Donor Lobar Research Articles

Update on cystic fibrosis: selected aspects related to lung transplantation.

Survival after lung transplantation for cystic fibrosis has improved substantially. To date, 1-year survival is as much as 80-90% and 5-year survival 60-70%. Experience of surgical techniques, periand postoperative management and long-term follow-up care has grown. High risk patients for whom transplantation was contraindicated ten years ago are today being transplanted. Prerequisites for a successful outcome are appropriate timing of referral, careful consideration of medical issues in other organs, and psychosocial support systems. Panresistant organisms are a special problem in candidates with cystic fibrosis, and advances in microbiological testing and characterisation of these organisms are warranted. Living donor lobar transplantation has become an option in rapidly deteriorating children and young adults. Selected aspects of the evolving field of lung transplantation are discussed.

Screening potential donors for living donor lobar lung transplantation

Bilateral living donor lobar lung transplantation requires 2 live donors per transplant candidate. The Live Donor Consensus Conference Guidelines for accepting donors for lobar transplantation include: individuals in good health; age 18 yrs-55 yrs; normal PFTs; normal ABG on room air; normal weight-for-height; must be taller than proposed recipient; and have no significant cardiopulmonary disease. Pre-screening candidates is essential to reduce overall costs and conserve resources. Subsequent evaluation of potential donors who pass the pre-screening process is expensive and time-consuming. To date, no one has reported the number of candidates who are pre-screened and eventually evaluated in order to select 2 donors. A cohort of 28 consecutive bilateral lobar lung transplant recipients were reviewed to determine the number of lobar donors who were evaluated and the primary reason for not being accepted. A total of 220 (138 M:82 F) were referred for lobar donor evaluation by potential recipients and their families. 164 pts (almost 75%) were not accepted as lobar donors. The average number was 8 (range 2-29) potential donors screened per lung transplant candidate. The primary reasons for not accepting a lobar donor: decreased expiratory flows 55 pts (33.5%); height 32 pts (19.5%); did not want to donate 18 pts (11%); not accepted for miscellaneous medical/social reasons by transplant team 18 pts (11%); too obese 12 pts (7.3%); and too old 9 pts (5.5%). Although 2/total 28 (7%) lobar recipients required only 2 donors screened, the majority of lobar candidates required more donor evaluations. While lobar transplant is an option for critically ill patients, the need to evaluate more than 2 potential donors, as well as the time necessary to properly screen lobar donors safely, supports the concept that this surgery should not be considered as a routine emergent procedure. Living lobar transplant requires the ability to screen multiple potential donors in a time-effective manner to maintain both cost effectiveness and recipient/donor safety.

Single center comparison of pediatric living donor lobar and cadaveric lung transplant

Living donor lobar transplant (LDLT) has been used to address the ongoing shortage of cadaveric lungs and unpredictable course of end-stage lung disease. Because LDLT involves putting two healthy patients at risk, we compared outcomes between cadaveric lung transplant and LDLT. From July 1994 to May 2002, 38 LDLTs were performed at this center. A cohort of cadaveric recipients, also transplanted here during that era, matched by age at transplant, sex and underlying disease was selected to serve as a controls. LDLT recipients were less stable at the time of transplant: more patients (12/38) in the LDLT cohort were mechanically ventilated compared to 2/38 in the controls. The average ischemic times were significantly shorter in the LDLT patients (1:32) compared to controls (4:46). One and 3 year survival for the LDLT recipients was 60 % and 48% compared to 89% and 58% for the control cohort. The difference in Kaplan-Meier survival curves was statistically significant (P=0.03). There was no difference in the incidence of acute rejection between the LDLT and control cohorts. Post-transplant FEV1 and FVC were not significantly different. However, freedom from bronchiolitis obliterans syndrome (BOS) at 1 and 3 years was 92% and 85% compared to 75% and 53% in the cadaveric cohort (P=0.03). Not surprisingly, the causes of death in the LDLT population reflected this difference. Only 2/24 (8%) of deaths in the LDLT cohort were due to BOS compared to 8/18 (45%) of deaths in the control cohort. In contrast, 11/24 (46%) of deaths in the LDLT cohort were related to infection compared to 2/18 (11%) in the control population. Based on this comparison, we conclude that LDLT can be performed successfully in pediatric patients. Although the decreased incidence of BOS makes us optimistic about the long-term survival of LDLT recipients, efforts focusing on minimizing infectious complications are necessary to improve overall survival.

Does lung growth occur when mature lobes are transplanted into children?

Lung volume increases after living donor lobar lung transplantation (LD) in children. The mechanism responsible for this increase may be alveolarization (lung growth) or alveolar dilation. The diffusing capacity of the lung for carbon monoxide adjusted for lung volume (DLco/VA) should decrease if alveolar dilation occurs, but not if lung growth occurs. Pulmonary function tests were measured 1-12 months after transplant in 20 children receiving LD transplants and in 11 children receiving cadaveric whole lung transplantation (CL). One month after transplant there were no differences between LD and CL recipients in age, gender, or height. Compared to the first month after transplant, height increased at 6-12 months after LD (p < 0.05), and only at 12 months after CL (p = 0.02). Total lung capacity (TLC) showed an 11-22% increase at 3-12 months after LD, and an 11-14% increase at 6-12 months after CL. DLco/VA showed an 11-17% decrease at 3-12 months after LD. However, in recipients of CL, DLco/VA showed a transient decrease of 10% at 3-6 months post-transplant, but was not significantly lower at 9-12 months. LD recipients had lower DLco/VA values than CL recipients at 6-12 months after transplant (p < 0.05). We conclude that following LD, lung volume increases, but DLco/VA decreases. We speculate that alveolar dilation, rather than alveolarization, is the primary mechanism of increased lung volume in children following LD.

Pediatric Recipients of Living Donor Lobar Lung Transplants: Postoperative Care

Bilateral living donor lobar lung transplantation is a treatment option for selected children and adults with end-stage lung disease. Careful donor evaluation, skilled intraoperative management and surgical technique, and diligent immediate postoperative care and follow-up all contribute to better outcomes. Although medical management of whole lung transplant recipients in the immediate postoperative period is similar to that of lobar lung transplant recipients, there are specific differences. Anatomical distinctions, such as the entire cardiac output flowing to 2 lobes instead of 5, and thoracic space issues with simultaneous mechanical ventilation and chest tube suction, contribute to these differences. Early postoperative care, including initial postoperative stabilization, ventilation, fluid management, rejection/infection surveillance and prophylaxis, and beginning rehabilitation, can be adapted to ensure successful outcomes in these patients.

Pediatric recipients of living donor lobar lung transplants: postoperative care.

Bilateral living donor lobar lung transplantation is a treatment option for selected children and adults with end-stage lung disease. Careful donor evaluation, skilled intraoperative management and surgical technique, and diligent immediate postoperative care and follow-up all contribute to better outcomes. Although medical management of whole lung transplant recipients in the immediate postoperative period is similar to that of lobar lung transplant recipients, there are specific differences. Anatomical distinctions, such as the entire cardiac output flowing to 2 lobes instead of 5, and thoracic space issues with simultaneous mechanical ventilation and chest tube suction, contribute to these differences. Early postoperative care, including initial postoperative stabilization, ventilation, fluid management, rejection/infection surveillance and prophylaxis, and beginning rehabilitation, can be adapted to ensure successful outcomes in these patients.

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.

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.

Pediatric living donor lung transplantation: psychosocial considerations

LDLT is indicated in pediatric recipients with severe lung disease who are unlikely to survive long enough to receive cadaveric organs. The first living donor lobar transplant (LDLT) at this pediatric center was performed in 1994. Since then, we have developed a collaborative program involving autonomous pediatric and adult multidisciplinary teams of health care providers. As of 10/00, 32 of 221 lung and heart/lung transplants at this center were LDLTs. Twenty-three were primary recipients, 9 were retransplants. Recipient survival is 56% at 5 years, comparable to 63% 5 year survival for cadaveric recipients. Recipients have been predominantly female (71 %) with a mean age of 15.2 (7 - 21) years. We have screened 471 potential donors and evaluated 185. There were no donor fatalities. Of 64 donors, 83% were related to the recipient, 12% unrelated with a prior relationship, and 5% unrelated with no prior relationship (altruistic). The LDLT program has evolved from a reactive approach (LDLT offered only to critically ill recipients) to a proactive approach where recommendations to identify potential LDLT donors as an ‘insurance policy’ are made during the recipient’s initial evaluation. Also, an increasing number of recipient families are pursuing LDLT over cadaveric transplant (0% in 1994 to 17% in 2000). Due to both factors, the ratio of number of potential donors screened to number evaluated annually has significantly increased from 4:4 in 1994 to 225:31 in 2000 (as of 10/00). Adopting a proactive approach has yielded enhanced decision-making for families and greater inclusion of the pediatric recipients in the process of identifying potential donors. Psychosocial considerations of LDLT in children ages 7-12 years express their ‘wanting new lungs’ from donors ‘who could help; who loved them’. Adolescent recipients express multiple concerns about potential LDLT donors from moral, social and pragmatic reasons (i.e. divorced parent, quality of life of donor pre/post-lobectomy) and indicate clear preferences for acceptability of lobes from given donors. Psychosocial impact on donors has been positive. However, significant difficulties for donors have arisen when the recipient suffered rejection or post-op complications involving the donor’s lobe. Conclusions: LDLT is increasing as a response to organ shortage. A proactive approach to LDLT promotes informed consent, enhances decision-making and promotes early psychosocial assessment and intervention.

Organ Procurement-Strategies to Optimize Donor Availability

Increasing donor availability for organ transplantation requires attention to factors that are potentially modifiable. The potential pool of available organs can theoretically be enlarged by considering new sources of organs, including non-beating heart donors, live donor lobar transplants, xenotransplants, and in vitro organ culture. Increased utilization of the current pool of organs can be achieved by creating a system that identifies, considers, and optimizes all possible donors. Although protocols have been drawn up regarding general and specifically lung donor acceptance criteria, many of these can be now recognized as unduly conservative and without a proven clinical basis. Careful reanalysis of these acceptance criteria and active donor management can be balanced against the particular circumstance of an individual potential recipient to increase lung transplantation rates.

Assessment for lung transplantation in cystic fibrosis.

Lung transplantation has been available as a therapeutic option for patients with end-stage cystic fibrosis (CF) lung disease from the mid-1980s. Since this time, in excess of 700 CF patients have undergone the procedure worldwide, as recipients of heart-lung, double lung, or more rarely single lung cadaveric transplants. A small number of CF patients have received living donor lobar transplants, but this procedure has been performed rarely in the UK. Survival following heart-lung or double lung cadaveric transplantation is poorer than for other solid organ transplants, with the International Registry reporting survival of 60-70% at 1 year and 30-40% at 5 years for both procedures1 (Figure 1). These survival figures vary little between major centres, and are improving only slowly. However, there is increasing evidence that correctly timed transplantation does provide patients with a significant increase in longevity, in addition to an improved quality of life2'3. As the potential benefits of the procedure become better understood, the number of potential recipients is increasingly outweighing the number of suitable donors. This has the effect of increasing waiting times for organs, with a number of patients not surviving the waiting period. This is an international problem, affecting all solid organ transplants, and is unlikely to be resolved in the near future. As post-transplant survival is relatively poor, patients must not be transplanted too early, or the potential survival benefit from the procedure is reduced. Conversely, if patients are accepted for transplantation too late, the likelihood of them receiving organs is reduced, with the assessment and acceptance for transplantation merely offering them false hope. The first goal of transplant assessment is, therefore, assessment of risk. Furthermore, if patients with particularly poor posttransplant survival potential can be identified, they can either be counselled against transplantation, or offered tailored post-transplant care in an attempt to improve their outcome. The second goal of transplant assessment is, therefore, identification of absolute and relative contraindications. ii

Pulmonary volume increases with linear growth in pediatric living donor lobar lung transplant recipients: MS Woo, EF MacLaughlin, MV Horn, VA Starnes. Cardiothoracic Transplant Team. Childrens Hospital Los Angeles. University of Southern California School of Medicine. Los Angeles, California. USA

Pulmonary volume increases with linear growth in pediatric living donor lobar lung transplant recipients: MS Woo, EF MacLaughlin, MV Horn, VA Starnes. Cardiothoracic Transplant Team. Childrens Hospital Los Angeles. University of Southern California School of Medicine. Los Angeles, California. USA

Living donor lobar lung transplants and HLA matching: A preliminary report

Living donor lobar lung transplants and HLA matching: A preliminary report

Reduced-size lung transplantation from adult to neonatal sheep

Lung transplantation continues to be limited by donor availability. This shortage is particularly acute in the pediatric population. A model was developed in sheep to simulate human pulmonary transplantation from adults into newborns. Pulmonary allografts were performed in 8 neonatal lambs (<10 days old) weighing between 2.5 and 5 kg. Unrelated adult sheep donors were used (weighing 55 to 82 kg). The recipient body weight was approximately 6% that of the donor, but ranged from 4% to 8%. Ipsilateral or contralateral upper lobe allografts were used, although the latter required inversion prior to implantation. All venous anastomoses utilized left atrial cuffs. The pulmonary arterial and bronchial anastomoses were constructed end-to-end. Following implantation the lobes were further contoured to fit within the recipient hemithorax using a linear surgical stapler. Animals were immunosuppressed with cyclosporine. Two animals died 1 week postoperatively but the remaining six survived 1 to 5 months. Postoperative lung scans at 10 to 14 days confirmed satisfactory ventilation and perfusion of the allografts. All vascular anastomoses were intact at postmortem examination. Primary bronchial healing was accomplished without an omental wrap. We conclude that successful lung transplantation can be performed from adult donors into neonatal recipients. Preservation of the maximal arterial and venous length during native pneumonectomy is essential to allow matching of the vascular cuffs. Short donor lobar bronchi may be responsible for the reliable primary healing. Improved immunosuppression will be required to assess long-term function and growth of these reduced-size allografts.