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1.
ASAIO J ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38819317

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) is often used in acute respiratory distress syndrome (ARDS) with refractory hypoxemia. There is limited literature highlighting the development of right ventricular (RV) failure while on ECMO. We conducted a retrospective multicenter observational study including 70 patients who were placed on veno-venous (VV)-ECMO for respiratory failure at Mayo Clinic, Jacksonville, and Mayo Clinic, Rochester, between January 2018 and June 2022 and had at least two post-ECMO transthoracic echoes. The primary outcomes were the incidence and progression of RV dysfunction and dilatation. The secondary outcome was in-patient mortality. Among 70 patients in our cohort, 60.6% had a normal RV function at the time of ECMO placement, whereas only 42% had a normal RV function at the second post-ECMO echo. On multinomial regression, a moderate decrease in RV function was associated with ECMO flow (odds ratio [OR] = 2.32, p = 0.001) and ECMO duration (OR = 1.01, p = 0.01). A moderately dilated RV size was also associated with ECMO flow (OR = 2.62, p < 0.001) and ECMO duration (OR = 1.02, p = 0.02). An increasing degree of RV dysfunction was associated with worse outcomes. Our study showed that the increasing duration and flow of VV-ECMO correlated with progressive RV dilatation and dysfunction, which were associated with poor survival.

2.
Sci Rep ; 12(1): 16137, 2022 09 27.
Article in English | MEDLINE | ID: mdl-36167867

ABSTRACT

The clinical use of circulating biomarkers for primary graft dysfunction (PGD) after lung transplantation has been limited. In a prospective single-center cohort, we examined the use of plasma protein biomarkers as indicators of PGD severity and duration after lung transplantation. The study comprised 40 consecutive lung transplant patients who consented to blood sample collection immediately pretransplant and at 6, 24, 48, and 72 h after lung transplant. An expert grader determined the severity and duration of PGD and scored PGD at T0 (6 h after reperfusion), T24, T48, and T72 h post-reperfusion using the 2016 ISHLT consensus guidelines. A bead-based multiplex assay was used to measure 27 plasma proteins including cytokines, growth factors, and chemokines. Enzyme-linked immunoassay was used to measure cell injury markers including M30, M65, soluble receptor of advanced glycation end-products (sRAGE), and plasminogen activator inhibitor-1 (PAI-1). A pairwise comparisons analysis was used to assess differences in protein levels between PGD severity scores (1, 2, and 3) at T0, T24, T48, and T72 h. Sensitivity and temporal analyses were used to explore the association of protein expression patterns and PGD3 at T48-72 h (the most severe, persistent form of PGD). We used the Benjamini-Hochberg method to adjust for multiple testing. Of the 40 patients, 22 (55%) had PGD3 at some point post-transplant from T0 to T72 h; 12 (30%) had PGD3 at T48-72 h. In the pairwise comparison, we identified a robust plasma protein expression signature for PGD severity. In the sensitivity analysis, using a linear model for microarray data, we found that differential perioperative expression of IP-10, MIP1B, RANTES, IL-8, IL-1Ra, G-CSF, and PDGF-BB correlated with PGD3 development at T48-72 h (FDR < 0.1 and p < 0.05). In the temporal analysis, using linear mixed modeling with overlap weighting, we identified unique protein patterns in patients who did or did not develop PGD3 at T48-72 h. Our findings suggest that unique inflammatory protein expression patterns may be informative of PGD severity and duration. PGD biomarker panels may improve early detection of PGD, predict its clinical course, and help monitor treatment efficacy in the current era of lung transplantation.


Subject(s)
Lung Transplantation , Primary Graft Dysfunction , Becaplermin , Biomarkers , Chemokine CCL5 , Chemokine CXCL10 , Cohort Studies , Granulocyte Colony-Stimulating Factor , Humans , Interleukin 1 Receptor Antagonist Protein , Interleukin-8 , Lung Transplantation/adverse effects , Plasminogen Activator Inhibitor 1 , Primary Graft Dysfunction/diagnosis , Primary Graft Dysfunction/etiology , Prospective Studies , Retrospective Studies
3.
Ann Pharmacother ; 56(4): 387-392, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34323121

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. OBJECTIVE: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. METHODS: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. RESULTS: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. CONCLUSION AND RELEVANCE: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Insufficiency , Anticoagulants/adverse effects , COVID-19/complications , COVID-19/therapy , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/methods , Hirudins , Humans , Peptide Fragments , Recombinant Proteins , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2
4.
Indian J Thorac Cardiovasc Surg ; 37(Suppl 3): 366-379, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34483506

ABSTRACT

Ambulatory extracorporeal membrane oxygenation (ECMO) has shown promise as a bridge to lung transplantation. The primary goal of ambulatory ECMO is to provide enough gas exchange to allow patients to participate in preoperative physical therapy. Various strategies of ambulatory ECMO are utilized depending upon patients' need. A wide spectrum of ECMO configurations is available to tackle this situation. We discuss those configurations in this article.

5.
Cureus ; 13(8): e17152, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34548969

ABSTRACT

Coronavirus disease 2019 (COVID-19) is currently a significant cause of acute respiratory failure worldwide, leading to irreversible fibrotic lung disease. In patients with persistent respiratory failure after acute COVID-19 infection, lung transplant is an emerging option. Here, we have presented a case where the patient required venovenous extracorporeal membrane oxygenation (VV-ECMO) support for 33 days until a bilateral lung transplant was performed on day 71 after the initial COVID-19 infection. The early outcomes have been favorable. Currently, no guidelines exist for an acceptable time period after initial COVID-19 infection, duration of negative COVID polymerase chain reaction (PCR) testing, or negative Vero cell culture in the setting of persistent positive COVID PCR testing before listing for a lung transplant. Due to a lack of standardized guidelines, this patient was not listed for a lung transplant until the COVID-19 PCRs came negative on days 47 and 49 after the infection.

6.
Transplant Proc ; 53(1): 288-295, 2021.
Article in English | MEDLINE | ID: mdl-32950260

ABSTRACT

INTRODUCTION: The primary objective of this study was to determine whether pretransplant physical function is correlated with posttransplantation outcomes. METHODS: We performed a retrospective study of patients that participated in pretransplantation screening and subsequently underwent lung transplantation. Pretransplant variables of interest included demographics, muscle mass, body composition, physical function, and physical frailty. Correlation tests were performed to assess relationships with significance set at 0.05. RESULTS: Twenty-five patients with a mean age of 57 ± 13 years (68% male) with pretransplant lung allocation score of 45 ± 14 were included. This cohort had a 3-year mortality rate of 32% (n = 8). Pretransplant 4-m gait speed was significantly related to performance on the Short Physical Performance Battery (r = 0.74, P = .02) and distance ambulated on the 6-minute walk test (r = 0.62, P = .07) at hospital discharge. Older age was associated with slower gait speed and worse performance on sit-to-stand testing at hospital discharge (r = -0.76, P = .01 and r = -0.75, P = .01, respectively). Statistically, only diagnosis of cystic fibrosis was associated with 3-year mortality. DISCUSSION: Our study demonstrates that demographic, clinical, and physical function assessed prior to lung transplantation may be indicators of functional recovery.


Subject(s)
Lung Transplantation , Physical Fitness , Treatment Outcome , Adult , Aged , Body Composition , Female , Humans , Lung Transplantation/mortality , Male , Middle Aged , Patient Selection , Retrospective Studies , Walk Test , Walking Speed
8.
Monaldi Arch Chest Dis ; 90(1)2020 Feb 12.
Article in English | MEDLINE | ID: mdl-32072801

ABSTRACT

The six-minute walk test (6MWT) is a useful tool to predict outcomes in patients with advanced lung diseases. Greater distance walked has been shown to have more favorable prognostic value compared to other recorded variables.  We reviewed the medical records of 164 patients with advanced lung disease who underwent lung transplant evaluation. Results of the 6MWT (distance walked, oxygen required, and mean gait speed) were recorded and analyzed with respect to mortality. 6MWT mean oxygen (O2) flow via nasal cannula was 3.5 ± 3.7 L/min. The distance walked in meters (m) and % predicted were inversely associated with mortality, OR: 0.995 (0.992-0.998) and 0.970 (0.950-0.990), respectively. Patients who walked < 200 meters (OR: 2.1 (1.1-4.0)) or < 45% of predicted, OR: 2.7 (1.2-5.7) had higher mortality. O2 flow during the test had a direct association with mortality (OR: 1.1 (1.0-1.2). In multivariate analysis, O2 flow > 3.5 L/min remained predictive of mortality, OR: 1.1 (1.0-1.2). Mean gait speed was higher in patient who lived compared with patients who died (mean 0.83 ± 0.35 m/mim vs mean 0.69 ± 0.33 m/min, respectively, p= 0.03). Gait speed was a predictor of survival, OR 3.4 (1.1, 10.6). O2 flow during the 6MWT was an independent predictor of mortality in patients with advanced lung disease. The patients that required more than 3.5 L/m of O2 had a higher mortality. Faster gait speed during the 6MWT was also associated with better survival.


Subject(s)
Lung Diseases/mortality , Oxygen Inhalation Therapy/statistics & numerical data , Walk Test/methods , Walking Speed/physiology , Cannula , Female , Florida/epidemiology , Humans , Lung Diseases/physiopathology , Lung Diseases/surgery , Lung Transplantation/standards , Male , Middle Aged , Predictive Value of Tests , Prognosis , Respiratory Function Tests/methods , Retrospective Studies , Survival Analysis
9.
Cureus ; 12(12): e11935, 2020 Dec 06.
Article in English | MEDLINE | ID: mdl-33425515

ABSTRACT

Pregabalin is a gamma-aminobutyric acid (GABA) derivative that was commercially approved by the Food and Drug Administration (FDA) in 2004. It is commonly used in the treatment of diabetic neuropathy, peripheral neuropathy, and spinal cord injury. We present the case of a 36-year-old Caucasian male double lung transplant recipient who presented with an 18-month history of fatigue and muscle weakness. He had elevated creatinine kinase level and his muscle biopsy showed evidence of drug-induced myopathy that improved after the cessation of pregabalin. We present a case of drug-induced myopathy as a rare complication of pregabalin therapy in a double lung transplant recipient.

10.
Prog Transplant ; 29(3): 220-224, 2019 09.
Article in English | MEDLINE | ID: mdl-31159656

ABSTRACT

INTRODUCTION: Since the largest study on extensively drug-resistant organisms and lung transplantation in patients with cystic fibrosis, there have been innovations and advancements in the treatment of Pseudomonas aeruginosa. RESEARCH QUESTION: What differences exist for patients with cystic fibrosis with a history of extensively drug-resistant infections who undergo lung transplantation despite treatment advances with antimicrobial therapy? STUDY DESIGN: Two-center, retrospective, cohort study conducted in 44 patients with cystic fibrosis chronically infected with extensively drug-resistant organisms who received a lung transplant from January 2008 through August 2016. Patients in the resistant cohort were chronically infected with pan-resistant P aeruginosa, polymyxin-sensitive only, or sensitive to 2 antibiotic classes (polymyxin plus one other); remaining patients with more susceptible P aeruginosa or no P aeruginosa remained in the control cohort. The primary outcome is a composite of patient survival, retransplantation, chronic lung allograft dysfunction, and acute rejection 12 months posttransplant. Categorical variables were analyzed using χ2 testing. The independent samples t test was utilized for continuous variables. RESULTS: There was no difference in the primary outcome (40% vs 37%, P = .831). Differences between patient survival (84% vs 95%, P = .487), the incidence of acute rejection (20% vs 33%, P = .323), and the incidence of chronic lung allograft rejection (12% vs 5%, P = .441) were not different between groups. DISCUSSION: Recipients chronically infected with an extensively resistant P aeruginosa had similar outcomes compared to those infected with more sensitive organisms.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Cystic Fibrosis/surgery , Drug Resistance, Multiple, Bacterial , Graft Rejection/epidemiology , Pseudomonas Infections/therapy , Pseudomonas aeruginosa/physiology , Survival Rate , Adolescent , Adult , Case-Control Studies , Chronic Disease , Cystic Fibrosis/complications , Female , Humans , Lung Diseases/epidemiology , Lung Transplantation , Male , Polymyxins/therapeutic use , Prognosis , Pseudomonas Infections/complications , Pseudomonas Infections/microbiology , Reoperation/statistics & numerical data , Retrospective Studies , Young Adult
11.
Perfusion ; 34(2): 143-146, 2019 03.
Article in English | MEDLINE | ID: mdl-30124117

ABSTRACT

INTRODUCTION: Tracheostomy has been utilized in combination with venovenous extracorporeal membrane oxygenation (VV-ECMO) to enable early spontaneous breathing and minimize sedation requirements. Tracheostomy has been previously reported to be safe in patients supported on VV-ECMO; however, the impact of tracheostomy on blood loss in VV-ECMO patients is unknown. METHODS: We analyzed VV-ECMO patients with and without tracheostomy over a 5-year period. In order to avoid other potential sources of blood loss not related to tracheostomy or ECMO-related blood loss, patients who underwent a recent surgery prior to ECMO or during ECMO (other than tracheostomy) were excluded. RESULTS: Sixty-three patients meeting the inclusion criteria were identified (tracheostomy n=30, non-tracheostomy n=33). Tracheostomy patients were found to require more daily transfusions of red blood cells (RBC) (0.47 [0.20-1.0] vs. 0.23 [0.06-0.40] units/day, p=0.02) and total blood products (0.60 [0.32-1.0] vs. 0.31 [0.10-0.50] units/day, p=0.01). CONCLUSIONS: These results suggest that tracheostomy while on VV-ECMO predisposes patients to increased transfusion burden. Based on previous research, this increased transfusion burden could potentially be linked to increased complications and mortality.


Subject(s)
Blood Transfusion/methods , Extracorporeal Membrane Oxygenation/methods , Tracheostomy/adverse effects , Female , Humans , Male , Middle Aged , Tracheostomy/methods
12.
Transpl Infect Dis ; 20(6): e12986, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30171789

ABSTRACT

BACKGROUND: Patient outcomes post-lung transplant remain inferior to other types of solid organ transplantation. We investigated whether the presence of potentially pathogenic bacteria (PPB) in donor lung bronchial cultures was associated with adverse outcomes postoperatively. METHODS: All patients who underwent lung transplantation between August 2015 and April 2017 at the University of Kentucky Medical Center were retrospectively reviewed. Retransplants, patients with bronchiectasis (including cystic fibrosis), and individuals who received organs from donation after cardiac death (DCD) donors were excluded. The remaining subjects were separated into two groups: individuals whose donor bronchial cultures grew PPB, and those whose cultures either returned negative for PPB or were sterile. 30-day mortality rates as well as the incidence of grade 3 primary graft dysfunction (PGD) and acute kidney injury (AKI) at both 24 and 72 hours post-transplant were calculated. The duration of mechanical ventilation postoperatively was also recorded. RESULTS: Thirty two subjects comprised the study population. 20 patients (63%) had growth of PPB on donor cultures, while 12 (37%) did not. Patients with PPB had a significantly greater number of days on the ventilator postoperatively compared to those with no PPB (mean = 11.3 and median = 5.0 vs mean = 5.8 and median = 3.0, respectively, P = 0.0232). Subsequent regression analysis revealed this association to not be influenced by recipient lung allocation score (LAS), donor age, donor smoking history, recipient mean pulmonary artery pressure (mPAP) value, and/or use of cardiopulmonary bypass at the time of transplantation. Neither 30-day survival nor incidence of Grade 3 PGD and AKI at 24 or 72 hours post-transplant differed between the two groups (P > 0.05). CONCLUSION: The recovery of PPB in donor lung cultures was associated with a longer duration of mechanical ventilation postoperatively in lung transplant recipients.


Subject(s)
Acute Lung Injury/epidemiology , Allografts/microbiology , Bacteria/isolation & purification , Graft Rejection/epidemiology , Lung Transplantation/adverse effects , Lung/microbiology , Acute Lung Injury/drug therapy , Acute Lung Injury/microbiology , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Female , Graft Rejection/drug therapy , Graft Rejection/microbiology , Humans , Incidence , Male , Middle Aged , Mortality , Postoperative Period , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Time Factors , Tissue Donors/statistics & numerical data , Treatment Outcome
14.
Ann Thorac Surg ; 103(4): 1076-1083, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28017335

ABSTRACT

BACKGROUND: Lung retransplantation (ReTx) comprises an increasing share of lung transplants and recently has shown improved outcomes. The aim of this study was to identify risk factors affecting overall survival after pulmonary ReTx. METHODS: The United Network for Organ Sharing database was used to identify patients undergoing lung transplantation at our institution from 1995 to 2014. Of the total 542 lung transplants performed, 87 (16.1%) were ReTxs. The primary outcome was overall survival. Multivariate Cox regression models were used to assess the effect of recipient and donor characteristics on survival. RESULTS: Of the patients who underwent ReTx, median survival was 2 years. Predictors of worse survival include recipient age between 50 and 60 years (relative risk, 4.3; p = 0.02) or older than 60 years (relative risk, 10.2; p < 0.001), and time to ReTx of less than 2 years (relative risk, 3.8; p = 0.01). ReTx for bronchiolitis obliterans syndrome had longer median survival than for restrictive chronic lung allograft dysfunction (2.7 years vs 0.9 years; p = 0.055). Overall survival of ReTx patients after initiation of the lung allocation score was not significantly different (p = 0.21). CONCLUSIONS: Lung ReTx outcomes are significantly worse than for primary transplantation but may be appropriate in well-selected patients with certain diagnoses. Lung ReTx in patients older than 50 years or within 2 years of primary lung transplantation was associated with decreased survival. Further work is warranted to identify patients who benefit most from ReTx.


Subject(s)
Lung Transplantation/mortality , Reoperation/mortality , Adolescent , Adult , Age Factors , Bronchiolitis Obliterans/surgery , Female , Forced Expiratory Volume , Graft Rejection , Humans , Lung/physiopathology , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Analysis , Transplantation, Homologous , Young Adult
15.
Transplantation ; 99(10): 2190-5, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25769073

ABSTRACT

BACKGROUND: Acute cellular rejection (ACR) is a major early complication after lung transplantation (LT) and is a risk factor for chronic rejection. Induction immunosuppression has been used as a strategy to reduce early ACR. Recently, our LT program changed our primary induction protocol from basiliximab with standard maintenance immunosuppression to alemtuzumab induction with reduced dose maintenance immunosuppression. The objective of this study was to compare incidence of ACR after this change in the first 6 months after transplantation. METHODS: A retrospective, cohort review of patients 18 years or older, which received their first LT between January 2010 and September 2012. RESULTS: The primary outcome was comparison of average lung biopsy scores at 6 months. Secondary outcomes included development of grade A2 or higher rejection, infectious outcomes, overall graft and patient survival. At 6 months, the average biopsy score was significantly lower in the alemtuzumab group than the basiliximab group (0.12 ± 0.29 vs 0.74 ± 0.67; P < 0.0001) (Table 2). Grade 2 or higher rejection was significantly higher in the basiliximab group (P < 0.0001). CONCLUSIONS: Alemtuzumab provided superior outcomes in regard to average biopsy score and lower incidence of grade 2 or higher rejection at 6 months. There were no differences in infectious complications or overall graft or patient survival between the 2 groups.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal/administration & dosage , Immunosuppressive Agents/administration & dosage , Lung Transplantation , Recombinant Fusion Proteins/administration & dosage , Adult , Aged , Alemtuzumab , Basiliximab , Biopsy , Female , Graft Rejection/epidemiology , Humans , Immunosuppression Therapy , Male , Middle Aged , Retrospective Studies , Risk Factors , Transplant Recipients , Treatment Outcome
16.
J Heart Lung Transplant ; 34(1): 65-74, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25447585

ABSTRACT

BACKGROUND: Long-term outcomes after lung transplantation are limited due to chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS) is the most common form of obstructive CLAD and its definition derives from spirometric measurements. Given the importance of this diagnosis, both the accuracy and reliability of the definition of CLAD are crucial in understanding the pathophysiology of this disease to develop therapeutic options and influence outcome after lung transplantation. METHODS: A web-based survey was designed and distributed to members of the Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) to better understand the accuracy and reliability of pulmonary function criteria in diagnosing BOS. Spirometric data from five patient scenarios that were discordant among reviewers regarding BOS determination from the Assessment of Immunosuppressive Regimen in Suppressing Acute and Chronic Rejection (AIRSAC) trial were randomly selected and summarized in this survey. Survey questions included the respondent's general understanding of the BOS definition, the determination of BOS, and difficulties with the current BOS definition. RESULTS: Eighty-seven respondents from the Pulmonary Council of the ISHLT responded to this survey. There was an overall 70% interobserver agreement regarding the presence or absence of BOS. Among those who agreed upon the presence of BOS, there was a 41% interobserver agreement regarding its time of onset. Despite this variability, the majority of respondents were not only familiar and agreed with the BOS criteria, they also felt confident in applying these criteria. CONCLUSIONS: Our survey identified potential limitations with the current criteria for diagnosing BOS. With recognition of the various CLAD phenotypes, further refinements of these diagnostic criteria will allow for an improved ability to identify and characterize patients who develop or are at risk for BOS, prognosticate outcomes, and, most importantly, marshal in future strategies directed at treating and preventing chronic lung dysfunction after lung transplantation.


Subject(s)
Bronchiolitis Obliterans/diagnosis , Forced Expiratory Volume/physiology , Lung Transplantation , Postoperative Complications/diagnosis , Surveys and Questionnaires , Bronchiolitis Obliterans/epidemiology , Bronchiolitis Obliterans/physiopathology , Follow-Up Studies , Humans , Incidence , Postoperative Complications/epidemiology , ROC Curve , Reproducibility of Results , Retrospective Studies , Risk Factors , Spirometry/methods , Survival Rate/trends , Time Factors , United States/epidemiology
17.
J Heart Lung Transplant ; 32(7): 701-6, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23664526

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection in lung transplantation. A recent multicenter, randomized trial (the AIRSAC study) comparing sirolimus to azathioprine in lung transplant recipients showed a decreased incidence of CMV events in the sirolimus cohort. To better characterize this relationship of decreased incidence of CMV events with sirolimus, we examined known risk factors and characteristics of CMV events from the AIRSAC database. METHODS: The AIRSAC database included 181 lung transplant patients from 8 U.S.-based lung transplant centers that were randomized to sirolimus or azathioprine at 3 months post-transplantation. CMV incidence, prophylaxis, diagnosis and treatment data were all prospectively collected. Prophylaxis and treatment of CMV were at the discretion of each institution. RESULTS: The overall incidence of any CMV event was decreased in the sirolimus arm when compared with the azathioprine arm at 1 year after lung transplantation (relative risk [RR] = 0.67, confidence interval [CI] 0.55 to 0.82, p < 0.01). This decreased incidence of CMV events with sirolimus remained significant after adjusting for confounding factors of CMV serostatus and CMV prophylaxis. CONCLUSIONS: These data support results from other solid-organ transplantation studies and suggest further investigation of this agent in the treatment of lung transplant recipients at high risk for CMV events.


Subject(s)
Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/prevention & control , Immunosuppressive Agents/therapeutic use , Lung Transplantation , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Sirolimus/therapeutic use , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies
18.
Chest ; 143(6): 1717-1724, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23370547

ABSTRACT

BACKGROUND: Acute rejection remains a major source of morbidity after lung transplantation. Given the importance of this diagnosis, an international grading system was developed to standardize the diagnosis of acute lung-allograft rejection. The reliability of this grading system has not been adequately assessed by previous studies. METHODS: We examined the level of agreement in grading transbronchial biopsy specimens obtained from a large multicenter study (AIRSAC [Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen vs Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation] trial). Biopsy specimens were initially graded for acute rejection and lymphocytic bronchiolitis by the site pathologist and subsequently graded by a central pathologist. Reliability of interobserver grading was evaluated using Cohen κ coefficients. RESULTS: A total of 481 transbronchial biopsy specimens were graded by both the site and central pathologists. The overall concordance rates were 74% and 89% for grade A and grade B biopsy specimens, respectively. When samples from biopsies performed at different time points after transplantation were assessed, there was a higher level of agreement early (≤ 6 weeks) after transplant compared with later time points for acute rejection. However, there was still only moderate agreement for both grade A (κ score 0.479; 95% CI, 0.29-0.67) and grade B (κ score 0.465; 95% CI, 0.08-0.85) rejection. CONCLUSIONS: These results expand upon previous reports of interobserver variability in grading transbronchial biopsy specimens after lung transplantation. Given the variability in grading these specimens, we advocate further education of the histopathologic findings in lung transplant biopsy specimens, as well as revisiting the current criteria for grading transbronchial biopsy specimens to improve concordance among lung transplant pathologists. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT00321906; URL: www.clinicaltrials.gov.


Subject(s)
Biopsy/methods , Graft Rejection/diagnosis , Lung Transplantation/pathology , Lung/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Bronchoscopy , Female , Graft Rejection/pathology , Humans , Immunosuppression Therapy/methods , Male , Middle Aged , Observer Variation , Prospective Studies , United States
19.
Interact Cardiovasc Thorac Surg ; 15(4): 603-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22815323

ABSTRACT

OBJECTIVES: Although lung transplantation is an accepted therapy for end-stage disease, recipient outcomes continue to be hindered by early primary graft dysfunction (PGD) as well as late rejection and bronchiolitis obliterans syndrome (BOS). We have previously shown that the pro-inflammatory cytokine response following transplantation correlates with the severity of PGD. We hypothesized that lung-transplant recipients with an increased inflammatory response immediately following surgery would also have a greater incidence of unfavorable long-term outcomes including rejection, BOS and ultimately death. METHODS: A retrospective study of lung-transplant recipients (n = 19) for whom serial blood sampling of cytokines was performed for 24 h following transplantation between March 2002 and June 2003 at a single institution. Long-term follow-up was examined for rejection, BOS and survival. RESULTS: Thirteen single and six bilateral lung recipients were examined. Eleven (58%) developed BOS and eight (42%) did not. Subgroup analysis revealed an association between elevated IL-6 concentrations 4 h after reperfusion of the allograft and development of BOS (P = 0.068). The correlation between IL-6 and survival time was found to be significant (corr = -0.46, P = 0.047), indicating that higher IL-6 response had shorter survival following transplantation. CONCLUSIONS: An elevation in interleukin (IL)-6 concentration immediately following lung transplantation is associated with a trend towards development of bronchiolitis obliterans, rejection and significantly decreased survival time. Further studies are warranted to confirm the correlation between the immediate inflammatory response, PGD and BOS. Identification of patients at risk for BOS based on the cytokine response after surgery may allow for early intervention.


Subject(s)
Bronchiolitis Obliterans/etiology , Cytokines/blood , Graft Rejection/etiology , Inflammation/etiology , Lung Transplantation/adverse effects , Adult , Aged , Biomarkers/blood , Bronchiolitis Obliterans/blood , Bronchiolitis Obliterans/mortality , Female , Graft Rejection/blood , Graft Rejection/mortality , Humans , Inflammation/blood , Inflammation/immunology , Inflammation/mortality , Interleukin-6/blood , Kaplan-Meier Estimate , Logistic Models , Lung Transplantation/mortality , Male , Middle Aged , Odds Ratio , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Up-Regulation
20.
Clin Transplant ; 26(5): 672-8, 2012.
Article in English | MEDLINE | ID: mdl-22320224

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) is frequently encountered in patients with advanced lung disease before the first and second lung transplantation. We sought to determine whether there is any relationship between pulmonary hemodynamics obtained before first and second lung transplantation. We also assessed whether PH has prognostic implications in lung transplant patients going for second transplantation. METHODS: We included consecutive adult (16-yr-old or older) patients who underwent lung re-transplantation, between 1997 and 2009, and had right heart catheterization before their first and second lung transplantation. RESULTS: Eighteen patients were included in the study. Age at first transplantation was 50.4 (SD 10.4) yr, and bronchiolitis obliterans syndrome (BOS) in the transplanted lung was the only indication for re-transplantation. PH was observed in 39% of the patients before the first lung transplant and in 56% of the subjects before re-transplantation (p = 0.91). Pre-capillary PH was present in 28% (n = 5) and 33% (n = 6) of the patients before first and second lung transplantation, respectively. None of the hemodynamic variables obtained before the first transplant predicted the development of PH before re-transplantation. PH before re-transplantation did not predict survival or development of BOS after re-transplantation. CONCLUSIONS: PH before initial lung transplantation did not predict the development of PH before the second transplantation. In our cohort, PH before second lung transplantation did not predict outcomes after re-transplantation.


Subject(s)
Bronchiolitis Obliterans/complications , Hypertension, Pulmonary/diagnosis , Lung Transplantation/adverse effects , Postoperative Complications , Adolescent , Adult , Bronchiolitis Obliterans/mortality , Bronchiolitis Obliterans/surgery , Cardiac Catheterization , Female , Follow-Up Studies , Humans , Hypertension, Pulmonary/etiology , Male , Middle Aged , Prognosis , Reoperation , Young Adult
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