Thoracic organ transplantation in the United States, 1995-2004.

This article reviews trends in thoracic organ transplantation based on OPTN/SRTR data from 1995 to 2004. The number of active waiting list patients for heart transplants continues to decline, primarily because there are fewer patients with coronary artery disease listed for transplantation. Waiting times for heart transplantation have decreased, and waiting list deaths also have declined, from 259 per 1000 patient-years at risk in 1995 to 156 in 2004. Fewer heart transplants were performed in 2004 than in 1995, but adjusted patient survival increased to 88% at 1 year and 73% at 5 years. Emphysema, idiopathic pulmonary fibrosis and cystic fibrosis were the most common indications among lung transplant recipients in 2004. Waiting time for lung transplantation decreased between 1999 and 2004. Waiting list mortality decreased to 134 per 1000 patient-years at risk in 2004. One-year survival following transplantation has improved significantly in the past decade. The number of combined heart-lung transplants performed in the United States remains low, with only 39 performed in 2004. Overall unadjusted survival, at 58% at 1 year and 40% at 5 years, is lower among heart-lung recipients than among either heart or lung recipients alone.

Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients.

BACKGROUND: We prospectively compared the hybrid capture system (HCS) assay with conventional cell culture and shell vial assay for the detection of cytomegalovirus (CMV) infection and disease in the lung transplant population. METHODS: Between January 1999 and February 2000, 34 lung transplant patients at Loyola University Medical Center, who were considered to be at risk for CMV disease, underwent surveillance testing for CMV cell culture, shell vial assay and HCS assay according to a pre-determined schedule. In addition, bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed at regular intervals and for clinical indications. All BAL samples were sent for CMV cultures and biopsy specimens were analyzed for histopathologic evidence of CMV by immunoperoxidase staining using antibody to early immediate nuclear antigen. RESULTS: Ten patients developed CMV disease/syndrome during the course of the study. The sensitivity, specificity, positive predictive value and negative predictive value were >90% for the HCS assay. The sensitivity of the HCS assay (90%) was statistically significantly higher than the sensitivity of either the SV assay (40%) or the cell culture (50%). In addition, the HCS assay was able to detect CMV 50 +/- 67 days prior to clinical evidence of CMV disease and an average of 36 days prior to the other detection techniques. CONCLUSION: The HCS assay is a sensitive diagnostic technique able to reliably detect CMV disease earlier than other diagnostic methods in the lung transplant population. Future studies may be able to evaluate whether pre-emptive anti-viral therapy targeted to specific viral loads using the HCS assay will be beneficial in preventing morbidity associated with CMV disease.

Low rate of acute lung allograft rejection after the use of daclizumab, an interleukin 2 receptor antibody.

BACKGROUND: The incidence and the severity of acute lung allograft rejection has been linked to the development of bronchiolitis obliterans syndrome. Therefore, we investigated the effects of daclizumab, a humanized monoclonal antibody directed against the alpha subunit of the interleukin 2 receptor, in reducing acute rejection after transplantation. METHODS: We retrospectively evaluated 27 patients who received daclizumab as induction immunosuppression and compared them with a historical control group of 34 patients. Both groups received similar immunosuppressive regimens involving tacrolimus, prednisone, and either azathioprine or mycophenolate mofetil. All patients received cytomegalovirus and aspergillus prophylaxis. RESULTS: Twenty-one patients in the control group and 22 patients in the daclizumab group were available for analysis at 6 months after lung transplantation. Ten (48%) patients in the control group had at least grade 2 acute rejection compared with four (18%) in the daclizumab group (P<0.04). The incidence of infection was similar in both groups. One patient in each group developed posttransplant lymphoproliferative disease. CONCLUSION: Therapy with daclizumab resulted in a significant decrease in the incidence of grade 2 or greater acute rejection after lung transplantation compared with historical controls. There seems to be no increase in the incidence of adverse effects in the patients treated with daclizumab.

Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation.

BACKGROUND: Currently the most important limitation in lung transplantation is donor availability. Although liberalization of donor criteria may aid in expanding the donor pool, the long-term effects of the use of "marginal" or "extended" donors remains unexplored. METHODS: In this study, we included all patients who underwent lung transplantation from January 1996 to December 1999 at Loyola University Medical Center. We categorized patients as either receiving lungs from an "ideal" donor or an "extended" donor. Extended donors were defined as having any 1 of the following criteria: donor age > 55 years, tobacco history > 20 pack years, presence of infiltrate on chest x-ray, donor ventilator time > 5 days, or donor use of inhaled drugs (cocaine or marijuana). We then compared the 2 groups with regard to short-term (operating room [OR] complications, intensive care unit [ICU] complications) and long-term outcomes (1-year pulmonary function and survival). RESULTS: Sixty-one (54%) patients received lungs from ideal donors and 52 (46%) patients received lungs from extended donors as defined above. We observed no significant differences between the 2 groups in OR complications (cardiopulmonary bypass, bleeding complications, life-threatening arrhythmias) or ICU complications (pneumonia, airway dehiscence, reoperation within 30 days related to transplantation). In addition, the 2 groups had similar median intubation times (21 hours in the ideal donor group and 20 hours in the extended donor group; p = n.s.), hospital length of stay (14+/-12 days in the ideal donor group and 12+/-8 days in the extended donor group; p = n.s.), and hospital survival (80% and 88% in the ideal and extended donor groups, respectively). One-year follow-up revealed similar pulmonary function (forced expiratory volume in 1 sec [FEV(1)] = 2.4 liters and 2.4 liters in the recipients of bilateral ideal and extended donors, respectively, and FEV(1) = 1.9 liters and 1.5 liters in the recipients of single ideal and extended donors) and survival (72% and 79% in the ideal and extended donor groups, respectively; p = n.s.) between the 2 groups. CONCLUSIONS: Liberalization of donor criteria does not affect outcome in the first year after lung transplantation. By liberalizing donor criteria, we can expand the donor pool while assessing other possible mechanisms to increase donor availability.

Extracorporeal photopheresis for the treatment of lung allograft rejection.

OBJECTIVES: Acute and chronic rejection continue to limit the survival of lung transplant recipients. Extracorporeal photopheresis has evolved as a possible therapy for patients with acute nd chronic lung allograft rejection. METHODS: We retrospectively reviewed 14 patients diagnosed with BOS who underwent therapy with extracorporeal photopheresis. RESULTS: Three patients were classified as BOS 0'b', five as BOS 1, three as BOS 2, and, three as BOS 3 at the time of diagnosis. Of the patients with BOS 0'b' or BOS 1 seven remain alive and one died of lung cancer. Two have progressed to BOS 2. Of the patients with BOS 2 or 3, four have died of BOS, one died of lung cancer, and one was re-transplanted. In three patients with BOS and concurrent acute rejection, therapy with extracorporeal photopheresis led to the resolution of the acute rejection episode. Two of the 14 patients developed line related sepsis. CONCLUSION: Extracorporeal photopheresis appears to be a promising therapy for patients with early BOS. It may also have a role in the treatment of acute lung allograft rejection.

The incidence of and clinical variables associated with vancomycin-resistant enterococcal colonization in mechanically ventilated patients.

STUDY OBJECTIVES: (1) To determine in our ICU the incidence of vancomycin-resistant enterococcus (VRE) colonization in mechanically ventilated patients without a history of VRE infection or colonization; and (2) to determine the risk factors and outcome variables associated with VRE colonization in these patients. DESIGN: A prospective cohort study conducted between January 1996 and March 1998. SETTING: Medical and cardiac critical care units in a tertiary care urban university hospital. PATIENTS: Mechanically ventilated patients without evidence of pneumonia at the onset of ventilation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients underwent rectal cultures by standard methods on day 1, day 3 or 4, day 6 or 7, and day 14 of intubation to detect VRE. Thirteen of 83 patients (16%) had rectal cultures positive for VRE (VRE+) at some point while being mechanically ventilated during their stay in the ICU. In comparison, approximately 15 of 2,100 medical ICU patients (0.7%) had clinical VRE infections as determined by the hospital's infection control program during a 2-year period. VRE+ patients had a higher incidence of immunosuppression than patients who had rectal cultures negative for VRE (VRE-) (9 of 13 [69%] vs 16 of 70 [23%], respectively; p < 0.01) and neutropenia (4 of 13 [31%] vs 5 of 70 [7%], respectively; p < 0.01). Hospital length of stay (LOS) was longer in VRE+ patients than in VRE- patients (27+/-17 days vs 17+/-14 days, respectively; p = 0.05), whereas pre-ICU hospital LOS and ICU LOS were similar in both patient groups. Five of 67 patients (7%) were VRE+ on day 1 of intubation, suggesting colonization at a prior site of care. Three of 29 patients who had subsequent rectal cultures converted to VRE+ while in the ICU. This group had a higher incidence of immunosuppression and neutropenia, and received more vancomycin compared with the patients who remained VRE- (p < 0.01). However, there was no significant difference in the use of other broad-spectrum antibiotics (such as antipseudomonal penicillins, third-generation cephalosporins, quinolones, and clindamycin), enteral tube feedings, or sucralfate between the two groups. In addition, a topical antibiotic paste (a gentamicin, nystatin, polymixin slurry) that was placed in the oropharynx to prevent bacterial overgrowth was not found to increase the incidence of VRE colonization in this patient population. CONCLUSIONS: The incidence of VRE colonization was surprisingly high: 16% in mechanically ventilated patients in a hospital in which VRE was not previously known to be endemic. Risk factors for the acquisition of VRE colonization included immunosuppression, neutropenia, and vancomycin use. Increased LOSs and hospital costs were seen in VRE+ patients compared to VRE- patients. Whether VRE colonization is a contributor to severe disease that leads to prolonged hospitalization and increased resource allocation or whether it is simply a marker of disease severity cannot be determined from this study. To the extent that specific antibiotic protocols are used to reduce antibiotic-resistant flora in the ICU, monitoring the incidence of VRE in the stool specimens of immunocompromised, mechanically ventilated patients can be a simple and useful tool to assess one effect of these strategies.

Lung transplantation at Loyola University Medical Center.

The Loyola Lung Transplant Program shows a long record of offering transplants to suitable recipients, with good clinical results. The overall one-year survival rate was 84% for 53 lung transplant recipients in 1998-99. Our local perception on donor management appears to be successful at increasing donor organ availability. In addition, continuous evolution in posttransplant care and willingness to utilize newer immunosuppressive agents has reduced our incidence of acute rejection episodes to 23% during the past 2 years. Time will tell if there is also a measurable reduction in bronchiolitis obliterans syndrome. Finally, longitudinal research on QOL after lung transplantation continues to buoy our spirits based on patient acceptance and satisfaction with results. We continue to be strong advocates for transplantation and organ donation.