[Possible Significance of Bronchoalveolar Lavage Cytology at Initial Diagnosis and Follow-up of Lung Cancer]. / Evaluation zum möglichen Stellenwert der Bronchiallavagezytologie bei Erstdiagnose und Nachsorge des Lungenkarzinoms.

Bronchoalveolar lavage [BAL] is an important procedure in the diagnosis of a variety of lung diseases. While it has enormous value in the diagnostics of inflammatory parenchymal diseases, its significance in lung cancer is unclear. Keeping in mind that immune therapy (e. g. application of checkpoint inhibitors) is gaining importance in the management of lung carcinoma, it is important to know if there are typical cellular patterns in BAL of lung cancer patients. Methods In a retrospective proof of principle-study, we analyzed 38 patients who underwent BAL at the initial diagnosis of lung cancer. Results We observed an elevated level of CD25 lymphocytes as well as an increased expression of DR antigen, both signaling lymphocyte activation. We could not find a typical cytologic pattern of inflammatory cells in lung carcinoma patients. Sensitivity of BAL to malignant cells was rare, thus confirming earlier analysis. Conclusion We could not demonstrate typical cellular patterns in BAL of lung cancer patients. Evaluation of specific microRNA patterns might play a supporting role in the initial diagnosis as well as follow-up of lung cancer patients.

[Epitheloid cell granulomas in bronchial invasive mucinous adenocarcinoma]. / Epitheloidzellige Granulome bei bronchialem Adenokarzinom vom überwiegend muzinösen Typ.

Granulomatous lung diseases are frequently occurring pulmonary diseases.Important granulomatous lung diseases are sarcoidosis and pulmonary tuberculosis. Furthermore, granulomas can be caused by foreign body reactions like berylliosis or silicosis as well as by other infections (e. g. by nocardia spp.).Granulomatous systemic inflammatory diseases such as the Churg Strauss syndrome or the Wegener's granulomatosis can harm the lung as well.In this case report, we describe a patient who visited our emergency room because of apparent refractory pneumonia. First histologic specimens showed sarcoid-like lesions. Subsequent investigation showed invasive mucinous adenocarcinoma of the lung.

Erratum to "Practical guidelines: lung transplantation in patients with cystic fibrosis".

[This corrects the article DOI: 10.1155/2014/621342.].

[Measures to improve the health situation of patients with rare diseases in Germany. A comparison with the National Action Plan]. / Maßnahmen zur Verbesserung der gesundheitlichen Situation von Menschen mit seltenen Erkrankungen in Deutschland. Ein Vergleich mit dem Nationalen Aktionsplan.

BACKGROUND: Approximately 4 million patients with a rare disease live in Germany. The medical care of these patients is problematic because of the rarity and heterogeneity of different clinical pictures. The Federal Ministry of Health has therefore published a research report on "Measures to improve the health situation of people with rare diseases in Germany" in 2009. OBJECTIVE: The aim of this paper is to present the main recommendations of this research report and relate it to current developments in the field of medical care for people with rare diseases. METHODOLOGY: The care situation of patients with rare diseases was determined using questionnaires, expert interviews and focus group discussions with representatives of patients, service providers and stakeholders from the health institutions. RESULTS: The main range of actions that have been identified in the research report were centre and network formation, specialized forms of medical care, diagnosis and treatment, information and experience exchange, performance fees and reimbursement of the costs, guidelines and patient pathways, the research, the implementation of a National Action Alliance and the development of a National Action Plan. DISCUSSION: In March 2010 a National Action League for People with Rare Diseases (NAMSE) was founded. The NAMSE created a national plan of action for people with rare diseases for improving medical care in the field of rare diseases which was approved by the Federal Government in August 2013. Thus, two important areas of the research report have already been implemented. In a comparison of the areas of activity of the research report with those of the National Action Plan it becomes clear that priorities will be in the context of health services research in rare diseases, for example the introduction of centres of reference for rare diseases, measures to accelerate the diagnostic process and the promotion of research and information management in the future.

Practical guidelines: lung transplantation in patients with cystic fibrosis.

There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation.

[Emergencies in adult mucoviscidosis patients]. / Notfälle bei erwachsenen Mukoviszidosepatienten.

Cystic fibrosis is an inherited autosomal recessive metabolic disease caused by mutations on the CFTR gene. This leads to defective chloride channels on epithelial cell membranes and causes various disorders of the respiratory, gastrointestinal, and urogenital tracts.As a result, all exocrine glands produce a viscous secretion, leading to pulmonary symptoms such as chronic cough, secretion retention, recurring infections as well as bronchiectasis and obstructive lung emphysema. Gastrointestinal effects include exocrine and often also endocrine pancreatic insufficiency with chronic diarrhea and maldigestion syndrome as well as pancreoprivic diabetes mellitus; biliary cirrhosis occurs in 10% of cases. Additional effects include reduced fertility in women and infertility in men.Life-threatening complications include bleeding from the bronchial arteries, pneumothorax, and distal intestinal obstruction syndrome (DIOS), previously known as meconium ileus equivalent. Treatment requires rapid diagnosis and should be carried out in experienced centres, since the mortality rate can otherwise be up to 50%.

Travelling with cystic fibrosis: recommendations for patients and care team members.

There are no European Guidelines on issues specifically related to travel for people with cystic fibrosis (CF). The contributors to these recommendations included 30 members of the ECORN-CF project. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Executive Agency of Health and Consumers of the European Union and the Christiane Herzog Foundation. The main goal of this paper is to provide patient-oriented advice that complements medical aspects by offering practical suggestions for all aspects involved in planning and taking a trip. The report consists of three main sections, preparation for travel, important considerations during travel and at the destination, and issues specific to immunocompromised travellers. People with CF should be encouraged to consult with their CF centre prior to travel to another country. The CF centre can advise on the necessary preparation for travel, the need for vaccinations, essential medications that should be brought on the trip and also provide information relating to CF care in the region and plan of action in case of an emergency.

A phase II study on safety and efficacy of high-dose N-acetylcysteine in patients with cystic fibrosis.

OBJECTIVE: We conducted a single-centre, randomised, double-blinded, placebo-controlled phase II clinical study to test safety and efficacy of a 12-week therapy with low-dose (700 mg/daily) or high-dose (2800 mg/daily) of NAC. METHODS: Twenty-one patients (DeltaF508 homo/heterozygous, FEV1>40% pred.) were included in the study. After a 3-weeks placebo run-in phase, 11 patients received low-dose NAC, and 10 patients received high-dose NAC. Outcomes included safety and clinical parameters, inflammatory (total leukocyte numbers, cell differentials, TNF-alpha, IL-8) measures in induced sputum, and concentrations of extracellular glutathione in induced sputum and blood. RESULTS: High-dose NAC was a well-tolerated and safe medication. High-dose NAC did not alter clinical or inflammatory parameters. However, extracellular glutathione in induced sputum tended to increase on high-dose NAC. CONCLUSIONS: High-dose NAC is a well-tolerated and safe medication for a prolonged therapy of patients with CF with a potential to increase extracellular glutathione in CF airways.

Variables affecting the risk of pneumothorax and intrapulmonal hemorrhage in CT-guided transthoracic biopsy.

The influence of various variables on the rate of pneumothorax and intrapulmonal hemorrhage associated with computed tomography (CT)-guided transthoracic needle biopsy of the lung were evaluated retrospectively. One hundred and thirty-three patients underwent CT guided biopsy of a pulmonary lesion. Two patients were biopsied twice. Variables analyzed were lesion size, lesion location, number of pleural needle passes, lesion margin, length of intrapulmonal biopsy path and puncture time. Eighteen-gauge (18G) cutting needles (Trucut, Somatex, Teltow, Germany) were used for biopsy. Pneumothorax occurred in 23 of 135 biopsies (17%). Chest tube placement was required in three out of 23 cases of pneumothorax (2% of all biopsies). Pneumothorax rate was significantly higher when the lesions were located in the lung parenchyma compared with locations at the pleura or chest wall (P < 0.05), but all pneumothorax cases which required chest tube treatment occurred in lesions located less than 2 cm from the pleura. Longer puncture time led to an increase in pneumothorax rate (P < 0.05). Thirty-seven (27%) out of 135 biopsies showed perifocal hemorrhage. Intrapulmonal biopsy paths longer than 4 cm showed significantly higher numbers of perifocal hemorrhage and pneumothorax (P < 0.05). Significantly more hemorrhage occurred when the pleura was penetrated twice during the puncture (P < 0.05). Lesion size <4 cm is strongly correlated with higher occurrence of perifocal hemorrhage (P < 0.05). Lesion margination showed no significant effect on complication rate. CT-guided biopsy of smaller lesions correlates with a higher bleeding rate. Puncture time should be minimized to reduce pneumothorax rate. Passing the pleura twice significantly increases the risk of hemorrhage. Intrapulmonal biopsy paths longer than 4 cm showed significantly higher numbers of perifocal hemorrhage as well as pneumothorax.

[Damage to the respiratory tract due to aspirated alendronate]. / Schädigung des Respirationstrakts durch aspiriertes Alendronat.

We describe the rare case of a high-grade chemical irritating-toxic damage to the larynx, the trachea and the bronchial system due to the aspiration of the bisphosphonate alendronate. The aspiration of alendronate was caused by oropharyngeal dysphagia. The 68-year-old female patient was sent to hospital with increasing hoarseness and a tormenting continuous cough of high intensity. X-Ray pictures of the thorax showed dystelectasis of the right middle lobe. Severe damage to the bronchial system caused by the aspirated alendronate was demonstrated by flexible bronchoscopy. Anti-obstructive, antiphlogistic and antibiotic treatment led to a gradual improvement of the symptoms. The administration of alendronate should be avoided in cases of dysphagia. Besides the danger of oesophageal injury, there is also the risk of aspiration that can be associated with severe damage to the bronchial system as this case study demonstrates.

Determination of the optimal MRI sequence for the detection of malignant lung nodules.

OBJECTIVE: For staging, follow-up and even screening (www.screening.info) an "all-in-one" imaging examination is desirable. In the concept of whole body MRI, lung imaging prevails as the weakest link. The purpose of our study was to determine the optimal MRI sequences for the detection of malignant lung nodules. PATIENTS AND METHODS: On the basis of 6 lung cancer, 46 metastases and one tuberculoma in 13 patients eight MRI sequences--HASTE, IR-HASTE, fat saturated TrueFISP, STIR, VIBEipat = 2, and contrast-enhanced (CE) VIBE (with ipat = 2, 0, 4) performed with parallel imaging and 12 matrix coil elements--were compared in terms of contrast-to-noise ratio (CNR) and quality in the visualization of the lung nodules using multidetector CT as standard of reference. The parameters of the sequences were pragmatically selected to minimize the imaging time to allow for imaging the entire lung within one breathold interval. RESULTS: The STIR sequence was found to be the best for detecting malignant lung nodules (p<0.01) followed by the FS TrueFISP, CE VIBE subsetipat = 0, CE VIBE subsetipat = 2, IR-HASTE, HASTE, CE VIBE subsetipat = 4, and VIBE. The STIR sequence visualized malignant nodules down to 2 mm in size and did not display the 19 mm tuberculoma. CONCLUSION: The STIR sequence should be included in future studies investigating if MRI can compete with CT in the early identification (detection and classification) of malignant lung nodules.

[Location of mechanical ventilation in the specialized centre--intensive care unit, respiratory intermediate care unit and the specialized normal ward]. / Ort der maschinellen Beatmung im Beatmungszentrum--Intensivstation, Intermediate care oder spezialisierte Normalstation.

Until recently "mechanical ventilation" meant "intensive care unit (ICU)". Important arguments for more flexibility concerning the locality where patients are mechanically ventilated are the increase in number of patients, costs and reduced resources. The pulmonary centre for mechanical ventilation, where ICU, respiratory intermediate care unit (RICU) and the specialized normal ward are complementary, is an attractive option for the future. The RICU is the key player in this concept, since as a step down unit it represents a cost-effective approach to the care of substantial numbers of selected patients requiring specialized respiratory care, e. g. intensive respiratory monitoring and therapy, particularly those requiring prolonged mechanical ventilation and non-invasive mechanical ventilation. Success of the RICU requires an experienced team, adequate location and high quality of technical equipment, experienced team, adequate location and high quality of technical equipment.

[New concepts of pathophysiology and therapy in cystic fibrosis]. / Neue Konzepte zur Pathophysiologie und Therapie der Mukoviszidose.

Today, the majority of cystic fibrosis (CF) patients treated in Germany have reached adulthood. However, with increasing age the morbidity and frequency of severe pulmonary complications continues to rise. Further optimization of conventional therapy alone will be insufficient to compensate for this development. In recent years, there has been impressive progress in our understanding of the molecular basis of the CF gene and its product, the cystic fibrosis transmembrane conductance regulator (CFTR). This knowledge can now be applied to develop new therapeutic strategies. However, important questions remain to be solved, i. e., little is known about the pathways that link the malfunctioning of the CFTR protein with the observed clinical phenotype. This review briefly touches on CF genetics as it applies to lung disease and will focus on the current hypotheses of CFTR (dys)function and its impact on pulmonary fluid homeostasis. New treatment options that target the molecular basis of the disease will be discussed.

Glutathione and glutathione peroxidase in sputum samples of adult patients with cystic fibrosis.

BACKGROUND: Reduced glutathione (GSH) is a major antioxidant in the lung. In cystic fibrosis (CF) patients, extracellular GSH levels of lower airways, obtained by bronchoalveolar lavage (BAL), were reported to be lower than non-CF individuals. METHODS: Upper airway secretions of stable adult CF patients (29 spontaneous and 13 induced sputum) and non-CF individuals (14 healthy and 12 asthmatics; all induced sputum) were analyzed for total glutathione (i.e. the sum of reduced, GSH, and oxidized, GSSG, forms), GSH and GSSG levels by enzymatic kinetic assay. RESULTS: In CF, both spontaneous and induced sputum samples were comparable in total glutathione levels which were surprisingly high (median concentration of 9.2 (range 1.4-65.2) and 11.6 (1.1-69.8) microM, respectively). In non-CF individuals, total glutathione levels were significantly lower (healthy 2.8 (1.0-12.3), asthmatics (5.3 (1.3-19.2) microM; p<0.001, both vs. CF). In CF, more than 90% of total glutathione was represented by GSH, whereas in non-CF controls, GSH made up less than 50% of total glutathione (p<0.001). CONCLUSIONS: In contrast to BAL, CF sputum contains high levels of GSH. Sputum induction is a potentially useful procedure to monitor antioxidant levels in upper airways of CF patients.

Incorporation of biodegradable nanoparticles into human airway epithelium cells-in vitro study of the suitability as a vehicle for drug or gene delivery in pulmonary diseases.

PURPOSE: Nanoparticles are able to enhance drug or DNA stability for purposes of optimised deposition to targeted tissues. Surface modifications can mediate drug targeting. The suitability of nanoparticles synthesised out of porcine gelatin, human serum albumin, and polyalkylcyanoacrylate as drug and gene carriers for pulmonary application was investigated in vitro on primary airway epithelium cells and the cell line 16HBE14o-. METHODS: The uptake of nanoparticles into these cells was examined by confocal laser scan microscopy (CLSM) and flow cytometry (FACS). Further the cytotoxicity of nanoparticles was evaluated by an LDH-release-test and the inflammatory potential of the nanoparticles was assessed by measuring IL-8 release. RESULTS: CLSM and FACS experiments showed that the nanoparticles were incorporated into bronchial epithelial cells provoking little or no cytotoxicity and no inflammation as measured by IL-8 release. CONCLUSIONS: Based on their low cytotoxicity and the missing inflammatory potential in combination with an efficient uptake in human bronchial epithelial cells, protein-based nanoparticles are suitable drug and gene carriers for pulmonary application.