Comparison of outcomes between living donor and cadaveric lung transplantation in children

Background. Long-term survival in lung transplant is limited by bronchiolitis obliterans (BOS). We compared outcomes in pediatric living donor bilateral lobar (LL) vs cadaveric lung transplant (CL).

Methods. Children were studied who had LL or CL with at least 1 year follow-up. Data collected included acute rejection episodes, pulmonary function tests (PFT), BOS, and survival. Mean age was 13.36 ± 3.16 years in LL and 12.00 ± 4.19 years in CL patients (p = 0.37, ns).

Results. There was no difference in rejection (p = 0.41, ns). CL had rejection earlier (2.48 ± 3.84 months) than LL (13.60 ± 10.74 months; p = 0.02). There was no difference in 12 month PFT. But at 24 months, LL had greater forced expiratory volume in 1 second (FEV₁) (p = 0.001) and FEF_25–75% (p = 0.01) than CL. BOS was found in 0/14 LL vs 9/11 (82%) CL after 1 year (p = 0.04). After 2 years, 0/8 LL and 6/7 (86%) CL had BOS (p < 0.05). LL had 85% survival vs 79% for CL at 12 months. At 24 months, LL survival was 77% vs 67% for CL.

Conclusions. Pediatric LL had less BOS and better pulmonary function than CL. As BOS is a determinant of long-term outcome, we believe LL is the preferred lung transplant method for children.     

Impact of Lung Transplant Operation on Bronchiolitis Obliterans Syndrome in Patients with Chronic Obstructive Pulmonary Disease

Previous studies suggest that bilateral (BLT) compared with single lung transplantation (SLT) for patients with chronic obstructive pulmonary disease (COPD) results in improved long-term survival. The effect of transplant operation on bronchiolitis obliterans syndrome (BOS) is unknown. A retrospective study of all lung transplant recipients with pre-transplant diagnoses of COPD at the University of Toronto and at Duke University was performed. Data collected were age, gender, date and type of transplant, acute rejection, survival, presence and time of BOS. 221 (bilateral n = 101, single n = 120) patients met our criteria. Patients with BLT were younger (53.0 vs. 55.3 years; p = 0.034), more likely to be male (56.3% vs. 42.4%; p = 0.039) and more likely to be transplanted at the University of Toronto (79.6% vs. 16.1%; p < 0.001). Freedom from BOS was similar at 1 year post-transplant. However, BLT recipients were more commonly free from BOS 3 years (57.4% vs. 50.7%) and 5 years (44.5% vs. 17.9%) post-transplant (p = 0.024). Survival of BLT was better than SLT recipients at 3 and 5 years post-transplant (BLT vs. SLT: 67.5% vs. 61.1% and 60.7% vs. 34.1%, respectively; p = 0.018). Similar trends on survival were observed after development of BOS. BLT results in lower rates of BOS in patients with COPD that are eligible for both SLT and BLT.     

Predictors of perioperative morbidity and mortality in lung volume reduction surgery

Background. Selection criteria for lung volume reduction surgery are still being refined. We sought to determine whether preoperative features could be used to predict early morbidity or mortality.

Methods. We reviewed preoperative characteristics of the first 89 patients who underwent lung volume reduction surgery at the Alfred Hospital. Data included arterial blood gases, prednisolone use, pulmonary function tests, 6-minute walk test, and anesthetic time. Length of stay and reintubation for respiratory failure were used as markers of morbidity.

Results. Findings included Paco₂ of 43 ± 0.7 mm Hg, Pao₂ 70 ± 1.1 mm Hg, percent predicted values for forced expiratory volume in 1 second 29.6% ± 0.8%, TLCO% predicted 35.2 ± 1.4%, and 6-minute walk test of 315 ± 10.6 m (mean ± SEM). Mean length of stay was 19 ± 2 days, with 17 (19%) patients reintubated for respiratory failure. Mortality rate was 5.6% at 1 year post surgery, with no deaths in patients less than 65 years old. Multivariate analysis revealed that length of stay, reintubation and mortality were predicted by age and surgical time (p < 0.05), with no correlation with any other variables tested. Age greater than 70 years was associated with a significant risk of mortality (OR 9.0; p = 0.04).

Conclusions. Age greater than 70 years and anesthetic time greater than 210 minutes predict both perioperative morbidity and mortality.     

Twenty-year experience of lung transplantation at a single center: Influence of recipient diagnosis on long-term survival

OBJECTIVES: The objective of this study was to examine the long-term patient outcomes of lung transplantation in a single center. METHODS: Between 1983 and 2003, 521 lung transplants were performed in 501 patients. Major indications were cystic fibrosis (n = 124), chronic obstructive pulmonary disease (n = 88), alpha-1 antitrypsin deficiency (n = 63), pulmonary fibrosis (n = 97), primary pulmonary hypertension (n = 35), Eisenmenger syndrome (n = 21), and miscellaneous end-stage lung diseases (n = 93). RESULTS: The 5-, 10-, and 15-year survivals for all recipients were 55.1% (95% confidence interval: +/-5%), 35.3% (+/-6%), and 26.5% (+/-11%), respectively. The most common causes of death were sepsis and bronchiolitis obliterans syndrome. Despite an increased postoperative mortality rate, patients with primary pulmonary hypertension achieved the best long-term survival (10-year survival: 59%). Recipients with cystic fibrosis without Burkholderia cepacia infection achieved significantly better long-term survival (10-year survival: 52%) than those with Burkholderia cepacia infection (10-year survival: 15%). The 10-year survival was also significantly better in recipients with chronic obstructive pulmonary disease (43%) than in recipients with alpha-1 antitrypsin deficiency (23%). Although the incidence of bronchiolitis obliterans syndrome was similar between recipients with chronic obstructive pulmonary disease (39%) and alpha-1 antitrypsin deficiency (46%), recipients with alpha-1 antitrypsin deficiency died of sepsis more frequently than recipients with chronic obstructive pulmonary disease (27% vs 6%, respectively; P =.0003). CONCLUSIONS: Although bronchiolitis obliterans syndrome and sepsis still limit the durability of the benefit, lung transplantation returns many patients with end-stage lung disease to active and productive lives. Differences in the complications and long-term survival show the important contribution of the recipient diagnosis to the success of lung transplantation.     

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.     

Successful bilateral lung transplant outcomes in recipients 61 years of age and older

BACKGROUND: Controversy exists regarding the optimal use of bilateral lung transplant (BLT) in older recipients in diseases where either single or bilateral transplant is appropriate. International Society for Heart and Lung Transplant (ISHLT) guidelines suggest an upper age limit of 60 for BLT, despite limited data regarding outcomes with BLT in patients over 60. We hypothesize that BLT offers comparable, if not superior, clinical outcomes to SLT in all patients independent of recipient age. METHODS: In order to test our hypothesis, we conducted a case-control study to compare the effect of transplant operation on survival and the onset of bronchiolitis obliterans syndrome (BOS) in consecutive lung transplant recipients 61 years of age or older using Kaplan- Meier analysis and Cox proportional hazard models. RESULTS: We identified 107 consecutive lung transplant recipients 61 or older at the time of transplant. Patients received SLT (n=46) or BLT (n=61) based on donor organ availability. Comparable survival was achieved with BLT in older patients vs. SLT P=0.19). One-, two-, and five-year survival estimates in BLT were 82%, 75% and 68%, respectively, vs. in SLT 78%, 70% and 44%, respectively. A comparable onset of BOS was also observed in the patients who received BLT vs. SLT (P=0.23). CONCLUSION: Successful short- and medium-term outcomes are achieved with BLT in older recipients and are comparable to those achieved with SLT. Our results suggest that age over 60 should not exclude patients from consideration of BLT.     

Comparison of clinical results for unilateral and bilateral thoracoscopic lung volume reduction

Background. It is widely believed that bilateral thoracoscopic lung volume reduction (BTLVR) yields superior results when compared with unilateral thoracoscopic lung volume reduction (UTLVR) with regard to spirometry, functional capacity, oxygenation and quality of life results.

Methods. To address these issues, we compared the results of patients undergoing UTLVR (N = 338 patients) and BTLVR (N = 344 patients) from 1993 to 1998 at five institutions. Follow-up data were available on 671 patients (98.4%) between 6 and 12 months after surgery, and a patient self-assessment was obtained at a mean of 24 months.

Results. It was found that BTLVR provides superior improvement in measured postoperative percent change in FEV₁ (L) (UTLVR 23.3% ± 55.3 vs BTLVR 33% ± 41, p = 0.04), FVC(L) (10.5% ± 31.6 vs 20.3% ± 34.3, p = 0.002) and RV(L) (−13% ± −22 vs −22% ± 17.9, p = 0.015). BTLVR also provides a slight improvement over UTLVR in patient’s perception regarding improved quality of life (UTLVR 79% vs BTLVR 88%, p = 0.03) and dyspnea relief (71% vs 61%, p = 0.03). There was no difference in mean changes in Po₂ (mm Hg) (UTLV 4.5 ± 12.3 vs BTLVR 4.9 ± 13.3, p = NS), 6-minute walk (UTLVR 26% ± 66.1 vs BTLVR 31% ± 59.6, p = NS) or decreased oxygen utilization (UTLVR 78% vs BTLVR 74%, p = NS).

Conclusions. These data suggest that both UTLVR and BTLVR yield significant improvement, but the results of BTLVR seem to be superior with regard to spirometry, lung volumes, and quality of life.     

Chronic lung allograft dysfunction after lung transplantation: the moving target

Chronic lung allograft dysfunction is a major challenge in long-term management of lung transplant recipients. Both alloimmune-dependent factors (rejection) and alloimmune-independent factors contribute to the development of chronic lung allograft dysfunction. Thus, use of the term “chronic rejection” tends to be intentionally avoided among specialists in the field, although “chronic rejection” is still an acceptable lay word understood by many patients. Several different phenotypes have been identified in chronic lung allograft dysfunction, including restrictive allograft syndrome, neutrophilic reversible allograft dysfunction, and fibrous bronchiolitis obliterans syndrome. Restrictive allograft syndrome is characterized by restrictive physiology and peripheral foci of inflammation and fibrosis, which contrasts the obstructive physiology and pathological foci in small airways in conventional bronchiolitis obliterans syndrome. Among patients with bronchiolitis obliterans syndrome, there is a subpopulation that responds relatively well to azithromycin. Because these patients show airway neutrophilia, this subtype of chronic lung allograft dysfunction was named neutrophilic reversible allograft dysfunction. Conversely, patients with bronchiolitis obliterans syndrome unresponsive to azithromycin show airway fibrosis with less inflammation (fibrous bronchiolitis obliterans syndrome). In general, restrictive allograft syndrome shows poorer survival than does bronchiolitis obliterans syndrome, and early-onset bronchiolitis obliterans syndrome (within 2 years) shows a worse prognosis than does late-onset bronchiolitis obliterans syndrome. Until preventive and therapeutic options are refined, chronic lung allograft dysfunction will remain a major life-limiting factor. It has significant psychological, physical, social, and economic impacts. Early introduction of palliative care is another important strategy to improve patients’ quality of life.     

Rebound Pulmonary Hypertension After Inhalation of Nitric Oxide

Background. We describe the hemodynamic response to initiation and withdrawal of inhaled nitric oxide (NO) in infants with pulmonary hypertension after surgical repair of total anomalous pulmonary venous connection.

Methods. Between January 1, 1992, and January 1, 1995, 20 patients underwent repair of total anomalous pulmonary venous connection. Nine patients had postoperative pulmonary hypertension and received a 15-minute trial of inhaled NO at 80 parts per million. Five of these patients received prolonged treatment with NO at 20 parts per million or less.

Results. Mean pulmonary artery pressure decreased from 35.6 ± 2.4 to 23.7 ± 2.0 mm Hg (mean ± standard error of the mean) (p = 0.008), and pulmonary vascular resistance decreased from 11.5 ± 2.0 to 6.4 ± 1.0 U · m² (p = 0.03). After prolonged treatment with NO, pulmonary artery pressure increased transiently in all patients when NO was discontinued.

Conclusions. After operative repair of total anomalous pulmonary venous connection, inhaled NO selectively vasodilated all patients with pulmonary hypertension. Withdrawal of NO after prolonged inhalation was associated with transient rebound pulmonary hypertension that dissipated within 60 minutes. Appreciation of rebound pulmonary hypertension may have important implications for patients with pulmonary hypertensive disorders when interruption of NO inhalation is necessary or when withdrawal of NO is planned.     

Valved homograft replacement of aneurysmal pulmonary arteries for severely symptomatic absent pulmonary valve syndrome

Background. Patients with absent pulmonary valve syndrome (APVS) with respiratory distress (RD) have previously had a high mortality. In 1990 we adopted a strategy of primary repair including total replacement of the aneurysmal central pulmonary arteries (PAs) for patients with RD.

Methods. Retrospective review was made of 54 consecutive patients with APVS between 1960 and 1998. Median age and weight were 4 months and 4.8 kg. RD was present in 23 patients (10 neonates, 16 required ventilation). Fifteen patients had repair with homograft replacement of the PAs and VSD closure (group 1). Twenty-seven patients had transannular patch with VSD closure with PA-plasty (group 2, n = 21) or without PA plasty (group 3, n = 6). Twelve had miscellaneous procedures (group 4); in 6 the VSD was left open.

Results. Operative, 1-, 5-, and 10-year survivals were 83%, 80%, 78%, and 78%, respectively. Risk factors for operative mortality in multivariate analysis were RD (p = 0.04), neonates (p = 0.02), weight less than 3 kg (p = 0.02), open VSD (p = 0.02) and surgery before 1990 (p = 0.04). Since 1990 operative mortality has decreased to 11% (p = 0.04). RD was the only time-related predictor of survival in multivariate analysis (p = 0.004). In patients with RD, survival with homograft was 73% versus 41% with other techniques (p = 0.2). Mean follow-up was 72 ± 50 months. There were no significant differences in freedom from reintervention rates among the surgical groups (p = 0.08).

Conclusions. Aggressive homograft replacement of the central pulmonary arteries has been associated with improved survival in patients with APVS especially in neonates with severe RD.     

Partial left ventriculectomy for idiopathic dilated cardiomyopathy: early results and six-month follow-up

Background. Recent reports show that partial left ventriculectomy improves hemodynamic and functional status in patients with dilated cardiomyopathy. This study sought to determine the effects of partial left ventriculectomy on clinical outcome and left ventricular function during 6-month follow-up.

Methods. Twenty-two patients underwent partial left ventriculectomy. Mitral valve repair was performed whenever possible, otherwise the valve was replaced. Hemodynamic and functional data were obtained at baseline, as well as 2 weeks and 6 months postoperatively.

Results. Overall, 7 of 22 patients died; there were three early and four late deaths. One-year survival was 68% ± 10%. Ejection fraction increased from 23.9% ± 6.8% before the operation to 40.7% ± 12.5% at 2 weeks and to 36.8% ± 7.7% at 6 months (p < 0.001, for both). The cardiac index before the operation, at 2 weeks, and at 6 months was 2.3 ± 0.8, 2.9 ± 0.6, and 3.4 ± 1.0 L/m² per minute, respectively (p = 0.035, and p = 0.009, compared with baseline). The increase in ejection fraction 2 weeks postoperatively was less in patients with left circumflex artery dominance (10.9% ± 3.2% compared with 19.9% ± 10.7%, respectively, p = 0.017). At 6-month follow up, all surviving patients except one improved New York Heart Association functional class when compared with preoperative status (from 3.8 ± 0.4 to 1.4 ± 0.6, p = 0.0002).

Conclusions. Early hemodynamic improvement after partial left ventriculectomy was maintained during midterm follow-up.     

Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation

OBJECTIVES: Bronchiolitis obliterans is the greatest limitation to the long-term applicability of lung transplantation. Although alloimmune events are important, nonimmune events, such as gastroesophageal reflux, might contribute to lung injury and the development of bronchiolitis obliterans syndrome. METHODS: We retrospectively studied the 396 patients who underwent lung transplantation at the Duke Lung Transplant Program from April 1992 to April 2002. Reflux was assessed for using an ambulatory 24-hour esophageal pH probe. RESULTS: Reflux assessment with an esophageal pH probe was obtained in 128 patients after lung transplantation. Abnormal pH study results were present in 93 (73%) patients. Forty-three patients underwent a surgical fundoplication. There was no in-hospital or 30-day mortality in the patients undergoing fundoplication. At the time of fundoplication, 26 patients met the criteria for bronchiolitis obliterans syndrome. After fundoplication, 16 patients had improved bronchiolitis obliterans syndrome scores, with 13 of these patients no longer meeting the criteria for bronchiolitis obliterans syndrome. In patients at least 6 months after lung transplantation and 6 months after fundoplication, the forced expiratory volume in 1 second improved by an average of 24% (mean forced expiratory volume in 1 second before fundoplication, 1.87 L; mean forced expiratory volume in 1 second after fundoplication, 2.19 L/sec; P <.0002). Overall actuarial survival was significantly better in patients who had either normal pH studies or who had fundoplication. CONCLUSIONS: Gastroesophageal reflux disease is very common after lung transplantation and appears to contribute to mortality and development of bronchiolitis obliterans syndrome. Fundoplication in lung transplant recipients with gastroesophageal reflux disease is associated with significant improvements in lung function, particularly if performed before the late stages of bronchiolitis obliterans syndrome.     

Effect of hemofiltrated whole blood pump priming on hemodynamics and respiratory function after the arterial switch operation in neonates

Background. Primed blood might have some deleterious effects on neonates during cardiopulmonary bypass (CPB) due to unbalanced electrolytes and inflammatory mediators. We hemofiltrated pump-primed blood before CPB to reduce inflammatory mediators and to adjust pH and the concentrations of electrolytes. The current study investigated the effects of hemofiltrated whole blood priming on hemodynamics and respiratory function after CPB in neonates.

Methods. Patients who underwent the arterial switch operation in the neonatal period for transposition of the great arteries with intact ventricular septum were chosen for this study. Seventeen patients underwent CPB with hemofiltrated blood priming (group HF) and 23 patients underwent CPB with nonhemofiltrated blood priming (group N). The concentrations of electrolytes and bradykinin and high molecular weight kininogen of the primed blood before and after hemofiltration were measured. At 4 hours after completion of CPB, the left ventricular percent fractional shortening, and the relation between the mean velocity of shortening and the end-systolic wall stress (stress velocity index), were measured by echocardiogram in 7 patients in group HF and 6 patients in group N. Alveolar − arterial oxygen tension difference (AaDO₂) and respiratory index (AaDO₂ divided by arterial oxygen tension) were measured at several points for 48 hours after CPB in all patients.

Results. Hemofiltration of the primed blood maintained electrolytes within a physiologic level and significantly reduced the concentrations of bradykinin (5,649 ± 1,353 pg/mL versus 510 ± 35 pg/mL, p < 0.05) and high molecular weight kininogen (52.7% ± 3.2% versus 40.1% ± 3.0% of normal plasma value, p < 0.05). The percent of fractional shortening at 4 hours after completion of CPB was significantly higher in group HF (n = 7) than in group N (n = 6) (22.0% ± 0.7% versus 16.0% ± 0.4%, p < 0.01). There was also a trend toward better stress velocity index in group HF than in group N (0.81 ± 0.81 versus −2.17 ± 0.45, p = 0.09). AaDO₂ and respiratory index were significantly lower in group HF than in group N for 48 hours after CPB, respectively (p < 0.05).

Conclusions. Hemofiltrated fresh whole blood used for CPB priming attenuated cardiac impairment at early reperfusion periods and reduced pulmonary dysfunction in neonates with transposition of the great arteries with intact ventricular septum. This therapeutic strategy may have an advantage in preventing lung and heart dysfunction in pediatric patients who need CPB priming with blood.     

Single vs bilateral, sequential lung transplantation for end-stage emphysema: influence of recipient age on survival and secondary end-points.

BACKGROUND: The appropriate age to perform bilateral, sequential lung transplants (BSLT) in patients with chronic obstructive pulmonary disease (COPD) remains controversial. Although single lung transplant (SLT) offers an advantage in terms of organ availability, the long-term survival may not warrant this strategy in all age groups. METHODS: We analyzed 2,260 lung transplant recipients (1835 SLT, 425 BSLT) with COPD recorded in the International Society for Heart and Lung Transplantation/United Network for Organ Sharing thoracic registry between January 1991 and December 1997. To assess mortality, we performed univariate (Kaplan-Meier method and the chi-square statistic) and multivariate analyses (proportional hazards method). Because of incomplete morbidity data in the international registry, only data from U.S. centers (n = 1778, 1467 SLT, 311 BSLT) were used in the morbidity analysis. RESULTS: Survival rates (%) computed using the Kaplan-Meier method at 30 days, 1 year, and 5 years for the patients aged < 50 years were 93.6, 80.2, and 43.6, respectively, for the SLT patients, and 94.9, 84.7, and 68.2, respectively, for the BSLT patients. For patients aged 50 to 60 years, survival rates (%) were 93.5, 79.4, and 39.8 for the SLT patients compared with 93.0, 79.7, and 60.5 for the BSLT patients. For those aged > 60 years, SLT survival (%) was 93.0, 72.9, and 36.4, compared with 77.8 and 66.0 for the BSLT group (a 5-year rate could not be completed in this group). The multivariate model showed a higher risk ratio for mortality in patients aged 40 to 57 years who received SLT vs BSLT. Recipient age and procedure type did not appear to affect the development of rejection, bronchiolitis obliterans, bronchial stricture, or lung infection. CONCLUSIONS: Single lung transplant may offer acceptable early survival for patients with end-stage respiratory failure. However, long-term survival data favors BSLT in recipients until approximately age 60 years. These data suggest that a BSLT approach offers a significant survival advantage to recipients younger than 60 years of age.     

Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation

Background. Reperfusion injury after pulmonary transplantation can contribute significantly to postoperative pulmonary dysfunction. We hypothesized that posttransplantation reperfusion injury would result in an increase in both in-hospital mortality and morbidity. We also hypothesized that the incidence of reperfusion injury would be dependent upon the cause of recipient lung disease and the interval of donor allograft ischemia.

Methods. We performed a retrospective study of all lung transplant recipients at our institution from June 1990 until June 1998. One hundred patients received 120 organs during this time period. We compared two groups of patients in this study: those experiencing a significant reperfusion injury (22%) and those who did not (78%).

Results. In-hospital mortality was significantly greater in patients experiencing reperfusion injury (40.9% versus 11.7%, p < 0.02). Posttransplantation reperfusion injury also resulted in prolonged ventilation (393.5 versus 56.8 hours, p < 0.001) and an increased length of stay in both the intensive care unit (22.2 versus 10.5 days, p < 0.01) and in the hospital (48.8 versus 25.6 days, p < 0.03). The incidence of reperfusion injury could not be attributed to length of donor organ ischemia (221.5 versus 252.9 minutes, p < 0.20). The clinical impact of reperfusion injury was significantly greater in patients undergoing transplantation for preexisting pulmonary hypertension (6/14) than those with chronic obstructive pulmonary disease or emphysema alone (6/54) (42.9% versus 11.1%, p < 0.012).

Conclusions. Clinically significant pulmonary reperfusion injury increased in-hospital mortality and morbidity resulting in prolonged ventilation, length of stay in the intensive care unit, and cost of hospitalization. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia but increased with the presence of preoperative pulmonary hypertension. These findings suggest that recipient pathophysiology and donor allograft quality may play important roles in determining the incidence of reperfusion injury.     

Quality of life and bronchiolitis obliterans syndrome in patients after lung transplantation

BACKGROUND: Lung transplantation has become an established and effective treatment for patients with end-stage pulmonary disease. OBJECTIVE: To investigate health-related quality of life in correlation with occurrence and degree of bronchiolitis obliterans syndrome after transplantation. METHODS: In a cross-sectional study design, 119 consecutive lung transplant recipients (63.9% bilateral and 36.1% single lung transplants) responded voluntarily to a set of standardized questionnaires (12-Item Short-Form Health Survey, Center for Epidemiologic Studies-Depression Scale, Coping With Everyday Life, Beck Anxiety Inventory, Zerssen list of complaints) that covered health-related quality of life and psychological well being. Also, we performed pulmonary function studies to clinically grade bronchiolitis obliterans syndrome in all patients. RESULTS: In this cohort, 41.2% of patients developed bronchiolitis obliterans syndrome at a mean interval of 5.6 years after lung transplantation. Actuarial freedom from bronchiolitis obliterans syndrome was 90.1% +/- 2.3% at 1 year, 79.9% +/- 3.7% at 3 years, and 59.5% +/- 4.8% at 5 years after lung transplantation. Recipients with bronchiolitis obliterans syndrome reported significantly lower well being and quality of life than those without bronchiolitis obliterans syndrome, who scored similar to healthy volunteers. In a subanalysis, body functioning (P < .001) and related areas of coping (P < .001) were mostly affected by bronchiolitis obliterans syndrome. CONCLUSIONS: Quality of life was negatively affected by the onset of bronchiolitis obliterans syndrome. However, even patients who develop bronchiolitis obliterans syndrome reported a temporary benefit from lung transplantation. In addition to optimal medical care and efforts in preventing bronchiolitis obliterans syndrome, psychological support of lung recipients seems to be essential, especially when bronchiolitis obliterans syndrome occurs.     

Secondary pulmonary hypertension does not adversely affect outcome after single lung transplantation

OBJECTIVE: Primary and secondary pulmonary hypertension have been associated with poor outcomes after single lung transplantation. Some groups advocate double lung transplantation and the routine use of cardiopulmonary bypass during transplantation in this population. However, the optimal procedure for these patients remains controversial. The goal of our study was to determine the safety of single lung transplantation without cardiopulmonary bypass in patients with secondary pulmonary hypertension. METHODS: We retrospectively reviewed 76 consecutive patients with pulmonary parenchymal disease who underwent single lung transplantation from 1992 to 1998. Recipients were stratified according to preoperative mean pulmonary artery pressure. Secondary pulmonary hypertension was defined as parenchymal lung disease with a preoperative mean pulmonary artery pressure of 30 mm Hg or more. Patients with primary pulmonary hypertension or Eisenmenger's syndrome were excluded from analysis. RESULTS: Eighteen of 76 patients had secondary pulmonary hypertension. No patient with secondary pulmonary hypertension required cardiopulmonary bypass, whereas 1 patient without pulmonary hypertension required bypass. After the operation, no significant differences were seen in lung injury as measured by chest radiograph score and PaO(2)/FIO(2) ratio, the requirement for inhaled nitric oxide, the length of mechanical ventilation, the intensive care unit or hospital length of stay, and 30-day survival. There were no differences in the forced expiratory volume in 1 second or 6-minute walk at 1 year, or the incidence of rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. Survival at 1, 2, and 4 years after transplantation was 86%, 79%, and 65%, respectively, in the low pulmonary artery pressure group and 81%, 81%, and 61%, respectively, in the group with secondary pulmonary hypertension (P >.2). CONCLUSION: We found that patients with pulmonary parenchymal disease and concomitant secondary pulmonary hypertension had successful outcomes as measured by early and late allograft function and appear to have acceptable long-term survival after single lung transplantation. Our results do not support the routine use of cardiopulmonary bypass or double lung transplantation for patients with this disorder.     

TNFα From Classically Activated Macrophages Accentuates Epithelial to Mesenchymal Transition in Obliterative Bronchiolitis

Bronchiolitis obliterans syndrome is characterized by fibrotic obliteration of small airways which severely impairs graft function and survival after lung transplantation. Bronchial epithelial cells from the transplanted lung can undergo epithelial to mesenchymal transition and this can be accentuated by activated macrophages. Macrophages demonstrate significant plasticity and change phenotype in response to their microenvironment. In this study we aimed to identify secretory products from macrophages that might be therapeutic targets for limiting the inflammatory accentuation of epithelial to mesenchymal transition in bronchiolitis obliterans syndrome. TNFα, IL‐1β and IL‐8 are elevated in bronchoalveolar lavage from lung transplant patients prior to diagnosis of bronchiolitis obliterans syndrome. Classically activated macrophages secrete more TNFα and IL‐1β than alternatively activated macrophages and dramatically accentuate TGF‐β1‐driven epithelial to mesenchymal transition in bronchial epithelial cells isolated from lung transplant patients. Blocking TNFα, but not IL‐1β, inhibits the accentuation of epithelial to mesenchymal transition. In a pilot unblinded therapeutic intervention in five patients with progressive bronchiolitis obliterans syndrome, anti‐TNFα treatment improved forced expiratory volume in 1 second and 6‐min walk distances in four patients. Our data identify TNFα as a potential new therapeutic target in bronchiolitis obliterans syndrome deserving of a randomized placebo controlled clinical trial.     

单肺移植治疗终末期慢性阻塞性肺疾病患者单中心经验

目的探讨单肺移植治疗终末期慢性阻塞性肺疾病（COPD）患者的疗效、预后相关因素及术后并发症防治。方法回顾性分析同济大学附属上海市肺科医院2003年1月至2011年2月施行的23例终末期COPD患者单肺移植的临床资料,分析术后临床疗效、预后和并发症发生情况,并探讨性别、年龄、原发病等因素对受者预后的影响。结果 COPD患者术后肺通气功能和动脉血气分析结果均明显改善。气管吻合口并发症发生率为13.0%;围手术期病死率为4.3%。术后肺部真菌感染发生率为39.1%,伊曲康唑或卡泊芬净＋两性霉素B预防性抗真菌治疗的受者术后真菌感染的发生率明显降低（P=0.035）。急性排斥反应发生率为34.8%,闭塞性细支气管炎发生率为26.1%。受者术后1、3和5年存活率分别为83%、66%和45%。单肺再次移植2例。结论单肺移植治疗终末期COPD是安全、有效的方法,受者选择和术后并发症的防治对受者长期生存有重要意义。     

Chlamydia pneumoniae infection after lung transplantation.

BACKGROUND: Chlamydia pneumoniae is established as a common agent of acute respiratory tract infection and has been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease. Airway disease is a prominent cause of morbidity and mortality after lung transplantation. We investigated the role of C pneumoniae as a pulmonary pathogen after lung transplantation. METHODS: Eighty lung transplant recipients underwent 232 bronchoscopies with bronchoalveolar lavage with or without transbronchial lung biopsy during 1 year for surveillance of rejection and infection, or where clinically indicated. RESULTS: C pneumoniae was detected using nested polymerase chain reaction in 9 of 36 (25%) recipients studied within 30 days of lung transplantation, 3 of whom remained positive on repeat lavage and died from airway disease in the first year post-operatively. By comparison, all 27 recipients with negative lavage survived >1 year. Lavage was positive for C pneumoniae in 18 of 71 (25%) recipients studied >30 days after lung transplantation, 5 of whom had pneumonia and 8 of whom had bronchiolitis obliterans syndrome. Eleven also had acute pulmonary allograft rejection. CONCLUSIONS: Persistent infection with C pneumoniae (whether donor-derived, de novo or re-activated) appears deleterious to pulmonary allograft function and is associated with early mortality, rejection and bronchiolitis obliterans syndrome after lung transplantation. A trial of empiric antibiotic therapy for C pneumoniae may therefore be warranted in the attempt to prevent progressive inflammatory airway disease.