Previous Lung Transplantation Research Articles

Veno-arterial extracorporeal membrane oxygenation as bridge for fluid resuscitation in a patient with acute respiratory failure and circulatory shock two years post lung transplantation.

The use of extracorporeal membrane oxygenation (ECMO) continues to evolve and is recognized as an important adjunct as a bridge to recovery or a bridge to transplant. We wanted to share our experience of using veno-arterial (VA) ECMO as an adjunct to lung recovery and an aide for fluid resuscitation. We present the case of a 77-year-old man with a history of previous single lung transplant who had acute respiratory decompensation and cardiovascular collapse secondary to CMV pneumonia and septic shock. He was cannulated for VA ECMO, treated for CMV pneumonia and resuscitated with 5L of albumin 5% and antibiotics, within 12 hours of cannulation. He required twodays of VA ECMO and was ultimately decannulated and discharged to a rehabilitation facility on hospital day 73. This case emphasizes the challenging clinical scenario of fluid resuscitation in a lung transplant patient. With adequate patient selection, a multidisciplinary team and the use of VA ECMO, success can be achieved.

Ceftolozane/Tazobactam for the Treatment of Adults With Cystic Fibrosis: Results From a French Prospective Cohort Study.

People with cystic fibrosis (pwCF) are particularly susceptible to respiratory infections, including those caused by multidrug-resistant (MDR) pathogens. Ceftolozane/tazobactam (C/T) is an antibacterial agent combination active against MDR gram-negative bacteria that has shown promising results in isolates from pwCF. This subanalysis is the first extensive observation of real-world C/T use in pwCF. The multicenter observational CONDUCT study included consecutive patients, some with cystic fibrosis, who received ≥1 dose of C/T at 28 centers throughout France. Patients were treated according to hospital standards and followed up until the end of C/T treatment (EOT). Among 260 patients who had received ≥1 dose of C/T, 63 were pwCF, including 12 with previous lung transplant. The median age was 34 years and 55.6% of patients were female. Pseudomonas aeruginosa was the most frequently isolated pathogen (n = 40/41 [97.6%]). Most tested P aeruginosa strains (n = 65/73 [91.5%]) and all other isolated strains (Escherichia coli, Citrobacter koseri, Proteus mirabilis, and Serratia marcescens) were susceptible to C/T. Most patients completed the treatment duration, including those with historical β-lactam hypersensitivity. Reasons for stopping treatment were planned EOT and improvement in condition; overall, 88.9% of patients (n = 56/63) experienced improvement in condition. No new safety signals were identified. Mean forced expiratory volume in 1 second improved from 1.33 L to 1.47 L before and after C/T treatment, respectively (n = 52; P = .057). C/T treatment was well tolerated and effective in pwCF, including those with previous β-lactam hypersensitivity.

Impact of total ischaemic time and disease severity class on graft function after bilateral lung transplantation.

Total ischaemic time (IT) is considered a limiting factor in lung transplantation. In this retrospective study, we investigate effects of IT and disease burden on outcomes after bilateral lung transplantation. A total of 1298 patients undergoing bilateral lung transplantation between January 2010 and May 2022 (follow-up 100%, median 54 months) were included. Pre-transplant diseases' severity (recipient body mass index, recipient age, previous lung transplantation, Tacrolimus immunosuppression, preoperative recipient extracorporeal membrane oxygenation support, lung volume reduction) for graft failure was individually calculated and-as IT-categorized. Vice versa adjusted Cox models were calculated. Considering competing risks, we assessed cumulative incidences of airway obstructive complications and chronic lung allograft dysfunction with death as competing risk factors for primary graft dysfunction were assessed by binary logistic regression. Higher disease burden significantly accelerated chronic lung allograft dysfunction and death occurrence (P < 0.001); IT did not. IT-adjusted disease burden strata showed 50% graft survival differences at 11 years after transplantation (range 24-74%), disease burden-adjusted IT strata 18% for all and 6% (54-60%) among those above 7 h. All significant primary graft dysfunction risk factors were diagnoses related, IT was not significantly important and odds ratios did not increase with IT. The eventual graft survival disadvantage that results from an IT between 7 and at least 11 h is negligible in contrast to frequent recipients' disease-based risk levels.

Management of Native Lung Malignancy in a Lung Transplant Recipient.

A 75-year-old male patient with a history of previous right lung transplant presented with left upper lobe squamous cell carcinoma. Endobronchial ultrasound and positron emission tomography displayed no mediastinal lymphadenopathy. A ventilation-perfusion scan displayed minimal perfusion to the native lung. Left robot-assisted lysis of adhesions, decortication, left upper lobectomy, and mediastinal lymphadenectomy were performed. The patient tolerated the procedure well. Final pathology displayed pT2a, n0, m0. Lobectomy is a safe and efficient treatment of native lung malignancy in the setting of previous lung transplant with minimally functioning native lung.

Two consecutive major lower limb operations in a heart-lung transplant recipient during COVID pandemic: A case report and literature review

Introduction: Combined heart and lung transplant is a rare procedure performed for patients with congenital heart disease and end stage pulmonary disease. Due to improvement in survival, non-cardiac surgeries are frequently performed in these patients and anaesthetists are involved in their perioperative management. Apart from increasing the physical and mental health risks, COVID-19 pandemic has posed an additional challenge to health care providers in the management of these immunosuppressed patients. Case presentation: We report a case of a 64-year-old female patient with a previous combined heart and lung transplant who underwent two consecutive lower limb surgeries during COVID pandemic.Conclusion: Meticulous preoperative assessment involving multidisciplinary team, knowledge of the pathophysiology of heart–lung transplant patients, choosing appropriate anaesthetic technique is vital in successful management of these patients. Psychological implications of COVID-19 pandemic in immunosuppressed patients should be considered.

Risk factors of invasive fungal infections in lung transplant recipients: A systematic review and meta-analysis

Invasive fungal infection (IFI) remains a common complication after lung transplantation, causing significant morbidity and mortality. We have attempted to quantify systematically risk factors of IFI in lung transplant recipients. Studies were retrieved from Ovid MEDLINE, Ovid Embase, Cochrane database of systematic reviews and Cochrane central register of controlled trials. All case-control and cohort studies evaluating the risk factors of IFI in adult lung transplant recipients were screened. Two researchers reviewed and assessed all studies independently. We pooled the estimated effect of each factor associated with IFI by using a random effect model. Eight studies were included in the systematic review and 5 studies were eligible for the meta-analysis. Rates of IFI range from 8% to 33% in lung transplant recipients. Independent risk factors for invasive aspergillosis (IA) in lung transplantation include previous fungal colonization (odds ratio [OR] 2.44; 95% confidence interval [CI] 0.08-0.47), cytomegalovirus infection (OR 1.96; 95% CI 1.08-3.56), and single lung transplantation (OR 1.77; 95% CI 1.08-2.91). Pre-emptive antifungal therapy is a protective factor for IA in lung transplant (OR 0.2; 95% CI 0.08-0.47). Cytomegalovirus infection, previous fungal colonization and single lung transplantation independently increase the risk of IA in lung transplant recipients. Pre-emptive antifungal therapy is a protective factor for IA in the lung transplant population.

Intrabronchial migration of hemostatic agent through a bronchial fistula after lung transplantation: a case report

BackgroundA bronchial fistula is a relatively rare and potentially fatal complication after lung transplantation. Thoracic surgeons and pulmonologists often face challenges when selecting treatment options. We herein report an exceptional case of intrabronchial migration of a nonabsorbable hemostatic agent, which had been placed around the pulmonary artery at the time of lung transplantation, through a bronchial fistula.Case presentationA 61-year-old man developed respiratory distress 1 year after left single-lung transplantation for idiopathic interstitial pneumonia. Bronchoscopic examination revealed an apparent foreign body protruding from the mediastinum into the distal site of the bronchial anastomosis. The foreign body was easily removed bronchoscopically and appeared to be a hemostatic agent that had been placed during the previous lung transplantation. The patient developed a similar clinical episode and finally developed hemoptysis. Computed tomography revealed a foreign body located between the bronchus and pulmonary artery, partially protruding into the bronchial lumen. Given the possibility of a bronchopulmonary arterial fistula, surgical treatment was performed. The foreign body was located between the bronchus and left pulmonary artery and was easily removed. Multiple bronchial fistulas were found, and all were closed with direct sutures. Bypass grafting of the left pulmonary artery was then performed, initially with a homograft but eventually with an extended polytetrafluoroethylene graft. The patient was finally discharged 5 months after the surgery.ConclusionWe experienced an extremely rare case of intrabronchial migration of hemostatic agents used during the previous lung transplantation through a bronchial fistula, which were successfully managed by direct bronchial closure and bypass grafting of the left pulmonary artery.

Colorectal Cancer Prevention in Lung Transplant Recipients: The Need for an Enhanced Surveillance Protocol

Solid organ transplant recipients are at increased risk for noncutaneous neoplasms, including colorectal cancer (CRC). We evaluated precancerous lesions detected by post-transplant surveillance colonoscopy to infer the rate at which new adenomas develop in this population. We reviewed all patients who underwent lung transplant between January 2013 and August 2017 at our institution. Those with post-transplant survival <1 year, personal history of CRC, previous lung transplant, and lack of pretransplant colonoscopy were excluded. During the study period, 411 patients underwent lung transplant; 237 met inclusion criteria. Median age at transplant was 63.6 (interquartile range [IQR] 59.2-68.3) years. Most recipients were immunosuppressed with a combination of prednisone, tacrolimus, and mycophenolate mofetil. At least 1 adenoma was found in 92 patients (38.8%) pretransplant and in 118 patients (49.8%) from 1 to 5 years post-transplant, with 68.6% identified at 1 year. Most adenomas were identified proximal to the splenic flexure. Multiple (≥3) adenomas were found in 31.4% of positive colonoscopies. Within 5 years after transplant, patients with a positive pretransplant colonoscopy had significantly more positive post-transplant colonoscopies than patients with a negative pretransplant colonoscopy (63.0% vs 41.4%, p < 0.001). No de novo CRC was identified. Lung transplant recipients have a significantly higher risk of adenoma formation than average-risk adults (25%-30% national detection rate). This increase occurs in the early post-transplant period (within 3 years). An enhanced CRC surveillance protocol for lung transplant recipients is needed.

P137 COVID-19 in cystic fibrosis patients with and without lung transplantation: the Zurich cohort

Objectives: Reports on short- and long-term presentations of COVID-19 in CF patients is limited. We aimed to describe clinical features and outcomes of all our CF patients with laboratory confirmed COVID-19 between March 2020 and January 2021 (ongoing observation). Methods: Retrospective review of clinical data and treatment of CF patients with COVID-19 confirmed by RT-PCR or serological evidence (n = 11). Results: Mean age at presentation was 32 (23–48) years, 27% (n = 3) were female. Six patients (55%) had a previous lung transplantation (post-Ltx). Two patients were on modulator therapy (Trikafta® and Symdeco®). The most common presenting symptoms were cough (36%), fever (27%), headache (27%) and dyspnea (18%). Nine patients (82%) had mild disease and were treated as outpatients. Two patients (18%) were post-LTx and were hospitalised with severe disease (1 on the normal ward, 1 in the intensive care unit). The most notable laboratory findings were lymphopenia, and elevated levels of C-reactive protein. In the two hospitalised patients, computed tomography of the chest showed ground-glass opacities with consolidations;1 patient additionally had a small pleural effusion. These 2 patients were treated with remdesivir, as well as broad-spectrum antibiotics (meropenem). The patients with mild disease were treated with co-amoxicillin (n = 3, 27%). Dexamethasone was given in selected cases. Mechanical ventilation was not necessary for any of these patients. The hospitalised patients received oxygen by nasal cannula and high-flow oxygen therapy. All patients recovered. Residual symptoms are being monitored. Conclusion: This is the first study of an adult CF-COVID-19 cohort in Switzerland, which included patients who underwent lung transplantation. Cough, fever, headache and dyspnea were the most common symptoms. Two patients (27%) had severe disease. The majority had a benign course and long-term symptoms are still under investigation.

A proof-of principal study using phase-contrast imaging for the detection of large airway pathologies after lung transplantation

In this study we aim to evaluate the assessment of bronchial pathologies in a murine model of lung transplantation with grating-based X-ray interferometry in vivo. Imaging was performed using a dedicated grating-based small-animal X-ray dark-field and phase-contrast scanner. While the contrast modality of the dark-field signal already showed several promising applications for diagnosing various types of pulmonary diseases, the phase-shifting contrast mechanism of the phase contrast has not yet been evaluated in vivo. For this purpose, qualitative analysis of phase-contrast images was performed and revealed pathologies due to previous lung transplantation, such as unilateral bronchial stenosis or bronchial truncation. Dependent lung parenchyma showed a strong loss in dark-field and absorption signal intensity, possibly caused by several post transplantational pathologies such as atelectasis, pleural effusion, or pulmonary infiltrates. With this study, we are able to show that bronchial pathologies can be visualized in vivo using conventional X-ray imaging when phase-contrast information is analysed. Absorption and dark-field images can be used to quantify the severity of lack of ventilation in the affected lung.

Chart-Review Based Frailty Assessment Can Predict Readmission after Lung Transplantation: A Pilot Study

Chart-based frailty assessment is an attractive option for evaluation of older transplant candidates, as it has been shown to be predictive of morbidity and mortality in the community-dwelling elderly population. We proposed to evaluate frailty in lung transplant candidates to determine whether retrospective frailty could be calculated, and whether it was associated with patient outcomes after transplantation. In this retrospective study, in a previously evaluated cohort of lung transplant recipients, Frailty Risk Score (FRS) as described by Lekan et al. was calculated using a standardized assessment tool. Electronic medical record notes from pulmonologists, psychiatrists, and social workers; laboratory measures, and ICD-10 codes were reviewed. Length of hospitalization, number of readmissions, and time in hospital during the first year after transplantation were assessed. High FRS was defined as >3. 31 subjects were reviewed. The median age was 63 (range 42-77). Median FRS was 3 (range 1-7). The most common positive FRS components were dyspnea, fatigue, chronic pain, depression, and abnormal WBC. 21 patients (68%) were readmitted in the first year after transplantation, for a median of 1 readmission per patient (range 0-5). Patients spent a median of 19 days inpatient during the first year (range 7-82). There was no association between FRS and patient age (p=0.983). A significant association was seen between readmission and FRS, both by numeric score (p<0.001) and by FRS high versus low assessment (p=0.004) (Figure). FRS was also significantly associated with inpatient days by FRS high versus low assessment (p=0.020) (Figure). Chart based frailty and comorbidity assessments can be readily performed in previous lung transplant recipients. Frailty as measured by FRS score was able to predict need for readmission and length of total inpatient hospitalizations, suggesting its promise as a tool for patient risk stratification.

An unusual cause of a multifocal bone lesion: Epstein–Barr Virus-Associated Smooth Muscle Tumour (EBV-SMT) involving bone

Epstein–Barr virus-associated smooth muscle tumours (EBV-SMTs) are rare neoplasms of uncertain biological potential, which occur in the setting of immunodeficiency of a variety of causes, including HIV infection and post-transplant immunosuppression. The association between SMTs and immunosuppression was first described by Pritzker et al. in 1970. They have a male predominance and occur at unusual sites in adults. The CNS is the most common site in the setting of HIV while post transplantation cases are more likely to occur in liver, lungs and GIT. Other sites have also been reported including bone. We report a case of an EBV-SMT presenting as multifocal, lucent lesions of proximal tibia, proximal fibula and distal femur in a 45-year-old female patient with previous lung transplantation. A biopsy of the tibial lesion showed a smooth muscle tumour with positive staining for EBER (EBV ISH) supporting a diagnosis of EBV-SMT. EBV-SMTs of bone are rare and to our knowledge this is the first example of multifocal EBV-SMT confined to bone.

Predictors of blood loss in lung transplant surgery-a single center retrospective cohort analysis.

This retrospective study aims to identify clinical predictors of intraoperative blood loss during lung transplantation. While for other surgical specialties predictors of blood loss have been identified such as previous likewise located surgery, poor preoperative health status of patients, blood coagulation status, and use of extra corporeal circulation, predictors of blood loss during lung transplantation are not yet established. A total of 326 lung transplants were performed between January 2000 and February 2014 at a tertiary hospital. The primary aim was to associate blood loss with the following potential predictors: pulmonary arterial hypertension, pre- or intraoperative extracorporeal life support (ECLS), previous thoracic surgery, previous lung transplant, and Charlson Comorbidity Index (CCI). Postoperative complications and 30-day mortality were secondary endpoints of the study. Median estimated blood loss during lung transplant was 1,500 mL (IQR, 1,000-2,875 mL). Pre- and intraoperative ECLS (P=0.02, P<0.001) independently increased blood loss by 59% and 107%, respectively. The higher blood loss during re-transplant marginally missed the significance level (P=0.05). Pulmonary arterial hypertension, previous thoracic surgery and high CCI were not associated with increased blood loss. As secondary outcomes, postoperative complications were more common in patients with a higher blood loss (P=0.04) but was not associated with higher 30-day mortality (P=0.18). Pre- and intraoperative ECLS were significant risk factors for higher blood loss during lung transplantation. Higher blood loss was associated with higher incidence of postoperative complications but not with a higher 30-day mortality.

Exploring the implications of different approaches to estimate centre-level adherence using objective adherence data in an adult cystic fibrosis centre – a retrospective observational study

BackgroundAccurate centre-level medication adherence measurement allows identification of highly performing CF centres, drives shared learning and informs quality improvement. Self-reported adherence is unreliable but data-logging nebulisers can capture objective data. However, adherence levels in current literature are limited by the use of agreed prescriptions and convenience sampling. In this single-centre retrospective study, we quantified the differences in centre-level adherence with different methods of calculating adherence (unadjusted vs normative adherence) and different data sampling frames (convenience sampling vs including difficult to obtain data). MethodsAdherence data were objectively captured using I-neb® from 2013-2016 in Sheffield Adult CF Centre. Adults on non data-logging devices, on ivacaftor or with previous lung transplantation were excluded. Adherence was calculated based on agreed regimen (‘unadjusted adherence’) or minimum required regimen (‘normative adherence’). I-nebs® not brought to clinic were downloaded during home visits. Adults not on any inhaled therapy but with chronic Pseudomonas aeruginosa infection were included by counting their adherence as “0”. ResultsOf the 131 included adults, 126 provided I-neb® data. Calculating unadjusted adherence from I-nebs® brought to clinics resulted in the highest centre-level adherence (median 41.8% in 2013). Median adherence reduced after sequentially accounting for minimum required regimen (40.0% in 2013), I-nebs® not brought to clinics (32.9% in 2013) and adults not on any inhaled therapy (31.0% in 2013). ConclusionsDifferent approaches of calculating adherence produced different adherence levels. Adherence levels based only on agreed regimen among adults who readily brought their nebulisers to clinics can over-estimate the effective adherence of CF centres.

Colorectal Cancer Prevention in Lung Transplant Recipients: The Need for an Enhanced Surveillance Protocol

BACKGROUND Solid organ transplant recipients are at increased risk for noncutaneous neoplasms, including colorectal cancer (CRC). We evaluated precancerous lesions detected by post-transplant surveillance colonoscopy to infer the rate at which new adenomas develop in this population. STUDY DESIGN We reviewed all patients who underwent lung transplant between January 2013 and August 2017 at our institution. Those with post-transplant survival <1 year, personal history of CRC, previous lung transplant, and lack of pretransplant colonoscopy were excluded. RESULTS During the study period, 411 patients underwent lung transplant; 237 met inclusion criteria. Median age at transplant was 63.6 (interquartile range [IQR] 59.2-68.3) years. Most recipients were immunosuppressed with a combination of prednisone, tacrolimus, and mycophenolate mofetil. At least 1 adenoma was found in 92 patients (38.8%) pretransplant and in 118 patients (49.8%) from 1 to 5 years post-transplant, with 68.6% identified at 1 year. Most adenomas were identified proximal to the splenic flexure. Multiple (≥3) adenomas were found in 31.4% of positive colonoscopies. Within 5 years after transplant, patients with a positive pretransplant colonoscopy had significantly more positive post-transplant colonoscopies than patients with a negative pretransplant colonoscopy (63.0% vs 41.4%, p < 0.001). No de novo CRC was identified. CONCLUSIONS Lung transplant recipients have a significantly higher risk of adenoma formation than average-risk adults (25%-30% national detection rate). This increase occurs in the early post-transplant period (within 3 years). An enhanced CRC surveillance protocol for lung transplant recipients is needed.

Kidney Transplantation in Patients With Chronic Kidney Disease After a Previous Lung Transplantation

BackgroundThe development of chronic kidney disease is a common complication after a lung transplantation, especially since the introduction of immunosuppressive treatments based on calcineurin inhibitors. Many of these patients reach end-stage renal disease and even need renal replacement therapy. Among the different options of renal replacement therapy, we consider kidney transplantation as a feasible option for these patients. MethodsA single center, observational retrospective study including 8 lung transplanted patients who have received a kidney transplant in the period between 2013 and 2017 with at least 1 year of follow-up was used. ResultsSeven patients maintained an adequate function of the graft 1 year after kidney transplantation, and 1 patient died because of a pulmonary condition in spite of a previous kidney transplant. Two patients presented delayed graft function in the first days after surgery. ConclusionsThe kidney transplantation is a technique of renal replacement therapy that should be considered in patients with previous lung transplantation. Experienced centers in double sequential lung and kidney transplantation should be established to assess and treat these types of patients.

Long-term survival following kidney transplantation in previous lung transplant recipients-An analysis of the unos registry.

Kidney transplantation has been advocated as a therapeutic option in lung recipients who develop end-stage renal disease (ESRD). This analysis outlines patterns of allograft survival following kidney transplantation in previous lung recipients (KAL). Data from the UNOS lung and kidney transplantation registries (1987-2013) were cross-linked to identify lung recipients who were subsequently listed for and/or underwent kidney transplantation. Time-dependent Cox models compared the survival rates in KAL patients with those waitlisted for renal transplantation who never received kidneys. Survival analyses compared outcomes between KAL patients and risk-matched recipients of primary, kidney-only transplantation with no history of lung transplantation (KTx). A total of 270 lung recipients subsequently underwent kidney transplantation (KAL). Regression models demonstrated a lower risk of post-listing mortality for KAL patients compared with 346 lung recipients on the kidney waitlist who never received kidneys (P<.05). Comparisons between matched KAL and KTx patients demonstrated significantly increased risk of death and graft loss (P<.05), but not death-censored graft loss, for KAL patients (P=.86). KAL patients enjoy a significant survival benefit compared with waitlisted lung recipients who do not receive kidneys. However, KAL patients do poorly compared with KTx patients. Decisions about KAL transplantation must be made on a case-by-case basis considering patient and donor factors.

Graft and Patient Survival Following Kidney Transplantation in Previous Lung Transplant Recipients.

Graft and Patient Survival Following Kidney Transplantation in Previous Lung Transplant Recipients.

Lung re-transplantation

Re-transplantation of the lung has come of age. Here, we wish to review the recent literature on the topic and discuss clinical implications. Many large volume transplant centres routinely perform lung re-transplantation with satisfactory outcomes. The main indication is bronchiolitis obliterans syndrome, that is chronic rejection of a previous lung transplant. Other indications, such as primary graft failure or early airway complications, are regarded with more caution, as outcomes compare less favourably with those following primary transplantation. Re-transplantation of the lung can be performed safely and with outcomes rivalling those of primary transplants in carefully selected recipients with chronic rejection of a previous transplant.

Percutaneous endoscopic jejunostomy in patients with gastroparesis following lung transplantation: feasibility and clinical outcome

The aim of the present study was to describe success rates, complications, and outcome in patients who underwent percutaneous endoscopic jejunostomy (PEJ) because of gastroparesis due to previous lung transplantation. Between October 2008 and May 2011, 14 attempts at PEJ placement were made in 12 patients in our center. Of the 14 attempts, 11 were successful, giving a technical success rate of 78.6 %. Median duration of followup was8.5 months (2–15 months). No immediate complications were reported. Two severe complications occurred during follow up (one volvulus and one jejunocolic fistula). Jejunal nutrition was well tolerated in most of patients (9 /10). PEJ insertion is a feasible technique, which could help to provide nutritional support for patients with gastroparesis and previous lung transplantation.