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L R Kaiser

Publications and source records attributed to L R Kaiser.

At least 55 records · Page 3Linked to original sources
PubMed1999

Evaluation of an E1E4-deleted adenovirus expressing the herpes simplex thymidine kinase suicide gene in cancer gene therapy.

Studies with first-generation adenoviral vectors have uncovered limitations that include finite transgene persistence, potential hepatotoxicity, and contamination with replication-competent adenovirus (RCA). To address these limitations within the context of cancer suicide gene therapy, a new adenoviral vector was developed containing the herpes simplex virus type 1 thymidine kinase (HSV tk) gene inserted in the E1 region of a recombinant vector containing deletions in the E1 and E4 regions of the Ad5 genome. The HSV tk minigene was placed under transcriptional control of a Rous sarcoma virus (RSV) promoter. This new E1E4-deleted vector was compared with the first-generation E1E3-deleted Ad.RSVtk vector. Generation of replication-competent adenovirus during production was eliminated. Using semiquantitative immunoblotting, the two vectors produced equivalent amounts of the expected 44-kDa tk-encoded protein in three different cell lines tested. The ability of the E1E4-deleted vector to sensitize tumor cells to ganciclovir (GCV) using in vitro assays and mixing studies was comparable to that of the E1E3-deleted vector. In vivo bystander effects were investigated using mixing studies in a syngeneic flank tumor model and demonstrated no difference between vectors in either immunocompetent or immunodeficient mice. To test the efficiency of these vectors in treating tumors in clinically relevant models, virus was injected intraperitoneally into tumor-bearing SCID mice and intrapleurally in a syngeneic rat mesothelioma model. After treatment of animals with ganciclovir, both vectors were roughly equivalent in their ability to increase mean survival (from approximately 40 to approximately 70 days) and markedly reduce tumor burden. Finally, formal toxicology studies were performed and showed similar amounts of local inflammation without systemic toxicity. In summary, this series of in vitro and in vivo experiments indicates that the performance of the recombinant E1E4-deleted adenoviral vector was virtually identical to that of the E1E3-deleted vector. Since the E1E4 vector has a much lower rate of recombination during production and has been shown to be less hepatotoxic in animal models, this new vector should prove superior to the first-generation Ad.HSVtk vectors in clinical cancer gene therapy trials.

Adenoviridae↗
PubMed1999

Management of exsanguinating hemoptysis during cardiopulmonary bypass.

BACKGROUND: Large-volume hemoptysis during cardiopulmonary bypass is an infrequent, but life-threatening event. Rapid airway clearance and control are the primary prerequisites for successful management. METHODS: The cases of 3 patients with different sources of exsanguinating hemoptysis during cardiopulmonary bypass managed initially with rigid bronchoscopy were reviewed. RESULTS: In all patients, airway control was rapidly established and weaning from cardiopulmonary bypass CPB was accomplished. Two patients survived the operative procedure. The other patient died in the operating room of unremitting bilateral pulmonary hemorrhage. CONCLUSIONS: Major hemoptysis during cardiopulmonary bypass is best dealt with initially by rapid airway control and cessation of bypass in an expeditious manner. An algorithm for suggested management is provided. The rigid bronchoscope is the optimal tool for initial management and it should always be available. Definitive treatment is determined by the cause and the persistence of hemorrhage once these maneuvers have been performed.

Aged↗
PubMed1999

Oncolytic therapy using a mutant type-1 herpes simplex virus and the role of the immune system.

BACKGROUND: Herpes simplex virus (HSV)-1716, a replication-restricted herpes simplex virus type 1, has shown efficacy as an oncolytic treatment for central nervous system tumors, breast cancer, ovarian cancer, and malignant mesothelioma. We evaluated the efficacy of HSV-1716 in a murine lung cancer model, Lewis lung carcinoma. METHODS: Lewis lung carcinoma cells were infected with HSV-1716 and implanted in the flanks of mice at varying ratios of infected to uninfected cells. Tumor burden was assessed by measurement of the weight of the tumor nodule. The role of the immune system was examined by performing experiments in both immunocompetent and SCID mice. Tumors were implanted in the opposite flank to evaluate the vaccine effect. RESULTS: In immunocompetent and SCID animals, ratio of 1:10 (infected-to-uninfected) cells completely prevented tumor formation and ratio of 1:100 suppressed tumor growth. Established tumors at a distant site in the groups receiving HSV-1716 infected cells showed no difference in size versus control, suggesting absence of a vaccine effect. CONCLUSIONS: We conclude that HSV-1716 may provide a oncolytic therapy for lung cancer even in the absence of immune system induction and a "carrier" cell could potentially deliver this vector.

Animals↗
PubMed1999

Long-term survival after thoracoscopic lung volume reduction: a multiinstitutional review.

BACKGROUND: It has been suggested that bilateral thoracoscopic lung volume reduction (BTLVR) yields significantly better long-term survival than unilateral thoracoscopic lung volume reduction (UTLVR). METHODS: All perioperative data were collected at the time of the procedure. Follow-up data were obtained during office visits or by telephone. RESULTS: A total of 673 patients underwent thoracoscopic LVR: 343 had either simultaneous or staged BTLVR and 330, UTLVR. As of July 1998, follow-up was available on 667 (99%) of the 673 patients with a mean follow-up of 24.3 months. The patients in the BTLVR group were significantly younger (62.6+/-8.0 years versus 65.4+/-8.1 years; p < 0.0001), had a higher preoperative arterial oxygen tension (69.7+/-12 mm Hg versus 65.3+/-11 mm Hg; p < 0.0001), and had a superior preoperative 6-minute walk performance (279.9+/-93.6 m [933+/-312 feet] versus 244.5+/-101.4 m [815+/-338 feet] p < 0.0001). There was no difference in the operative mortality rate between the two groups (UTLVR, 5.1%, and BTLVR, 7%). Actuarial survival rates for the UTLVR group at 1 year, 2 years, and 3 years were 86%, 75%, and 69%, respectively versus 90%, 81%, and 74%, respectively, for the BTLVR group (p = not significant). CONCLUSIONS: Contrary to previous reports, survival after BTLVR was not superior to that after UTLVR even though the former group appeared to have a lower risk preoperatively because of younger age, higher arterial oxygen tension, more advantageous anatomy, and better functional status. Despite thoracoscopic LVR, the actuarial mortality rate approached 30% at 3 years, and this calls into question whether this procedure offers any survival advantage to patients with end-stage emphysema.

Aged↗
PubMed1999

Cadherin and catenin expression in normal human bronchial epithelium and non-small cell lung cancer.

Cadherins are transmembrane cell adhesion molecules (CAMS) that mediate cell-cell interactions and are important for maintenance of epithelial cell integrity. This function is dependent on an indirect interaction between the cytoplasmic domain of the cadherin molecule with three cytoplasmic proteins known as alpha-, beta-, and gamma-catenin (-cat). Growing evidence suggests that alterations in cadherin or catenin expression or function may be important to the development of an invasive or metastatic phenotype. Immunohistochemical techniques were used to study the expression of the two major epithelial cadherins, E-cadherin (E-cad) and P-cadherin (P-cad) as well as alpha- and gamma-cat in normal bronchial epithelium and in a series of carefully TMN-staged pulmonary adenocarcinomas (n = 21) and squamous cell carcinomas (n = 7). The cadherin profile of normal pseudostratified bronchial epithelium was heterogeneous. Basilar cells strongly expressed P-cad, alpha- and gamma-cat, while columnar cells moderately expressed E-cad, alpha- and gamma-cat. In contrast to other epithelial tumors, E-cad on non-small cell lung carcinomas was actually upregulated, however, a decrease in P-cad expression was noted in 68%. At least one cadherin or catenin was downregulated, compared to normal bronchial epithelium, in 82% of tumors examined. With the exception of an association between loss of P-cad expression and poorly differentiated state, changes in cadherin and catenin expression levels were not significantly correlated to tumor stage, cell type, or nodal status. These findings illustrate that alteration of expression of cadherins and catenins are often found in non-small cell lung carcinoma when compared to the progenitor bronchial epithelium, and may play a role in the development of the malignant phenotype.

Bronchi↗
PubMed1999

Management of chylothorax by percutaneous catheterization and embolization of the thoracic duct: prospective trial.

PURPOSE: To prospectively assess the efficacy of percutaneous transabdominal thoracic duct catheterization and embolization in the management of patients with high-output chylothoracic effusions. MATERIALS AND METHODS: Eleven consecutive patients (four women and seven men; mean age, 53 years) were referred with chylothorax secondary to esophagectomy (n = 4), lobectomy (n = 1), lung transplant (n = 1), coronary artery bypass (n = 1), aortic graft (n = 2), lymphangioleiomyomatosis (n = 1), and gunshot wound (n = 1). Two patients were brought by ambulance and referred back to their hospital on the same day. Pedal lymphography was used to opacify the cisterna chyli or major retroperitoneal lymphatic trunks. When patent, these were punctured under local anesthesia with a fine needle and the thoracic duct was catheterized over a microguide wire with use of a 3-F catheter; the duct was embolized with platinum coils. Patients were followed up for decrease in thoracic drainage output and morbidity. RESULTS: There were no retroperitoneal ducts suitable for catheterization in six patients because of previous abdominal surgery, trauma, or lymphangioleiomyomatosis; the thoracic duct was successfully catheterized in five patients, a 45% technical success rate. Thoracic duct embolization was performed in four patients, with cure of effusion in two. In the other two patients, one with lymphangioleiomyomatosis and the other with nonchylous pleural fluid, continued effusion was successfully treated by means of pleurodesis. Of two patients with previous thoracic duct ligation, one was found to have the duct incompletely tied. The authors were surprised to find that previous major abdominal surgery, chronic aortic dissection, and lymphangioleiomyomatosis could obliterate major retroperitoneal lymphatic ducts and the cisterna chyli. Percutaneous study of the thoracic duct with aqueous contrast medium was more sensitive than lymphography with iodinated oil. There was no morbidity. CONCLUSIONS: Catheterization of the thoracic duct was possible in all patients who had patent major retroperitoneal lymphatic trunks. Thoracic duct embolization was curative in patients with demonstrable duct leakage. Previous abdominal surgery, aortic dissection, and lymphangioleiomyomatosis can lead to silent occlusion of retroperitoneal lymphatic trunks. Percutaneous thoracic duct catheterization and embolization is safe and can replace surgical ligation in some patients.

Adult↗
PubMed1999

Non-small cell lung cancer: prognostic factors in patients treated with surgery and postoperative radiation therapy.

PURPOSE: To determine survival outcomes, to identify adverse prognostic factors for relapse, and to compare American Joint Commission on Cancer (AJCC) staging systems in patients with non-small cell lung cancer (NSCLC) treated with surgery and postoperative radiation therapy. MATERIALS AND METHODS: Between 1980 and 1995, 211 patients with NSCLC underwent surgery and postoperative radiation therapy. Surgery consisted of wedge resection (12.5%), lobectomy (67.8%), or pneumonectomy (19.7%). Pathologic stages (1992 AJCC) included I (n = 22), II (n = 70), IIIA (n = 104), and IIIB (n = 12). Indications for radiation therapy included compromised margins (n = 81) and/or positive mediastinal nodes (n = 55). Prognostic factors were identified by using univariate and multivariate models. RESULTS: Overall 3-year survival for patients with stage I, II, and IIIA cancer was 58.9%, 44.1%, and 43.2%, respectively. Older age (P = .008), male sex (P = .021), large primary tumor (P = .004), and multiple positive mediastinal nodes (P = .046) were associated with worse rates of survival. Actuarial risk of local-regional relapse (36 patients) was 21.4% at 3 years. In a multivariate model, use of wedge resection (P = .001), positive margins (P = .010), and larger pathologic tumor (P = .059) were risk factors for local-regional recurrence. Actuarial rate of distant failure was 55.2% at 3 years. CONCLUSION: Local-regional control can be achieved with surgery and radiation therapy in approximately 80% of patients; however, the rate of distant metastasis remains unacceptably high. Other variables, such as multiple positive nodes, may serve to identify patients at higher risk for relapse and poorer survival. Methods for improving treatment outcomes in these patients should be pursued.

Aged↗
PubMed1999

Hyperacute rejection of a pulmonary allograft. Immediate clinical and pathologic findings.

The clinical and pathologic findings seen in hyperacute rejection are well documented in renal and cardiac allografts. We describe the second case of hyperacute rejection in a pulmonary allograft and detail the immediate clinicopathologic findings. The patient underwent a single lung transplant for severe COPD with postoperative course complicated by acute rejection and graft failure. Eleven days later, the patient underwent a second transplant with intra-operative course complicated by rapid pulmonary edema and copious production of frothy, pink fluid from the bronchial orifice of the allograft followed by death within four hours of anastomoses. Intraoperative biopsy and autopsy demonstrated platelet/fibrin thrombi, marked interstitial neutrophilia, alveolar edema, and antibody deposition on the endothelial surface and vasculature walls. Prior to the first transplant, the patient's serum had 0% panel reactive antibody and was crossmatch compatible with the first allograft. The patient's serum prior to the second transplant contained cross-reacting antibodies to the donor's B and T lymphocytes. The immediate clinical findings in this case are similar to the findings in a previously reported case. This report is the first documentation of the immediate pathologic features of hyperacute rejection in a lung allograft which are similar to those seen with other organ allografts.

Fatal Outcome↗
PubMed1999

Advances in the treatment of malignant pleural mesothelioma.

Malignant pleural mesothelioma is a neoplasm that is commonly fatal and for which there are no widely accepted curative approaches. Mesothelioma is unresponsive to most chemotherapy and radiotherapy regimens, and it typically recurs even after the most aggressive attempts at surgical resection. Multimodality approaches have been of some benefit in prolonging survival of very highly selected subgroups of patients, but they have had a relatively small impact on the majority of the patients diagnosed with this disease. As the incidence of pleural mesothelioma peaks in the United States and Europe over the next 10 to 20 years, new therapeutic measures will be necessary. This review will discuss the roles of chemotherapy, radiotherapy, surgery, and combined modality approaches in the treatment of pleural mesothelioma, as well as scientific advances made in the past decade that have led to the development of experimental techniques, such as photodynamic therapy, immunotherapy, and gene therapy, that are currently undergoing human clinical trials. These promising new avenues may modify the therapeutic nihilism that is rampant among clinicians dealing with mesothelioma.

Combined Modality Therapy↗
PubMed1999

Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) remains localized within the peritoneal cavity in a large number of patients, lending itself to i.p. approaches of therapy. In the present study, we investigated the effect of replication-selective herpes simplex virus-1 (HSV-1) used as an oncolytic agent against EOC and the use of human teratocarcinoma PA-1 as carrier cells for i.p. therapy. HSV-1716, a replication-competent attenuated strain lacking ICP34.5, caused a direct dose-dependent oncolytic effect on EOC cells in vitro. A single i.p. administration of 5 x 10(6) plaque-forming units resulted in a significant reduction of tumor volume and tumor spread and an increase in survival in a mouse xenograft model. PA-1 cells supported HSV replication in vitro and bound preferentially to human ovarian carcinoma surfaces compared with mesothelial surfaces in vitro and in vivo. In comparison with the administration of HSV-1716 alone, irradiated PA-1 cells, infected at two multiplicities of infection with HSV-1716 and injected i.p. at 5 x 10(6) cells/animal, led to a significant tumor reduction in the two models tested and the significant prolongation of mean survival in one model. Histological evaluation revealed extensive necrosis in tumor areas infected by HSV-1716. Immunohistochemistry against HSV-1 revealed areas of viral infection within tumor nodules, which persisted for several weeks after treatment. Administration of HSV-infected PA-1 carrier cells resulted in larger areas of tumor infected by the virus. Our results indicate that replication-competent attenuated HSV-1 exerts a potent oncolytic effect on EOC, which may be further enhanced by the utilization of a delivery system with carrier cells, based on amplification of the viral load and possibly on preferential binding of carrier cells to tumor surfaces.

Animals↗
PubMed1999

Prognostic value of FDG PET imaging in malignant pleural mesothelioma.

UNLABELLED: Despite several attempts at treating malignant pleural mesothelioma with various modalities, mortality remains high, with median survival between 12 and 18 mo. This disease may have a highly variable clinical course, with occasional long-term survivors. The purpose of this study was to assess whether tumor metabolic activity, as assessed by fluorodeoxyglucose (FDG) PET imaging, correlates inversely with survival. METHODS: Twenty-eight patients with suspected mesothelioma underwent FDG PET scanning between September 1995 and May 1997. A diagnosis of mesothelioma was confirmed in 22. Fully corrected scans with attenuation correction of the entire chest were available in 17 patients with sufficient follow-up for survival analysis. Standardized uptake values (SUVs) were determined from the most active tumor site in each patient. RESULTS: Seven patients died during follow-up, at a median period of 5.3 mo after FDG PET scanning. Follow-up information was available on the remaining 10 patients for a median period of 15.6 mo after the PET study. The mean SUV of the deceased patients was 6.6+/-2.9, compared with 3.2+/-1.6 among the combined survivors. The deceased patients had tumor SUVs that were highly correlated with duration of survival after the PET study (r = 0.87, P < 0.05). The cumulative survival estimate by the Kaplan-Meier product limit method was 0.17 at 12 mo for the patients with tumor SUVs greater than the median value and 0.86 for those with lower SUVs. The survival distribution of the high SUV group showed significantly shorter survivals compared with the low SUV group (P < 0.01). CONCLUSION: Patients with highly active mesotheliomas on FDG PET imaging have a poor prognosis. High FDG uptake in these tumors indicates shorter patient survival.

Aged↗
PubMed1998

Impact of preexisting and induced humoral and cellular immune responses in an adenovirus-based gene therapy phase I clinical trial for localized mesothelioma.

Little is known about the immune responses induced by recombinant adenoviral (Ad) vectors in humans. The humoral and cellular immune responses were therefore analyzed in 21 patients with localized malignancy (mesothelioma), who received intrapleurally high doses of a replication-defective Ad5 vector carrying a suicide gene. Eight of 21 patients had pretreatment titers of neutralizing antibodies (NAb) to Ad at > or =1:100. Peripheral blood mononuclear cells (PBMCs) proliferated in response to adenoviral 5 structural proteins before treatment in 17 of 21 patients. Preexisting humoral and cellular immunity did not preclude gene transfer. Vector instillation induced high titers of nonneutralizing and neutralizing anti-Ad antibody (4- to 341-fold increase in 18 of 20 patients) in a dose-dependent manner. Three patients generated antibodies to the transgene, herpes simplex virus thymidine kinase. Ad5-specific proliferation of PBMCs increased significantly (>3-fold) after vector administration in 12 of 21 patients in a dose-dependent manner. Thus, replication-defective Ad5 administered intrapleurally induced significant humoral and cellular immune responses that induced no obvious adverse clinical sequelae.

Adenoviridae↗
PubMed1998

Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma.

Malignant pleural mesothelioma is a fatal neoplasm that is unresponsive to standard modalities of cancer therapy. We conducted a phase I dose-escalation clinical trial of adenoviral (Ad)-mediated intrapleural herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy in patients with mesothelioma as a model for treatment of a localized malignancy. The goals of this phase I trial were to assess the safety, toxicity, and maximally tolerated dose of intrapleural Ad.HSVtk, to examine patient inflammatory response to the viral vector, and to evaluate the efficiency of intratumoral gene transfer. Twenty-one previously untreated patients were enrolled in this single-arm, dose-escalation study with viral doses ranging from 1 x 10(9) plaque-forming units (pfu) to 1 x 10(12) pfu. A replication-incompetent recombinant adenoviral vector containing the HSVtk gene under control of the Rous sarcoma virus (RSV) promoter-enhancer was introduced into the pleural cavity of patients with malignant mesothelioma followed by 2 weeks of systemic therapy with GCV at a dose of 5 mg/kg twice a day. The initial 15 patients underwent thoracoscopic pleural biopsy prior to, and 3 days after, vector delivery. The last six patients underwent only the post-vector instillation biopsy. Dose-limiting toxicity was not reached. Side effects were minimal and included fever, anemia, transient liver enzyme elevations, and bullous skin eruptions, as well as a temporary systemic inflammatory response in those receiving the highest dose. Strong intrapleural and intratumoral immune responses were generated. Using RNA PCR, in situ hybridization, immunohistochemistry, and immunoblotting, HSVtk gene transfer was documented in 11 of 20 evaluable patients in a dose-related fashion. This study demonstrates that intrapleural administration of an adenoviral vector containing the HSVtk gene is well tolerated and results in detectable gene transfer when delivered at high doses. Further development of therapeutic trials for treatment of localized malignancy using this vector is thus warranted.

Adenoviruses, Human↗
PubMed1998

Comparison of open and thoracoscopic bilateral volume reduction surgery: complications analysis.

BACKGROUND: The effectiveness of lung volume reduction for the treatment of patients with emphysema is well established, but data about the surgical approach, the postoperative management, and complications are limited. We report a comparison of patients undergoing bilateral lung volume reduction (BLVRS) via median sternotomy and thoracoscopic techniques with emphasis on hospital course and complications. METHODS: All patients undergoing BLVRS at Hospital of University of Pennsylvania were analyzed for mortality and morbidity, using a combination of prospective data analysis and retrospective chart review. RESULTS: Patients undergoing BLVRS via median sternotomy were older than those undergoing video-assisted thoracoscopic surgery (VATS) procedures (63.9+/-6.89 vs 59.3+/-9.4 years, p = 0.005). Operating time was longer for the VATS procedure (147 versus 129 minutes, p = 0.006) while estimated blood less was greater for median sternotomy (209 versus 82 L, p = 0.0000017). Significant differences were found in intensive care unit stay, days intubated, life-threatening complications, respiratory complications, requirement for tracheostomy, and death that favored VATS BLVRS. When only later cohorts of patients were compared, more life-threatening complications and deaths were found in patients undergoing BLVRS by median sternotomy. There were no differences between early and late median sternotomy BLVRS patients. Twenty-six percent of the lethal complications in median sternotomy BLVRS patients were bowel perforations, equally divided between duodenal ulcers and colons. CONCLUSIONS: Managing patients after BLVRS remains complex. Bilateral video-assisted volume reduction offers equivalent functional outcome with potentially decreased morbidity and mortality. Gastrointestinal perforations can complicate the management of these patients.

Blood Loss, Surgical↗
PubMed1998

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

BACKGROUND: 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 < or = 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 alpha 1-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 alpha 1-antitrypsin deficiency.

Algorithms↗