Endobronchial Ultrasound in Suspected Non-Malignant Mediastinal Lymphadenopathy.

BACKGROUND: Endobronchial ultrasound (EBUS) bronchoscopy with transbronchial needle aspiration (TBNA) is a well-established tool in mediastinal staging in lung cancer and gains importance in exploration of non-malignant lymphadenopathy. The aim of this study was to evaluate the role of EBUS-TBNA in suspected non-malignant diseases. METHODS: A retrospective, single-center, observation analysis of endobronchial ultrasound bronchoscopy procedures was performed in a university medical center between March 2013 and July 2015. All patients with suspected non-malignant mediastinal lymphadenopathy were included. Cytopathological and microbiological results of EBUS were compared to clinical diagnosis 6 months after procedure and performance of EBUS was contrasted to malignant indications. RESULTS: During study period, 333 EBUS bronchoscopies in 315 patients with mediastinal lymphadenopathy were performed. 111 out of 315 (35 %) patients had neither primary signs nor history of a malignant disease, categorised as patients with suspected non-malignant disease. 245 lymph nodes were sampled (median size 15 mm [IQR10 - 19]). Preferred station for TBNA was lymph node station 7 (38 %). Cytopathological findings revealed non-specific inflammation (n = 81; 70 %), carcinoma (n = 7; 6 %), epithelioid cell granulomas (n = 20; 17 %). 7 samples (6 %) were non-representative. Microbiologic testing of lymph nodes identified 3 infections (Mycobacteria tuberculosis [n = 2] and Nocardia nova [n = 1]) relevant to antibiotic therapy. Minor adverse events were observed in 9 out of 115 (8 %) patients. Sensitivity of EBUS-TBNA intervention in suspected non-malignant disease was 76 % and specificity 96 %. CONCLUSIONS: EBUS-TBNA revealed a specific cause for suspected non-malignant lymphadenopathy in one-third of cases and was associated with excellent specificity. Predominant specific causes were granuloma, besides from tumor. In 3 patients pathogen could be isolated by TBNA.

Phenotyping Chronic Lung Allograft Dysfunction Using Body Plethysmography and Computed Tomography.

Restrictive subtype of chronic lung allograft dysfunction (CLAD) was recently described after lung transplantation. This study compares different definitions of a restrictive phenotype in CLAD patients and impact on survival. Eighty-nine CLAD patients out of 1191 screened patients (September 1987 to July 2012) were included as complete longitudinal lung volume measurements and chest computed tomography (CT) after CLAD onset was available. CT findings and lung volumes were quantified and survival was calculated for distinctive groups and predictive factors for worse survival were investigated. Graft survival in patients with total lung capacity (TLC) between 90% and 81% of baseline (BL) (n = 13, 15%) in CLAD course was similar to those with TLC >90% BL (n = 64, 56%; log-rank test p = 0.9). Twelve patients (13%) developed a TLC ≤80% BL and 10 (11%) had significant parenchymal changes on CT, of whom 6 (46%) also had TLC ≤80% BL. CT changes correlated with TLC ≤80% BL (Φ-coefficient = 0.48, p = 0.001). Patients with either TLC ≤80% or significant CT changes (n = 16, 18%) had a significantly reduced survival (log-rank p < 0.001). Forced vital capacity loss at CLAD onset was associated with poorer survival but did not correlate with the TLC or CT changes. A restrictive subtype of CLAD may be defined by either TLC ≤80% BL or severe parenchymal changes on chest CT.

Paclitaxel-coated balloons in refractory nonanastomostic airway stenosis following lung transplantation.

Airway stenosis represents the commonest airway complication following lung transplantation, affecting between 7% and 18% of patients. Existing treatment options offer limited efficacy and can cause additional patient morbidity. Paclitaxel-coated balloons (PCB) have proved effective in managing postinterventional coronary artery re-stenosis. In a first-in-man study, we evaluated similar PCBs in refractory nonanastomotic airway stenosis in 12 patients. Following a single application, luminal patency was maintained in 50% at 270 days. No significant peri-interventional or early postinterventional complications occurred. Given these encouraging initial findings, further studies appear warranted.

Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality in lung transplant recipients after the first year. Treatment remains limited and unpredictable. Existing data suggests extracorporeal photopheresis (ECP) may be beneficial. This study aimed to identify factors predicting treatment response and the prognostic implications. A single center retrospective analysis of all patients commencing ECP for CLAD between November 1, 2007 and September 1, 2011 was performed. In total 65 patients were included, 64 of whom had deteriorated under azithromycin. Median follow-up after commencing ECP was 503 days. Upon commencing ECP, all patients were classified using proposed criteria for emerging clinical phenotypes, including "restrictive allograft syndrome (RAS)", "neutrophilic CLAD (nCLAD)" and "rapid decliners". At follow-up, 8 patients demonstrated ≥10% improvement in FEV1 , 27 patients had stabilized and 30 patients exhibited ≥10% decline in FEV1 . Patients fulfilling criteria for "rapid decliners" (n=21, p=0.005), RAS (n=22, p=0.002) and those not exhibiting neutrophilia in bronchoalveolar lavage (n=44, p=0.01) exhibited poorer outcomes. ECP appears an effective second line treatment in CLAD patients progressing under azithromycin. ECP responders demonstrated improved progression-free survival (median 401 vs. 133 days). Proposed CLAD phenotypes require refinement, but appear to predict the likelihood of ECP response.

Clinical significance of quantitative cytomegalovirus detection in bronchoalveolar lavage fluid in lung transplant recipients.

OBJECTIVES: Cytomegalovirus (CMV) is an important pathogen after lung transplant (LTx) and may be associated with bronchiolitis obliterans syndrome (BOS). We assessed the outcome of LTx patients with CMV DNA-positive bronchoalveolar lavage (BAL) during surveillance. METHODS: A single-center retrospective study was performed. Outpatients transplanted between September 2007 and February 2010, who had undergone at least 3 BALs, were included. CMV DNA load in BAL was measured by polymerase chain reaction (PCR). Monitoring of peripheral blood antigenemia was performed simultaneously. RESULTS: In total, 103 LTx patients underwent 1118 BALs. During median follow-up of 639 days (interquartile range, 495-780), 53 (51%) patients exhibited at least 1 positive CMV PCR in BAL. The incidence of positive CMV PCR varied post transplantation, with 6%, 30%, and 25% of BALs testing positive at <6 months, 6-24 months, and >24 months, respectively. Neither CMV BAL positivity, positive CMV antigenemia, nor dual positivity were significantly associated with BOS-free survival during follow-up. Patients with CMV-positive BAL more frequently developed CMV antigenemia in the first year (44% vs. 5%, respectively, log-rank P < 0.001). CONCLUSIONS: Detection of CMV-positive BAL after the sixth month appears common, but did not correlate with BOS-free survival after LTx in this study. An increased risk of developing blood antigenemia was observed in patients with positive CMV PCR in BAL, warranting close follow-up.

[Lung transplantation]. / Lungentransplantation.

Since the early days of lung transplantation the demand for donor organs has outstripped donor organ availability. Consequently waiting times continue to increase with patients of highest priority often waiting several weeks or even months until a suitable donor organ becomes available resulting in considerable mortality on the waiting list. These issues have led to renewed interest in bridging strategies for patients with end-stage lung disease. The use of endotracheal intubation and mechanical ventilation (MV) has been viewed as a last resort as the majority of intubated patients fail to reach transplantation and those who do tend to have a poor postoperative outcome. New bridging strategies with awake extracorporeal membrane oxygenation (ECMO) seem to be hopeful alternatives in some patients. In the early intensive care unit (ICU) phase primary graft dysfunction, acute rejection, infections and surgical complications are common problems. Later, rejection, infection and sepsis, special airway complications and pulmonary bleeding may be reasons for ICU treatment.

Self-expanding metallic stent placement with laryngeal mask in lung transplant recipients.

BACKGROUND: Bronchial stent insertion is a suitable method to treat airway complications. We present our experience with laryngeal mask airway (LMA) for stent insertion in lung transplant (LT) recipients. METHODS: From April 2007 to March 2009, 27 LT recipients underwent insertion of self-expanding nitinol stents to manage airway complications after LT, using LMA for general anesthesia. All procedures were performed with flexible fiberoptic bronchoscopy without fluoroscopy; stent release was visualized with ultrathin bronchoscopes. We followed technical success, safety, improvement of lung function, and clinical symptoms. RESULTS: Forty-one stents were inserted in 27 patients in 32 sessions. The indications for stent insertion were necrotic lesions (7%) and obstructive lesions (90%). Technical success and safety were 94%. Twice, the stent dislocated, requiring replacements. In 91% of patients, postinterventional improvement in graft function (1 minute forced expiratory volume) was >10% after the intervention. Improvement of clinical symptoms was achieved in 94%. The median procedure time was 38 minutes (range, 30-85 minutes). CONCLUSIONS: LMA offered an excellent condition for stent insertion in LT recipients with airway complications. It provided adequate ventilation and safe airway control during the procedure. This technique may serve as alternative to established techniques using fluoroscopy and rigid bronchoscopy.

Extracorporeal membrane oxygenation in nonintubated patients as bridge to lung transplantation.

We report on the use of veno-arterial extracorporeal membrane oxygenation (ECMO) as a bridging strategy to lung transplantation in awake and spontaneously breathing patients. All five patients described in this series presented with cardiopulmonary failure due to pulmonary hypertension with or without concomitant lung disease. ECMO insertion was performed under local anesthesia without sedation and resulted in immediate stabilization of hemodynamics and gas exchange as well as recovery from secondary organ dysfunction. Two patients later required endotracheal intubation because of bleeding complications and both of them eventually died. The other three patients remained awake on ECMO support for 18-35 days until the time of transplantation. These patients were able to breathe spontaneously, to eat and drink, and they received passive and active physiotherapy as well as psychological support. All of them made a full recovery after transplantation, which demonstrates the feasibility of using ECMO support in nonintubated patients with cardiopulmonary failure as a bridging strategy to lung transplantation.

[Lung transplantation. Indications, long-term results and special impact of follow-up care]. / Lungentransplantation. Indikationen, Langzeitergebnisse und die besondere Bedeutung der Nachsorge.

Lung transplantation has been established as an appropriate ultimate treatment strategy in end-stage lung disease, when all conventional therapeutic options have been exhausted. A successful transplantation should result in an improved quality of life as well as an increase in life-expectancy for certain diseases (cystic fibrosis, pulmonary fibrosis and pulmonary hypertension). There is still a critical need regarding the number of available donor organs. Presently, one out of six patients dies on the waiting list. In order to identify suitable candidates for transplantation a number of criteria require consideration. These include the exact etiology of the pulmonary or cardiac disease, but also patient age, physical mobility, nutritional and muscular status as well as a comprehensive assessment to exclude significant extra-pulmonary co-morbidities. Complications arising after transplantation occur because of general perioperative risks, but also as a result of specific issues such as acute or chronic graft rejection, airway stenoses, infections of the newly immunosuppressed patient as well as a complete spectrum of secondary extra-pulmonary conditions. Comprehensive follow-up care in lung transplantation patients remains a vital issue. Analyses have shown a relevant improvement in long-term outcome, when follow-up care is delivered in cooperation with an established large volume transplant centre.

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.

Indicators for steroid response in biopsy proven acute graft rejection after lung transplantation.

OBJECTIVE: Acute rejection (AR) after lung transplantation (LTx) requires prompt intervention. Most episodes respond to steroid pulse therapy. The aim of this study was to evaluate clinical indicators for non-response to steroid treatment in biopsy proven AR after the early postoperative period. METHODS: We prospectively analysed 85 patients more than 6 months after LTx with symptomatic biopsy proven AR (>or=grade A1) from Jan. 2005 until Nov. 2007 in a single centre. In 47 patients, AR was steroid-sensitive (group 1), 38 patients did not respond to steroid pulse therapy (group 2). All AR episodes were associated with clinical symptoms. Fifty-seven (67%) were low-grade rejections (ISHLT A1). RESULTS: Independent clinical predictors for steroid response vs. non-steroid response in biopsy proven AR were "days after transplantation" (p=0.01, adjusted hazard ratio (HR) 1.2), "decline in home spirometry slope" (p=0.03, HR 0.97), "adherence to home spirometry" (p=0.05, HR 0.98) and "serum CRP" (p=0.02, HR 0.87). Eight patients (21%) of group 2 developed BOS during the following 6 months. CONCLUSIONS: Early detection of deterioration in graft function seems to be crucial for effective treatment of AR. Home spirometry seems to be useful in detecting early changes in graft function and surveillance protocols could be potentially helpful in predicting patients likely to demonstrate a steroid response.

Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis.

Bronchiolitis obliterans syndrome (BOS) represents the leading cause of late mortality after lung transplantation (LTx). Cystic fibrosis (CF) patients frequently show airway colonization with gram-negative bacteria (GNB) both before and after LTx. Graft colonization with GNB and its relevance towards BOS development were investigated in a CF population after LTx. Adult CF patients receiving LTx and surviving at least 6 months were included in this prospective observational study between 1/1/2002 and 30/6/2006 in a single center and followed until 31/3/2007. Pre- and post-LTx respiratory culture samples were compared for the presence of identical GNB. BOS-free survival was compared in colonized and non-colonized patients. Fifty-nine adult CF patients with a median age at LTx of 25.5 (18-49) years were included and had a median follow-up of 966 (128-1889) days. Seven patients (15%) demonstrated immediate eradication of GNB in lower respiratory tract samples. A further 18 patients (34%) demonstrated transient colonization. Thirty-four recipients had further positive samples after LTx. Eighteen patients (31%) developed BOS >or=stage 1, 508 (114-1167) days after LTx. Freedom of graft colonization with pseudomonads was independently associated with less frequent development of BOS (p=0.006). Persistent graft colonization with pseudomonads increases the prevalence of BOS after LTx in CF patients. A significant proportion of post-LTx CF patients demonstrates subsequent GNB eradication during later follow-up and this may have a protective role against development of BOS. Strategies to eradicate airway colonization or reduce bacterial load may prevent BOS in CF patients after LTx.

[Complications after lung transplantation: gastroenterological, hematological and cardiovascular involvement]. / Komplikationen nach Lungentransplantation. Teil 2: gastroenterologische, hämatologische, nephrologische und kardiovaskuläre Komplikationen.

Intestinal perforation after lung transplantation is common in elderly patients with diverticulitis. The distal intestinal obstruction syndrome (DIOS) is a current complication in patients with cystic fibrosis. Myelosuppressive drugs as in most immunosuppressive regimens can cause cytopenia. Thrombotic microangiopathy is often caused by immunosuppressive regimen with a calcineurin-inhibitor in combination with a proliferation signal-inhibitor. Although renal failure and neurological symptoms are often additional side effects of the immunosuppressive therapy there are no reliable data on CNI-free protocols. Studies have shown that administration of statins is associated with improved function and survival of lung allografts.

[Complications after lung transplantation. Part 1: Intensive medical and pneumologic complications]. / Komplikationen nach Lungentransplantation. Teil 1: Intensivmedizinische und pneumologische Komplikationen.

Primary graft dysfunction and/or phrenic nerve lesion are common complications in the early phase after lung transplantation. Respiratory insufficiency is the most common reason for admission to the intensive care unit for patients after lung transplantation. Pulmonary complications in the post transplant management are acute allograft rejection (50% in the first year), infections, endobronchial bleeding, necrosis and fibrinous bronchitis. Chronic graft dysfunction (bronchiolitis obliterans syndrome) and infections are major obstacles to long-term survival.