Lung transplant recipients on long-term extracorporeal photopheresis.

Extracorporeal photophoresis (ECP) is an increasingly used therapy to address chronic lung allograft dysfunction (CLAD) following lung transplantation. In 2008, we reported the first single-center experience showing that ECP not only reduces lung function decline in patients with bronchiolitis obliterans syndrome (BOS) but results in stabilization of patients with recurrent acute cellular rejection (ACR). In this study, the original cohort was followed up further 5 years. In addition, patients with CLAD were retrospectively classified according to recently published phenotypes. The current cohort included 21 of the original 24 patients, of which nine were initially treated for CLAD, 12 were initially treated for recurrent ACR. Our results show that survival of patients treated with ECP for CLAD was inferior to patients treated for recurrent ACR (66% vs. 82% survival rate). Long-term survivors in the CLAD subgroup were mostly classified as BOS 1 at time of ECP initiation. These long-term data show that patients started on ECP at early BOS stages have better long-term outcome. The subgroup of ECP patients with recurrent ACR has an overall superior survival. To assist prediction of therapy response, we agree with other authors that patients with CLAD should be aimed to be phenotyped and evaluated for an early treatment with ECP.

Isolation of Stenotrophomonas maltophilia in asymptomatic lung transplant recipients: effects of treatment on eradication and outcome.

In this retrospective, single-center data analysis, we audited our clinical practice to treat Stenotrophomonas maltophilia in asymptomatic lung transplant recipients (LTRs). Eighteen LTRs with confirmed isolation of S. maltophilia were identified. Twelve of these LTRs have been treated with antibiotics, while 6 were managed without treatment. Treatment was based on antibiograms (trimethoprim/sulfamethoxazole [TMP/SMX] (8/12), levofloxacin (1/12), or both (3/12). Clearance (12/12 vs 6/6), eradication (10/12 vs 3/6, P=.27), and freedom from S. maltophilia recurrence (83%±11% vs 40%±22% after one year, log-rank P=.09) were not found to differ significantly between treated and untreated patients. None of the patient groups showed significant changes in lung function or biochemical variables. Creatinine levels at the end of the study period were found to be higher in treated patients compared to the untreated group (P=.049). De novo acquired TMP/SMX resistance in S. maltophilia strains was not observed. These results indicate no evidence that antibiotic treatment for S. maltophilia in asymptomatic LTRs alters lung function or the clinical outcome.

Coronary artery disease in lung transplant candidates: role of routine invasive assessment.

BACKGROUND: An atherosclerotic disease burden sufficient to put lung transplant candidates at risk for end-organ disease after transplantation is considered to be a relative contraindication for lung transplantation. OBJECTIVES: The aim of this study was to assess our current practice of cardiac workup by coronary angiography in lung transplant candidates ≥50 years of age. METHODS: We retrospectively analyzed 50 consecutive lung transplant candidates ≥50 years of age in which coronary angiography was performed at the University Hospital Zurich (2009-2013). For every patient, the risk of developing an acute coronary event was estimated by using a recalibrated version of the PROCAM study calculator for the Swiss population. RESULTS: The median estimated risk of developing an acute coronary event within 10 years in the study cohort (n = 50) was 4.2% (interquartile range 1.9-7.6), which is considered to be a low risk. Sixteen percent of patients were considered to be at intermediate risk. In 66% of patients, coronary angiography showed no coronary artery disease (CAD). In 28% of patients, CAD without significant stenosis was diagnosed. In 6% of patients, significant coronary stenosis was detected requiring percutaneous coronary intervention. No correlation between the coronary status and the risk score or cardiovascular risk profile was found. CONCLUSIONS: The high prevalence of asymptomatic CAD in lung transplant candidates without correlation to a common clinical risk score supports the important role of coronary angiography for the assessment of coronary artery status. This approach might prevent cardiovascular events and improve long-term survival after transplantation.

Favorable outcome of children and adolescents undergoing lung transplantation at a European adult center in the new era.

Lung transplantation (LTx) is an accepted therapy in children with end-stage lung diseases. Pediatric-specific experience is considered important in pediatric LTx. We present our institutional experience and its outcome since the year 2000, asking whether different treatment strategies produce comparable outcomes in pediatric lung transplant recipients at our predominantly adult center. This is a retrospective analysis of children and adolescents aged ≤20 years, undergoing LTx between January 2001 and December 2013. Minimum follow-up was 12 months. Primary endpoints were re-transplantation or death. We performed 33 lung transplant procedures in 29 patients. Survival 1 month post-operatively was 96.6%, at 3 months 93.1% and at 12 months 82.8%, respectively. At the end of our follow up, 72.4% of our pediatric cohort was still alive - median post-transplant survival was 59 months (range 0-159). 72.4% of the children were transplanted with support of extracorporeal membrane oxygenation (ECMO), size-reduced donor grafts were used in 69.0%. The differences between post-transplant survival of the "non-ECMO-group" versus the "ECMO-group" (137 vs. 28 months, P=0.7) and "full size" versus "size-reduced bilateral transplants" (61 vs. 28 months, P = 0.7) were not significant, though. There were no anastomotic complications, also not in size-reduced lungs. Our results are well comparable to the international data and show excellent short- and mid-term outcomes. We advocate ECMO-bridge to be considered as a valuable treatment option to prolong time on the waiting list in highly selected patients, as well as size reduction and lobar transplants as a strong strategy to increase the donor pool and reduce donor-recipient size-mismatches. Pediatr Pulmonol. 2016;51:1222-1228. © 2016 Wiley Periodicals, Inc.

[Diagnosis, therapy and prevention of respiratory virus infections in lung transplant recipients]. / Diagnostik, Therapie und Prophylaxe von respiratorischen Viren bei lungentransplantierten Patienten.

Lung transplant recipients have a life-long profound immunosuppression which makes them prone to respiratory tract infections, in particular viral infections during the winter season. Since the respiratory tract infections may have potentially severe consequences, we recommend early diagnosis and treatment. We obtain nasopharyngeal swabs for viral and bacteriological examination and then treat pre-emptively with antivirals, broad-band antibiotics and often also with intravenous immunoglobulins. Treatment duration is often longer than in immunocompetent patients. As preventive measures we provide vaccination against seasonal influenza and recommend specific daily hygiene measures.

Les receveurs d'un transplant pulmonaire requièrent à vie une immunosuppression profonde, ce qui les expose à un risque accru d'infections des voies respiratoires, en particulier d'infections virales pendant l'hiver. Puis que ces infections peuvent avoir des conséquences sérieuses, nous recommandons un diagnostic et un traitement précoce. Nous obtenons des prélèvements naso-pharyngés pour examens virologiques et bactériologiques et traitons ensuite préventivement avec des antiviraux, des antibiotiques à large spectre et souvent aussi par des immunoglobines administrées par vois intraveineuses. La durée du traitement est souvent plus longue que chez les malades immunocompétents. Comme mesures préventives nous avons recours à la vaccination contre la grippe saisonnière et recommandons des mesures d'hygiène de vie spécifiques à suivre quotidiennement.

Comorbidities and burden of COPD: a population based case-control study.

COPD is associated with a relevant burden of disease and a high mortality worldwide. Only recently, the importance of comorbidities of COPD has been recognized. Studies postulated an association with inflammatory conditions potentially sharing pathogenic pathways and worsening overall prognosis. More evidence is required to estimate the role of comorbidities of COPD. Our aim was to investigate the prevalence and clustering of comorbidities associated with COPD, and to estimate their impact on clinically relevant outcomes. In this population-based case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002-2010 (n = 12'888'075) was analyzed using MySQL and R statistical software. Statistical methods included non-parametric hypothesis testing by means of Fisher's exact test and Wilcoxon rank sum test, as well as linear models with generalized estimating equation to account for intra-patient variability. Exploratory multivariate approaches were also used for the identification of clusters of comorbidities in COPD patients. In 2.6% (6.3% in patients aged >70 years) of all hospitalization cases an active diagnosis of COPD was recorded. In 21% of these cases, COPD was the main reason for hospitalization. Patients with a diagnosis of COPD had more comorbidities (7 [IQR 4-9] vs. 3 [IQR 1-6]; [Formula: see text]), were more frequently rehospitalized (annual hospitalization rate 0.33 [IQR 0.20-0.67] vs. 0.25 [IQR 0.14-0.43]/year; [Formula: see text]), had a longer hospital stay (9 [IQR 4-15] vs. 5 [IQR 2-11] days; [Formula: see text]), and had higher in-hospital mortality (5.9% [95% CI 5.8%-5.9%] vs. 3.4% [95% CI 3.3%-3.5%]; [Formula: see text]) compared to matched controls. A set of comorbidities was associated with worse outcome. We could identify COPD-related clusters of COPD-comorbidities.