A single center Israeli experience in pregnancy post lung transplantation: Feasibility of successful two or more full-term pregnancies in individual lung transplant recipients.

INTRODUCTION: Female lung transplant recipients (LTRs) of reproductive age are increasingly considering pregnancy due to advances in post-transplant management and improved survival. We report our experience with pregnancy in LTRs, with an emphasis on two or more successful full-term pregnancies in individual transplant recipients. METHODS: We conducted a retrospective analysis of pregnancies in LTRs at our transplant center and collected maternal and fetal outcomes. RESULTS: In our patient cohort, eight female LTRs conceived a total of 17 pregnancies, resulting in 13 newborns, 12 at full term, and 11 with a birth weight > 2.5 kg. Three of the LTRs had two or more successful full-term pregnancies. LTRs required a significant tacrolimus dose increase to maintain target trough levels during pregnancy. Six recipients are currently clinically stable and active, three with lung function comparable to pre-pregnancy values, and three with evidence of chronic lung allograft dysfunction (CLAD), but stable lung function. Two of the eight LTRs died subsequent to childbirth secondary to chronic respiratory failure due to CLAD, at a mean of 11 years post-transplantation and a mean of 4.5 years after childbirth. CONCLUSION: Pregnancy following lung transplantation is feasible and can be achieved with acceptable maternal and newborn outcomes. Importantly, LTRs can successfully have two or more full-term pregnancies.

Renal function preservation with the mTOR inhibitor, Everolimus, after lung transplant.

Chronic kidney disease (CKD) is a common complication of calcineurin inhibitors (CNIs) in solid organ transplantation. Previous data suggest that the use of everolimus as an immunosuppressant drug leads to improvement in renal function. The aim of our study was to establish the effect of everolimus in combination with lower doses of CNIs on renal function among lung transplant recipients. Data regarding renal function and pulmonary function were collected from 41 lung transplanted patients in whom treatment was converted to a combination of everolimus with lower doses of CNIs. Patients transferred to everolimus and low dose CNIs showed an improvement in renal function. Patients who continued treatment with everolimus showed improvement in renal function, as opposed to patients who discontinued the treatment. Subjects without proteinuria at baseline showed a better improvement compared with subjects with proteinuria. The incidence of graft rejection did not increase. We concluded that a protocol that includes everolimus and lower doses of CNIs is effective for preserving renal function in lung transplant recipients with CKD. We also believe that an early implementation of everolimus, before proteinuria occurs or creatinine clearance is reduced, could lead to better outcomes.

Immunogenicity of a Third Dose of BNT162b2 Vaccine among Lung Transplant Recipients-A Prospective Cohort Study.

Two doses of mRNA SARS-CoV-2 vaccines elicit an attenuated humoral immune response among immunocompromised patients. Our study aimed to assess the immunogenicity of a third dose of the BNT162b2 vaccine among lung transplant recipients (LTRs). We prospectively evaluated the humoral response by measuring anti-spike SARS-CoV-2 and neutralizing antibodies in 139 vaccinated LTRs ~4-6 weeks following the third vaccine dose. The t-cell response was evaluated by IFNγ assay. The primary outcome was the seropositivity rate following the third vaccine dose. Secondary outcomes included: positive neutralizing antibody and cellular immune response rate, adverse events, and COVID-19 infections. Results were compared to a control group of 41 healthcare workers. Among LTRs, 42.4% had a seropositive antibody titer, and 17.2% had a positive t-cell response. Seropositivity was associated with younger age (t = 3.736, p < 0.001), higher GFR (t = 2.355, p = 0.011), and longer duration from transplantation (t = -1.992, p = 0.024). Antibody titer positively correlated with neutralizing antibodies (r = 0.955, p < 0.001). The current study may suggest the enhancement of immunogenicity by using booster doses. Since monoclonal antibodies have limited effectiveness against prevalent sub-variants and LTRs are prone to severe COVID-19 morbidity, vaccination remains crucial for this vulnerable population.

The impact of fluoroquinolone resistance of Gram-negative bacteria in respiratory secretions on the outcome of lung transplant (non-cystic fibrosis) recipients.

Bacterial airway colonization is frequent among lung transplant recipients. These patients are often treated with antibiotics, which may lead to selection of resistant bacteria. The purpose of this study was to assess whether antibiotic treatment causes acquisition of quinolone-resistant Gram-negative bacteria (QR-GNB), and the effect of such colonization on mortality and on lung rejection. We retrospectively examined data from non-cystic fibrosis, non-bronchiectases lung transplant recipients for antibiotic treatment, GNB in respiratory secretions, bronchiolitis obliterans syndrome (BOS), and mortality. Of 126 patients included, 86 patients had QR-GNB, 22 had quinolone-sensitive bacteria (QS-GNB), and 17 had no growth. Median antibiotic exposure, defined as the fraction of days with antibiotic treatment, was 2.8% in patients without growth, 11.1% in patients with QS-GNB (p=0.012), and 26% in patients with QR-GNB (p<0.0001). Age-adjusted mortality hazard ratio was 9.2 (95% CI 1.272-78.9) for patients with QR-GNB compared with QS-GNB. Age-adjusted hazard ratios for BOS was 3.7 (95% CI 1.33-10.3) for QR-GNB compared with QS-GNB. We found a positive correlation between antibiotic treatment and emergence of QR-GNB. Airway colonization with QR-GNB was significantly associated with mortality and with BOS. Further research is needed to determine whether a change in antibiotic subscription policy is required.

Multidrug-resistant Klebsiella pneumoniae acquisition in lung transplant recipients.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a pathogen that emerged in the late twentieth century and was associated with significant morbidity and mortality. We report for the first time the outcomes of lung transplant recipients infected with CRKP or extended spectrum-ß lactamases K. pneumoniae (ESBL-KP). METHODS: Retrospective review of 136 lung transplant recipients who underwent transplantation between 2004 and 2007 in Rabin Medical Center, Israel. MAIN RESULTS: There were 52 episodes of positive cultures for K. pneumoniae (KP) in 136 recipients - of them 11 (8.1%) with CRKP, 12 (8.8%) with ESBL-KP, and 29 (21.3%) with carbapenem-sensitive ESBL-negative KP. Isolation of CRKP/ESBL-KP was associated with death in the cohort (p < 0.0001) as well as recipients' age at transplantation (p < 0.005). Time-dependent age-adjusted CRKP or ESBL-KP acquisition was an independent factor for death in patients after lung transplant, compared to patients without KP isolation or carbapenem-sensitive ESBL-negative KP (p < 0.0001). CONCLUSION: CRKP and KP-ESBL acquisition was associated with reduced survival among lung transplant recipients.

Development of malignancy following lung transplantation.

BACKGROUND: A substantial excess risk of certain malignancies has been demonstrated after organ transplantation. Immunosuppressive treatment to prevent allograft rejection is probably the main cause. METHODS: We reviewed retrospectively all medical records of the 121 patients that underwent lung and heart-lung transplantation from 1992 until December 2004. We compared our results to the International Society for Heart and Lung Transplantation (ISHLT) registry data and previous reports concerning lung transplantation. RESULTS: 102 of the 121 patients survived for 3 months to 12 years. Malignancies developed in 16 patients, as follows: lymphoproliferative disorder in 3, Kaposi's sarcoma in 3, other nonmelanoma skin cancers in 7, urinary bladder transitional cel carcinoma in 3, and colon cancer in 1. Patients with malignancy were older at transplantation than those without (mean +/- SD, 54.1+/-7.8 vs. 49.5+/-14.2 years; P=0.03). Fourteen had smoked in the past. Four died of bronchiolitis obliterans. In comparison with the ISHLT, we observed more skin cancer and transitional cell carcinoma (12.8% vs. 0.7% and 3.8% vs. 0.03%, respectively) and a similar frequency of posttransplant lymphoproliferative disease. CONCLUSIONS: We conclude that malignancy is a common complication after lung transplantation. In Israel, which is sunny most of the year, skin cancers and transitional cell carcinoma of bladder are more common. Modification of the immunosuppression late posttransplantation may reduce the risk of cancer. Patients should also be counseled to avoid sun exposure and ensure adequate hydration.

Lung transplantation in patients with cystic fibrosis: the Israeli experience.

BACKGROUND: Lung transplantation is a well-established therapeutic option for end-stage lung disease in cystic fibrosis. Although it confers a clear survival advantage, outcome differs among centers according to local experience, patient selection, transplantation procedure, and postoperative care. OBJECTIVES: To evaluate the national Israeli experience with lung transplantation in patients with CF. METHODS: We reviewed the medical charts of all CF patients who underwent lung transplantation between January 1996 and June 2005 at the two Israeli centers that perform this procedure. RESULTS: Eighteen transplantations were performed in 17 patients. Mean patient age at transplantation was 25.3 +/- 9.1 years, and mean duration of follow-up in survivors (n=14) was 37.2 months (range 1-113 months). The actuarial survival rate was 88% at 1 year and 74% at 5 years. Pulmonary function, expressed as percent of predicted normal forced expiratory volume in 1 sec, improved from 22.4 +/- 8.1% to 76 +/- 16.8% at one year after transplantation. Bronchiolitis obliterans syndrome was diagnosed in 5 patients (29%), of whom 2 died and 2 are currently candidates for retransplantation. Median time to onset of BOS was 34.2 months (range 17-64 months). CONCLUSION: In Israel, the early and intermediate-term results of lung transplantation for cystic fibrosis are encouraging. BOS remains a major complication that threatens long-term outcome.

The effect of donor age on survival after lung transplantation.

BACKGROUND: Historically, donor age above 55 years has been considered to be a relative contraindication for organ transplantation. The shortage of organs for transplantation has led to the expansion of the donor pool by accepling older donors. OBJECTIVES: To compare the 1 year follow-up in patients after lung transplantation from older donors (> 50 years old) and in patients after transplantation from younger donors (< or = 50 years). METHODS: The study group comprised all adult patients who underwent lung transplantation at the Rabin Medical Center between May 1997 and August 2001. Donors were classified into two groups according to their age: < or = 50 years (n = 20) and > 50 years (n = 9). Survival, number and total days of hospitalization, development of bronchiolitis obliterans syndrome, and pulmonary function tests, were examined 1 year after transplantation. RESULTS: We performed 29 lung transplantations in our center during the observed period. Donor age had no statistically significant impact on 1 year survival after lung transplantation. There was no statistically significant effect on lung function parameters, the incidence of hospitalization or the incidence of bronchiolitis obliterans between both donor age groups at 1 year after transplantation. CONCLUSIONS: Donor age did not influence survival or important secondary end-points 1 year after lung transplantation By liberalizing donor criteria of age up to 65 years, we can expand the donor pool, while assessing other possible mechanisms to increase donor availability.

[Lung and heart-lung transplantation in Rabin medical center: early experience with 70 cases].

Lung transplantation is a relatively new field in solid organ transplantation. We present our early experience with the first 70 cases at the Rabin Medical Center during the years 1997-2003. Forty seven patients underwent single lung, eight double lung and eight heart-lung transplantations. The patients treated included 49 men and 21 women aged 5-66 years. There were 26 cases with emphysema COPD. 30 patients with pulmonary fibrosis. 5 patients with pulmonary hypertension/Eisenmenger and 9 patients with cystic fibrosis and bronchiectasis. Although early results (1997-1999) showed 1 and 3 year survival of only 50%, in the last 3 years (2000-2003), survival reached 84% and 82% at 1 and 3 years respectively. Improvement in the success rate is due to better patient selection, new immunosuppressive regimen and, most importantly, excellent teamwork. We conclude that lung transplantation is a viable option for selected patients with end-stage lung disease.

Posttransplantation lymphoproliferative disorder in lung transplant recipients: a 15-year single institution experience.

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication after solid-organ transplantation. Historically, most cases of PTLD among lung transplant recipients occurred within the first year from transplantation and were associated with Epstein-Barr virus (EBV) infection. However, there are increasing reports on a late-onset form of PTLD. METHODS: We reviewed all charts of patients undergoing either lung or heart-lung transplantation in a tertiary transplantation center between the years 1997 and 2012 and compared clinical and pathologic parameters between early- and late-onset PTLD. RESULTS: Ten patients with PTLD were identified. Median (range) time from transplantation to PTLD diagnosis was 41 (4-128) months. Three patients developed early PTLD. All were pretransplantation EBV seronegative and asymptomatic when diagnosed during surveillance chest imaging. In contrast, the seven patients with late-onset PTLD were all EBV seropositive before transplantation and were symptomatic at diagnosis. Although early-onset PTLD uniformly involved the transplanted lung, this was relatively rare in late-onset PTLD (3 of 3 vs. 1 of 7). All patients were initially treated with reduction of immunosuppression, with at least one additional treatment modality used, mainly chemoimmunotherapy. Eight patients attained complete remission. With a median follow-up of 17 months, 8 patients died, mainly from treatment-related causes rather than disease progression. CONCLUSION: Our cohort of lung transplant recipients demonstrates a trend of late-onset PTLD with the majority of patients who died of treatment-related causes rather than disease progression. Therefore, substantial efforts should be focused on treatment-related mortality reduction.

Outcome of lung transplant recipients requiring readmission to the intensive care unit.

BACKGROUND: Lung transplantation is the recognized therapy for end-stage respiratory failure. Many serious medical complications have been described occurring from months to years after lung transplantation, often necessitating admission to an intensive care unit (ICU). We examined the factors associated with death. METHODS: All consecutive lung transplant recipients who were readmitted to the ICU > 30 days after transplantation from 2000 to 2009 were included in this retrospective study. Data were collected regarding demographic parameters, ICU stay, and outcome. RESULTS: During the study period, 40 patients were admitted to the ICU. The main pre-transplant diagnosis was idiopathic pulmonary fibrosis, followed by chronic obstructive pulmonary disease. Most patients (93%) required mechanical ventilation during their ICU stay. The main reason for ICU admission was septic shock in 22 patients (55%). An organism was isolated from 19 of these patients; in 11 patients, the organism was multidrug resistant. The ICU mortality was 62.5%. Non-survivors were characterized by more frequent readmissions to hospital (p = 0.02), a higher admission Sequential Organ Failure Assessment score (p = 0.02), an admission diagnosis of sepsis (87.5% vs 37.5% for all other diagnoses, p < 0.001), and a requirement for mechanical ventilation (p = 0.02). The incidence of bronchiolitis obliterans syndrome was also significantly higher in non-survivors (p = 0.02). CONCLUSIONS: Severe sepsis remains the most important factor associated with a poor outcome after readmission to ICU. New strategies are required to alter the course of this common complication of lung transplantation.

Lung cancer in lung transplant recipients: experience of a tertiary hospital and literature review.

BACKGROUND: Lung transplantation is a viable therapy for patients with end-stage lung disease and is being increasingly performed worldwide. The incidence of lung cancer after lung transplantation has increased concomitantly, although data are still sparse. METHODS: The computerized medical records of the Pulmonary Institute of a tertiary care medical center were searched for patients who underwent lung transplantation from 1997 to 2009 and acquired lung cancer postoperatively. The prevalence, potential contributing factors, and outcome of bronchogenic cancer were determined, and the medical literature was reviewed. RESULTS: Bronchogenic cancer developed in 7 of the 290 lung transplant recipients (2.4%). All had received a single lung transplant and in most cases, the cancer developed in the native lung. These findings were similar to reports in the literature. The indication for transplantation was chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis/interstitial lung disease. All had a history of smoking. The average interval from transplantation to development of lung cancer was 5 years (range 1-9). Five patients had stage 4 cancer at diagnosis and 2 had stage 1. Six patients died from 10 days to 1 year after diagnosis. CONCLUSION: Lung transplantation is associated with a relatively high prevalence of bronchogenic cancer, particularly in the native lung, in patients with primary chronic obstructive pulmonary disease/idiopathic pulmonary fibrosis, and a history of smoking. The cancer is usually diagnosed at an advanced stage with poor outcome. Efforts to improve screening are recommended, as aggressive management and treatment may be beneficial for earlier stage disease.

Pandemic influenza (H1N1): impact on lung transplant recipients and candidates.

BACKGROUND: The year 2009 was notable for the outbreak of a novel strain of influenza A (H1N1). We report the outcomes of H1N1 infection in a large cohort of lung transplant (LTx) recipients and candidates. METHODS: This was a retrospective review of 22 suspected cases of H1N1 influenza screened using real-time polymerase chain reaction from nasal secretions. There were 15 confirmed cases (10 LTx recipients, 5 LTx candidates). RESULTS: All patients were treated with oseltamivir at the time of the first clinical assessment. In the LTx recipients group, 7 of the 10 confirmed cases were treated at home with oseltamivir alone. Three patients were admitted with complications (2 pneumonia, 1 acute rejection). Two patients required mechanical ventilation. Two patients had prolonged viral shedding. No deaths occurred among the LTx recipients. In the 5 LTx candidates with confirmed H1N1, 2 deaths occurred from pneumonia and acute respiratory distress syndrome. CONCLUSIONS: Influenza H1N1 had a significant complication rate amongst LTx recipients and a high mortality rate amongst LTx candidates.

Herpes zoster after lung transplantation: incidence, timing, and outcome.

BACKGROUND: Although herpes zoster is a common complication of lung transplantation, the epidemiologic data are limited. The aims of the present study were to determine the incidence and clinical manifestations of herpes zoster in a large cohort of lung transplant recipients and to identify risk factors associated with its development. METHODS: The files of all adult patients who underwent lung transplantation at a major tertiary medical center from January 2001 to December 2007 were reviewed. Data were extracted on background, transplant-related, and posttransplantation factors. The occurrence and clinical characteristics of all episodes of herpes zoster were recorded. RESULTS: Of the 198 lung transplant recipients, 23 had a herpes zoster infection, of whom 18 had herpes in a single dermatome. Disseminated cutaneous infection was documented in 4 cases (17%) and visceral involvement in 1. The median duration of follow-up was 34 months (range, 1 to 85 months). There were no recurrent infections. Postherpetic neuralgia was detected in 26% of cases. Antiviral prophylaxis, primarily for cytomegalovirus, was effective (during treatment) against herpes zoster. The incidence of herpes zoster was higher in patients treated with rabbit antithymocyte globulin. CONCLUSIONS: The occurrence of herpes zoster peaks between 12 and 36 months after lung transplantation. Additional immunosuppression may increase the risk. Further studies on preventive strategies against herpes zoster in this population are warranted.

Surfactant as salvage therapy in life threatening primary graft dysfunction in lung transplantation.

OBJECTIVE: Impaired surfactant activity may contribute to primary graft dysfunction after lung transplantation. We assessed the role of surfactant treatment in lung transplant recipients with severe life threatening primary lung graft dysfunction. PATIENTS AND METHODS: Five patients after lung transplantation: 4 after single-lung transplantation, for emphysema (n=3) or idiopathic pulmonary fibrosis (n=1), and 1 patient after double-lung transplantation for cystic fibrosis. All had severe life threatening primary graft dysfunction that failed to respond to conventional measures. Treatment consisted of bronchoscopic instillation of mammalian surfactant, 20-90cc, at 3 (n=1) or 7 days (n=4) after transplantation. RESULTS: There was a significant improvement in the ratio of partial arterial oxygen tension (PaO(2)) to fractional concentration of oxygen in inspired gas (FIO(2)), from a mean of 98.8+/-21.7 to 236.8+/-52.3 mmHg (p=0.0006), within hours of treatment. All were eventually discharged home and showed a satisfactory FEV(1) (44-67% predicted) at the 6-month follow-up. All patients were still alive 6 months or more after transplantation. CONCLUSION: Surfactant treatment improves oxygenation and may be life saving in patients with primary lung graft dysfunction.

Graft side-mismatching for single-lung transplantation does not affect outcomes: role of the pre-operative quantitative lung perfusion scan.

BACKGROUND: There are concerns about which lung to explant during single-lung transplantation (SLT). Traditionally, a quantitative lung perfusion scan (QLPS) is performed, and the better-perfused lung is retained. Occasionally, there is transplantation with graft "side-mismatching," where the less-well-perfused lung is retained. We performed a retrospective study of patients undergoing SLT at our institution to evaluate the effects of side-mismatching (according to the QLPS) on graft performance and outcome. METHODS: We defined graft side-mismatching with a prospectively designed formula using baseline QLPS, and defined patients as either side-matched or side-mismatched. Data on mortality, requirement for cardiopulmonary bypass, relative graft perfusion, lung function and exercise capacity were obtained from institutional databases and patients' files. RESULTS: In a cohort of 114 patients, we defined 97 as having received a side-matched SLT and 17 as having received a side-mismatched graft. After lung transplantation, forced expiratory volume in 1 second (FEV(1)) and exercise capacity improved in both groups (p < 0.001). Patients with mismatched lungs had significantly higher relative graft perfusion post-operatively (p = 0.0012). There was no significant difference between the two groups (matched vs mismatched) in mortality, physiologic parameters and need for cardiopulmonary bypass. CONCLUSIONS: There is no apparent risk to the patient when a side-mismatched lung graft is transplanted. We conclude that side-mismatched lung transplantation appears to be feasible when required.

Endobronchial metastases from colon cancer without liver metastases: report of eight cases.

PURPOSE: The liver is the most common site of hematogenous spread from colon tumors. Pulmonary metastases from colon cancer result, in most of the cases, from hepatic metastases. METHODS: We describe eight cases of colorectal cancers in which endobronchial metastases have been developed without any evidence of liver involvement. RESULTS: Median age was 62 years old. In most of the patients, the primary cancer developed in the left side. The median time from colorectal presentation to pulmonary onset was four years. Dyspnea was the major symptom in all cases. Pulmonary involvement included endobronchial metastasis in all cases. CT scan of the chest showed bilateral, diffuse, large, nodular infiltrates without lymph nodes enlargement and without pleural effusion. Endobronchial therapy brought symptomatic relief in all cases; however, two-year follow-up showed only 50 percent survival rate. CONCLUSIONS: Endobronchial metastasis should be suspected in patients with colon cancer with respiratory symptoms, even without known liver metastasis. To the best of our knowledge, such a case series has not been published yet.

Lamivudine prophylaxis for hepatitis B virus infection after lung transplantation.

BACKGROUND: Several reports have shown the efficacy of prophylactic lamivudine treatment for hepatitis B virus (HBV) infection in liver and renal transplantations. No data are available, however, after lung transplantation. We report our experience with prophylactic lamivudine treatment in lung transplant recipients with HBV infection or when the donor was HBc antibody positive. METHODS: All our 120 lung transplant recipients and their donors were routinely screened for HBV markers. All recipients who tested positive for hepatitis B surface antigen and negative for HBV-DNA, or had organs from donors who tested positive for hepatitis B core antibody, were treated prophylactically with lamivudine for 12 months after lung transplantation. Patients whose liver functions became abnormal during follow-up were tested for HBV serology and HBV-DNA. RESULTS: Eleven of 120 lung transplant recipients (9.2%) were treated with prophylaxis lamivudine. Four recipients were hepatitis B surface antigen positive, and 7 recipients received organs from donors positive for HBc antibodies. Median follow-up after treatment was 24 months. All patients had normal alanine transaminase and undetectable levels of HBV-DNA before treatment. No side effects of lamivudine therapy were reported by any of the patients. Reactivation with alanine transaminase elevation and high HBV-DNA levels occurred in 2 patients. Both of them were recipients positive for hepatitis B surface antigen. In the first patient, lamivudine-resistant strain was detected and adefovir dipivoxil was started. In the other, reactivation developed 2 months after the end of lamivudine treatment. Lamivudine treatment was resumed, with rapid normalization of the HBV-DNA. CONCLUSIONS: Use of lamivudine is considered safe for suppressing HBV infection after lung transplantation.

Long-term azithromycin use for treatment of bronchiolitis obliterans syndrome in lung transplant recipients.

Short-term improvement in lung function was observed in 5 of 6 lung transplant recipients with bronchiolitis obliterans syndrome (BOS) who were treated with oral azithromycin. We assessed the long-term effect (mean duration 10 months) of treatment with oral azithromycin in 11 lung transplant recipients with BOS. Mean forced expiratory volume in 1 second (FEV1) was 40 +/- 9% at initiation of azithromycin treatment, 39 +/- 10% after 1 month, 39 +/- 12% after 4 months, 38 +/- 10% after 7 months and 38 +/- 10% after 10 months, respectively (statistically non-significant for all data). We conclude that long-term administration with oral azithromycin does not reverse BOS in lung transplant recipients, but may slow progression of the disease.

Itraconazole prophylaxis in lung transplant recipients receiving tacrolimus (FK 506): efficacy and drug interaction.

BACKGROUND: Itraconazole is often given for fungal prophylaxis to lung transplant recipients after transplantation. The aim of this study was to determine the extent of interaction between tacrolimus and itraconazole in lung transplant recipients and the efficacy of itraconazole prophylaxis. METHODS: The study group included 40 lung transplant recipients followed for at least 12 months. All received prophylactic itraconazole, 200 mg twice a day, for the first 6 months after transplantation. Tacrolimus levels and dosage requirements were compared during and after itraconazole therapy. Rejection rate, fungal infection rate, and renal function were assessed. The mean cost per daily treatment of the itraconazole/tacrolimus combination and tacrolimus alone was calculated. RESULTS: The mean tacrolimus dose during itraconazole treatment was 3.26 +/- 2.1 mg/day compared with 5.74 +/- 2.9 mg/day after itraconazole was stopped (p < 0.0001) for a mean total daily dose elevation of tacrolimus of 76%. When the cost of itraconazole was taken into account, the average total daily cost of the combined treatment was US5.86 dollars less than the treatment with tacrolimus alone. No differences in the rejection or fungal infection rate, or in renal toxicity, were observed between the periods with and without itraconazole treatment, although less positive fungal isolates were identified during itraconazole therapy. CONCLUSION: Prophylaxis therapy with itraconazole is highly effective. Itraconazole reduces the dose of tacrolimus and therefore lowers the cost of therapy without causing an increase in rejection rate and with renal function preservation.