Elbert P. Trulock

Results of 150 consecutive bilateral lung volume reduction procedures in patients with severe emphysema

Between January 1993 and February 1996, we performed 150 bilateral lung volume reduction procedures for patients with severe emphysema. Patients were selected on the basis of severe dyspnea, increased lung capacity, and a pattern of emphysema that included regions of severe destruction, hyperinflation, and poor perfusion. Twenty percent to 30% of the volume of each lung was excised with the use of a linear stapler and bovine pericardial strips attached to buttress the staple line. Patients were between 36 and 77 years old, with an average 1-second forced expiratory volume of 25% of predicted, total lung capacity of 142% of predicted, and residual volume of 283% of predicted. Ninety-three percent of patients required supplemental oxygen, continuously or with exertion. All patients but one were extubated at the end of the procedure. The 90-day mortality was 4%. Hospital stay progressively decreased with experience, and for the last 50 patients the median hospital stay was 7 days. Prolonged air leakage was the major complication. Results at 6 months show a 51% increase in the 1-second forced expiratory volume and a 28% reduction in the residual volume. The Pao2 increased by an average of 8 mm Hg, and 70% of the patients who had previously required continuous supplemental oxygen no longer had this requirement. The improvements in measured pulmonary function were paralleled by a significant reduction in dyspnea and an improvement in the quality of life. Reevaluation at 1 year and 2 years after operation showed the benefit to be well maintained. We conclude that lung volume reduction offers benefits not achievable by any means other than lung transplantation for highly selected patients with severe emphysema.

Improved technique for bilateral lung transplantation: Rationale and initial clinical experience

We previously described a technique for en bloc double-lung transplantation that was initially applied to select patients with cystic fibrosis and emphysema. This procedure is quite complex and associated with several limitations, including a substantial incidence of airway ischemia, postoperative myocardial depression, and cardiac denervation. To address these problems we have developed a simpler procedure for replacing both lungs. The operation is done through a transverse thoracosternotomy and involves sequential replacement of the two lungs. Positive features include separate bronchial anastomoses to reduce ischemic airway complications, elimination of the need for total cardiopulmonary bypass and a period of ischemic cardiac arrest, improved exposure to reduce intraoperative and postoperative hemorrhage, and maintenance of cardiac innervation. Additionally, the technique can be more easily mastered and widely applied. Details of the procedure and its initial clinical application in 3 patients having emphysema, cystic fibrosis, and bronchiolitis obliterans following previous double-lung transplantation, respectively, are described. All 3 patients recovered without complication. Postoperative function was excellent in spite of lung ischemic times ranging up to 91/2 hours.

Clinical outcome following nerve allograft transplantation.

The clinical outcome of seven patients who underwent reconstruction of long upper‐ and lower‐extremity peripheral nerve gaps with interposition peripheral nerve allografts is reported. Patients were selected for transplantation when the nerve gaps exceeded the length that could be reconstructed with available autograft tissue. Before transplantation, cadaveric allografts were harvested and preserved for 7 days in University of Wisconsin Cold Storage Solution at 5°C. In the interim, patients were started on an immunosuppressive regimen consisting of either cyclosporin A or tacrolimus (FK506), azathioprine, and prednisone. Immunosuppression was discontinued 6 months after regeneration across the allograft(s) was evident. Six patients demonstrated return of motor function and sensation in the affected limb, and one patient experienced rejection of the allograft secondary to subtherapeutic immunosuppression. In addition to providing the ability to restore nerve continuity in severe extremity injuries, successful nerve allografting protocols have direct applicability to composite tissue transplantation. (Plast. Reconstr. Surg. 107: 1419, 2001.)

Successful outcome of lung transplantation is not compromised by the use of marginal donor lungs

Lung transplantation is limited by a shortage of suitable donors. To address this shortage, we have begun using donor lungs that do not meet all of our previous rigorous donor criteria. Of 133 consecutive lung transplants done between June 1991 and March 1994, 89 donors were considered ideal because they satisfied all of the following accepted donor criteria (group I): age younger than 55 years, smoking less than 20 pack-years, arterial oxygen tension greater than 300 mm Hg (using inspired oxygen fraction of 1.0 and positive end-expiratory pressure 5 cm H2O), and chest radiograph negative for infiltrate or trauma (contusion or pneumothorax). Thirty-seven donors failed to satisfy one of these criteria and seven donors failed to satisfy two of them, yielding 51 criteria denoting marginal status in the 44 donors in the marginal group (group II) as follows: age older than 55 years, 2; smoking history 20 or more pack-years, 9; unsatisfactory chest radiograph, 34; and arterial oxygen tension less than 300 mm Hg, 6. Sixty-three single lung transplants were done (group I, 44 versus group II, 19) compared with 70 bilateral sequential transplants (group I, 45 versus group II, 25). In 24 cases in group II, at least one of the lungs actually being implanted contained contusion or infiltrate. Evaluation of recipients from the two groups showed no significant difference in median duration of postoperative mechanical ventilation (3 days in both group I and group II) nor in alveolar-arterial oxygen gradient immediately after transplantation (group I, 304 +/- 14 mm Hg versus group II, 275 +/- 22 mm Hg; p = 0.266) or at 24 hours (group I, 125 +/- 12 mm Hg versus group II, 122 +/- 18 mm Hg; p = 0.933) (all values represent mean plus or minus the standard error). However, cardiopulmonary bypass was required to facilitate second graft insertion in bilateral sequential transplants more often in the marginal group (5 of 25, 20%) than in group I (6 of 45, 13%). There were three deaths within 30 days in group I (operative mortality, 3.4%) and none in group II. Currently, 74 (83.2%) of 89 remain alive in group I compared with 38 (86.4%) of 44 in group II. On the basis of these data, we conclude that successful outcome of lung transplantation can be achieved with the use of marginal donor lungs.

Inhaled nitric oxide reduces human lung allograft dysfunction.

OBJECTIVE Early severe graft dysfunction, as manifested by hypoxia and pulmonary hypertension, occurs in 10% to 20% of lung transplant recipients. We retrospectively investigated whether inhaled nitric oxide would reduce human lung allograft dysfunction by comparing postoperative hemodynamic data, gas exchange, and outcome in lung transplant recipients with early graft dysfunction treated with or without nitric oxide. METHOD Among 243 adult lung transplant procedures, there were 32 patients (13.2%) in whom immediate severe allograft dysfunction developed (arterial oxygen tension/inspired oxygen concentration ratio <150). Group 1 (n = 17) included patients who underwent transplantation before nitric oxide became available in our center and were treated conventionally. Group 2 (n = 15) included those treated with nitric oxide as soon as severe allograft dysfunction was diagnosed. Duration of nitric oxide therapy (20 to 60 ppm) was 15 to 217 hours (average 84 hours). RESULTS In group 2, nitric oxide lowered mean pulmonary artery pressure from 30 +/- 2 to 26 +/- 2 mm Hg (p < 0.05), improved the ratio of arterial oxygen tension to inspired oxygen fraction from 88 +/- 10 to 153 +/- 30 (p < 0.05) within 1 hour, and caused a sustained improvement in these parameters during extended therapy. Mean arterial pressure and cardiac index were unchanged during nitric oxide therapy. Transient methemoglobinemia (>6%) developed in two patients. However, no complications were associated with nitric oxide use. Duration of mechanical ventilation was 17 +/- 5 days in group 1 and 12 +/- 3 days in group 2. Four patients had airway complications in group 1, whereas no airway complication was encountered in group 2. Mortality was 24% (4/17) in group 1 and 7% (1/15) in group 2. CONCLUSION Nitric oxide improves oxygenation and decreases pulmonary artery pressure without systemic circulatory effects in patients with severe allograft dysfunction. Furthermore, in these patients, nitric oxide may shorten postoperative mechanical ventilation time and reduce airway complications and mortality.

Single Lung Transplantation for Pulmonary Hypertension Single Institution Experience in 34 Patients

BACKGROUND The present study considered the uniformity and durability of the cardiopulmonary response to single lung transplantation in patients with severe pulmonary hypertension, as well as its effect on length and quality of survival. METHODS AND RESULTS Thirty-four patients with pulmonary hypertension underwent evaluation, single lung transplantation, and follow-up assessment between November 1, 1989, and June 1, 1994. Operative survival for the entire group of patients was reasonable, with 91% (31 of 34 patients) surviving and being discharged from the hospital following transplantation. The actuarial survival for these 34 patients at 1-, 2-, and 3-year follow-up was 78%, 66%, and 61%, respectively. In the subgroup of 24 patients with primary pulmonary hypertension (PPH), 96% (23 of 24) were successfully discharged from the hospital after transplantation. The actuarial survival for this isolated PPH subgroup at 1-, 2-, and 3-year follow-up was 87%, 76%, and 68%, respectively. The uniform, early posttransplant normalization of pulmonary vascular resistance and right ventricular ejection fraction appears to persist throughout the 4-year follow-up period. Despite a high prevalence of bronchiolitis obliterans, the majority of survivors remain in New York Heart Association functional class I or II and are employed. CONCLUSIONS Single lung transplantation can be performed in patients with end-stage pulmonary vascular disease with reasonable expectations for a relatively low operative mortality; immediate, complete, and durable amelioration of pulmonary hypertension and right ventricular failure; and optimal use of limited donor organ supply.

The registry of the international society for heart and lung transplantation: twentieth official adult heart transplant report—2003

Although only a small number of lung and heart– lung transplantation procedures were performed between 1963 and 1973, the current eras of heart–lung and lung transplantation, which began in 1981 and 1983, respectively, are now entering their third decades. The optimism of the considerable success of these modalities has been tempered by limitations, such as the shortage of donor organs, and by problems, such as chronic allograft dysfunction. This portion of the Twentieth Official Report summarizes the current status of adult heart–lung and lung transplantation from data submitted to the Registry from centers around the world. The Registry now contains information on more than 2000 adult heart–lung recipients and almost 14,000 adult lung recipients, and provides a robust database for analysis.

HLA-A locus mismatches and development of antibodies to HLA after lung transplantation correlate with the development of bronchiolitis obliterans syndrome

BACKGROUND Bronchiolitis obliterans syndrome (BOS) is the most common cause of morbidity and mortality after lung transplantation (LT). A retrospective analysis of clinical and immunologic variables were done to identify those that might predict the development of BOS. METHODS Of 112 LT performed over a 42-month interval, 94 survived at least 3 months and form the basis of this analysis. There was a minimum of 21 months follow-up. BOS was defined on the basis of declining spirometry (FEV1 <80% of baseline) and/or the presence of histologic obliterative bronchiolitis. All variables analyzed were subjected first to a univariate analysis; those variables appearing to carry significance were then subjected to a multivariate logistic regression analysis. RESULTS Univariate analysis revealed the following to be predictors of the development of BOS: age (the probability of developing BOS declined with advancing age); donor/recipient HLA-A locus mismatch, with actuarial freedom from BOS being significantly greater with no A-locus mismatches versus cases with one or two mismatches (P=0.031); and development of anti-HLA antibodies after transplantation (P=0.006 vs. recipients without detectable antibodies). In multivariate analysis, only HLA locus mismatch and development of anti-HLA antibodies were significant independent predictors of the development of BOS. The remaining clinical variables (gender, type of LT, indication for LT, graft ischemic time, use of cardiopulmonary bypass, cytomegalovirus) and immunologic variables (crossmatch, frequent early acute rejection) did not correlate with the development of BOS. CONCLUSIONS These data suggest that BOS is the result of an immune process, that differences at the HLA-A locus may play an important role in this process, and antibody-mediated injury may play a role in BOS.

Development of ELISA-detected anti-HLA antibodies precedes the development of bronchiolitis obliterans syndrome and correlates with progressive decline in pulmonary function after lung transplantation.

BACKGROUND Development of anti-HLA antibodies after lung transplantation (LT) is thought to play an important role in the etiology of bronchiolitis obliterans syndrome (BOS). However, a cause-effect relationship between anti-HLA antibodies and BOS has not been established. This study was conducted to determine the temporal relationship between the development of anti-HLA antibodies and BOS after LT, and to determine the antigenic specificity of the antibodies developed in BOS patients. METHODS Sera from 15 BOS+ LT patients and 12 BOS- LT patients were obtained before LT and collected again at 6, 12, 24, 36, and 48 months after LT. Anti-HLA antibodies were detected by the PRA-STAT ELISA system and by complement-dependent cytotoxicity assays. Anti-HLA reactivity was further characterized by flow cytometry and absorption/elution with human platelets. RESULTS When analyzed by ELISA, 10 of 15 BOS+ patients developed anti-HLA antibodies, whereas 0 of 12 BOS- patients developed anti-HLA antibodies (P<0.001). When analyzed by complement-dependent cytotoxicity, only 2 of 15 BOS+ patients developed anti-HLA antibodies and 1 of 12 BOS- patients developed anti-HLA antibodies (P = 0.99). There was a significant difference of 20.1 months between the time of anti-HLA antibody detection and the time of BOS diagnosis (P = 0.005). A progressive decrease in pulmonary function correlated with a progressive increase in the anti-HLA reactivity 36 months after LT. The anti-HLA reactivity was directed to one of the donor HLA class I antigens and to other unrelated HLA class I antigens. No anti-HLA reactivity was found against HLA class II molecules. CONCLUSIONS Our study indicates that anti-HLA class I antibodies play an important role in the pathogenesis of BOS and that monitoring of anti-HLA class I antibody development by a highly sensitive assay such as the PRA-STAT ELISA after LT can provide an early identification of an important subset of LT patients with an increased risk of developing BOS.

Prevalence and outcome of bronchiolitis obliterans syndrome after lung transplantation

Background. Bronchiolitis obliterans syndrome (BOS) is the main cause of late morbidity and mortality in lung transplantation. This study was designed to accurately determine the prevalence of this syndrome of chronic lung allograft dysfunction (which is presumed to be due to chronic rejection). Methods. A retrospective analysis was done of 212 consecutive lung transplantations performed at Barnes Hospital between July 1988 and March 1994 to characterize the prevalence and course of BOS. One hundred eighty-seven transplant recipients survived at least 3 months after transplantation, putting them at risk for BOS. Recipients free of BOS (group I) were distinguished from those with BOS (group II) based on the presence of declining spirometry (forced expiratory volume in 1 second persistently less than 80% of previous baseline) or histologic obliterative bronchiolitis in group II. Results. There were 110 transplantations in group I (59%) and 77 in group II (41%). At follow-up, BOS was detected using the following criteria: declining forced expiratory volume in 1 second alone, 40 of 77 (52%); positive histologic results alone, 7 of 77 (9.1%); and both, 30 of 77 (38.9%). Declining spirometry was the most common initial sign of BOS onset (57 of 77, 74%). There were no differences between groups with respect to age, sex, indication for transplantation, or type of transplantation performed. The mortality rate was significantly higher with BOS (group II, 22 of 77 [28.6%] versus group I, 8 of 110 [7.3%]; p = 0.001) and was not related to either the type of transplantation performed or the indication for transplantation. Follow-up of group II (mean 35.1 months; range, 7.1 to 63.7 months) showed a delay until BOS onset (16.1 ± 1.2 months); when BOS was fatal, death ensued within 11.5 ± 2.4 months of its onset. Comparison of the first and last quartiles of recipients in this series (QTR1 versus QTR4, 53 patients in each) demonstrated a higher prevalence of BOS in QTR1 (24 with BOS of 43 at risk [55.8%] versus QTR4, 5 with BOS of 52 at risk [9.6%]; p p = 0.007). Conclusions. (1) Bronchiolitis obliterans syndrome is truly a clinical syndrome, not simply a pathologic entity; (2) BOS displays considerable latency in onset and progression; (3) lung transplant recipients must therefore be followed up for a sufficient interval to determine the actual prevalence and mortality rate of BOS; and (4) the prevalence and mortality rates of BOS are higher than previously appreciated, exceeding 50% and 40%, respectively.