Effect of volume reduction on lung transplant timing and selection for chronic obstructive pulmonary disease

AbstractBackground: End-stage chronic obstructive pulmonary disease has traditionally been treated with lung transplantation. For 2 years, our lung transplantation program has placed patients with appropriate criteria for lung transplantation and volume reduction into a prospective management algorithm. These patients are offered the lung volume reduction option as a “bridge” to “extend” the eventual time to transplantation. We examine the results of this pilot program. Methods: From October 11, 1993, to April 17, 1997, 31 patients were evaluated for lung transplantation who also had physiologic criteria for volume reduction (forced expiratory volume in 1 second ≤ 25%; residual volume > 200%; significant ventilation/perfusion heterogeneity). All patients completed 6 weeks of pulmonary rehabilitation and then had baseline pulmonary function and 6-minute walk tests. These patients were then offered volume reduction as a “bridge” and were simultaneously listed for transplantation. Postoperatively, these 31 patients were then divided into two groups: Those with satisfactory results at 4 to 6 months after volume reduction and those with unsatisfactory results. Volume reduction was performed through a video thoracic approach in 87% of the patients and bilateral median sternotomy in the remaining 13%. The condition of the patients was monitored after the operation with repeated pulmonary function tests and 6-minute walk tests at 3-month intervals. Results: Twenty-four of 31 patients (77.4%) had primary success (at 4 to 6 months) results after lung volume reduction and 7 patients (22.6%) had primary failure, including 1 patient who died in the perioperative period (3.2%). Four patients (16.7%) from the primary success cohort had significant deterioration in their pulmonary function during intermediate-term follow-up and were then reconsidered for lung transplantation. Two of them have subsequently undergone transplantation with good postoperative pulmonary function results. Interestingly, three patients had α1-antitrypsin deficiency; two had a poor outcome of lung volume reduction and primary failure. Conclusions: Lung volume reduction in these patients is safe. Seventy-seven percent of otherwise suitable candidates for lung transplantation achieved initial good results from volume reduction and were deactivated from the list (placed on status 7). Most patients entering our prospective management algorithm have either significantly delayed or completely avoided lung transplantation after volume reduction. Lung volume reduction has substantially affected the practice, timing, and selection of patients for lung transplantation. Our waiting list now has a reduced percentage of patients with a diagnosis of chronic obstructive pulmonary disease compared with 3 years ago. Our experience suggests that lung volume reduction may be limited as a “bridge” in α1-antitrypsin deficiency. (J Thorac Cardiovasc Surg 1998;115:9-18

Thoracic transplantation

Note on Sources: The articles in this supplement are based on the reference tables in the 2002 OPTN/SRTR Annual Report, which are not included in this publication. Many relevant data appear in figures and tables directly referred to in the article; other tables from the Annual Report that serve as the basis for this article include the following: Tables 1.5, 1.6, 1.12, 1.13, 11.1–11.4, 11.8, 11.9, 12.1–12.4, 12.7–12.9, 13.1–13.4, and 13.7–13.9. All of these tables are also available online at http://www.ustransplant.org.The Scientific Registry of Transplant Recipients (SRTR) is funded by contract #231-00-0116 from the Health Resources and Services Administration (HRSA). The views expressed herein are those of the authors and not necessarily those of the US Government. This is a US Government-funded work. There are no restrictions on its use.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91976/1/2003 AJT Thoracic Transplantation.pd

Pattern Specification and Immune Response Transcriptional Signatures of Pericardial and Subcutaneous Adipose Tissue

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Recent studies suggest that pericardial adipose tissue (PCAT) secretes inflammatory factors that contribute to the development of CVD. To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between PCAT and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. As it was unknown whether PCAT-secreted factors are produced by adipocytes or cells in the supporting stromal fraction, we also sought to identify differentially expressed genes in isolated pericardial adipocytes vs. isolated subcutaneous adipocytes. Using microarray analysis, we found that: 1) pericardial adipose tissue and isolated pericardial adipocytes both overexpress atherosclerosis-promoting chemokines and 2) pericardial and subcutaneous fat depots, as well as isolated pericardial adipocytes and subcutaneous adipocytes, express specific patterns of homeobox genes. In contrast, a core set of lipid processing genes showed no significant overlap with differentially expressed transcripts. These depot-specific homeobox signatures and transcriptional profiles strongly suggest different functional roles for the pericardial and subcutaneous adipose depots. Further characterization of these inter-depot differences should be a research priority

Induction of kidney transplantation tolerance across major histocompatibility complex barriers by bone marrow transplantation in miniature swine

Previous studies from our laboratory have shown that permanent lymphohematopoietic chimerism can be induced in MHC-disparate miniature swine by bone marrow transplantation after lethal total-body irradiation. The purpose of the present study was to determine in this large animal model whether such chimerism would lead to permanent tolerance to a vascularized allograft without a requirement for exogenous immunosuppression. Eight miniature swine that had received MHC-mismatched BMT more than five months earlier underwent kidney transplantation (KTx) from a donor MHC matched (n=5) or MHC mismatched (n=3) with the BMT donor. All animals had regained in vitro responsiveness to third-party MHC antigens, as measured by mixed lymphocyte reaction (MLR), before KTx but remained nonresponsive to MHC antigens of the BMT donor and self. All three animals that received KTx mismatched for BMT donor MHC rejected promptly (mean survival time 7.0 days). Of the five animals that received KTx matched for BMT donor MHC, four showed no evidence of rejection and have functioning KTx \u3e200 days after KTx. The fifth animal had excellent renal function for 60 days but then developed a slowly rising BUN and serum Creatinine, and died 75 days after KTx. The course of this animal’s rejection is consistent with that previously described for rejection due to minor antigen disparities. The difference in survival of KTx matched or mismatched for the MHC of the BMT donor was statistically significant (P=0.0062). The survival of KTx matched for the MHC of the BMT donor was significantly different from that of control animals without BMT receiving KTx mismatched for MHC (P=0.0018). We therefore conclude that BMT is an effective means for induction of tolerance to an MHC mismatched KTx in this large animal model. © 1991 by Williams & Wilkins

Successful induction of long-term specific tolerance to fully allogeneic renal allografts in miniature swine

Major histocompatibility complex class II matching is of overwhelming importance for achieving tolerance to kidney transplants (KTX) in miniature swine. When class II antigens are matched, long-term specific tolerance across complete MHC class I antigen barriers can uniformly be induced by a 12-day perioperative course of cyclosporine. This same regimen is ineffective in fully MHC-mismatched combinations. We hypothesized that initial induction of tolerance to kidney donor class II antigens by bone marrow transplantation might allow tolerance to be induced to a subsequent fully allogeneic KTX in combination with CsA therapy. We report here the results of such fully allogeneic KTX performed in 4 recipients of prior single-haplotype class II-mismatched BMT. All animals received KTX from donors class II matched to the BMT donor and received a 12-day course of intravenous CsA (10 mg/kg/day). All four animals have maintained normal serum creatinine values (less than 2.0 mg/dl) for greater than 200 days posttrans-plant. Specific hyporesponsiveness to both BMT and KTX donor-type MHC antigens was found in mixed lymphocyte culture and cell-mediated lympholysis assays. Compared with third-party grafts, significantly prolonged survival of BMT donor-specific (P=0.031) and KTX donor-specific (P=0.031) skin grafts was observed. These results demonstrate that induction of tolerance to class II antigens by BMT allows a short course of CsA to induce specific tolerance to fully allogeneic renal allografts. © 1992 by Williams and Wilkins

Transplantation in miniature swine: analysis of graft-infiltrating lymphocytes provides evidence for local suppression

Previous studies from this laboratory have demonstrated that swine tolerant of class I disparate renal allografts show peripheral antidonor cellular reactivity which can be augmented by skin grafting. To assess the possibility of local suppression, cell-mediated lymphocytotoxicity of graft-infiltrating lymphocytes was compared to that of peripheral blood lymphocytes from three tolerant and four acutely rejecting recipients of class I-disparate renal allografts. Mixed lymphocyte cultures using peripheral blood lymphocytes or graft-infiltrating lymphocytes and an equal number of irradiated peripheral blood lymphocyte stimulators were incubated for 6 days and tested in a 6-hr 51Cr release assay. Graft-infiltrating lymphocytes from rejecting animals had potent anti-donor cell-mediated lymphocytotoxic activity with or without in vitro stimulation. Anti-third-party reactivity was seen with appropriate stimulation, suggesting heterogeneity of graft-infiltrating lymphocyte cultures. Peripheral blood lymphocytes from rejectors generated donor-specific cell-mediated lymphocytotoxicity. Graft-infiltrating lymphocytes from tolerant animals generated no antidonor cell-mediated lymphocytotoxicity with or without in vitro stimulation, but generated an anti-third-party response. Peripheral blood lymphocytes from tolerant animals displayed both antidonor and anti-third-party reactivity with appropriate in vitro stimulation. These data support the hypothesis that local suppression may contribute significantly to maintenance of tolerance to class I disparate renal allografts in miniature swine. © 1990