Single Lung Transplantation Research Articles

Comparing Bronchoalveolar Lavage Microbiological Culture Positivity Between Right versus Left Single Lung Transplants

<h3>Purpose</h3> Lung transplant recipients are at elevated risk of aspiration and subsequent microbial colonization and infection of the lungs, which portend worse clinical outcomes. Although aspiration is thought to affect the right lung more commonly than the left lung due to anatomical factors, such association has not been shown in lung transplant recipients. We hypothesized that bronchoalveolar lavage (BAL) from right single lung transplants (SLT) have higher microbiological culture positivity compared to BAL from left SLT, leading to worse outcomes in right SLT recipients. <h3>Methods</h3> All first adult SLT performed at our institution up to June 2021 with at least one BAL microbiological culture result were included. All BAL from surveillance and clinically indicated bronchoscopies were included. By our protocol, BAL is obtained from the transplanted lung, either the right middle lobe or lingula, unless clinically indicated otherwise. Fisher's exact test and univariable Cox proportional hazards model were used to compare culture positivity and outcomes, respectively. <h3>Results</h3> 165 right SLT recipients with 1505 cultures and 164 left SLT recipients with 1450 cultures were included. Baseline patient characteristics were comparable. BAL from right SLT had 17% positivity for significant respiratory pathogens, compared to 12% from left SLT (p<0.0001). Right SLT had higher positivity for <i>P. aeruginosa</i> (7% right vs. 4% left, p<0.001) and <i>S. aureus</i> (2% right vs. 1% left, p=0.04). There was similar positivity for high commensal flora (34% right vs. 36% left, p=0.26). There was a trend towards lower risk of chronic lung allograft dysfunction (HR 0.77 [0.55-1.09], p=0.1) and death/retransplant (HR 0.76 [0.58-1.01], p=0.06) in right SLT recipients. <h3>Conclusion</h3> BAL from right SLT have higher BAL microbiological culture positivity for significant respiratory pathogens, <i>P. aeruginosa</i>, and <i>S. aureus</i> compared to BAL from left SLT, with no difference in outcomes between right and left SLT recipients.

The Mystery of Inappropriate Hypoxia After Single Lung Transplant

<h3>Introduction</h3> Single lung transplantation (SLT) is a treatment option for end stage lung disease in select patients, increasing utilization of a scarce resource. Increase in relative perfusion to the allograft from hypoxic vasoconstriction typically ameliorates hypoxia despite native lung disease. We present a SLT recipient with idiopathic pulmonary fibrosis (IPF) who developed hypoxia due to inappropriate shunting to the native lung after an IPF exacerbation. <h3>Case Report</h3> A 66 year old female with IPF had a left SLT eight months prior to presentation. Four months post transplant, she developed submassive bilateral extensive pulmonary embolism (PE) requiring suction thrombectomy, catheter-directed thrombolysis and anticoagulation without subsequent oxygen requirement. Three months later, she presented with two weeks of productive cough and hypoxia requiring high flow nasal cannula. CT chest showed worsening native lung fibrosis with ground glass opacities without PE or allograft infiltrate. Bronchoalveolar lavage was negative for infection, recent transbronchial biopsies were negative for rejection, and no donor specific antibodies were identified. Despite empiric antibiotics and pulse dose steroids for native lung exacerbation, she developed worsening hypoxia with progressive native lung infiltrates. A perfusion scan revealed 68% and 32% perfusion to the left and right lung, respectively. A right heart catheterization was performed, showing no intracardiac or pulmonary shunt, a mildly increased gradient across the left pulmonary artery (PA) anastomosis, and a marked improvement in left PA PaO2 during right PA balloon occlusion. On hospital day 16, repeat perfusion scan demonstrated an increase in relative perfusion to the allograft (83%). The patient was discharged on 3L oxygen and remains stable as an outpatient. <h3>Summary</h3> Severe hypoxia in the setting of a functioning SLT during a native lung exacerbation is rare. Literature on normal perfusion after SLT remains limited, with small studies suggesting ∼75% of fractional perfusion to the allograft without native lung exacerbation. Similar cases of inappropriate shunting after SLT had improvement in oxygenation after contralateral PA banding with other options including intravascular interventions or contralateral SLT. Further studies characterizing optimal perfusion after SLT and interventions for inappropriate shunting are needed.

Clinical features and outcomes of unplanned single lung transplants

ObjectiveThe decision to perform single lung transplants or double lung transplants is usually made before the operation. We have previously reported that a proportion of single lung transplants were unexpectedly performed in the setting of an aborted double lung transplant, and these patients may be at a higher risk of worse short-term outcomes. Long-term outcomes in unplanned single lung transplants remain unknown. MethodsWe analyzed a single-center database of lung transplants from 2000 to 2020. Single lung transplants were classified into planned and unplanned groups after reviewing operative notes. Root cause analysis was performed for unplanned single lung transplants. ResultsOf the 1326 lung transplants, 1265 (95%) were double lung transplants and 61 (5%) were single lung transplants (22 planned [36%], 39 unplanned [64%]). Underlying indications for transplant were significantly different; planned single lung transplant: chronic obstructive pulmonary disease (55%) and idiopathic pulmonary fibrosis (45%); unplanned single lung transplants: chronic obstructive pulmonary disease (23%), idiopathic pulmonary fibrosis (39%), and bronchiolitis obliterans syndrome (13%). The primary reasons for unplanned single lung transplant were donor-related (3, 7.7%), recipient-related (31, 80%), and donor and recipient-related factors (5, 13%). Unplanned single lung transplants were more likely to require cardiopulmonary bypass during the operation (planned: 4/22, 18% vs unplanned: 20/39, 51%) but had shorter ischemic times (planned: 251 ± 58 minutes vs unplanned: 221 ± 48 minutes). The 5-year overall survival was 53% in the planned and 58% in the unplanned groups, respectively (P = .323). No difference in chronic lung allograft dysfunction–free survival (P = .995) was observed. ConclusionsUnplanned single lung transplants in the setting of aborted double lung transplant may be associated with acceptable long-term outcomes.

Comparative Influence of Primary Healthcare Payer Types on Patient Outcomes After Lung Transplantation

<h3>Purpose</h3> Optimal outcomes in patients undergoing lung transplantation requires significant utilization of resources. We, therefore, evaluated the association of primary payer type with outcomes after lung transplantation. <h3>Methods</h3> Using the UNOS (United Network for Organ Sharing) registry we studied 15129 first-time lung transplant recipients from January 2000 to December 2017 and compared all-cause mortality at 1 year. Single lung (N=4524) and double lung (N=10605) recipients were subgrouped by payer type: Medicaid (32% and 27% respectively), Medicare (26% and 18%), and commercial insurance (42% and 54%). <h3>Results</h3> Primary payer type was not significantly associated with inferior outcomes at 1 year following both single-lung (P=0.447) and double lung transplant (P=0.531). Insurance was also not a predictor of worse outcomes following single lung transplant after 3 years (P=0.107). However, insurance type was associated with different outcomes in double lung recipients at 3 years (P=0.028) and remained significant predictors of early mortality after adjustment for covariates in multivariate Cox proportional hazard ratio analyses (P<0.05). <h3>Conclusion</h3> These data are among the first to provide insight into the impact of insurance status on patient outcomes for a modern cohort of lung transplant recipients. All-cause mortality after single-lung and double-lung transplantation did not differ significantly by payer type after 1 year. However, primary payer type was associated with 3-year outcomes following double lung transplant. More research is needed to confirm and define the reasons for insurance type playing a role in outcomes after double lung transplant as compared to single lung transplant.

Safety of Single Lung Transplantation Post Donation Service Area-Specific Organ Distribution

<h3>Purpose</h3> The organ allocation change in 2017 removed donation service area (DSA) and was aimed at prioritizing donor lungs for patients with a higher lung allocation score (LAS). Given that patients who are listed for singe lung transplantation alone have, on average, a lower LAS, we hypothesized that this allocation change would negatively impact those listed for a single lung transplant. <h3>Methods</h3> A UNOS database analysis was performed for patients listed for an isolated single lung transplant. Data was queried 2.5 years prior to and after the allocation change with recipients from 1/2015-6/2017 deemed as pre-allocation and recipients from 1/2018-6/2020 as post-allocation. The primary outcome was waitlist time and post-transplant survival. <h3>Results</h3> 1,435 patients were identified: 753 pre-allocation patients and 682 post-allocation patients. In the post-allocation era, patients were less likely to be listed for single lung transplant alone (15% vs 12%, P<0.001). Post-allocation recipients were older (P<0.001), more likely to be hospitalized (P=0.033), and had a nominally higher LAS score at transplant (P=0.002). While donor distance was greater (P<0.001) in the post-allocation era, demographics were similar and PaO2/FiO2 was higher in post-allocation era donors (P<0.001). The change in allocation did not impact waitlist times (42 (16-114) vs 45 (13-122), P=0.898). Survival (87% vs 87%, P=0.889) and freedom from graft failure (P=0.964) at 1 year was similar in both groups. Patients in the post-allocation group were less likely to have severe primary graft dysfunction at 72h (24% vs 31%, P=0.043). <h3>Conclusion</h3> After removal of the DSA, there was a lower prevalence of listing for only single lung transplantation. However, waitlist times, available donor lungs, and post-transplant outcomes were similar, or potentially improved, after the allocation change. Given this, single lung transplantation appears to be a reasonable strategy for appropriate patients requiring lung transplantation.

Comparative Performance Analysis of Donor-Derived Cell-Free DNA to Detect Acute Rejection in Single and Double Lung Transplant Recipients

<h3>Purpose</h3> Plasma donor-derived cell-free DNA (ddcfDNA) is a sensitive biomarker for acute rejection (AR). However, its performance remains unknown for single (SL) vs double lung (DL) transplant recipients, where differences in lung mass may affect interpretation. In this study, we aim to distinguish the performance characteristics of ddcfDNA to detect AR in SL vs DL transplant patients. <h3>Methods</h3> Lung transplant recipients (n=105) enrolled in two prospective cohort studies were adjudicated for acute cellular rejection (ACR) and antibody mediated rejection (AMR). <b>Measurement:</b> 337 serially-collected plasma samples were assayed for ddcfDNA by shotgun sequencing. <b>Analysis:</b> Area-under-the-receiver-operating-characteristic-curves (AUROC) of ddcfDNA and performance characteristics for the detection of AR were calculated separately for both DL and SL transplant recipients; cfDNA values were not doubled for SL transplant as in prior studies. <h3>Results</h3> The AUROC for ddcfDNA to detect AR was 0.86 and 0.89 in DL and SL transplants, respectively. The optimal ddcfDNA threshold of 0.54% for SL transplant showed a 92% sensitivity and 80% specificity for detecting AR. For DL transplant, the optimal threshold of 1.1% showed 78% sensitivity and 83% specificity for detecting AR. When ddcfDNA was doubled for single lung transplant, the 1.1% threshold showed 92% sensitivity and 80% specificity for detecting rejection. The AUROC for detection of AMR was 0.91 for both DL and SL transplants. However, the AUROC for detection of ACR was 0.73 for DL and 0.87 for SL transplants. <h3>Conclusion</h3> Plasma ddcfDNA showed similar accuracy to detect AR in both SL and DL transplant recipients, however, the accuracy of ddcfDNA for the detection of ACR appears higher in SL vs DL transplant recipients. Correcting ddcfDNA levels in SL transplant patients by doubling their value appears to be a reasonable method of preserving the performance characteristics of the test for the detection of acute rejection.

The outcome of lung transplantation for end-stage pulmonary diseases with pulmonary hypertension: a single-center experience

BackgroundLung transplantation is a treatment for end-stage lung disease. The optimal transplant strategy for patients with end-stage lung disease complicated by pulmonary hypertension (PH) is controversial. The aim of this study is to review this experience and analyze the outcomes of lung transplantation for PH.MethodsThis retrospective study collected data on patients with PH undergoing lung transplantation between March 2016 and December 2019 at a single center in China. The perioperative features and short- and medium-term outcomes between single-lung transplantation (SLT) and double-lung transplantation (DLT) were compared. Kaplan-Meier methods were used to analyze overall survival across a variety of transplantation procedures, age, mean pulmonary artery pressure (mPAP), body mass index (BMI), and indications of transplantation.ResultsA total of 63 patients with PH were finally included in the analysis. The mean age, mean BMI, and mPAP were 56.37 years, 19.56 kg/m2, and 35.4 mmHg respectively. The overall 1-, 2-, and 3-year survival was 70%, 63%, and 60%, respectively. Five (7.94%) patients died within 30 days after surgery and nine patients (14.3%) died from infection during the followed-up period. There were no significant differences in the short- and medium-term survival outcomes of SLT and DLT, but postoperative pulmonary function was better in DLT. Patients older than 60 years of age had worse survival (P=0.01).ConclusionsThe short- and medium-term survival outcomes between SLT and DLT are similar in selected patients with PH. DLT provides better pulmonary function. Patients older than 60 years are associated with worse survival.

Impact of Surgical Approach for Lung Transplantation on Clinical Outcomes Regarding Patient Recovery

<h3>Purpose</h3> There is a paucity of evidence on surgical approach within lung transplantation and clinically relevant outcomes. <h3>Methods</h3> Retrospective cohort single-centre study of patients who underwent single and double lung transplantation between September 2017 and August 2021. Outcome variables were: length of stay in our Intensive Care Unit (ICU), duration of mechanical ventilation, postoperative haemorrhage within the first 24 hours, and pain scores. Comparisons of outcomes were dependent on the type of surgical access performed (Thoracotomy (T), Sternotomy (S) and Clamshell (C)). <h3>Results</h3> 140 patients met inclusion criteria and were included in our analysis. Sternotomy was the most frequent route of access (n=64) followed by Thoracotomy (n=54) and Clamshell incision (n=22). T group was associated with lower volumes of postoperative haemorrhage compared with S (P<0.001) and C (P=0.038) (Table 1). Additionally, T resulted in shorter durations of mechanical ventilation (vs S, P=0.0061; vs C, P<0.001) and lower length of ICU stay (vs S, P=0.021; vs C, P=0.54). However, mean pain scores were significantly higher for T compared with S (P=0.0072) and C (P=0.002). Outcome variables between S and C groups were statistically insignificant. Median blood loss in the first 24 hours from patients undergoing bilateral lung transplantation was 518mL [interquartile range (IQR) 300; 1027], single transplant patients had 375mL [175; 450]. Despite C having the lowest average pain score, the percentage requirement for epidural analgesia was highest in this group, followed by T and S. <h3>Conclusion</h3> These data support the use of Thoracotomy for single and bilateral lung transplantation where decreased risk of haemorrhagic complications, shorter recovery times and reduced hospital stay are favourable outcomes to consider. However, this may result in increasingly complex pain management postoperatively and potential for complications associated with prolonged opioid administration and epidural analgesia.

Lung Transplant from a DCD Donor with a Previous Symptomatic COVID Infection

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide pandemic affecting more than 172 million confirmed cases. The likelihood of historic donor infection is increasing. Here we report a lung transplantation of a previously SARS-CoV-2 positive organ donor.Case ReportA 49-year-old female who underwent left single lung transplantation for interstitial lung disease. The lung was obtained from a donation after cardiac death (DCD) using abdominal rerperfusion of a 23 years old female donor died of intracranial bleeding with history of covid infection 8 month prior to lung donation. According to the donor records, the symptoms were mild, and required no hospital admission. She had ongoing loss of taste and smell till time of donation. There were no respiratory symptoms. At time of retrieval, chest x ray was normal and blood gases were normal, however, bronchoscopy revealed severe inflammation of the right-side mucosa so the decision was to proceed with the left lung only as it had normal blood gases, good recruitment and no consolidation as well as non inflamed bronchial mucosa. patient had single off pump left lung transplant through left anterior thoracotomy approach. After the surgery, patient was extubated on day 1 in ICU, discharged from ICU on day 3 and discharged from the hospital after 27 days. There was no evidence for primary graft dysfunction or acute rejection. After 6 month of the surgery, FVC is 2.26 L (78.2% predicted) and FEV1 is 1.9L (70.2% predicted).SummaryThis case showed that it is possible to proceed with lung transplant from a donors who had previous mild covid infection. As DCD donation might limit preoperative invasive investigations such as bronchoscopies careful examination and proper radiological and functional assessment for the donor lung after donation including EVLP needs to be considered.

Feasibility of Single Lung Transplant for Post-COVID Fibrosis: A Case Report

IntroductionPreviously we reported bilateral lung transplantation is the last treatment option for irrecoverable COVID ARDS and post-COVID fibrosis. Now we report our first single lung transplant (SLTx) for post-COVID fibrosis.Case ReportA 59-year-old, never-smoker, female, with history of obstructive sleep apnea, hypertension and hyperlipidemia, presented to an outside hospital with COVID-19, shortness of breath, and bilateral pulmonary infiltrates on chest X-ray (CXR) (Figure 1a). She was admitted to the intensive care unit, never requiring intubation, for an overall 40-day hospitalization. At discharge, she had shortness of breath with minimal activity and required continuous oxygen (O2) therapy.One year later she presented to our institution for an outpatient lung transplant evaluation for her post-COVID fibrosis. Her cardiac work up was unremarkable, with the absence of pulmonary hypertension on echocardiogram and right heart catheterization. Computed Tomography of her chest showed only significant fibrosis in the upper lobes with traction bronchiectasis and volume loss (Figure 1c). Her lung ventilation perfusion scan showed grossly normal perfusion to both lungs. Thus, she was listed for left, right, and bilateral lungs with a Lung Allocation Score of 42.After 39 days of listing, she underwent left SLTx. Final pathology of her explanted lung (Figure 1d) showed both uninvolved lung parenchyma and interstitial fibrosis and capillary congestion (Figure 1e). Post-operatively, her course was unremarkable and she was discharged home on POD 19. She was seen in clinic on POD 22 and doing well with no need for supplemental O2 and improving CXR (Figure 1b).SummarySLTx can be used to treat debilitating post-COVID lung fibrosis when there is the absence of severe lung damage and pulmonary hypertension. Considering SLTx in these patients is necessary to expand the donor pool of lungs for a population of patients that will continue to grow with the continued COVID-19 pandemic.

Tales of the Unexpected: Donor Lung with CTEPH, a Unique Case Report

<h3>Introduction</h3> Whilst chronic thromboembolic pulmonary hypertension (CTEPH) is a recognised indication for lung transplantation, it is an undesirable finding in a lung donor. We present the case of an individual who underwent a single lung transplant with an allograft that was subsequently identified as having CTEPH. <h3>Case Report</h3> This 65 year old, 167cm, blood group A RhD+ female with fibrotic organising pneumonia was listed for a left single lung transplant on the basis of a hypokinetic right hemi-diaphragm. She received an organ from a 55year old, 159cm, blood group A RhD+, non-smoking female DBD donor, who died from a subarachnoid haemorrhage. The donor had possible asthma (not formally diagnosed) and an unenhanced CT chest demonstrated non-specific mosaic attenuation. A donor echocardiogram showed mild tricuspid regurgitation with normal right ventricular (RV) size but impaired radial systolic function. Donor blood gases on FiO₂ 1.0 demonstrated PaO₂ 35kPA in the left upper lobe and 64kPa in the left lower lobe pulmonary veins. The recipient surgery was uneventful, although she developed primary graft dysfunction with RV impairment. She was stabilised and extubated after 24 hours onto 2L/min supplemental oxygen. Day 10 post-transplant she developed increasing oxygen requirements. CT pulmonary angiography demonstrated patent vascular anastomoses, left lower lobe pulmonary artery occlusion and features of CTEPH, but no lung necrosis. A right heart catheter study confirmed mild pulmonary hypertension with a mean pulmonary artery pressure 25mmHg and pulmonary vascular resistance 6 Wood Units. She underwent pulmonary endarterectomy (PEA) with good clearance of the donor vasculature. She weaned easily from cardiopulmonary bypass and her supplemental oxygen was down-titrated. She was discharged home 6 weeks post-transplant to complete 12 weeks of anticoagulation. 5 months post-transplant she developed fever and hypoxia with imaging features of left lower lobe consolidation, but no new thrombus. In the context of poor physiological reserve, the patient and family requested palliation. <h3>Summary</h3> CTEPH is rare in the general population, with a prevalence 3-30 per million. In this case, the diagnosis of CTEPH only came to light after transplantation and this is the first report of PEA performed in a lung recipient. Transplant teams should be alert for CTEPH in potential lung donors.

Feeling the Burn: Esophageal PH and CLAD

<h3>Purpose</h3> After lung transplantation, there is an association between chronic allograft dysfunction and pre-transplant esophageal dysfunction. While many centers perform esophageal pH monitoring as part of the pre-transplantation workup, it is unclear whether this evaluation needs to be performed prior to transplant for all patients. We aim to evaluate the relationship between pre-transplant esophageal pH studies and the incidence of chronic lung allograft dysfunction (CLAD). <h3>Methods</h3> A retrospective cohort study was conducted in a single lung transplant center. Patients who underwent single or bilateral lung transplantation between January 2016 and September 2020 were included. Patient demographics, pre-transplant esophageal pH studies, and post-transplant spirometry data were collected. CLAD was defined using the 2019 ISHLT Consensus report. Esophageal pH studies were analyzed using the DeMeester score, and a value > 14.72 was considered abnormal. <h3>Results</h3> A total of 84 patients were evaluated; 67 were included for analysis. The median age at transplant was 66 years (58 - 70 years, IQR). 49.3% of patients were female (n=33), and median BMI was 25.02. The median follow-up was 856 days. A total of 21 patients (31.3%) developed CLAD. The median DeMeester Score was 11.7, and 30 patients were found to have an abnormal DeMeester score. Pre-transplant DeMeester scores did not vary significantly between patients with and without CLAD (22.7 vs. 11.0 respectively, p=0.42). The average time until CLAD development was not statistically different between those with normal and abnormal DeMeester scores (665.0 days vs. 484.4 days respectively, p=0.18). After adjusting for age, BMI and gender, those with abnormal DeMeester scores did not have a higher odds of developing CLAD (OR 1.42, p=0.53). <h3>Conclusion</h3> There was no significant association between abnormal DeMeester studies and the development of CLAD, or the timing of CLAD onset. Further studies should evaluate the impact of a protocol of only evaluating clinically significant GERD as part of the pre-transplant evaluation.

Donor Derived Coccidioides in a Lung Transplant Recipient

<h3>Introduction</h3> There are no universal guidelines on screening donors for coccidioides. We describe a fatal case of coccidioides empyema from a donor previously residing in an endemic region. <h3>Case Report</h3> This is a 72 year old male, status post right single lung transplantation 3 weeks prior for chronic hypersensitivity pneumonitis, who presents to clinic with a productive cough. The donor was a 31 year old male with no medical history from the southern inland region of California. A chest X-ray in clinic demonstrated a right pleural effusion. He underwent thoracentesis and bronchoscopy on post-operative day (POD) 22. Pleural fluid was lymphocytic and exudative with negative cultures, and transbronchial biopsies showed mild acute cellular rejection. He was treated with pulse dose steroids. His symptoms worsened one week later when he was seen in the emergency department. Chest CT showed a large right loculated pleural effusion. The patient was started on broad spectrum antibiotics, and a thoracostomy tube was placed, demonstrating a neutrophil predominant exudate. Repeat chest CT showed the effusion extending through the chest wall, and an additional thoracostomy tube was placed. The patient became more hypoxemic requiring mechanical ventilation and VV-ECMO. Pleural cultures taken two-days prior demonstrated mold and the patient underwent irrigation with amphotericin in the operating room, along with intravenous amphotericin. Ultimately, the patient had multi-organ failure and cardiac arrest. Following his passing, pleural fluid cultures confirmed growth of Coccidioides immitis. <h3>Summary</h3> This case describes a patient with initial negative serologies to coccidioides and a donor from the southern inland region of California, where the incidence of coccidioides is increasing. Transmission of donor-derived coccidioides has been shown to be 43% within 30 days post-transplant, with a 29% mortality. Given the high mortality and treatment availability, screening donors in endemic areas with serologies may prevent post-transplant complications.

Bilateral Lung Transplantation in Severe Chest Asymmetry: Case Series from a Single Center

<h3>Purpose</h3> Suppurative lung disease, such as bronchiectasis and cystic fibrosis, are typical indications for bilateral lung transplantation. Some cases may present a severe chest asymmetry as a sign of recurrent infections. To treat this condition, pneumonectomy and a single lung transplantation is a feasible option, even if this type of surgery is associated with a high complication risk. A second option is bilateral lung transplant with surgical reduction of the graft implanted in the smaller pleural cavity. <h3>Methods</h3> From 2017 to 2021 five patients with significant pleural cavities asymmetry where referred to our centre and underwent bilateral lung transplantation. One patient was affected by bronchiectasis and four by cystic fibrosis. Table 1 shows patients data. <h3>Results</h3> Surgery was performed by means of a clamshell incision through the fourth intercostal space. Three patients where bridged to transplant on VV-ECMO. Graft reduction was not necessary due to median realignment of the mediastinum. All patients were extubated within the second postoperative day. Mean ICU stay was 4 days. Postoperative radiological evaluation did not show clustering or atelectasis of graft implanted in the smaller hemithorax (picture). No major complications were recorded and the average length of hospital stay was 23.8 days. Patients are currently alive at 4,8,12,17 and 40 months after transplantation with excellent functional recovery (mean best FEV1 88.4%). <h3>Conclusion</h3> Bilateral lung transplantation in patients with severe chest asymmetry is a possible procedure, with good functional results even without sacrificing part of graft parenchyma.

Single Lung Transplantation for Pulmonary Fibrosis Secondary to COVID-19

IntroductionAs of April 2021, 78 lung transplants (LTx) were performed for a diagnosis of COVID-19: 50 for COVID-19 ARDS and 28 for pulmonary fibrosis. Bilateral LTx has been recommended as many patients develop significant pulmonary hypertension. Additionally, native lung explants may include cavitary areas of pneumonia, which could serve as a nidus for infection. Single LTx (SLTx) can be considered in patients who have chronic pulmonary fibrosis secondary to COVID-19 with a short window to receive a transplant, or who would otherwise be considered for a single lung. There have been no published cases of a single lung transplant for COVID-19 pulmonary fibrosis. We present a case of a patient with pulmonary fibrosis from COVID-19 who underwent SLTx.Case ReportA 70yo male with O+ blood type was hospitalized 8/2020 to 10/2020 with COVID-19 pneumonia, treated with Remdesivir and Tocilizumab. He had hypoxia but never required intubation. His course was complicated by bilateral pneumothoraces requiring chest tubes. He developed pulmonary fibrosis requiring 6 L of oxygen at rest. CT scan of his chest showed multifocal, peripheral prominent ground glass opacities and interlobal septal thickening with traction bronchiectasis. Ventilation-perfusion scan demonstrated 22% perfusion to the left lung and 78% to the right lung. Right heart catheterization showed pulmonary artery pressures of 36/12 mmHg. His pulmonary function test was suggestive of restrictive disease (FEV 0.81 L [30%], FVC 0.96 L [27%], and FEV1/FVC 85%) that had worsened over time. He was presented at multidisciplinary review board with recommendation to list for left SLTx, which was activated August 2021. The patient was admitted in September 2021 and underwent left single lung transplant via left anterolateral thoracotomy, off cardiopulmonary bypass. Total ischemia time was 3:54. Explant pathology showed end stage pulmonary fibrosis. The patient was extubated on postoperative day 1 with an uneventful postoperative course. He was discharged to skilled nursing facility on postoperative day 26 for rehabilitation.SummarySLTxp is safe and feasible for COVID-19 related pulmonary fibrosis in well-selected patients who have a short window to receive a transplant.

Does Pre-Lung Transplant Grip Strength Correlate with Post-Transplant Lung Function in the First Year?

<h3>Purpose</h3> To determine the correlation between pre-lung transplant grip strength and post-transplant lung function measured by FEV1. <h3>Methods</h3> The study was designed as a retrospective cohort analysis of lung transplant recipients at our institution from 2016 to 2020. Grip strength was collected for patients at the time of evaluation, prior to lung transplantation, using the patient's best measurement on hand dynamometer. Post-transplant reference FEV1 (measured as the mean of the patient's two best measurements within the first year post-transplant) was evaluated for its correlation with the grip strength using Spearman Correlation. Analyses were done using SAS, Version 9.4. P < .05 was considered statistically significant. <h3>Results</h3> Overall, 33 patients were included in the study. Median age was 57 years (IQR 47.1, 62.1), 18 (55%) were males, 15 (45%) were females. The median lung allocation score for the study group was 35.63 (IQR 33.1, 40.9). Underlying conditions included chronic obstructive pulmonary disorder (n=13), interstitial lung disease (n=11), cystic fibrosis (n=8), pulmonary hypertension (n=1). There were 30 bilateral and 3 single-lung transplants. Grip strength was found to have a significant positive correlation with post-transplant reference FEV1 at 1 year (R=0.57, P = .0017). <h3>Conclusion</h3> Stronger grip strength prior to transplant correlated with greater FEV1 performance in the first year, post-transplant. Pre-transplant grip strength may predict lung function after transplant.

Is Pre-Lung Transplant Evaluation of Physical Performance and Frailty Correlated with Post-Transplantation Lung Function?

<h3>Purpose</h3> To evaluate if pre-lung transplant measures of physical performance and frailty correlate with post-transplant lung function. <h3>Methods</h3> The study was designed as a retrospective cohort analysis of lung transplant recipients at our institution from 2016 to 2020. Patients underwent pre-transplant evaluation which included 6-minute walk distance (6MWD) and timed up and go (TUG). TUG was measured as the amount of time required for a patient to stand from a chair, walk 3 meters, then return and sit down. Pulmonary function was performed at protocol specified times within the first year after transplant and if clinically warranted. Reference FEV1 was calculated as the mean of the patient's two best measurements within the first year, post-transplant. Pre-transplant data was evaluated for correlation with post-transplant FEV1 using Spearman Correlation. Analyses were done using SAS, Version 9.4. P < .05 was considered statistically significant. <h3>Results</h3> Overall, 33 patients were included in the study. Median age was 57 years (IQR 47.1, 62.1), 18 (55%) were males, 15 (45%) were females. The median lung allocation score for the study group was 35.63 (IQR 33.1, 40.9). Underlying conditions included chronic obstructive pulmonary disorder (n=13), interstitial lung disease (n=11), cystic fibrosis (n=8), pulmonary hypertension (n=1). There were 30 bilateral and 3 single-lung transplants. Longer pre-transplant 6MWD was found to have a correlation with post-transplant FEV1 (R=0.47, P = .0082). Faster pre-transplant TUG was found to have a correlation with post-transplant FEV1 (R=0.44, P = .030). <h3>Conclusion</h3> Patients who walk limited distances in 6 minutes or take longer to get up and go prior to transplant may have poorer FEV1 performance post-transplant. 6MWD and TUG are simple measures that may be correlated with post-transplant lung function.

Cardiac Disease Increased Risk of Death and Early Comorbidities Impacting Prognosis of Lung Transplant Recipients with Extreme Ages

<h3>Purpose</h3> Current organ allocation rules prioritized aged patients on the lung transplantation waiting list. Optimizing decision-making algorithms to evaluate candidates, transplant and minimize morbidity, has become the goal of lung transplant programs worldwide. <h3>Methods</h3> This was a retrospective cohort study recruiting patients who underwent lung transplantation, between January 2016 and October 2020, at Wuxi Lung Transplant Center. <b>The transplanted organs were obtained from volunteer donations, and the next of kin voluntarily provided written informed consent. No lungs were obtained from executed prisoners.</b> <h3>Results</h3> Among the entire study cohort of 166 lung transplant recipients aged ≥65 years, subgroups of aged 65-70 years (111 recipients, Group 65-70) and ≥70 years (55 recipients, Group≥70) were included. Group D restrictive lung disease was the main indication of recipients ≥65 years, followed. We found significantly higher percentage of coronary artery stenosis (mid-to severe) in the Group≥70 (30.9% vs. 14.4%). Further, we found valve structural abnormality in both groups, ranging from 8.1% to 16.4%, including medium to severe valve stenosis or regurgitation. ECMO bridging to LT was performed in 5.4% (Group 65-70) and 7.3% (Group≥70). The average cold ischemic time was 434.6 minutes in Group 65-70 and 395.9 minutes in Group≥70, over 6.5 hours. We did more single left lateral lung transplantation in Group≥70 patients mainly consisted of pulmonary fibrosis. Significantly higher occurrence rate of acute rejection, cardiac arrhythmia, pleural effusion were observed in Group≥70. Subjects with cardiac abnormality had significantly increased risk of mortality compared to those without cardiac abnormality (Figure 1). <h3>Conclusion</h3> Our experience from the largest aged lung transplant recipients cohort in eastern population, supported that lung transplantation can be performed in candidates with advanced chronological age and provided life-extending benefits.

Intra-Tracheal Adeno-Associated Virus Mediates Gene Transduction During Static Cold Storage in Rodent Lung Transplantation

<h3>Purpose</h3> We tested the efficacy of intra-tracheal Adeno-associated Virus (AAV) to deliver reporter genes during static cold storage (SCS) in rat lung grafts. <h3>Methods</h3> Recombinant AAV subtype-9 vectors encoding firefly luciferase were produced in HEK293 cells (AAV-Luc). Lewis rat lung grafts received either 8e10 viral genomes (VGs) in 100 μL saline ([8e8 VG/μL], N=3), 4e11 VGs in 100 μL saline ([4e9VG/μL], N=3), or 100 μL saline only (N=2) via the trachea during 1 hour of SCS. Syngeneic rats underwent single left lung transplantation. Animals underwent bioluminescence imaging on post-operative weeks 1, 2, 4, and 8, then were sacrificed. Explanted tissues were lysed and incubated with luciferin to quantify reporter activity. Immunohistochemistry was performed using tissue from rats transplanted with lungs treated with 4e11 VGs of AAV encoding Green Fluorescent Protein (GFP) and sacrificed at day 14 (N=2). <h3>Results</h3> Following transplant, in vivo bioluminescence was observed in the left chest of animals that received AAV-Luc (Figure 1A). In vivo signal was similar in both groups (mean radiance 7.6e4 vs 7.1e4 photons per second per square cm per steradian (p/s/cm2/sr) at the terminal time point (p=0.41), and similar to that of control animals (mean 6.1e4 p/s/cm2/sr Figure 1B). In the explanted transplant lung, mean luminescent activity was 9.2e2 relative luminescent units (RLU) per gram tissue in controls, compared to 3.0e4 RLU/g in grafts receiving [8e8 VG/μL] and 2.0e5 RLU/g in grafts receiving [4e9 VG/μL] AAV-Luc (Figure 1C). Immunohistochemistry revealed positive GFP staining primarily in pneumocytes of the AAV-GFP treated lung only (Figure 1D). <h3>Conclusion</h3> Here we demonstrate for the first time successful intra-tracheal AAV-mediated gene transduction during SCS, with subsequent expression in the donor lung for at least 8 weeks without apparent off-target expression. Gene expression appears to be primarily seen in alveolar pneumocytes with this route of administration.

Anti-HLA DQ Antibodies Are Associated with Chronic Lung Allograft Dysfunction in a Pediatric Lung Transplant Population

<h3>Purpose</h3> Chronic lung allograft dysfunction (CLAD) limits long term survival after lung transplantation. Antibody mediated rejection (AMR) has been associated with earlier CLAD development, but studies are limited in children. Clinical AMR can exist on a spectrum from subclinical to definite AMR based on the presence of anti-HLA donor specific antibodies (DSA), allograft dysfunction, and histopathologic findings, with DSA development first to appear. This study aims to describe the relationship of elevated DSA with clinical outcomes in a single center pediatric lung transplant population. <h3>Methods</h3> This was a single center, retrospective study. Pediatric bilateral lung transplant recipients were included from 2002-2020 if they had longitudinal HLA and lung function data for at least 6 months after transplantation. Preliminary analyses with chi-squared or Fisher's exact test for categorical variables and ANOVA or Kruskal-Wallis for continuous variables were used. DSA were detected with single-antigen bead arrays, and elevated DSA was defined as a mean fluorescence intensity level above 500. <h3>Results</h3> 34 patients were included: 19 with elevated DSA and 15 without. Most patients had subclinical AMR (n=10) without allograft dysfunction and two patients had definite AMR, based on the 2018 Banff consensus statement. The proportion of patients who developed CLAD was significantly higher in the elevated DSA group and had an earlier onset of CLAD. Average graft longevity and rates of acute cellular rejection, while not significant, trended towards shorter survival and higher rates of rejection in the elevated DSA group. All persistently elevated DSA were directed against HLA Class II DQ (6 of 14 patients) epitopes. Survival analysis and the significance of different HLA antigens remains ongoing. <h3>Conclusion</h3> The development of persistently elevated HLA Class II DQ DSA is associated with CLAD and likely decreased survival in the pediatric lung transplant population.