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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.)

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.)

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.)

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: 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.

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.)

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.

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.