Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.

Lung Volume Reduction Surgery Reduces Pulmonary Arterial Hypertension Associated With Severe Lung Emphysema and Hypercapnia.

Lung volume reduction surgery (LVRS) represents a standard surgical approach for patients with severe pulmonary emphysema. One of the relevant risk factors for LVRS is the presence of pulmonary arterial hypertension (PAH). The aim of this study is to assess the postoperative changes in pulmonary arterial pressure (PAP) after LVRS for patients with severe pulmonary emphysema compared with preoperative measures. N = 61 consecutive patients with severe pulmonary emphysema and preoperative evidence for PAH (pulmonary arterial systolic pressure [PASP] ≥ 35 mmHg) were prospectively included into this study. In all patients, thoracoscopic LVRS was performed. PASP was assessed by echocardiography before surgery, early postoperatively, and 3 months after surgery. Data were prospectively recorded and analyzed retrospectively. Primary end points were the postoperative changes in PASP as well as the 90 day mortality rate. Secondary endpoints included: pulmonary function test, exercise capacity, quality of life, and dyspnea symptoms (Borg scale). Early after surgery, a significant reduction in PASP was observed at the day of discharge and at 3 month follow-up. In n = 34 patients, no tricuspid valve regurgitation was detectable anymore suggesting normal PAP. In n = 3 patients, venovenous extracorporeal lung support (VV ECLS) was already implemented preoperatively. In the remaining cases, VV ECLS was applied intraoperatively and continued postoperatively. Mean duration of postoperative ECLS support was 2 days. Four patients died due to acute right heart failure, two patients from sepsis with multiorgan failure, and one patient from acute pulmonary embolism. Ninety day mortality was 11.5 %. A significant improvement was postoperatively observed regarding the performance status, dyspnea scale, as well as quality of life. This study suggests a beneficial effect of LVRS on PAP, which may ultimately help to protect and stabilize right ventricular function. Further studies, implementing pre- and postoperative right heart catheterizations including invasive PAP evaluation, are necessary to support the findings in this study in greater detail.

Veno-Venous Extracorporeal Lung Support as a Bridge to or Through Lung Volume Reduction Surgery in Patients with Severe Hypercapnia.

Extracorporeal lung support (ECLS) represents an essential support tool especially for critically ill patients undergoing thoracic surgical procedures. Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we report the efficacy of veno-venous ECLS (VV ECLS) as a bridge to or through LVRS in patients with end-stage lung emphysema and severe hypercapnia. Between January 2016 and May 2017, 125 patients with end-stage lung emphysema undergoing LVRS were prospectively enrolled into this study. Patients with severe hypercapnia caused by chronic respiratory failure were bridged to or through LVRS with low-flow VV ECLS (65 patients, group 1). Patients with preoperative normocapnia served as a control group (60 patients, group 2). In group 1, VV ECLS was implemented preoperatively in five patients and in 60 patients intraoperatively. Extracorporeal lung support was continued postoperatively in all 65 patients. Mean length of postoperative VV ECLS support was 3 ± 1 day. The 90 day mortality rate was 7.8% in group 1 compared with 5% in group 2 (p = 0.5). Postoperatively, a significant improvement was observed in quality of life, exercise capacity, and dyspnea symptoms in both groups. VV ECLS in patients with severe hypercapnia undergoing LVRS is an effective and well-tolerated treatment option. In particular, it increases the intraoperative safety, supports de-escalation of ventilatory strategies, and reduces the rate of postoperative complications in a cohort of patients considered "high risk" for LVRS in the current literature.

Intraoperative veno-venous extracorporeal lung support in thoracic surgery: a single-centre experience.

OBJECTIVES: Intraoperative extracorporeal lung support (ECLS) during thoracic surgical procedures is a modern concept that is gaining increasing acceptance. So far, cardiopulmonary bypass (CPB), veno-arterial extracorporeal membrane oxygenation (v-a-ECMO) or pumpless arterio-venous interventional lung assist (iLA) were utilized for intraoperative support. Only a few case reports have described the use of veno-venous ECMO for intraoperative ECLS. Here, we report our experience with intraoperative ECLS using different veno-venous low-flow and high-flow settings adapted to the individual patient requirements. METHODS: Between April 2014 and April 2015, 9 patients underwent pulmonary resections under ECLS. In 6 patients, a twin-port double-lumen cannula was inserted percutaneously into the right femoral vein for low-flow ECLS. In 3 patients, high-flow ECLS was achieved either by femoro-atrial (n = 1) or femoro-jugular cannulation. RESULTS: Indications for ECLS were severely impaired lung function (n = 3), previous pulmonary resections including contralateral pneumonectomy (n = 4), previous single-lung transplantation (sLTX) (n = 1) and extended carinal pneumonectomy (n = 1). Procedures included segmentectomy (n = 3), extended lobectomy with bronchial and vascular anastomoses (n = 1), VATS lobectomy (n = 2), extended left-sided carinal pneumonectomy (n = 1) as well as extended metastasectomy (n = 2). Low-flow ECLS allowed for apnoea up to 45 min in patients with previous pneumonectomy (n = 3) and facilitated protective single-lung ventilation in patients (n = 3) with severely impaired pulmonary function. During trans-sternal carinal pneumonectomy (n = 1), high-flow ECLS achieved by femoro-atrial cannulation allowed for apnoea for 40 min, avoiding cross-field ventilation. In 2 patients requiring extended metastasectomy after previous lobectomy of the contralateral lower lobe (n = 1) or pulmonary metastases in the graft after sLTX for end-stage fibrosis (n = 1), high-flow ECLS by percutaneous femoro-jugular cannulation allowed for extensive metastasectomy under optimal atelectasis of the lung. CONCLUSIONS: For intraoperative ECLS, different modes may be applied depending on the intended procedures and required mechanical ventilation. In our experience, different settings of veno-venous ECLS provide sufficient partial or complete lung support, avoiding possible complications associated with other forms of extracorporeal support such as CPB or v-a-ECMO.

[Acute renal failure and hypercalcemia in an AIDS patient on tenofovir and low-dose vitamin D therapy with immune reconstitution inflammatory syndrome]. / Akutes Nierenversagen und Hyperkalzämie unter tenofovirhaltiger antiretroviraler Therapie bei einer Patientin mit AIDS und Immunrekonstitutionssyndrom nach niedrigdosierter Vitamin-D-Substitution.

BACKGROUND: Tenofovir-containing antiviral therapy might result in acute renal failure and is able to induce tubular dysfunction with hypocalcemia. On the other hand, hypercalcemia induced by intoxication with colecalciferol has been described to induce renal failure in HIV-positive individuals as well. Here, the authors describe the unusual case of reversible renal failure due to hypercalcemia in a patient with low-dose colecalciferol substitution treated with tenofovir. CASE REPORT: A 31-year-old HIV-positive female, CDC stage C3, was admitted to the authors' hospital with progressive renal failure and hypercalcemia. Antiretroviral therapy consisted of tenofovir and emtricitabine in combination with efavirenz. Additionally, she was on low-dose vitamin D(3) substitution (25 microg/d) and calcium supplementation (500 mg/d) due to systemic steroid treatment. CONCLUSION: Additionally to regular control of renal function, serologic level of calcium should be supervised in patients concomitantly treated with tenofovir and colecalciferol.