Heart-lung Transplant Patients Research Articles

Cost analysis of home monitoring in lung transplant recipients

The University of Minnesota has maintained a home monitoring program for over 10 years for lung and heart-lung transplant patients. A cost analysis was completed to assess the impact of home monitoring on the cost of post-transplant medical care. Clinical information gathered with the monitoring system includes spirometry, vital signs, and symptom data. To estimate the impact of this system on medical costs, we completed a retrospective analysis of the effects of home monitoring on the cost of post-lung transplant medical care. The cost analysis used multivariate linear regression with inpatient, outpatient, and total medical care costs as the dependent variables. The independent variables for the regression include home monitoring adherence, underlying disease, ambulatory diagnostic group mapping variables, transplant type, and patient demographics. The multivariate regression of the overall cost results predicts a 52.4 percent reduction in total costs with 100 percent patient adherence; this rate includes a 72.24 percent reduction in inpatient costs and a 46.6 percent increase in outpatient costs. The actual first year average patient adherence was 74 percent. Adherence to home monitoring increases outpatient costs and reduces inpatient costs and provides an overall cost savings. The break-even point for patient adherence was 25.28 percent, where the net savings covered the cost of home monitoring. This is well within the actual first year adherence rates (74 percent) for subjects in the lung transplant home monitoring program, providing a net savings with adherence to home monitoring.

Effect of Azithromycin on Bronchiectasis and Pulmonary Function in a Heart-Lung Transplant Patient With Severe Chronic Allograft Dysfunction: A Case Report

Azithromycin has been shown to be beneficial in several diseases with chronic neutrophilic inflammation of the airways, such as cystic fibrosis and bronchiolitis obliterans syndrome (BOS) after lung transplantation. Up to now, however, its healing effect on bronchiectasis has never been demonstrated. We report a heart-lung transplant patient who developed chronic rejection (BOS stage 3) with the appearance of gross bronchiectasis on a spiral computed tomography (CT) chest scan. Within 2 weeks after starting azithromycin, the patient's forced expiratory volume in 1 second increased significantly and a repeat spiral CT chest scan 5 months later, showed a major improvement of the bronchiectasis. This case report illustrates that bronchiectasis may greatly improve after treatment with azithromycin and no longer needs to be considered an endstage finding in patients with severe BOS.

Previous thoracic surgery does not increase peri-operative mortality in pediatric heart-lung transplant recipients

Background Heart-lung transplant (HLT) is indicated in select children with end-stage cardiopulmonary disease. We sought to determine whether previous thoracic surgery increases peri-operative morbidity and mortality. Methods Retrospective data were analyzed using unpaired Student’s t-test and Fisher’s exact test. Results are reported as mean ± SD. Peri-operative mortality was defined as death at ≤30 days post-transplant. Results From August 1993 through April 2001, 13 patients (mean age 7.9 ± 5.3 years; 9 girls, 4 boys) underwent HLT at our center. Eight of 13 (62%) had previous thoracic surgery and 5 of 13 (38%) did not. Interval of last surgery to transplant date was 45.5 ± 26.4 months (range 6 to 79 months). We compared HLT patients who had previous thoracic surgery to HLT recipients who did not. There was no significant difference in weight (18.6 ± 14.3 vs 36.5 ± 20.7 kg, p = 0.09), age (6.5 ± 4.5 vs 10.2 ± 6.1 years, p = 0.23) or duration of intubation (14.1 ± 12.9 vs 17.0 ± 30.3 days, p = 0.83). There were no caval or tracheal anastomotic stenoses in either group. There was no significant difference in blood products transfused ≤48 hours after HLT: packed red blood cells ( p = 0.16); fresh frozen plasma ( p = 0.13); platelets ( p = 0.59), and cryoprecipitate ( p = 0.27). There was no difference in cardiopulmonary bypass time (129.3 ± 48.2 vs 160.6 ± 73.9 minutes, p 0.39); post-operative diaphragm dysfunction (4 of 8 vs 0 of 5, p = 0.1); re-exploration for bleeding (2 of 8 vs 1 of 5, p = 1.0); or peri-operative mortality (2 of 8 vs 0 of 5, p = 0.48). Conclusions We conclude that previous thoracic surgery in HLT recipients does not significantly increase blood product transfusion, cardiopulmonary bypass time or peri-operative mortality.

Cardiothoracic transplantation for congenital heart disease in teenagers and adults

Since 1980, 194 patients aged between 10–52 years have undergone cardiothoracic transplantation for congenital heart disease (CHD) at our institution. Sixty underwent heart transplantation, 129 heart-lung transplantation, and 5 bilateral lung transplantation with repair of the underlying defect. This represented 4%, 27% and 3 % of all patients undergoing heart, heart-lung and bilateral lung transplantation respectively. Patients undergoing heart transplantation either had complex abnormalities with low pulmonary artery pressure (n = 37) or myocardial failure after previous reparative operations (n = 23). Fourteen patients undergoing heart-lung transplantation had complex pulmonary atresia and 115 had CHD with pulmonary hypertension. The type of operation has been modified during the period under review to take account of the increasing scarcity of donor organs. Operative techniques are adapted according to the complexity of the underlying anatomy. In-hospital mortality was 20/60 (33%) for hearts, 41/115 (36%) in heart-lung transplantation for CHD and pulmonary hypertension and 12/14 (85%) for complex pulmonary atresia. There were no deaths in the five patients undergoing bilateral lung transplantation and repair. Major risk factors for early death in the heart-lung transplant group were complex pulmonary atresia, previous lateral thoracotomy and age greater than 35 years at transplant. Actuarial survival in the heart transplants was 60%, 54% and 46% at 1 year, 5 years, and 10 years respectively and 61%, 45% and 36% at 1 year, 5 years and 10 years respectively for heart-lung transplant patients with CHD and pulmonary hypertension. It is concluded that risk of early death is greater in patients with complex CHD undergoing heart transplantation than in patients with acquired heart disease. Thereafter survival in patients with CHD is similar to other patients undergoing heart or heart-lung transplantation.

Aspects of adherence to the treatment regimen following heart or heart-lung transplantation in young people

Non-adherence to medical treatment has emerged as a significant problem in transplantation (tx) and has particularly been associated with adolescence. There is little research on the risk factors for non-adherence in heart and heart-lung transplant patients but it has been suggested that up to a third of patients are non-adherent to some aspects of the treatment regimen. Fifty adolescents and young adults (24 males, 26 females; mean age: 17.9 years, range 12.3-24.9 years) who had undergone heart (n=42) or heart-lung (n=8) tx 1.4-14.9 years (mean 8.8 years) previously were asked to complete the Beliefs about Medication Questionnaire (BMQ), Perceived Illness Experience (PIE) scale and a demographics questionnaire. The notes of all patients were reviewed for information regarding previous psychiatric referral, rejection episodes and complications and noted concerns about adherence. Forty completed questionnaires were received and in 11 (28%) non-adherence to treatment was reported. It was also documented in the clinical notes of 9 (18%) of the patients. Non-adherence recorded in the notes was classified as intentional non-adherence and was correlated with lack of exercise (p=.032), psychiatric referral (p=.009) and lymphoma (p=.009). Non-adherence determined from the questionnaires was classified as unintentional and related to forgetting to take medication. Unintentional non-adherence was correlated with high scores on the preoccupation with illness (p=.041) and difficulties at school (p=.009) subscales of the PIE. In conclusion, more than a quarter of the sample demonstrated non-adherence to the treatment regimen. In contrast to previous research, we found that unintentional non-adherence is associated with different factors to intentional non-adherence. Future research is required to determine whether unintentional non-adherence results in significant medical complications in the longer term and how a reduction in the prevalence of non-adherence can be facilitated.

Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation: a comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone.

Cytomegalovirus (CMV) disease was previously shown to be unaltered by a 28-day course of ganciclovir compared with placebo in seronegative recipients of hearts from seropositive donors (D+/R-). This study tests the hypothesis that a combination of ganciclovir plus CMV hyperimmune globulin (CMVIG) is more effective than ganciclovir alone for preventing acute CMV illness and its long-term sequelae. The study population receiving CMVIG (n=80) included 27 heart transplant recipients (D+/R-) and 53 heart-lung and lung transplant recipients (R+ and/or D+). Each group was matched with historical controls who underwent transplantation within the preceding 2-3 years. Outcome measures compared were as follows: 3-year incidence of CMV disease; fungal infection; acute rejection; survival; rates and severity of transplant coronary artery disease (in heart patients) defined by intimal thickness (ultrasound) and coronary artery stenosis (angiographic); and incidence and death from obliterative bronchiolitis defined by pathological criteria on endobronchial biopsy specimens (in heart-lung/lung patients). Patients treated with CMVIG had a higher disease-free incidence of CMV, lower rejection incidence, and higher survival rate compared with the patients treated with ganciclovir alone. The coronary artery intimal thickness and the prevalence of intimal thickening were lower in the patients receiving CMVIG. Heart-lung and lung transplant patients treated with CMVIG had lower incidences of obliterative bronchiolitis and death from obliterative bronchiolitis and longer survival compared with the patients treated with ganciclovir alone. CMVIG plus ganciclovir seems to be more effective that ganciclovir alone for preventing the sequelae of CMV infection. A prospective randomized study is required to confirm these observations.

Cytological monitoring of peripheral blood, bronchoalveolar lavage fluid, and transbronchial biopsy specimens during acute rejection and cytomegalovirus infection in lung and heart–lung allograft recipients

Acute rejection and cytomegalovirus (CMV) infection are important complications after lung and heart--lung transplantation. We sought to investigate whether acute rejection and CMV infection demonstrated as CMV antigenemia had an effect on the cell profiles of peripheral blood (PB), bronchoalveolar lavage fluid (BAL-F), or TBB histology. In this prospective study, composition of cells in PB, BAL-F, and TBB samples from 20 lung or heart-lung transplantation patients were analyzed during episodes of acute rejection or CMV antigenemia. Rejection was graded according to the International Society for Heart and Lung Transplantation criteria. As controls, samples with no evidence of rejection or infection were used. To evaluate the effect of time on cellular findings, samples were divided into three groups according to time after transplantation: 1--30, 31--180, and more than 180 d after transplantation. Acute rejection was associated with mild blood basophilia (p<0.05; specificity 94%, sensitivity 42%). In BAL-F during rejection, the number of basophils (p<0.05), eosinophils (p<0.05), and lymphocytes (p<0.05; specificity 77%, sensitivity 64%) was increased compared to controls during the post-operative month 1. Later-occurring rejections were associated with increased amounts of neutrophils in BAL-F (p<0.05; specificity 82%, sensitivity 74%). In TBB histology, acute rejections were associated with perivascular and/or peribronchial infiltration of lymphocytes (p<0.001) and plasma cells (p<0.05) compared to controls. In our patients receiving gancyclovir prophylaxis, CMV antigenemia did not significantly alter the cell profiles in PB and BAL-F nor the inflammatory cell picture in TBB histology. TBB histology remains the 'gold standard' for diagnosing rejection in lung and heart-lung transplantation patients, as the inflammatory cell findings in TBB specimens are highly specific for rejection. The cellular changes associated with rejection, mild PB basophilia and increased proportions of lymphocytes in early- and neutrophils in later-occurring rejection, observed in BAL-F cannot be considered specific for rejection, but may warrant clinical suspicion of rejection.

Quantification of cytotoxic T-cell gene transcripts in human lung transplantation.

Differentiating between acute rejection and cytomegalovirus (CMV) infection is one of the major challenges of lung transplantation. The aims of this study were to: (1) quantify the transcription of the cytotoxic T lymphocyte (CTL) effector molecules in the bronchoalveolar lavage (BAL) of lung transplant recipients and (2) evaluate the clinical usefulness of this technique. Sixty-six single-lung, double-lung, or heart-lung transplant patients were prospectively enrolled in the study. BAL was performed either for routine surveillance or for acute graft dysfunction. RNA was extracted from BAL cell pellets and underwent competitive reverse transcription-assisted polymerase chain reaction (RT-PCR) for perforin, granzyme B, granulysin, and Fas ligand. Gene transcript analysis was compared to clinical diagnosis established by conventional methods [BAL microbiological and transbronchial biopsy (TBB) analyses]. After exclusion of several BAL according to the study criteria, 62 BAL were submitted for data analysis. Significantly higher expression of all the analyzed transcripts was found during CMV infection, compared with each of the other defined diagnostic categories, namely nonsignificant pathology, acute rejection, and nonviral pulmonary infection. Quantification by competitive RT-PCR of the CTL effector molecule transcripts (perforin, granzyme B, granulysin, and Fas ligand) could represent a valuable tool for the differential diagnosis of graft dysfunction in lung transplantation.

Procalcitonin for differential diagnosis of graft rejection and infection in patients with heart and/or lung grafts

Objectives: Investigation of the reliability of Procalcitonin (PCT) for differential diagnosis of acute rejections and non-viral infections in heart and lung transplanted patients.¶Design: Retrospective study.¶Setting: Transplant intensive care unit (ICU) at a university hospital.¶Patients: 57 heart, 18 lung and 3 heart-lung transplant patients.¶Measurements: PCT was measured in plasma samples of heart and lung transplanted patients using a commercial immuno-luminescence assay and was compared with values of C-reactive protein (CRP) and leukocytes (WBC).¶Results: PCT was elevated in patients suffering from bacterial and fungal infections. The magnitude of values was clearly associated with the severity of the infection. Rejections and viral infections did not interfere with the PCT release.¶Conclusion: PCT is a reliable predictor with discriminating power for non-viral systemic infections in patients after heart and/or lung transplantation. PCT allows an early differential diagnosis between rejection (AR) and bacterial/fungal infection (IF) and thus a rapid and focused therapeutic intervention. It avoids unnecessary antibiotic treatment which could be toxic for the graft itself in patients with rejection only. PCT provides vital information early to clinicians and allows them to improve the management of bacterial/fungal infections in immunocompromized transplant patients. PCT thus facilitates and improves the outcome of survival rate and the quality of life in the postoperative period of patients with heart and/or lung grafts.

Intravenous ganciclovir prophylaxis for cytomegalovirus in heart, heart-lung, and lung transplant recipients

Abstract Cytomegalovirus (CMV) disease has had a significant clinical impact on the heart, heart-lung and lung transplant recipients in our centre. CMV disease has been so severe with CMV antibody-negative heart-lung transplant patients receiving organs from CMV antibody-positive donors (CMV-mismatched patients) that in 1986 we adopted the policy of not transplanting CMV-positive organs into CMV-negative heart-lung or lung recipients. In December 1992, we instituted a policy of providing intravenous ganciclovir (5 mg/kg twice a day for 28 days) during the immediate postoperative period for CMV-mismatched heart recipients and CMV antibody-positive heart-lung and lung patients, who have been the patients at greatest risk of severe CMV disease in our centre. A placebo group was not employed because of ethical considerations, ganciclovir having been shown to be effective for the treatment of CMV infections among transplant patients. Compared with a historical control group of patients receiving no prophylaxis, prophylactic ganciclovir reduced the incidence of CMV infection (39 % vs 91 %, P = 0.0006) and CMV disease (17 % vs 74%, P = 0.0004) among CMV antibody-positive heart-lung recipients. Prophylactic ganciclovir did not significantly reduce the incidence of CMV infection or disease among heart or isolated lung recipients. Ganciclovir was well tolerated, with few adverse reactions. In the case of heart-lung transplant patients, one month of intravenous prophylactic ganciclovir significantly reduced the incidence of both CMV infection and disease when compared with patients who received no prophylaxis. With the lung transplant and heart transplant patients, there were no significant differences between the prophylaxis and nonprophylaxis groups, although there was a consistent trend towards less infection and disease in the prophylaxis groups.

Breakthrough pneumocystis carinii infections in lung and heart–lung transplant patients with chemoprophylaxis

Breakthrough pneumocystis carinii infections in lung and heart–lung transplant patients with chemoprophylaxis

Cyclosporine plasma unbound fraction in heart and lung transplantation recipients.

To investigate the variability in the unbound fraction (fu) of cyclosporine in recipients of heart, heart-lung, and lung transplantation, cyclosporine fu was determined ex vivo in plasma by equilibrium dialysis. In a retrospective study, 260 samples of plasma (one to seven per patient) were obtained from 89 heart (86%), lung (9%), and heart-lung (5%) transplant patients. The unbound fraction (x100) of cyclosporine ranged from 0.52% to 3.94%, with an overall mean of 1.53%+/-0.375% (SD). The mean percentage unbound for individual patients ranged from 0.71% to 1.98%, giving a 2.8-fold interpatient variation. In heart transplant recipients (66 patients), the values of fu were significantly lower (p < 0.01) during more severe rejection episodes, which required antirejection treatment (endomycardial biopsy result of grade 3a and higher) than in the absence of rejection (grade 0) or during grade la rejections. The value of fu did not vary with organ transplanted (p = 0.35) or etiology of organ failure (p = 0.32). Cyclosporine fu was negatively correlated with the age of the patient (r = -0.18, p < 0.05). Correlations were not observed between fu and blood biochemical and cytologic indices. However, fu was significantly lower (p < 0.01) in hypercholesterolemic transplant recipients (1.37+/-0.52%) than in normocholesterolemic patients (1.60+/-0.63%). Administration of simvastatin resulted in a significant increase in the mean fu from 1.40+/-0.09%) to 1.82+/-0.13% (paired t test, n = 13; p < 0.01). In patients who received ketoconazole, fu was not different from controls. These findings suggest that the level of cyclosporine fu may be an important determinant of immunosuppressive activity of cyclosporine. Moreover, the variation in fu could be strongly related to the concentration of serum lipoproteins; interpretation of the results of cyclosporine monitoring thus requires consideration of the lipidemic status of the patient.

Early cyclosporine blood levels impact the incidence of acute rejection and overall mortality in the first year after heart transplantation

THE USE of cyclosporine A (CyA) has been important in clinical transplantation since its introduction in the early 1980s, but the ideal dose of CyA that maximizes its immunosuppressive properties and minimizes its toxicity has remained an enigma. CyA monitoring is usually performed according the whole blood trough levels, although it has been reported that these levels do not provide a reliable measure of immunosuppression in heart and heart-lung transplant patients. However, it has been suggested that CyA level seems to be better correlated with risk of acute rejection than with CyA dose in heart transplantation (HT) recipients. To investigate the relationships of CyA blood levels with the incidence of acute rejection (AR) and mortality, we analyzed retrospectively our series of heart transplanted patients.

Improving the oral absorption of cyclosporine in malabsorbers: a review of the neoral compassionate need program

ALTHOUGH cyclosporine is the cornerstone of transplant immunosuppression, certain patient subpopulations have not derived full clinical benefit due to suboptimal absorption from the conventional formulation, Sandimmune. Specifically in the area of kidney transplantation, variable oral absorption of cyclosporine has been identified as a biopharmaceutical risk factor for chronic allograft rejection. Across several transplant indications, characteristics associated with poor or variable absorption have been identified. Given the dependence of cyclosporine solubilization on the presence of bile in the gastrointestinal tract, cholestasis and biliary diversion in liver transplantation often necessitates the use of intravenous cyclosporine for the first postoperative days or weeks until more reliable oral absorption is established. Cystic fibrosis and diabetes are frequent comorbidities in heart-lung and kidney-pancreas transplant patients; decreased pancreatic exocrine secretions, diabetic gastroparesis, and gastrointestinal neuropathy associated with these diseases may contribute to poor systemic absorption of cyclosporine posttransplant. Decreased intestinal length and diarrhea can also impair the absorption of cyclosporine from Sandimmune in small bowel transplantation and in pediatric transplant patients in general, regardless of the transplanted organ. Neoral, a cyclosporine microemulsion, was developed in part to overcome these absorption problems by incorporating the drug in a microemulsion preconcentrate that immediately forms a microemulsion in situ upon contact with the aqueous gastrointestinal environment. Prior to its regulatory approval, a compassionate need program was conducted from 1993 to 1996 in advance of local licensing to assess the acute tolerability, safety and pharmacokinetics of Neoral. Enrolled in this open-label, international study were patients who needed very high doses of Sandimmune (.10 mg/kg per day) or who did not achieve a therapeutically acceptable trough concentration despite significant dose increases. They were converted on a milligram-tomilligram basis to Neoral with subsequent dose adjustments as necessary. Short-term safety and tolerability were assessed in all patients, and pharmacokinetic profiles were obtained in a subset. The purpose of this communication is to summarize the experience from this study across a wide variety of transplant indications in this particularly challenging group of cyclosporine malabsorbers on Sandimmune.

Bronchiolitis obliterans.

Hospital survival rates in experienced lung transplantation centers exceed 90%, but late survival for lung allograft recipients is clouded by bronchiolitis obliterans syndrome (BOS). Bronchiolitis obliterans is the characteristic pathological feature of this late syndrome of chronic lung allograft dysfunction, which is thought to represent chronic lung allograft rejection. BOS seems to affect all lung transplant recipients, including single, bilateral, and heart-lung transplantation patients. Although specific symptoms are lacking, patients typically experience worsening respiratory debilitation, with the characteristic physiological hallmark being airflow limitation, as evidenced by progressive decline in several spirometric parameters. Because the clinical and functional aspects of this syndrome are not always coexistent with the typical pathology, a staging and classification system was devised that allows for diagnosis of BOS even in the absence of bronchiolitis obliterans. Data from Stanford University, featuring very prolonged follow-up, have shown that actuarial freedom from OB is only 29% at 5 years post lung transplantation. Overwhelming experimental evidence suggest that OB is the result of an immune-mediated process, and therefore the usual treatment for this condition has been to increase the maintenance immunosuppression regimen, and to further augment immunosuppression using a variety of strategies. Most of these strategies have been effective in achieving some reduction in the rate of decline in graft function, although true "cure" of BOS has been rare. Re-transplantation has been the most aggressive therapeutic strategy for OB, but for a number of logistic reasons, is applicable for only a tiny minority of lung transplant recipients with OB.

Activation of Eosinophils and Fibroblasts Assessed by Eosinophil Cationic Protein and Hyaluronan in BAL: Association With Acute Rejection in Lung Transplant Recipients

Lung transplantation has become an accepted therapy for end-stage lung disease. Acute rejection of the transplanted hung still remains a major clinical problem since it decreases graft survival. Eosinophil cationic protein (ECP) from activated eosinophils, hyaluronan (HYA) from fibroblasts, and circulating intercellular adhesion molecule 1 (1CAM-1) have been associated with acute rejection in kidney and liver grafts. We investigated whether these, as well as other molecules, were increased in acute rejection of lung allografts. Serum and BAL fluid from 38 bronchoscopies performed in 9 single lung, 2 bilateral lung, and 4 heart-lung transplant patients were studied. Differential cell counts were made from the BAL fluid. Levels of ECP, myeloperoxidase (MPO), and HYA were used as indirect markers for activation of eosinophils, neutrophils, and fibroblasts, respectively. In addition, levels of circulating ICAM-1, cVCAM-1, and cE-selectin were analyzed. Twenty-two episodes with acute rejection were diagnosed. Of these, 7 were minimal, 13 were mild, and 2 were of moderate character. We found increased levels of ECP and HYA in BAL fluid during mild acute rejection of the allograft. Numbers of eosinophils were also increased. Activation of neutrophils or neutrophil numbers were not significantly increased. Levels of circulating ICAM-1, cVCAM-1, and cE-selectin did not differ between the groups. This retrospective study shows that measurements of ECP and HYA can give information about the inflammatory process present during acute rejection in patients who have undergone lung transplants. Analysis of cCAMS, however, appears to be of limited value as markers for acute rejection.

Monitoring progress after lung transplantation from home-patient adherence.

A paperless electronic spirometer/diary instrument has been employed in a home monitoring programme for lung and heart-lung transplant patients at the University of Minnesota. The monitoring programme is part of a long term study to develop a system which will detect the earliest signs of developing rejection or infection in the transplanted organs. It is based on patient daily self-measurements of standard spirometry, vital signs, and symptoms recorded at home and transmitted weekly to the study data center over the telephone using a modern built into the instrument. This report summarizes adherence behaviour for 41 subjects enrolled in the study over a 12 month period. The number of subjects from whom home data has been received each week was used to measure adherence at the subject level. The number of records received each week measured adherence at the daily recording level. A data record consists of a daily set of spirometry, vital signs, and symptom values from a given subject. Approximately 82% of subjects transmitted records each week, over the 52 week review period. There was an average of 4.5 records received each week from each subject. Transmitted records had missing vital sign or symptom items in less than 2% of cases, spirometry data was always present. This evaluation showed than lung transplant recipients are willing and able to use a home-monitoring instrument, and that basic spirometry, data entry, and data transmission can be performed satisfactorily.

The incidence of renal failure in one hundred consecutive heart-lung transplant recipients

Between March 1981 and November 1992, 100 heart-lung transplantations were performed at our institution. We report on the renal function in the 67 patients who survived a minimum of 6 months posttransplantation, and who were aged more than 10 years at the time of transplant. Renal function was determined by serial measurement of serum creatinine. Mean serum creatinine increased from 0.96 ± 0.03 mg/dL at baseline to 1.55 ± 0.07 mg/dL at 6 months posttransplantation, to 1.88 ± 0.11 mg/dL at the end of follow-up (mean follow-up, 50.0 months; range, 6 to 140 months). The decline in renal function was biphasic, with a rapid decrease in the first 6 months, followed by a much slower decline. Three patients developed end-stage renal failure. This compares with 14 of 416 cardiac transplant recipients at Stanford who developed end-stage renal failure over the same period. We conclude that in our large series at a single center the incidence of renal impairment and end-stage renal failure is low and similar between heart-lung and heart transplant patients.

Regulation of breathholding time and sensation after heart-lung transplantation.

To assess whether pulmonary vagal afferents affect the duration of breathholding, the associated respiratory distress and their dependence on lung volume, we studied seven heart-lung transplant (HLT) patients with chronic pulmonary denervation and seven matched control subjects. Voluntary breathholds were performed at 20% and 80% vital capacity (VC) after rebreathing a 7% CO2-93% O2 gas mixture. Time to breakpoint, oxygen saturation, and end-tidal PCO2 were measured. All subjects were questioned on their sensations during breathholding; in addition, quantitative assessment of the sensations was obtained using a visual analog scale (VAS) in the seven control subjects and four HLT subjects. Breathholding time was comparable in both groups at each lung volume but was invariably shorter (p < 0.0005) at 20% VC (mean +/- SD; HLT versus control subjects: 68 +/- 29 versus 79 +/- 29 s) than at 80% VC (corresponding values: 92 +/- 35 versus 103 +/- 30 s). Similar results were obtained after anesthesia of intact tracheal and upper airway receptors in five HLT subjects. Six subjects from each group spontaneously reported air hunger and found it easier to perform breathholding at 80% than at 20% VC. The VAS ratings generally showed a maximum score at breakpoint, which implies that the distress increased more rapidly at low than at high lung volume. We conclude that in the absence of vagal afferent innervation from the lungs: (1) the air hunger form of dyspnea is maintained; (2) the duration of breathholding is not substantially modified; and (3) breathholding time and sensations still vary as a function of lung volume.

Comparative quantitation of human cytomegalovirus DNA in blood leukocytes and plasma of transplant and AIDS patients

A new method for the quantitation of human cytomegalovirus (HCMV) DNA was used to determine the levels of viral DNA in parallel in 120 blood leukocyte (leukoDNAemia) and plasma (plasmaDNAemia) samples from 8 heart or heart-lung transplant patients and 17 AIDS patients with disseminated HCMV infection. PlasmaDNAemia was consistently associated with leukoDNAemia in both groups of patients. However, at least in the transplant patients, plasmaDNAemia was not necessarily associated with clinical symptoms, appearing later and disappearing earlier than leukoDNAemia during the course of infection. Quantitative mean levels of leukoDNAemia were mostly higher than those of plasmaDNAemia in both transplant and AIDS patients. However, in the absence of antiviral treatment, plasmaDNAemia levels were significantly higher in AIDS patients than in transplant recipients, whereas leukoDNAemia levels were not significantly different between the two groups of patients. A significant correlation was found between leukoDNAemia and plasmaDNAemia in AIDS patients, as well as in transplant recipients, although to a lesser degree. However, from a diagnostic standpoint, quantitative determination of plasmaDNAemia appears to represent a much less sensitive parameter than that of leukoDNAemia (or antigenemia) for monitoring HCMV infections and antiviral treatment.