Bilateral lung transplantation for cystic fibrosis. The Toronto Lung Transplant Group.

Between March 1988 and March 1991, 17 patients underwent bilateral lung transplantation for end-stage lung disease caused by cystic fibrosis. There were 11 male and six female patients. Ages ranged from 19 to 41 years (mean age 28 years). Preoperative mean arterial oxygen tension with the patient breathing room air was 54 +/- 6 mm Hg; forced vital capacity, 1.8 +/- 0.7 L; forced expiratory volume in 1 second, 0.9 +/- 0.3 L; and 6-minute walk test, 506 +/- 44 m. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone. Induction immunosuppression was obtained with Minnesota antilymphocyte globulin. All patients received perioperative antibiotics according to sputum cultures and sensitivities. There were six operative deaths, four of which resulted from bacterial infection. Two patients required a second transplantation, one receiving a single lung and one undergoing bilateral lung replacement. Significant functional improvement was observed in all survivors. At 3 months follow-up, mean arterial oxygen tension on room air was 95 +/- 6 mm Hg (p less than 0.01); forced vital capacity, 3 +/- 0.8 L (p less than 0.01); forced expiratory volume in 1 second, 2.6 +/- 0.9 L (p less than 0.01); and 6-minute walk test, 678 +/- 47 m (p less than 0.01). The actuarial survival rate was 66% at 3 months and 58% at 6, 12, and 24 months. The most frequent cause of morbidity and mortality was acute pneumonia resulting from Pseudomonas cepacia. For patients with respiratory failure caused by cystic fibrosis, bilateral lung transplantation is an effective treatment option associated with significant functional improvement.     

Anesthesia in single and bilateral sequential lung transplantation. Lung Transplantation Group

BACKGROUND: Anesthesia for lung transplantation: intraoperative complications and long term results. METHODS: 52 patients were scheduled for 16 single lung transplantations (SLT) (9 fibrosis and 7 emphysema) and 36 bilateral sequential lung transplantations (DLT) (4 bronchiectasis, 6 emphysema, 3 fibrosis, 22 cystic fibrosis and 1 pulmonary hypertension). Anesthesia was induced with propofol or midazolam, and fentanyl or alfentanil. As muscle relaxant vecuronium bromide was used. Anesthesia was maintained with isoflurane, fentanyl in boluses or sufentanil continuous infusion in O2 100%. Prostaglandin E1 (20-300 ng/kg/min), inhaled nitric oxide (10-40 ppm), dobutamine (5-15 mcg/kg/min), norepinephrine (0.05-3 mcg/kg/min) and ephedrine (5-10 mg per bolus) were used for hemodynamic management. In 2 patients inhaled areosolized prostacyclin were administered. RESULTS: Mean pulmonary arterial pressure (mPA) and pulmonary vascular resistance (PVRI) increased after pulmonary artery clamping during first lung (mPA: 3347 nel DLT, 3643 nel SLT; PVRI; 375488 nel DLT, 377420 nel SLT) and second lung implantation (mPA: 3746; PVRI: 263553) and decreased after reperfusion of the first (mPA: 4737 nel DLT, 4329 nel SLT; PVRI: 488263 nel DLT, 420233 nel SLT) and the second lung (mPA: 4629; PVRI: 553260). Only in 9 cases (7 DLT and 2 SLT) C-P bypass was used. CONCLUSIONS: With a strong drug support with pulmonary vasodilators, positive inotropic and systemic vasoconstrictor drugs, in most patients we transplanted C-P bypass can be avoided. Intraoperative deaths were not observed. Two years actuarial survival is 65% for DLT and 60% for SLT.     

Lung transplantation for cystic fibrosis

BACKGROUND: Lung transplantation is a robust therapeutic option to treat patients with cystic fibrosis. PATIENTS AND METHODS: Since 1996, 109 patients with cystic fibrosis were accepted onto our waiting list with 58 bilateral sequential lung transplants performed in 56 patients and two patients retransplanted for obliterative bronchiolitis syndrome. RESULTS: Preoperative mean FEV(1) was 0.64 L/s, mean PaO(2) with supplemental oxygen was 56 mm Hg, and the mean 6-minute walking test was 320 m. Transplantation was performed through a "clam shell incision" in the first 29 patients and via bilateral anterolateral thoracotomies without sternal division in the remaining patients. Cardiopulmonary bypass was required in 14 patients. In 21 patients the donor lungs had to be trimmed by wedge resections with mechanical staplers and bovine pericardium buttressing to fit the recipient chest size. Eleven patients were extubated in the operating room immediately after the procedure. Hospital mortality of 13.8% was related to infection (n = 5), primary graft failure (n = 2), and myocardial infarction (n = 1). Acute rejection episodes occurred 1.6 times per patient/year; lower respiratory tract infections occurred 1.4 times per patient in the first year after transplantation. The mean FEV(1) increased to 82% at 1 year after operation. The 5-year survival rate was 61%. A cyclosporine-based immunosuppressive regimen was initially employed in all patients; 24 were subsequently switched to tacrolimus because of central nervous system toxicity, cyclosporine-related myopathy, or renal failure, obliterative bronchiolitis syndrome, gingival hyperplasia, or hypertrichosis. Ten patients were subsequently switched to sirolimus. Freedom from bronchiolitis obliterans at 5 years was 60%. CONCLUSIONS: Our results confirm that bilateral sequential lung transplantation is a robust therapeutic option for patients with cystic fibrosis.     

Cardiopulmonary bypass for lung transplantation in cystic fibrosis: pilot evaluation of perioperative outcome

OBJECTIVE: The purpose of this study was to determine whether cardiopulmonary bypass (CPB) reduces the incidence of perioperative graft infection after lung transplantation in adults with cystic fibrosis (CF). DESIGN: Retrospective and observational. SETTING: University hospital. PARTICIPANTS: Adults with CF who underwent lung transplantation (1998-2003). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cohort size was 26: group A (n = 10) who underwent CPB for implantation of both lungs, group B (n = 8) who underwent CPB only for implantation of the second lung, and group C (n = 8) who did not undergo CPB. The 3 cohort subgroups were similar (p > 0.05) in demographics, preoperative lung function, and anesthetic management. Group A had a lower incidence of perioperative pneumonia (p = 0.02). CPB exposure increased transfusion (B > A > C) of fresh frozen plasma and platelets but not packed red blood cells. There were no differences (p > 0.05) in clinical outcome as reflected by duration of mechanical ventilation, tracheal re-intubation, re-exploration for bleeding, sepsis, primary graft dysfunction, renal dysfunction, length of stay, and mortality. CONCLUSIONS: CPB is associated with decreased incidence of early graft infection after lung transplantation for adult CF when used for implantation of both lungs. This may be because of improved decontamination of the operative field before graft implantation.     

Lung transplantation for cystic fibrosis: 6-year follow-up.

Lung transplantation is currently the most effective means of improving survival and quality of life in patients with end-stage cystic fibrosis. In reviewing our 6-year experience we sought to evaluate complications and survival after sequential bilateral lung transplantation. Between October 1996 and October 2002, 114 patients with cystic fibrosis were referred to us from 15 Italian regional centers and 2 support centers for cystic fibrosis as possible candidates for lung transplantation. Of these 114 patients, 99 were included in the waiting list and 15 were refused. The mean time spent on the waiting list was 6.8+/-5.2 months (range 1 day-21 months) for those patients receiving lung transplantation, and 5.4+/-4.5 months (range 10 days-18 months) for those 35 patients who died while on the waiting list. A total 55 patients (6 children and 49 adults), mean age 25.6+/-6.6 years (range 9-52 years), 29 males, underwent bilateral sequential lung transplantation. One patient had a second transplantation 14 months after the first. The most frequent medical non-infective complications after transplantation were chronic renal failure (n=27 patients), diabetes (n=31), osteoporosis (n=17), arterial hypertension (n=14), seizures (n=4), transient cerebral ischaemia (n=1), and transient bilateral blindness (n=1). Bacterial lower airways respiratory infections with the organisms that colonized patients' airways before lung transplantation developed in 42 patients; cytomegalovirus (CMV) infection in 41; and opportunistic infections of the lung with Pneumocystis carinii in 3 patients. Cultures of sputum or bronchoalveolar lavage fluid grew Aspergillus fumigatus in nine patients; aspergillosis of right bronchial anastomosis developed in one patient and a lung infection in another. Another patient had a pulmonary infection secondary to Aspergillus niger. An average of 1.3 episodes of acute rejection developed per patient in the first 6 months after lung transplantation. Freedom from bronchiolitis obliterans syndrome was 95% at 1 year, 82.5% at 2 years, 70% at 3 years, and 65% at 4, 5 and 6 years. Actuarial survival rates were 80% at 1 month, 79% at 1 year, 74% at 2 years, 70% at 3 years and 58% at 4, 5 and 6 years. Ten patients (17.8%) died in the early postoperative period (1-30 days) for the following reasons: primary graft failure (n=4), multiorgan failure (n=3), Burkholderia cepacia sepsis (n=1), myocardial infarction (n=1), and pulmonary embolism (n=1). Mortality was accounted for by 9 patients (16%) who died from 9 to 43 months after lung transplantation, for the following reasons: P. carinii infection (n=2), bronchiolitis obliterans syndrome (n=4), A. fumigatus pulmonary infection (n=1), unknown cause (n=1) and suicide (n=1). In conclusion, the leading causes of morbidity after lung transplantation for cystic fibrosis are pulmonary bacterial infection and opportunistic infections. Bronchiolitis obliterans develops in more than half of lung transplant recipients who survive for more than 3 years and is an important cause of death in the late post transplantation period.     

Lung transplantation for cystic fibrosis in Italy

Lung transplantation (LT) is the only effective form of therapy for cystic fibrosis (CF) associated with end-stage pulmonary failure. In Italy, the management of CF is regulated by national law, which has instituted regional centers for care and follow-up of all CF patients. LT has been performed since 1992 in only nine LT certified centers. The structured national organization has led to a unified database for LT for CF. As of December 2006, 197 bilateral LT (96 male and 94 female patients; 7 retransplants) have been performed. Of these, four had also liver or heart and liver transplantation, and three are long-term survivors. Overall median survival is 7 years. Mean age at transplantation is 26.5 years, and the mortality on the waiting list is 33.6%. Patients listed for transplant either received a suitable donor within a mean of 10 months or died within a mean of 5.5 months. The most frequent cause of death is bronchiolitis obliterans syndrome (BOS). Our nationwide database indicates the excellent results obtained by LT in FC. Still, mortality on the waiting list remains a challenge and long-term outcome is limited by BOS.     

Lung transplantation in patients with cystic fibrosis and Mycobacterium abscessus infection

Mycobacterium abscessus lung disease is difficult to treat and has been considered a strong relative contraindication to lung transplantation. We performed double lung transplantation in three cystic fibrosis patients with ongoing, and a fourth with recent treatment for Mycobacterium abscessus lung infection. Despite prolonged antibiotic courses and adjustment of immunosuppressive therapy the first three patients developed skin infection and abscesses. At follow-up after 1, 3, 5 and 7 years respectively no patient had evidence of M abscessus infection and all had stable lung function. Lung transplantation in patients with M abscessus lung infection is feasible but may involve severe complications.     

Pediatric lung transplantation for cystic fibrosis

Pediatric lung transplantation for cystic fibrosis has uncertain survival effects. Three retrospective studies disagree on survival benefit. The US Lung Allocation Score has changed patient selection for lung transplantation but confounds the analysis of survival outcomes. A prospective trial is needed to resolve clinical equipoise and explore quality-of-life effects.     

Lung transplantation in cystic fibrosis patients in the Czech Republic: initial single-center experience

Background

Lung transplantation is a well established treatment for advanced lung diseases.

Methods

We compared the clinical results of patients with cystic fibrosis (CF) entered into the waiting list with those of patients after lung transplantation.

Results

Among 36 patients with CF on the waiting list, 23 underwent lung transplantation, 8 died, 3 are still on the waiting list, and 2 were excluded from the waiting list. The median waiting list time of 0.48 years (range, 0.03-2.37) was insignificantly longer for patients who died compared with transplanted patients (0.97 vs 0.44 years). Mortality of waiting-list patients was 25.8%. The median survival of transplant patients of 7.48 years (range 0.00-10.85 years) was significantly lower among patients who were colonized (BCC) versus those who were not Burkholderia cepacia complex (0.19 vs 7.48 years; P = .041). The 1-, 3-, and 5-year patient survivals after lung transplantation were 72.9, 54.4, and 54.4, respectively.

Conclusion

The results of patients with cystic fibrosis on the waiting list versus after lung transplantation in our center were similar to those reported in the literature. We confirmed a less favorable prognosis of BCC-colonized patients.     

Lung transplantation for pulmonary fibrosis: perioperative morbidity and mortality

Lung transplantation has become a valid therapeutic option for patients with pulmonary fibrosis in terminal stage, and the number of such interventions has increased exponentially in recent years. We undertook a retrospective study of 46 pulmonary fibrosis patients who received lung transplants from 1992 through 2002 with the aim of describing the most common intra- and early postoperative complications in the recovery unit. We also aimed to analyze the impact of each complication on mortality during the study period. The most frequent complications during surgery were reperfusion syndrome (47.5%), hemodynamic instability (41%), arrhythmias (23.9%), and pulmonary hypertension (15%), with exitus secondary to reperfusion syndrome. The most common postoperative complications were infection (56.5%), reimplantation response (45.7%), and kidney failure (19.6%). Overall mortality during the study period was 23.9%. The following complications were statistically significant in the univariate analysis of the relation with mortality: reperfusion syndrome (p=0.039), reimplantation response (p=0.039), kidney failure (p=0.013), rejection (p=0.016), and sepsis (p<0.001). The only complication that remained significant in the multivariate analysis was sepsis (p<0.001). In spite of the considerable progress made, intra- and postoperative complications continue to be a real threat for the transplanted lung patient. Sepsis was the strongest predictor of poor prognosis in the early recovery period.     

Pseudomembranous colitis in four patients with cystic fibrosis following lung transplantation

Pseudomembranous colitis is an uncommon complication in patients with cystic fibrosis, despite the use of multiple high-dose antibiotic regimens and the frequency of hospital admissions. Four patients from a total of 137 patients with cystic fibrosis undergoing lung transplantation are described who developed fulminant pseudomembranous colitis. Initial presentation was variable and the mortality rate was 50% despite urgent colectomy. In one case the presenting abdominal distension was thought to be due to meconium ileus equivalent. It is concluded that Clostridium difficile colitis may be a difficult diagnosis in patients with cystic fibrosis and follows a fulminant course after lung transplantation.     

Lung and heart-lung transplantation in patients with end-stage cystic fibrosis: the Stanford experience

BACKGROUND: Bilateral lung (BLTx) and heart-lung transplantation have gained wide acceptance as treatment of end-stage lung disease from cystic fibrosis. We reviewed our 13-year experience with thoracic transplantation for cystic fibrosis with an operative approach that favors use of cardiopulmonary bypass for BLTx. METHODS: Sixty-four patients with cystic fibrosis underwent heart-lung transplantation (n = 22, 34.4%) or BLTx (n = 42, 65.6%) between 1988 and 2000. Mean age and weight at transplantation were 29 +/- 8 years and 51 +/- 11 kg, respectively. Mean follow-up for survivors was 4.4 +/- 3.6 years. Immunosuppression regimen included cyclosporine, tapered corticosteroids, azathioprine, and induction therapy with OKT3 (murine monoclonal antibodies) or rabbit antithymocyte globulin. Cardiopulmonary bypass was used in all but 5 patients (7.8%). However, in 8 (19%) of the 42 patients having BLTx, only the grafting of the second lung was performed with cardiopulmonary bypass. RESULTS: The operative mortality rate was 1.6%. The actuarial survival rates at 1 year, 3 years, 5 years and 10 years were 93.2%, 77.7%, 61.8%, and 48.1%, respectively, with no significant difference between BLTx and heart-lung transplantation. The major hospital complications were pneumonia (n = 11, 17.2%) and bleeding (n = 8, 12.5%). Clinically significant reperfusion injury was observed in 6 patients, 3 of whom required reintubation. Freedom from acute lung rejection beyond 1 year was 47.7%. One patient underwent late retransplantation, and 4 required bronchial stenting. Obliterative bronchiolitis accounted for eight (50.0%) of 16 late deaths. CONCLUSIONS: Though postoperative bleeding and pneumonia are still of concern, satisfactory early and intermediate-term results can be expected in patients undergoing BLTx or heart-lung transplantation for cystic fibrosis. Cardiopulmonary bypass can be used for BLTx with no adverse impact on intermediate and long-term outcomes.     

Diabetes mellitus and survival in cystic fibrosis patients after lung transplantation

BackgroundDiabetes mellitus (DM) is common in CF and associated with more severe disease. It is unclear whether DM influences outcome of lung transplantation (LTx).MethodsOne hundred twenty-three CF patients evaluated for LTx at our centre were included. Survival was calculated.ResultsPatients with and without DM did not differ with regard to gender, age, FEV₁ and BMI prior to LTx. Eighty patients (65%) had a diagnosis of DM before and 13 (11%) only after LTx. Recipients with DM had a significantly higher 1- and 5-year survival (89% and 71%) than those without (71% and 51%). In the multivariate Cox-regression analysis, DM had no impact on LTx-survival.ConclusionsOne- and five-year survival rates after LTx tend to be better in CF recipients with DM compared to those without DM. No impact of DM on the development of BOS was found.     

Cumulative radiation dose after lung transplantation in patients with cystic fibrosis

Purpose

The purpose of this study was first to evaluate the imaging-related cumulative post-transplantation radiation dose in cystic fibrosis (CF) lung transplantation (LT) recipients and second, to identify the occurrence and type of malignancies observed after LT.