Living-donor lobar lung transplantation experience: intermediate results.

OBJECTIVE: Living-donor lobar lung transplantation offers an alternative for patients with a life expectancy of less than a few months. We report on our intermediate results with respect to recipient survival, complications, pulmonary function, and hemodynamic reserve. METHODS: Thirty-eight living-donor lobar lung transplants were performed in 27 adult and 10 pediatric patients for cystic fibrosis (32), pulmonary hypertension (two), pulmonary fibrosis (one), viral bronchiolitis (one), bronchopulmonary dysplasia (one), and posttransplantation obliterative bronchiolitis (one). Seventy-six donors underwent donor lobectomies. RESULTS: There were 14 deaths among the 37 patients, with an average follow-up of 14 months. Predominant cause of death was infection, consistent with the large percentage of patients with cystic fibrosis in our population. The overall incidence of rejection was 0.07 episodes/patient-month, representing 0.8 episodes/patient. Postoperative pulmonary function testing generally showed a steady improvement that plateaued by postoperative months 9 to 12. Fourteen patients who were followed up for at least 1 year underwent right heart catheterization; pressures and pulmonary vascular resistances were within normal ranges. Bronchiolitis obliterans was definitively diagnosed in three patients. Among the 76 donors, complications in the postoperative period included postpericardiotomy syndrome (three), atrial fibrillation (one), and surgical reexploration (three). CONCLUSIONS: We believe that these data support an expanded role for living-donor lobar lung transplantation. Our intermediate data are encouraging with respect to the functional outcome and survival of these critically ill patients, who would have died without this option.

Experience with living-donor lobar transplantation for indications other than cystic fibrosis.

OBJECTIVE: Since development of a living donor bilateral lobar transplantation protocol for patients with cystic fibrosis, our indications have expanded to include recipients with other diagnoses. METHODS: We report on our experience in eight patients with primary pulmonary hypertension, postchemotherapy pulmonary fibrosis, bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, and obliterative bronchiolitis. The average age of the eight patients was 19.1 years (range 9 to 40). The mean preoperative carbon dioxide tension for the four patients who did not have primary pulmonary hypertension was 92 mm Hg (range 64 to 120 mm Hg), and the two patients with pulmonary fibrosis were intubated (one on high-frequency jet ventilation). Each recipient received a right lower lobe (n = 7) or middle lobe (n = 1) and a left lower lobe (n = 8) from a total of 16 donors representing various combinations of the recipient's family (n = 15) and an unrelated friend (n = 1). RESULTS: With an average follow-up of 1 year the overall survival is 75%. For the five patients followed up for at least 1 year, mean forced vital capacity was 80.6%, forced expiratory volume in 1 second was 75.6%, mid-forced expiratory flow was 64%, and diffusing lung capacity corrected for alveolar volume was 73% of predicted. For those patients with primary pulmonary hypertension, preoperative hemodynamics revealed mean pressures as follows: blood pressure 84.8 mm Hg, right atrial pressure 7.8 mm Hg, pulmonary artery pressure 71.3 mm Hg, pulmonary capillary wedge pressure 9.5 mm Hg, cardiac index 2.9 L/min per square meter, and pulmonary vascular resistance index 22.8 Wood units. Postoperative hemodynamics revealed a mean blood pressure of 84.3 mm Hg, right atrial pressure of 2.7 mm Hg, pulmonary artery pressure of 16 mm Hg, pulmonary capillary wedge pressure of 7.3 mm Hg, cardiac index of 4.2 L/min per square meter, and pulmonary vascular resistance index of 1.9 Wood units. CONCLUSIONS: Early results of living-donor bilateral lobar transplantation for diseases other than cystic fibrosis have resulted in satisfactory survival and pulmonary function. Additionally, patients with severe primary pulmonary hypertension have had dramatic normalization of their hemodynamics despite the limited amount of lung tissue transplanted. We believe that the data from this small cohort experience compares favorably with our larger series with cystic fibrosis and supports an expanded role for living-donor lobar transplantation in patients with alternate indications.

Bronchiolitis obliterans is not the primary cause of death in pediatric living donor lobar lung transplant recipients.

BACKGROUND: Obliterative bronchiolitis (OB) is the chief cause of mortality in cadaveric lung transplant patients (CL). But, is OB the primary cause of mortality for living donor lobar recipients? To answer this question, we reviewed the causes of mortality in our pediatric patients who underwent living donor lobar lung transplantation (LD) and compared them with our pediatric patients who received whole cadaveric lungs (CL). METHODS: Data collected included demographics, transplant type, hospital days, immunosuppression regimen, and cause of death. Statistical analysis was done using Fisher's Exact test and Student's t-test (mean +/- SD). RESULTS: From May 1993 to December 1999, 53 patients underwent lung transplantation (21 males, 32 females; mean age 12.4 +/- 5.4 years). Twenty-nine patients had LD procedures (12 males, 17 females; mean age 14.4 +/- 3.6 years) and 24 patients had CL surgery (9 males, 15 females; p = .78 [not significant]; mean age 9.8 +/- 6.3 years; p =.001). All patients received triple immunosuppression without induction. During the study period, 9 LD (6 males, 3 females; mean age 15.7 +/- 5.0 years) and 14 CL (3 males, 11 females; mean age 11.3 +/- 6.9 years) patients died. There was no significant difference between patients in the LD and CL groups who died with regard to gender (p = .08), age at the time of death (p = .12), mortality rate (p = .06), number of hospital days (p = .09), immunosuppressive medications (p > .08), incidence of non-specific graft failure (p = .26), or incidence of infection (p = .18). However, there was a significant difference in the incidence of OB between LD and CL recipients (p = .002). CONCLUSIONS: OB was not found to be the chief cause of mortality in pediatric LD recipients. We speculate that prevention of infections, possibly by a modest reduction in immunosuppressive therapy and aggressive antimicrobial therapy, may improve long-term survival in pediatric living donor lobar lung transplant recipients.

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 FEF25-71% (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.

The effect of pleural adhesions on pediatric cystic fibrosis patients undergoing lung transplantation.

The degree of pleural scarring complicating cystic fibrosis (CF) lung disease is thought to impact on the outcome of adult lung transplantation. This has not been previously studied in the pediatric population. We studied all patients undergoing lung transplantation at Children's Hospital Los Angeles from 1993 through 2000. Operative times, grade of pleural scarring, blood product transfusion requirements, and perioperative mortality were compared for patients with cystic fibrosis (35) versus those without this diagnosis (11). Patients with CF were slightly older (14.7+/-3.8 vs 10.6+/-5.6 years; P = 0.01) but had similar weights (34.8+/-8.7 vs 34.4+/-12.3 kg). The degree of pleural scarring was greater in the CF group but was only severe in four patients. Scarring did not impact on operative times (237+/-46 vs 219+/-39 minutes; P = 0.22) or cardiopulmonary bypass times (127+/-40 vs 133+/-49 minutes). Total perioperative blood requirements for the two groups were similar (35.6+/-14.9 vs 42.8+/-76.7 cm3/kg; P = 0.82). Pleural scarring in the pediatric CF patients undergoing lung transplantation is only severe in a minority of patients. It does not increase duration of operation nor blood transfusion requirements. CT scanning is consequently unnecessary in the preoperative workup of CF patients being evaluated for transplantation. CF patients undergoing transplantation have perioperative outcomes similar to those of noncystic patients.

Psychosocial responses of adolescent cystic fibrosis patients to lung transplantation.

What psychosocial issues do adolescent cystic fibrosis (CF) patients experience after undergoing lung transplantation (Tx)? The aim of this study was to determine, using an ethnographic study design, the common themes and emotional responses in post-lung transplant adolescent CF patients of the Cardiothoracic Transplant Clinic at the Childrens Hospital Los Angeles. Nineteen CF lung transplant recipients were studied (eight males, 11 females: mean age at time of transplant, 15.7 +/- 2.7 yr). The mean time interval from Tx to interview was 25.4 months (range 1-58 months). Sixteen patients had living donor lobar lung Tx while three patients received cadaveric lungs. A series of 25 questions was used to assess the psychosocial impact of Tx, and a semi-structured interview focused on the following five domains: lifestyle, family functioning, social functioning, body image, and psychological functioning. The major themes identified by patients included: a strong desire to set and attain meaningful long-range goals, the need to control as many aspects of their lives as possible while dealing with parental over-protectiveness, and the adjustment to a new lifestyle. Common emotional responses included manageable fear/anxiety of lung rejection and uncertainty of the future, impatience with disruptions of daily routines caused by post-transplant medical management and its effect on the attainment of set goals, and frustration with parental over-protectiveness. In general, patients reported a positive outlook on life, with greater emphasis on sought-after goals as well as inter-personal relationships. This study demonstrates that adolescent CF transplant recipients develop long-term goals and plans for independence. By identifying and anticipating the emotional needs of this population, health care providers can assist patients in improving the quality of their lives from a physiological, as well as a psychological, viewpoint.

Human leukocyte antigen-DR expression on peripheral blood monocytes and the risk of pneumonia in pediatric lung transplant recipients.

BACKGROUND: Pneumonia is the leading cause of morbidity and mortality after living lobar lung transplantation (LT). Low levels of human leukocyte antigen-DR (HLA-DR) expression on peripheral blood monocytes, have been demonstrated to correlate with risk of infection in surgical, trauma, and adult transplant patients. In addition, interleukin (IL)-10 has been shown to be a negative regulator of HLA-DR expression. This study investigates whether HLA-DR expression and serum IL-10 levels correlate with the development of pneumonia after pediatric LT. METHODS: Thirteen LT recipients were prospectively monitored with blood samples obtained pre-LT (baseline) and post-LT weeks 1-4. Mean fluorescence intensity (MFI) of HLA-DR on CD14+ monocytes was measured by flow cytometry. IL-10 levels were determined by ELISA from frozen serum collected at the same time points as monocyte HLA-DR expression. Correlates of pneumonia were abstracted from the medical record. RESULTS: Monocyte HLA-DR expression declined in 11 of 13 patients in the first week post-LT. Two patients without an initial decline and four others whose HLA-DR expression recovered by week 2 post-LT, did not develop pneumonia or other infection or rejection. Pneumonia was observed in seven patients, six of whom failed to recover their monocyte HLA-DR expression by 2 weeks post-LT. Six of seven patients with pneumonia recovered, and one patient died of aspergillosis. During weeks 1-4, a statistically significant difference was seen in the profile of mean monocyte HLA-DR expression levels, analyzed as percent of baseline, between the patients with and without pneumonia (P=0.002). The greatest difference between groups over time was seen from post-LT weeks 1-2 (P=0.003). In addition, when comparing the values at each week, a significant difference was seen between the two groups at post-LT week 2 (P=0.006) and week 4 (P=0.05). Analysis of IL-10 concentrations revealed that the overall difference between the groups (patients with and without pneumonia) was statistically significant (P=0.014), with a paradoxical positive correlation between HLA-DR expression at post-LT week 4 and IL-10 concentrations. CONCLUSIONS: Persistent low monocyte HLA-DR expression was associated with the risk of post-LT pneumonia in these patients. This measurement may be useful for monitoring risk of infection and stratifying patients into higher and lower risk groups. Increased IL-10 levels may be protective for infection in this group of patients. At present it is unknown whether the predictive power of HLA-DR expression is indicative of a global defect in monocytic function or a specific abnormality.

Living donor lobar lung transplantation: the pediatric experience.

Living donor (LD) lobar lung transplantation is now an accepted alternative to cadaveric lung transplantation in selected patients with end-stage lung disease. This study reviews the Childrens Hospital Los Angeles LD experience of 17 patients (mean 13.2 +/- 2.7 yrs; range 9.3-18.5 yrs). 12 LD patients had end-stage cystic fibrosis, 4 had primary pulmonary hypertension, and 1 child had bronchiolitis obliterans. LD candidates must meet the same criteria as for cadaveric lung transplant candidates. Donor candidates are rigorously screened (physically and psychologically) prior to acceptance for lobectomy. LD patients receive the same triple immunosuppression regimen as our cadaveric recipients (prednisone, cyclosporine/FK506, and azathioprine/mycophenolate). Comparison of rejection episodes, incidence of bronchiolitis obliterans, pulmonary function tests, exercise stress tests, and cardiac catheterization data was made between LD and cadaveric lung transplantation (CL) pediatric recipients. Donor outcomes were also reviewed. In our pediatric program, the 1-year survival rate for LD recipients is currently 81%, which compares favorably with the ISHLT average of 70% for pediatric transplant patients. The incidence of rejection is about the same for LD and CL recipients, but the episodes are less severe for pediatric LD patients. There have been no histological cases of bronchiolitis obliterans syndrome in our LD recipients. Although there have been questions as to whether transplanted lobes can supply comparable pulmonary reserve to whole cadaveric lungs, the lung volumes (TLC and VC), expiratory flow rates, maximal exercise stress tests, and pulmonary artery pressures (no evidence of pulmonary hypertension) in LD patients are not significantly different to CL recipients in our institution. Besides pain from the thoracotomy, the donors have a decrease of 16% (right lower lobe donor) and 18% (left lower lobe donor) in their vital capacity. Otherwise, there have been no major complications to the donors and most have resumed their usual activities. Based on outcomes, pulmonary function tests, exercise stress tests, and hemodynamic studies as well as low donor morbidity, living donor double lobar lung transplantation is a viable alternative to cadaveric lung transplantation in selected pediatric patients with end-stage lung disease.

Paecilomyces variotii in a pediatric patient with lung transplantation.

Aspergillus has been noted to be the most common species of filamentous fungus isolated from the airways of lung transplantation (Tx) patients. In general, the bronchi are colonized asymptomatically with Aspergillus but this places such a patient population at greater risk of invasive infection. Other filamentous fungal species may also assume importance in this patient population. Here we report the post-transplant isolation of Paecilomyces variotii from the airways of a pediatric patient with cystic fibrosis (CF) who underwent bilateral living-donor lobar lung Tx. This is the first report of isolation of P. variotii in the pediatric lung Tx population. The isolation of filamentous fungi, such as Paecilomyces, with variable in vitro susceptibility to currently available antifungal agents further complicates the approach to post-transplant antifungal therapy in patients with lung Tx.