Ilana Bakal

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.

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.

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.

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.

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.

Multidrug-resistant Klebsiella pneumoniae acquisition in lung transplant recipients.

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–β lactamases K. pneumoniae (ESBL‐KP).

The role of fiberoptic bronchoscopy evaluating transplant recipients with suspected pulmonary infections: analysis of 168 cases in a multi-organ transplantation center

ULMONARY INFECTIOUS complications are common in patients after solid organ transplantation (SOT) or bone marrow transplantation (BMT) and are responsible for significant morbidity and mortality. Early diagnosis of infectious complications is extremely important for the outcome of transplant recipients 1‐3 The purpose of this study was to examine the role of fiberoptic bronchoscopy (FOB) in transplant recipients with suspected pulmonary infections. METHODS The study was conducted at the Institute of Pulmonary Medicine. Rabin Medical Center, Beilinson Campus (a tertiary-care university hospital). We retrospectively examined data of patients posttransplantation who required FOB from May 5, 1999 until May 2002. Indications for FOB were suspected pulmonary infection by either abnormal chest X-ray or respiratory symptoms. Lung transplant recipients with surveillance bronchoscopies were excluded from the study. Patients underwent bronchoalveolar lavage (BAL); specimens were analyzed as bacteriology, virology, fungal, and mycobacterial cultures. In 65% of cases, transbronchial biopsies (TBBs) were done; specimens were sent to pathological examination as well as silver and cytomegalovirus (CMV)-specific stains.

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.

Does side matter? Effect of single lung transplant laterality on outcomes.

BACKGROUND Previous works have suggested that recipients of left single lung transplant (SLT) have a worse outcome than those receiving right SLT. We evaluated the effect of SLT laterality on outcomes. METHODS We performed a retrospective study of SLT recipients followed up at our center. One hundred and nineteen patients were reviewed (53 left SLT, 66 right SLT). We extracted data on lung function, exercise capacity, relative graft perfusion, airway complications, acute rejection episodes, infections and mortality. RESULTS There was no significant difference between right and left lung recipients with regard to baseline demographic and physiological characteristics. Lung function, exercise capacity and relative graft perfusion improved in both groups following transplantation. We observed a higher graft perfusion in right-sided grafts compared to left ( P = 0.048). There was no significant difference between the two groups in physiological outcomes, rejection or infection episodes, the presence of chronic rejection or mortality. We observed a statistically higher need for bronchial stent insertion during early follow-up amongst the left lung recipients ( P = 0.022). CONCLUSIONS Both right and left lungs are equally suitable for transplantation. The left-sided bronchial anastomosis may be more vulnerable to complications.