Prashant N. Chhajed

Prospective analysis of 1,235 transbronchial lung biopsies in lung transplant recipients

OBJECTIVEnFiber-optic bronchoscopy with multiple transbronchial lung biopsies (TBB) is the gold standard of evaluation of the pulmonary allograft post-lung transplantation (LT). However, controversy exists regarding the need for surveillance procedures and number of biopsy specimens required for satisfactory yield. The potential morbidity in obtaining multiple TBB specimens remains poorly described. We report the largest series of TBB in LT recipients to date, highlighting the occurrence of acute rejection and infection for surveillance and diagnostic procedures. The safety of TBB is analyzed and a biopsy schedule proposed.nnnMETHODSnProspective analysis of 1,235 TBB in 230 LT recipients performed at St Vincents Hospital from January 1995 to June 2000.nnnRESULTSnEight hundred thirty-six (67.7%) TBB were performed as surveillance and 399 (32.3%) for a clinical indication. No significant acute rejection (AR) or infection was disclosed in 53.3% of procedures. The Lung Rejection Study Group requirement of at least five pieces of evaluable lung parenchyma was achieved in 98.2% of procedures. The average number of evaluable fragments per procedure was 6.4, whereas only 3 TBB (0.24%) contained no lung parenchyma and 44 (3.6%) no bronchial wall. Histologic features of AR, lymphocytic bronchiolitis or infection were found in 18.9% of surveillance and 86.4% of clinical TBBs. The yield of surveillance procedures between 4 and 12 months was just 1.1% for cytomegalovirus and 6.1% for AR. The overall complication rate was 6.35% with no deaths recorded.nnnCONCLUSIONnTaking 10 to 12 TBB specimens has a high diagnostic yield and rarely fails to provide adequate tissue. The role of surveillance procedures post-lung transplantation remains controversial.

Anti-viral prophylaxis reduces the incidence of lymphoproliferative disease in lung transplant recipients

BACKGROUNDnPost-transplant lymphoproliferative disease (PTLD) is a serious, often fatal complication after solid organ transplantation. Primary Epstein-Barr virus (EBV) infection is the major risk factor for PTLD after lung transplantation, with 30% to 50% of EBV-naive patients who seroconvert and are diagnosed with PTLD.nnnMETHODnIn this study, we analyzed the incidence of PTLD in lung and heart-lung transplant recipients before 1996 (historic group) and then compared the impact of long-term anti-viral prophylaxis on the development of PTLD in EBV-seronegative recipients from January 1996 to December 2000 (post-1996 group). Routine induction therapy was not given after 1995. Patients not surviving 30 days, 25 of 341 (7.3%), were excluded.nnnRESULTSnHistoric group: PTLD developed in 7 of 167 (4.2%) patients, at a mean of 394 +/- 278 (95-885) days. The mortality was 87.5% at a mean follow-up of 186 +/- 207 (17-520) days after diagnosis. Post-1996 group: Eighteen of 149 (12.3%) patients were EBV seronegative at the time of transplantation, and of these 15 (83%) began receiving continuous anti-viral prophylaxis: acyclovir or valacyclovir or ganciclovir from January 1996. None of the EBV-seronegative recipients receiving continuous anti-viral prophylaxis were diagnosed with PTLD; however, 1 of 3 (33%) of the EBV-seronegative recipients who did not receive anti-viral prophylaxis were diagnosed with PTLD. In the EBV-seronegative recipients, no deaths had been caused by PTLD at a mean follow-up of 806 +/- 534 (39-1,084) days. In the post-1996 group, PTLD developed in 1 of 131 (0.76%) EBV-seropositive recipients.nnnCONCLUSIONnContinuous, specific anti-viral prophylaxis in high-risk EBV-seronegative recipients significantly reduces the incidence of PTLD after lung transplantation in the absence of induction therapy.

Ultraflex stents for the management of airway complications in lung transplant recipients.

Objective:u2003 We present our experience with the use of the Ultraflex (nitinol) stents in the management of airway complications in lung transplant (LT) recipients.

Management of hypoxemia during flexible bronchoscopy

Under controlled conditions, FB is a safe procedure that has few significant adverse events. Significant hypoxemia may sometimes occur during FB despite the use of supplemental oxygen. UAO has been shown to be the dominant cause of hypoxemia during FB, and this is successfully managed with nasopharyngeal tube insertion. Other strategies that may need to be implemented include oxygen supplementation with intratracheal catheter, administration of sedation reversal medication, removal of the bronchoscope, bag-and-mask ventilation, and, rarely, endotracheal intubation and ventilation. Access to an anesthetist, availability of propofol, backup rigid bronchoscopy, and fluoroscopy are optional but desirable components in the bronchoscopy suite.

Achilles tendon disease in lung transplant recipients: association with ciprofloxacin

Achilles tendonitis or rupture are uncommon complications following the use of fluoroquinolones, with a reported incidence in the general population of 0.4%. The aims of the current study were to determine the incidence of Achilles tendon disease (ATD) in lung transplant recipients (LTR) and to identify risk factors. Questionnaires were sent to 150 LTR of whom 101 responded (67%). Twenty-two LTR (21.8%) experienced ATD (tendonitis 16, rupture six). The mean age of LTR who developed ATD was 52.9±6.1u2005yrs (range: 19–63.5u2005yrs). Only the use of ciprofloxacin was significantly associated with ATD (p<0.05). Age, sex, underlying disease necessitating transplantation, serum creatinine and cyclosporine levels were not associated with ATD. The association between ciprofloxacin and ATD was not dose related. Of the 72 LTR who had received ciprofloxacin, 20 (28%) developed ATD (tendonitis 15, rupture five). In patients receiving ciprofloxacin, there was no association between the mean cumulative dose of prednisolone and ATD. Tendon rupture occurred with a lower ciprofloxacin dosage than tendonitis and the mean recovery duration was significantly longer. To conclude, lung transplant recipients receiving ciprofloxacin are at significant risk of developing Achilles tendon disease. The association between ciprofloxacin and Achilles tendon disease appears to be idiosyncratic rather than dose-related.

Risk factors and management of bleeding associated with transbronchial lung biopsy in lung transplant recipients

The aim of this study was to assess specific risk factors associated with bleeding during transbronchial biopsy (TBBx) in lung transplant recipients. Risk factors analyzed included gender, type of transplant, acute rejection, bronchiolitis obliterans syndrome (BOS) status, infections, number of biopsies obtained per procedures, serum creatinine level and post-operative day since transplantation. The bronchoscope was not wedged to obtain TBBx and associated bleeding was managed using the back-and-forth technique. The severity of bleeding is shown to be independent of any specific risk factor and the back-and-forth technique described herein can be safely employed in lung transplant recipients to manage bleeding associated with TBBx performed without wedging of the bronchoscope.

Mycoplasma hominis infection in heart and lung transplantation

Culture-negative wound infection and mediastinitis secondary to Mycoplasma hominis have been reported after cardiothoracic surgery but no case cluster has ever been described. We report 4 cases of infection in 3 cardiac and 1 bilateral sequential lung transplant recipient over 3 weeks of hospitalization. Successful treatment was achieved with early aggressive surgical intervention and combination antibiotics of clindamycin, doxycycline and/or ciprofloxacin. This cluster raises the question of nosocomial transmission of infection and supports a recommendation for single-room isolation and universal precautions for infected individuals.

Indirect fluorescent antibody testing of nasopharyngeal swabs for influenza diagnosis in lung transplant recipients

n Abstractn n Background:n Rapid and reliable diagnosis of respiratory viral infections (RVI) in lung transplant recipients is essential to direct therapy of acute graft dysfunction and identify epidemic trends. Traditional techniques of serology and viral culture are limited by the lack of antibody response and delay in diagnosis.n n n Methods:n We examined the clinical utility of indirect fluorescent antibody (IFA) testing in adult lung transplant patients with suspected RVI, compared with serology and culture. Nasopharyngeal and throat swabs (NT) were obtained to sample epithelial cells, followed by application of monoclonal antibody to respiratory syncytial virus, adenovirus, parainfluenza 1–3 and influenza A and B. The Bartels Respiratory Viral Detection kit was used with IFA results available within 24 hours.n n n Results:n Nine of 18 patients tested positive for RVI with influenza A (n = 8) and influenza B (n = 1) detected. The sensitivity of IFA (67%) was higher than that of cell culture (45%). With intensive supportive therapy, infection was self-limiting in bronchiolitis obliterans syndrome (BOS) Grade 0–2 patients. However, patients with BOS Grade 3 manifested an acute exacerbation of airflow obstruction, which proved to be irreversible.n n n Conclusions:n Lung transplant patients with “flu-like” symptoms should proceed to IFA testing of NT swab specimens for early diagnosis. Samples collected within 7 days of symptom onset have high sensitivity as compared with serology and viral culture techniques.n n

Prophylactic nasopharyngeal tube insertion prevents acute hypoxaemia due to upper-airway obstruction during flexible bronchoscopy

Abstract

Antiviral prophylaxis prevents lymphoprofilerative disease in lung transplant recipients

Introduction: Epstein-Barr virus (EBV)-associated Posttransplant Lymphoproliferative Disease (PTLD) is a severe complication in transplant recipients. We used quantitativecompetitive-PCR to investigate the correlation between EBV DNA load and PTLD in whole blood and serum samples of lung transplant (LTx) patients with and without PTLD. Prospective sampling was done weekly during admission and at all outpatient visits. Analysis was retrospectively done. Methods: Between 1997 and 1999 6 patients developed PTLD (2,19,32,55,67 and 78 months after Ltx). The first 8 patients transplanted after start of the study and who survived for . 8 months were used as control patients. Results: Of the PTLD patients 5 out of 6 had samples positive for EBV DNA before diagnosis of PTLD (50/64 samples 578%). Of the non-PTLD transplant patients 2 out of 8 had a positive sample (4/117 53.4%, p,0.001). Samples of PTLD patients became positive during the first months after transplantation or first taken samples were positive 6 to 71 months before PTLD. The increased EBV DNA loads in PTLD patients were restricted to the cellular blood compartment, as parallel serum samples were all negative for EBV DNA. Conclusion: We demonstrate a high EBV DNA load already a long period before clinical diagnosis of PTLD or even during the first month after transplantation. We recommend frequent monitoring of EBV viral load during high risk periods especially the first months after transplantation.