Chronic lung allograft dysfunction phenotype and prognosis by machine learning CT analysis

2021 ◽  
pp. 2101652
Author(s):  
Micheal C. McInnis ◽  
Jin Ma ◽  
Gauri Rani Karur ◽  
Christian Houbois ◽  
Liran Levy ◽  
...  

BackgroundChronic lung allograft dysfunction (CLAD) is the principal cause of graft failure in lung transplant recipients and prognosis depends on CLAD phenotype. We used machine learning computed tomography (CT) lung texture analysis tool at CLAD diagnosis for phenotyping and prognostication compared to radiologists’ scoring.MethodsThis retrospective study included all adult first double-lung transplant patients (01/2010–12/2015) with CLAD (censored 12/2019) and inspiratory CT near CLAD diagnosis. The machine learning tool quantified ground-glass opacity, reticulation, hyperlucent lung, and pulmonary vessel volume (PVV). Two radiologists scored for ground-glass opacity, reticulation, consolidation, pleural effusion, air trapping and bronchiectasis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of machine learning and radiologist for CLAD phenotype. Multivariable Cox proportional-hazards regression analysis for allograft survival controlled for age, sex, native lung disease, cytomegalovirus serostatus, and CLAD phenotype (bronchiolitis obliterans syndrome [BOS] and restrictive allograft syndrome [RAS]/mixed).Results88 patients were included (57 BOS, 20 RAS/mixed, and 11 unclassified/undefined) with CT a median 9.5 days from CLAD onset. Radiologist and machine learning parameters phenotyped RAS/mixed with PVV as the strongest indicator (AUC 0.85). Machine learning hyperlucent lung phenotyped BOS using only inspiratory CT (AUC=0.76). Radiologist and machine learning parameters predicted graft failure in the multivariable analysis, best with PVV (HR=1.23, 95%CI 1.05–1.44, p=0.01).ConclusionsMachine learning discriminated between CLAD phenotypes on CT. Both radiologist and machine learning scoring were associated with graft failure, independent of CLAD phenotype. PVV, unique to machine learning, was the strongest in phenotyping and prognostication.

2021 ◽  
Vol 12 ◽  
pp. 204062232199344
Author(s):  
Filippo Patrucco ◽  
Elias Allara ◽  
Massimo Boffini ◽  
Mauro Rinaldi ◽  
Cristina Costa ◽  
...  

Background: Chronic lung allograft dysfunction (CLAD), a complication affecting the survival of lung transplanted patients, includes two clinical phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Everolimus is used in CLAD because of its antiproliferative mechanism. In lung transplant patients treated with everolimus, the clinical course of renal and lung function has not yet been assessed systematically in CLAD, BOS and RAS patients for more than 6 months. Methods: We retrospectively evaluated the 12-month follow-up of renal and lung function of lung-transplanted patients switched to everolimus and evaluated the reduction in immunosuppressant dosage (ISD) and mortality. Subgroups were based on indication for everolimus treatment: CLAD and non-CLAD patients, BOS and RAS among CLAD patients. Results: We included 26 patients, 17 with CLAD (10 BOS, seven RAS). After 1 year from the everolimus switch, we observed renal function improvement (serum creatinine −17%, estimated glomerular filtration rate +24%) and stable pulmonary function [forced expiratory volume in the first second (FEV1) −0.5%, forced vital capacity (FVC) +0.05%]. RAS patients had progressive functional loss, whereas BOS patients had FEV1 improvement and FVC stability. All-cause mortality was higher in the CLAD versus non-CLAD group (41% versus 11%), without differences between BOS and RAS patients ( p > 0.05). All patients had significant and persistent ISD reduction. Conclusion: Lung transplant patients treated with everolimus had improvements in renal function and reduced ISD. We observed sustained improvements in lung function for CLAD related to BOS subgroup results, whereas RAS confirmed the 1-year worsening functional trend. Data seem to suggest one more piece of the puzzle in CLAD phenotyping.


2021 ◽  
Vol 10 (5) ◽  
pp. 1078
Author(s):  
Jesper Rømhild Davidsen ◽  
Christian B. Laursen ◽  
Mikkel Højlund ◽  
Thomas Kromann Lund ◽  
Klaus Nielsen Jeschke ◽  
...  

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.


2018 ◽  
Vol 29 (1) ◽  
pp. 18-25
Author(s):  
Alicia B. Lichvar ◽  
Christopher R. Ensor ◽  
Adriana Zeevi ◽  
Matthew R. Morrell ◽  
Joseph M. Pilewski ◽  
...  

Background: Hypogammaglobulinemia (HGG), immunoglobulin G (IgG) <700 mg/dL, is associated with infections, chronic lung allograft dysfunction, and death following lung transplantation. This study evaluates the use of on-demand intravenous IgG in lung transplant recipients with HGG. Materials and Methods: This single-center retrospective cohort study of adult lung recipients evaluated 3 groups, no, untreated (u), or treated (t) HGG at first IgG administration or a matched time posttransplant. Primary outcome was freedom from allograft dysfunction. Secondary outcomes included development of advanced dysfunction, rejection, infection burden, and mortality. Results: Recipients included 484 (no HGG: 76, uHGG: 192, tHGG: 216). Freedom from chronic allograph dysfunction was highest in the non-HGG group 2 years post-enrollment (no HGG 77.9% vs uHGG 56.4% vs tHGG 52.5%; P = .002). Freedom from advanced dysfunction was significantly different 2 years post-enrollment (no HGG 90.5% vs uHGG 84.7% vs tHGG 75.4%; P = .017). Patients without HGG and those with uHGG had less mortality at 2 years post-enrollment (no HGG 84.2% vs uHGG 81.3% vs tHGG 64.8%; P < .001). Gram-negative pneumonias occurred more often in the tHGG group ( P = .02). Conclusions: Development of chronic lung allograft dysfunction, patient survival, rejection burden, and key infectious outcomes in lung transplant recipients were still problematic in the context of on-demand IgG therapy. Prospective studies are warranted.


2019 ◽  
Vol 54 (5) ◽  
pp. 1900847 ◽  
Author(s):  
Annelore Sacreas ◽  
Jean-Luc Taupin ◽  
Marie-Paule Emonds ◽  
Liesbeth Daniëls ◽  
Dirk E. Van Raemdonck ◽  
...  

IntroductionCirculating anti-human leukocyte antigen (HLA) serum donor-specific antibodies (sDSAs) increase the risk of chronic lung allograft dysfunction (CLAD) and mortality. Discrepancies between serological and pathological/clinical findings are common. Therefore, we aimed to assess the presence of tissue-bound graft DSAs (gDSAs) in CLAD explant tissue compared with sDSAs.MethodsTissue cores, obtained from explant lungs of unused donors (n=10) and patients with bronchiolitis obliterans syndrome (BOS; n=18) and restrictive allograft syndrome (RAS; n=18), were scanned with micro-computed tomography before elution of antibodies. Total IgG levels were measured via ELISA. Anti-HLA class I and II IgG gDSAs were identified using Luminex single antigen beads and compared with DSAs found in serum samples.ResultsOverall, mean fluorescence intensity was higher in RAS eluates compared with BOS and controls (p<0.0001). In BOS, two patients were sDSA+/gDSA+ and two patients were sDSA−/gDSA+. In RAS, four patients were sDSA+/gDSA+, one patient was sDSA+/gDSA− and five patients were sDSA−/gDSA+. Serum and graft results combined, DSAs were more prevalent in RAS compared with BOS (56% versus 22%; p=0.04). There was spatial variability in gDSA detection in one BOS patient and three RAS patients, who were all sDSA−. Total graft IgG levels were higher in RAS than BOS (p<0.0001) and in gDSA+versus gDSA− (p=0.0008), but not in sDSA+versus sDSA− (p=0.33). In RAS, total IgG levels correlated with fibrosis (r= −0.39; p=0.02).ConclusionsThis study underlines the potential of gDSA assessment as complementary information to sDSA findings. The relevance and applications of gDSAs need further investigation.


2018 ◽  
Vol 39 (02) ◽  
pp. 155-171 ◽  
Author(s):  
Ariss DerHovanessian ◽  
W. Wallace ◽  
Joseph Lynch ◽  
John Belperio ◽  
S. Weigt

AbstractLung transplantation has become an established therapeutic option for a variety of end-stage lung diseases. Technical advances in graft procurement, implantation, perioperative care, immunosuppression, and posttransplant medical management have led to significant improvements in 1-year survival, but outcomes after the first year have improved minimally over the last two decades. The main limitation to better long-term survival after lung transplantation is chronic lung allograft dysfunction (CLAD). CLAD also impairs quality of life and increases the costs of medical care. Our understanding of CLAD manifestations, risk factors, and mechanisms is rapidly evolving. Recognition of different CLAD phenotypes (e.g., bronchiolitis obliterans syndrome and restrictive allograft syndrome) and the unique pathogenic mechanisms will be important for developing novel therapies. In addition to alloimmune-mediated rejection, we now recognize the importance of alloimmune-independent mechanisms of injury to the allograft. CLAD is the consequence of dysregulated repair of allograft injury. Unfortunately, currently available therapies for CLAD are usually not effective. However, the advances in knowledge, reviewed in this manuscript, should lead to novel strategies for CLAD prevention and treatment, as well as improvement in long-term outcomes after lung transplantation. We provide an overview of the evolving terminology related to CLAD, its varying clinical phenotypes and their diagnosis, natural history, pathogenesis, and potential treatments.


2018 ◽  
Vol 32 (10) ◽  
pp. e13397 ◽  
Author(s):  
Atif S. Siddiqui ◽  
Gagan Kumar ◽  
Tilottama Majumdar ◽  
Edward A. Graviss ◽  
Duc T. Nguyen ◽  
...  

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