E Clinton Lawrence

Emory University | EU · Emory Transplant Center

SESSION TITLE: Transplantation Posters SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: Lung transplantation (LT) is an accepted therapy for many end-stage lung disorders. UNOS Regions 3 and 11, the Southeastern US, have been observed to transplant proportionally more AAs than the...

Once lung transplant candidates are listed for transplantation, the waiting time to transplant may vary from weeks to months, to possibly more than a year in certain individuals. This chapter will review the current scoring system used for allocating lungs, the Lung Allocation Score (LAS). It will address the pragmatic issues that lung transplant c...

In chronic viral infections, CD4 exhaustion correlates with poor containment of virus. We predicted that high levels of CD4 exhaustion would be beneficial in lung transplantation.Methods and MaterialsA retrospective review was performed on 96 lung transplant recipients from Feb 2006 to April 2010 with at least 1 bronchoscopy or peripheral blood (PB...

SESSION TYPE: Cancer Case Report Posters IIPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PMINTRODUCTION: Since the first case of donor-acquired lung cancer following pulmonary transplantation was described in 2001, only 4 cases of lung cancer of donor origin have been reported. We present one more patient with non-small cell lung carc...

SESSION TYPE: Miscellaneous Cases IIIPRESENTED ON: Wednesday, October 24, 2012 at 11:15 AM - 12:30 PMINTRODUCTION: This case describes a patient who developed a nut allergy after lung transplantation.CASE PRESENTATION: A 71 year-old man with idiopathic pulmonary fibrosis underwent bilateral lung transplantation in August 2011. The donor was an 15 y...

Outcomes following lung transplant are suboptimal owing to chronic allograft failure termed bronchiolitis obliterans syndrome (BOS). Prior work in both mice and humans has shown that interferon gamma (IFNG)-induced chemokines, including CXCL9 and CXCL10, are elevated in patients with established BOS. We hypothesized that patients who ultimately dev...

Outcomes following lung transplant remain suboptimal. This is attributable to variable posttransplant recovery of lung function, and inconsistent degrees of lung function loss after peak function is reached. Granzyme B is elevated in the blood and bronchoalveolar lavage (BAL) in acute rejection. We hypothesized that persistent exposure to T cells h...

Lung transplantation is associated with a high incidence of gastroesophageal reflux disease (GERD). The presence of GERD is considered a risk factor for the subsequent development of obliterative bronchiolitis (OB), and surgical correction of GERD by gastric fundoplication (GF) may be associated with increased freedom from OB. The mechanisms underl...

Gastric fundoplication (GF) for gastroesophageal reflux disease (GERD) may protect against the progression of chronic rejection in lung transplant (LT) recipients. However, the association of GERD with acute rejection episodes (ARE) is uncertain. This study sought to identify if ARE were linked to GERD in LT patients. This single-center retrospecti...

Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients. To determine whether extending prophylaxis with oral valganciclovir from the standard 3 months to 12 months after lung transplantation is efficacious. Randomized, clinical trial. Patients we...

Development of primary graft dysfunction (PGD) is associated with poor outcomes after transplantation. We hypothesized that Receptor for Advanced Glycation End-products (RAGE) levels in donor lungs is associated with the development of PGD. Furthermore, we hypothesized that RAGE levels would be increased with PGD in recipients after transplantation...

: Primary graft dysfunction (PGD) following lung transplantation is clinically similar to the acute respiratory distress syndrome. Because alcohol abuse independently increases the incidence of acute respiratory distress syndrome in at-risk individuals, we hypothesized that donor alcohol use is correlated with an increased risk of PGD. As a pilot s...

Despite advances in the field of lung transplantation, the median survival after lung transplant remains below 5 years. Early rejection is a risk factor for the development of chronic rejection. In animal models of transplant tolerance, regulatory T cells (Tregs) can prevent the establishment of rejection. This study was designed to explore the dyn...

Portopulmonary hypertension (PoPH) is a common and feared complication of end-stage liver disease, and imposes increased risk of perioperative morbidity in the liver transplant patient. Herein, we present the first successful use of Imatinib in the perioperative management of a patient who was not responding to conventional treatments as well as ou...

Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infection (LRI) and is a risk factor for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). Currently, the most widely used therapy for RSV is inhaled ribavirin. However, this therapy is costly and cumbersome. We investigated the uti...

Lung transplant (LT) recipients often receive dapsone for Pneumocystis jirovecii pneumonia (PCP) prophylaxis. However, the prevalence of dapsone-induced hematologic toxicity in LT recipients is unknown. We report a high prevalence of hemolytic anemia (HA) associated with dapsone use in LT patients when compared with other patients described in the...

Patients with secondary pulmonary hypertension frequently present for evaluation for lung transplantation. In some of these patients, Eisenmenger's syndrome has developed from chronic left to right intracardiac shunts. A smaller group of these patients will also have associated pulmonary artery aneurysms. There is a paucity of literature discussing...

Over the past decade effective medical treatments for idio- pathic pulmonary arterial hypertension (IPAH) have de- creased but not eliminated the need for lung transplantation for this disease. Timing of referral for transplant and listing remain critical judgments in the management of many PAH patients but are still subjects of significant debate....

PURPOSE: Dapsone is commonly used for prophylaxis against Pneumocystis jirovecii pneumonia in patients intolerant to first line agents such as sulfamethoxazole. Allograft recipients may receive dapsone due to renal dysfunction or reported allergies to sulfa. Though dapsone prophylaxis may cause hemolytic anemia and methemoglobinemia, the prevalence...

Bosentan, an oral ET(A)/ET(B) receptor antagonist, is approved for the treatment of pulmonary arterial hypertension (PAH). However, some patients discontinue bosentan because of hepatotoxicity or inadequate efficacy. Sitaxsentan, an oral, ET(A)-selective endothelin antagonist currently under investigation, may be an alternative treatment option. In...

Delayed chest closure (DCC) may be used after bilateral lung transplantation when significant bleeding/coagulopathy or severe pulmonary edema exists. Primary chest closure (PCC) in these patients can lead to heart and lung compression causing cardiopulmonary instability. The purpose of this study is to describe factors associated with DCC and evalu...

We sought to determine the optimal dose of the selective endothelin A (ET(A)) receptor antagonist sitaxsentan for the treatment of pulmonary arterial hypertension (PAH); for observation only, an open-label (OL) bosentan arm was included. Endothelin is a mediator of PAH. In a preliminary PAH study, the selective ET(A) receptor antagonist sitaxsentan...

Inhaled vasodilator therapy for pulmonary hypertension may decrease the systemic side effects commonly observed with systemic administration. Inhaled medications only reach ventilated areas of the lung, so local vasodilation may improve ventilation-perfusion matching and oxygenation. We compared the effects of intravenous vs. aerosolized treprostin...

Pulmonary alveolar proteinosis is a disorder of unknown origin that occurs rarely after lung transplantation. We identified a patient with pulmonary alveolar proteinosis 66 days after undergoing single lung transplantation for idiopathic pulmonary fibrosis. We based the diagnosis on the presence of amorphous clumps or globules of acellular and fine...

Airway complications after lung transplantation remain a major cause of postoperative morbidity and mortality. Interventional bronchoscopic management continues to be the main modality in the management of these problems. Four patients with airway stenoses after lung transplantation received high dose rate brachytherapy for management of recurrent...

To demonstrate an association between saprophytic fungal infections occurring at the bronchial anastomosis (BA) and the development of additional complications arising at this site. Retrospective review. University lung transplant center. Review of all single-lung and double-lung transplant (LTX) recipients who underwent transplantation between Jun...

Lung transplantation is a viable therapeutic option for patients with end-stage lung disease. Quality of life and survival are improved for most recipients. Donor availability remains an impediment to widespread application. The development of OB after lung transplantation continues to affect long-term survival. Clinical and basic science research...

Lung transplantation is now an accepted therapeutic option for many patients with incurable end-stage lung or pulmonary vascular disease processes for which other treatment options have been expended. However, as lung transplantation has evolved as a recognized discipline over the past decade, a variety of ethical issues related to the transplant p...

Purpose: Single Lung Transplantation (SLT) is an effective treatment for both advanced emphysema (Emp) and pulmonary fibrosis (PF). Serial pulmonary function testing (PFT) is important for assessing the transplanted lung but combines the function of both native (N) and transplanted (Tx) lungs. We postulated that computed tomography (CT) calculated...

Single lung transplantation for emphysema is now standard practice despite initial concerns, including the possibility that the compliant diseased lung would compress the transplanted lung as a result of hyperinflation. We describe a patient with severe bilateral bullous emphysema and alpha-1-antitrypsin deficiency who underwent single lung transpl...

Noninvasive methods to assess immune activation would be helpful in optimizing therapy after heart transplantation to reduce rejection (acute and chronic) and complications caused by excessive immunosuppressive therapy. Intercellular adhesion molecule 1 has been shown to play an important role in T-cell activation and allograft rejection. A soluble...

Polymerase chain reaction (PCR) amplification of CMV DNA recovered from bronchial alveolar lavage (BAL) and peripheral blood samples was compared with tissue culture, cytology, and/or histology for the earlier detection of CMV pneumonitis in 12 recipients of single-lung or heart/lung transplants. In patients with confirmed CMV pneumonitis, cytologi...

Certain dynamics of rejection after heart transplantation can be characterized by measuring soluble interleukin-2 receptor levels. To determine whether elevated levels could predict development of coronary artery disease, the mean of three weekly determinations the first month after heart transplantation, as well as values obtained at 6 months, 12...

We report the cases of two lung transplant recipients (one heart-lung and one single lung) who eventually developed cytomegalovirus (CMV) pneumonitis after documentation of increasing CMV DNA titers in sequential bronchoalveolar lavage (BAL) specimens by polymerase chain reaction (PCR) amplification. To our knowledge, this is the first report that...

Quantification of T cell activation after cardiac transplant by measuring serum soluble interleukin 2 receptor levels daily may give insight into immunologic dynamics after cardiac allograft implantation. It was our hypothesis that this protein would demonstrate a characteristic rise after heart transplant not related to severe rejection that was d...

Successful cardiac transplantation requires suppression of rejection, and endomyocardial biopsy is generally used to quantify this and guide immunotherapy. Biopsy, however, is an invasive, costly, cardiac catheterization with repetition limited. Since rejection requires lymphocyte activation, an alternative method of assessing rejection dynamics mi...

Rejection dynamics after heart transplantation might be characterized by soluble interleukin-2 receptor levels. To determine whether elevated levels early (measured by enzyme-linked immunosorbent assay once weekly the first 3 weeks at time of heart biopsy) after transplantation predict mortality and development of coronary disease, the means of the...

The long-term success of heart-lung transplantation is limited by the development of bronchiolitis obliterans, possibly as a form of chronic lung allograft rejection. In the present study, we have characterized by immunohistochemical staining the lymphocytes infiltrating the lesions of bronchiolitis obliterans in one patient following heart-lung tr...

Single lung transplantation may be performed without pump oxygenation in the majority of patients. From April 1987 to August 1989, 3 of 12 patients undergoing single lung transplantation required pump oxygenation. One patient required pump oxygenation because of a marked drop in oxygen saturation during test clamping of the pulmonary artery; one pa...

Restrictive pulmonary function after heart-lung transplantation (HLT) has been attributed to the use of smaller donor lungs and/or an inability to generate normal negative pleural pressures. Pleural pressure generation depends on both the size of the recipient thoracic cage and its neuromuscular integrity. To determine whether lung volumes after he...

Improvements in our understanding of the mechanisms underlying the rejection coupled with the development of novel approaches to dealing with the rejection process have allowed successful lung and heart-lung transplantation. Nonetheless, successful lung transplantation is still limited by acute rejection. This article defines the rejection process...

Activation of T-lymphocytes is accompanied by the release of interleukin-2 receptors (IL-2R) in a soluble form that can be measured as an index of the activation process. We performed a prospective, blinded study of the dynamic changes in soluble IL-2R levels in serum in 12 patients undergoing lung or heart-lung transplantation. The levels of solub...

The histopathologic changes of acute rejection in experimental and therapeutic lung transplantation have been described with emphasis on perivascular lymphocytic infiltrates. However, the clinical usefulness of these changes in the differentiation of acute rejection from opportunistic infection on lung biopsy is not clear. Since 1985, 5 single-lung...

This study examined different markers of lung immunologic and inflammatory responses to previous asbestos exposure. We performed bronchoalveolar lavage (BAL) and gallium-67 (67Ga) lung scans and measured serum and BAL soluble interleukin-2 receptor (IL-2R) and angiotensin-converting enzyme (SACE) levels in 32 subjects with a history of significant...

Despite improved surgical techniques and advances in immunosuppressive therapy, posttransplant mortality rates remain significantly high in lung transplant patients. Since 1985, 3 of 6 single lung recipients, 3 of 3 double lung recipients, and 4 of 7 heart-lung recipients have died and undergone autopsy. We reviewed the autopsy findings in these pa...

Pulmonary toxicity developed in 15 (17%) of 89 patients treated with amiodarone during a follow-up period of 2 weeks to 54 (mean 20 +/- 15) months. Prospective evaluation of serial pulmonary function tests in 67 patients demonstrated both a significant decrease from baseline in three of six variables in patients with toxicity at the time of diagnos...

Reported is an instance of bronchiolitis obliterans due to the accumulation of lipid-laden cells within bronchiolar walls and lumina. The bronchiolar lining had extensive squamous and goblet cell metaplasia with focal ulceration. Scattered foci of cholesterol pneumonia, composed of acicular crystals with an associated foamy lipid material and type...

Sarcoidosis is a granulomatous disorder of unknown cause characterized by activation of T-lymphocytes. We here report the use of an enzyme-linked immunosorbent assay for the soluble interleukin-2 receptor (IL-2R) as a measure of T-cell activation in serum samples and bronchoalveolar lavage fluids in 15 patients with active sarcoidosis. The geometri...

We have previously reported serum elevations of the soluble form of the interleukin-2 receptor (IL-2R), a marker of T-cell activation, in sarcoidosis. In the present study, an enzyme-linked immunosorbent assay for soluble IL-2R was employed to compare sera from normal controls with those from patients with active sarcoidosis or idiopathic pulmonary...

The susceptibility of smokers to pneumonia caused by Haemophilus influenzae may result from impairment of phagocytic or bactericidal function of pulmonary alveolar macrophages (PAM). We compared ingestion and killing of non-typable H. influenzae and H. influenzae type B by alveolar macrophages from asymptomatic smokers and non-smokers. Three times...

Though successfully transplanted hearts respond in such a way that individuals remain remarkably asymptomatic, they do not function normally. Characterization of early hemodynamic patterns and their evolvement has not been done. The evolution of hemodynamic indices in 20 patients receiving orthotopic heart (n = 17) or combined heart-lung (n = 3) tr...

The majority of cases of bronchogenic carcinoma remain incurable, and many of these patients require palliation of the effects of the tumor on the airway. We have developed a technique for implanting radioactive (198Au) seeds via the fiberoptic bronchoscope. We now retrospectively review the results obtained in 111 procedures in 54 patients. Respon...

Human pulmonary alveolar macrophages were used to quantitate the cytotoxic effect of surface-altered chrysotile asbestos. Little difference was observed in mortality between chrysotile asbestos that was surface-treated to a 42% extent by a hydrophobic organosilane or untreated chrysotile. Little or no effect on mortality was observed when human pul...

We report a patient who, 3 weeks after initiation of therapy, experienced a hypersensitivity reaction to phenytoin manifested as rash, lymphadenopathy, elevated serum transaminase levels, and subsequent panhypogammaglobulinemia with IgG, 180 mg/dl (control range 639 to 1349); IgA, 15 mg/dl (control range 70 to 312); and IgM, 0 mg/dl (control range...

A luminol-enhanced chemiluminescence assay was used to measure light elaborated by peripheral blood polymorphonuclear leukocytes (PMNs) and by pulmonary alveolar macrophages (PAMs) from 14 healthy, normal subjects and 16 patients with sarcoidosis. Resting peripheral blood PMNs (incubated only in medium) from patients with sarcoidosis generated subs...

To investigate the possible antibacterial properties of human alveolar lining material (ALM), we obtained ALM and pulmonary alveolar macrophages (PAM) by bronchoalveolar lavage of healthy nonsmokers. Alveolar lining material was isolated by centrifugation or micropore filtration; electron microscopy revealed lamellar bodies, and lipid analysis show...

To investigate factors that determine susceptibility of the lungs to infection with common respiratory pathogens, we studied phagocytosis and killing of nontypable Haemophilus influenzae, H. influenzae type b, Streptococcus pneumoniae types III, VI, and XIV, an unencapsulated variant of S. pneumoniae type III, and Staphylococcus aureus Cowan I, by...

We report the evaluation of in vitro immunoregulation in a 12-year-old untreated boy with severe combined immunodeficiency (SCID). Severely hypogammaglobulinemic, the patient was incapable of a specific antibody response to either natural substances or administered antigens. Ficoll-Hypaque-isolated peripheral blood mononuclear cells (MNL) from the...

We report the evaluation of in vitro immunoregulation in a 12-year-old untreated boy with severe combined immunodeficiency (SCID). Severely hypogammaglobulinemic, the patient was incapable of a specific antibody response to either natural substances or administered antigens. Ficoll-Hypaque-isolated peripheral blood mononuclear cells (MNL) from the...

The subsets of T lymphocytes in two infants affected with Omenn's syndrome and in 109 healthy members of the highly inbred pedigree were studied. Eighteen homozygotes in this pedigree had previously died from infection at less than 6 months of age. Both infants displayed normal numbers of peripheral blood T (E-rosette) lynphocytes, poor mitogen rea...

Serial changes in various markers of disease activity with corticosteroid therapy were assessed in 12 patients with active sarcoidosis. After six weeks of treatment with 40 mg daily of prednisone, all but one patient demonstrated symptomatic and radiographic improvement. For the entire patient group, there were corresponding improvements in forced...

We investigated the in vitro effects of amosite asbestos on immunoglobulin (Ig) secretion by human peripheral blood mononuclear leukocytes (MNL). Concentrations of 100 to 300 micrograms/ml of amosite asbestos reduced the number of Ig-secreting cells recovered from 6-day cultures of unstimulated MNL or MNL stimulated with Epstein Barr virus. By cont...

The effects of human bronchoalveolar cells on pokeweed-mitogen-induced immunoglobulin(Ig) secretion in vitro were investigated, using a reverse hemolytic plaque assay. Unfractionated peripheral blood mononuclear cells from 7 nonsmoking normal subjects responded to pokeweed mitogen with a geometric mean of 6,550 Ig-secreting cells per million cultur...

We studied in vitro immunoregulation of immunoglobulin (Ig) secretion in 21 patients with sarcoidosis. While peripheral blood mononuclear cells from normal individuals responded to pokeweed mitogen with a 10-fold or greater increment in Ig-secreting cells, cells from sarcoid patients failed to respond to pokeweed mitogen at any concentration employ...