Bilateral Lung Transplant Recipients Research Articles

Differential effects of donor factors on post-transplant survival in lung transplantation

BackgroundPredicting post-transplant (PT) survival in lung allocation remains an elusive goal. We analyzed the impact of donor factors on PT survival and how these relationships vary among transplant recipients. MethodsWe studied primary bilateral lung transplant recipients (n=7,609) from the US Scientific Registry of Transplant Recipients (19 February 2015 - 1 February 2020). Main and interaction effects were evaluated and adjusted across candidate age, sex, and diagnosis. Models predicting PT survival were compared to the PT composite allocation score model (PT-CAS): 1. Cox regression donor multivariable model (COX), 2. COX + PT-CAS, 3. random forest model (RF), 4. RF + PT-CAS. Model discrimination and calibration measures were compared. ResultsInteractions between donor and recipient factors emerged by – age: lower survival for DCD organs for recipients aged 55-69 years, donor smoking for recipients aged 30-54 and 70+, Hispanic donor for recipients < 30, non-Hispanic Black (NHB) donor for recipients aged 30+; sex: CMV mismatch for males; diagnosis: higher donor recipient weight ratio for diagnosis Group C (e.g.CF), donor diabetes for diagnosis Group D (e.g. IPF). COX and RF models performed similarly to PT-CAS; however, the combined COX PT-CAS model had improved discrimination (1y AUC PT-CAS 0.609 vs. 1y AUC COX + PT-CAS 0.626) and improved calibration across a broader range of predicted risk. ConclusionThe influence of donor factors on recipient post-transplant survival differed by age, sex, and diagnosis. The addition of donor factors to existing models predicting posttransplant survival led to only modest improvement in prediction accuracy. Future efforts may focus on optimizing matching strategies to improve donor utilization.

Hyperpolarized 129Xe MRI and spectroscopy of gas-exchange abnormalities in bilateral lung transplant recipients

BACKGROUNDThere is currently no sensitive, non-invasive method of screening for chronic lung allograft dysfunction (CLAD), the primary barrier to long-term survival after lung transplant. Conventional pulmonary function testing is imprecise absent a sustained decline. Hyperpolarized 129Xe MRI is a sensitive tool for 3D imaging of regional pulmonary ventilation and gas exchange abnormalities and may aid in early detection of CLAD. METHODSAdult patients post bilateral lung transplant were screened for CLAD based on the ISHLT criteria. Those with established allografts (n=10) underwent 129Xe gas exchange MRI and spectroscopy and were compared to results from 16 young healthy volunteers and 16 age-matched healthy volunteers. One lung transplant recipient was excluded from final data analysis due to a concurrent lung infection found incidentally after MRI. Imaging provided quantitative maps of the ventilation defect percent (VDP), membrane high percent, and RBC defect percent. Spectroscopy yielded RBC/membrane ratio, oxygenation-dependent RBC shift, and RBC oscillation amplitude. RESULTSThe analysis included nine lung transplant recipients, seven with CLAD and two without. CLAD patients exhibited VDP values consistent with their FEV1 decline (rho=0.79, p=0.048). Hemoglobin-corrected RBC transfer was reduced in all transplant recipients vs. young healthy controls (median [first quartile–third quartile] of 13% [9%-22%] vs 2% [1.75%-3%], P=0.003) as well as vs. age-matched controls (5.5% [2% - 9.25%], p=0.039). Spectroscopy demonstrated reduced RBC/membrane signal (0.26 [0.17-0.31] vs. 0.62 [0.50-0.66], p< 0.001 and vs. 0.48 [0.42-0.55], p = 0.002), reduced RBC chemical shift (217.4 [217.2-217.7]ppm vs 218.2 [218.0-218.5]ppm, p=0.009 and vs. 218.3 [218.2-218.5]ppm, p=0.003), and increased RBC oscillation amplitude vs. the young healthy controls (14.1% [12.2%-16.4%] vs 11.1% [9.9%-11.9%], p=0.003). CONCLUSIONSPatients with CLAD exhibited significant ventilation defects that correlated with FEV1 decline, that, along with RBC transfer defects and other 129Xe gas exchange and hemodynamic abnormalities, could provide a promising means of early detection of physiological changes in patients with CLAD.

Frequency of Unplanned Readmissions Following Lung Transplantation During the SAR-COV-2 Pandemic When Hospital Resources Were Strained

Despite the concerted efforts by lung transplant recipients (LTR) and their medical teams, hospital readmissions are common in the first year following transplantation. Reasons for unplanned readmissions include allograft rejection, infections, and respiratory failure before the SARS-COV-2 pandemic. Clinical predictors of readmissions have changed over time with the higher risk factors of acceptable criteria for recipients and donors. We aimed to assess more recent readmission rates based on group classifications to better understand specific groups that are at risk for various readmissions during the SARS-COV-2 pandemic when hospital resources were strained. A retrospective analysis for LTR at UCSD was performed from 1/1/2018 to 6/30/2022. We recorded the baseline demographics; LAS at the time of lung transplant; mechanical ventilation prior to lung transplant; the need for VV-or VA-ECMO prior to or after lung transplantation; categories for UNOS listing (groups A, B, C, D); PGD grade 3 based on the ISHLT definition; and acquisition of serious donor-derived infections. We recorded the primary reason for all the readmissions and the duration of admission. Descriptive statistics were used for the analysis of this 4.5-year patient cohort. 149 LT were performed. 29 were single LTR while 120 were bilateral LTR. Median age of 57 years, 63 patients (42%) were female. Indications for transplantation included 28 (19%) group A, 19 (13%) group B, 12 (8%) group C, and 90 (60%) group D. The median length of follow-up following lung transplant was 1.7 years. Collectively, there were 73 patients (49%) that required readmissions. On average, there are 2.5 readmissions per patient for our cohort. Most common reasons for unplanned readmission included infections, transplant-related (transplant rejection, other complications of transplant, etc.), and GI Related. This was primarily seen in the group D cohort. The median hospital LOS at readmission was 3.8 days (4 hours to 34.6 days). Despite infection being the leading cause of readmission, only 11 cases were related to COVID-19 infection. No death occurred with a readmission. Groups B and D appear to be at a higher risk for readmission, irrespective of the pre-LT LAS and need for mech vent or VV-ECMO.

(1052) - A Case of Takotsubo Cardiomyopathy in a Bilateral Lung Transplant Recipient

(1052) - A Case of Takotsubo Cardiomyopathy in a Bilateral Lung Transplant Recipient

Gram-negative bacterial colonizations before bilateral lung transplant. The impact of ‘targeted’ versus ‘standard’ surgical prophylaxis

BackgroundInfections are one of the most common causes of death after lung transplant (LT). However, the benefit of ‘targeted’ prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear.MethodsAll consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016–2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis (‘standard’ vs. ‘targeted’ on the preoperative bacterial isolation).ResultsOne hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to ‘targeted’ prophylaxis, while 24 (52%) to ‘standard’ prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with ‘standard’ prophylaxis and twelve (75%) with ‘targeted’ therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the ‘standard’ and 11 to the ‘targeted’ prophylaxis (p = 0.027).ConclusionsThe administration of a ‘targeted’ prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections.

Resistin Pathway as Novel Mechanism of Post-lung Transplantation Bronchial Stenosis.

Bronchial stenosis remains a significant source of morbidity among lung transplant recipients. Though infection and anastomotic ischemia have been proposed etiologies of the development of bronchial stenosis, the pathophysiologic mechanism has not been well elucidated. In this single-centered prospective study, from January 2013 through September 2015, we prospectively collected bronchoalveolar lavage (BAL) and endobronchial epithelial brushings from the direct anastomotic site of bronchial stenosis of bilateral lung transplant recipients who developed unilateral post-transplant bronchial stenosis. Endobronchial epithelial brushings from the contralateral anastomotic site without bronchial stenosis and BAL from bilateral lung transplant recipients who did not develop post-transplant bronchial stenosis were used as controls. Total RNA was isolated from the endobronchial brushings and real-time polymerase chain reaction reactions were performed. Electrochemiluminescence biomarker assay was used to measure 10 cytokines from the BAL. Out of 60 bilateral lung transplant recipients, 9 were found to have developed bronchial stenosis with 17 samples adequate for analysis. We observed a 1.56 to 70.8 mean-fold increase in human resistin gene expression in the anastomotic bronchial stenosis epithelial cells compared with nonstenotic airways. Furthermore, IL-1β (21.76±10.96pg/mL; control 0.86±0.44pg/mL; P <0.01) and IL-8 levels (990.56±326.60pg/mL; control 20.33±1.17pg/mL; P <0.01) were significantly elevated in the BAL of the lung transplant patients who developed anastomotic bronchial stenosis. Our data suggest that the development of postlung transplantation bronchial stenosis may be in part mediated through the human resistin pathway by IL-1β induced transcription factor nuclear factor-κβ activation and downstream upregulation of IL-8 in alveolar macrophages. Further study is needed in the larger patient cohorts and to determine its potential therapeutic role in the management of post-transplant bronchial stenosis.

Impulse Oscillometry Versus Spirometry to Detect Bronchiolitis Obliterans Syndrome in Bilateral Lung Transplant Recipients: A Prospective Diagnostic Study.

Chronic lung allograft dysfunction (CLAD), and especially bronchiolitis obliterans syndrome (BOS), remain dominant causes of morbidity and mortality after lung transplantation. Interest is growing in the forced oscillation technique, of which impulse oscillometry (IOS) is a form, as a tool to improve our understanding of these disorders. However, data remain limited and no longitudinal studies have been published, meaning there is no information regarding any capacity IOS may have for the early detection of CLAD. We conducted a prospective longitudinal study enrolling a consecutive sample of adult bilateral lung transplant recipients with healthy lung allografts or CLAD and performed ongoing paired IOS and spirometry tests on a clinically determined basis. We assessed for correlations between IOS and spirometry and examined any predictive value either modality may hold for the early detection of BOS. We enrolled 91 patients and conducted testing for 43 mo, collecting 558 analyzable paired IOS and spirometry tests, with a median of 9 tests per subject (interquartile range, 5-12) and a median testing interval of 92 d (interquartile range, 62-161). Statistically significant moderate-to-strong correlations were demonstrated between all IOS parameters and spirometry, except resistance at 20 Hz, which is a proximal airway measure. No predictive value for the early detection of BOS was found for IOS or spirometry. This study presents the first longitudinal data from IOS after lung transplantation and adds considerably to the growing literature, showing unequivocal correlations with spirometry but failing to demonstrate a predictive value for BOS.

Nutritional and Sarcopenia Assessment in Bilateral Lung Transplantation Recipient: Can “The Strongest One” Expect Improved Short-Term Outcomes?

Background: Scant data are available on nutritional status in bilateral lung transplant (BLT) candidates. Methods: All consecutive recipients admitted to the intensive care unit (ICU) of the University Hospital of Padua (February 2016–2020) after bilateral-lung transplant (BLT) were retrospectively screened. Data collected: (i) nutritional indices (body mass index (BMI), albumin level, prognostic nutritional index (PNI), mini nutritional assessment short-form (MNA-SF)); and (ii) muscular indices (creatinine height index (CHI)), skeletal muscle index (SMI), densitometry of paravertebral muscles on chest CT). Results: 108 BLT recipients were enrolled: 55% had a normal BMI, 83% had serum albumin levels &gt; 35 g/L; high PNI and MNA-SF scores were recorded in most of patients. A total of 74% had a “normal or slightly reduced protein state“ according to the CHI score; 17% were identified as “sarcopenic” according to muscle densitometry (Hu &lt; 30). Lower serum albumin was associated with longer invasive mechanical ventilation days (IMV) and ICU length of stay (p-value for non-linearity &lt; 0.01). PNI and BMI were also associated with an increased ICU length of stay (p-value for non-linearity &lt; 0.01). Conclusions: Most of the BLT recipients had normal nutritional and sarcopenia status. Pre-transplant albumin values correlated with the duration of IMV; serum albumin, PNI and BMI were associated with ICU stay. No nutritional or muscle parameters predicted re-intubation, 30-days rejection and overall length of hospital stay.

Prognostic Value of Chest CT Findings at BOS Diagnosis in Lung Transplant Recipients.

Bronchiolitis obliterans syndrome (BOS) after lung transplantation is characterized by fibrotic small airway remodeling, recognizable on high-resolution computed tomography (HRCT). We studied the prognostic value of key HRCT features at BOS diagnosis after lung transplantation. The presence and severity of bronchiectasis, mucous plugging, peribronchial thickening, parenchymal anomalies, and air trapping, summarized in a total severity score, were assessed using a simplified Brody II scoring system on HRCT at BOS diagnosis, in a cohort of 106 bilateral lung transplant recipients transplanted between January 2004 and January 2016. Obtained scores were subsequently evaluated regarding post-BOS graft survival, spirometric parameters, and preceding airway infections. A high total Brody II severity score at BOS diagnosis (P = 0.046) and high subscores for mucous plugging (P = 0.0018), peribronchial thickening (P = 0.0004), or parenchymal involvement (P = 0.0121) are related to worse graft survival. A high total Brody II score was associated with a shorter time to BOS onset (P = 0.0058), lower forced expiratory volume in 1 s (P = 0.0006) forced vital capacity (0.0418), more preceding airway infections (P = 0.004), specifically with Pseudomonas aeruginosa (P = 0.002), and increased airway inflammation (P = 0.032). HRCT findings at BOS diagnosis after lung transplantation provide additional information regarding its underlying pathophysiology and for future prognosis of graft survival.

Impact of lung transplantation on diastolic dysfunction in recipients with pretransplant pulmonary hypertension

ObjectivePulmonary hypertension can cause left ventricular diastolic dysfunction through ventricular interdependence. Moreover, diastolic dysfunction has been linked to adverse outcomes after lung transplant. The impact of lung transplant on diastolic dysfunction in recipients with pretransplant pulmonary hypertension is not defined. In this cohort, we aimed to assess the prevalence of diastolic dysfunction, the change in diastolic dysfunction after lung transplant, and the impact of diastolic dysfunction on lung transplant outcomes. MethodsIn a large, single-center database from January 2011 to September 2021, single or bilateral lung transplant recipients with pulmonary hypertension (mean pulmonary artery pressure > 20 mm Hg) were retrospectively identified. Those without a pre- or post-transplant echocardiogram within 1 year were excluded. Diastolic dysfunction was diagnosed and graded according to the American Society of Echocardiography 2016 guideline on assessment of diastolic dysfunction (present, absent, indeterminate). McNemar's test was used to examine association between diastolic dysfunction pre- and post-transplant. Kaplan–Meier and Cox regression analysis were used to assess associations between pre–lung transplant diastolic dysfunction and post–lung transplant 1-year outcomes, including mortality, major adverse cardiac events, and bronchiolitis obliterans syndrome grade 1 or higher–free survival. ResultsOf 476 primary lung transplant recipients, 205 with pulmonary hypertension formed the study cohort (mean age, 56.6 ± 11.9 years, men 61.5%, mean pulmonary artery pressure 30.5 ± 9.8 mm Hg, left ventricular ejection fraction < 55% 9 [4.3%]). Pretransplant, diastolic dysfunction was present in 93 patients (45.4%) (grade I = 8, II = 84, III = 1), absent in 16 patients (7.8%), and indeterminate in 89 patients (43.4%), and 7 patients (3.4%) had missing data. Post-transplant, diastolic dysfunction was present in 7 patients (3.4%) (grade I = 2, II = 5, III = 0), absent in 164 patients (80.0%), and indeterminate in 15 patients (7.3%), and 19 patients (9.3%) had missing data. For those with diastolic dysfunction grades in both time periods (n = 180), there was a significant decrease in diastolic dysfunction post-transplant (148/169 patients with resolved diastolic dysfunction; McNemar's test P < .001). Pretransplant diastolic dysfunction was not associated with major adverse cardiac events (hazard ratio [HR], 1.08, 95% CI, 0.72-1.62; P = .71), bronchiolitis obliterans syndrome–free survival (HR, 0.67, 95% CI, 0.39-1.56; P = .15), or mortality (HR, 0.70, 95% CI, 0.33-1.46; P = .34) at 1 year. ConclusionsDiastolic dysfunction is highly prevalent in lung transplant candidates with normal left ventricular systolic function and pulmonary hypertension, and resolves in most patients after lung transplant regardless of patient characteristics. Pre–lung transplant diastolic dysfunction was not associated with adverse lung or cardiac outcomes after lung transplant. Collectively, these findings suggest that the presence of diastolic dysfunction in lung transplant recipients with pulmonary hypertension has no prognostic significance, and as such diastolic dysfunction and the associated clinical syndrome of heart failure with preserved ejection fraction should not be considered a relative contraindication to lung transplant in such patients.

Diaphragm dysfunction predicts weaning outcome after bilateral lung transplant.

Diaphragm dysfunction and its effects on outcomes of ventilator weaning have been evaluated in mixed critical care populations using diaphragm thickening fraction (TFdi; the ratio of the difference between ultrasound diaphragm thickness at end-inspiration and end-expiration to diaphragm thickness at end-expiration) or neuro-ventilatory efficiency (NVE; the ratio of tidal volume and peak electrical activity of the diaphragm). Such data are not available in bilateral-lung transplant recipients. We hypothesized that: i) diaphragm dysfunction, as defined by a TFdi<29%, is more likely to occur in difficult weaning; ii) TFdi and NVE predict weaning outcome; iii) and duration of mechanical ventilation before the first spontaneous breathing trial (SBT) is associated with diaphragm dysfunction. Adult bilateral-lung transplant patients admitted to our ICU were screened at the time of the first SBT (pressure-support of 5cmH2O and zero positive end-expiratory pressure). At the fifth minute, TFdi and NVE were measured over three respiratory cycles. Weaning was classified as simple, difficult or prolonged (successful extubation at the first SBT, within three or after three SBTs, respectively). Forty-four subjects were enrolled. Diaphragm dysfunction occurred in 14 subjects (32%); all of whom had difficult weaning (78% of the subgroup of 18 patients experiencing difficult weaning). Both TFdi (24[20-29] vs 39[35-45]%) and NVE (34[26-45] vs 55[43-62]ml/µV) were lower in difficult weaning (both p<0.001). The areas under the receiver operator curve predicting difficult weaning were 0.88 [95%CI 0.73-0.99] for TFdi, and 0.85 [95%CI 0.71-0.95] for NVE. Duration of ventilation demonstrated a linear inverse correlation with both TFdi and NVE. Diaphragm dysfunction is common following bilateral-lung transplantation and associated with difficult weaning. In such patients, average values for TFdi and NVE were reduced compared to patients with simple weaning. Both parameters showed similar accuracy for predicting success of ventilator weaning, demonstrating an inverse relationship with duration of ventilation.

Magnetic Resonance Guided Focused Ultrasound Thalamotomy for Treatment of Severe Essential Tremor in a Lung Transplant Recipient–A Case Report

Calcineurin inhibitor-related tremors occur in up to 50% of solid organ transplant recipients and are disabling in severe cases. We describe a bilateral lung transplant recipient with essential tremors that significantly worsened after tacrolimus initiation. She did not have improvement with the change to extended-release tacrolimus, the use of everolimus as a calcineurin inhibitor-sparing agent, or the addition of primidone, clonazepam, or propranolol. She underwent magnetic resonance-guided focused ultrasound thalamotomy with significant improvement in her tremor and activities of daily living.

Tocilizumab for antibody-mediated rejection treatment in lung transplantation

Tocilizumab (TCZ), an IL-6 inhibitor, has shown promise in the treatment of donor-specific antibodies (DSA) and chronic antibody-mediated rejection (AMR) in renal transplant recipients. However, its use in lung transplantation has not been described. This retrospective case-control study compared AMR treatments containing TCZ in 9 bilateral lung transplant recipients to 18 patients treated for AMR without TCZ. Treatment with TCZ resulted in more clearance of DSA, lower recurrence of DSA, lower incidence of new DSA, and lower rates of graft failure when compared to those treated for AMR without TCZ. The incidence of infusion reactions, elevation in transaminases, and infections were similar between the 2 groups. These data support a role for TCZ in pulmonary AMR and establish preliminary evidence to design a randomized controlled trial of IL-6 inhibition for the management of AMR.

0975 Severe Central Sleep Apnea After Bilateral Lung Transplantation

Abstract Introduction Central sleep apnea (CSA) is characterized by repetitive disruptions in airflow during sleep due to impaired central respiratory drive. Multiple studies have described an increased incidence of sleep disordered breathing after lung transplantation. However, these studies implicate obstructive sleep apnea as the primary sleep disturbance related to post-transplant weight gain, increased neck circumference, and fluid retention from immunosuppressive therapy. We report an uncommon presentation of new onset severe central predominant sleep apnea in a bilateral lung transplant recipient. Report of case(s) A 61-year-old female with a history of end stage COPD with chronic hypoxic respiratory failure status post bilateral lung transplantation in 2020 presented to sleep medicine clinic with several months of witnessed apneic episodes, excessive daytime sleepiness, morning headaches, and insomnia. Physical exam was notable for an increased body mass index (BMI) of 35 kg/m² from pre-transplant BMI of 29 kg/m². Epworth Sleepiness Scale was 15, compared to 4 prior to transplant. Polysomnogram showed an apnea hypopnea index (AHI) of 94.5 events/hour with central AHI of 54.6, consistent with severe central predominant sleep apnea. Titration on CPAP at 5 cmH2O and 7 cmH2O improved the AHI to 13.3 and 20.3, respectively, with residual central hypopneas. On follow-up, downloaded therapy data revealed a residual AHI of 23.3 on CPAP at 5 cmH2O and 1.5 L/min O2, suggesting the need for a BiPAP/ASV titration study if control remains suboptimal. Conclusion Common etiologies of CSA include heart failure with Cheyne-Stokes respirations, neurologic disease, high altitude, and the use of centrally acting medications. This patient did not have clearly identifiable risk factors. Pre- and post-transplant echocardiograms showed preserved left ventricular function with no regional wall motion abnormalities. She lacks history of neurologic disease or narcotic use, and her current immunosuppressive regimen has not been linked to worsened sleep apnea. Proposed pathogenesis of CSA in lung transplant recipients include abnormalities in respiratory mechanics due to pulmonary denervation and altered chemoreceptor sensitivity. Prompt diagnosis and treatment of sleep disordered breathing is crucial in organ transplant recipients to prevent adverse cardiovascular outcomes. Thus, further investigation is warranted to better characterize the changes in respiratory parameters that occur after lung transplantation. Support (if any)

Phase-resolved Functional Lung (PREFUL) MRI-derived Ventilation and Perfusion Parameters Predict Future Lung Transplant Loss.

Background Chronic lung allograft dysfunction (CLAD), the physiologic correlate of chronic rejection, remains a major barrier to long-term survival following lung transplant. Biomarkers for early prediction of future transplant loss or death due to CLAD might open a window of opportunity for early diagnosis and treatment of CLAD. Purpose To evaluate the prognostic use of phase-resolved functional lung (PREFUL) MRI in predicting CLAD-related transplant loss or death. Materials and Methods In this prospective, longitudinal, single-center study, PREFUL MRI-derived ventilation and parenchymal lung perfusion parameters of bilateral lung transplant recipients without clinically suspected CLAD were assessed 6-12 months (baseline) and 2.5 years (follow-up) after transplant. MRI scans were acquired between August 2013 and December 2018. Regional flow volume loop (RFVL)-based ventilated volume (VV) and perfused volume were calculated using thresholds and spatially combined as ventilation-perfusion (V/Q) matching. Spirometry data were obtained on the same day. Exploratory models were calculated using receiver operating characteristic analysis, and subsequent survival analyses (Kaplan-Meier, hazard ratios [HRs]) of CLAD-related graft loss were performed to compare clinical and MRI parameters as clinical end points. Results At baseline MRI examination, 132 clinically stable patients of 141 patients (median age, 53 years [IQR, 43-59 years]; 78 men) were included (nine were excluded for deaths not associated with CLAD), 24 of which had CLAD-related graft loss (death or retransplant) within the observational period of 5.6 years. PREFUL MRI-derived RFVL VV was a predictor of poorer survival (cutoff, 92.3%; log-rank P = .02; HR for graft loss, 2.5 [95% CI: 1.1, 5.7]; P = .02), while perfused volume (P = .12) and spirometry (P = .33) were not predictive of differences in survival. In the evaluation of percentage change at follow-up MRI (92 stable patients vs 11 with CLAD-related graft loss), mean RFVL (cutoff, 97.1%; log-rank P < .001; HR, 7.7 [95% CI: 2.3, 25.3]), V/Q defect (cutoff, 498%; log-rank P = .003; HR, 6.6 [95% CI: 1.7, 25.0]), and forced expiratory volume in the first second of expiration (cutoff, 60.8%; log-rank P < .001; HR, 7.9 [95% CI: 2.3, 27.4]; P = .001) were predictive of poorer survival within 2.7 years (IQR, 2.2-3.5 years) after follow-up MRI. Conclusion Phase-resolved functional lung MRI ventilation-perfusion matching parameters were predictive of future chronic lung allograft dysfunction-related death or transplant loss in a large prospective cohort who had undergone lung transplant. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Fain and Schiebler in this issue.

(929) Long-Term Survival Among Single Lung Transplant Recipients is Shorter Than That of Matched Bilateral Lung Transplant Recipients

(929) Long-Term Survival Among Single Lung Transplant Recipients is Shorter Than That of Matched Bilateral Lung Transplant Recipients

Lung Cancer in Lung Transplant Recipients: Clinical, Radiologic, and Pathologic Characteristics and Treatment Outcome.

This study aimed to investigate clinical and radiologic characteristics of lung cancer in lung transplant recipients and evaluate the treatment course and prognosis. The study included 448 patients who underwent lung transplant between 2005 and 2021. All patients had pretransplant chest computed tomography (CT), 429 patients had posttransplant CT, whereas 19 had no posttransplant CT (median number of posttransplant CT, 6; range, 0-24). Medical records of these patients were reviewed to identify patients who developed lung cancer after lung transplant. Computed tomography and positron emission tomography/CT at the time of lung cancer diagnoses were reviewed to obtain imaging features. Demographics, tumor histology, stages, and survival were compared using Fisher exact test and Wilcoxon rank sum test. Among 448 lung transplant recipients with a median follow-up of 71.3 months after lung transplant, 15 patients (3.3%) developed posttransplant lung cancer (13 unilateral, 2 bilateral; 10 men, 5 women; median age, 63.1 years; median time from transplantation to cancer diagnosis, 3.1 years). Twelve cancers were in native lung, and 3 were in transplanted lung. The incidence of lung cancer was higher in single lung transplant recipients than in bilateral lung transplant recipients (10.3% vs 0.6%, respectively; P < 0.0001). Imaging manifestations varied according to tumor stages. Among 12 patients treated for lung cancer, 2 patients developed posttreatment acute respiratory distress syndrome. The median survival from cancer diagnosis of cancer was 6.2 months. Posttransplant lung cancer was noted in 3% of lung transplant recipients and was more common in unilateral transplant recipients. The prognosis upon diagnosis was poor with rapid clinical deterioration and serious posttreatment complications.

A CASE OF ERDHEIM-CHESTER DISEASE IDENTIFIED SIX MONTHS AFTER LUNG TRANSPLANT

TYPE: Case Report TOPIC: Transplantation INTRODUCTION: Erdheim-Chester disease is a rare type of non-Langerhans histiocytosis that can manifest with bone pain, marked elevation of alkaline phosphatase, and osteosclerotic lesions of long bones. CASE PRESENTATION: A 37-year-old female, bilateral lung transplant recipient (10/2020) with a history of post-COVID-19 acute respiratory distress syndrome, complicated by acute cellular rejection, antibody-mediated rejection, and refractory gastroparesis, was found to have Erdheim-Chester disease in the work-up of infiltrative pattern of liver enzymes at 6-months after transplant. DISCUSSION: The early postoperative course was complicated as described above; during her most recent hospital admission, she had an isolated elevation of alkaline phosphatase (208 U/L) with no obvious gastrointestinal symptoms, excluding gastroesophageal reflux or other hepatobiliary pathology. Over the course of one week, her alkaline phosphatase increased to 928 U/L, and the patient described a new onset, mild and non-specific lower tibial pain. A gamma-glutamyl transferase was elevated, necessitating a skeletal work-up. A bone scan and lower extremity radiographs both showed subtle, patchy, intramedullary sclerosis and cortical thickening in the right lower extremity. Together, her bone pain, elevated alkaline phosphatase, and radiologic features were consistent with Erdheim-Chester disease. Although a bone biopsy was warranted, given her guarded prognosis, this intervention was not pursued. CONCLUSIONS: Erdheim-Chester disease generally requires careful observation for disease progression. Unfortunately, in a lung transplant recipient with worsening allograft function and repeated hospitalization, the prognosis is poor. DISCLOSURE: Nothing to declare. KEYWORD: Erdheim-Chester Disease

RAPIDLY PROGRESSIVE POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER AFTER LUNG TRANSPLANTATION

TYPE: Case Report TOPIC: Transplantation INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) after lung transplantation occurs due to immunosuppressant therapy, which limits antiviral host immunity and permits Epstein-Barr viral (EBV) replication and B cell transformation. CASE PRESENTATION: A 67-year-old female, bilateral lung transplant recipient (07/2019) with a history of idiopathic pulmonary fibrosis developed rapidly progressive PTLD in the early postoperative course. DISCUSSION: At 6-months after transplant, chest radiographs revealed left hilar fullness; subsequent chest CT showed evidence of fluid in the fissure, with no obvious lymphadenopathy. Chest CT performed just two weeks later revealed a left hilar mass measuring 6.1 × 2.7 cm with encasement of the left main pulmonary artery and partial collapse of the left main bronchus. Endobronchial ultrasound-guided biopsies led to the diagnosis of CD20-positive, EBV-positive PTLD. Initial PET scan demonstrated multiple hilar lymph nodes, the largest measuring 2.2 × 2.8 cm. Immunosuppression was reduced, and because the PTLD involved only one area in an EBV-mismatched bilateral lung transplant recipient, she qualified for single-agent rituximab once/week. Unfortunately, repeat imaging after five doses of rituximab demonstrated significant disease progression. She required repeat bronchoscopy with tumor debulking for a necrotic, endobronchial tumor occluding up to one-half of the left lower lobe bronchus. She started R-mini-CHOP, and after three cycles of chemotherapy, complete response was observed on the most recent PET/CT scan. CONCLUSIONS: PTLD may progress quickly, as the initial chest CT scan showing fluid collection advanced rapidly into a hilar mass. Reduction in immunosuppression, anti-CD20 biologic therapy, and chemotherapy for refractory PTLD remains an appropriate treatment paradigm. DISCLOSURE: Nothing to declare. KEYWORD: Post-lung transplant lymphoproliferative disorder

Quantitative Image Analysis at Chronic Lung Allograft Dysfunction Onset Predicts Mortality.

Background.Chronic lung allograft dysfunction (CLAD) phenotype determines prognosis and may have therapeutic implications. Despite the clarity achieved by recent consensus statement definitions, their reliance on radiologic interpretation introduces subjectivity. The Center for Computer Vision and Imaging Biomarkers at the University of California, Los Angeles (UCLA) has established protocols for chest high-resolution computed tomography (HRCT)-based computer-aided quantification of both interstitial disease and air-trapping. We applied quantitative image analysis (QIA) at CLAD onset to demonstrate radiographic phenotypes with clinical implications.Methods.We studied 47 first bilateral lung transplant recipients at UCLA with chest HRCT performed within 90 d of CLAD onset and 47 no-CLAD control HRCTs. QIA determined the proportion of lung volume affected by interstitial disease and air-trapping in total lung capacity and residual volume images, respectively. We compared QIA scores between no-CLAD and CLAD, and between phenotypes. We also assigned radiographic phenotypes based solely on QIA, and compared their survival outcomes.Results.CLAD onset HRCTs had more lung affected by the interstitial disease (P = 0.003) than no-CLAD controls. Bronchiolitis obliterans syndrome (BOS) cases had lower scores for interstitial disease as compared with probable restrictive allograft syndrome (RAS) (P < 0.0001) and mixed CLAD (P = 0.02) phenotypes. BOS cases had more air-trapping than probable RAS (P < 0.0001). Among phenotypes assigned by QIA, the relative risk of death was greatest for mixed (relative risk [RR] 11.81), followed by RAS (RR 6.27) and BOS (RR 3.15).Conclusions.Chest HRCT QIA at CLAD onset appears promising as a method for precise determination of CLAD phenotypes with survival implications.