Size matching in lung transplantation using predicted total lung capacity.

Height is used in allocation of donor lungs as an indirect estimate of thoracic size. Total lung capacity (TLC), determined by both height and sex, could be a more accurate functional estimation of thoracic size. Size-matching criteria based on height versus predicted TLC was retrospectively evaluated, and, furthermore, whether a TLC mismatch was related to clinical and functional complications. The ratio of donor and recipient height, as well as the ratio of predicted TLC in donors and recipients, were calculated in 80 patients after bilateral lung transplantation. Complications evaluated included persistent atelectasis, persistent pneumothorax and increased number of days in intensive care, occurrence of bronchiolitis obliterans syndrome and limitation of exercise capacity. Median height donor/recipient ratio was 1.01 (0.93-1.12). Median predicted TLC donor/recipient ratio was 1.01 (with a clearly broader range 0.72-1.41). Neither sex mismatch nor TLC mismatch were related to clinical or functional complications. Allocation of donor lungs based upon height alone leads to a substantial mismatch in total lung capacity caused by sex mismatch. The absence of complications suggests that a greater height donor/recipient discrepancy can be accepted for allocation than previously assumed.

Simulated waiting list prioritization for equitable allocation of donor lungs.

BACKGROUND: In lung transplantation (LTx), allocation of donor lungs is usually based on blood group, height and waiting time. Long waiting times favor patients with a slowly progressive end-stage lung disease and make the current allocation system the subject of discussion. In an attempt to equalize the chances for transplantation for every patient, irrespective of diagnosis, we investigated the effect of diagnosis-dependent prioritization on the waiting list, using a simulation model. METHODS: For the main disease categories on the waiting list, the relative risks of dying while on the waiting list were calculated using empirical data from the Dutch LTx program gathered over a period of 10 years. In a microsimulation model of the Dutch LTx program based on data from the actual situation, patients with diagnoses associated with a statistically significant increased risk of death while on the waiting list were prioritized by multiplying the time on the waiting list by the relative risk. RESULTS: Relative risks of death on the waiting list were increased significantly in patients with cystic fibrosis, primary pulmonary hypertension and pulmonary fibrosis. Prioritization resulted in an increased chance of transplantation for the prioritized diagnoses and a decreased chance for the non-prioritized diagnoses. The distribution of diagnoses after LTx was almost equal to the distribution of diagnoses on the waiting list. CONCLUSION: The simulated method of prioritization on the waiting list is a step forward to a more equitable allocation of donor lungs. Moreover, this method is clinically feasible, as long as the waiting list is updated frequently.

Long-term survival despite early loss of graft function after single lung transplantation for pulmonary fibrosis.

We report a patient who received a single, left lung transplantation for idiopathic pulmonary fibrosis. The effect of the graft on pulmonary improvement was only temporary, because the patient developed obliterative bronchiolitis (OB), resulting in complete destruction of the graft. The patient, however, remains alive 6 years after OB was diagnosed, apparently as a consequence of native lung improvement with triple-immunosuppressive medicine. This case is of interest for several reasons: first, it shows that pulmonary fibrosis may respond to intensive immunosuppressive therapy; second, it demonstrates that ventilation scintigraphy is useful in addition to pulmonary function tests in estimating the actual function of the graft after single lung transplantation; and third, it appears that the gradation of bronchiolitis obliterans syndrome (BOS) after single lung transplantation may overestimate the true function of the transplant.

Extracorporeal membrane oxygenation before induction of anesthesia in critically ill thoracic transplant patients.

Cardiorespiratory failure just before surgery in critically ill thoracic transplant patients can have catastrophic consequences. We judged the cardiorespiratory condition in three of 160 thoracic transplant procedures performed in our center too unstable for a safe induction of anesthesia. In these 3 patients, extracorporeal membrane oxygenation support was installed before induction of anesthesia to maintain an adequate cardiorespiratory state. This strategy was successful for all 3 patients, and long-term survival was achieved with a good quality of life. Guidelines for indications to follow this strategy are discussed.

Gastrointestinal complications in lung transplant survivors that require surgical intervention.

BACKGROUND: Lung transplantation is widely accepted as a treatment for end-stage lung disease. At present, information regarding the incidence and outcome of acute gastrointestinal complications in lung transplant survivors is limited. METHODS: Since 1990, 127 lung transplantations have been performed in 125 patients: 73 males (58 per cent) and 52 females (42 per cent) of median age 43 (range 9-64) years. Patients received a standard induction and maintenance regimen of immunosuppression. RESULTS: At a median follow-up of 2.6 (range 0-8.6) years the overall survival rate was 68 per cent. An acute abdomen requiring surgical intervention was diagnosed in 12 patients (10 per cent). The median time following lung transplantation was 19 (range 3-68) months. Eight cases of bowel perforation, two of appendicitis, one of colitis, one of cholecystitis, and one pneumoperitoneum were encountered. Four Hartmann procedures, two sigmoid resections, one small bowel resection, two appendicectomies, a subtotal colectomy, a cholecystectomy and an exploratory laparotomy were performed with minimal morbidity and no postoperative death. CONCLUSION: Lung transplant survivors are at increased risk of developing an acute abdomen because of the use of high-dose immunosuppressive agents. Physicians who evaluate lung transplant patients for an acute abdomen should have a low threshold for surgical intervention.

Long-term outcome of lung transplantation is predicted by the number of HLA-DR mismatches.

BACKGROUND: The importance of HLA mismatch in determining long-term outcome in lung transplantation remains largely uncertain. METHODS: A retrospective analysis of 102 consecutive primary lung transplants was performed to identify risk factors for poor long-term outcome after lung transplantation defined as graft survival and bronchiolitis obliterans syndrome (BOS) stage I and II. Variables included were patient characteristics (age, sex, prior diagnosis), the number of HLA mismatches between donor and recipient, cold ischemic time, cytomegalovirus serologic concordance, number of acute rejections, and time to first rejection. Variables carrying significance in a univariate analysis were subjected to a proportional hazard regression analysis. RESULTS: In the multivariate analysis, an increased number of acute rejections correlated positively with decreased graft survival (risk ratio [RR] = 1.25; 95% confidence interval [CI], 1.05-1.5; P = 0.011), development of BOS stage I (RR = 1.36/episode; 95% CI, 1.16-1.58;P < 0.001), and BOS stage II (RR = 1.42/episode; 95% CI, 1.2-1.67; P < 0.001). An increased time to rejection correlated positively with reduced graft survival (RR = 1.03/day; 95% CI, 1.01-1.06; P = 0.02), and BOS stage I and II (both RR = 1.04/day; 95% CI, 1.01-1.07; P < 0.005). Compared with 2 HLA-DR mismatches, 0 or 1 mismatch was associated with improved graft survival (RR = 0.43; 95% CI, 0.19-0.98; P = 0.045) and protected against development of BOS stage I (RR = 0.47; 95% CI, 0.23-0.98; P = 0.044) and BOS stage II (RR = 0.35; 95% CI, 0.15-0.83; P = 0.017). CONCLUSIONS: HLA-DR mismatching appears to be a risk factor for the development of BOS and graft loss. Improved outcome after lung transplantation might be achieved with prospective matching for HLA-DR. Alternatively, the amount and type of immunosuppressive drugs may be guided by the degree of HLA-DR (mis)matching.

Quality of life before and after lung transplantation in patients with emphysema versus other indications.

Whether lung transplantation improves Health-related Quality of Life in patients with emphysema and other end-stage lung diseases before and after lung transplantation was examined. Between 1992 and 1999, 23 patients with emphysema and 19 patients with other indications completed self-administered questionnaires before lung transplantation, and at 4, 7, 13, and 25 mo. after transplantation. The questionnaire included the Nottingham Health Profile, the State-Trait Anxiety Inventory, the Self-rating Depression Scale, the Index of Well-being, the self-report Karnofsky Index, and four respiratory-specific questions. Neither before nor after transplantation were significant differences found on most dimensions of Health-related Quality of Life between patients with emphysema and other indications. Before transplantation, both groups report major restrictions on the dimensions Energy and Mobility of the Nottingham Health Profile, low experienced well-being, depressive symptoms, and high dyspnea. About 4 mo. after transplantation, most Health-related Quality of Life measures improved significantly in both groups. These improvements were maintained in the following 21 mo.

Eosinophilic granulocytes and interleukin-6 level in bronchoalveolar lavage fluid are associated with the development of obliterative bronchiolitis after lung transplantation.

In a prospective cohort study, we assessed whether changes in total cell counts and differentiation and interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) concentrations in bronchoalveolar lavage fluid (BALF) are associated with a higher risk to develop obliterative bronchiolitis (OB). We investigated 60 lung transplant patients (follow-up of 2 to 8 yr) with either histologic evidence of OB within 1 yr after lung transplantation (n = 19) or no pathology, good outcome (GO) for at least 24 mo and well-preserved lung function, i.e., FEV > or = 80% of baseline (n = 41). Median time between lung transplantation and the first BAL was 42 d for the GO group and 41 d for the OB group (p > 0.05). In the bronchial fraction, median total cell counts (0.06 x 10(3)/ml versus 0.04 x 10(3)/ml), lymphocyte (9 x 10(3)/ml versus 2 x 10(3)/ml), and eosinophilic granulocyte counts (1 x 10(3)/ml versus 0) were significantly higher in the OB group than in the GO group (p < 0.05). In the alveolar fraction, this was the case for the median value of neutrophilic granulocyte counts (19 x 10(3)/ml versus 4 x 10(3)/ml), respectively. Median values of IL-6 and IL-8 concentrations in both bronchial (IL-6: 23 versus 6 pg/ml, IL-8: 744 versus 102 pg/ml) and alveolar fractions (IL-6: 13 versus 3 pg/ml, IL-8: 110 versus 30 pg/ml) of the BALF were significantly higher in the OB group than in the GO group. By means of logistic regression, we showed that higher total cell, neutrophilic granulocyte, and lymphocyte counts, the presence of eosinophilic granulocytes, and higher concentrations of IL-6 and IL-8 were significantly associated with an increased risk to develop OB. We conclude that monitoring cell counts, neutrophilic and eosinophilic granulocytes, IL-6, and IL-8 in BALF within 2 mo after lung transplantation in addition to the transbronchial lung biopsy (TBB) pathology will contribute to a better identification and management of the group of patients at risk for developing OB within a year.

Long-term renal outcome after lung transplantation is predicted by the 1-month postoperative renal function loss.

BACKGROUND: Progressive renal function loss is common after lung transplantation. To facilitate the design of renoprotective strategies, identification of early predictors for long-term renal function loss would be useful. METHODS: We prospectively analyzed renal function [glomerular filtration rate (GFR); 125I-iothalamate clearance] in a closely monitored cohort (minimum 24-month follow-up) of 57 patients who received lung transplants between November 1990 and September 1996 in our center. The analyzed end points were the slope of the GFR from 6 months posttransplant onward and the GFR at 24 months after transplantation. RESULTS: Before transplantation, the GFR was 100 ml/min (median, range 59-163). It decreased to 67 ml/min (29-123) at 6 months, 53 ml/min (17-116) at 24 months, and 51 ml/min (20-87) at 36 months after transplantation. The magnitude of the loss of GFR 1 month post-transplantation was the only factor significantly correlated with absolute GFR at 24 months after transplantation. Pulmonary diagnosis was significantly associated with long-term rate of renal function loss. Median loss of GFR was greatest in patients with cystic fibrosis (-10 ml/min/year, range -14 to -6 ml/min/year), preserved in pulmonary hypertension (-1 ml/min/year, range -6 to +7 ml/min/year), and in between in emphysema (-6 ml/min/year, range -27 to +12 ml/min/year). No other factors could be identified. CONCLUSIONS: In lung transplant recipients, the 1-month postoperative loss of GFR is an early marker for long-term renal prognosis. Pulmonary diagnosis appears to be a relevant predictor as well. These factors may guide further research and the development of preventive strategies.