Jan Fuge

Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension: the initial German experience

Balloon pulmonary angioplasty (BPA) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We report on a prospective series of 56 consecutive patients who underwent 266 BPA interventions (median, five per patient) at two German institutions. All patients underwent a comprehensive diagnostic work-up including right heart catheterisation at baseline and 24 weeks after their last intervention. BPA resulted in improvements in WHO functional class, 6 min walk distance (mean change, +33 m), right ventricular function and haemodynamics, including a decline in mean pulmonary artery pressure by 18% and in pulmonary vascular resistance by 26%. Procedure-related adverse events occurred in 9.4% of the interventions. The most common complications were related to pulmonary vascular injury and consecutive pulmonary bleeding. Most of these events were asymptomatic and self-limiting, but one patient died from pulmonary bleeding, resulting in a mortality rate of 1.8%. BPA resulted in haemodynamic and clinical improvements but was also associated with a considerable number of complications, including one fatal pulmonary bleeding. As the effects of BPA on survival are unknown, randomised controlled outcome trials comparing BPA with approved medical therapies in patients with inoperable CTEPH are required to allow for appropriate risk–benefit assessments. BPA improves haemodynamics and exercise capacity in patients with inoperable CTEPH but complications are not uncommon http://ow.ly/mMYY30b1rch

Conventional vs. Tablet Computer-Based Patient Education following Lung Transplantation – A Randomized Controlled Trial

Background Accurate immunosuppression is of critical importance in preventing rejection, while avoiding toxicity following lung transplantation. The mainstay immunosuppressants are calcineurin inhibitors, which require regular monitoring due to interactions with other medications and diet. Adherence to immunosuppression and patient knowledge is vital and can be improved through patient education. Education using tablet-computers was investigated. Objective To compare tablet-PC education and conventional education in improving immunosuppression trough levels in target range 6 months after a single education. Secondary parameters were ratio of immunosuppression level measurements divided by per protocol recommended measurements, time and patient satisfaction regarding education. Design Single-centre, open labelled randomised controlled trial. Participants Patients >6 months after lung-transplantation with <50% of calcineurin inhibitor trough levels in target range. Intervention Tablet-pc education versus personal, nurse-led education. Measurements Calcineurin inhibitor levels in target range 6 months after education, level variability, interval adherence, knowledge and adherence was studied. As outcome parameter, renal function was measured and adverse events registered. Results Sixty-four patients were 1:1 randomised for either intervention. Levels of immunosuppression 6 months after education were equal (tablet-PC 58% vs. conventional 48%, p = 0.27), both groups improved in achieving a CNI trough level within target range by either education method (delta tablet-PC 29% vs. conventional 20%). In all patients, level variability decreased (−20.4%), whereas interval adherence remained unchanged. Knowledge about immunosuppression improved by 7% and compliance tests demonstrated universal improvements with no significant difference between groups. Conclusion Education is a simple, effective tool in improving adherence to immunosuppression. Tablet-PC education was non-inferior to conventional education. Trial Registration ClinicalTrials.gov NCT01398488 http://clinicaltrials.gov/ct2/show/NCT01398488?term=gottlieb+tablet+pc+education&rank=1.

Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: A Prospective, Randomized, Open-Label Trial.

The role of mammalian target of rapamycin (mTOR) inhibitors in de novo immunosuppression after lung transplantation is not well defined. We compared Everolimus versus mycophenolate mofetil in an investigator‐initiated single‐center trial in Hannover, Germany. A total of 190 patients were randomly assigned 1:1 on day 28 posttransplantation to mycophenolate mofetil (MMF) or Everolimus combined with cyclosporine A (CsA) and steroids. Patients were followed up for 2 years. The primary endpoint was freedom from bronchiolitis obliterans syndrome (BOS). The secondary endpoints were incidence of acute rejections, infections, treatment failure and kidney function. BOS‐free survival in intention‐to‐treat (ITT) analysis was similar in both groups (p = 0.174). The study protocol was completed by 51% of enrolled patients. The per‐protocol analysis shows incidence of bronchiolitis obliterans syndrome (BOS): 1/43 in the Everolimus group and 8/54 in the MMF group (p = 0.041). Less biopsy‐proven acute rejection (AR) (p = 0.005), cytomegalovirus (CMV) antigenemia (p = 0.005) and lower respiratory tract infection (p = 0.003) and no leucopenia were seen in the Everolimus group. The glomerular filtration rate (GFR) decreased in both groups about 50% within 6 months. Due to a high withdrawal rate, the study was underpowered to prove a difference in BOS‐free survival. The dropout rate was more pronounced in the Everolimus group. Secondary endpoints indicate potential advantages of Everolimus‐based protocols but also a potentially higher rate of drug‐related serious adverse events.

Lung transplantation for non-cystic fibrosis bronchiectasis

BACKGROUND Lung transplantation (LTx) is a well-established treatment for end-stage pulmonary disease. However, data regarding microbiology and outcome of patients with non-cystic fibrosis bronchiectasis (NCFB) after lung transplantation are limited. METHODS A retrospective analysis between August 1992 and September 2014 of all patients undergoing lung transplantation at our program of all recipients with a primary diagnosis of bronchiectasis was performed. Microbiology of sputum and bronchoalveolar lavage specimens, lung function and clinical parameters pre- and post-LTx were assessed retrospectively. Overall survival was compared to the total cohort of lung transplant recipients at institution. The survival and development of chronic lung allograft dysfunction (CLAD) was compared in patients with and without chronic Pseudomonas aeruginosa (PSA) infection after LTx. RESULTS 34 patients were transplanted. Median age at transplantation was 40 (IQR 33-52) years. The most common etiologies of bronchiectasis were idiopathic (41%), chronic obstructive pulmonary disease (COPD) (21%) and post-infectious (15%). The most common organism of pre- and posttransplant chronic airway infection was PSA. One-year Kaplan-Meier survival for patients with bronchiectasis was 85% and 5-year survival was 73% and similar to the entire cohort. All three patients with an associated diagnosis of immunodeficiency died due to infection and sepsis within the first year. Patients with persistent colonization with Pseudomonas aeruginosa after transplantation had worse long-term survival by trend and developed chronic lung allograft dysfunction more frequently. CONCLUSIONS Overall survival of patients with bronchiectasis after LTx is comparable to other underlying diseases. A reduced survival was observed in patients with the underlying diagnosis of immunodeficiency.

Prolonged Mechanical Ventilation After Lung Transplantation-A Single-Center Study.

This single‐center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82–21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42–31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86–16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98–12.81], p = 0.001), among others. Overall 1‐year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long‐term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40–5.25], p < 0.001), post‐LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06–5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39–2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in‐hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.

Lung Transplantation after Endoscopic Lung Volume Reduction

Background: Endoscopic lung volume reduction (ELVR) has become an established treatment option in selected patients with end-stage lung emphysema. ELVR, however, does not always prevent disease progression, and patients may inevitably be considered for lung transplantation. Objectives: Currently, limited data exist regarding the impact of preceding ELVR on lung transplantation outcomes. Methods: A retrospective, single-center analysis of lung transplantation (LTx) waiting list candidates, who had previously undergone ELVR for emphysema between 2010 and 2014, was performed. Outcomes were compared to matched (1:2) controls who underwent LTx for emphysema without previous ELVR. The 12-month survival after LTx represented the primary end point. Results: In total 23/693 (3%) patients listed for LTx between January 2010 and May 2014 had undergone ELVR, of whom 20/23 (87%) proceeded to LTx (ELVR group). Forty matched non-ELVR emphysema patients acted as controls. Bronchiectasis on CT prior to LTx was more evident in ELVR patients [11/20 (55%) vs. 12/40 (30%); p = 0.04] as well as airway colonization after LTx [10/20 (50%) vs. 6/40 (15%); p = 0.004]. Among ELVR patients, the most prevalent colonizing organism was Stenotrophomonas maltophilia (4/10 patients, 40%). No significant differences were observed in LTx waiting list time, duration of LTx procedure, ventilatory support, ICU stay after LTx or time to hospital discharge. One ELVR patient (5%) died 189 days after LTx from pneumonia, compared to 1 non-ELVR patient (3%) who died after 269 days (p = 0.61). Conclusions: Previous ELVR treatment was not associated with differing outcomes following LTx. Increased bacterial colonization rates were evident and warrant further investigation.

More on idiopathic pulmonary arterial hypertension with a low diffusing capacity

Pulmonary arterial hypertension (PAH) is defined by the presence of pre-capillary pulmonary hypertension (PH) in the absence of underlying causes such as lung diseases, chronic thromboembolic pulmonary hypertension (CTEPH) or other rare conditions [1, 2]. While the idiopathic form of PAH (IPAH) was originally described as a disease affecting primarily younger women [3, 4], it is now increasingly being diagnosed in elderly patients, many of whom present with cardiopulmonary comorbidities, which can make the exact diagnostic classification of such patients difficult [5–8]. Elderly patients with IPAH, a smoking history and a low DLCO may suffer from a distinct pulmonary vasculopathy http://ow.ly/sdGh30dxd0G

CXCL13 in idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

BackgroundChemokine CXC ligand 13 (CXCL13) has been implicated in perivascular inflammation and pulmonary vascular remodeling in patients with idiopathic pulmonary artery hypertension (IPAH). We wondered whether CXCL13 may also play a role in chronic thromboembolic pulmonary hypertension (CTEPH) and whether serum levels of CXCL13 might serve as biomarkers in these conditions.MethodsLung tissue from patients with IPAH or CTEPH was immunostained for CXCL13. Serum samples were obtained from patients with IPAH (n = 42) or CTEPH (n = 50) and from healthy controls (n = 13). Serum CXCL13 concentrations were measured by enzyme-linked immunosorbent assay technology and were evaluated for associations with markers of disease severity and survival.ResultsCXCL13 was expressed in pulmonary vascular lesions and lymphocytes of patients with IPAH and inoperable CTEPH, respectively. Serum CXCL13 was elevated in patients compared to healthy controls [median, interquartile range, 83 (55,114) pg/ml versus 40 (28, 48) pg/ml; p < 0.001]. Serum CXCL13 showed only weak and inconsistent correlations with markers of inflammation or disease severity. In both populations, patients with serum CXCL13 above the median of the respective groups did not have a higher risk of death than patients with lower serum CXCL13.ConclusionsCXCL13 was overexpressed in pulmonary vascular lesions of patients with IPAH and CTEPH, and increased serum concentrations were found in patients with IPAH and CTEPH, suggesting a potential pathogenic role of CXCL13 in both diseases. However, given the weak associations between serum CXCL13 and markers of disease severity and outcome, CXCL13 is unlikely to become a promising biomarker in these patient populations.

Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic disease

Symptomatic patients with residual pulmonary perfusion defects or vascular lesions but no pulmonary hypertension at rest are diagnosed with chronic thromboembolic disease (CTED). Balloon pulmonary angioplasty (BPA) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but data regarding the safety and efficacy of BPA in patients with CTED are lacking. We report a prospective series of ten consecutive patients with CTED who underwent 35 BPA interventions (median of four per patient) at two German institutions. All patients underwent a comprehensive diagnostic workup at baseline and 24 weeks after their last intervention. BPA was safe, with one pulmonary vascular injury and subsequent self-limiting pulmonary bleeding as the only complication (2.9% of the interventions, 10% of the patients). After the procedures, World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, and pulmonary arterial compliance improved, and NT-proBNP concentrations declined in 9/10 patients. BPA may be a new treatment option for carefully selected patients with CTED. A larger, prospective, international registry is required to confirm these results.

Complications and risk factors in pediatric bronchoscopy in a tertiary pediatric respiratory center

Bronchoscopy is an established procedure routinely used by pediatric pulmonologists. Despite its frequent application, data on complications and specific risk factors are scarce and sometimes conflicting.