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Background: Infections are one of the most common causes of death after lung transplant (LT). However, the benefit of 'targeted' prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear., Methods: All consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016-2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis ('standard' vs. 'targeted' on the preoperative bacterial isolation)., Results: One hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to 'targeted' prophylaxis, while 24 (52%) to 'standard' prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with 'standard' prophylaxis and twelve (75%) with 'targeted' therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the 'standard' and 11 to the 'targeted' prophylaxis (p = 0.027)., Conclusions: The administration of a 'targeted' prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections., (© 2024. The Author(s).)

Background: Diaphragm dysfunction and its effects on outcomes of ventilator weaning have been evaluated in mixed critical care populations using diaphragm thickening fraction (the ratio of the difference between ultrasound diaphragm thickness at end-inspiration and end-expiration to diaphragm thickness at end-expiration) or neuroventilatory efficiency (the ratio of tidal volume and peak electrical activity of the diaphragm). Such data are not available in bilateral-lung transplant recipients. The authors hypothesized that (1) diaphragm dysfunction, as defined by a diaphragm thickening fraction less than 29%, is more likely to occur in difficult weaning; (2) diaphragm thickening fraction and neuroventilatory efficiency predict weaning outcome; and (3) duration of mechanical ventilation before the first spontaneous breathing trial is associated with diaphragm dysfunction., Methods: Adult bilateral-lung transplant patients admitted to the intensive care unit were screened at the time of the first spontaneous breathing trial (pressure-support of 5 cm H2O and 0 positive end-expiratory pressure). At the fifth minute, diaphragm thickening fraction and neuroventilatory efficiency were measured during three respiratory cycles. Weaning was classified as simple, difficult, or prolonged (successful extubation at the first spontaneous breathing trial, within three or after three spontaneous breathing trials, respectively)., Results: Forty-four subjects were enrolled. Diaphragm dysfunction occurred in 14 subjects (32%), all of whom had difficult weaning (78% of the subgroup of 18 patients experiencing difficult weaning). Both diaphragm thickening fraction (24 [20 to 29] vs. 39 [35 to 45]%) and neuroventilatory efficiency (34 [26 to 45] vs. 55 [43 to 62] ml/µV) were lower in difficult weaning (both P < 0.001). The areas under the receiver operator curve predicting difficult weaning were 0.88 (95% CI, 0.73 to 0.99) for diaphragm thickening fraction and 0.85 (95% CI, 0.71 to 0.95) for neuroventilatory efficiency. The duration of ventilation demonstrated a linear inverse correlation with both diaphragm thickening fraction and neuroventilatory efficiency., Conclusions: Diaphragm dysfunction is common after bilateral-lung transplantation and associated with difficult weaning. In such patients, average values for diaphragm thickening fraction and neuroventilatory efficiency were reduced compared to patients with simple weaning. Both parameters showed similar accuracy for predicting success of ventilator weaning, demonstrating an inverse relationship with duration of ventilation., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Selection of patients who may benefit from extracorporeal life support (ECLS) as a bridge to lung transplant (LTx) is crucial. The aim was to assess if validated prognostic scores could help in selecting patients who may benefit from ECLS-bridging predicting their outcomes. Clinical data of patients successfully ECLS-bridged to LTx from 2009 to 2021 were collected from two European centers. For each patient, we calculated Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score III (SAPS III), Acute Physiology and Chronic Health Evaluation II (APACHE II), before placing ECLS support, and then correlated with outcome. Median values of SOFA, SAPS III, and APACHE II were 5 (IQR 3-9), 57 (IQR 47.5-65), and 21 (IQR 15-26). In-hospital, 30 and 90 days mortality were 21%, 14%, and 22%. SOFA, SAPS III, and APACHE II were analyzed as predictors of in-hospital, 30 and 90 days mortality (SOFA C-Index: 0.67, 0.78, 0.72; SAPS III C-index: 0.48, 0.45, 0.51; APACHE II C-Index: 0.49, 0.45, 0.52). For SOFA, the score with the best performance, a value ≥9 was identified to be the optimal cut-off for the prediction of the outcomes of interest. SOFA may be considered an adequate predictor in these patients, helping clinical decision-making. More specific and simplified scores for this population are necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Faccioli, Lorenzoni, Schneiter, Dell’Amore, Hillinger, Schiavon, Caviezel, Gregori, Rea, Opitz and Inci.)

Purpose: To assess the role of muscle composition and radiomics in predicting allograft rejection in lung transplant., Material and Methods: The last available HRCT before surgery of lung transplant candidates referring to our tertiary center from January 2010 to February 2020 was retrospectively examined. Only scans with B30 kernel reconstructions and 1 mm slice thickness were included. One radiologist segmented the spinal muscles of each patient at the level of the 11th dorsal vertebra by an open-source software. The same software was used to extract Hu values and 72 radiomic features of first and second order. Factor analysis was applied to select highly correlating features and then their prognostic value for allograft rejection was investigated by logistic regression analysis (level of significance p < 0.05). In case of significant results, the diagnostic value of the model was computed by ROC curves., Results: Overall 200 patients had a HRCT prior to the transplant but only 97 matched the inclusion criteria (29 women; mean age 50.4 ± 13 years old). Twenty-one patients showed allograft rejection. The following features were selected by the factor analysis: cluster prominence, Imc2, gray level non-uniformity normalized, median, kurtosis, gray level non-uniformity, and inverse variance. The radiomic-based model including also Hu demonstrated that only the feature Imc2 acts as a predictor of allograft rejection (p = 0.021). The model showed 76.6% accuracy and the Imc2 value of 0.19 demonstrated 81% sensitivity and 64.5% specificity in predicting lung transplant rejection., Conclusion: The radiomic feature Imc2 demonstrated to be a predictor of allograft rejection in lung transplant., (© 2023. The Author(s).)

Background: Pediatric lung transplantation is performed in highly experienced centers due to the peculiar population characteristics. The literature is limited and not representative of individual countries' differences. The purpose of this study was to analyze the Italian experience., Methods: A multicentric retrospective analysis was performed on 110 pediatric patients (<18 years old) who underwent lung transplantation from 1992 to 2019 at 9 Italian centers. Heart-lung transplantations and lung retransplantations were excluded., Results: The population was composed of 44 male and 66 female patients, with a median age of 15 years. The most frequent indication was cystic fibrosis (83%). One quarter of patients were transplanted in an emergency setting. Median donors' Oto score and age were 1 and 15 years, respectively, with 43% of adult donors. In 17% of patients a graft reduction was performed. Postoperatively, the median duration of mechanical ventilation, intensive care unit, and in-hospital stay were 48 hours, 11 and 35 days, respectively. Thirty-day mortality was 6%, and 1-, 5-, and 10-year survival was 72%, 52%, and 33%, respectively. Risk factors for mortality were Oto score and recipients' body mass index., Conclusions: The outcomes of pediatric lung transplantation in Italy are comparable with current literature. Particular attention should be paid to the Oto score and recipient body mass index. Conversely, adult donors and graft reductions can be safely used to expand the donor pool., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marro, Leiva-Juárez, D’Ovidio, Chan, Van Raemdonck, Ceulemans, Moreno, Kindelan, Krueger, Koutsokera, Ehrsam, Inci, Yazicioglu, Yekeler, Boffini, Brioude, Thomas, Pizanis, Aigner, Schiavon, Rea, Anile, Venuta and Keshavjee.)

Background: In recent decades, the incidence of multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL) gram-negative (GN) bacteria has increased progressively among lung transplantation (LT) recipients. A prompt diagnosis, prevention, and management of these pathogens remain the cornerstone for successful organ transplantation., Research Question: What are the incidence of MDR and ESBL GN bacteria within the first 30 days after LT and related risk of in-hospital mortality? What are the potential clinical predictors of isolation of MDR and ESBL GN bacteria?, Study Design and Methods: All consecutive LT recipients admitted to the ICU of the University Hospital of Padua (February 2016-December 2021) were screened retrospectively. Only adult patients undergoing the first bilateral LT and not requiring invasive mechanical ventilation, extracorporeal membrane oxygenation, or both before surgery were included. MDR and ESBL GN bacteria were identified using in vitro susceptibility tests and were isolated from the respiratory tract, blood, urine, rectal swab, or surgical wound or drainage according to a routine protocol., Results: One hundred fifty-three LT recipients were screened, and 132 were considered for analysis. Median age was 52 years (interquartile range, 41-60 years) and 46 patients (35%) were women. MDR and ESBL GN bacteria were identified in 45 patients (34%), and 60% of patients demonstrated clinically relevant infection. Pseudomonas aeruginosa (n = 22 [49%]) and Klebsiella pneumoniae (n = 17 [38%]) were frequently isolated after LT from the respiratory tract (n = 21 [47%]) and multiple sites (n = 18 [40%]). Previous recipient-related colonization (hazard ratio [HR], 2.48 [95% CI, 1.04-5.90]; P = .04) and empirical exposure to broad-spectrum antibiotics (HR, 6.94 [95% CI, 2.93-16.46]; P < .01) were independent predictors of isolation of MDR and ESBL GN bacteria. In-hospital mortality of the MDR and ESBL group was 27% (HR, 6.38 [95% CI, 1.98-20.63]; P < .01)., Interpretation: The incidence of MDR and ESBL GN bacteria after LT was 34%, and in-hospital mortality was six times greater. Previous recipient-related colonization and empirical exposure to broad-spectrum antibiotics were clinical predictors of isolation of MDR and ESBL GN bacteria., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: For small-sized recipients of lung transplantation, the time span for organ reception from standard donors is generally longer than for normal-sized patients. Despite its underuse, lobar reduction may be a concrete option for these patients. This study aims to assess early and long-term outcomes associated with lobar reduction in lung transplantation., Methods: A retrospective study was performed on 608 consecutive lung transplantations at 2 centers between January 2005 and August 2019 (559 standard lung transplantations [standard transplantation] and 49 with lobar reduction [lung transplantation group]). A propensity-score weighting approach was used to account for potential confounding related to patients' nonrandom allocation to the 2 intervention groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach., Results: The propensity score was estimated on 571 patients (522 in standard transplantation group and 49 in lung transplantation group). In terms of early outcomes, the lung transplantation group showed a higher percentage of severe primary graft dysfunction at 0 hours and reported longer intensive care unit stay than the standard transplantation group. No other differences in terms of morbidity, mortality, mechanical ventilation time, hospital stay, and anastomotic complications were observed. Although the lung transplantation group showed worse long-term pulmonary function, the 2 populations had comparable survival outcomes., Conclusions: The use of lobar reduction showed early and long-term results comparable to those after standard lung transplantation. Although a higher rate of early severe primary graft dysfunction and slightly reduced respiratory function were detected in the lobar group, these did not affect patients' morbidity and survival., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

SARS‑CoV‑2 mostly affects the respiratory system with clinical patterns ranging from the common cold to fatal pneumonia. During the first wave of the COVID-19 pandemic, owing to the high number of patients who were infected with SARS‑CoV‑2 and subsequently recovered, it has been shown that some patients with post-COVID-19 terminal respiratory failure need lung transplantation for survival. There is increasing evidence coming from worldwide observations that this procedure can be performed successfully in post-COVID-19 patients. However, owing to the scarcity of organs, there is a need to define the safety and efficacy of lung transplant for post-COVID-19 patients as compared to patients waiting for a lung transplant for other pre-existing conditions, in order to ensure that sound ethical criteria are applied in organ allocation. The Milan's Policlinic Lung Transplant Surgery Unit, with the revision of the National Second Opinion for Infectious Diseases and the contribution of the Italian Lung Transplant Centres and the Italian National Transplant Centre, set up a pivotal observational protocol for the lung transplant of patients infected and successively turned negative for SARS‑CoV‑2, albeit with lung consequences such as acute respiratory distress syndrome or some chronic interstitial lung disease. The protocol was revised and approved by the Italian National Institute of Health Ethics Committee. Description of the protocol and some ethical considerations are reported in this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nosotti, Leiva-Juarez, D’Ovidio, Van Raemdonck, Ceulemans, Keshavjee, Rackauskas, Paladini, Luzzi, Casado, Alvarez, Inci, Ehrsam, Krueger, Roth, Rea, Schiavon and Rosso.)

Purpose: Bronchial stenoses are challenging complications after lung transplantation and are associated with high rates of morbidity and mortality. We report a series of patients who underwent bronchoplasty or sleeve resection for bronchial stenoses that did not resolve with endoscopic treatment after lung transplantation., Methods: Between 1995 and 2020, 497 patients underwent lung transplantation at our Institution. 35 patients (7.0%) experienced bronchial stenoses with a median time from transplantation of 3 months. Endoscopic management was effective in 28 cases (5.6%) while 1 patient required re-transplantation. Six patients (1.2%) underwent bronchoplasty or sleeve resection., Results: The procedures of the six patients who underwent bronchoplasty or sleeve resection were as follows: lower sleeve bilobectomy (n = 3), wedge bronchoplasty of the bronchus intermedius (n = 1), isolated sleeve resection of the bronchus intermedius (n = 1), and isolated sleeve resection of the bronchus intermedius (n = 1), associated with a middle lobectomy. All patients were discharged after a median time of 11 days. At a median of 12 months from surgery, two patients remain alive with a preserved pulmonary function. Four patients died after a median time of 56 months from bronchoplasty of causes that were not related to surgery., Conclusions: Bronchial reconstructions are challenging procedures that can be performed in highly specialized centers. Despite this, they can be considered a good strategy to obtain a definitive resolution of stenosis after lung transplantation., (© 2021. The Author(s).)

A recent history of malignancy is an absolute contraindication for lung transplantation according to the International Society of Heart and Lung Transplantation; however, a 5-year disease-free interval should be demonstrated in most cases of malignancies to consider the patient a suitable recipient. Currently, no specific guidelines are reported for addressing previous lung cancer in the selection of recipients. We report a case of a patient who underwent right upper lobectomy for small cell lung cancer in 2013 followed by adjuvant chemotherapy and prophylactic encephalic radiotherapy. In 2019 she underwent lung transplantation for emphysema. Currently she is alive with no recurrence of neoplastic disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ischemia-reperfusion (IR) injury after lung transplantation is still today an important complication in up to 25% of patients. The Organ Care System (OCS) Lung, an advanced normothermic ex vivo lung perfusion system, was found to be effective in reducing primary graft dysfunction compared to standard organ care (SOC) but studies on tissue/molecular pathways that could explain these more effective clinical results are lacking. This observational longitudinal study aimed to investigate IR injury in 68 tissue specimens collected before and after reperfusion from 17 OCS and 17 SOC preserved donor lungs. Several tissue analyses including apoptosis evaluation and inducible nitric oxide synthase (iNOS) expression (by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction) were performed. Lower iNOS expression and apoptotic index were distinctive of OCS preserved tissues at pre- and post-reperfusion times, independently from potential confounding factors. Moreover, OCS recipients had lower acute cellular rejection at the first 6-month follow-up. In conclusion, IR injury, in terms of apoptosis and iNOS expression, was less frequent in OCS- than in SOC-preserved lungs, which could eventually explain a better clinical outcome. Further studies are needed to validate our data and determine the role of iNOS expression as a predictive biomarker of the complex IR injury mechanism., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: The European Society of Thoracic Surgeons Lung Transplantation Working Group promoted a survey to evaluate overall survival in a large cohort of patients receiving lung transplants for rare pulmonary diseases., Methods: We conducted a retrospective multicentre study. The primary end point was overall survival; secondary end points were survival of patients with the most common diagnoses in the context of rare pulmonary diseases and chronic lung allograft dysfunction (CLAD)-free survival. Finally, we analysed risk factors for overall survival and CLAD-free survival., Results: Clinical records of 674 patients were extracted and collected from 13 lung transplant centres; diagnoses included 46 rare pulmonary diseases. Patients were followed for a median of 3.1 years. The median survival after a lung transplant was 8.5 years. The median CLAD-free survival was 8 years. The multivariable analysis for mortality identified CLAD as a strong negative predictor [hazard ratio (HR) 6.73)], whereas induction therapy was a protective factor (HR 0.68). The multivariable analysis for CLAD occurrence identified induction therapy as a protective factor (HR 0.51). When we stratified patients by CLAD occurrence in a Kaplan-Meier plot, the survival curves diverged significantly (log-rank test: P < 0.001). Patients with rare diseases who received transplants had chronic rejection rates similar to those of the general population who received transplants., Conclusions: We observed that overall survival and CLAD-free survival were excellent. We support the practice of allocating lungs to patients with rare pulmonary diseases because a lung transplant is both effective and ethically acceptable., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Despite improvement in lung function, most lung transplant (LTx) recipients show an unexpectedly reduced exercise capacity that could be explained by persisting peripheral muscle dysfunction of multifactorial origin. We analyzed the course of symptoms, including dyspnea, muscle effort and muscle pain and its relation with cardiac and pulmonary function parameters during an incremental exercise testing., Methods: Twenty-four bilateral LTx recipients were evaluated in an observational cross-sectional study. Recruited patients underwent incremental cardio-pulmonary exercise testing (CPET). Arterial blood gases at rest and peak exercise were measured. Dyspnea, muscle effort and muscle pain were scored according to the Borg modified scale. Potential associations between the severity of symptoms and exercise testing parameters were analyzed using a Forest-Tree Machine Learning approach, which accomplishes for a ratio between number of observations and number of screened variables less than unit., Results: Dyspnea score was significantly associated with maximum power output (WR, watts), and minute ventilation (VE, L/min) at peak exercise. In a controlled subgroup analysis, dyspnea score was a limiting symptom only in LTx recipients who reached the higher levels of WR (≥ 101 watts) and V E (≥ 53 L/min). Muscle effort score was significantly associated with breathing reserve as percent of maximal voluntary ventilation (BR%MVV). The lower the BR%MVV at peak exercise (< 32) the higher the muscle effort perception. Muscle pain score was significantly associated with VO 2 peak, arterial [HCO 3 - ] at rest, and V E /VCO 2 slope. In a subgroup analysis, muscle pain was the limiting symptom in LTx recipients with a lower VO 2 peak (< 15 mL/Kg/min) and a higher V E /VCO 2 slope (≥ 32)., Conclusions: The majority of our LTx recipients reported peripheral limitation as the prevalent reason for exercise termination. Muscle pain at peak exercise was strictly associated with basal and exercise-induced metabolic altered pathways. The onset of dyspnea (breathing effort) was associated with the intensity of ventilatory response to meet metabolic demands for increasing WR. Our study suggests that only an accurate assessment of symptoms combined with cardio-pulmonary parameters allows a correct interpretation of exercise limitation and a tailored exercise prescription. The role and mechanisms of muscle pain during exercise in LTx recipients requires further investigations.

Despite the availability of antifibrotic therapies, many patients with idiopathic pulmonary fibrosis (IPF) will progress to advanced disease and require lung transplantation. International guidelines for transplant referral and listing of patients with interstitial lung disease are not specific to those with IPF and were published before the widespread use of antifibrotic therapy. In this review, we discussed difficulties in decision-making when dealing with patients with IPF due to the wide variability in clinical course and life expectancy, as well as the acute deterioration associated with exacerbations. Indeed, the ideal timing for referral and listing for lung transplant remains challenging, and the acute deterioration might be influenced after transplant outcomes. Of note, patients with IPF are frequently affected by multimorbidity, thus a screening program for occurring conditions, such as coronary artery disease and pulmonary hypertension, before lung transplant listing is crucial to candidate selection, risk stratification, and optimal outcomes. Among several comorbidities, it is of extreme importance to highlight that the prevalence of lung cancer is increased amongst patients affected by IPF; therefore, candidates' surveillance is critical to avoid organ allocation to unsuitable patients. For all these reasons, early referral and close longitudinal follow-up for potential lung transplant candidates are widely encouraged.

Background: The rat orthotopic lung transplant model is not widely used yet because of the complexity of the procedure, in particular, venous anastomosis. Here, we performed a rat orthotopic lung transplantation using either the suture (ST) or cuff (CT) method for vein anastomosis., Objectives: To compare the vein ST and CT techniques in terms of operative time, success, recipient survival, and early histological outcomes was the objective of this study., Methods: A total of 24 left lung transplants in rats were performed. Twelve syngeneic (Lewis to Lewis) and 12 allogeneic (Brown-Norway to Lewis) lung transplants were performed using either the vein ST or the CT procedure. Arterial and bronchial anastomoses were performed with the CT technique. Graft histological damage was evaluated 3-7 days post-transplant in all rat lungs., Results: The surgical success rate was 75% in both the ST and CT groups. Failures related mainly to vein bleeding (n = 2 in the ST group) and thrombosis (n = 1 in the ST group; n = 2 in the CT group). Total ischemia time was longer in the ST group (122 ± 25 min in ST group vs. 83 ± 10 min in CT group, mean ± SD), due to prolonged warm ischemia time (60 ± 12 min in the ST group vs. 21 ± 5 min in the CT group, mean ± SD), reflecting the time required to complete the vein ST procedure. The prolonged warm ischemia time resulted in significantly higher vascular inflammation in syngeneic grafts (2.3 ± 1.2 ST group vs. 0 in the CT group, mean ± SD) and in increased severity of ischemia/reperfusion injury and acute graft rejection (3.6 ± 0.4 in the ST group vs. 2.6 ± 0.4 in the CT group, mean ± SD) in allogeneic lung transplants., Conclusions: The vein ST technique is a more time-consuming procedure than the CT method and the prolonged anastomosis time has a deleterious impact on transplant outcomes. These findings suggest that warm ischemia time - one of the modifiable transplant factors - should be considered a major risk factor in lung transplantation, particularly in the setting of donation after cardiac death., (© 2019 S. Karger AG, Basel.)

Introduction: Extracorporeal membrane oxygenation (ECMO) is considered a reliable technique in lung transplantation requiring cardiorespiratory support. However, the impact of this technology on blood product transfusion rate and outcomes compared to off-pump lung transplantation has been rarely investigated., Methods: Between January 2012 and June 2015, 52 elective adult lung transplants were performed at our institution. Of these, 15 recipients required intraoperative venoarterial extracorporeal support and 37 did not. We compared blood product consumption and other outcome variables between the 2 groups., Results: We found comparable in-hospital (86.7% vs 97.3%, P = .14) and 6-month (86.7% vs 91.9%, P = .56) survival between patients with and without extracorporeal support, respectively. Survival at 30 days was lower in the ECMO group (86.7% vs 100%, P = .02). Although patients who underwent ECMO received more intraoperative transfusions, postoperative transfusion rate was similar between the 2 groups. The ECMO group experienced longer mechanical ventilation (median 3 vs 2 days, P = .02) and intensive care unit stay (median 7 vs 5 days, P = .02), besides more cardiogenic shock and deep vein thrombosis. However, we observed no difference in other major and minor in-hospital complications and 6-month complications., Conclusions: In our experience, despite the higher need for intraoperative transfusions, lung transplantation performed with ECMO support is comparable to the off-pump procedure as to short-term survival and outcomes.

Background: Severe primary graft dysfunction (PGD) of grade 3 (PGD3) is a common serious complication following lung transplantation. We aimed to assess physiological donor lung preservation using the Organ Care System (OCS) Lung device compared with cold static storage., Methods: In this non-inferiority, randomised, controlled, open-label, phase 3 trial (INSPIRE) recipients were aged 18 years or older and were registered as standard criteria primary double lung transplant candidates. Eligible donors were younger than 65 years old with a ratio of partial pressure of oxygen in arterial blood to the fraction of inspired oxygen of more than 300 mm Hg. Transplant recipients were randomly assigned (1:1) with permuted blocks, stratified by centre, to receive standard criteria donor lungs preserved in the OCS Lung device (OCS arm) or cold storage at 4°C (control arm). The composite primary effectiveness endpoint was absence of PGD3 within the first 72 h after transplant and 30-day survival in the per-protocol population, with a stringent 4% non-inferiority margin. Superiority was tested upon meeting non-inferiority. The primary safety endpoint was the mean number of lung graft-related serious adverse events within 30 days of transplant. We did analyses in the per-protocol and intention-to-treat populations. This trial is registered with ClinicalTrials.gov, number NCT01630434., Findings: Between Nov 17, 2011, and Nov 24, 2014, we randomly assigned 370 patients, and 320 (86%) underwent transplantation (n=151 OCS and n=169 control); follow-up was completed in Nov 24, 2016. The primary endpoint was met in 112 (79·4%) of 141 patients (95% CI 71·8 to 85·8) in the OCS group compared with 116 (70·3%) of 165 patients (62·7 to 77·2) in the control group (non-inferiority point estimate -9·1%; 95% CI -∞ to -1·0; p=0·0038; and superiority test p=0·068). Patient survival at day 30 post-transplant was 135 (95·7%) of 141 patients (95% CI 91·0-98·4) in the OCS group and 165 patients (100%; 97·8-100·0) in the control group (p=0·0090) and at 12 months was 126 (89·4%) of 141 patients (83·1-93·9) for the OCS group compared with 146 (88·1%) of 165 patients (81·8-92·8) for the control group. Incidence of PGD3 within 72 h was reported in 25 (17·7%) of 141 patients in the OCS group (95% CI 11·8 to 25·1) and 49 (29·7%) of 165 patients in the control group (22·8 to 37·3; superiority test p=0·015). The primary safety endpoint was met (0·23 lung graft-related serious adverse events in the OCS group compared with 0·28 events in the control group [point estimate -0·045%; 95% CI -∞ to 0·047; non-inferiority test p=0·020]). In the intention-to-treat population, causes of death at 30 days and in hospital were lung graft failure or lung infection (n=2 for OCS vs n=7 for control), cardiac causes (n=4 vs n=1), vascular or stroke (n=3 vs n=0), metabolic coma (n=0 vs n=2), and generalised sepsis (n=0 vs n=1)., Interpretation: The INSPIRE trial met its primary effectiveness and safety endpoints. Although no short-term survival benefit was reported, further research is needed to see whether the reduced incidence of PGD3 within 72 h of a transplant might translate into earlier recovery and improved long-term outcomes after lung transplantation., Funding: TransMedics Inc., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In rapidly deteriorating patients awaiting lung transplantation (LT), supportive strategies are only temporary and urgent lung transplant (ULT) remains the last option. The few publications on this topic report conflicting results. According to the Italian national program, patients on mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) may be included in urgent list. We reviewed our experience from January 2012 to December 2014 with ULT and elective lung transplantation (ELT), focusing on outcomes. In the study period, 16 patients received ULT, while 51 received ELT. Among ULT, 1 patient (5.8%) died in waiting list (WL) while 16 patients underwent LT with a median WL time of 6 days. ELT WL mortality was 13.5%, and median WL time 368 days. In-hospital mortality was lower in ELT group (5.8% vs 37.5%, P < .01), while the other postoperative outcomes were not significantly different. For ULT patients, the highest impact risk factors for in-hospital mortality were pretransplant plasma transfusion, recipient Pseudomonas aeruginosa colonization, and high level of reactive C-protein and lactic acid. A ULT program with an accurate recipient selection allows earlier transplantation, reducing WL mortality, with acceptable outcomes, although with a higher in-hospital mortality. Larger studies are needed to validate our results., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Solid-organ transplant recipients are at high risk of developing malignancies. A greater risk of Kaposi sarcoma has been reported in lung recipients in our country, particularly in those from Southern Italy, probably due to the high prevalence of Human herpes virus 8 infection. Kaposi sarcoma affecting only the lung allograft is extremely rare. We describe a case of a lung recipient who developed Kaposi sarcoma only in the graft, 22 months after transplant. The patient, a 65-year-old man from Southern Italy, underwent bilateral lung transplant for idiopathic pulmonary fibrosis in January 2009. He developed mild/moderate acute cellular rejection (≥A2) in 4 of 6 scheduled transbronchial biopsies thus was treated with increased immunosuppressive therapy, shifting from cyclosporine to tacrolimus and mycophenolate mofetil. In July 2010, a high-resolution computed tomography scan showed small bilateral lung nodules, despite a generally good condition. After 2 months, his condition worsened with a severe weight loss. A positron emission tomography scan showed mild metabolic activity in the lesions with no other localizations. In October 2010, a lung biopsy was performed, with results showing typical histologic and immunohistochemical features of Kaposi sarcoma. Molecular tissue evaluations and serologic analyses were positive for Human herpes virus 8. The patient's immunosuppressive therapy was suspended, and he started liposomal doxorubicin treatment; however, after the first cycle, he developed severe respiratory dysfunction. The patient died 27 months after lung transplant for neoplasm. Our report highlights the importance of considering Kaposi sarcoma in the differential diagnosis for lung nodules in lung transplant recipients, even in the absence of any initial specific symptom or cutaneous lesion.

Background: Lung transplantation (LTx) is limited by the shortage of suitable donors. To overcome this problem, many programs have begun to use donors with extended criteria (marginal donors). However, brain-dead patients with implanted mechanical circulatory support system have rarely been considered as potential lung donors. This case demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system despite the possible difficulties of lung retrieval., Case Presentation: Our case presents a successful procurement and bilateral lung transplantation from a donor supported by a left ventricular assist device (LVAD) who experienced an intraoperatively haemodynamic complication. The use of portable normothermic perfusion device let us to reduce ischemic injury and assess these marginal donor lungs helping us to determine the clinical suitability for transplantation. Given our extensive experience with the device instrumentation and management, the EVLP process was uneventful with excellent post-transplant course., Conclusions: This case report demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system using the portable normothermic perfusion platform to assess and preserve these donor lungs.

Background: Primary graft dysfunction (PGD) is the major cause of early morbidity and mortality after transplantation. A high rate of PGD is a frequent complication in orthotopic lung transplantation (OLT) models, which are currently used to investigate acute and chronic rejection pathways. Hypoxia-inducible factor (HIF)-1α is a heterodimeric αβ transcription factor that mediates tissue response to hypoxia. In other solid organ transplantations, a significant correlation between HIF-1α expression and PGD was detected. To our knowledge no data are available on HIF-1α expression in PGD developing in lung transplantation. The aims of this study were to investigate HIF-1α expression (using immunohistochemistry) and correlate it to the main histological parameters related to ischemia-reperfusion (IR) injury, including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) -positive apoptotic cells)., Methods: OLT was performed in 32 inbred rat strains and 11 of them died in the early postoperative period (from day 0-3) for IR injury. The histological and molecular evaluations were done in all lung tissues. Unimplanted donor rat lungs were used as controls. HIF-1α expression was correlated with all morphological parameters., Results: Lung samples of animals with IR injury showed high scores of HIF-1α expression, edema, blood extravasation, granulocyte margination, apoptotic index, and necrosis in 91% of cases. Tissue overexpression of HIF-1α was detected in all lung samples with high scores of histological parameters and with high apoptotic indexes., Conclusion: Our data demonstrate that HIF-1α was overexpressed in more severe rat lung IR injury. The use of HIF-1α inhibitors could provide a translatable route into manipulating this complex system in vivo., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cytomegalovirus (CMV) infection negatively influences both short- and long-term outcomes after cardiothoracic transplantation. In heart transplantation, registry analyses have shown that CMV immunoglobulin (CMVIG) with or without virostatic prophylaxis is associated with a significant reduction in mortality and graft loss versus no prophylaxis, particularly in high-risk donor (D)+/recipient (R)- transplants. Randomized comparative trials are lacking but retrospective data suggest that addition of CMVIG to antiviral prophylaxis may reduce rates of CMV-related events after heart transplantation, including the incidence of acute rejection or chronic allograft vasculopathy. However, available data consistently indicate that when CMVIG is used, it should be administered with concomitant antiviral therapy, and that evidence concerning preemptive management with CMVIG is limited, but promising. In lung transplantation, CMVIG should again only be used with concomitant antiviral therapy. Retrospective studies have shown convincing evidence that addition of CMVIG to antiviral prophylaxis lowers CMV endpoints and mortality. The current balance of evidence suggests that CMVIG prophylaxis reduces the risk of bronchiolitis obliterans syndrome, but a controlled trial is awaited. Overall, the relatively limited current data set suggests that prophylaxis with CMVIG in combination with antiviral therapy appears effective in D+/R- heart transplant patients, whereas in lung transplantation, addition of CMVIG in recipients of a CMV-positive graft may offer an advantage in terms of CMV infection and disease.

BACKGROUND Acute cellular rejection (ACR) affects up to 40% of recipients within the first year after lung transplant (LTx). The aim of this study was to determine the frequency of ACR and associated major risk factors in cystic fibrosis (CF) recipients. Bronchiolitis obliterans syndrome (BOS) and 1-year/long-term survival were also evaluated. MATERIAL AND METHODS ACR was reviewed in 643 scheduled biopsies from 44 CF (Group 1) versus 89 other recipients (Group 2). We performed univariate/multivariate analyses of risk factors for ACR and BOS, and survival analysis. RESULTS Group 1 showed higher ACR frequency, especially for ACR ≥ A2. Multivariable generalized linear models considering both native lung disease and age showed that higher values of ACR index were significantly related to the pretransplant diagnosis of CF. BOS and long-term survival were not influenced by the increased incidence of ACR. Poorer long-term survival was observed in Group 2. CONCLUSIONS CF recipients have a higher ACR risk, which may be due to enhanced immune activation related to a genetic disorder, and younger age.

Objectives: Lung transplantation (LTx) is the only effective treatment for end-stage lung disease. In rapidly deteriorating patients awaiting transplant, supportive strategies for lung function allow only a short period of support and lung transplantation remains the definitive therapy. An urgent transplant programme may reduce the waiting time, allowing lung transplantation in these patients., Methods: Since November 2010 a nation-wide urgent lung transplant programme has been established in Italy and patients on the waiting list dependent on mechanical ventilation and/or extracorporeal lung support (ECLS) can be transplanted on an emergency basis with the first available graft in the country. Results of the first 14 months of this programme are analysed here., Results: From November 2010 to December 2011, 28 patients (14 males, mean age 33.6 ± 14.4 years) were considered for urgent LTx. Rapidly deteriorating lung function was supported with mechanical ventilation alone in 4 patients (14.3%), ECLS in 13 patients (46.4%) and mechanical ventilation plus ECLS in the remaining 11 patients (39.3%). Three patients (10.7%) were excluded because of worsening conditions, 3 patients (10.7%) while on the urgent listed and 22 patients (78.6%) underwent transplantation after 9.8 ± 6.2 days of being on the urgent list. The 30-day mortality rate after LTx was 18%, and the 1-year survival rate was 71.4%., Conclusions: The urgent lung transplant programme allowed transplantation in a significant percentage of prioritized patients with acceptable 30-day and 1-year mortality rates. An accurate selection of recipients may further improve the clinical impact of this programme, reducing the ethical concerns about transplantation in high-risk patients., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Noninvasive positive-pressure ventilation (NIV), which represents a consolidated treatment of both acute and chronic respiratory failure, is increasingly being used to maintain spontaneous ventilation in lung transplant patients with impending pulmonary complications. Adding a noninvasive inspiratory support plus positive end-expiratory pressure (PEEP) has proven to be useful in preventing endotracheal mechanical ventilation, airway injury, and infections. Lung recipients with closure of the small airways in the dependent regions may also benefit from the prone position, which is helpful to promote recruitment of nonaerated alveoli and faster healing of consolidated atelectatic areas. In patients with localized or diffuse lung infiltrates, high-frequency percussive ventilation (HFPV), by either an invasive airway or a facial mask, has been adopted as an alternative ventilatory mode to enhance airway opening, limit potential respirator-associated lung injury, and improve mucus clearance. In nonintubated lung recipients at risk for volubarotrauma with conventional mechanical ventilation, it allows oxygen diffusion into the distal airways at lower mean airway pressures while avoiding repetitive cyclical opening and closing of the terminal airways. We summarize the clinical course of 3 patients with post-lung transplantation respiratory complications who were noninvasively ventilated with HFPV in the prone position. Major advantages of this treatment included gradual improvement of spontaneous clearance of bronchial secretions, significant attenuation of graft infiltrates and consolidations, a reduction in the number of bronchoscopies required, a decrease in spontaneous respiratory rate and work of breathing, and a significant improvement in gas exchange. The patients found HFPV with either standard facial mask or total mask interface to be comfortable or only mildly uncomfortable, and after the sessions they felt more restored. HFPV by facial mask in the prone position may be an interesting and attractive alternative to standard NIV, one that is more useful when implemented before full-blown respiratory failure is established., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Despite the common use of tracheostomy in lung transplant (LT) patients, little data exist regarding the indications, timing, periprocedural complications, and impact on outcomes of the procedure., Methods: We retrospectively analyzed some characteristics and timing of all tracheostomies performed in our lung transplant recipients during a 5-year period., Results: Between January 2004 and November 2009, 31 of 126 lung transplant patients (24.6%) underwent a tracheostomy. They included 14 men with a mean age of 42 years (range, 10 to 61 years) and 17 women with a mean age of 45 years (range, 10 to 64 years). Twenty eight patients undergoing a tracheostomy had a prior bilateral sequential LT and 4 had accepted a single lung. Tracheostomy was surgically performed (ST) in 6 of 31 patients (19.3%); percutaneous tracheostomy (PT) techniques were applied for the other 25 (80.6%) cases. The decision to perform a tracheostomy was made within 4 days from LT in 21 of 31 patients (67.7%), within 8 days in 6 (19.3%) and after 10 days for the other 4 (12.9%) cases. There were no major complications during the PT procedures; no conversion to ST, no loss of airway, no paratracheal insertion, and no accidental tracheal extubation. No pneumothorax, pneumomediastinum, hypotension, hypoxemia, or arrythmyas were recorded in the early post-procedural period. The mean post-LT duration of cannulation was 17 days (range, 5 to 72 days)., Discussion: An early tracheostomy may be of considerable benefit for the debilitated patient who will likely require prolonged mechanical ventilation because of a complicated intraoperative course and poor recovery of graft function. PT was performed more quickly and was associated with fewer postoperative complications than ST. We recommend an aggressive strategy in the immediate posttransplant period when extubation fails or is delayed for various reasons., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We report the case of an 18-year-old male who underwent bilateral lung transplantation for end-stage cystic fibrosis. No Epstein-Barr virus (EBV) or cytomegalovirus serology mismatch was detected on pre-transplant evaluation (donor and recipient were both positive). Two months after lung transplantation a computed tomography scan showed multiple nodules throughout both lungs. At that time a low EBV DNA blood level was detected (<300 copies/100,000 lymphomonocytes). Scheduled follow-up transbronchial biopsy (TBB) revealed a prevalent finding characterized by perivascular lymphoid infiltrates with endothelitis. Extensive tissue coagulative necrosis with peripheral areas of dense aggregates of larger lymphoid cells were detected in the trans-thoracic fine needle core biopsy (FNCB) performed on the largest nodule. The immunophenotypic profile characterized the perivascular lymphoid cells in TBB as mainly composed of T lymphocytes (CD3 positive) while the larger number of lymphocytes in FNCB as B cells (CD20 positive). In situ hybridization for EBV (EBER mRNA) was negative in TBB while it was positive in many lymphocytes of the FNCB. Real-time polymerase chain reaction (PCR) for EBV was performed on paraffin-embedded FNCB and detected a high quantity of EBV genomes (1260 copies/cell). IgH gene rearrangement using a fragment size PCR technique revealed a monoclonal B-cell population in FNCB. Morphological and molecular findings suggest a final diagnosis of acute cellular rejection and a post-transplant lymphoproliferative disorder (PTLD) EBV-related in a lung transplant recipient with a low EBV DNA blood level. A possible coexistence of PTLD and acute rejection should be considered both for diagnosis and treatment. EBV PCR in the peripheral blood is a useful screening tool in transplant recipients; however, rare cases with PTLD may not have detectable levels of EBV DNA. This aspect should be taken into consideration to avoid false negatives.

Background: The donor organs available for lung transplantation remain far fewer than the number of recipients. Therefore, it is of primary importance to optimize this resource, especially by carefully selecting potential recipients. The diagnosis of end-stage diseases referred for transplantation is mainly based on clinical/radiologic assessment and rarely on histology., Methods: A clinicopathologic study was performed on 175 patients who underwent lung transplantation over a 12-year period (1995 to 2007). Diagnoses on native lungs were compared with referral diagnoses to assess the presence of discrepancies. In particular, major discrepancies included complete mismatch between referral and pathologic diagnoses and other additional findings likely to affect patient management., Results: Major discrepancies were found in 18 of 175 cases (10%). The highest percentage of discordance was found in diffuse parenchymal lung diseases, more frequently idiopathic pulmonary fibrosis (IPF). In the majority of IPF and other non-IPF idiopathic forms, there was often an imprecise nosographic definition of the diseases. Unsuspected additional findings included Aspergillus and mycobacterial infections, carcinomas and carcinoids. Short-term survival is significantly lower in patients with discrepancies than in those without., Conclusions: On the basis of the high rate and importance of discrepancies, more accurate and repeated clinicopathologic investigations should be planned in the waiting list period.

Temporary graft dysfunction with gas exchange abnormalities is a common finding during the postoperative course of a lung transplant and is often determined by the post-reimplantation syndrome. Supportive measures including oxygen by mask, inotropes, diuretics, and pulmonary vasodilators are usually effective in non-severe post-reimplantation syndromes. However, in less-responsive clinical pictures, tracheal intubation with positive pressure ventilation, or non-invasive positive pressure ventilation (NIV), is necessary. We report on the clinical course of two patients suffering from refractory hypoxemia due to post-reimplantation syndrome treated with NIV in the prone and Trendelenburg positions. NIV was well tolerated and led to resolution of atelectactic areas and dishomogeneous lung infiltrates. Repeated turning from supine to prone under non invasive ventilation determined a stable improvement of gas exchange and prevented a more invasive approach. Even though NIV in the prone position has not yet entered into clinical practice, it could be an interesting option to achieve a better match between ventilation and perfusion. This technique, which we successfully applied in lung transplantation, can be easily extended to other lung diseases with non-recruitable dorso-basal areas.

Noninvasive positive pressure ventilation (NIPPV), which provides consolidated treatment of both acute and chronic respiratory failure, is increasingly being used in the postoperative care of lung transplant patients. Graft- and patient-related respiratory insufficiency requiring mechanical ventilation are common features in the postoperative period; they may persist for hours to days. Prolonged intubation, particularly in these immunocompromised patients, has been considered one of the main predisposing factors for developing nosocomial pneumonia. It has been associated with increased length of intensive care unit (ICU) stay as well. Noninvasive mechanical ventilation is nowadays an attractive choice to shorten weaning time and avoid reintubation following lung transplantation. Rapid extubation plus prompt NIPPV application is a useful strategy for lung recipients who do not completely fulfill the criteria for safe extubation. Unloading respiratory muscles, decreasing respiratory rate and sensation of dyspnea, improving ventilation/perfusion abnormalities, decreasing the heart rate, and improving hemodynamics are among the recognized benefits. Adding a noninvasive inspiratory support plus positive end-expiratory pressure (PEEP) to lung transplant recipients has been helpful to prevent airway injury and infections, avoiding the need for reintubation in cases of extubation failure, facilitating nocturnal sedation, treating the post-reimplantation syndrome and postoperative phrenic nerve dysfunction, and preventing reintubation in cases of readmission to the ICU. In our practice, the helmet system has emerged as the preferred interface; in cases of dyshomogeneous dorsobasal lung infiltrates, it allows effective ventilatory support in the prone position as well.

In this report we present a successful clamshell approach for lung harvest, with subsequent two single lung transplantations in two different patients, from a donor who had previous median sternotomy for aortic valve substitution.

Background: Lung transplantation has been accepted widely as therapy for end-stage pulmonary lymphangioleiomyomatosis (LAM); however, single-center and national experience is limited due to the rarity of LAM., Methods: We report the recent European experience of lung transplantation for LAM. A self-administered questionnaire was distributed to 30 European lung transplant centers to evaluate patients who underwent primary lung transplantation for LAM (1997 to 2007)., Results: Seventy percent of centers responded to the questionnaire. A total of 61 lung transplants were undertaken in women only, with mean age at transplant 41.3 years (SD 5.1). Centers performed a median of 2 (0 to 9) transplant operations. Severe pleural adhesions were the most common intra-operative complication. Early deaths (N = 6) were due to primary graft or multiple-organ failure or sepsis. Twelve recipients were diagnosed with bronchiolitis obliterans syndrome at a median of 20 months (range 10 to 86 months) post-transplant. LAM-related complications included renal angiomyolipoma and pneumothorax in the native lung. Recurrence of LAM occurred in 4 recipients. As of December 2007, actuarial Kaplan-Meier survival was 79% at 1 year and 73% at 3 years post-transplant., Conclusions: Post-transplant outcome for pulmonary LAM in the recent era appears to have improved compared with the previous era. LAM-related complications remain common, but recurrence of LAM in the allograft is rare.

Emphysema is a major cause of morbidity and mortality worldwide. Despite optimal medical therapy, smoking cessation, and pulmonary rehabilitation, a large number of patients remain symptomatic with a poor quality of life. A pool of patients with end-stage disease can benefit from surgical treatments like bullectomy, lung volume reduction, or lung transplantation. Emphysema represents the most common indication leading to lung transplantation. A functional improvement and better quality of life are clear benefits deriving from lung transplantation, while a survival advantage has not yet been proven.

Lung transplantation has become a consolidated treatment for patients with severe pulmonary hypertension (PH). Several difficulties are encountered during the procedure in such candidates, who are still recognized as more severely affected by perioperative morbility and mortality than those undergoing lung transplantation for other diseases. Right ventricular (RV) enlargement with tricuspid regurgitation, small left ventricle (LV) with an asymmetric hypetrophic wall, interventricular septal shift toward the left, with ventricular stiffness and diastolic incompetence, are typical preoperative echocardiographic findings of end-stage PH. A smooth induction and tracheal intubation will help prevent hypertensive crisis in highly susceptible candidates. Uncompensated vasodilatation or myocardial depression caused by anesthetics and mechanical ventilation may be responsible for acute RV dysfunction associated with low systemic blood pressure. Resuscitation and emergency adoption of cardiopulmonary by-pass (CPB) has been described for near-fatal anesthesia induction. Cardiovascular instability can develop after institution of one-lung ventilation and pulmonary artery clamping. An acute increase in pulmonary pressure results in a decrease in RV ejection fraction and then in acute RV failure. Interdependence of the right and left ventricles occurs such that RV function can alter LV function. Early detection of impending circulatory and/or respiratory deterioration is warranted to prevent an irreversible decline in cardiac output, resulting in hazardous cardiac arrest. Inhaled nitric oxide represents the first choice for treatment of PH and RV failure associated with systemic hypotension during lung transplantation. Intraoperative situations requiring CPB must be identified before development of systemic shock, which represents a late ominous sign of RV failure.

Background: Bronchial stenoses are still a frequent complication after lung transplantation. The stenosis usually involves the anastomotic site, but rarely a distal site. The first choice treatment is an endoscopic balloon dilatation, laser ablation, and stenting. Unrelenting strictures may require an open surgical approach., Materials and Methods: Between 1995 and 2006, 154 patients underwent lung transplantation, including 134 who survived the perioperative period and were followed to evaluate the incidence of bronchial stenosis. Among 219 anastomoses at risk, 13 (5.9%) stenoses occurred in 11 patients. Conservative endoscopic management was effective for eight patients, but a surgical approach was necessary for three patients with segmental distal stenosis., Results: One patient received a lower sleeve bilobectomy; one patient, wedge bronchoplasty of the bronchus intermedius; and another patient, an isolated sleeve resection of the bronchus intermedius. All patients had good outcomes with resolution of stenosis., Conclusions: Although rare, the surgical approach for bronchial strictures after lung transplantation is a good option. Parenchyma-sparing techniques are feasible and effective.