Cigarette smoke alters inflammatory genes and the extracellular matrix - investigations on viable sections of peripheral human lungs.

Chronic obstructive pulmonary disease (COPD) is a complex chronic respiratory disorder often caused by cigarette smoke. Cigarette smoke contains hundreds of toxic substances. In our study, we wanted to identify initial mechanisms of cigarette smoke induced changes in the distal lung.

Rhinovirus-induced Human Lung Tissue Responses Mimic Chronic Obstructive Pulmonary Disease and Asthma Gene Signatures.

Human rhinovirus (RV) is a major risk factor for chronic obstructive pulmonary disease (COPD) and asthma exacerbations. The exploration of RV pathogenesis has been hampered by a lack of disease-relevant model systems. We performed a detailed characterization of host responses to RV infection in human lung tissue and investigated whether these responses are disease relevant for patients with COPD and asthma.

TMEM16A/ANO1 calcium-activated chloride channel as a novel target for the treatment of human respiratory syncytial virus infection.

Introduction: Human respiratory syncytial virus (HRSV) is a common cause of respiratory tract infections (RTIs) globally and is one of the most fatal infectious diseases for infants in developing countries. Of those infected, 25%-40% aged ≤1 year develop severe lower RTIs leading to pneumonia and bronchiolitis, with ~10% requiring hospitalisation. Evidence also suggests that HRSV infection early in life is a major cause of adult asthma.

Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human Precision-cut Lung Slices.

Respiratory diseases in their broad diversity need appropriate model systems to understand the underlying mechanisms and enable development of new therapeutics. Additionally, registration of new substances requires appropriate risk assessment with adequate testing systems to avoid the risk of individuals being harmed, for example, in the working environment. Such risk assessments are usually conducted in animal studies.

Coagulation factor XII regulates inflammatory responses in human lungs.

Increased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of the acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact phase system of coagulation is activated and may regulate inflammatory responses in human lungs. Components of the contact phase system were characterized in bronchoalveolar lavage fluids (BALF) from 54 ARDS patients and 43 controls, and their impact on cytokine/chemokine expression in human precision cut lung slices (PCLS) was assessed by a PCR array.

Assessment of long-term cultivated human precision-cut lung slices as an ex vivo system for evaluation of chronic cytotoxicity and functionality.

Background: Investigation of basic chronic inflammatory mechanisms and development of new therapeutics targeting the respiratory tract requires appropriate testing systems, including those to monitor long- persistence. Human precision-cut lung slices (PCLS) have been demonstrated to mimic the human respiratory tract and have potential of an alternative, ex-vivo system to replace or augment in-vitro testing and animal models. So far, most research on PCLS has been conducted for short cultivation periods (≤72 h), while analyses of slowly metabolized therapeutics require long-term survival of PCLS in culture.

FXII promotes proteolytic processing of the LRP1 ectodomain.

Background: Factor XII (FXII) is a serine protease that is involved in activation of the intrinsic blood coagulation, the kallikrein-kinin system and the complement cascade. Although the binding of FXII to the cell surface has been demonstrated, the consequence of this event for proteolytic processing of membrane-anchored proteins has never been described.

Methods: The effect of FXII on the proteolytic processing of the low-density lipoprotein receptor-related protein 1 (LRP1) ectodomain was tested in human primary lung fibroblasts (hLF), alveolar macrophages (hAM) and in human precision cut lung slices (hPCLS).

Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS).

Occupational asthma can be induced by a number of chemicals at the workplace. Risk assessment of potential sensitizers is mostly performed in animal experiments. With increasing public demand for alternative methods, human precision-cut lung slices (PCLS) have been developed as an ex vivo model.

Functional testing of an inhalable nanoparticle based influenza vaccine using a human precision cut lung slice technique.

Annual outbreaks of influenza infections, caused by new influenza virus subtypes and high incidences of zoonosis, make seasonal influenza one of the most unpredictable and serious health threats worldwide. Currently available vaccines, though the main prevention strategy, can neither efficiently be adapted to new circulating virus subtypes nor provide high amounts to meet the global demand fast enough. New influenza vaccines quickly adapted to current virus strains are needed.

LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing.

Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS)-induced inflammation model was established in marmoset monkeys (Callithrix jacchus) to reflect crucial features of inflammatory lung diseases.

Natural innate cytokine response to immunomodulators and adjuvants in human precision-cut lung slices.

Prediction of lung innate immune responses is critical for developing new drugs. Well-established immune modulators like lipopolysaccharides (LPS) can elicit a wide range of immunological effects. They are involved in acute lung diseases such as infections or chronic airway diseases such as COPD.

[100 years Heidehaus--from sanatorium for tuberculosis to a modern chest hospital].

When the sanatorium "Heidehaus" was founded on June 1, 1907 in the northern countryside of Hannover with Dr. Otto Ziegler as head about 120 beds for patients with tuberculosis were available. By 1914 about 200 patients were being treated by 4 physicians and 10 nurses.

Aortopexy in infants and children--long-term follow-up in twenty patients.

Background: Aortopexy has become an established surgical procedure for the treatment of tracheomalacia (TM) in infants and children. The aim of the present study was to evaluate the clinical outcome and respiratory function after aortopexy in the long term.

Methods: Between 1992 and 2006, 20 patients (6 female, 14 male) with TM were treated by bronchoscopically monitored pexis of the aorta via a right anterior thoracotomy.

Disseminated Aspergillus fumigatus infection with consecutive mitral valve endocarditis in a lung transplant recipient.

Aspergillus infection is a known complication of lung transplantation and remains associated with high mortality rates. The manifestation of the infection varies from simple colonization of the lung to disseminated complicated infections. Early Aspergillus infection has been rarely observed in a small number of lung transplant recipients; most cases occur during the late post-operative period.

[Laser-induced thermotherapy of lung metastases and primary lung tumors].

We present laser-induced thermotherapy (LITT) of primary and secondary lung tumors analysing indications and technical concepts. Thirty patients with lung metastases of different primary tumors (n=24) as well as localized lung tumors (n=6) were prospectively treated in 41 sessions using laser-induced thermotherapy (LITT). An MR-compatible puncture system was used with direct puncture technique.

Emergent endovascular interventions for contained rupture of thoracic aortic aneurysms.

Background: The purpose of our study was to assess in an emergency setting the feasibility of endovascular stent graft treatment of contained ruptures of thoracic aortic aneurysms.

Methods: Seven patients with contained ruptures of thoracic aortic aneurysms from a series of 54 endovascular interventions were treated by the deployment of an aortic stent graft. In all cases, hemothorax was present.

Surgical versus endovascular treatment of acute thoracic aortic rupture: a single-center experience.

Background: Surgical management of acute thoracic aortic ruptures is controversial, especially in patients with preexisting comorbidities; associated mortality and paraplegia rates remain high. It was our objective to evaluate whether treating these patients acutely with endovascular stent grafts would improve their outcome.

Methods: From November 1999 to February 2002 a total of 54 patients, age 28 to 83 years, were admitted to our institution with an acute rupture of the thoracic aorta (24 ruptured aneurysms, 14 perforated type B dissections, 16 traumatic ruptures).

Emergent endovascular stent grafting for perforated acute type B dissections and ruptured thoracic aortic aneurysms.

Background: The purpose of our study was to demonstrate the effectiveness of endovascular stent grafts in the treatment of acutely ruptured thoracic aortic aneurysms and type B dissections as an alternative to the conventional surgical approach in an emergency setting.

Methods: From January 2001 to October 2001, we deployed 11 emergent endovascular stent grafts into the thoracic aorta. We treated seven ruptured aortic aneurysms and four acutely perforated type B dissections.

Urgent thoracic aortal dissection and aneurysm: treatment with stent-graft implantation in an angiographic suite.

The aim of this study was to evaluate the feasibility of endoluminal stent-graft placement in an angiographic suite for the treatment of emergent type-B aortic dissections and ruptured thoracic aortal aneurysms. Twenty-six patients with either urgent type-B dissection (n=8) or aneurysms (n=18) of the descending thoracic aorta were chosen for stent-graft implantation. All patients received a multidetector-row CT angiography of the whole aorta and pelvic arteries prior to stent-graft implantation.