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1.
Clin Transplant ; 38(5): e15325, 2024 May.
Article in English | MEDLINE | ID: mdl-38716770

ABSTRACT

BACKGROUND/AIMS: Direct-acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV-viremic donors. Though transplantation of HCV-viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post-transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post-transplant, including patient and graft survival between HCV-viremic transplantation (D+) and HCV-aviremic transplantation (D-). METHODS: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D- grafts. Recipients of HCV antibody+ but PCR- grafts were treated as D- recipients. RESULTS: We identified 470 D- and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p = .43). Patient survival at years 1 and 2 did not differ between D+ and D- patients (p = .89, p = .87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p = .90, p = .88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D- patients had similar rates of post-transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p = .3), acute cellular rejection (60.0% vs. 58.0%, p = .8) and antibody-mediated rejection (16.7% vs. 14.2%, p = .7). CONCLUSION: There is no difference in midterm patient or graft survival between D+ and D-LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow-up for CLAD was limited. These results provide additional support for the use of HCV-viremic organs in selected recipients in LT.


Subject(s)
Graft Rejection , Graft Survival , Hepacivirus , Hepatitis C , Lung Transplantation , Postoperative Complications , Viremia , Humans , Lung Transplantation/adverse effects , Female , Male , Retrospective Studies , Middle Aged , Follow-Up Studies , Prognosis , Hepatitis C/surgery , Hepatitis C/virology , Hepacivirus/isolation & purification , Viremia/virology , Viremia/etiology , Survival Rate , Graft Rejection/etiology , Risk Factors , Tissue Donors/supply & distribution , Adult , Antiviral Agents/therapeutic use , Transplant Recipients
2.
Transpl Infect Dis ; : e14319, 2024 Jun 17.
Article in Italian | MEDLINE | ID: mdl-38884771

ABSTRACT

BACKGROUND: Multidrug-resistant organisms are increasing and are a significant cause of mortality among lung transplant recipients (LTRs). To assist with this issue, novel pharmacotherapies are being developed. This study describes the utilization of a novel antibiotic, cefiderocol (FDC), in LTRs where limited data exists in the current literature. We primarily assessed the clinical indications, duration of therapy, resistance, and adverse effects. METHODS: Conducted as a single-center retrospective review, this study included adult LTRs who received FDC for at least 24 h. Data, extracted from electronic medical records, encompassed patient demographics, transplant history, antimicrobial dosing, adverse effects, bacterial cultures, and outcomes. The research protocol received institutional review board approval. RESULTS: FDC exhibited effectiveness against multidrug-resistant Pseudomonas aeruginosa, with 26% 30-day mortality and microbiological clearance observed in nine out of 13 cases. Notably, FDC was used in diverse clinical settings, including for prophylaxis, empiric, and targeted treatment. CONCLUSION: Further studies are needed to evaluate optimal clinical indications for FDC use in LTRs.

3.
Clin Transplant ; 37(9): e15079, 2023 09.
Article in English | MEDLINE | ID: mdl-37477286

ABSTRACT

Lung transplant recipients are at an increased risk for Clostridioides difficile infection (CDI), and those who develop CDI post-transplant can have worsened outcomes including graft failure and death. We sought to describe the efficacy and safety of primary CDI prophylaxis with oral vancomycin among 86 adult lung transplant recipients. Overall, we observed a 9.3% (8/86) incidence of CDI among patients receiving prophylaxis, with the majority of infections occurring a median of 25 days after completion of prophylaxis. Furthermore, we observed a 4.7% incidence of VRE infection/colonization. Opportunities exist to optimize the duration of CDI prophylaxis to balance the benefits and risks in lung transplant recipients.


Subject(s)
Anti-Bacterial Agents , Clostridioides difficile , Clostridium Infections , Lung Transplantation , Primary Prevention , Vancomycin , Clostridium Infections/epidemiology , Clostridium Infections/prevention & control , Lung Transplantation/adverse effects , Primary Prevention/methods , Humans , Male , Female , Middle Aged , Aged , Retrospective Studies , Vancomycin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Administration, Oral , Incidence
4.
Am J Transplant ; 22(12): 2981-2989, 2022 12.
Article in English | MEDLINE | ID: mdl-35962587

ABSTRACT

Place is defined as a social or environmental area of residence with meaning to a patient. We hypothesize there is an association between place and the clinical outcomes of lung transplant recipients in the United States. In a retrospective cohort study of transplants between January 1, 2010, and December 31, 2019, in the Scientific Registry of Transplant Recipients, multivariable Cox regression models were used to test the association between place (through social and environmental factors) with readmission, lung rejection, and survival. Among 18,465 recipients, only 20% resided in the same county as the transplant center. Recipients from the most socially vulnerable counties when compared to the least vulnerable were more likely to have COPD as a native disease, Black or African American race, and travel long distances to reach a transplant center. Higher local life expectancy was associated with lower likelihood for readmission (odds ratio [OR] = 0.90, 95% confidence interval [CI]: 0.84, 0.98, p = .01). Higher social vulnerability was associated with a higher likelihood of lung rejection (OR = 1.37, [CI]: 1.07, 1.76, p = .01). There was no association of residence with posttransplant survival. Recipient place-based factors were associated with complications and processes of care after transplant and warrant further investigation.


Subject(s)
Lung Transplantation , Transplant Recipients , Humans , United States/epidemiology , Graft Rejection/etiology , Retrospective Studies , Lung Transplantation/adverse effects , Lung , Registries
5.
Am J Transplant ; 22(9): 2169-2179, 2022 09.
Article in English | MEDLINE | ID: mdl-35634722

ABSTRACT

Histopathologic lung allograft injuries are putative harbingers for chronic lung allograft dysfunction (CLAD). However, the mechanisms responsible are not well understood. CXCL9 and CXCL10 are potent chemoattractants of mononuclear cells and potential propagators of allograft injury. We hypothesized that these chemokines would be quantifiable in plasma, and would associate with subsequent CLAD development. In this prospective multicenter study, we evaluated 721 plasma samples for CXCL9/CXCL10 levels from 184 participants at the time of transbronchial biopsies during their first-year post-transplantation. We determined the association between plasma chemokines, histopathologic injury, and CLAD risk using Cox proportional hazards models. We also evaluated CXCL9/CXCL10 levels in bronchoalveolar lavage (BAL) fluid and compared plasma to BAL with respect to CLAD risk. Plasma CXCL9/CXCL10 levels were elevated during the injury patterns associated with CLAD, acute rejection, and acute lung injury, with a dose-response relationship between chemokine levels and CLAD risk. Importantly, there were strong interactions between injury and plasma CXCL9/CXCL10, where histopathologic injury associated with CLAD only in the presence of elevated plasma chemokines. We observed similar associations and interactions with BAL CXCL9/CXCL10 levels. Elevated plasma CXCL9/CXCL10 during allograft injury may contribute to CLAD pathogenesis and has potential as a minimally invasive immune monitoring biomarker.


Subject(s)
Graft vs Host Disease , Lung Transplantation , Allografts , Biomarkers , Chemokine CXCL10 , Chemokine CXCL9 , Graft Rejection/diagnosis , Graft Rejection/etiology , Humans , Lung , Lung Transplantation/adverse effects , Prospective Studies
6.
Am J Transplant ; 22(12): 3002-3011, 2022 12.
Article in English | MEDLINE | ID: mdl-36031951

ABSTRACT

We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.


Subject(s)
Acute Lung Injury , Lung Transplantation , Pneumonia , Adult , Humans , Prospective Studies , Prognosis , Retrospective Studies , Lung Transplantation/adverse effects , Acute Lung Injury/etiology , Acute Lung Injury/pathology , Lung , Pneumonia/epidemiology , Pneumonia/etiology , Pneumonia/pathology , Risk Factors , Cohort Studies
7.
Am J Transplant ; 21(1): 272-280, 2021 01.
Article in English | MEDLINE | ID: mdl-32654414

ABSTRACT

There is a broad range of patient travel distances to reach a lung transplant hospital in the United States. Whether patient travel distance is associated with waitlist outcomes is unknown. We present a cohort study of patients listed between January 1, 2006 and May 31, 2017 using the Scientific Registry of Transplant Recipients. Travel distance was measured from the patient's permanent zip code to the transplant hospital using shared access signature URL access to Google Maps, and assessed using multivariable competing risk regression models. There were 22 958 patients who met inclusion criteria. Median travel distance was 69.7 miles. Among patients who traveled > 60 miles, 41.2% bypassed a closer hospital and sought listing at a more distant hospital. In the adjusted models, when compared to patients who traveled ≤60 miles, patients who traveled >360 miles had a 27% lower subhazard ratio (SHR) for waitlist removal (SHR 0.73, 95% confidence interval [CI]: 0.60, 0.89, P = .002), 16% lower subhazard for waitlist death (SHR 0.84; 95% CI 0.73-0.95, P = .07), and 13% increased likelihood for transplant (SHR 1.13, 95% CI: 1.07, 1.20, P < .001). Many patients bypassed the nearest transplant hospital, and longer patient travel distance was associated with favorable waitlist outcomes.


Subject(s)
Lung Transplantation , Waiting Lists , Cohort Studies , Humans , Retrospective Studies , Transplant Recipients , Travel , United States
8.
Am J Transplant ; 21(10): 3401-3410, 2021 10.
Article in English | MEDLINE | ID: mdl-33840162

ABSTRACT

The histopathologic diagnosis of acute allograft injury is prognostically important in lung transplantation with evidence demonstrating a strong and consistent association between acute rejection (AR), acute lung injury (ALI), and the subsequent development of chronic lung allograft dysfunction (CLAD). The pathogenesis of these allograft injuries, however, remains poorly understood. CXCL9 and CXCL10 are CXC chemokines induced by interferon-γ and act as potent chemoattractants of mononuclear cells. We hypothesized that these chemokines are involved in the mononuclear cell recruitment associated with AR and ALI. We further hypothesized that the increased activity of these chemokines could be quantified as increased levels in the bronchoalveolar lavage fluid. In this prospective multicenter study, we evaluate the incidence of histopathologic allograft injury development during the first-year post-transplant and measure bronchoalveolar CXCL9 and CXCL10 levels at the time of the biopsy. In multivariable models, CXCL9 levels were 1.7-fold and 2.1-fold higher during AR and ALI compared with "normal" biopsies without histopathology. Similarly, CXCL10 levels were 1.6-fold and 2.2-fold higher during these histopathologies, respectively. These findings support the association of CXCL9 and CXCL10 with episodes of AR and ALI and provide potential insight into the pathogenesis of these deleterious events.


Subject(s)
Chemokine CXCL10 , Graft Rejection , Allografts , Chemokine CXCL9 , Graft Rejection/etiology , Lung , Prospective Studies
9.
Clin Transplant ; 35(11): e14464, 2021 11.
Article in English | MEDLINE | ID: mdl-34405461

ABSTRACT

BACKGROUND: Vaccine preventable diseases can affect solid organ transplant recipients post-transplant. Therefore, the administration of vaccines and assessment of serologic response should be prioritized in the pre-transplant period. METHODS: This single-center, retrospective study included 349 adult heart or lung transplant candidates between December 1, 2017 and November 30, 2019. We describe vaccination or serologic status for hepatitis A, hepatitis B, tetanus, pneumococcal, influenza, and other recommended vaccinations among heart or lung transplant candidates. RESULTS: Eighty-two heart transplant candidates (91%) and 77 lung transplant candidates (30%) received an ID consult prior to transplant. More patients completed the pneumococcal series (66.7% vs. 28.6%, P = .045) in the heart transplant group that received an ID consult. In the lung transplant group, patients with an ID consult demonstrated higher rates of immunity to hepatitis A (84.4% vs. 72.9%, P = .047), hepatitis B (75.3% vs. 56.9%, P = .005), and measles (71.4% vs. 52.5%, P = .005) compared to those without. CONCLUSIONS: Our results demonstrate the value of consulting ID and administering vaccinations in the early evaluation phase, prior to transplant listing. Opportunities remain to better optimize vaccination rates prior to transplant in heart and lung transplant candidates.


Subject(s)
Influenza Vaccines , Transplant Recipients , Adult , Humans , Lung , Retrospective Studies , Vaccination
10.
Am J Respir Crit Care Med ; 202(4): 576-585, 2020 08 15.
Article in English | MEDLINE | ID: mdl-32379979

ABSTRACT

Rationale: Acute rejection, manifesting as lymphocytic inflammation in a perivascular (acute perivascular rejection [AR]) or peribronchiolar (lymphocytic bronchiolitis [LB]) distribution, is common in lung transplant recipients and increases the risk for chronic graft dysfunction.Objectives: To evaluate clinical factors associated with biopsy-proven acute rejection during the first post-transplant year in a present-day, five-center lung transplant cohort.Methods: We analyzed prospective diagnoses of AR and LB from over 2,000 lung biopsies in 400 newly transplanted adult lung recipients. Because LB without simultaneous AR was rare, our analyses focused on risk factors for AR. Multivariable Cox proportional hazards models were used to assess donor and recipient factors associated with the time to the first AR occurrence.Measurements and Main Results: During the first post-transplant year, 53.3% of patients experienced at least one AR episode. Multivariable proportional hazards analyses accounting for enrolling center effects identified four or more HLA mismatches (hazard ratio [HR], 2.06; P ≤ 0.01) as associated with increased AR hazards, whereas bilateral transplantation (HR, 0.57; P ≤ 0.01) was associated with protection from AR. In addition, Wilcoxon rank-sum analyses demonstrated bilateral (vs. single) lung recipients, and those with fewer than four (vs. more than four) HLA mismatches demonstrated reduced AR frequency and/or severity during the first post-transplant year.Conclusions: We found a high incidence of AR in a contemporary multicenter lung transplant cohort undergoing consistent biopsy sampling. Although not previously recognized, the finding of reduced AR in bilateral lung recipients is intriguing, warranting replication and mechanistic exploration.


Subject(s)
Bronchiolitis/epidemiology , Graft Rejection/epidemiology , Lung Transplantation , Postoperative Complications/epidemiology , Acute Disease , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Risk Factors , Time Factors
11.
Am J Transplant ; 20(11): 3191-3197, 2020 11.
Article in English | MEDLINE | ID: mdl-32476261

ABSTRACT

There are emerging data depicting the clinical presentation of coronavirus disease 19 (COVID-19) in solid organ transplant recipients but negligible data-driven guidance on clinical management. A biphasic course has been described in some infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), beginning with a flu-like illness followed by an intense inflammatory response characterized by elevated c-reactive protein (CRP), interleukin 6 (IL-6), and acute respiratory distress syndrome (ARDS) associated with high mortality. The exuberant and possibly dysregulated immune response has prompted interest in therapeutic agents that target the cytokines involved, particularly IL-6. Tocilizumab is an IL-6 receptor antagonist with a record of use for a variety of rheumatologic conditions and cytokine release syndrome due to chimeric antigen receptor T-cell therapy but experience in solid organ and composite tissue transplant recipients (SOT/CTTRs) with SARS-CoV-2-related ARDS has not been previously reported in detail. We present the clinical course of 5 SOT/CTTRs with SARS-CoV-2-related ARDS that received tocilizumab with favorable short-term outcomes in 4. Responses were characterized by reductions in CRP, discontinuation of vasopressors, improved oxygenation and respiratory mechanics, and variable duration of ventilator support. Four bacterial infections occurred within 2 weeks of tocilizumab administration. We discuss safety concerns and the need for randomized comparative trials to delineate tocilizumab's clinical utility in this population.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Graft Rejection/prevention & control , Organ Transplantation/methods , Pandemics , SARS-CoV-2 , Aged , Comorbidity , Female , Follow-Up Studies , Humans , Male , Middle Aged , Time Factors , Transplant Recipients
12.
Am J Transplant ; 20(6): 1489-1494, 2020 06.
Article in English | MEDLINE | ID: mdl-32342596

ABSTRACT

Long-term survival after lung transplant lags behind that of other commonly transplanted organs, reflecting the current incomplete understanding of the mechanisms involved in the development of posttransplant lung injury, rejection, infection, and chronic allograft dysfunction. To address this unmet need, 2 ongoing National Institute of Allergy and Infectious Disease funded studies through the Clinical Trials in Organ Transplant Consortium (CTOT) CTOT-20 and CTOT-22 were dedicated to understanding the clinical factors and biological mechanisms that drive chronic lung allograft dysfunction and those that maintain cytomegalovirus polyfunctional protective immunity. The CTOT-20 and CTOT-22 studies enrolled 800 lung transplant recipients at 5 North American centers over 3 years. Given the number and complexity of subjects included, CTOT-20 and CTOT-22 utilized innovative data transfers and capitalized on patient-entered data collection to minimize site manual data entry. The data were coupled with an extensive biosample collection strategy that included DNA, RNA, plasma, serum, bronchoalveolar lavage fluid, and bronchoalveolar lavage cell pellet. This Special Article describes the CTOT-20 and CTOT-22 protocols, data and biosample strategy, initial results, and lessons learned through study execution.


Subject(s)
Lung Transplantation , Organ Transplantation , Bronchoalveolar Lavage Fluid , Cytomegalovirus , Graft Rejection/etiology , Humans , Lung Transplantation/adverse effects , Organ Transplantation/adverse effects , Transplant Recipients
13.
Clin Transplant ; 34(7): e13873, 2020 07.
Article in English | MEDLINE | ID: mdl-32274840

ABSTRACT

Donor lung allocation in the United States focuses on decreasing waitlist mortality and improving recipient outcomes. The implementation of allocation policy to match deceased donor lungs to waitlisted patients occurs through a unique partnership between government and private organizations, namely the Organ Procurement and Transplantation Network under the Department of Health and Human Services and the United Network for Organ Sharing. In 2005, the donor lung allocation algorithm shifted toward the prioritization of medical urgency of waitlisted patients instead of time accrued on the waitlist. This led to the Lung Allocation Score, which weighs over a dozen clinical variables to predict a 1-year estimate of survival benefit, and is used to prioritize waitlisted patients. In 2017, the use of local allocation boundaries was eliminated in favor of a 250 nautical mile radius from the donor hospital as the first unit of distance used in allocation. The next upcoming iteration of donor allocation policy is expected to use a continuous distribution algorithm where all geographic boundaries are eliminated. There are additional opportunities to improve donor lung allocation, such as for patients with high antibody titers with access to a limited number of donors.


Subject(s)
Lung Transplantation , Tissue and Organ Procurement , Waiting Lists , Humans , Lung , Resource Allocation , Tissue Donors , United States , United States Dept. of Health and Human Services
14.
Clin Transplant ; 34(10): e14056, 2020 10.
Article in English | MEDLINE | ID: mdl-32748982

ABSTRACT

BACKGROUND: Resilience represents the capacity to adapt to adversity. Resilience can improve following behavioral interventions. We examined lung transplant candidates' resilience as a novel predictor using the Connor-Davidson Resilience Scale (RISC-10). METHODS: Waitlisted candidates at six centers were mailed questionnaires from 9/16/2015 to 10/1/2019. Follow-up surveys were collected annually and post-transplant. Outcomes were recorded through February 17, 2020. Primary outcome was pre-transplant death/delisting. Analyses included t test or chi-square for group comparisons, Pearson's correlation coefficients for strength of relationships, and Cox proportional-hazard models to evaluate associations with outcomes, adjusting for age, sex, and mood. RESULTS: Participation was 55.3% (N = 199). Baseline RISC-10 averaged 32.0 ± 5.6 and did not differ by demographics, primary transplant diagnosis, or disease severity markers. RISC-10 did not correlate to the commonly utilized Psychosocial Assessment of Candidates for Transplant [PACT] or Stanford Integrated Psychosocial Assessment for Transplantation [SIPAT] tools. Scores < 26.3 (representing > 1 standard deviation below population average) occurred in 16% and were associated with pre-transplant death or delisting, adjusted Hazard Ratio of 2.60 (95% Confidence Interval 1.23-5.77; P = .01). CONCLUSION: One in six lung candidates had low resilience, predicting increased pre-transplant death/delisting. RISC-10 did not correlate with PACT or SIPAT; resilience may represent a novel risk factor.


Subject(s)
Lung Transplantation , Humans , Proportional Hazards Models , Risk Factors , Surveys and Questionnaires
15.
Am J Transplant ; 19(4): 984-994, 2019 04.
Article in English | MEDLINE | ID: mdl-30506632

ABSTRACT

A consensus conference on frailty in kidney, liver, heart, and lung transplantation sponsored by the American Society of Transplantation (AST) and endorsed by the American Society of Nephrology (ASN), the American Society of Transplant Surgeons (ASTS), and the Canadian Society of Transplantation (CST) took place on February 11, 2018 in Phoenix, Arizona. Input from the transplant community through scheduled conference calls enabled wide discussion of current concepts in frailty, exploration of best practices for frailty risk assessment of transplant candidates and for management after transplant, and development of ideas for future research. A current understanding of frailty was compiled by each of the solid organ groups and is presented in this paper. Frailty is a common entity in patients with end-stage organ disease who are awaiting organ transplantation, and affects mortality on the waitlist and in the posttransplant period. The optimal methods by which frailty should be measured in each organ group are yet to be determined, but studies are underway. Interventions to reverse frailty vary among organ groups and appear promising. This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.


Subject(s)
Frailty , Organ Transplantation , Societies, Medical , Health Care Rationing , Humans , United States
16.
BMC Pulm Med ; 19(1): 20, 2019 Jan 21.
Article in English | MEDLINE | ID: mdl-30665375

ABSTRACT

BACKGROUND: By comparing diagnoses made by pre-transplant surgical lung biopsy (SLB) and the final pathologic diagnosis of the explanted pathology (EP), we aimed to study the factors that could impact pathologic diagnoses in patients with interstitial lung disease (ILD). METHODS: We retrospectively reviewed the lung transplant database at Cleveland Clinic [01/01/2006-12/31/2013] to include all lung transplant recipients with a prior diagnosis of ILD. Two pulmonary pathologists independently reviewed each SLB and lung explant. The diagnoses were labeled as concordant (same diagnosis on SLB and explant) or discordant (diagnosis on SLB and explant were different) by consensus. RESULTS: Of 389 patients transplanted for ILD, 217 had an SLB before transplant. Pathological diagnoses were concordant in 190 patients (87.6%) [165 UIP (86.8%), 13 NSIP (6.8%), 8 CHP (4.2%) and 4 other diagnoses (2.1%). In 27 cases (12.4%), the diagnosis on SLB differed from EP. 8/27 were diagnosed with UIP on SLB and of these, 5 were re-classified as NSIP. 14/19 (73.7%) patients with a SLB diagnosis "other than UIP" were re-categorized as UIP based on explant. Discordant cases had a greater time between SLB and EP than concordant cases (1553 days vs 1248 days). CONCLUSIONS: The pathologic diagnosis of ILD by SLB prior to lung transplant is accurate in most patients, but may be misleading in a small subset of patients. The majority of discordant cases that were reclassified as UIP could be due to a sampling error, or perhaps, an increased time from the date of the SLB to transplant. Future studies examining how multidisciplinary consensus diagnosis affects this discordance are necessary.


Subject(s)
Lung Diseases, Interstitial/pathology , Lung Transplantation , Lung/pathology , Alveolitis, Extrinsic Allergic/diagnosis , Alveolitis, Extrinsic Allergic/pathology , Alveolitis, Extrinsic Allergic/surgery , Biopsy , Female , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/pathology , Idiopathic Pulmonary Fibrosis/surgery , Lung/surgery , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/surgery , Male , Middle Aged , Pneumonectomy , Retrospective Studies
17.
Am J Transplant ; 18(9): 2285-2294, 2018 09.
Article in English | MEDLINE | ID: mdl-29687961

ABSTRACT

Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P = .047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P = .039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.


Subject(s)
Graft Rejection/mortality , Graft Survival/immunology , HLA Antigens/immunology , Isoantibodies/adverse effects , Lung Transplantation/mortality , Tissue Donors , Adult , Aged , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Rejection/pathology , Histocompatibility Testing , Humans , Isoantibodies/immunology , Lung Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications , Prognosis , Prospective Studies , Risk Factors , Survival Rate
18.
Clin Transplant ; 32(8): e13307, 2018 08.
Article in English | MEDLINE | ID: mdl-29862567

ABSTRACT

BACKGROUND: Lung transplant remains an established treatment for end-stage lung disease, but limited organ availability remains a major barrier and contributor to waitlist mortality.1 Only 20% of available organs are considered suitable for lung transplantation (Am J Transplant, 16, 2016 and 141; Thorac Surg Clin, 25, 2015 and 35). Successful lung transplantation has been reported from donors infected with bacterial or fungal organisms, but there is a paucity of evidence regarding the use of donors with bacterial meningitis (Transplant Proc, 32, 2000 and 75; Transplantation, 64, 1997 and 365; Ann Thorac Surg, 86, 2008 and 1554). METHOD: The Cleveland Clinic lung transplant database was retrospectively reviewed for patients between January 1998 and December 2014. Post-transplantation outcomes collected included graft dysfunction, infectious complications, and survival. RESULTS: The recipients were identified as having lungs from donors with bacterial meningitis. All recipients remained free of infectious organisms responsible for bacterial meningitis related in the donor. Severe primary graft dysfunction (PGD) was not seen in these recipients. CONCLUSION: In our study, lung transplantation from increased risk donors with bacterial meningitis was not associated with an increased risk of early infectious complications in recipients. Donors with bacterial meningitis should be considered for lung donation and may expand the donor pool safely.


Subject(s)
Donor Selection , Lung Transplantation/mortality , Meningitis, Bacterial/epidemiology , Resource Allocation , Tissue Donors/statistics & numerical data , Tissue and Organ Procurement/statistics & numerical data , Adult , Aged , Cause of Death , Female , Follow-Up Studies , Humans , Lung Transplantation/statistics & numerical data , Male , Meningitis, Bacterial/microbiology , Middle Aged , Prevalence , Prognosis , Retrospective Studies , Survival Rate , Young Adult
19.
Clin Transplant ; 32(5): e13236, 2018 05.
Article in English | MEDLINE | ID: mdl-29528522

ABSTRACT

Cystic fibrosis (CF) with severe lung disease is a well-recognized indication for lung transplantation. Colonization with various organisms in CF patients may impact post-transplant morbidity and mortality. Burkholderia cepacia complex (BCC) is made up of distinct genomovars with significant morbidity and mortality associated with B. cenocepacia (genomovar III) following lung transplant. The outcomes of patients infected with genomovar B. dolosa (genomovar VI) have yet to be described in the literature. We performed a retrospective chart review of all cystic fibrosis patients colonized with B. dolosa from our center who underwent lung transplantation (n = 11) at various medical centers across the US between 2000 and 2014. Survival rates were 73%, 53%, and 30% for 1, 3, and 5 years, respectively. Median survival was 44 months (95% CI = 11.1-76.8). CF patients with B. dolosa that have undergone lung transplantation have decreased one-year survival when compared to all patients transplanted with cystic fibrosis. Conditional 5-year survival for B. dolosa-infected patients was 43% in patients that survived the first year post-transplant, suggesting that this first year is crucial in managing the infection. Importantly, the survival of the B. dolosa patients was higher than compared to previously reported survival rates of B. cenocepacia patients post-transplant.


Subject(s)
Burkholderia Infections/mortality , Cystic Fibrosis/surgery , Lung Transplantation/adverse effects , Postoperative Complications/mortality , Adolescent , Adult , Burkholderia Infections/epidemiology , Burkholderia Infections/microbiology , Burkholderia cepacia complex , Child , Female , Follow-Up Studies , Humans , Incidence , Male , North Carolina/epidemiology , Prognosis , Retrospective Studies , Survival Rate , Young Adult
20.
Prog Transplant ; 28(3): 231-235, 2018 09.
Article in English | MEDLINE | ID: mdl-29945482

ABSTRACT

INTRODUCTION: Recipient travel distance may be an unrecognized burden in lung transplantation. DESIGN: Retrospective single-center cohort study of all adult (≥18 years) first-time lung-only transplants from January 1, 2010, until February 28, 2017. Recipient distance to transplant center was calculated using the linear distance from the recipient's home zip code to the Cleveland Clinic in Cleveland, Ohio. RESULTS: 569 recipients met inclusion criteria. Posttransplant graft survival was 85%, 88%, 91%, and 91% at 1 year and 49%, 52%, 57%, and 56% at 5 years posttransplant for recipient travel distances of ≤50, >50 to ≤250, >250 to ≤500, and >500 miles, respectively ( P = .10). DISCUSSION: We found no significant relationship between recipient travel distance and posttransplant graft survival. In carefully selected recipients, travel distance is not a significant barrier to successful posttransplant outcomes which may be important for patient decision-making and donor allocation policy. These data should be validated in a national cohort.


Subject(s)
Graft Survival , Lung Transplantation/mortality , Lung Transplantation/statistics & numerical data , Survivors/statistics & numerical data , Transplant Recipients/statistics & numerical data , Travel/statistics & numerical data , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Ohio , Retrospective Studies , Time Factors
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