Mortality In Lung Transplant Recipients Research Articles

Cytomegalovirus viremia associated with death or retransplantation in pediatric lung-transplant recipients.

Cytomegalovirus (CMV) infection is a frequent complication of lung transplantation. However, there is limited information regarding the incidence and sequelae of CMV infections in pediatric lung-transplant recipients. On the basis of case series suggesting that CMV infection was associated with excess morbidity and mortality in lung-transplant recipients, we hypothesize that CMV viremia increases the risk of bronchiolitis obliterans (BOS) or death and retransplantation in the first year following transplantation. A case-cohort study of pediatric primary lung-transplant recipients was performed. Univariate analysis was used to assess whether CMV viremia was associated with BOS or death and retransplantation within 1 year after transplantation. Patients at high risk for CMV infection received ganciclovir prophylaxis for 42 days posttransplantation. From July 1990 to November 2000, 194 pediatric patients received primary lung transplants. Twenty-three percent of patients developed CMV viremia. Eighty percent of CMV viremia episodes occurred before 120 days posttransplant. A first episode of CMV viremia was associated with retransplantation or death between days 90 and 365 (RR=4.1, 95% confidence interval [CI] 1.1-14.5) and was not associated with BOS (RR=1.3, 95% CI 0.5-3.3). CMV viremia in the first year after pediatric primary lung transplantation is associated with increased risk of death or retransplantation between 90 and 365 days posttransplant, when CMV prophylaxis has stopped. A phase II pilot trial is warranted to assess safety and short-term efficacy of increasing the duration of CMV prophylaxis from 42 to 120 days.

Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management

Background: Invasive aspergillosis is a serious opportunistic infection in lung transplant recipients. It has not been fully discerned whether there are differences in the characteristics, risk factors and outcome of Aspergillus infection in single as compared with bilateral lung transplant recipients. Methods: English-language articles identified by a M edline search through December 2000 and bibliographies were used as data sources to identify cases of Aspergillus infections in lung transplant recipients. The studies selected had to have provided a definition of invasive aspergillosis to distinguish colonization from infection. Results: The median incidence of Aspergillus infections in lung transplant recipients was 6.2%. In total, 58% (45 of 78) of the Aspergillus infections were tracheobronchitis or bronchial anastomotic infections, 32% (25 of 78) were invasive pulmonary, and 22% (25 of 78) were disseminated infections. Single lung transplant recipients with Aspergillus infections were significantly older ( p = 0.006), more likely to have had chronic obstructive pulmonary disease as an underlying illness ( p = 0.05), more likely to have developed Aspergillus infections later after transplantation ( p = 0.019), and tended to have a higher incidence of invasive aspergillosis ( p = 0.11) than all other lung transplant recipients. Overall mortality in lung transplant recipients with Aspergillus infections was 52%. Single lung transplant recipients ( p = 0.03), and patients with late-onset infections (occurring at least 3 months after transplantation ([ p = 0.045]) infections had significantly higher mortality. Conclusions: Single lung transplant recipients with Aspergillus infections had an overall greater morbidity and poorer outcome than other types of lung transplant recipients. Recognition of the unique characteristics of Aspergillus infections in single lung (vs bilateral or heart–lung) transplant recipients has implications relevant for the management of lung transplant recipients with aspergillosis.

Fungal infection in lung transplantation.

Fungal infection remains a significant cause of postoperative morbidity and mortality in lung transplant recipients. The lung recipient remains the only solid-organ allograft continuously open to the environment and to the myriad of fungal spores and pathogens. Many factors may predispose to fungal infection in these patients, including: preoperative chronic lung diseases and inherent palliative immunosuppression, intraoperative complications such as abnormalities in the bronchial anastomosis or lung injury, and postoperative complications such as enhanced immunosuppression for early rejection, graft dysfunction, concurrent viral and bacterial infections, and bronchiolitis obliterans syndrome. The risk factors and time course for fungal infection in lung transplant recipients parallel the observations in other solid-organ transplant recipients. Early fungal infections are related to surgical complications, while the period of 1-6 months reflect opportunistic, relapsed, or residual infections; fungal infections greater than 6 months and thereafter are usually associated with treatments for chronic rejection or bronchial airway mechanical abnormalities. The majority of fungal infections in lung transplant recipients involve Aspergillus species, followed by Candida, Pneumocystis, Cryptococcus, geographically-restricted agents, and newly emerging fungal pathogens. The identification of at-risk patients (preoperatively and postoperatively) is essential in implementing prophylaxis or preemptive management. Some anti-fungal strategies and future options for clinical research are discussed.

Tolerability, safety and efficacy of conventional amphotericin B administered by 24-hour infusion to lung transplant recipients.

Fungal infections cause serious morbidity and mortality in lung transplant recipients. Expensive lipid formulations of amphotericin B (AmB) are generally used because of fear of adverse effects due to concomitant cyclosporine A and other nephrotoxic drugs. However, a 24-hour dosing regimen of AmB may be well tolerated even in these patients. In an open pilot study 6 out of 94 lung transplant recipients with invasive or semi-invasive bronchopulmonary azole-resistant candidal infections (3 paraspilosis, 2 glabrata, 1 krusei) were treated for 40 (17-73) days by 24-hour continuous infusions of AmB 1 mg/kg. Additionally, patients received at least 1000 ml of 0.9% saline intravenously per day. Beside cyclosporine A at serum trough levels of 240 (195-273) microg/l, five patients additionally received aminoglycosides for at least 2 weeks, and 4 were treated with ganciclovir. Calculated creatinine clearance decreased from 57 (43-73) ml/min to a nadir of 35 (28-39) and recovered to 52 (33-60) after cessation of therapy. One patient needed temporary haemofiltration for 7 days after 30 days of AmB, most probably because of the use of contrast media in conjunction with furosemide and hypovolaemia. Besides three episodes of mild hypokalaemia no other side effects attributable to AmB were recorded. While in one case an asymptomatic candidal colonisation persisted for 10 months, the other 5 were cured from their infection. These preliminary data show that conventional AmB administered by 24-hour infusion is well tolerated, safe, and efficacious in lung transplant recipients receiving cyclosporine A and other nephrotoxic substances.

Tolerability, safety and efficacy of conventional amphotericin B administered by 24-hour infusion to lung transplant recipients.

Fungal infections cause serious morbidity and mortality in lung transplant recipients. Expensive lipid formulations of amphotericin B (AmB) are generally used because of fear of adverse effects due to concomitant cyclosporine A and other nephrotoxic drugs. However, a 24-hour dosing regimen of AmB may be well tolerated even in these patients. In an open pilot study 6 out of 94 lung transplant recipients with invasive or semi-invasive bronchopulmonary azole-resistant candidal infections (3 paraspilosis, 2 glabrata, 1 krusei) were treated for 40 (17-73) days by 24-hour continuous infusions of AmB 1 mg/kg. Additionally, patients received at least 1000 ml of 0.9% saline intravenously per day. Beside cyclosporine A at serum trough levels of 240 (195-273) microg/l, five patients additionally received aminoglycosides for at least 2 weeks, and 4 were treated with ganciclovir. Calculated creatinine clearance decreased from 57 (43-73) ml/min to a nadir of 35 (28-39) and recovered to 52 (33-60) after cessation of therapy. One patient needed temporary haemofiltration for 7 days after 30 days of AmB, most probably because of the use of contrast media in conjunction with furosemide and hypovolaemia. Besides three episodes of mild hypokalaemia no other side effects attributable to AmB were recorded. While in one case an asymptomatic candidal colonisation persisted for 10 months, the other 5 were cured from their infection. These preliminary data show that conventional AmB administered by 24-hour infusion is well tolerated, safe, and efficacious in lung transplant recipients receiving cyclosporine A and other nephrotoxic substances.

Use of cytomegalovirus immune globulin and ganciclovir for the prevention of cytomegalovirus disease in lung transplantation.

Cytomegalovirus (CMV) infection and disease continue to be significant causes of morbidity and mortality in lung transplant recipients. The potential benefits of CMV prophylaxis extend beyond prevention of the immediate CMV infection to potentially preventing CMV-associated complications, including superinfection due to Aspergillus bacteria, and other opportunistic infections, and bronchiolitis obliterans syndrome (BOS). Longer courses of prophylactic intravenous (IV) ganciclovir, sequential IV/oral therapy, addition of intravenous CMV immune globulin (CMV-IGIV), surveillance tests, and investigation of the role of hypogammaglobulinemia are a few of the strategies and issues being evaluated to improve CMV prophylaxis and, consequently, graft and patient survival.

Safety of aerosolized amphotericin B lipid complex in lung transplant recipients.

Fungal infections remain an important cause of morbidity and mortality in lung transplant recipients. Aerosolized amphotericin B lipid complex (ABLC) may be more efficacious than conventional amphotericin B in the prevention of fungal infections in animal models, but experience with aerosolized ABLC in humans is lacking. We conducted a prospective, noncomparative study designed to evaluate safety of aerosolized ABLC in lung or heart-lung transplant recipients. A total of 381 treatments were administered to 51 patients. Complete spirometry records were available for 335 treatments (69 in intubated patients, 266 in extubated patients). ABLC was subjectively well tolerated in 98% of patients. Pulmonary mechanics worsened by 20% or more posttreatment in less than 5% of all treatments. There were no significant adverse events related to study medication in any patient, and 1-year survival for all enrolled patients was 78%. Administration of nebulized ABLC is safe in the short-term and well-tolerated in lung transplant recipients. Additional prospective, randomized studies are needed to determine the efficacy of aerosolized ABLC alone or in conjunction with systemic therapies in the prevention of fungal infections in lung transplant recipients.

Epidemiology and management of infections after lung transplantation.

Lung transplantation has become an accepted treatment for end-stage pulmonary parenchymal and vascular diseases. Infections still are the most common cause of early and late morbidity and mortality in lung transplant recipients. Bacterial infections comprise approximately half of all infectious complications. Cytomegalovirus (CMV) infections and disease have become less frequent, because of prophylaxis with ganciclovir. Because CMV is also involved in the pathogenesis of obliterative bronchiolitis, the frequency of this infection may also reduce the occurrence of this main obstacle to successful lung transplantation. Invasive fungal infections remain a problem, but they have also decreased in frequency because of better control of risk factors such as CMV disease and preemptive antifungal therapy. Nonherpes respiratory viral infections have emerged as a serious problem. Their severity may be reduced by treatment with ribavirin. Meticulous postoperative surveillance, however, is still crucial for the management of lung transplant patients with respect to early detection and treatment of rejection and infection.

Enhanced cyclosporine-itraconazole interaction with cola in lung transplant recipients.

Invasive aspergillosis is a major cause of morbidity and mortality in lung transplant recipients (LTR), occurring in up to 15% of patients post-transplant. The 14% aspergillus incidence at the Cleveland Clinic Foundation prompted institution of universal prophylaxis with oral itraconazole (ICZ) in 1997. We report our experience with two protocols of ICZ administration in non-cystic fibrosis LTR and the interaction with cyclosporine (CSA). Group 1 patients (n=12) were administered ICZ capsules in a fasting or fed state, with or without a histamine-2 (H-2) receptor antagonist or proton pump inhibitor. Group 2 patients (n=12) received the same protocol as group I, but in a fed state with a carbonated beverage (cola) to increase acidity in the stomach to enhance absorption of ICZ. The ICZ dose was 200 mg/d, given as one daily dose. A historical control group (n=10) did not receive chemoprophylaxis with ICZ. CSA daily doses, dose intervals, concentration, cost, and random ICZ levels were documented over a 4-month period of time and compared using generalized estimating equations. The daily CSA mg/kg/d dose decreased over time in all three groups, but no differences were found between the three groups. The CSA dosing interval over time was significantly prolonged in group 2 compared to group 1 or the control group (p< or =0.003). Over time, there was no difference in CSA concentration between all groups. There was no difference in cost over time between the three groups; however, the mean cost of CSA therapy was significantly lower in group 2 compared to the control group (p=0.025). Group 2 administered ICZ with cola had greater random blood concentrations of ICZ (p=0.019). ICZ capsules administered in a fed state with a cola resulted in greater random levels of ICZ, a decrease in cost/d of CSA, and a prolongation of CSA dosing interval. Although daily CSA dosage trended lower in group 2, it did not reach statistical significance. We believe these changes in CSA dosing over time reflect increased absorption of ICZ and recommend verifying ICZ absorption with an itraconazole level, especially when CSA intervals are not prolonged.

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients.

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991-92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community-acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre-intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high-risk solid organ transplant patients.

Respiratory viral infections in lung transplant recipients: radiologic findings with clinical correlation.

To evaluate radiologic finding of respiratory viral infection in lung transplant recipients with clinical correlation. Over 5 years, 21 episodes of respiratory viral infection (parainfluenza [n = 9], respiratory syncytial virus [n = 8], adenovirus [n = 5], influenza [n = 2]) were diagnosed 6-727 days (mean, 270 days) after lung transplantation in 20 recipients. Chest radiographs, computed tomographic (CT) images, and clinical records were reviewed. Sixteen episodes of respiratory viral infection were diagnosed in patients with symptoms of lower respiratory tract infection or acute allograft dysfunction; five were diagnosed in asymptomatic patients. Chest radiographs were abnormal in 11 (52%) episodes; findings included heterogeneous or homogeneous opacities and masslike consolidation. All patients with radiographic abnormalities were symptomatic. Chest radiographs were unchanged from baseline in 10 (48%) episodes; in one, CT revealed findings not depicted at radiography. Adenoviral infection (n = 5) was typically symptomatic, was associated with new radiographic abnormalities, and was rapidly lethal (n = 4). Infection with parainfluenza and/or respiratory syncytial virus was commonly asymptomatic and was not associated with radiographic abnormalities; affected patients had good outcomes. Respiratory viral infections are important causes of morbidity and mortality in lung transplant recipients. Radiographic abnormalities in patients with respiratory viral infections were usually accompanied by symptoms of lower respiratory tract infection. Adenoviral infection was frequently accompanied by progressive pulmonary opacity and fatal outcome.

Current status of airway management in lung transplant patients

Airway complications are the cause of significant morbidity and mortality in lung transplant recipients. Problems with airway healing were the major obstruction to successful lung transplantation, but these problems have been largely overcome by improved management of the pulmonary donor, the bronchial anastomosis, and early postoperative care. Although the etiology of these complications appears to be related to the lack of reestablishment of the systemic bronchial blood supply, airway complications do not appear to be less frequent with the use of more complex procedures to provide direct bronchial artery revascularization, or with use of indirect techniques to provide neovascularization. Advances in endobronchial therapeutics successfully manage the majority of these airway complications.

Community Respiratory Viral Infection in Adult Lung Transplant Recipients

To define the epidemiology, clinical manifestations, and long-term complications of respiratory viral infections in adult lung transplant recipients. Retrospective review of the records of 122 adult lung transplant recipients over a 5-year period at one institution. Ten episodes of infection with respiratory syncytial virus, parainfluenza, influenza, or adenovirus were identified. All patients presented with symptoms of respiratory tract infection. Two patients died acutely and four patients subsequently had development of obliterative bronchiolitis (OB). These data suggest community respiratory viral infections cause significant morbidity and mortality in lung transplant recipients. Further prospective studies are warranted to clarify the relationship between respiratory viral infection and OB and to define the optimal therapy for these viral infections.

Perioperative management of patients undergoing lung transplantation

This review focuses on recent developments in the perioperative management of patients undergoing lung transplantation. Relevant current literature and the experience of the Munich Lung Transplant Group were taken into consideration. Recent advances include the use of inhalational nitric oxide for the treatment of early graft dysfunction and the use of aerosolized cyclosporine for the treatment of recurrent and steroid-resistant acute rejection. Opportunistic infections remain a major source of morbidity and mortality in lung transplant recipients.

Nutritional status, ICU duration and ICU mortality in lung transplant recipients

ObjectiveTo determine the relation of malnutrition and underlying diagnosis to the length of stay in the Intensive Care Unit (ICU) and to mortality after lung transplantation (LTX).DesignRetrospective ICU chart review.SettingCardiothoracic ICU in a University hospital.PatientsFifty-one consecutive patients who suffered from end-stage lung disease from. April 1992 to January 1994.InterventionsNone.Measurements and resultsThe median time spent in the ICU was 5 days (range, 2–123 days). Patients with an underlying diagnosis of obstructive lung disease had significantly shorter ICU stays (median 4 days; range, 2–28 days) than those with restrictive lung disease (median 7 days; range, 2–123 days) (p=0.005) or pulmonary hypertension (median 10 days; range, 2–38 days) (p=0.041). Significant differences in ICU duration were observed between patients after double lung transplantation (median 10 days; range, 2–123 days) and those after single lung transplantation (median 4 days; range, 2–36 days) (p=0.004). No statistically significant difference in ICU duration was found between patients with different nutritional statuses. In those patients who could not be discharged from the ICU before the 5th day, a body mass index (BMI) below the 25th percentile was a statistically significant risk factor for ICU mortality (p<0.05).ConclusionsWe conclude that the type of transplant procedure and the underlying diagnosis are important predictive indicators of ICU duration. A poor nutritional status (BMI below the 25th percentile) is a risk factor for ICU mortality in cases of patients who stay for 5 days or longer in the ICU.

Nutritional status, ICU duration and ICU mortality in lung transplant recipients.

To determine the relation of malnutrition and underlying diagnosis to the length of stay in the Intensive Care Unit (ICU) and to mortality after lung transplantation (LTX). Retrospective ICU chart review. Cardiothoracic ICU in a University hospital. Fifty-one consecutive patients who suffered from end-stage lung disease from April 1992 to January 1994. None. The median time spent in the ICU was 5 days (range, 2-123 days). Patients with an underlying diagnosis of obstructive lung disease had significantly shorter ICU stays (median 4 days; range, 2-28 days) than those with restrictive lung disease (median 7 days; range, 2-123 days) (p = 0.005) or pulmonary hypertension (median 10 days' range, 2-38 days) (p = 0.041). Significant differences in ICU duration were observed between patients after double lung transplantation (median 10 days; range, 2-123 days) and those after single lung transplantation (median 4 days; range, 2-36 days) (p = 0.004). No statistically significant difference in ICU duration was found between patients with different nutritional statuses. In those patients who could not be discharged from the ICU before the 5th day, a body mass index (BMI) below the 25th percentile was a statistically significant risk factor for ICU mortality (p = 0.05). We conclude that the type of transplant procedure and the underlying diagnosis are important predictive indicators of ICU duration. A poor nutritional status (BMI below the 25th percentile) is a risk factor for ICU mortality in cases of patients who stay for 5 days or longer in the ICU.

LUNG TRANSPLANTATION IN CHRONIC AIRFLOW LIMITATION

Lung transplantation is an option for appropriately selected patients with end-stage chronic airflow limitation. The functional results have been excellent after single or bilateral lung transplantation, and the medium-term survival results have been good. Obliterative bronchiolitis, however, thought to be a manifestation of chronic rejection, occurs in approximately 40% of recipients, and it is the major cause of late morbidity and mortality in lung transplant recipients.