Complications In Lung Transplant Recipients Research Articles

A retrospective study of silicone stent placement for management of anastomotic airway complications in lung transplant recipients: Short- and long-term outcomes

Airway anastomotic complications remain a major cause of morbidity and mortality after lung transplantation (LT). Few data are available with regard to the use of silicone stents for these airway disorders. The aim of this retrospective study was to evaluate the clinical efficacy and safety of silicone stents for such an indication. Data of adult lung transplant recipients who had procedures performed between January 1997 and December 2007 at our institution were reviewed retrospectively. We included patients with post-transplant airway complications who required bronchoscopic intervention with a silicone stent. In 17 of 117 (14.5%) LT recipients, silicone stents were inserted at a mean time of 165 (range 5 to 360) days after surgery in order to palliate 23 anastomotic airway stenoses. Symptomatic improvement was noted in all patients, and mean forced expiratory volume in 1 second (FEV(1)) increased by 672 +/- 496 ml (p < 0.001) after stent insertion. The stent-related complication rate was 0.13/patient per month. The latter consisted of obstructive granulomas (n = 10), mucus plugging (n = 7) and migration (n = 7), which were of mild to moderate severity and were successfully managed endoscopically. Mean stent duration was 266 days (range 24 to 1,407 days). Successful stent removal was achieved in 16 of 23 cases (69.5%) without recurrence of stenosis. Overall survival was similar in patients with and without airway complications (p = 0.36). Silicone stents allow clinical and lung function improvement in patients with LT-related airway complications. Stent-related complications were of mild to moderate severity, and were appropriately managed endoscopically. Permanent resolution of airway stenosis was obtained in most patients, allowing definitive stent removal without recurrence.

Infections in lung transplantation: new insights

Infections represent a major source of complications in lung transplant recipients (LTR), especially when compared with recipients of other solid organ transplants. Within the past year, new data on the impact and prevention of specific pathogens in the setting of lung transplant have been published. Specifically, this review will assess the effect of Burkholderia infection on cystic fibrosis (CF) patients following lung transplant (LTx), the role that Gram-negative bacilli (GNB) play in the development of bronchiolitis obliterans syndrome (BOS), and the optimal duration of cytomegalovirus (CMV) prophylaxis in LTR. Recent data support the hypothesis that certain Burkholderia species, potentially B. gladioli and specific B. cenocepacia subtypes, pose a greater risk for death in CF LTR than do other Burkholderia species. Additionally, recent data suggest that colonization with GNB, particularly Pseudomonas species, may play a role in the pathogenesis of BOS, the leading cause of late-term mortality in LTR. Finally, recent studies suggest that extended prophylactic regimens may be more efficacious in reducing CMV-related events. Recent data have broadened our understanding of the role that infections play in affecting LTR outcomes. Prospective multicenter studies are needed to further optimize pathogen specific prevention strategies.

Are metallic stents really safe? A long-term analysis in lung transplant recipients

Airway complications affect 20% of all lung transplant recipients. Self-expandable metallic stents (SEMS) are one treatment option but their use in benign airway disorders is controversial. We studies the long-term safety of SEMS in lung transplant recipients. Between January 1998 and February 2008, all lung transplant recipients with SEMS were analysed retrospectively at a single centre. Complications were recorded until September 2008. In 65 (9.2%) out of 706 recipients, 111 (91% noncovered) bronchial SEMS were implanted a median (range) 133 (55-903) days after lung transplantation; follow-up was 777 (7-3.655) days. Clinical improvement was noted in 80% of recipients. The forced expiratory volume in 1 s increased by (mean+/-SD) 21+/-33%. Most frequent early complications were migration (3%) and mucus plugging (11%). No procedure-related deaths were noted. Re-stenosis occurred in 34 (52%) out of 65 recipients 85 (7-629) days after insertion. In multivariate analysis, stent insertion before post-operative day 90 was independently associated with an increased risk of re-stenosis (HR 3.29, 95% CI 1.50-7.18; p = 0.003). In 40% of recipients, new bacterial airway colonisation occurred after SEMS insertion. In SEMS patients, 5-yr survival was significantly lower than in the total cohort (60% versus 76%; p = 0.02). Late complications in lung transplant recipients treated with SEMS are frequent. The major problems are re-stenosis and airway colonisation.

MDCT Evaluation of Central Airway and Vascular Complications of Lung Transplantation

The purpose of this article is to illustrate the spectrum of central airway and vascular complications in lung transplantation using MDCT, with an emphasis on the usefulness of advanced postprocessing techniques. MDCT is an invaluable tool in the diagnosis, evaluation, and posttreatment assessment of central airway and vascular complications in lung transplant recipients. Advanced postprocessing techniques provide complementary information that is visually accessible and anatomically meaningful for the clinician.

Thioredoxin as a biomarker for graft rejection in lung transplant recipients

Primary graft dysfunction and rejection are common complications in lung transplant recipients. Increased expression of thioredoxin-1 (Trx), a 12-kDa redox-regulatory protein, has been reported in multiple lung pathophysiological conditions involving oxidative and inflammatory mediated injury including graft rejection in canine and rat models of lung transplantation. Our objective was to determine whether increased Trx expression is associated with progression of rejection pathophysiology in human lung transplant recipients. Bronchoalveolar lavage (BAL) fluid and transbronchial biopsy samples were collected as a routine part of post-transplant clinical care from 18 lung transplant patients from our adult lung transplant programme. Lung transplant recipient profile included age/sex, ethnic background, days on ventilator, total ischaemic time, and cytomegalovirus (CMV) status. Based on histopathological grading criteria, patients were divided into two groups, rejecting (A1/A2 or B1) and non-rejecting (A0/B0). Rejecting and non-rejecting group total BAL cell counts and differential cell counts for neutrophils, macrophages, lymphocytes and eosinophils as well as total BAL cell Trx levels were analysed. Total BAL cell counts were significantly (p<0.05) elevated in graft rejecting versus non-rejecting patients. Differential BAL macrophage counts were comparable in rejection and non-rejection groups, whereas there were significant increases in neutrophils and lymphocytes but not eosinophils in patients with rejection versus non-rejection pathology (p<0.05). Total ischaemic time and days on ventilator in rejection and non-rejection groups were comparable. However, Trx levels were significantly elevated in BAL cells from graft-rejecting patients compared with non-rejecting patients (p<0.05). These data suggest that surveillance monitoring of BAL Trx levels after lung transplantation can serve as a biomarker to assess severity of graft rejection.

Bacteremia in Lung Transplant Recipients in the Current Era

Current trends in the epidemiology, outcome and variables influencing mortality in bacteremic lung transplant recipients have not been fully described. We prospectively studied bacteremias in lung transplant recipients in a multicenter study between 2000-2004. Bacteremia was documented in 56 lung transplant recipients, an average of 172 days after transplantation. Multiple antibiotic resistance was documented in 48% of the isolates; these included 57% of the Gram-negative and 38% of the Gram-positive bacteria. Pulmonary infection was the most common source of resistant gram-negative bacteremias. Mortality rate at 28 days after the onset of bacteremia was 25% (14/56). Mechanical ventilation and abnormal mental status correlated independently with higher mortality (p < 0.05 for both variables). Bacteremia remains a significant complication in lung transplant recipients and is associated with considerable mortality. Recognition of variables portending a high risk for antibiotic resistance and for poor outcome has implications relevant for optimizing antibiotic prescription and for improving outcomes in lung transplant recipients.

Salvage Right Pneumonectomy in a Patient With Bronchial–Pulmonary Artery Fistula After Bilateral Sequential Lung Transplantation

Bronchovascular fistula is a rare but fatal complication in lung transplant recipients. We report the successful salvage of a right pneumonectomy performed in a patient with a fistula between the right main bronchus and the pulmonary artery after ulcerative bronchitis caused by Aspergillus fumigatus.

Intraabdominal Complications after Lung Transplantation

Because more lung transplant recipients survive the perioperative period, nonpulmonary complications become a major source of morbidity and mortality. Of these, intraabdominal complications are of particular concern because of the potential need for surgical intervention. So appropriate management of these complications becomes paramount. We retrospectively reviewed 229 lung transplant recipients in a university medical center, between January 1997 and December 2004 developed in forty-seven patients. Abdominal complications. Detailed reviews of these patients' hospital charts were performed. Complications were categorized as early or late depending on if they occurred within 30 days of transplantation or later. The primary outcomes variable studied was mortality. Fifty-three surgical consultations for abdominal symptoms were requested in these 47 patients. Twenty-two of the 47 patients (47%) with intraabdominal complications required 24 operative interventions. Overall 5-year survival was substantially worse in patients with intraabdominal complications (34%) than in those without (62%, p=0.01). There was no marked difference in the 30-day mortality for patients experiencing early (27%, 4 of 15) versus late (24%, 9 of 38) complications. Mortality in patients with intraabdominal complications was lower among those treated operatively (n=2, 9%) compared with those treated nonoperatively (n=11, 44%, p=0.02). Mortality for patients with intraabdominal complications is high after lung transplantation. Operative intervention is well tolerated and associated with lower mortality. A high index of suspicion and timely operative intervention are necessary for the treatment of intraabdominal complications in lung transplant recipients.

Chlamydia pneumoniae Serology in Donors and Recipients and the Risk of Bronchiolitis Obliterans Syndrome after Lung Transplantation

Bronchiolitis obliterans syndrome (BOS) is a common late complication in lung transplant recipients (LTR). Chlamydia pneumoniae (C. pneumoniae) is a common but difficult to diagnose respiratory pathogen with a propensity to latency. We studied the impact of C. pneumoniae on BOS development using donor-recipient serology obtained before transplantation in a cohort of 76 LTR. BOS was present in 29.9% patients (mean follow-up 866 days). High donor C. pneumoniae immunoglobulin (Ig)G titers were associated with BOS in the recipient (area under the curve [AUC] 0.71, 95% confidence interval [CI] 0.52-0.91, P=0.027), whereas high recipient titers were inversely associated with BOS (AUC 0.27, 95% CI 0.11-0.44, P=0.018). The risk of developing BOS was 75.0% in the case of a primary seromismatch for C. pneumoniae (D+/R-), whereas a reverse mismatch had a risk of 4.6% (likelihood ratio 9.8, P=0.02). In a multivariate model that included human leukocyte antigen matching, acute rejection and cytomegalovirus pneumonitis, C. pneumoniae IgG donor 32 or greater and C. pneumoniae IgG recipient 32 or greater remained positive and negative independent risk factors, respectively, for BOS in LTR. In the freedom from BOS analysis, BOS occurred more frequently and earlier in C. pneumoniae seropositive donors, and the reverse was true in seronegative recipients. C. pneumoniae serology in donor and recipient is associated with the development of BOS in LTR.

Standardized guidelines for surveillance bronchoscopy reduce complications in lung transplant recipients

Standardized guidelines for surveillance bronchoscopy reduce complications in lung transplant recipients

Pulmonary embolism on postmortem examination: an under-recognized complication in lung-transplant recipients?

Postmortem reports highlight the importance of factors that individually or collectively limit survival. The prevalence of pulmonary embolism (PE) at autopsy in lung-transplant recipients has not been characterized previously. We aimed to describe the prevalence of PE, infection, and acute and chronic rejection at autopsy and their respective contributions to death in lung-transplant recipients according to survival posttransplantation. We retrospectively reviewed 126 autopsy reports performed in lung-and heart-lung-transplant recipients between June 1990 and September 2002. PE was identified at autopsy in 34 (27.0%) of 126 lung- and heart-lung-transplant recipients. The prevalence of autopsy-established PE was highest, at 36.4%, in the early group (1-30 days) compared with 20.0% and 23.8% in the intermediate (31-365 days) and late (>365 days) groups, respectively. Although fungal and viral pneumonia were noted most frequently in the early and intermediate groups, bacterial pneumonia was noted in 32% to 45% of autopsies over the posttransplant period. Acute cellular rejection and bronchiolitis obliterans were present in 29.5% and 2.3%, 40.0% and 17.5%, and 35.7% and 42.9% of patients in the early, intermediate, and late groups, respectively. The most frequent cause of death was bacterial infection. The prevalence of PE was highest in mechanically ventilated lung-transplant recipients in the early postoperative period. Heart-lung recipients were at lower risk for PE compared with double- and single-lung recipients. PE may be an under-appreciated complication contributing to respiratory failure in the early postoperative period.

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

Respirology 2003;8:59–64. Chhajed PN, Malouf MA, Tamm M, Glanville AR. Comments: In this study, Chhajed and coworkers report their experience with the use of an uncovered Ultraflex (nitinol) stent in the management of airway stenosis in 9 lung transplant recipients. The indications for stent placement were stenosis of the large airway in 4 patients, combined stenosis and bronchomalacia in 3 patients, and tracheomalacia and bronchomalacia in 1 patient each. A total of 11 stents were deployed in 9 patients. Stents were placed using a flexible bronchoscope with fluoroscopy guidance under conscious sedation. Proximal release stents were used in 6 patients and distal release stents in 3 patients. The mean ± standard deviation increase in forced expiratory volume in 1 second (FEV1) after insertion of the procedure was 522 ± 391 mL (range, 120–1150 mL). Successful stent deployment led to improvement in dyspnea in all patients. In 2 patients, initial placement of the stent was unsatisfactory as a result of proximal displacement of the stent delivery device. This problem occurred with the proximal release stent delivery device in both cases. Stricture resulting from excessive growth of granulation tissue formed in 1 patient, and it was treated with balloon dilatation and laser resection. Stent migrated in 1 patient from its original position, and it had to be removed. No patient developed stenosis at the stent extremities or mucus plugging during the follow-up period of 263 ± 278 days after the procedure. Airway complications are common after lung transplantation. Common complications include anastomotic stenosis, bronchomalacia, or a combination of stenosis and malacia, granulation tissue, and anastomosis dehiscence. The majority of patients with symptomatic airway stenosis after lung transplantation require interventional bronchoscopic treatment (Chest 2001;120:1894–9). The choice of treatment depends on endoscopic findings. For stenosis, balloon dilatation is the first-line treatment. However, despite its high initial success, the majority of patients eventually require airway stent as a result of recurrence of stenosis or as a result of development of bronchomalacia. There is no single ideal stent for this purpose. Recent reports indicate successful deployment of self-expandable metal stents in these patients. Uncovered wall stents have been considered more suitable than prior designs of metallic stents (such as Gianturco and Palmaz stents) for this purpose. However, in a prior study, Chhajed and coworkers reported granulation tissue and mucus plugging in 27% patients each after placement of uncovered wall stents in lung transplant recipients (Chest 2001;120:1894–9). The present study by Chhajed and coworkers suggests that the Ultraflex stent could be better than uncovered wall stents for managing airway stenosis after lung transplantation as a result of the very low risk of secretion accumulation, mucus plugging, and development of granulation tissue at the ends of the stent. Although the sample size was small, the results indicate that the Ultraflex stent is presently the most useful metal stent for management of airway stenosis in lung transplant recipients.

Standardized guidelines for surveillance bronchoscopy reduce complications in lung transplant recipients

Background The role of surveillance bronchoscopy in the care of lung transplant recipients remains controversial. Although there are no controlled studies to suggest a survival advantage, many transplant physicians support the practice. The procedure is generally safe but is associated with some complications. A review of practices at our institution revealed significant variation in patient preparation, management of risk related to the procedure, and in the technical aspects of the bronchoscopy itself. In an effort to minimize these differences and potentially improve outcomes, a standard set of procedural guidelines for all bronchoscopies was adopted in January 2000. Methods Reports from 1,028 surveillance bronchoscopies performed in our outpatient facility from January 1999 to December 2001 were reviewed. Baseline patient data and procedure-related complications were identified. Specific complications recorded included oversedation, the need for prolonged supplemental oxygen, major and minor bleeding, pneumothorax, bronchospasm, vomiting, arrhythmia, hypotension and death. Differences between groups were analyzed using chi-square or Student’s t-tests as appropriate. Results The incidence of complications after the introduction of the guidelines (2000 and 2001) was significantly lower than in the year prior (1999) (1.95% vs 6.45%, p < 0.001). The lower rate of adverse events was mainly a result of a reduction in the incidence of minor bleeding (0.28% vs 2.26% p = 0.006) and of sedation-related complications (0.97% vs 2.90%, p = 0.04). Conclusions The use of a standardized set of guidelines for surveillance fiber-optic bronchoscopy reduces complication rates. Similar guidelines should be considered by transplant centers performing the procedure.

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

We present our experience with the use of the Ultraflex (nitinol) stents in the management of airway complications in lung transplant (LT) recipients. Nine LT recipients underwent insertion of uncovered Ultraflex stents. Mean change in FEV1, duration to formation of granulation tissue and follow-up post-stent insertion were compared with results obtained in LT recipients who had undergone Gianturco stent (n = 10) and Wallstent insertion (n = 16). Mean improvement in FEV1 after insertion of Gianturco, Wallstent and Ultraflex stents was 670 +/- 591 mL, 613 +/- 221 mL and 522 +/- 391 mL, respectively. No patient with an Ultraflex stent developed mucus plugging or stenosis at stent extremity at a follow up of 263 +/- 278 days. The mean and median duration to stenosis at stent extremity for patients with Gianturco stents was 102 +/- 85 days and 73 days, respectively, compared with 132 +/- 87 days and 142 days, respectively, for patients with Wallstents. Stricture formation in the middle of the Ultraflex stent occurred bilaterally, at the level of anastomosis in one patient in whom stent placement was undertaken in the presence of inflammation. Stent migration in one patient was related to undersizing of the stent diameter relative to the airway diameter. A larger diameter relative stent was subsequently inserted successfully. Ultraflex stents appear to have fewer long-term complications when used in the management of airway complications following LT.

Infectious pulmonary complications in lung transplant recipients.

Pulmonary infections are the most common cause of morbidity in the lung transplant population. Prompt recognition and treatment is necessary to prevent poor outcomes. An understanding of the temporal relationship between immunosuppression and the risk for developing infection can assist the clinician with appropriate treatment. Bacterial pneumonia is common within the first 4 months after transplantation whereas cytomegalovirus (CMV) infection or disease becomes prevalent after the discontinuation of prophylaxis in at-risk patients. Fungal infections, especially aspergillosis, can be fatal if not treated early and the risk for infection is present throughout the transplant period. Community-acquired viral infections present with upper-respiratory symptoms and wheezing that may lead to a chronic decline in lung function. Suspicion of a pulmonary infection in these immunosuppressed individuals should lead to an urgent diagnostic bronchoscopy and empiric antimicrobial therapy.

Lung transplant rejection: obliterative bronchiolitis

More centers are performing lung transplants for a variety of pulmonary conditions. Chronic rejection, manifested as obliterative bronchiolitis, is the most common cause of late death (greater than 6 months after transplant) in this population. To review published literature on obliterative bronchiolitis to determine the current terminology and definition, pathophysiology, incidence, diagnosis, treatment, and outcome of this condition. A MEDLINE search was done using the medical subject headings of bronchiolitis obliterans and lung transplantation. Studies were selected based on sample size and reporting of obliterative bronchiolitis statistics. Sources that were not data-based discussions also were selected if they were comprehensive reviews or provided insight into relevant issues. Obliterative bronchiolitis terminology is not used consistently in the literature. It is an obstructive defect that affects the airways, causing progressive occlusion. Diagnosis is based on clinical findings or on histological analysis; early markers are sought, to aid in diagnosis. Incidence of obliterative bronchiolitis varies from 7% to 54%, with a mortality rate of 30% to 40%. Currently, enhanced immunosuppression is the treatment of choice, although research is being carried out to evaluate methods of inhibiting growth factor activity for use in future treatment strategies. Obliterative bronchiolitis is a common complication in lung transplant recipients, and future research will focus on treatment and early diagnosis. Efforts are under way to standardize nomenclature and reporting of incidence and mortality rates.

Pleural complications in lung transplant recipients

Pleural complications occurred in 30 (22%) of 138 patients after 53 single and 91 double lung transplants between September 1986 and February 1993. These were defined for the purpose of this study as pneumothorax persisting beyond the first 14 postoperative days, recurrent pneumothorax, or any other pleural process that necessitated diagnostic or therapeutic intervention. Overall, a higher pleural complication rate was seen in double lung transplantation (25 of 30) than in single lung transplantation (5 of 30) with no differences noted in the frequency among preoperative diagnostic groups (p > 0.05). Pneumothorax was the most frequent complication, affecting 14 of 30 patients, with 6 of 14 cases occurring after transbronchial biopsy. All pneumothoraces in single (n = 4) and double lung transplantation (n = 10) resolved spontaneously or with chest tube thoracostomy. One patient required placement of a Clagett window after open lung biopsy and another required thoracotomy and pleural abrasion after transbronchial biopsy. Parapneumonic effusion was observed in 4 of 30 double lung transplantations with spontaneous resolution in all cases. Empyema affected 7 of 30 patients and occurred exclusively in the double lung transplant group. Sepsis developed in three of the patients with this complication and they subsequently died. The risk of empyema was independent of preoperative diagnosis (p > 0.05). Of interest, all patients with cystic fibrosis (n = 3) with complicating empyema had Pseudomonas cepacia in the pleural fluid. Other miscellaneous complications included subpleural hematoma, chylothorax, and hemothorax. The latter two necessitated thoracic duct and bronchial artery ligation, respectively. In summary, a significant proportion of lung transplant recipients will have pleural space complications. The vast majority of these will resolve spontaneously or with conservative procedures. These complications were not related to preoperative diagnosis nor associated with a significant prolongation of hospital stay (p > 0.05). Empyema is the only pleural space complication associated with increased patient mortality and, as such, is an important clinical marker for those at risk for sepsis and death.

Monitoring of alveolar macrophage production of tumor necrosis factor-alpha and interleukin-6 in lung transplant recipients. Marseille and Montreal Lung Transplantation Group.

Bronchiolitis obliterans (BO), a common complication in lung transplant recipients, is a fibrotic process probably related to acute rejection (AR) and cytomegalovirus pneumonitis (CMVP). Because the pathogenesis of pulmonary fibrotic diseases involves activation of alveolar macrophages (AM), the present study was carried out to determine if AM were activated during AR, CMVP, and BO. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured in 157 AM supernatants obtained from 29 transplant recipients by immunoradiometric assay. Five groups were analyzed: AR (n = 21), CMVP (n = 12), BO (n = 15), bacterial pneumonia (BP) (n = 8), and control subjects (n = 70). Cytokines were also assayed 15 d (n = 15) and 30 d (n = 9) after AR and 30 d (n = 9) after CMVP. Cytokine secretion was elevated during AR (TNF-alpha = 3,709 +/- 1,409 pg/10(6) cells, IL-6 = 5,482 +/- 2,058 pg/10(6) cells, p < 0.005), and they returned to control values within 15 d. A similar pattern was observed during CMVP (TNF-alpha = 5,000 +/- 2,773 pg/10(6) cells, IL-6 = 12,280 +/- 3,939 pg/10(6) cells, p < 0.005), and values returned to control levels within 30 d. During BP, cytokine production values were higher than control values, but to a lesser extent than in AR and CMVP (TNF-alpha = 2,502 +/- 1,072, p < 0.05; IL-6 = 3,734 +/- 1,440, p < 0.005). In contrast, cytokine secretion during BO was not statistically different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)