Search

Background: Lower airway enrichment with oral commensals has been previously associated with severe primary graft dysfunction (PGD) after lung transplantation (LT). We aimed to determine whether this dysbiotic signature is present across all PGD severity grades and whether it is associated with a distinct host inflammatory endotype., Methods: Lower airway samples from 96 LT recipients were used to evaluate the lung allograft microbiota via 16S rRNA gene sequencing. Bronchoalveolar lavage (BAL) cytokine concentrations and cell differential percentages were compared across PGD grades. In a subset of samples, we evaluated the lower airway host transcriptome using RNA sequencing methods., Results: Differential analyses demonstrated lower airway enrichment with supraglottic-predominant taxa (SPT) in moderate and severe PGD. Dirichlet multinomial mixtures modeling identified 2 distinct microbial clusters. A greater percentage of subjects with moderate-severe PGD than no PGD were identified within the dysbiotic cluster (C-SPT, 48% and 29%, respectively) though this did not reach statistical significance (p = 0.06). PGD severity associated with increased BAL neutrophil concentration (p = 0.03) and correlated with BAL concentrations of MCP-1/CCL2, IP-10/CXCL10, IL-10, and TNF-α (p < 0.05). Furthermore, signatures of dysbiosis correlated with neutrophils, MCP-1/CCL-2, IL-10, and TNF-α (p < 0.05). C-SPT exhibited differential expression of TNF, SERPINE1, MPO, and MMP1 genes and upregulation of MAPK pathways, host signling associated with neutrophilic inflammation., Conclusions: Lower airway dysbiosis within the lung allograft is associated with a neutrophilic inflammatory endotype, an immune profile commonly recognized as the hallmark for PGD. These data highlight a putative role of lower airway microbial dysbiosis in the pathogenesis of this syndrome., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Competing Interests: Disclosures None.

Background: The effect of prolonged allograft ischemic time on lung transplant outcomes remains controversial, with most studies associating it with increased mortality, but this effect is partly mitigated by center volume. This study sought to evaluate the mechanism of these findings and clarify the impact of ischemic time on short-term outcomes in a national sample., Methods: Data on lung transplants (January 2010-Janary 2017) were extracted from the Scientific Registry of Transplant Recipients database. Ischemic time was dichotomized as prolonged ischemic time (PIT) or no PIT (N-PIT) at 6 hours. High-volume centers were defined as the top quintile. The primary outcome was 30-day, 1-year, and 3-year mortality; secondary outcomes included in-hospital complications and 72-hour oxygenation., Results: Among 11,809 records, there were significant differences between PIT and N-PIT recipients by demographics, lung allocation score, and donor organ metrics. In a 1:1 propensity score-matched cohort (n = 6422), PIT recipients had reduced survival compared with N-PIT at 3 years (66.5% vs 68.8%, P = .031). On multivariable analysis, this effect persisted among low-volume but not high-volume centers. PIT recipients were more likely to require reintubation, prolonged (>5 days) mechanical ventilation, hemodialysis, longer stay, and acute rejection (all P < .01). Except for reintubation, these disparities were present at both high- and low-volume centers independently. Ischemic time had no effect on 72-hour oxygenation., Conclusions: PIT remains associated with higher rates of postoperative complications and reduced short-term survival. While center volume ameliorated the survival impact, this was not achieved by reducing postoperative complications. Further research is warranted before broadening ischemic time thresholds among low-volume centers., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Lung transplantation is the only potentially curative treatment for end-stage lung failure and successfully improves both long-term survival and quality of life. However, lung transplantation is limited by the shortage of suitable donor lungs. This discrepancy in organ supply and demand has prompted researchers to seek alternative therapies for end-stage lung failure. Tissue engineering (bioengineering) organs has become an attractive and promising avenue of research, allowing for the customized production of organs on demand, with potentially perfect biocompatibility. While breakthroughs in tissue engineering have shown feasibility in practice, they have also uncovered challenges in solid organ applications due to the need not only for structural support, but also vascular membrane integrity and gas exchange. This requires a complex engineered interaction of multiple cell types in precise anatomical locations. In this article, we discuss the process of creating bioengineered lungs and the challenges inherent therein. We summarize the relevant literature for selecting appropriate lung scaffolds, creating decellularization protocols, and using bioreactors. The development of completely artificial lung substitutes will also be reviewed. Lastly, we describe the state of current research, as well as future studies required for bioengineered lungs to become a realistic therapeutic modality for end-stage lung disease. Applications of bioengineering may allow for earlier intervention in end-stage lung disease and have the potential to not only halt organ failure, but also significantly reverse disease progression., 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., (© 2023 Hsiung, James, Chang, Geraci, Angel and Chan.)

Rates of lung donation have increased over the past several years. This has been accomplished through the utilization of donors with extended criteria, the creation of donor hospitals or centers, and the optimization of lungs through the implementation of donor management protocols. These measures have resulted in augmenting the pool of available donors thereby decreasing the wait time for lung transplantation candidates. Although transplant programs vary significantly in their acceptance rates of these organs, studies have not shown any difference in the incidence of primary graft dysfunction or overall mortality for the recipient when higher match-run sequence organs are accepted. Yet, the level of comfort in accepting these donors varies among transplant programs. This deviation in practice results in these organs going to lower-priority candidates thereby increasing the waitlist time of other recipients and ultimately has a deleterious effect on an institution's waitlist mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Xenotransplantation promises to alleviate the issue of donor organ shortages and to decrease waiting times for transplantation. Recent advances in genetic engineering have allowed for the creation of pigs with up to 16 genetic modifications. Several combinations of genetic modifications have been associated with extended graft survival and life-supporting function in experimental heart and kidney xenotransplants. Lung xenotransplantation carries specific challenges related to the large surface area of the lung vascular bed, its innate immune system's intrinsic hyperreactivity to perceived 'danger', and its anatomic vulnerability to airway flooding after even localized loss of alveolocapillary barrier function. This article discusses the current status of lung xenotransplantation, and challenges related to immunology, physiology, anatomy, and infection. Tissue engineering as a feasible alternative to develop a viable lung replacement solution is discussed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Little is known about the effects of hepatitis C viremia on immunologic outcomes in the era of direct-acting antivirals. We conducted a prospective, single-arm trial of lung transplantation from hepatitis C-infected donors into hepatitis C-naïve recipients (n = 21). Recipients were initiated on glecaprevir-pibrentasvir immediately post-transplant and were continued on therapy for a total of 8 weeks. A control group of recipients of hepatitis C-negative lungs were matched 1:1 on baseline variables (n = 21). The primary outcome was the frequency of acute cellular rejection over 1-year post-transplant. Treatment with glecaprevir-pibrentasvir was well tolerated and resulted in viremia clearance after a median of 16 days of therapy (IQR 10-24 days). At one year, there was no difference in incidence of acute cellular rejection (71.4% vs. 85.7%, P = .17) or rejection requiring treatment (33.3% vs. 57.1%, P = .12). Mean cumulative acute rejection scores were similar between groups (.46 [SD ± .53] vs. .52 [SD ± .37], P = .67). Receipt of HCV+ organs was not associated with acute rejection on unadjusted Cox regression analysis (HR .55, 95% CI .28-1.11, P = .09), or when adjusted for risk factors known to be associated with acute rejection (HR .57, 95% CI .27-1.21, P = .14). Utilization of hepatitis C infected lungs with immediate treatment leads to equivalent immunologic outcomes at 1 year., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Opioid analgesics are commonly used post-lung transplant, but have many side effects and are associated with worse outcomes. We conducted a retrospective review of all lung transplant recipients who were treated with a multimodal opioid-sparing pain protocol. The use of liposomal bupivacaine intercostal nerve block was variable due to hospital restrictions. The primary objective was to describe opioid requirements and patient-reported pain scores early post-lung transplant and to assess the impact of intraoperative liposomal bupivacaine intercostal nerve block. We treated 64 lung transplant recipients with our protocol. Opioid utilization decreased to a mean of 43 milligram oral morphine equivalents by postoperative day 4. Median pain scores peaked at 4 on postoperative day 1 and decreased thereafter. Only three patients were discharged home with opioids, all of whom were taking opioid agonist therapy pre-transplant for opioid use disorder. Patients who received liposomal bupivacaine intercostal nerve block in the operating room had a significant reduction in opioid consumption over postoperative day 1 through 4 (228 mg vs. 517 mg, P= .032). A multimodal opioid-sparing pain management protocol is feasible and resulted in weaning of opioids prior to hospital discharge., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: Disclosure: There is no conflict of interest or other disclosures.

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays., Methods: At our institution, 2 strategies for providing DAA therapy to HCV - recipients of HCV + transplants have been used. For thoracic organ recipients, an institution-subsidized course of initial therapy was provided to ensure an early treatment initiation date. For abdominal organ recipients, insurance approval for DAA coverage was sought once viremia developed, and treatment was initiated only once the insurance-authorized supply of drug was received. To evaluate the clinical impact of these 2 strategies, we retrospectively collected data pertaining to the timing of DAA initiation, duration of recipient viremia, and monetary costs incurred by patients and the institution for patients managed under these 2 DAA coverage strategies., Results: One hundred fifty-two transplants were performed using HCV viremic donor organs. Eighty-nine patients received DAA treatment without subsidy, and 62 received DAA treatment with subsidy. One patient who never developed viremia posttransplant received no treatment. Subsidizing the initial course enabled earlier treatment initiation (median, 4 d [interquartile range (IQR), 2-7] vs 10 [IQR, 8-13]; P  < 0.001) and shorter duration of viremia (median, 16 d [IQR, 12-29] vs 36 [IQR, 30-47]; P  < 0.001). Institutional costs averaged $9173 per subsidized patient and $168 per nonsubsidized patient. Three needlestick exposures occurred in caregivers of viremic patients., Conclusions: Recipients and their caregivers stand to benefit from earlier DAA treatment initiation; however, institutional costs to subsidize DAA therapy before insurance authorization are substantial. Insurance authorization processes for DAAs should be revised to accommodate this unique patient group., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Objectives: To assess the impact of percutaneous dilational tracheostomy in coronavirus disease 2019 patients requiring mechanical ventilation and the risk for healthcare providers., Design: Prospective cohort study; patients were enrolled between March 11, and April 29, 2020. The date of final follow-up was July 30, 2020. We used a propensity score matching approach to compare outcomes. Study outcomes were formulated before data collection and analysis., Setting: Critical care units at two large metropolitan hospitals in New York City., Patients: Five-hundred forty-one patients with confirmed severe coronavirus disease 2019 respiratory failure requiring mechanical ventilation., Interventions: Bedside percutaneous dilational tracheostomy with modified visualization and ventilation., Measurements and Main Results: Required time for discontinuation off mechanical ventilation, total length of hospitalization, and overall patient survival. Of the 541 patients, 394 patients were eligible for a tracheostomy. One-hundred sixteen were early percutaneous dilational tracheostomies with median time of 9 days after initiation of mechanical ventilation (interquartile range, 7-12 d), whereas 89 were late percutaneous dilational tracheostomies with a median time of 19 days after initiation of mechanical ventilation (interquartile range, 16-24 d). Compared with patients with no tracheostomy, patients with an early percutaneous dilational tracheostomy had a higher probability of discontinuation from mechanical ventilation (absolute difference, 30%; p < 0.001; hazard ratio for successful discontinuation, 2.8; 95% CI, 1.34-5.84; p = 0.006) and a lower mortality (absolute difference, 34%, p < 0.001; hazard ratio for death, 0.11; 95% CI, 0.06-0.22; p < 0.001). Compared with patients with late percutaneous dilational tracheostomy, patients with early percutaneous dilational tracheostomy had higher discontinuation rates from mechanical ventilation (absolute difference 7%; p < 0.35; hazard ratio for successful discontinuation, 1.53; 95% CI, 1.01-2.3; p = 0.04) and had a shorter median duration of mechanical ventilation in survivors (absolute difference, -15 d; p < 0.001). None of the healthcare providers who performed all the percutaneous dilational tracheostomies procedures had clinical symptoms or any positive laboratory test for severe acute respiratory syndrome coronavirus 2 infection., Conclusions: In coronavirus disease 2019 patients on mechanical ventilation, an early modified percutaneous dilational tracheostomy was safe for patients and healthcare providers and associated with improved clinical outcomes., Competing Interests: Dr. Kon received funding from Abiomed/Breethe and Medtronic. Dr. Cerfolio received funding from Intuitive Surgical and Expert Testimony. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The lung allocation score (LAS) was designed to optimize the use of pulmonary allografts based on anticipated pretransplant survival and posttransplant outcome. Hospital admission status, not included in the LAS, has not been comprehensively investigated with regard to organ allocation. The objective of this study was to determine whether pretransplant hospital admission status was independently associated with posttransplant mortality and whether high center volume was associated with improved survival in that cohort., Methods: All consecutive adult lung transplants provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (from 2007 to 2017). Group stratification was performed based on admission status at the time of transplantation. A Cox proportional hazard regression was used to determine independent associations with posttransplant mortality., Results: During the study period, 3747 of 18,416 recipients (20%) were admitted to the hospital at the time of transplantation. Compared with nonadmitted recipients, LAS were significantly higher and waitlist times significantly shorter. Admitted recipients had higher rates of prolonged mechanical ventilation, higher rates of posttransplant dialysis, and longer posttransplant lengths of stay. Pretransplant admission to a low-volume center conferred significantly worse survival compared with nonadmitted patients, and high-volume centers were independently associated with improved survival compared with low-volume centers., Conclusions: Hospital admission status is associated with increased posttransplant mortality independent of the LAS and the factors from which it is calculated. However, adjusted survival analysis demonstrates that admission to a high-volume center appears to be independently associated with improved survival compared with low-volume centers., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) remains a worldwide pandemic with a high mortality rate among patients requiring mechanical ventilation. The limited data that exist regarding the utility of extracorporeal membrane oxygenation (ECMO) in these critically ill patients show poor overall outcomes. This report describes our institutional practice regarding the application and management of ECMO support for patients with COVID-19 and reports promising early outcomes., Methods: All critically ill patients with confirmed COVID-19 evaluated for ECMO support from March 10, 2020, to April 24, 2020, were retrospectively reviewed. Patients were evaluated for ECMO support based on a partial pressure of arterial oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg or pH of less than 7.25 with a partial pressure of arterial carbon dioxide exceeding 60 mm Hg with no life-limiting comorbidities. Patients were cannulated at bedside and were managed with protective lung ventilation, early tracheostomy, bronchoscopies, and proning, as clinically indicated., Results: Among 321 patients intubated for COVID-19, 77 patients (24%) were evaluated for ECMO support, and 27 patients (8.4%) were placed on ECMO. All patients were supported with venovenous ECMO. Current survival is 96.3%, with only 1 death to date in more than 350 days of total ECMO support. Thirteen patients (48.1%) remain on ECMO support, and 13 patients (48.1%) have been successfully decannulated. Seven patients (25.9%) have been discharged from the hospital. Six patients (22.2%) remain in the hospital, of which 4 are on room air. No health care workers who participated in ECMO cannulation developed symptoms of or tested positive for COVID-19., Conclusions: The early outcomes presented here suggest that the judicious use of ECMO support in severe COVID-19 may be clinically beneficial., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Several studies have described improved survival with double lung transplant (DLT) compared with single lung transplant (SLT) in pulmonary fibrosis. To avoid the innate selection bias of including patients exclusively listed for SLT or DLT, this study analyzed those deemed appropriate for either procedure at time of listing., Methods: All consecutive adult lung transplants for idiopathic pulmonary fibrosis provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Isolated lobar transplants (n = 11) or patients listed only for SLT (n = 1834) or DLT (n = 2372) were excluded. Group stratification was based on the ultimate procedure (SLT vs DLT). Group propensity matching was performed based on 24 recipient and donor characteristics. Recipient demographics, donor demographics, and outcomes were compared between groups., Results: During the study period 45% (974/2179) and 55% (1205/2179) of patients ultimately received SLT and DLT, respectively. After propensity matching 466 matched patients remained in each group. SLT patients were less likely to require prolonged (>48 hours) ventilator support than DLT patients. There was also a trend toward reduced rates of posttransplant renal failure and hospital length of stay in SLT recipients. Whether analyzed by time of listing or time of transplant, survival was similar between groups., Conclusions: In recipients concurrently listed for SLT and DLT overall survival was similar regardless of the eventual procedure. These data suggest that the previously purported survival advantage for DLT may purely represent selection bias and should not preclude the use of SLT in appropriately selected idiopathic pulmonary fibrosis patients., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The aims of this work were to evaluate whether the treatment of patients with fibromyalgia with memantine is associated with significant changes in metabolite concentrations in the brain, and to explore any changes in clinical outcome measures. Magnetic resonance spectroscopy was performed of the right anterior and posterior insula, both hippocampi and the posterior cingulate cortex. Questionnaires on pain, anxiety, depression, global function, quality of life and cognitive impairment were used. Ten patients were studied at baseline and after three months of treatment with memantine. Significant increases were observed in the following areas: N-acetylaspartate (4.47 at baseline vs. 4.71 at three months, p  = 0.02) and N-acetylaspartate+N-acetylaspartate glutamate in the left hippocampus (5.89 vs. 5.98; p  = 0.007); N-acetylaspartate+N-acetylaspartate glutamate in the right hippocampus (5.31 vs 5.79; p  = 0.01) and the anterior insula (7.56 vs. 7.70; p  = 0.033); glutamate+glutamine/creatine ratio in the anterior insula (2.03 vs. 2.17; p  = 0.022) and the posterior insula (1.77 vs. 2.00; p  = 0.004); choline/creatine ratio in the posterior cingulate (0.18 vs. 0.19; p  = 0.023); and creatine in the right hippocampus (3.60 vs. 3.85; p  = 0.007). At the three-month follow-up, memantine improved cognitive function assessed by the Cognition Mini-Exam (31.50, SD  = 2.95 vs. 34.40, SD  = 0.6; p  = 0.005), depression measured by the Hamilton Depression Scale (7.70, SD = 0.81 vs. 7.56, SD  = 0.68; p  = 0.042) and severity of illness measured by the Clinical Global Impression severity scale (5.79, SD  = 0.96 vs. 5.31, SD  = 1.12; p  = 0.007). Depression, clinical global impression and cognitive function showed improvement with memantine. Magnetic resonance spectroscopy could be useful in monitoring response to the pharmacological treatment of fibromyalgia.

Background: The national opioid epidemic may have expanded the donor pool for lung transplant, but concerns remain regarding infectious risks and allograft function. This study compared donor and recipient characteristics, outcomes, and reasons for organ discard between overdose death donors (ODDs) and all other mechanism-of-death donors., Methods: Data on adult lung transplants from 2000 to 2017 were provided by the Scientific Registry of Transplant Recipients. Pulmonary allografts used in multiple organ transplants were excluded. Donor and recipient demographics, outcomes, and organ discard were analyzed with regards to ODDs since 2010. Discard analysis was limited to donors who had at least 1 organ transplanted but their pulmonary allografts discarded., Results: From 2010 to 2017, 7.3% of lung transplants (962/13,196) were from ODDs, over a 3-fold increase from the 2.1% (164/7969) in 2000 to 2007. ODDs were younger but more likely to have a history of smoking and hepatitis C or an abnormal bronchoscopy finding. Overall survival was similar between ODD and non-ODD groups. ODDs of discarded pulmonary allografts were younger and more likely to be hepatitis C positive but were less likely to have a history of smoking than their non-ODD counterparts., Conclusions: Rates of ODD use in lung transplant have increased in accordance with the opioid epidemic, but there remains a significant pool of ODD pulmonary allografts with favorable characteristics that are discarded. With no significant difference in survival between ODD and non-ODD recipients, further expansion of this donor pool may be appropriate, and pulmonary allografts should not be discarded based solely on ODD status., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Anastomotic complications occur in 7% to 18% of lung transplant recipients, among which airway dehiscence (AD) is particularly catastrophic. Using multi-institutional registry data, this study compared preoperative recipient/donor risk factors and outcomes in patients with and without AD and analyzed the effect of extracorporeal membrane oxygenation (ECMO) on the incidence of AD., Methods: Data on adult lung transplants from 2007 to 2017 were provided by the Scientific Registry of Transplant Recipients. Patients receiving isolated lobar transplantation and patients with unknown AD status were excluded. Multivariable logistic regression identified independent risk factors for AD. Kaplan-Meier curves and log-rank tests describe mortality and graft survival., Results: Of 18 122 lung transplants, 275 (1.5%) experienced AD. While the incidence of ECMO steadily increased from 0.7% to 5.9% over the study period, the incidence of AD remained relatively constant. Multivariable analysis revealed recipient male gender and prolonged ( > 48 hours) posttransplant mechanical ventilation as independent predictive factors for AD, while advanced donor age and single left lung transplant were protective factors. Recipient chronic steroid use, recipient diabetes, donor diabetes, and donor smoking history were not predictive of AD. Mortality and graft failure were significantly worse in the AD group., Conclusions: Despite increased ECMO utilization, the incidence of AD has remained stable. Multiple independent risk factors for AD were identified and poor postoperative outcomes confirmed. However, many known impediments to wound healing such as recipient chronic steroid use, recipient and donor diabetes, and donor smoking were not identified as risk factors for AD, reinforcing the critical role of technical performance., (© 2019 Wiley Periodicals, Inc.)

Pulmonary lymphangioleiomyomatosis (LAM) is a slow-progressing metastatic disease that is driven by mutations in the tumor suppressor tuberous sclerosis complex 1/2 (TSC1/2). Rapamycin inhibits LAM cell proliferation and is the only approved treatment, but it cannot cause the regression of existing lesions and can only stabilize the disease. However, in other cancers, immunotherapies such as checkpoint blockade against PD-1 and its ligand PD-L1 have shown promise in causing tumor regression and even curing some patients. Thus, we asked whether PD-L1 has a role in LAM progression. In vitro, PD-L1 expression in murine Tsc2-null cells is unaffected by mTOR inhibition with torin but can be upregulated by IFN-γ. Using immunohistochemistry and single-cell flow cytometry, we found increased PD-L1 expression both in human lung tissue from patients with LAM and in Tsc2-null lesions in a murine model of LAM. In this model, PD-L1 is highly expressed in the lung by antigen-presenting and stromal cells, and activated T cells expressing PD-1 infiltrate the affected lung. In vivo treatment with anti-PD-1 antibody significantly prolongs mouse survival in the model of LAM. Together, these data demonstrate that PD-1/PD-L1-mediated immunosuppression may occur in LAM, and suggest new opportunities for therapeutic targeting that may provide benefits beyond those of rapamycin.

This series details two cases of benign pneumatosis intestinalis (PI) in patients post-lung transplant, which were discovered incidentally on routine surveillance chest radiographs during ambulatory clinic visits. Both patients had uneventful post-transplant recovery and were asymptomatic at presentation. The patients were admitted for observation. Contrast-enhanced abdominal CT scans confirmed the plain film findings. Both cases were managed conservatively with bowel rest, intravenous hydration and serial abdominal examinations. The patients had unremarkable hospital courses and were both discharged in good condition. Our current understanding of benign PI in patients post-transplant is limited to a few case series and case reports. Greater awareness of this entity may decrease unnecessary invasive procedures and improve management of these patients., (2015 BMJ Publishing Group Ltd.)

Background: Limited data are available regarding the etiologic impact of health care-associated pneumonia (HCAP) in lung transplant recipients. Therefore, our aim was to evaluate the microbiologic differences between HCAP and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in lung transplant recipients with a radiographically confirmed diagnosis of pneumonia., Methods: We performed a retrospective cohort study of lung transplant recipients with pneumonia at one transplant center over a 7-year period. Eligible patients included lung transplant recipients who developed a first episode of radiographically confirmed pneumonia ≥ 48 h following transplantation. HCAP, HAP, and VAP were classified according to the American Thoracic Society/Infectious Diseases Society of America 2005 guidelines. χ² and Student t tests were used to compare categorical and continuous variables, respectively., Results: Sixty-eight lung transplant recipients developed at least one episode of pneumonia. HCAP (n = 42; 62%) was most common, followed by HAP/VAP (n = 26; 38%) stratified in HAP (n = 20; 77%) and VAP (n = 6; 23%). Pseudomonas aeruginosa was the predominantly isolated organism (n = 22; 32%), whereas invasive aspergillosis was uncommon (< 10%). Multiple-drug resistant (MDR) pathogens were less frequently isolated in patients with HCAP compared with HAP/VAP (5% vs 27%; P = .009). Opportunistic pathogens were less frequently identified in lung transplant recipients with HCAP than in those with HAP/VAP (7% vs 27%; P = .02). Lung transplant recipients with HCAP had a similar mortality at 90 days (n = 9 [21%] vs n = 4 [15%]; P = .3) compared with patients with HAP/VAP., Conclusions: HCAP was the most frequent infection in lung transplant recipients. MDR pathogens and opportunistic pathogens were more frequently isolated in HAP/VAP. There were no differences in 30- and 90-day mortality between lung transplant recipients with HCAP and those with HAP/VAP.

Lung transplantation reduces mortality in patients with end-stage lung disease; however, only approximately 21% of lungs from potential donor patients undergo transplantation. A large number of donor lungs become categorized as unsuitable for lung transplantation as a result of lung injury around the time of brain death. Limiting this injury is key to increasing the number of successful lung procurements and subsequent transplants. This narrative review by a working group of pulmonologists, respiratory therapists, and lung transplant specialists elucidates principles of mechanical ventilatory support that can be used to limit lung injury in potential lung donor patients and examines the implementation of protocolized strategies in enhancing the procurement of donor lungs for transplantation.

The objectives of this pilot trial were to assess the safety of a new device for pulmonary embolism (PE) prophylaxis. The device, the Angel Catheter, was placed in eight patients who were in the intensive care unit and were at high risk of PE. The device was inserted at the bedside without fluoroscopic guidance via a femoral venous approach. All eight devices were inserted and subsequently retrieved without complications (follow-up, 33-36 d). One filter trapped a large clot., (Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.)

Williams-Campbell syndrome is a rare disorder characterized by deficiency of subsegmental bronchial cartilage and development of airway collapse and bronchiectasis that may subsequently progress to respiratory failure and death. There are only 2 published reports suggesting a familial association, and only one report of lung transplantation being used as a therapeutic modality. Due to postoperative airway complications, transplantation has not been recommended for this disease. We report the first lung transplant with prolonged survival, approaching 10 years, in a patient with Williams-Campbell syndrome, and provide further evidence to support a familial association., (Copyright 2012 Daedalus Enterprises)

Objectives: To investigate the characteristics, trends in management (permissive hypercapnia; mechanical ventilation (MV); neuromuscular blockade) and their impact on complications and outcomes in Status Asthmaticus (SA)., Methods: We performed a retrospective observational study of subjects admitted with SA to a single multidisciplinary MICU over a 30-year period. All laboratory, radiologic, respiratory care, physician notes and orders were extracted from an electronic medical record (EMR) maintained during the entire duration of the study., Results: Two hundred and twenty-seven subjects were admitted with 280 episodes of SA. While subjects reflected our regional population (52% Hispanic), African Americans were over-represented (22%) and Caucasians under-represented (21%). Thirty-eight percent reported childhood asthma, 27% were steroid dependent (10% in the last 10 years), and 18% had a recent steroid taper. One hundred and thirty-nine (61.2%) required intubation. The duration of hospitalization was similar between mechanically ventilated and non-ventilated subjects (5.8±4.41 vs. 6.8±7.22 days; p=0.07). The overall complication rate remained low irrespective of the use of permissive hypercapnia or mode of mechanical ventilation (overall mortality 0.4%; pneumothorax 2.5%; pneumonia 2.9%). The frequency of SA declined significantly in the last 10 years of the study (12.4 vs. 3.2 cases/year)., Conclusions: Despite the frequent use of mechanical ventilation, mortality/complication rates remained extremely low. MV did not significantly increase the duration of hospitalization. At our institution, the frequency of SA significantly decreased despite an increase in emergency room visits for asthma., (Published by Elsevier Ltd.)

Purpose: To review the available literature on retrievable inferior vena cava (IVC) filters to examine the effectiveness and risks of these devices., Materials and Methods: Investigators searched MEDLINE for clinical trials evaluating retrievable filters and reviewed the complications reported to the Manufacturer and User Facility Device Experience (MAUDE) database of the U.S. Food and Drug Administration (FDA)., Results: Eligibility criteria were met by 37 studies comprising 6,834 patients. All of the trials had limitations, and no studies were randomized. There were 11 prospective clinical trials; the rest were retrospective studies. Despite the limitations of the evidence, the IVC filters seemed to be effective in preventing pulmonary embolism (PE); the rate of PE after IVC placement was 1.7%. The mean retrieval rate was 34%. Most of the filters became permanent devices. Multiple complications associated with the use of IVC filters were described in the reviewed literature or were reported to the MAUDE database; most of these were associated with long-term use (> 30 days). At the present time, the objective comparison data of different filter designs do not support superiority of any particular design., Conclusions: In high-risk patients for whom anticoagulation is not feasible, retrievable IVC filters seem to be effective in preventing PE. Long-term complications are a serious concern with the use of these filters. The evidence of the effectiveness and the risks was limited by the small number of prospective studies., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

Lung transplantation is a viable treatment option for select patients with end-stage lung disease. Two issues hamper progress in transplantation: first, donor shortage is a major limitation to increasing the number of transplants performed. Secondly, recipient outcomes remain disappointing when compared with other solid organ transplant results. Outcomes are limited by primary graft dysfunction (PGD), the posttransplant acute lung injury that increases both short-and long-term mortality. Attempts to overcome donor shortage have included aggressively managing solid organ donors to increase the number of donor lungs suitable for transplantation. Yet, the quality of the lung donor is likely to be related to the probability of the recipient experiencing PGD. PGD is the culmination of a series of insults, hemodynamic, metabolic, and inflammatory, that begin with the brain dead donor and result in poor recipient outcomes. Understanding the mechanism of donor lung injury resulting from brain death and the possible treatment strategies for its inhibition could help to increase the number of usable lungs and decrease the rate of PGD in the recipient. Here we present a review of the key pathways which result in donor lung injury, and follow this with a brief review of recent biomarkers that are proving to be instrumental to our ability to predict truly unsuitable lungs, and our ability to predict and hopefully prevent or treat recipients with subsequent lung injury.

Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients. This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality. Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole.

Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Local expertise and waiting list issues are important in influencing the choice of SLT versus BLT. Most of the data support the use of BLT for the majority of COPD patients when available, and the use of SLT for the majority of idiopathic pulmonary fibrosis (IPF) patients. The ultimate choice of operation will depend on donor and recipient characteristics and local expertise and waiting list issues.

Rationale: One of the limitations associated with lung transplantation is the lack of available organs., Objective: To determine whether a lung donor-management protocol could increase the number of lungs for transplantation without affecting the survival rates of the recipients., Methods: We implemented the San Antonio Lung Transplant protocol for managing potential lung donors according to modifications of standard criteria for donor selection and strategies for donor management. We then compared information gathered during a 4-yr period, during which the protocol was used with information gathered during a 4-yr period before protocol implementation. Primary outcome measures were the procurement rate of lungs and the 30-d and 1-yr survival rates of recipients., Main Results: We reviewed data from 711 potential lung donors. The mean rate of lung procurement was significantly higher (p < 0.0001) during the protocol period (25.5%) than during the pre-protocol period (11.5%), with an estimated risk ratio of 2.2 in favor of the protocol period. More patients received transplants during the protocol period (n = 121) than during the pre-protocol period (n = 53; p < 0.0001). Of 98 actual lung donors during the protocol period, 53 (54%) had initially been considered poor donors; these donors provided 64 (53%) of the 121 lung transplants. The type of donor was not associated with significant differences in recipients' 30-d and 1-yr survival rates or any clinical measures of adequate graft function., Conclusions: The protocol was associated with a significant increase in the number of lung donors and transplant procedures without compromising pulmonary function, length of stay, or survival of the recipients.

Background: Associated comorbidities in potential lung transplant recipients may significantly impact operative morbidity and mortality. We undertook this review to specifically study whether patients who underwent associated cardiac procedures either before (as a prerequisite) or during their lung transplantation had different outcomes when compared with the overall cohort of lung transplant recipients., Methods: A retrospective chart review was performed of all patients who underwent lung transplantation at the University of Texas Health Science Center at San Antonio from January 1994 to June 2004. The records of these patients were analyzed for patient-days on the ventilator, hospital length of stay, operative morbidity and mortality, and long-term survival. The patients were then divided into two groups and compared: patients who had a cardiac intervention either prerequisite to or concurrent with their transplant (group C, n = 13) and patients who did not (group NC [no cardiac intervention], n = 120)., Results: Although the median length of stay was longer in group C when compared with group NC, the number of patient-days on the ventilator and the operative morbidity and mortality were similar for both groups. Likewise, overall long-term survival was not significantly different (Kaplan-Meier method, p = 0.70)., Conclusions: Patients who are otherwise deemed to be good candidates for lung transplantation but are found to have an associated cardiac condition that could adversely affect their candidacy may still be considered for transplantation in selected cases if the cardiac abnormality can be addressed either before or during transplantation.

Lung transplantation is now performed in patients with end-stage pulmonary parenchymal or vascular lung disease. The process of evaluating a patient for transplantation, managing the patient during the peri-operative period, and caring for the patient following transplantation is complex. Lung-transplant recipients are prone to unique complications of lung transplantation, as well as general complications of an immunosuppressed host. This article reviews the indications for, expected outcomes of, and management of complications that can develop following lung transplantation. Respiratory therapists play an instrumental role in assisting in the management of this group of patients in the pretransplant and post-transplant periods, and in their long-term management.

When significant clinical end points are considered, PDT is a cost-effective and safe alternative to ST in critically ill patients in the ICU when performed by skilled and experienced practitioners [1, 40]. There are insufficient data to establish clear superiority of either technique. Important advantages of PDT may include eliminating the need for operating room facilities and personnel by the performance of the procedure at the bedside and significantly decreasing the time interval between the decision to perform tracheostomy and the actual procedure [1, 2, 20].

Objective: Previous tracheostomy has been considered a relative contraindication for percutaneous dilational tracheostomy. The objective of this study was to assess the safety of percutaneous dilational tracheostomy in critically ill patients with a history of previous tracheostomy., Design: Retrospective, single-center case series of all consecutive patients requiring repeat tracheostomy for continued mechanical ventilatory support., Setting: Intensive care unit of a tertiary-care referral center., Subjects: Fourteen patients (eight female, six male) with a median age of 70 yrs (range, 33-94). All patients had previously undergone tracheostomy., Intervention: Bedside percutaneous dilational tracheostomy., Measurement and Main Results: Subjects' previous tracheostomies dated back between 10 days and 8 yrs. Present intubation time before percutaneous dilational tracheostomy varied between 4 and 30 days. Bedside percutaneous dilational tracheostomy was performed successfully in all 14 patients by trained pulmonologists and surgeons. Eleven patients received an 8-mm and three received a 7-mm tracheostomy tube. There were no significant periprocedural complications, and no patient required surgical revision. The only postprocedural complication was accidental decannulation in one patient, which was managed with repeat percutaneous dilational tracheostomy., Conclusions: Trained physicians can safely perform bedside percutaneous dilational tracheostomy after previous tracheostomy. Percutaneous dilational tracheostomy offers an alternative to surgical tracheostomy in this particular patient population and should not be considered contraindicated.

Objectives: Posttransplant lymphoproliferative disorders (PTLD) can be a significant cause of morbidity in lung transplant (LT) recipients. Risk factors include Epstein-Barr virus (EBV) infection, particularly primary infection, and immunosuppression. This article updates the incidence and presentation of PTLD at our lung transplant program., Methods: We retrospectively reviewed the immunosuppression, EBV serology, and cases of PTLD among 129 lung transplant recipients at risk who survived > 1 month., Results: There were two cases of PTLD among 129 LT patients, 2/129 (1.6%). One of these patients was among the 6 EBV seroconverters, 1/6 (16.7%), and had a typical presentation of PTLD in the allograft resulting in dissemination and death. The second case of PTLD developed in an EBV seropositive recipient who presented 33 months following LT with isolated colonic involvement. He subsequently died from chronic rejection., Conclusions: The incidence of PTLD in a LT program with a large EBV seropositive population is low, 1.6%. The presentation of PTLD in LT recipients is variable and may present typically with allograft involvement in the first year following transplantation, or late with isolated, extrapulmonic involvement.