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Objectives: We hypothesized that higher plasma levels of von Willebrand factor (vWF) and reduced ristocetin cofactor activity (RCA)/vWF ratios at baseline and follow-up would be associated with an increased risk of death in patients with pulmonary arterial hypertension (PAH)., Background: Endothelial injury and dysfunction cause increased vWF levels in patients with cardiovascular disease. Increased vWF is associated with a higher risk of death in patients with coronary artery disease, congestive heart failure, and ARDS. In PAH, vWF is elevated and functions abnormally, resulting in reduced platelet binding. The ability of vWF to bind platelets is reflected by RCA., Methods: We performed a retrospective cohort study of 66 PAH patients who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation., Results: vWF level was directly associated with Factor VIII activity, RCA, fibrinogen, and prothrombin time (p < or = 0.01). vWF levels at baseline and follow-up were associated with the risk of death (hazard ratio [HR] per 50% increase, 1.4; 95% confidence interval [CI], 1.1 to 1.8 [p = 0.02]; and HR per 50% increase, 1.5; 95% CI, 1.1 to 2.0 [p = 0.011]; n = 48, respectively). RCA/vWF ratios were not associated with outcome. These results were unaffected by adjustment for demographics, baseline hemodynamics, laboratory results, or PAH therapy in multivariate analyses., Conclusions: Increased vWF levels at baseline and follow-up are associated with worse survival in patients with PAH; however, RCA/vWF ratios are not. The hemostatic effects of vWF do not account for these findings. This suggests that endothelial injury and dysfunction may persist despite treatment and may impact on disease course. Therapies that target endothelial injury may therefore improve outcomes for patients with PAH.

Introduction: Among risk factors for the progression of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LT), the influence of time to BOS onset is not known. The aim of the study was to assess if BOS occurring earlier after LT is associated with worse functional prognosis and worse graft survival., Method: We retrospectively compared functional outcome and survival of all single-LT (SLT) recipients who had BOS develop during follow-up in our center according to time to onset of BOS (< 3 years or > or = 3 years after transplantation)., Results: Among the 29 SLT recipients with BOS identified during the study period, 20 patients had early-onset BOS and 9 patients had late-onset BOS. The mean decline of FEV(1) over time during the first 9 months in patients with early-onset BOS was significantly greater than in patients with of late-onset BOS (p = 0.04). At last follow-up, patients with early-onset BOS had a lower mean FEV(1) value (25% vs 39% of predicted, p = 0.004), a lower mean PaO(2) value (54 mm Hg vs 73 mm Hg, p = 0.0005), a lower 6-min walk test distance (241 m vs 414 m, p = 0.001), a higher Medical Research Council index value (3.6 vs 1.6, p = 0.0001), and a higher percentage of oxygen dependency (90% vs 11%, p = 0.001) compared with patients with late-onset BOS. In addition, graft survival of patients with early-onset BOS was significantly lower than that of patients with late-onset BOS (log-rank test, p = 0.04). There were 18 of 20 graft failures (90%) in the early-onset BOS group, directly attributable to BOS in all cases (deaths [n = 10] or retransplantation [n = 8]). In the late-onset BOS group, graft failure occurred in four of nine patients due to death from extrapulmonary causes in three of four cases. The median duration of follow-up after occurrence of BOS was not statistically different between patients with early-onset BOS and patients with late-onset BOS (31 +/- 28 months and 37 +/- 26 months, respectively; p = not significant)., Conclusion: The subgroup of patients who had BOS develop > or = 3 years after SLT are less likely to have worrisome functional impairment develop in long-term follow-up. Considering the balance between the advantages and risks, enhancement of immunosuppression should be regarded with more caution in this subgroup than in patients with early-onset BOS.

Background: A biphasic-plateau pattern in the maximal expiratory flow-volume (MEFV) curve has been described after single-lung transplantation (SLT) in patients with chronic airways obstruction (CAO). It has been theorized that this pattern is either related to stenosis at the anastomotic or subanastomotic site, or the sum of the airflow contribution from the native lung with airways obstruction and transplanted lung., Subjects and Methods: We analyzed data in 16 patients with CAO who had undergone transplantations (5 men, 11 women; mean age [+/- SD], 53.8 +/- 4.9 years), and 9 patients with pulmonary vascular disease (PVD) without airways obstruction who had undergone transplantations (2 men, 7 women; mean age, 35.4 +/- 11.4 years)., Results: In the patients with PVD, there were no significant changes in static or dynamic lung volumes or in the MEFV curve after SLT. In the patients with CAO, indexes of airways obstruction improved significantly after SLT, and the typical biphasic-plateau pattern developed in the MEFV curve. In one patient with CAO who required pneumonectomy of the native lung after SLT, the biphasic pattern was absent., Conclusions: These results support the view that this MEFV pattern is a result of airflow from the native and transplanted lungs in patients with CAO. In addition, the results show that in patients with no prior airways obstruction, SLT does not alter static or dynamic lung volumes or maximal expiratory flow rate.

Study Objectives: To determine levels of the vascular endothelial growth factor (VEGF) isoform consisting of 165 amino acids (VEGF(165)) in BAL fluid (BALF) from lung transplant recipients (LTXs)., Design: Bronchoscopy with BAL was performed on LTXs and normal volunteers (NVs)., Setting: University hospital., Participants: LTXs (n = 57) and NVs (n = 15). MEASUREMENTS AND RESULT: VEGF(165) concentrations in BALF were higher (mean +/- SEM, 240 +/- 32 pg/mL) for NVs (n = 15) vs 133 +/- 14 pg/mL for LTXs (n = 37) who were stable without evidence of significant rejection or infection at 6 months after transplantation (p < 0.0001). BALF VEGF concentrations sampled at 24 to 48 h, 2 weeks, 4 weeks, and 6 months after transplantation for 11 LTXs who lacked rejection or infection at any time point were 71 +/- 8 pg/mL, 80 +/- 20 pg/mL, 82 +/- 13 pg/mL, and 167 +/- 31 pg/mL, respectively. VEGF concentrations in BALF for LTXs with cytomegalovirus (CMV) pneumonia were 55 +/- 12 pg/mL (n = 10), 117 +/- 33 pg/mL for grade A3 acute rejection (n = 9), and 82 +/- 17 pg/mL (n = 14) for active bronchiolitis obliterans syndrome (BOS). Concentrations of VEGF in BALF at 6 months for the 32 stable recipients with bilateral lung transplantation were significantly higher for those with higher values for FEV(1), and BALF VEGF concentrations were significantly lower in BALF at 6 months for those recipients who subsequently went on to develop BOS (86 +/- 19 pg/mL) vs those who did not (158 +/- 18 pg/mL; p = 0.03). Serum concentrations of VEGF did not correlate with VEGF concentrations in BALF, but serum VEGF was 291 +/- 62 pg/mL at 10 to 14 days after transplantation vs 130 +/- 20 pg/mL at 4 weeks for nine LTXs with paired samples (p < 0.02). Serum VEGF concentrations for NVs (n = 15) were 102 +/- 15 pg/mL vs 94 +/- 17 for stable LTXs (n = 12) at 24 weeks after transplantation and 123 +/- 33 pg/mL for LTXs with active BOS (n = 10)., Conclusions: BALF VEGF concentrations are particularly depressed at early time points following lung transplantation, gradually improve in the absence of significant rejection or infection, and are lower with active rejection or CMV pneumonia.

Study Objective: Using the negative expiratory pressure (NEP) method, we have previously shown that patients receiving single lung transplantation (SLT) for COPD do not exhibit expiratory flow limitation and have little dyspnea at rest. In the present study, we assessed whether SLT patients exhibit flow limitation, overall hyperinflation, and dyspnea during exercise., Methods: Expiratory flow limitation assessed by the NEP method and inspiratory capacity maneuvers used to determine end-expiratory lung volume (EELV) and end-inspiratory lung volume (EILV) were performed at rest and during symptom-limited incremental cycle exercise in eight SLT patients., Results: At the time of the study, the mean (+/- SD) FEV(1), FVC, functional residual capacity, and total lung capacity (TLC) amounted to 55 +/- 14%, 67 +/- 12%, 137 +/- 16%, and 110 +/- 11% of predicted, respectively. At rest, all patients did not experience expiratory flow limitation and were without dyspnea. At peak exercise, the maximal mechanical power output and maximal oxygen consumption amounted to 72 +/- 20% and 65 +/- 8% of predicted, respectively, with a maximal dyspnea Borg score of 6 +/- 3. All but one patient exhibited flow limitation and dynamic hyperinflation; the EELV and EILV amounted to 74 +/- 5% and 95 +/- 9% TLC, respectively. The patient who did not exhibit flow limitation during exercise had the lowest dyspnea score., Conclusion: Most SLT patients for COPD exhibit expiratory flow limitation and dynamic hyperinflation during exercise, whereas maximal dyspnea is variable.

Objective: The purpose of this study was to examine the psychological functioning and quality of life (QOL) of lung transplant candidates and recipients., Methods: The following measures were completed by 36 lung transplant candidates (the pretransplant group [PRE]) and 73 recipients (the posttransplant group [POST]): the Rand-36 Item Health Survey 1.0 (RAND-36), visual analog scale of overall QOL (OQOL), Brief Symptoms Inventory (BSI), Derogatis Sexual Functioning Inventory (DSFI), Hospital Anxiety and Depression Scale (HAD), Rosenberg Self-Esteem Scale (RSES), and Body Cathexis Scale (BC)., Results: Compared to the PRE, POST patients had significantly better scores on the following measures: RAND-36 total, physical health, role limitations due to physical health, general health, vitality, and social functioning subscales (all p < 0.0001); visual analog scale of OQOL (p < 0.0001); BSI (p < 0.05); BC (p < 0.05); HAD anxiety (p < 0.05) and depression (p < 0.0001); and RSES (p < 0.05). Despite better scores, some areas did not differ between the PRE and the POST, and many patients continued to experience impairments in psychological functioning. Specifically, the RAND-36 emotional health and role limitations due to emotional health subscale scores did not differ between the PRE and the POST and they remained lower than published norms. A significant proportion of patients in both groups (44% of PRE patients and 28% of POST patients) had borderline or clinical levels of anxiety (ie, the HAD). Finally, PRE and POST mean scores were significantly lower than published norms on the RSES (p < 0.05) and the body image scale of the DSFI (p < 0.05)., Conclusions: Although lung transplant recipients have better general, physical, and psychological health than their pretransplant counterparts, the present research suggests that both groups experience impairment in several areas of psychological functioning. Future research into the QOL of the lung transplant population should be aimed at recognizing, intervening, and improving patients' psychological and emotional well-being.

Study Objective: Osteoporosis is a well-recognized complication of lung transplantation that may significantly impair the quality of life of transplant recipients. We performed a prospective study of bone mineral density (BMD) before and after transplantation to determine the degree of bone mass loss associated with lung transplantation Patients and design: We conducted a prospective study of BMD in 28 patients with various end-stage respiratory diseases pretransplantation and 6 to 12 months posttransplantation. The BMD of the lumbar spine (LS) and femoral neck (FN) were measured. All 28 patients were treated only with vitamin D and calcium supplementation posttransplant. The primary endpoint was the percentage change in BMD. The secondary endpoint was the incidence of fractures posttransplant. A univariate analysis was conducted to determine the various risk factors associated with bone mass loss pretransplant and posttransplant., Results: Prior to transplantation, moderate to severe bone disease was evident. The mean (+/- SD) pretransplant T score (the number of SDs from the peak bone mass) and Z score (the number of SDs from the age-matched mean) for the LS were -1.72 +/- 1.37 and -1.44 +/- 1.31, respectively. The mean pretransplant T score and Z score for the FN were -2.65 +/- 1.01 and -1.5 +/- 1.43, respectively. Within 6 to 12 months posttransplant, the mean BMD for the LS decreased by 4.76% (p < 0.001), while the mean BMD for the FN decreased by 5.3% (p < 0.001). Five of the 28 patients (18%) suffered osteoporotic fractures posttransplant, while no fractures were documented pretransplant. The cumulative steroid dose posttransplant was associated with a drop in BMD for the LS and FN (r = 0.39, p = 0.039 and r = 0.63, p < 0.001, respectively), while a negative association was found between cumulative steroid use pretransplant and baseline LS and FN T scores (r = -0.4, p = 0. 02 and r = -0.43, p = 0.023, respectively)., Conclusion: Within 6 to 12 months after lung transplantation, there is a significant decrease in BMD at both the LS and FN levels (approximately 5%) despite vitamin D and calcium supplementation. This drop in BMD is associated with a relatively high incidence of osteoporotic fractures posttransplant.

Introduction: Most experimental studies of orthotopic heart and lung graft failure are complicated by an inability to eliminate the rejection-specific inflammatory mediator from the cardiopulmonary bypass., Methods: The following model was developed in our laboratory to investigate the feasibility of performing an orthotopic heart and bilateral lung transplantation without performing a cardiopulmonary bypass. Nineteen transplants were attempted using 19 pairs of mongrel dogs. The recipient dog (mean weight, 23 kg) was anesthetized, and the ascending aorta, the superior vena cava (SVC), the inferior vena cava (IVC), and the main bronchus were dissected. Then, the donor dog (mean weight, 20 kg) was anesthetized, and the heart and lung block was prepared and explanted from the chest under cardioplegic arrest. A Gore-tex shunt (W. L. Gore; Flagstaff, AZ) was placed side-to-side between the recipient IVC and SVC, and then the donor right atrium was anastomosed to the Gore-tex shunt. The donor ascending aorta was anastomosed to the recipient ascending aorta with a partial clamp. On completion of these anastomoses, the donor heart was reperfused by the recipient heart and allowed to beat. When hemodynamic conditions were stable with double hearts, the recipient SVC and IVC were ligated just proximal to the venous anastomosis and the recipient aorta was ligated proximal to the anastomotic site. The recipient trachea was anastomosed to the donor trachea with an end-to-end anastomosis. Finally, the recipient heart and lungs were removed from the chest and the sternum was closed., Results: Four of the 19 transplants failed. Three died due to left ventricular dysfunction, and one died due to bleeding. Mean (+/- SD) ischemic time was 67 +/- 11 min with a mean (+/- SD) anastomotic time of 54 +/- 12 min. The 15 survivors were hemodynamically stable with or without the minimal use of inotropic support (dopamine, 2 to 3 microg/kg/min) 6 h after grafting, with normal cardiac output, satisfactory oxygenation, and normal wall motion. The sternotomy was repaired without loss of cardiopulmonary function., Conclusions: On the basis of our experiences, the experimental model of orthotopic heart and bilateral lung transplantation completed "off pump" can be technically feasible without the loss of cardiac and pulmonary functions.

Study Objectives: To determine whether long-term IV prostacyclin (PGI(2)) use improves exercise capacity in patients with primary pulmonary hypertension (PPH)., Design: Cycle ergometry and the 6-min walk was used to evaluate the exercise performance of patients with PPH. The patients underwent serial exercise testing after starting continuous IV PGI(2) and were followed up for 19.5 +/- 7.5 months. Peak work, peak oxygen consumption (f1.gif" BORDER="0">O(2)), peak O(2) pulse, and distance walked in 6 min were used to evaluate performance., Background: PPH is characterized by medial hypertrophy and intimal proliferation of the pulmonary arterioles, leading to elevation of pulmonary artery pressure, right ventricular failure, and death. Palliative treatment consists of vasodilators, anticoagulants, cardiac glycosides, diuretics, and transplantation. PGI(2), a potent vasodilator and inhibitor of platelet aggregation, has been used for long-term treatment when conventional therapy has been unsuccessful., Patients: Sixteen patients with PPH (10 women, 6 men; mean age, 24 years)., Results: At the initiation of PGI(2), peak work (+/- SD) was 35.5 +/- 11% of predicted; peak f1.gif" BORDER="0">O(2), 39 +/- 10.4%; peak O(2) pulse, 5.0 +/- 1.7 mL/min; and distance on the 6-min walk, 428 +/- 78 feet. At 18 to 27 months, peak work increased to 58.8 +/- 23% of predicted (p = 0.001), peak f1.gif" BORDER="0">O(2) increased to 52 +/- 15% of predicted (p = 0. 02), peak O(2) pulse increased to 7.1 +/- 3.0 mL/beat (p = 0.004), and performance on the 6-min walk increased to 526 +/- 62 feet (p = 0.001). There was a positive correlation between peak f1.gif" BORDER="0">O(2) and peak 6-min walk of 0.6 (p < 0.005) and between peak work and peak 6-min walk of 0.6 (p < 0.005)., Conclusions: Exercise capacity improved in our patients at up to 27 months of follow-up. Exercise testing is helpful in assessing the functional capacity of patients with PPH and may be useful in guiding therapy. Patients who deteriorate while receiving optimal conventional therapy should be considered for IV PGI(2) therapy.

Study Objectives: To review the experience of the Alfred Hospital in the systematic assessment of coronary artery disease (CAD) using coronary angiography (CA), and the subsequent management of CAD, in potential lung transplant recipients., Design: Retrospective study., Setting: The Alfred Hospital Lung and Heart Transplant Service., Patients: CAD risk factors were sought in potential recipients of lung transplantation (LTx) who were > 50 years old, including a history of smoking, male gender, hypertension, diabetes, hypercholesterolemia, angina, and a family history of CAD. When feasible, and in the presence of more than one cardiac risk factor, CA was performed., Results: From 243 referral patients who were > 50 years old, 97 were listed for LTx, and 77 underwent LTx. Four patients were refused LTx on the basis of CAD. Of 101 patients undergoing a detailed cardiac assessment for LTx, 83 had smoked, 56 were male, 48 had hypercholesterolemia, 22 had hypertension, 4 had diabetes, and 3 had a history consistent with angina. Eighty-five patients underwent CA. In 32 cases, CA revealed CAD, and half of these cases were significant stenoses. Eight patients who were assessed required intervention. Five patients of this group have been transplanted; of these, three patients underwent coronary artery grafting at the time of LTx, and two patients underwent preoperative angioplasty or stenting. Only one of these five patients died < 90 days postoperatively., Conclusion: Significant CAD is a common finding in older patients who are presenting for LTx. Coronary revascularization for severe large vessel stenoses can allow safe LTx. CAD risk factors may predict who should undergo CA, but further studies of clinical and noninvasive assessments of CAD are needed if CA is to be safely avoided in patients at low risk of CAD.

Study Objective: To determine whether an aerobic endurance training program (AET) in comparison to normal daily activities improves exercise capacity in lung transplant recipients., Patients and Study Design: Nine lung transplant recipients (12+/-6 months after transplant) were examined. All patients underwent incremental bicycle ergometry with the work rate increased in increments of 20 W every 3 min. Identical exercise tests were performed after 11+/-5 weeks of normal daily activities and then after a 6-week AET. The weekly aerobic training time increased from 60 min at the beginning to 120 min during the last week. Training intensity ranged from 30 to 60% of the maximum heart rate reserve., Results: Normal daily activities had no effect on exercise performance. The AET induced a significant decrease in resting minute ventilation from 14+/-5 to 11+/-3 L/min. At an identical, submaximal level of exercise, a significant decrease in minute ventilation from 47+/-14 L/min to 39+/-13 L/min and heart rate from 144+/-12 to 133+/-17 beats/min, before and after the AET, was noted. The increase in peak oxygen uptake after AET was statistically significant (1.13+/-0.32 to 1.26+/-0.27 L/min)., Conclusions: These data demonstrate that normal daily activities do not affect exercise performance in lung transplant recipients > or = 6 months after lung transplantation. An AET improves submaximal and peak exercise performance significantly.

Objective: Evaluate the reliability and validity of a new version of the University of California, San Diego Shortness of Breath Questionnaire (SOBQ), a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living., Design: PATIENTS enrolled in a pulmonary rehabilitation program were asked to complete the SOBQ, the Quality of Well-Being Scale, the Center for Epidemiologic Studies Depression Scale, and a 6-min walk with modified Borg scale ratings of perceived breathlessness following the walk., Setting: University medical center pulmonary rehabilitation program., Patients: Thirty-two male subjects and 22 female subjects with a variety of pulmonary diagnoses: COPD (n=28), cystic fibrosis (n=9), and postlung transplant (n=17)., Measurements and Results: The current version of the SOBQ was compared with the previous version, the format of which often resulted in a significant number of "not applicable" answers. The results demonstrated that the SOBQ had excellent internal consistency (alpha=0.96). The SOBQ was also significantly correlated with all validity criteria., Conclusions: The SOBQ is a valuable assessment tool in both clinical practice and research in patients with moderate-to-severe lung disease.

The aim of this study was to determine the lung levels of metallothionein (MT), a free radical scavenger, because oxygen-derivated free radicals (ODFRs) have been involved both in reperfusion injury of transplanted lungs and in cardiac or renal allograft destruction. First, MT localization was evaluated in 14 normal human lung biopsy specimens. Then, in lung transplant recipients, MT content in BAL fluid (BALF) and its transcription rate in alveolar macrophages (AMs) were determined. The BALFs of 69 patients were separated into six groups: lung transplant recipients in clinically stable condition (CSR), those with acute rejection (AR), asymptomatic cytomegalovirus infection (ACMV), cytomegalovirus pneumonitis (CMVP), bronchiolitis obliterans syndrome (BOS), and patients without transplants who served as control subjects (NTCs). In normal lungs, 83% of AMs were positively stained. MT staining was also observed in pleural endothelial cells and basal cells from bronchial epithelium. In lung transplant recipients, MT levels in BALF were significantly higher in patients with CSR, AR, ACMV, and CMVP compared with NTCs, while during BOS, MT had a significantly lower level compared with other lung transplant groups. However, no difference among groups was found concerning MT-II messenger RNA expression in AMs, showing that, as in normal lung, AMs are not the only cells that produce MT. These data report for the first time to our knowledge MT cell distribution in human lung with specific emphasis on its enhanced levels after lung transplantation, even in the absence of complication. Possible correlation among MT levels, ODFRs, cytokine levels, and corticosteroid treatment during complications of lung transplantation are discussed.

Unlabelled: Eosinophils are important inflammatory cells involved in liver and renal allograft rejection. The role of these cells is less well defined in lung allograft rejection. Eosinophils may be activated in lung rejection and release cytotoxic eosinophil cationic protein (ECP). Other states of disease in lung transplant recipients, such as cytomegalovirus (CMV) and bacterial infection, may also be associated with activated eosinophils. We postulated that ECP may be detectable and elevated in the airway lavage samples obtained from lung transplant patients and may contribute to disease pathogenesis., Methods: Fifty BAL samples were collected from 38 lung transplant patients. Their most recent pulmonary function test results within 1 week of collection were noted. The samples were analyzed for the concentration of ECP, WBC count and differential cell count, and total protein level. The results were analyzed to identify the presence of disease or abnormal lung function associated with a positive ECP test. Student's t test was used and a p value of <0.05 was considered significant., Results: We found that ECP levels were elevated in 36% (n=14) of the patients. Those patients with a positive test result were more likely to have acute rejection, CMV disease, or the presence of a cultured pathogen in BAL compared to patients with a negative test result (p<0.01)., Conclusions: The presence of BAL ECP is associated with disease in lung transplant patients. Since ECP is directly cytotoxic, it may contribute to disease pathogenesis.

Study Objective: To assess the potential utility of specific airway conductance (sGaw) in detecting small airways dysfunction, the postlung-transplant bronchiolitis obliterans syndrome (BOS) was used as a model of small airways dysfunction. BOS is defined as an otherwise unexplained 20% reduction in FEV1. We hypothesized that if sGaw is sensitive to small airways dysfunction, it should decrease before the decline in FEV1., Design/methods: The pulmonary function test and sGaw measurements of patients who underwent heart-lung or bilateral lung transplantation between May 1981 and January 1993 were reviewed. Patients with and without BOS were identified. A significant decrease in sGaw was defined as a 20% fall from baseline., Results: Twenty-six BOS and 15 non-BOS patients had at least three sGaw measurements such that trends could be examined. Eleven of the 26 BOS patients (42%) had a significant decrease in sGaw before a 20% decrease in FEV1, as compared to 2 of the 15 non-BOS patients (13%) (p=0.08). In comparison, 12 of the 26 BOS patients (46%) and 4 of the 15 non-BOS patients (27%) had a significant decrease in forced expiratory flow at 25 to 75% of the forced lung volume (FEF(25-75)) (p=0.32), an accepted test of small airways dysfunction., Conclusion: sGaw tended to decrease before FEV1 in BOS. The trend in sGaw was similar to the trend in FEF(25-75). We conclude that (1) small airways may contribute more to airway conductance than previously thought, and (2) further prospective studies are warranted to better define the relative contribution of small and large airways to sGaw.

The use of bronchial blocker to optimize gas exchange in a patient with marked differential lung disease is reported. This technique proved to be a useful alternative in an ICU setting to independent lung ventilation.

Study Objective: The aim was to identify potential predictors of ICU length of stay (LOS) for single lung transplant patients., Design: Retrospective chart review., Setting: University medical center., Patients: All single lung transplant recipients for 1992 and 1993 at our institution., Results: Data were collected from 69 patients. The median ICU LOS was 5 days, and this was highly correlated with the duration of mechanical ventilation. The mean acute physiology and chronic health evaluation (APACHE II) score was 10. Patients with pulmonary hypertension had the longest ICU LOS. Similarly, patients with a measured transpulmonary gradient of 20 mm Hg or less had a significantly shorter ICU LOS. Patients with an immediate postoperative PaO2/fraction of inspired oxygen (FIo2) ratio greater than 200 mm Hg and a flow mismatch between the two lungs of 30% or less also had a significantly shorter ICU LOS. Positive and negative predictive values for the immediate postoperative PaO2/FIo2 ratio of 200 mm Hg or less were 77% for an ICU LOS greater than 5 days, and the calculated receiver operating characteristic (ROC) curve area was 0.74., Conclusion: Overall, the immediate postoperative PaO2/FIo2 ratio of 200 mm Hg or less had the best positive and negative predictive values as well as the highest ROC curve area for predicting an ICU LOS greater than 5 days.

There is no consensus regarding the optimal induction immunosuppression regimen after lung transplantation (LT). In addition to the potential benefit of a reduced incidence of early acute allograft rejection, cytolytic induction immunosuppression may impact on long-term allograft function. We retrospectively assessed our incidence of obliterative bronchiolitis syndrome (OBS) stages Ia and IIa in LT survivors given two different cytolytic induction immunosuppression regimens: (between March 1989 and October 1990) OKT3 (5 mg/d)x10 to 14 days (n=11) vs (between November 1990 and April 1993) Minnesota antilymphocyte globulin (MALG) (10 to 15 mg/kgdx5 to 7 days. Cyclosporine (CSA) (whole blood polyclonal assay=600 to 800 ng/mL), azathioprine (1 to 2 mg/kg/d), and maintenance prednisone (0.2 mg/kg/d) were similar. Surveillance spirometry was performed monthly, in accordance with accepted American Thoracic Society criteria. Fiberoptic bronchoscopy with transbronchial biopsies (TBBs) were performed for clinical indications. Surveillance TBBs were not performed during the era of this study. As defined by the ISHLT "Working Formulation for the Standardization of Nomenclature and for Clinical Staging of Chronic Dysfunction in Lung Allografts," latencies to development of OBS stages Ia and IIa were determined by Kaplan-Meir analysis. Stepwise regression (Cox proportional hazards model) was performed for the variables: cytolytic induction regimen, episodes cytomegalovirus (CMV) pneumonitis, episodes CMV infection, serologic CMV donor (+): recipient (-) mismatch, prior pregnancy, HLA (A,B,DR +/- DQ) mismatches, episodes greater than grade A1 acute cellular rejection (ACR). We found that the OKT3 cohort experienced longer latencies for OBS stages Ia and IIa. Latencies to OBS stages Ia for OKT3 ve MALG were 962 +/- 65 vs 354 +/- 85 days (X +/- SEM) respectively. Brookmeyer-Crowley 95% confidence intervals for median latencies were 744 to 1,180 vs 266 to 510 days for OKT3 vs MALG, respectively. The Cox model was significant only for the variable of the induction cytolytic immunosuppression regimen (p=0.0015). By physiologic criteria, a longer course of OKT3 appeared superior to the short-course MALG protocol in delaying chronic lung allograft dysfunction. These effects may be related either to inherent differences in the antilymphocyte preparations or, alternatively, the difference in duration of treatment between groups. Surveillance TBB and treatment of detected occult ACR may serve to negate the observed differences in latencies for OBS.

Unlabelled: The bronchiolitis obliterans syndrome (BOS) is the major cause of late morbidity and mortality after lung transplant (LTx). Previous studies suggest cytolytic therapy may be effective for the BOS but this therapy has not been proved effective or safe., Method: A retrospective study of a predetermined treatment regimen to determine if the rate of fall in FEV1 can be reduced by corticosteroids and cytolytic therapy. Since August 1992, 10 to 65 long-term survivors of LTx (5 men, 5 women; mean age 36 +/- 10 years) developed BOS. All had previously had lymphocyte immune globulin, antithymocyte globulin (equine) (ATGAM sterile solution; Upjohn Pty Ltd; Sydney, Australia) induction therapy and corticosteroid avoidance for the first 7 to 10 days post-LTx. Therapy for the BOS was initiated with pulse methylprednisolone and ATGAM (aiming for an absolute CD3 count of < or - 100 cells per microliter for 5 days). ATGAM therapy was initiated at a mean 657 +/- 323 days post-LTx. Subsequent follow-up has been for 310 +/- 110 days (range, 163 to 530 days)., Results: Nine of ten patients had a response with tolerable side effects. Preintervention, there was a linear fall in FEV1 of 0.22 +/- 0.15% predicted FEV1 per day (mean +/- SD) (range, 0.06 to 0.56%) compared with a postintervention linear fall of 0.036 +/- 0.019% predicted per day (range, 0 to 0.13%) (paired t test; p<0.005). This effect is sustained over the follow-up period., Conclusion: The fall off in FEV1 that characterizes the BOS may be altered usefully by augmented immunotherapy. This effect can be rapid and sustained although it is neither completely arrested nor ever reversed. These data are preliminary but encourage a randomized control trial in the BOS.

In single-lung transplant recipients, the usefulness of spirometric indexes in detecting acute events involving the lung graft is limited due to the bias caused by the native lung. Selective functional monitoring is needed for the proper evaluation of complications after transplantation, but thus far, to our knowledge, no clinically feasible methods for selective graft-function assessment have been presented. In ten single-lung recipients, of whom six had a parenchymal lung disease and four had pulmonary hypertension, the relative ventilation (Vtx), perfusion (Qtx), and ventilation/perfusion ratio of the transplanted lung (V/Qtx) were determined with multidetector 133Xe radiospirometry. Additionally, the fractions of FEV1, FVC, and diffusing capacity for carbon monoxide (Dco) of the transplant (FEV1tx, FVCtx, Dcotx, respectively) were determined by using corresponding radiospirometric parameters for the calculation of their distribution between the lungs. The analysis included seven episodes of acute rejection and nine episodes of infection. The Qtx decreased during acute rejection but did not change during infection (p=0.001). Compared with the figures during infection, the V/Qtx increased during acute rejection significantly (p<0.05) in patients with underlying fibrosis or emphysema, but not in those with pulmonary hypertension. In detection of acute events, the sensitivity of the selective parameters, ie, FEV1tx (86%) and FVCtx (73%), was higher than that of the sum-function parameters, FEV1 (66%) and FVC (40%). Moreover, the sensitivity of Dcotx (80%) was higher than that of Dco (60%) in detecting acute rejection. The findings indicate that, in single-lung recipients with a parenchymal lung disease, the assessment of Qtx, V/Qtx, and Dcotx with a radioactive tracer can help to distinguish acute rejection from infection. The graft-selective parameters, ie, FEV1tx, FVCtx, and Dcotx, tended to be more sensitive than the corresponding sum-function parameters in detecting acute events, thus providing a more accurate functional profile of the single-lung graft.

Background: Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term lung allograft viability. The diagnosis often occurs after significant organ dysfunction is present, and BOS is often unresponsive to standard immunosuppressive agents. We have observed bronchodilator responses (BRs) at low lung volumes in many of our patients who have developed BOS. We therefore assessed whether BR could predict the development of BOS., Methods: We conducted a retrospective review of the clinical and pulmonary function laboratory records of 146 patients who underwent transplantation between March 1983 and November 1993. BR was defined as 25% or more increase in forced expiratory flow at 50% of vital capacity or 30% or more increase in forced expiratory flow at 75% of vital capacity. BOS was defined according to recently published FEV1 criteria. Bronchiolitis obliterans was defined histologically according to criteria of the Lung Rejection Study Group., Results: Of the total population, 52 were excluded because of death or insufficient information. BRs of the small airways were seen in 31 patients (33%), 25 of whom developed BOS (83%). Approximately half of those with BR who developed BOS had evidence of acute rejection in the month prior to the onset of BR. Two thirds (four of six) of patients with BR not developing BOS had acute rejection in the previous month. The sensitivity of BR in predicting BOS was 51% with a specificity of 87%. The positive predictive value was 81%., Conclusions: BR appears to be useful as an early marker of BOS. The development of BR in selected patients should lead to closer monitoring and possibly a trial of augmented immunosuppression to arrest the establishment of BOS.

Thioredoxin (TRX) production has been shown to be induced by a variety of stresses. In this study, we examined TRX expression in lung tissues after canine lung transplantation to determine whether it could be induced by allogenic stimulations and could be used to diagnose early rejection. Thirty-five adult mongrel dogs were used in all. In group A, 24 dogs underwent allotransplantation of the left lung with no immunosuppressant and were sacrificed at various times; 5 were sacrificed on postoperative day (POD) 1; 5 on POD 2; 7 on POD 3; and 7 on POD 5. In group B, 5 donor right lungs were used for negative control. In group C, 3 dogs underwent autotransplantation. In group D, 8 dogs underwent allotransplantation of the left lung with optimal immunosuppression and were sacrificed at POD 28. Lung tissues were stained with anti-TRX antibody, and the TRX high-producer (TRXh) cells in a randomly chosen field were counted as the index of TRX expression. In group A, the number of TRXh cells were as follows: 1.68 +/- 1.14 in grade 0; 4.87 +/- 1.07 in grade 1; 10.42 +/- 4.24 in grade 2; 27.34 +/- 17.96 in grade 3; and 50.90 +/- 17.36 in grade 4. In group B, the number of TRXh cells was 1.82 +/- 1.01. There was a significant difference between each rejection grade in group A and group B (p < 0.01), and we could observe TRXh cells in the early stage of rejection. These results suggest that analysis of TRXh cells in lung tissues may be useful in the early diagnosis of rejection.

Study Objective: To assess the relationship of distance ambulated during the 6-min walk test (6'WT) to maximal oxygen consumption (VO2 max)., Design: Multivariate analysis of patient characteristics to VO2 max., Setting: Pre-lung transplant evaluation., Patients: 60 patients (22 men, 38 women; mean age, 44 years) with end-stage lung disease (mean FEV1 and forced vital capacity of 0.97 and 1.93, respectively)., Measurements and Results: The 6'WT was performed on a level hallway surface, and VO2 max was obtained during maximal cycle ergometry exercise testing with respiratory gas analysis. Multivariate analysis of patient characteristics (age, sex, weight, FEV1, FVC, diffusing capacity for carbon monoxide (DCO), 6'WT distance ambulated, number of rests per 6'WT, and the maximal heart rate, blood pressure, rate-pressure product, respiratory rate, oxygen saturation, rating of perceived exertion, and amount of supplemental oxygen used during the 6'WT) was performed on two groups of 30 patients each (group A or B) who were randomly assigned to either group by a process of random selection using a computer-generated random numbers program. Distance ambulated was the strongest independent predictor of VO2 max (r = 0.73; p < 0.0001) in both groups, and adding age, weight, and pulmonary function test results (FVC, FEV1, and DCO) to the regression equation increased the correlation coefficient to 0.83. Because of the significant correlation of distance ambulated during the 6'WT to VO2 max, the prediction equation obtained from the multivariate analysis of group A, VO2 max = 0.006 x distance (feet) +3.38, was used to estimate the VO2 max of the group B patients. No significant difference was observed between the estimated (x +/- SD = 8.9 +/- 2.4 mL/kg/min) and observed (x +/- SD = 9.4 +/- 3.8 mL/kg/min) VO2 max (mean difference, 0.5 mL/kg/min; SD of the difference = 2.88)., Conclusions: The distance ambulated during a 6'WT can predict VO2 max in patients with end-stage lung disease. The addition of several patient characteristics can increase the ability to predict VO2 max and account for more of the variability. Such information is valuable when assessing patient response to therapeutic intervention if respiratory gas analysis is unavailable or impractical.

Cardiorespiratory responses to progressive exercise were examined in 38 children who had undergone heart (n = 16), heart-lung (n = 13), or double-lung (n = 9) transplantation, and in 41 healthy controls. The four groups were similar in age, but the control subjects and heart transplant recipients were significantly larger than the heart-lung and lung recipients as assessed by body mass index (BMI). Time since transplant was significantly longer in the heart (601 days) compared with heart-lung (146 days) and lung (125 days) transplant groups. Physical work capacity and peak oxygen uptake were significantly reduced (43 to 64% of predicted) in the three transplant groups compared with the control group. Peak heart rate (percent predicted) was significantly higher in the control subjects (94%) compared with the heart (66%), heart-lung (70%), and lung (77%) transplant recipients. Peak minute ventilation was significantly higher in the control (72.9 L/min) and heart transplant (51.0 L/min) groups than the heart-lung (37.4 L/min) and lung (41.3 L/min) transplant groups. The control group had a higher peak tidal volume than the three transplant groups, and a higher peak respiratory rate than the lung transplant recipients. Correlational analysis revealed that physical work capacity (PWC) was significantly related to heart rate at peak exercise (HRpeak) and minute ventilation at peak exercise (VE-peak) in the heart transplant recipients, BMI, VEpeak, and FEV1 in the heart-lung transplant recipients, and BMI, HRpeak, VEpeak, FEV1, and number of days posttransplant in the lung transplant recipients. In addition to these variables, physical deconditioning and factors related to pharmacotherapy, infection, and rejection may also contribute to the decreased PWC observed in the transplant recipients.

Objective: To report functional results and survival in patients undergoing single lung transplantation (SLT) for pulmonary involvement associated with systemic disease or prior malignancy, criteria traditionally considered contraindications to SLT., Design: Case series., Setting: The University of Texas Health Science Center at San Antonio., Patients: Nine patients who have undergone SLT for end-stage lung disease: four patients with sarcoidosis; two patients with limited scleroderma; and three patients with prior malignancies (two with prior lymphoma and bleomycin-induced pulmonary fibrosis and one who received two bone marrow transplants for acute lymphocytic leukemia and subsequently developed chemotherapy-induced pulmonary fibrosis)., Measurements: Pulmonary function testing, exercise oximetry, quantitative ventilation-perfusion lung scanning. Actuarial survival., Results: All patients had marked improvement in pulmonary function, exercise oximetry, and quantitative ventilation perfusion to the SLT. One patient with scleroderma died 90 days postoperatively from Pseudomonas pneumonia with a sepsis syndrome. One patient with sarcoidosis died 150 days postoperatively from disseminated aspergillosis. At autopsy, there was no evidence of recurrent fibrosis or sarcoidosis in the transplanted lungs in either of these two patients. The seven surviving patients have returned to work or school and are conducting all activities of daily living without pulmonary disability. The 1- and 2-year actuarial survival rates in these nine patients is 68.6 percent as compared with the 1- and 2-year actuarial survival rates of 66.3 percent and 55.8 percent in the remainder of our SLT group as a whole (n = 49). Despite pharmacologic immunosuppression, there is no evidence of recurrent malignancy in the 3 patients with prior malignancies., Conclusions: We conclude that carefully selected patients with end-stage lung involvement related to systemic disease or chemotherapy-induced fibrosis may benefit from SLT.

Cardiopulmonary exercise testing has previously demonstrated a reduced maximum oxygen uptake and anaerobic threshold, as well as abnormal wasted ventilation fraction and gas exchange after unilateral lung transplantation. To further explain the mechanisms of these abnormalities, we assessed the regional distribution of pulmonary blood flow and ventilation at rest and during steady-state exercise in nine recipients of unilateral lung transplants. Krypton-81 (81mKr) aerosol and technetium-99m (99mTc) were utilized to assess lung ventilation (V) and perfusion (Q), respectively. The digitalized images were trisected to analyze apical, mid-, and basilar lung perfusion and ventilation in both the transplanted and native lung, both at rest and steady-state upright exercise. Results were compared with previously reported data obtained in normal subjects in our laboratory using the identical technique. At rest, 75 +/- 13 percent of perfusion was directed to the transplanted lung; however, the corresponding fractional ventilation was only 67 +/- 14 percent. During exercise, there was no significant change in fractional perfusion or ventilation. Resting apical perfusion in the transplanted lung was higher than normal in four patients and comparable to normal in five patients. In contrast to the augmentation of apical perfusion observed in normal subjects during upright exercise, none of our patients increased the regional perfusion to the apices during exercise in either transplanted or native lungs. These unexpected responses suggest either more maximal allograft apical recruitment at rest due to the increased allograft perfusion or an abnormality in the apical pulmonary vasculature after transplantation. Furthermore, the relative mismatch in ventilation and perfusion in transplanted and native lungs suggests regions of high V/Q in the native, and low V/Q in the transplanted lung. This mismatch is most pronounced in recipients of single lung transplants for pulmonary vascular disease.

A reduced exercise tolerance, maximum oxygen uptake (VO2max), and anaerobic threshold have been reported after lung transplantation (LT). We prospectively assessed the hemodynamic responses to incremental cycle ergometry before and after LT in eight recipients. All recipients underwent a 6-week formal exercise training program. The VO2max increased after versus before LT (13.4 +/- 0.8 vs 9.2 +/- 0.8 ml/min/kg) (p < 0.01). No transition thresholds by analysis of arterial standard bicarbonate were discerned before LT, while the thresholds after LT were abnormally low (VO2 = 9.4 +/- 0.6 ml/min/kg or 35 +/- 3 percent of predicted maximum VO2). An early rise in arterial lactate was similarly observed after LT. Maximum stroke volume index increased in six of seven patients after versus before LT (51 +/- 4 vs 37 +/- 2 ml/beat/m2) (p < 0.05). Three patients demonstrated an increased mean pulmonary arterial pressure at rest, while pressures during exercise were elevated in six. Pulmonary vascular resistance was mildly elevated after LT but decreased appropriately during incremental exercise and was associated with normal cardiac output responses. We conclude that pulmonary vascular abnormalities occurred during hemodynamic exercise testing in the majority of LT recipients; however, exercise limitation was primarily attributed to cardiovascular limitation or to deconditioning in five of the recipients. In the remaining three, the exercise study was considered to be submaximal by virtue of low peak heart rates. A persistent state of deconditioning may have important implications with respect to exercise training regimens after LT.

We report a patient who received a right single lung transplant (SLT) for progressive lymphangioleiomyomatosis and required reintubation for postoperative respiratory distress. She developed hemodynamic instability due to mediastinal shift from unilateral auto-PEEP with hyperinflation of the native lung. Placement of a double lumen endotracheal tube (DLET) and institution of differential lung ventilation restored equal lung inflation and hemodynamic stability.

The study objective was to investigate bronchial mucociliary clearance after heart/lung and double lung transplantation. Bronchial mucociliary clearance was measured using a noninvasive radioaerosol technique: 99mTc-labeled albumin was aerosolized using a spinning-top generator (mass median aerodynamic diameter, 7.5 mu; geometric standard deviation, 1.5 mu). Radioactivity counts were acquired during 60 min with a gamma camera. A region of interest was drawn over the right lung delineated by a 133Xe lung ventilation image. Bronchial mucociliary clearance was assessed as the percentage of decrease in radioactivity per hour calculated on time-activity curves fitted by a monoexponential model. To exclude patients with acute lung rejection, opportunistic lung infection, and obliterative bronchiolitis, all patients with transplants underwent pulmonary function tests and bronchoscopic examination before clearance measurement. Eight heart/lung and five double-lung nonsmoking transplant patients with normal lung histology were studied 19.3 +/- 4.0 mo after surgery and compared to nine normal nonsmokers. A similar proximal deposition of the aerosol was obtained in patients with transplants and normal subjects; skew values of distribution histograms of aerosol radioactivity counts were 2.1 +/- 0.2 and 1.8 +/- 0.1, respectively, and the ratios between central and peripheral 99mTc radioactivity counts were 2.4 +/- 0.1 and 2.3 +/- 0.2, respectively. No significant difference was observed in bronchial clearance values between patients with heart/lung and double-lung transplants (26.4 +/- 3.0 percent/h vs 35.9 +/- 3.5 percent/h). Conversely, bronchial clearance was significantly lower in transplant recipients (30.0 +/- 2.5 percent/h) than in normal controls (58.7 +/- 6.2 percent/h; p < 0.001). This decreased bronchial clearance can be expected to increase the risk of lung infection in long-term survivors of heart/lung and double-lung transplantation.

Single lung transplantation (SLT) is now successfully used in patients with severe emphysema. Mechanical imbalance between the native emphysematous and the healthy transplanted lung can be easily managed, unless severe graft failure occurs, leading to acute respiratory failure. Emergency retransplantation has been used in this setting, since the conventional approach to adult respiratory distress syndrome (ARDS) (mechanical ventilation and positive end-expiratory pressure [PEEP]) fails, due to the mechanical discrepancy between the two lungs. We describe two cases of severe graft failure following SLT in emphysema patients that were successfully treated with prolonged independent respiratory treatment. Mechanical ventilation and PEEP were applied to the failing transplanted lung while the native emphysematous lung was maintained on spontaneous breathing to avoid hyperexpansion and barotrauma. The independent lung respiratory treatment lasted 35 and 25 days, respectively: to our knowledge, these are among the longest-lasting independent respiratory treatments reported. The management was simplified by the early use of a double-lumen tracheostomy cannula as an alternative to orotracheal double lumen tube.

During lung transplantation, a number of factors may cause endothelial injury to the donor organ, including ischemia, inadequate preservation, cardiopulmonary bypass, high potassium concentrations, and reperfusion. In this study, protein accumulation index (PAI) was used to assess pulmonary endothelial permeability (PEP) in ten patients immediately after lung transplantation. Six were studied sequentially every other day for ten days postoperatively. The PAI was also measured using the same technique in a group of 11 normal volunteers. Mean PAI x 10(-3)/min +/- (SEM) for ten patients measured within 36 h of transplantation was 1.27 (0.56) compared with 0.45 (0.08) for the normal group (p = 0.09). No correlation was found between preservation time and PAI following reperfusion. Three episodes of lung rejection were observed in two patients during the first ten postoperative days, during which PAI rose to 2.26 (0.26) compared with 0.73 (0.11) for all other studies in the group (p less than 0.01). We conclude that no increase in PEP could be demonstrated after graft reperfusion following lung transplantation as assessed by PAI in this small group of patients. However, further studies may show the technique to be useful in the detection of subsequent episodes of graft rejection.

In six single lung transplant (SLT) and six double lung transplant (DLT) recipients, the relationships of the recipient's posttransplantation vital capacity (posttx VCR) to the recipient's predicted normal vital capacity (pred VCR) and the donor's predicted normal vital capacity (pred VCD) were investigated. After left SLT the left posttx VCR was correlated with the left predicted VCD (r = 0.83; p less than 0.05); however, no correlation was found between these after DLT. In contrast, there was a tendency toward correlation between the posttx VCR and the predicted VCR after DLT (r = 0.75; p less than 0.1), but no such trend was apparent after SLT. These results suggest that posttx VCR depends primarily on predicted VCD after SLT and on pred VCR after DLT. Therefore, in donor-recipient size matching for lung transplantation a donor with a pred VCD greater than the pred VCR should be chosen for a left SLT recipient, whereas a donor with a pred VCD near the pred VCR would be suitable for a DLT recipient.

The cardiopulmonary response to exercise was investigated in six single and six double lung transplant recipients using a three-minute incremental work rate protocol on a cycle ergometer. Maximum VO2 averaged 44.2 +/- 9.2 percent and 48.5 +/- 5.0 percent of predicted maximal VO2 in the single and double lung transplant groups, respectively. No evidence of ventilatory limitation to exercise was found in either group. Circulatory factors that may have limited exercise capacity included anemia and submaximal heart rates. There was a strong correlation between VO2/kg at venous blood lactate level of 2.2 mEq/L and vital capacity/body surface area in the single, but not in the double, lung recipients. Maximum VO2 in these lung transplant recipients was comparable to previously published values in heart-lung transplant recipients. The factors that limit maximum exercise capacity after lung transplantation deserve further study.

Single lung transplantation (SLT) has been considered physiologically inappropriate for patients with chronic obstructive pulmonary disease (COPD). It has been postulated that the high static compliance and elevated pulmonary vascular resistance of the native lung functioning in parallel with the more normal allografted lung could cause unacceptable ventilation-perfusion mismatching and/or overinflation of the native lung with encroachment on the expansion of the transplanted lung. While some degree of ventilation-perfusion imbalance may be physiologically obligatory after SLT for COPD, a significant disruption in gas exchange may not occur unless a complication, such as rejection or infection, arises in the transplanted lung. A 60-year-old man with COPD who underwent successful SLT is presented and discussed. In spite of scintigraphic evidence of ventilation-perfusion mismatching between the native lung and the allograft during the first six postoperative weeks, the recipient had normal resting gas exchange on room air after the second postoperative week. Fourteen weeks after transplantation, his maximum oxygen uptake was 37.3 percent of the predicted maximal value, and no evidence of ventilatory limitation was detected. His functional status and lifestyle have been markedly improved by SLT. The role of SLT for COPD should be reconsidered. It may be a reasonable transplantation alternative for selected patients with COPD who are not candidates for double lung transplantation (DLT).