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Elbert P Trulock

Publications and source records attributed to Elbert P Trulock.

At least 19 recordsLinked to original sources
PubMed2006

Elevated soluble CD30 correlates with development of bronchiolitis obliterans syndrome following lung transplantation.

BACKGROUND: The long-term function of lung transplants is limited by chronic rejection (bronchiolitis obliterans syndrome, BOS). Due to lack of specific markers, BOS is diagnosed clinically. Because there is strong evidence that alloimmunity plays a significant role in the pathogenesis of BOS, we investigated whether soluble CD30 (sCD30), a T-cell activation marker, would correlate with BOS. METHODS: Sera collected serially from BOS+ (n = 20) and matched BOS- (n = 20) lung transplant (LT) patients were analyzed for sCD30 by enzyme-linked immunosorbent assay. Pretransplant sera and sera from normal donors were also analyzed. RESULTS: PreLT levels were comparable to normal subjects. However, posttransplant there was a significant elevation in sCD30 levels during BOS development in all BOS+ patients, compared to BOS- (mean 139.8+/-10.7 vs. 14.8+/-2.7 U/ml, P < 0.001). sCD30 levels declined in the BOS+ patients but were still elevated compared to BOS- (48.52+/-5.04 vs. 7.19+/-2.9, P < 0.0001). CONCLUSIONS: We conclude that sCD30 may represent a novel marker to monitor the development of BOS.

Adult↗
PubMed2006

Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome.

RATIONALE: Primary graft dysfunction is a common complication after lung transplantation and a significant risk factor for short- and long-term mortality. OBJECTIVE: We examined the impact of primary graft dysfunction on bronchiolitis obliterans syndrome. METHODS: We performed a retrospective cohort study of 334 adult lung transplant recipients at our program and graded the severity of primary graft dysfunction according to the International Society for Heart and Lung Transplantation definition. We evaluated the impact of primary graft dysfunction on acute rejection, lymphocytic bronchitis, and bronchiolitis obliterans syndrome stage 1, using univariable and multivariable Cox proportional hazards models. MAIN RESULTS: Among the 334 recipients, 65 did not have primary graft dysfunction (grade 0), 130 had grade 1, 69 had grade 2, and 70 had grade 3. In the univariable analysis, all grades of primary graft dysfunction were associated with a significantly increased risk of bronchiolitis obliterans syndrome stage 1 (grade 1: relative risk [RR] = 1.73; grade 2: RR = 2.13; and grade 3: RR = 2.53, compared with grade 0). The multivariable model demonstrated that the increased risk of bronchiolitis obliterans syndrome associated with primary graft dysfunction was independent of acute rejection, lymphocytic bronchitis, and community-acquired respiratory viral infections. However, there was no association between primary graft dysfunction and acute rejection or lymphocytic bronchitis. CONCLUSIONS: Primary graft dysfunction is associated with an increased risk of bronchiolitis obliterans syndrome independent of acute rejection, lymphocytic bronchitis, and community-acquired respiratory viral infections, and this risk is directly related to the severity of primary graft dysfunction.

Adult↗
PubMed2006

Induction of IL-10 suppressors in lung transplant patients by CD4+25+ regulatory T cells through CTLA-4 signaling.

T cell-mediated autoimmunity to collagen V (col-V), a sequestered yet immunogenic self-protein, can induce chronic lung allograft rejection in rodent models. In this study we characterized the role of CD4+ CD25+ regulatory T cells (Tregs) in regulating col-V autoimmunity in human lung transplant (LT) recipients. LT recipients revealed a high frequency of col-V-reactive, IL-10-producing CD4+ T cells (T IL-10 cells) with low IL-2-, IFN-gamma-, IL-5-, and no IL-4-producing T cells. These T(IL-10) cells were distinct from Tregs because they lacked constitutive expression of both CD25 and Foxp3. Expansion of T IL-10 cells during col-V stimulation in vitro involved CTLA-4 on Tregs, because both depleting and blocking Tregs with anti-CTLA4 F(ab')2 mAbs resulted in loss of T IL-10 cells with a concomitant increase in IFN-gamma producing Th1 cells (TIFN-gamma cells). A Transwell culture of col-V-specific T IL-10 cells with Th1 cells (those generated in absence of Tregs) from the same patient resulted in marked inhibition of IFN-gamma and proliferation of T(IFN-gamma) cells, which was reversed by neutralizing IL-10. Furthermore, the T IL-10 cells were HLA class II restricted because blocking HLA class II on APCs resulted in the loss of IL-10 production. Chronic lung allograft rejection was associated with the loss of Tregs with a concomitant decrease in T IL-10 cells and an increase in T IFN-gamma cells. We conclude that LT patients have col-V-specific T cells that can be detected in the peripheral blood. The predominant col-V-specific T cells produce IL-10 that suppresses autoreactive Th1 cells independently of direct cellular contact. Tregs are pivotal for the induction of these "suppressor" T IL-10 cells.

Antigens, CD↗
PubMed2006

IL-12 p80 is an innate epithelial cell effector that mediates chronic allograft dysfunction.

RATIONALE: Bronchiolitis obliterans syndrome is the leading cause of chronic lung allograft dysfunction. We have demonstrated that respiratory viral infection is a bronchiolitis obliterans syndrome risk factor and virus-dependent injury induces expression of innate airway epithelial genes belonging to the interleukin (IL)-12 family. Thus, we hypothesized that epithelial cell IL-12 family members could mediate lung allograft dysfunction. OBJECTIVES: We used mouse and human allograft specimens to evaluate the role of epithelial cell IL-12 family members in allograft dysfunction associated with and without viral infection. METHODS: Murine and human IL-12 family members were characterized and manipulated in allografts and then correlated with epithelial cell injury, immune cell accumulation, and collagen deposition. RESULTS: In a mouse model of lung transplantation, concurrent viral infection and allogeneic transplantation increased epithelial injury and this was followed by exaggerated accumulation of macrophages and collagen deposition. This virus-driven allograft dysfunction was associated with an epithelial innate response manifested by a synergistic increase in the production of the macrophage chemoattractant IL-12 p80 (p80), but not IL-12 or IL-23. Blockade or overexpression of donor epithelial p80 resulted in a corresponding abrogation or enhancement of macrophage accumulation and allograft dysfunction. We extended these findings to human recipients with viral infection and transplant bronchitis and again observed excessive epithelial p80 expression that correlated with increased macrophage accumulation. CONCLUSIONS: These experiments support a role for an enhanced epithelial innate response as a central process in allograft dysfunction and identify the macrophage chemoattractant p80 as an innate epithelial effector of disease progression.

Animals↗
PubMed2006

Thrombotic microangiopathy after lung transplantation.

BACKGROUND: Thrombotic microangiopathy (TMA) is a well-recognized complication after transplantation. The purpose of this study was to describe our center's experience with this complication after lung transplantation. METHODS: We retrospectively reviewed cases of TMA among patients who underwent lung transplantation between January 1, 1999 and December 31, 2003 (n = 257). The cases were characterized and the outcomes were analyzed. Univariate and multivariate Cox regression models were constructed to identify potential risk factors for TMA. RESULTS: Twenty-four cases of TMA developed in 20 recipients. Thirteen cases occurred in the setting of another illness and 11 cases were isolated complications. Multivariate Cox regression models identified female gender, history of TMA, and the immunosuppressive regimen as independent predictors of TMA. Maintenance immunosuppression with the combination of a calcineurin inhibitor and sirolimus carried a significantly higher risk of TMA than a calcineurin inhibitor alone. After the diagnosis of TMA, calcineurin inhibitors were stopped in 18 cases; however, in 6 cases in which the onset of TMA coincided with the addition of sirolimus to a calcineurin inhibitor, only sirolimus was discontinued. Plasmapheresis was performed for severe cases (n = 10). TMA remitted in all cases, and an alternate calcineurin inhibitor was introduced in 14 cases. TMA recurred in 4 recipients, a median 253 days after the initial episode. The median survival after the onset of TMA was 377 days. CONCLUSION: TMA is a serious complication after lung transplantation, and the risk is highest when sirolimus is used in combination with a calcineurin inhibitor.

Female↗
PubMed2006

Does the presence of preoperative mild or moderate coronary artery disease affect the outcomes of lung transplantation?

BACKGROUND: Significant coronary artery disease (CAD) is an exclusion criterion for lung transplantation at most centers. However, the impact of preoperative noncritical CAD (single or multivessel mild <30% or moderate 30% to 50% stenosis) on the outcomes of lung transplantation is unknown. METHODS: A retrospective review of 268 adult patients who underwent lung transplantation between June 1998 and June 2003 at Barnes-Jewish Hospital, a tertiary care center affiliated with Washington University School of Medicine, was performed. RESULTS: Two hundred ten patients had coronary angiography performed as part of their pretransplantation evaluation. Among these patients, 177 patients had no CAD, and 33 patients (mild, 16; moderate, 17) had noncritical CAD. Patients with noncritical CAD were older (59 versus 55 years, p < 0.001) and had a higher prevalence of diabetes (24% versus 9%, p = 0.014) and systemic hypertension (58% versus 36%, p = 0.004) than patients without CAD. There was no significant difference in the underlying lung disease, other comorbidities, type of lung transplantation performed, early postoperative complications, and hospital or late mortality between recipients with or without CAD. Among the patients with noncritical CAD, there was no hospital mortality and no late cardiac mortality. Three recipients with preoperative moderate CAD developed late ischemic cardiac events, and revascularization was performed in 2 of these recipients. Long-term survival was similar among recipients with or without preoperative CAD. CONCLUSIONS: Preoperative noncritical (mild or moderate) CAD was not associated with increased perioperative morbidity or mortality, and it did not adversely affect short-term or long-term survival. Late ischemic events developed in 18% of the recipients with moderate CAD disease with no effect on mortality.

Adult↗
PubMed2006

Recurrence of bilateral diffuse bronchiectasis after bilateral lung transplantation.

We report two cases of bilateral diffuse bronchiectasis in which early recurrence of the original lung disease occurred after bilateral lung transplantation (LT). Patient 1 underwent cadaveric LT. Recurrent bronchiectasis occurred 4 months later, and he died 6 years after LT. Patient 2 underwent living-related lobar LT, bronchiectasis relapsed 4 months later, and he died 13 months after LT. Both cases were finally diagnosed as bilateral diffuse bronchiectasis by the pathological features of the explanted lungs: infiltration of inflammatory cells predominantly in the conducting airways with dilation of the bronchi of bilateral lungs and scarcity of foamy macrophages in the wall of the respiratory bronchioles. Similar pathological features were seen in autopsy specimens from patient 1 and a transbronchial biopsy specimen from patient 2. LT should be carried out with caution in patients with bilateral diffuse bronchiectasis. When performing LT in such patients, it is suggested that sinusitis should be controlled perioperatively.

Adult↗
PubMed2005

The significance of a single episode of minimal acute rejection after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) remains the leading obstacle to better long-term outcomes after lung transplantation. Acute rejection has been identified as the primary risk factor for BOS, but the impact of minimal acute rejection, especially a solitary episode, has usually been discounted as clinically insignificant. METHODS: We performed a retrospective cohort study of 259 adult lung transplant recipients to determine the risk of BOS associated with a single episode of A1 rejection, without recurrence or subsequent progression to a higher grade. The cohort was divided into 3 groups based on the severity of acute rejection (none, single episode of A1, and single episode of A2). We determined the risks of BOS stages 1, 2, 3, and death for each group using univariate and multivariate Cox regression analyses. RESULTS: A solitary episode of A1 rejection was a significant risk factor for BOS stages 1 and 2, but not stage 3 or death, in the univariate analysis. Multivariate Cox regression models confirmed that the risk of BOS attributable to a single episode of A1 rejection was independent of other potential risk factors, such as community acquired respiratory viral infections, number of HLA mismatches, and cytomegalovirus pneumonitis. Likewise, univariate and multivariate analyses demonstrated that a single episode of A2 rejection was a significant risk factor for all stages of BOS but not death. CONCLUSIONS: A single episode of minimal acute rejection without recurrence or subsequent progression to a higher grade is a significant predictor of BOS independent of other risk factors.

Adult↗
PubMed2005

Detection of severe human metapneumovirus infection by real-time polymerase chain reaction and histopathological assessment.

BACKGROUND: Infections with common respiratory tract viruses can cause high mortality, especially in immunocompromised hosts, but the impact of human metapneumovirus (hMPV) in this setting was previously unknown. METHODS: We evaluated consecutive bronchoalveolar lavage and bronchial wash fluid samples from 688 patients--72% were immunocompromised and were predominantly lung transplant recipients--for hMPV by use of quantitative real-time polymerase chain reaction (PCR), and positive results were correlated with clinical outcome and results of viral cultures, in situ hybridization, and lung histopathological assessment. RESULTS: Six cases of hMPV infection were identified, and they had a similar frequency and occurred in a similar age range as other paramyxoviral infections. Four of 6 infections occurred in immunocompromised patients. Infection was confirmed by in situ hybridization for the viral nucleocapsid gene. Histopathological assessment of lung tissue samples showed acute and organizing injury, and smudge cell formation was distinct from findings in infections with other paramyxoviruses. Each patient with high titers of hMPV exhibited a complicated clinical course requiring prolonged hospitalization. CONCLUSIONS: Our results provide in situ evidence of hMPV infection in humans and suggest that hMPV is a cause of clinically severe lower respiratory tract infection that can be detected during bronchoscopy by use of real-time PCR and routine histopathological assessment.

Adolescent↗
PubMed2005

Pneumonia in the solid organ transplant patient.

As the field of solid organ transplantation has grown, so has the importance of infectious complications in this select group of patients. Chronic immunosuppression compromises the natural host defenses that typically prevent lower respiratory tract infections and makes the solid organ transplant recipient especially susceptible to pneumonia. Evaluation of pneumonia in this population differs owing to the potential for opportunistic infections. Lung transplant recipients are particularly susceptible to pneumonia and pose unique diagnostic dilemmas. An understanding of the time line for the different key pathogens after transplantation aids the initial evaluation and management.

Humans↗
PubMed2005

Reliability for grading acute rejection and airway inflammation after lung transplantation.

BACKGROUND: The Lung Rejection Study Group (LRSG) created a scheme for grading acute allograft rejection in 1990 and then revised it in 1996, but virtually no studies have evaluated the reliability of this formulation. This investigation assessed the reliability of the current LRSG system by determining inter- and intrareader agreement for grading transbronchial biopsy samples from lung transplant recipients. METHODS: Biopsy samples from a cohort of 204 recipients were reviewed and classified by a single pathologist who was blinded to original interpretations. The "A" and "B" rejection grades from this contemporary review were compared with original grades by the kappa statistic. RESULTS: For "A" grading, weighted kappa was 0.65 (95% confidence interval [CI] 0.60-0.70) for interreader agreement (n = 529 specimens) and 0.65 (95% CI 0.53-0.76) for intrareader agreement (n = 97 specimens). For "B" grading, weighted kappa was 0.26 (95% CI 0.14-0.39) for interreader agreement (n = 164 specimens) and 0.33 (95% CI 0.15-0.51) for intrareader agreement (n = 58 specimens). CONCLUSIONS: On the basis of the analysis of the LRSG scheme, "A" grades exhibit very good reliability, but "B" grades have only fair reliability, and steps to improve this shortcoming should be taken.

Acute Disease↗
PubMed2005

A comparison of basiliximab and anti-thymocyte globulin as induction agents after lung transplantation.

BACKGROUND: Interleukin-2 receptor antagonists have supplanted polyclonal antibody preparations as the most frequently used induction agents after lung transplantation, but the relative efficacy of these agents has not been firmly established. METHODS: We retrospectively analyzed the efficacy of basiliximab compared with antithymocyte globulin among 157 adult lung transplant recipients at our center. RESULTS: At 3, 6, and 12 months after transplantation, the median cumulative acute rejection A scores for the basiliximab group (2, 2, and 3, respectively) were significantly higher than those for the anti-thymocyte globulin group (1, 1, and 2, respectively; p = 0.003, 0.004, and 0.033, respectively). In addition, basiliximab recipients were more likely to develop acute rejection grade > or = A2 than anti-thymocyte globulin recipients; in fact, 60% of basiliximab recipients compared with 38% of anti-thymocyte globulin recipients developed their first episode of acute rejection grade > or = A2 in the first 100 days after transplantation (log-rank p = 0.04). Furthermore, basiliximab recipients were more likely to develop bronchiolitis obliterans syndrome than anti-thymocyte globulin recipients (log-rank p = 0.036). Two years after transplantation, 36% of basiliximab recipients and 26% of anti-thymocyte globulin recipients developed bronchiolitis obliterans syndrome. However, there were no significant differences in the incidences of cytomegalovirus viremia and pneumonitis between the 2 groups (p = 0.86 and 0.89, respectively). CONCLUSIONS: Induction with anti-thymocyte globulin is associated with a lower burden of acute rejection and bronchiolitis obliterans syndrome compared with basiliximab, without a significant difference in the incidence of cytomegalovirus infections.

Adult↗