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC trends in the four patients. Spirometry shows a restrictive pattern of decline in lung allograft function. The vertical dashed lines represent the onset of chronic lung allograft dysfunction (CLAD), marked by recurrent pleural effusions.
case_images: ti-37-12395-g001.jpg
case_images: PMC10866027_04_ti-37-12395-g001.jpg
case_images: F1
case_images: He had an uneventful posttransplant course until he developed a gradual spirometric decline 20 months after transplant (Figure 1). A pleural biopsy (Supplementary Figure S1) showed pleural fibrosis with organizing hemothorax, and he received two doses of intrapleural tissue plasminogen activator to break up loculations.
case_images: Chest CT of the four patients showing pleural effusions and plate-like atelectasis but no lung parenchymal changes typical of restrictive allograft syndrome.
case_images: ti-37-12395-g002.jpg
case_images: PMC10866027_04_ti-37-12395-g002.jpg
case_images: F2
case_images: His chest CT initially showed bilateral, loculated pleural effusions, and subsequent imaging revealed pleural thickening and plate-like and rounded atelectasis but no RAS-like lung parenchymal changes (Figure 2). In addition, sEVs isolated from the patient's plasma contained elevated levels of NFkB, 20S proteasome, lipocalin, TNFalpha, and TGFbeta compared to control samples from stable LTRs (Figure 3; Supplementary Figure S2), and the concentrations of these inflammatory immunologic markers increased before the onset of CLAD.
case_images: PMC10866027_02
case_images: Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC trends in the four patients. Spirometry shows a restrictive pattern of decline in lung allograft function. The vertical dashed lines represent the onset of chronic lung allograft dysfunction (CLAD), marked by recurrent pleural effusions.
case_images: ti-37-12395-g001.jpg
case_images: PMC10866027_04_ti-37-12395-g001.jpg
case_images: F1
case_images: He had an uneventful posttransplant course until he developed a gradual spirometric decline 20 months after transplant (Figure 1). A pleural biopsy (Supplementary Figure S1) showed pleural fibrosis with organizing hemothorax, and he received two doses of intrapleural tissue plasminogen activator to break up loculations.
case_images: Chest CT of the four patients showing pleural effusions and plate-like atelectasis but no lung parenchymal changes typical of restrictive allograft syndrome.
case_images: ti-37-12395-g002.jpg
case_images: PMC10866027_04_ti-37-12395-g002.jpg
case_images: F2
case_images: His chest CT initially showed bilateral, loculated pleural effusions, and subsequent imaging revealed pleural thickening and plate-like and rounded atelectasis but no RAS-like lung parenchymal changes (Figure 2). In addition, sEVs isolated from the patient's plasma contained elevated levels of NFkB, 20S proteasome, lipocalin, TNFalpha, and TGFbeta compared to control samples from stable LTRs (Figure 3; Supplementary Figure S2), and the concentrations of these inflammatory immunologic markers increased before the onset of CLAD.
case_images: PMC10866027_03
case_images: Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC trends in the four patients. Spirometry shows a restrictive pattern of decline in lung allograft function. The vertical dashed lines represent the onset of chronic lung allograft dysfunction (CLAD), marked by recurrent pleural effusions.
case_images: ti-37-12395-g001.jpg
case_images: PMC10866027_04_ti-37-12395-g001.jpg
case_images: F1
case_images: He had an uneventful posttransplant course until he developed a gradual spirometric decline 20 months after transplant (Figure 1). A pleural biopsy (Supplementary Figure S1) showed pleural fibrosis with organizing hemothorax, and he received two doses of intrapleural tissue plasminogen activator to break up loculations.
case_images: Chest CT of the four patients showing pleural effusions and plate-like atelectasis but no lung parenchymal changes typical of restrictive allograft syndrome.
case_images: ti-37-12395-g002.jpg
case_images: PMC10866027_04_ti-37-12395-g002.jpg
case_images: F2
case_images: His chest CT initially showed bilateral, loculated pleural effusions, and subsequent imaging revealed pleural thickening and plate-like and rounded atelectasis but no RAS-like lung parenchymal changes (Figure 2). In addition, sEVs isolated from the patient's plasma contained elevated levels of NFkB, 20S proteasome, lipocalin, TNFalpha, and TGFbeta compared to control samples from stable LTRs (Figure 3; Supplementary Figure S2), and the concentrations of these inflammatory immunologic markers increased before the onset of CLAD.
case_images: PMC10866027_04
case_images: Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC trends in the four patients. Spirometry shows a restrictive pattern of decline in lung allograft function. The vertical dashed lines represent the onset of chronic lung allograft dysfunction (CLAD), marked by recurrent pleural effusions.
case_images: ti-37-12395-g001.jpg
case_images: PMC10866027_04_ti-37-12395-g001.jpg
case_images: F1
case_images: He had an uneventful posttransplant course until he developed a gradual spirometric decline 20 months after transplant (Figure 1). A pleural biopsy (Supplementary Figure S1) showed pleural fibrosis with organizing hemothorax, and he received two doses of intrapleural tissue plasminogen activator to break up loculations.
case_images: Chest CT of the four patients showing pleural effusions and plate-like atelectasis but no lung parenchymal changes typical of restrictive allograft syndrome.
case_images: ti-37-12395-g002.jpg
case_images: PMC10866027_04_ti-37-12395-g002.jpg
case_images: F2
case_images: His chest CT initially showed bilateral, loculated pleural effusions, and subsequent imaging revealed pleural thickening and plate-like and rounded atelectasis but no RAS-like lung parenchymal changes (Figure 2). In addition, sEVs isolated from the patient's plasma contained elevated levels of NFkB, 20S proteasome, lipocalin, TNFalpha, and TGFbeta compared to control samples from stable LTRs (Figure 3; Supplementary Figure S2), and the concentrations of these inflammatory immunologic markers increased before the onset of CLAD.
case_images: (A): Western blot of small extracellular vesicle (sEV) proteins NFkB, 20S proteasome, lipocalin, TNFalpha, and TGFbeta from plasma samples of lung transplant recipients. SC1 and SC2 denote sEV proteins from 2 stable controls; P4A and P4B denote sEV proteins in the plasma of patient 4, 9 months before and 1 year after the onset of CLAD, respectively. CD9 and CD63 were used as controls to normalize the blots for NFkB, 20S proteasome, lipocalin, TNFalpha, and TGFbeta. (B): Densitometry and statistical analysis of western blots for stable controls and pre and post CLAD-onset samples of patient 4. Relative density graphs are represented as bar plots. (C): Nanosight images depicting the size of the sEVs isolated from both samples of patient 4.
case_images: ti-37-12395-g003.jpg
case_images: PMC10866027_04_ti-37-12395-g003.jpg
case_images: F3
case_images: In addition, sEVs isolated from the patient's plasma contained elevated levels of NFkB, 20S proteasome, lipocalin, TNFalpha, and TGFbeta compared to control samples from stable LTRs (Figure 3; Supplementary Figure S2), and the concentrations of these inflammatory immunologic markers increased before the onset of CLAD.