Patients Undergoing Lung Transplantation Research Articles

Bifurcated Silicone Stents for the Management of Anastomotic Complications in Lung Transplanted Patients: Ten Years’ Experience

Background: In lung transplantation (LT), the actual surgical practice is to cut the donor bronchus as short as possible in order to reduce anastomotic complications (AC). Consequently, the anastomosis is very close to the secondary carina. If AC occur, regular straight stents may be unsatisfactory and on-site modified bifurcated stents may represent an alternative. Objectives: This retrospective study sought to assess the short- and long-term outcomes of patients treated with customized bifurcated stent (CBS) for the management of AC following LT. Methods: Data from patients with AC following LT requiring CBS placement between June 2010 and June 2020 were analyzed. Results: Four hundred patients underwent lung transplant. AC requiring airway stenting occurred in 32 patients (8%), and CBS were inserted in 15 patients (3.5%). Indications were stenosis (n = 12; 80%) and bronchial dehiscence (n = 3; 20%). CBS were successfully deployed in 14 patients and failed in 1 patient. No migration was recorded during the follow-up. The median number of complication was 1 per patient (0–5). CBS could be removed in 11 patients (78.6%), and 3 died with their stents in place. AC recurrence or complications requiring new stenting occurred in 4/11 patients (36.3%), with a median time of 7 days (0–29). Seven patients (63.7%) had no AC recurrence, with a median follow-up of 925 days (118–3,249). Conclusions: The actual surgical anastomotic technique in LT provides new endoscopic challenges. CBS seem ideally positioned to address these difficulties safely and effectively but are associated with stent related complications requiring further endoscopic management.

Pre-transplant malignancy is associated with increased risk of de novo malignancy post-lung transplantation

BackgroundAt least 20% of lung transplant recipients will be diagnosed with a malignancy within 5 years of transplant. Transplant candidates with a history of pre-transplant malignancy must meet remission criteria before listing to minimize the risk of recurrence, however these patients may have an intrinsic predisposition to developing subsequent cancers which can be amplified by immunosuppression. We assessed whether pre-transplant malignancy was associated with an increased risk of developing malignancy of any type after lung transplant. MethodsWe conducted a single centre retrospective cohort study of patients undergoing lung transplant between January 2006 and December 2017. We used a proportional hazards regression model to test whether preTM was associated with the risk of developing one or more postTM after lung transplant, adjusted for known cancer risk factors. Results497 adult patients underwent lung transplantation during the study period and 26 (5.2%) had pre-transplant malignancies. Out of 29 pre-transplant cancer diagnoses, prostate cancer was the most common (17.2%), followed by breast cancer and basal cell carcinoma (13.8% each). 108 (22%) patients developed post-transplant malignancy with a total of 328 cancer diagnoses. The most common post-transplant malignancy was non-melanoma skin cancer (86.3%), followed by solid organ cancers (7.6%). Pre-transplant malignancy was associated with an adjusted HR of 3.24 (95% CI 1.71 to 6.14, p < 0.001) for the development of post-transplant malignancy. Recurrence of the pre-transplant malignancy only occurred in 3 patients post-transplant. ConclusionsHistory of pre-transplant malignancy was associated with a more than three times likelihood of development of a post-transplant malignancy compared to recipients without a previous history of cancer, the majority being unrelated to the initial malignancy. These findings highlight the importance of frequent cancer surveillance in lung transplant recipients, especially in those with a history of pre-transplant malignancy.

Influence of Fluid Therapy on Kidney Function in the Early Postoperative Period After Lung Transplantation

Perioperative fluid therapy among patients undergoing lung transplantation (LT) has a significant clinical importance, including developing of acute kidney injury (AKI). The presence of AKI in the early postoperative period is associated with increased mortality in lung transplant recipients. Analysis includes the relationship between the volume of infused fluids, the balances of crystalloids and colloids during LT procedure and in the first 24 hours and the estimated glomerular filtration rate (eGFR) values in the following days of the postoperative period. Retrospective study of 73 consecutive patients undergoing LT between 2015 and 2018 in our institution. Deterioration of renal function was defined as the change in eGFR that occurred between baseline eGFR and the first and 7 first postoperative days following transplantation. The Chronic Kidney Disease Epidemiology Collaboration formula was used to calculate the eGFR value. The greatest decline of eGFR in the early postoperative period was demonstrated on day 7 (ΔeGFR=75.76 ± 40.08). Increased negative crystalloid balances during the LT procedure were strongly associated to less decrease in eGFR value on the seventh day post-LT (r=-0.997, P < .05). Increased volumes of transfused colloids during LT were correlated to less decline of eGFR value on day 7 (r=-0.3981, P < .05). Negative crystalloid balance in the early postoperative period post-LT has a potentially protective effect on kidney function, although fluid balances management should be individually considered for potential clinical benefits. The impact of the fluid administration after LT on the occurrence and recovery of AKI among lung transplant recipients requires further investigation.

Volume Replacement Strategy with Albumin 5% and Bedside Coagulopathy Management Improves Cardiopulmonary Stability by Decreasing Norepinephrine Dosage and by Increasing P/F Ratio in Patients Undergoing Lung Transplantation (Preliminary Results)

<h3>Purpose</h3> Lung transplantation is a very demanding procedure often accompanied by circulatory instability, bleeding, and postoperative development of primary graft dysfunction. Circulatory instability is treated with a combination of fluid and vasopressor support. 5% Albumin appears to be a very promising volume replacement. The use of bedside methods such as thromboelastometry (ROTEM), platelet function analyzer (PFA 200), and aggregometer (Multiplate) seems very promising to correct coagulopathy and reduce bleeding symptoms during lung transplantation. <h3>Methods</h3> Patients undergoing lung transplantation were divided into two groups. 1. POC (Point Of Care) group - 5% albumin was used almost exclusively as a volume replacement, and bedside methods (ROTEM, PFA, Multiplate) were used to correct coagulopathy. 2. nonPOC group - volume replacement and correction of coagulopathy were solved according to the clinical experience of the anesthesiologist. <h3>Results</h3> The total number of analyzed patients is 46. In the POC group, there was a significant decrease in vasopressor support of noradrenaline (p <0.05) and a significant improvement in the P/F ratio (p <0.05). The results are shown in Figures I. and II. <h3>Conclusion</h3> The perioperative approach using 5% albumin volume replacement in combination with bedside methods for diagnosis and correction of coagulopathy contributes to improved circulatory stability (the lower dose of noradrenaline) and also helps to improve lung graft function (better P / F ratio) during and after lung transplantation. The current preliminary results seem to be promising in this area and we will continue in this study in the future.

Airway Complications After Lung Transplant for Post Coronaviral Disease (COVID-19) Acute Respiratory Distress Syndrome (ARDS) Related End Stage Lung Disease: Single Centre Experience

PurposeSevere COVID-19 ARDS related end stage lung fibrosis with irreversible changes is a newer indication for lung transplantation with acceptable survival rate. Airway complication post lung transplant is a major source of morbidity and mortality with incidence as high as 25 to 49 percent. Patients with end stage COVID-19 fibrosis are likely to be clinically deconditioned with long duration of extracorporeal oxygenator (ECMO) support, high burden of sepsis and prolonged respiratory support which may affect the airways post lung transplantation.MethodsThis is a retrospective observational study after obtaining institutional ethical clearance. We reviewed electronic medical data of patients who underwent lung transplantation for post COVID-19 ARDS related fibrosis. We evaluated the incidence and type of airway complications and the various therapeutic interventions applied for its management.ResultsBetween May 2020 and September 2021 our centre performed 23 bilateral lung transplants for end stage COVID-19 ARDS related fibrosis. 22 patients were on ECMO support with mean duration of 50.9 days before transplantation. All patients underwent lung transplantation with central Veno-Arterial ECMO support with mean organ ischaemia time of 360±154 minutes. The incidence of airway complication in our study group was 56%. We observed anastomotic narrowing in 3(13%), distal airway narrowing in 4(17%) and sloughing/coating of anastomotic site in 5(22%) patients. Nonspecific inflammatory polypi around the bronchial anastomotic site were noticed in 4(17%) and mild airway anastomotic dehiscence in 2 subjects. 8(34%) patients required serial bronchoscopy and balloon dilatation; 2 among them mandated additional cautery usage. 2 cases underwent polypectomy, further 4 subjects needed bronchial stent placement. 5 (21%) recipients were discharged with Tracheostomy while rest were successfully decannulated in the ward.ConclusionWe observed a high incidence of airway complications in post lung transplant for COVID-19 ARDS related fibrosis. Early detection, timely management and serial follow up is of paramount importance in this subset of patients.

Anti-S100A8/A9 Neutralizing Monoclonal Antibody Ameliorates Lung Injury Induced by Lung Ischemia Reperfusion Injury

<h3>Purpose</h3> Lung ischemia reperfusion (IR) injury is inevitable in the lung transplant and increases the mortality and morbidity in patients undergoing lung transplantation. S100A8/A9 is one of the damage-associated molecular patterns which is known as an early inflammatory mediator in IR injury. The aim of this study was to assess the therapeutic effect of neutralizing monoclonal antibody (mAb) against S100A8/A9. <h3>Methods</h3> A mice hilar clamp model of IR was used. Animals were divided into sham groups and IR groups with or without administration of anti-S100A8/A9 mAb. We assessed lung oxygenation, tissue injury, neutrophil infiltrations, expression of proinflammatory molecules and apoptosis. <h3>Results</h3> Plasma S100A8/A9 level was significantly reduced by anti-S100A8/A9 mAb treatment. The severity of IR injury represented by oxygenation capacity was significantly improved by the antibody treatment (Figure 1). Anti-S100A8/A9 mAb treatment reduced the S100A8/A9 positive cells in lung tissue detected by anti-S100A9 antibody (Figure 2) and neutrophil infiltrations. The neutralizing antibody significantly suppressed IR gene expression levels of IR injury-induced proinflammatory factors including IL-1β, IL-6, TNF-α, CXCL-1 and CXCL-2. Further investigations unveiled that the abrogation of S100A8/A9 function decreased TUNEL-positive cells indicating apoptotic cells. <h3>Conclusion</h3> The anti-S100A8/A9 mAb obviously ameliorated lung IR injury by reduction of neutrophil infiltrations, inflammatory molecules and apoptosis, indicating that S100A8/A9 is a novel therapeutic target for lung IR injury.

Using Donor Lungs ≥70 Years of Age for Transplantation - Do Long-Term Outcomes Justify the Use?

<h3>Purpose</h3> Donor shortage have led transplant centers in the past to extend acceptable criteria for lung donors, accepting older and more marginal donor organs for transplantation. Accepting donors ≥70 years of age as lung donors has shown good short-term outcomes in the past, however, no mid- and long-term outcome data on these extended criteria donors exists thus far. <h3>Methods</h3> All patients undergoing lung transplantation between 06/2010 and 12/2019 at our institution were included into the analysis, that compared outcomes between patients transplanted with donors <70 years of age vs. patients transplanted with donors ≥70 years old. Outcome parameters included pre-, peri- and postoperative clinical parameters as well as recipient overall survival and CLAD-free survival. Median follow-up was 8.9 years. <h3>Results</h3> Between 06/2010 and 12/2019, among the 1168 lung-transplanted patients, 62 (5.3%) patients received lungs from donors ≥70 years old. Recipient age of the patients receiving older organs was significantly higher as compared to recipients of <70 years old lungs (56.2±7.8 vs. 48.7±38.9 yrs; p<0.0001) and more patients with an obstructive disease pattern prior to transplantation received a donor lung ≥70 years old (40.3% vs. 27.6%; p=0.04). Mean donor age was 73.4±2.9 years in the ≥70 years old group as compared to 44.3±15.8 yrs in the other cohort (p<0.0001). Older donors were significantly shorter on mechanical ventilation prior to donation (4.0±3.6 vs 5.7±5.1 days; p=0.0007), had a higher median Horowitz index (412.5 (356;469) vs. 384 (316; 448); p=0.01) and fewer history of smoking (12.9% vs. 42.1%; p<0.0001).Primary graft dysfunction scores at 24 (p=0.99), 48 (p=0.60) and 72 (p=0.94) hours after transplant showed no significant difference between both groups. Similarly, time on mechanical ventilation (p=0.68), time on ICU (p=0.65) as well as total hospital stay (p=0.58) were comparable in both groups. One-, five- and 7-year survival in both groups showed no significant difference (1yr: 95.1 vs. 90.2%, 5yr: 77.8 vs. 73.2%, 7yr: 69.1 vs. 68.1%, p=0.71). CLAD-free survival showed no difference between both groups in the follow-up period (p=0.76). <h3>Conclusion</h3> Utilization of donor lungs ≥70 years of age leads to excellent mid- and long-term results that are similar to younger donor organs when carefully preselecting these older donor organs.

Post-Transplant Metabolomics Profiles in Patients Undergoing Lung Transplantation

<h3>Purpose</h3> Optimal nutrition is recognized as an essential component to successful outcomes for post procedure recovery after a major cardio-thoracic procedure. We developed a unique multi-modal rehabilitation program that combines physical therapy protocol with neuromuscular electric stimulation (NMES) and protein supplementation to achieve improved functional outcomes for advanced lung disease patients requiring transplantation <h3>Methods</h3> The patients were randomized to either the treatment arm (n=5) or usual care (n=6) 72 hours after the transplant. Both groups of patients underwent an initial global assessment of functional capabilities and blood metabolomic profile evaluation 72 hours post-transplantation. Patients in the treatment arm received additional physical therapy plus NMES (10 days) and nutrition supplementation with essential amino acids (3 times/day) during hospital recovery. Follow up metabolomic profile analysis was performed on 14 days and 3-month post-transplant plasma samples. <h3>Results</h3> Compared to the standard of care group, the treatment group decreased average time of intubation (1.6 vs 2.16 days), decreased average ICU length of stay (5.80 vs 8.67 days) and decreased average hospital length of stay (16.8 vs 19.5 days). The treatment group had increased hypotaurine levels indicating a cytoprotective anti-oxidant effect against free radicals and tissue damage. Preliminary results comparing hypotaurine levels at 72 hours,14 days and 3 month in the treatment group (T-72 hr T-14 days, T-3 months) compared to control group (C-72 hr C-14 days, C-3 months) are presented in figure 1. <h3>Conclusion</h3> Defining the role of metabolomics in post-transplant monitoring is still in its early stages. We intend to use the data obtained from this pilot study to develop a larger, randomized interventional trial evaluating the effects of an intense multimodal rehabilitation program on improving post-operative outcomes and defining blood biomarkers of muscle atrophy during ICU stay after lung transplantation.

Long Term Outcomes Following Double Lung Transplantation for Severe COVID-19 Infection

Purpose: Lung transplantation is a potentially lifesaving treatment for severe COVID-19 acute respiratory distress syndrome (ARDS), when optimized medical treatment fails to accomplish lung recovery. However, since the long-term outcomes remain unknown, concerns related to the use of lung transplantation in critically ill COVID-19 patients persist. In the current study, we evaluated consecutive patients that underwent lung transplantation for severe COVID-19 ARDS at our center and compared their post-transplant outcomes with those undergoing transplantation for non-COVID-19 pathology during the concurrent study period.MethodsAll consecutive patients undergoing lung transplantation between January 2020 to May 2021 were included. The study included two cohorts of patients that underwent transplantation for non-COVID-19 disease (nC19) or refractory COVID-19 ARDS (C19). For additional analysis, we included consecutive patients with severe COVID-19 that required veno-venous extracorporeal membrane oxygenation (ECMO).ResultsWe found that post-procedure complications and length of stay were significantly greater compared to transplants performed for non-COVID-19 lung diseases during the concurrent study period. Following transplant the COVID-19 cohort demonstrated a more rapid improvement in Karnofsky performance status. At one year, all recipients in COVID-19 cohort were alive with post-transplant survival no different than institutional non-COVID-19 recipients. Furthermore, when compared to propensity-matched recipients from SRTR, post-transplant survival of institutional COVID-19 ARDS patients was non-inferior. There was progressive reduction in the probability of separation from extracorporeal membrane oxygenation (ECMO) with time and ECMO support greater than 30 days was associated with a significantly greater risk of death in patients with COVID-19 ARDS. In those who remained unweanable from ECMO after 30 days, lung transplant was an independent predictor of survival.ConclusionWe conclude that lung transplantation in selected patients with severe COVID-19 ARDS who remain unweanable from extracorporeal life support can result in post-transplant outcomes comparable to recipients with chronic end-stage lung diseases and non-COVID-19 ARDS.

Lung Transplant for Patients with COVID-19 Bridged with VV ECMO: Initial Experience

PurposeDuring the COVID-19 pandemic, veno-venous Extracorporeal Membrane Oxygenation (VV ECMO) has been used extensively for respiratory failure refractory to conventional mechanical ventilation (MV) and rescue maneuvers. However, the worldwide experience with COVID-19 patients undergoing lung transplant (LTx) with pre-LTx VV ECMO support is limited. Therefore, we sought to report our institution's early experience with COVID-19 patients who underwent LTx after VV ECMO.MethodsWe retrospectively identified 5 COVID-19 patients who underwent LTx after VV ECMO support. Patients were required to have a negative nasopharyngeal swab and a negative bronchoalveolar lavage for COVID-19 prior to LTx listing. We analyzed preoperative and operative characteristics, details of VV ECMO support and early post-transplant outcomes.ResultsThe mean age of our cohort was 50 years (range 39-57 years) and all patients were male. Mean recipient BMI was 30 (range 22-37). Mean duration of VV ECMO pre-Ltx was 60 days (range 44-72 days). At the time of the LTx operation, 60% (3/5) of patients were on VV ECMO, 20% (1/5) were on mechanical ventilation (MV), and 20% (1/5) were on supplemental oxygen only. Preoperatively, 80% (4/5) had acute kidney injury and 20% (2/5) were on dialysis. LTx was performed via clamshell approach with intraoperative venoaterial ECMO support in all cases. For 60% (3/5) patients, VV ECMO support was continued after LTx and discontinued on postoperative days 0, 1 and 6, respectively. All-cause mortality was 40% (2/5), related to sepsis and multi-organ failure, and both deaths occurred an average of 115 days post-LTx. Mean length of stay for surviving patients was 59 days (range 22-117). In the first 3 months postop-LTx, grade A2 acute cellular rejection was noted in 2 patients, A1 in 2 patients, and antibody-mediated rejection in 1 patient.ConclusionOur early experience with LTx for COVID-19 patients supported with VV ECMO support is notable for 1) prolonged VV-ECMO duration and significant morbidity pre-LTx, and 2) early mortalities related to sepsis and multiple organ failure. These data highlight a uniquely complex patient population that carries high risk of multi-organ failure and other comorbidities dictating careful selection for transplant.

Short Term Outcomes of Patients Who Underwent Lung Transplant for COVID-19 ARDS

PurposeLung transplantation is a life saving treatment option for patients with COVID-19 ARDS. We aim to assess the short-term outcomes of patients who underwent lung transplantation for COVID ARDS.MethodsThis is a single-center retrospective cohort study of patients who underwent lung transplantation for COVID 19 ARDS between 7/1/2020 and 06/30/2021. Study was IRB-approved. Baseline demographic data, pre transplant variables, peri operative data and post transplant variables were extracted. Post-transplant graft function variables were followed until 09/30/2021.ResultsTwenty patients underwent lung transplantation alone, and one patient underwent lung kidney transplantation. Nineteen patients (90%) were ECMO bridge to transplant and twenty patients (95%) were on mechanical ventilator until the transplant. These patients were followed for a median of 234 days [IQR (188-339)]. Three patients (14%) completed a one-year follow-up. Eighteen patients (86%) completed six months follow-up. None of the patients required dialysis. At the end of the follow up period, all patients have good graft function and none of the patients are on supplemental oxygen.ConclusionWith careful selection, lung transplants can be performed with reasonable post-transplant outcomes in COVID 19 ARDS patients. However, these patients tend to have a prolonged post transplant hospital stay, a median of 48 days with IQR (28.5 - 73.5). 50% of patients had at least one return to operating room post transplant for hemothorax.

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.

Lung Transplant Outcomes in Patients with Pulmonary Veno-Occlusive Disease

<h3>Purpose</h3> Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Prognosis of PVOD is worse than PAH. Most patients need lung transplantation. Previous study showed that PVOD patients had higher waitlist mortality compared to PAH patients. To date, there are no study report outcomes of lung transplant in this population. We would like to study the outcome and compare with IPAH patients. <h3>Methods</h3> This is a retrospective observational study. Patients with a diagnosis of PVOD and PAH underwent lung transplant between 2005 and 2018 were identified from SRTR database. Numerical data were reported in mean and standard deviation. Categorical data were reported in count and percent. T-test and Chi-square test were performed to compare variables between 2 groups. Survival was compared using Kaplan-Meier (K-M) method. <h3>Results</h3> 61 PVOD patients and 970 PAH patients underwent lung transplant were identified. There was no significant difference in age and BMI. Patients with PVOD had significant lower post-transplant systolic, diastolic and mean PA pressure and higher cardiac output. LAS at matching were not significantly different. PVOD patients had shorter time on waiting list (152.7±263.34 vs 337.56±511.14, p<0.01). Proportion of patients requiring ECMO post lung transplant were higher in PVOD group (13.11% vs 4.23%, p<0.01). Proportion of patients developing primary graft dysfunction (PGD) were lower in PVOD group (37.5% vs 61.93%, p=0.056). There was no difference of length of stay, FEV1, FVC, PCO2 post lung transplant and acute rejection between 2 groups. Survivals were not different between 2 groups using K-M method (p=0.33). <h3>Conclusion</h3> We found that PVOD patients who underwent lung transplant had shorter waiting time compared to PAH patients which suggest that disease severity of PVOD is higher than PAH. Despite that more PVOD patients required ECMO support post-operative, patient survival and other long-term outcomes such as lung function or rejection were not different between from PAH patients.

Description and Characterization of Intraoperative Bacterial Cultures During Lung Transplant Surgery

<h3>Purpose</h3> Describe and characterize intraoperative bacterial cultures collected during lung transplant surgery. <h3>Methods</h3> This was a single-center retrospective chart review from 1/1/2018 through 5/31/2021. All adult patients undergoing lung transplant at Cedars Sinai Medical Center during the study period were included. No cystic fibrosis patients were transplanted during this time. Intraoperative cultures were collected by swabbing the bronchus. Given single and bilateral lung transplants were performed, a total of 84 patients yielded 116 cultures. The antibiotics utilized post-operatively were vancomycin and cefepime as per institutional protocol. Antibiotics were continued for at least 3 days until intraoperative cultures finalized. Further duration, consolidation, and/or de-escalation was based on clinical course and culture data. <h3>Results</h3> 56% (65/116) of cultures were positive for bacteria. Yearly breakdown yielded similar data: 53.3% (16/30) in 2018; 54.5% (12/22) in 2019; 66.7% (18/27) in 2020; 51.4% (19/37) in 2021. Forty-eight cultures had gram positive (GP) growth, with Staphylococcus being most common (42/48 of GP cultures). Methicillin-Resistant Staphylococcus Aureus (MRSA) accounted for 21.4% (9/42) of these cultures. Gram negative (GN) growth was seen in 38 cultures: Enterobacter (11/38), Klebsiella (10/38), Acinetobacter (7/38), Pseudomonas (4/38), Escherichia (2/38), Stenotrophomonas (1/38), Citrobacter (1/38), Neisseria (1/38), Haemophilus (1/38). <h3>Conclusion</h3> This culture data reinforces that broad spectrum antibiotics are warranted after lung transplant surgery. Given the high incidence of Staphylococcus, including MRSA, it is prudent to provide MRSA coverage until final culture data is available. Although Pseudomonas only accounted for 10.5% of GN cultures, this could be due to the patient population transplanted during the study period. Centers should continue to use their own culture data and population to guide antibiotic choice.

The changing landscape of pediatric lung transplantation.

There has been a shift over decades in the diagnostic indications for lung transplantation in children; in particular, there has been a reduction in the proportion of pediatric cystic fibrosis (CF) patients undergoing lung transplantation early in life, and more transplants occurring in other diagnostic groups. Here, we examine trends in pediatric lung transplantation with regards to indications by analyzing data from the United Network of Organ Sharing, the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, and other sources. Over the past two years, there has been a precipitous decline in both the number of transplants due to CF and the proportion of CF cases relative to the total number of transplants, likely not solely due to the COVID-19 pandemic. In 2020, primary pulmonary arterial hypertension for the first-time surpassed CF as main indication for pediatric lung transplantation in the United States, a finding that is also reflected in international data. We discuss the effect of novel CFTR modulator therapies as a major factor leading to this shifting landscape. Based on our trending, pulmonary hypertension-related diagnoses and pediatric interstitial lung diseases are rising indications, for which we suggest adjustments of consensus guidelines around candidate selection criteria.

Estimating Renal Function Following Lung Transplantation

Background: Patients undergoing lung transplantation (LTx) experience a rapid decline in glomerular filtration rate (GFR) in the acute postoperative period. However, no prospective longitudinal studies directly comparing the performance of equations for estimating GFR in this patient population currently exist. Methods: In total, 32 patients undergoing LTx met the study criteria. At pre-LTx and 1-, 3-, and 12-weeks post-LTx, GFR was determined by 51Cr-EDTA and by equations for estimating GFR based on plasma (P)-Creatinine, P-Cystatin C, or a combination of both. Results: Measured GFR declined from 98.0 mL/min/1.73 m2 at pre-LTx to 54.1 mL/min/1.73 m2 at 12-weeks post-LTx. Equations based on P-Creatinine underestimated GFR decline after LTx, whereas equations based on P-Cystatin C overestimated this decline. Overall, the 2021 CKD-EPI combination equation had the lowest bias and highest precision at both pre-LTx and post-LTx. Conclusions: Caution must be applied when interpreting renal function based on equations for estimating GFR in the acute postoperative period following LTx. Simplified methods for measuring GFR may allow for more widespread use of measured GFR in this vulnerable patient population.

Cover Image

Cover image: The cover image is based on the Original Article Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation by Naoya Ikegami et al., https://doi.org/10.1111/his.14595.

The role of mechanical ventilation in primary graft dysfunction in the postoperative lung transplant recipient: A single center study and literature review.

BackgroundPrimary graft dysfunction (PGD) is still a major complication in patients undergoing lung transplantation (LTx). Much is unknown about the effect of postoperative mechanical ventilation on outcomes, with debate on the best approach to ventilation.Aim/PurposeThe goal of this study was to generate hypotheses on the association between postoperative mechanical ventilation settings and allograft size matching in PGD development.MethodThis is a retrospective study of LTx patients between September 2011 and September 2018 (n = 116). PGD was assessed according to the International Society of Heart and Lung Transplantation (ISHLT) criteria. Data were collected from medical records, including chest x‐ray assessments, blood gas analysis, mechanical ventilator parameters and spirometry.ResultsPositive end‐expiratory pressures (PEEP) of 5 cm H2O were correlated with lower rates of grade 3 PGD. Graft size was important as tidal volumes calculated according to the recipient yielded greater rates of PGD when low volumes were used, a correlation that was lost when donor metrics were used.ConclusionOur results highlight a need for greater investigation of the role donor characteristics play in determining post‐operative ventilation of a lung transplant recipient. The mechanical ventilation settings on postoperative LTx recipients may have an implication for the development of acute graft dysfunction. Severe PGD was associated with the use of a PEEP higher than 5 and lower tidal volumes and oversized lungs were associated with lower long‐term mortality. Lack of association between ventilatory settings and survival may point to the importance of other variables than ventilation in the development of PGD.

Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation.

Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.

The effect of nutritional status on clinical outcome in lung transplantation.

Nutritional status greatly impacts the clinical outcome of the patients receiving lung transplantation. The objective of this study was to evaluate the effect of nutritional status on the clinical outcome in lung transplant recipients. A single-center retrospective study was conducted including 73 patients received lung transplantation from December 2015 to April 2022 in the Affiliated Henan Provincial People's Hospital of Zhengzhou University. Data were collected from the hospital information system. The records of BMI, malnutrition defined by the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria, hemoglobin and plasma albumin before operation were accessed. The primary outcome assessed was survival or mortality represented by Kaplan-Meier survival curves; the log-rank test and multivariate Cox proportional hazards regression were used to evaluate the influence of each factor on survival. Kaplan-Meier survival analysis showed that malnutrition, hemoglobin and plasma albumin were predictors of survival in lung transplantation (Log Rank p<0.05). Multivariate Cox regression showed that pre-operative hemoglobin <130 g/L (HR 2.532, p=0.036) and plasma albumin <35 g/L (HR 2.723, p=0.016) were associated with the decreased survival rate. Preoperative anemia and hypoalbuminemia increase the mortality risk of the lung transplantation patients. Pre-operative nutrition support, therefore, is likely to be critical for improving clinical outcome in patients undergoing lung transplantation.