[100 years DGP -100 years of pneumology in Germany]. / 100 Jahre DGP - 100 Jahre deutsche Pneumologie.

During the first half of its 100-year history, tuberculosis was predominant in the German Society of Pneumology (DGP). This led largely to the separation of pneumology from internal medicine, particularly in the universities. Since the 1960s, the spectrum of respiratory diseases has changed considerably. Asthma, COPD, lung cancer, and pneumonia today rank among the most widespread diseases. Numerous new diagnostic and therapeutic methods have induced dramatic changes in the field of pneumology. Today, pneumology, together with cardiology and gastroenterology, belongs to the major specialties of internal medicine. One of the most urgent tasks of the DGP is to improve the insufficient representation at German universities, and thus promote teaching and research in respiratory medicine.

[Sensitization to airborne ragweed pollen--a cause of allergic respiratory diseases in Germany?]. / Sensibilisierung gegen Ambrosiapollen--Eine Ursache für allergische Atemwegserkrankungen in Deutschland?

BACKGROUND AND OBJECTIVE: Allergic skin and respiratory diseases show a high prevalence in most industrial countries. In addition, during the last years ragweed colonization has increased in Europe. Ambrosia pollen ( AMBROSIA ARTEMISIIFOLIA L. - common ragweed) are highly allergenic. Due to the late flowering time (august/September) of ragweed this can result in increasing health threats for allergic populations. This is of particular importance for those who already are sensitive to some grass or tree pollen. These individuals can then suffer from allergies during nearly the whole year. The present study examined the prevalence of sensitization to ragweed in German children and possible health implications. METHODS: Between 2004 and 2007 sera of 1323 10-years old children in Baden Württemberg were tested in-vitro for specific IgE-antibodies against common aeroallergens including ragweed pollen. RESULTS: Specific IgE-antibodies to extracts of common ragweed pollen were present in 10 - 17 % of the tested sera depending on the year of investigation. CONCLUSION: The determined specific IgE-antibodies may be the result of a direct sensitization to ragweed pollen or correspond to cross-reactivity to other plants of the asteraceae subfamily or some nutritional allergens. The detection of sensitization to ragweed pollen does not prove actual allergic disease. However, a ragweed derived allergy should be considered in the differential diagnosis when allergic symptoms are present in direct connection to the flowering-time of ragweed. Ragweed plants should be removed and the spread of the plant 'restricted', as experiences in other countries with already wide spreading show.

[Assessment and outcome parameters in COPD]. / Beurteilungs- und Prognosekriterien bei COPD1.

BACKGROUND: A standard outcome parameter for pharmacological trials in COPD has not yet been defined. Therefore, it is the aim of this review to evaluate frequently used parameters for their eligibility as assessment and outcome parameters in COPD. METHODS: A review of the actual scientific literature was performed. RESULTS: It is recommended to continue to rely primarily on the FEV (1), which has been used as a primary variable in the vast majority of trials. In addition, further parameters, such as FVC and IC/TLC should be determined. If available, additional information is provided by RV/TLC, K (co), PaO (2) and PaCO (2). FEV (1) is not a surrogate parameter for dyspnoea, quality of life, and exercise tolerance, which should therefore be assessed separately. Frequency and severity of exacerbations and mortality are important outcome parameters in long-term trials. Complex indices, such as the BODE index, may be superior to single variables. CONCLUSIONS: No single additional parameter has been evaluated sufficiently in order to substitute FEV (1) as the standard parameter for the assessment and outcome in COPD.

["Erlangen broncho-trainer" -- newly developed training model with physiological ventilation for interventional bronchoscopy]. / Neuentwicklung eines Trainingsmodells mit physiologischer Ventilation für die interventionelle Bronchoskopie.

BACKGROUND: Biosimulation models have proved their value in numerous training courses for endoscopic procedures and play an important role in education and further training, as well as in the introduction of new techniques. In the field of interventional bronchoscopy, the level of realism is increased when biological lung tissue is available not only in a collapsed state, but also with physiological expansion. METHODS/RESULTS: A new modification of the well-known Erlangen Endo-Trainer has been developed, involving a transparent cover that provides airtight closure of the thoracic cavity. An integrated vacuum pump creates low pressure in the interior of the model. This allows a training lung from the pig to be fully expanded and "physiologically ventilated", with adjustable intermittent inspiration and expiration phases. The breathing and completely expandable biological training lung from the pig not only provides better anatomical orientation thanks to the lung's full three-dimensional expansion, but with the convincing and realistic quality of the tissue it also provides a good practice facility for various types of bronchoscopic intervention. CONCLUSIONS: In an initial training course, the new system successfully allowed various diagnostic techniques to be practiced, such as bronchoalveolar lavage (BAL), transbronchial needle aspiration (TBNA), and peripheral forceps biopsies with transillumination guidance and interventional techniques such as foreign-body removal and electrocautery as well. These initial positive results are also encouraging for the future provision of training facilities in additional interventional techniques.

[Persistent left superior vena cava with right-left shunt into the left atrium]. / Persistierende linke Vena cava superior mit Rechts-Links-Shunt zum linken Atrium.

UNLABELLED: Persistent left superior vena cava with right-left shunt into the left atrium. HISTORY AND CLINICAL FINDINGS: A 72-year-old patient was admitted to the hospital following bleeding into the basal ganglia secondary to a hypertensive crisis. INVESTIGATIONS: The patient was found to suffer from marked hypoxaemia (pO2 49 mmHg) and erythrocytosis (Hb 18,5 g/dl). Subsequent investigations raised suspicion of a right-left shunt. This was verified by a contrast echocardiogram which was performed transthoracically by injection of echo-contrast material from the left. To improve imaging of the shunt a transoesophageal contrast-echocardiogram was carried out. This showed that the persistent left superior vena cava did not, as previously expected, lead directly into the left atrium, but had a connection to the left superior pulmonary vein. This anatomical variant, which so far to our knowledge has not been reported in the literature, could be confirmed by spiral computed tomography. Apart from an atrial septal aneurysm no other cardiac anomaly could be identified. TREATMENT AND COURSE: Ligation of the left superior vena cava could have been a therapeutic option, but the patient declined operative intervention. CONCLUSION: In cases of profound hypoxemia and erythrocytosis the differential diagnosis must include a persistent left superior vena cava with anomalous connection to the left atrium. Trans-thoracic and transoesophageal contrast-echocardiography is a simple and reliable method to diagnose persistent left superior vena cava as well as concomitant cardiac anomalies.

[Measurement of transdiaphragmatic pressure in pulmonary emphysema, a relevant contribution to clinical management?]. / Messung des transdiaphragmalen Drucks beim Lungenemphysem, ein wichtiger Beitrag zum klinischen Management?

In 50 patients with advanced pulmonary emphysema, admitted for operative lung volume reduction, transdiaphragmatic pressure was measured by a double balloon catheter, using the sniff technique.Transdiaphragmatic pressure (pdi) is the difference between gastric pressure (pga) and esophageal pressure (pes). The mean value of pdi in the sitting position was 5,9 kPa (SD 1,6 kPa), in the lying position 5,6 kPa (SD 1,3 kPa). 94 % of the patients had a pathologic pdi (below 8,2 kPa). The reduction of diaphragm function in this patient group was quantified. No significant difference was found between sitting or lying position. There was no clear correlation between pdi and the reduction in lung function. Maybe there are other important factors, for example the influence of the deformation in the chest wall itself.

Variability of cyclophosphamide uptake into human bronchial carcinoma: consequences for local bioactivation.

PURPOSE: The alkylating cytostatic prodrug cyclophosphamide is bioactivated by the human cytochrome P450 enzyme system. Since these enzymes are not only expressed in human liver, but also in extrahepatic tissue, local bioactivation of this drug may play an important role in its antineoplastic effects, e.g., chemotherapy of lung tumors. This would require uptake of significant amounts of cyclophosphamide into tumor tissue, which has not yet been demonstrated. METHODS: We used a recently developed, ex vivo isolated, ventilated and perfused human lung model to study cyclophosphamide uptake into bronchial carcinoma and healthy lung tissue. Following a standard lobectomy, lung samples containing the tumor were perfused with buffer containing 2 mM cyclophosphamide for 2 h. Cyclophosphamide concentrations in perfusate and healthy peripheral tissue were measured during the perfusion and in tumors at the end of perfusion. RESULTS: In all tissue samples, cyclophosphamide uptake was relatively poor, indicated by a tissue to perfusate ratio of 0.021. Moreover, in tumor samples, cyclophosphamide concentrations were significantly lower (P < 0.05) than in healthy lung tissue and showed pronounced interindividual variability. Median concentrations were 36.8 microg/g (26.9 44.2 microg/g) in healthy tissue and 5.1 microg/g (0.0-26.8 microg/g) in tumor samples. Tumor cyclophosphamide concentrations varied between 0 and 75% of those reached in healthy tissue. CONCLUSIONS: Our results indicate that CP tumor concentrations are modulated by factors different from dose and that expression of bioactivating enzymes in human lung or transfection of genes encoding these enzymes into tumor cells does not necessarily lead to local bioactivation of cyclophosphamide.

Neoadjuvant chemoradiotherapy of stage III non-small-cell lung cancer.

Twenty to 30% of patients with non-small-cell lung cancer (NSCLC) in stage III are not resectable primarily with 5-year survival less than 10%. Since the majority of patients die from metastases, efforts have been made in the past to improve prognosis by application of neoadjuvant chemoradiotherapy regimens followed by subsequent resection. In a phase II study performed between 1993 and 1998, 93 patients in stage III (IIIA, 16%; IIIB, 84%) received an induction chemotherapy consisting of two cycles cisplatin (100 mg/m2) and vindesine (3 mg/m2) with subsequent sequential radiotherapy of 36 Gy. Sixty-five patients demonstrated partial or complete remission. Sixty underwent surgery; in 49 of them complete resection was possible. Five-year survival in the whole group was 24%, and that in the surgical cohort 39%. Six patients had no residual tumor. Postoperative N0 status was associated with a 5-year survival of 75%, and stage N1-3 with 13%. Thirty-day mortality was 7% postoperatively. Neoadjuvant chemoradiotherapy can significantly improve long-term survival in stage III NSCLC with an acceptable therapy-induced mortality.

Bronchoscopic aspects of renal cell carcinoma (RCC).

A symposium on RCC in July 1998 in Tübingen was where we to reviewed our patients with endobronchial metastatic RCC treated by bronchoscopy since 1981. 24 of 26 consecutive cases are the subject of the present study. Tumor history, X-ray findings, endobronchial appearance, treatment and the pathogenetic mechanisms of this special form of metastatic spread are demonstrated and discussed. In 5 patients > 10 years relapsed between nephrectomy and bronchoscopic tumor therapy. A thrombuslike tumor growth and bleeding were striking bronchoscopic features. In X-ray besides atelectasis, hilar or mediastinal masses were seen half of the patients, in 50% without parenchymal lung nodes, suggesting lymphogenic spread. In several patients bronchial recanalisation could be successfully repeated over long periods. Abnormal X-ray, haemoptysis or dyspnoa in patients with RCC demands bronchoscopy. In case of bronchial tumor obstruction bronchoscopic treatment offers excellent palliation.

Enhanced uptake of doxorubicin into bronchial carcinoma: beta-glucuronidase mediates release of doxorubicin from a glucuronide prodrug (HMR 1826) at the tumor site.

Lack of tumor selectivity is a severe limitation of cancer chemotherapy. Consequently, reducing dose-limiting organ toxicities such as the cardiac toxicity of doxorubicin (Dox) is of major clinical relevance. Approaches that would facilitate a more tumor-selective anticancer therapy by using nontoxic prodrugs that are converted to active anticancer agents at the tumor site have been the subject of intensive research. One potential method to overcome the cardiac toxicity of Dox is to apply a nontoxic, glucuronide prodrug (HMR 1826) from which Dox is released by the action of beta-glucuronidase, an enzyme present at high levels in many tumors. Using a recently developed, isolated, perfused human lung model, we compared the uptake of Dox into normal lung and lung tumors after a 2.5-h lung perfusion with doxorubicin (n = 8) and with the novel doxorubicin glucuronide prodrug (n = 8). Dox showed a poor uptake into lung tumors as compared with normal lung [mean Dox concentration at the end of perfusion, 1.78 +/- 3.11 (median, 0.66) microg/g versus 22.03 +/- 10.4 (median, 18.5) microg/g; P < 0.001]. However, after perfusion with HMR 1826, the level of Dox in tumor tissue was about 7-fold higher than after perfusion with Dox itself [14.04 +/- 12.9 (median, 12.9) microg/g versus 1.78 +/- 3.11 (median, 0.66) microg/g, P < 0.05, n = 8]. In vitro experiments showed a significantly higher beta-glucuronidase expression and activity in the tumors. The extent of in vitro cleavage of HMR 1826 by homogenized lung tissue was closely related to the content of beta-glucuronidase (r = 0.9834, P < 0.0001). When D-saccharolactone, a specific inhibitor of beta-glucuronidase, was added to the perfusate containing HMR 1826, no accumulation of Dox in lung tissue was seen. These data indicate that the high Dox levels achieved in the tumors with HMR 1826 resulted from cleavage of the prodrug by beta-glucuronidase at the tumor site. Thus, the problem of poor Dox uptake into lung tumors could be circumvented by applying the doxorubicin glucuronide prodrug. Several lines of evidence based on both ex vivo and in vitro results indicate that the approach described using a glucuronide prodrug may be useful in facilitating more selective delivery of chemotherapy to tumors in humans.

[Video bronchoscopy--the electronic view of the bronchus]. / Das Videobronchoskop--der elektronische Blick auf den Bronchus.

The optical resolution in the fibrescopes commonly in use is limited by the number and length of glass fibres used in the endoscopes. In the videoscope--i.e. in the direct videoscopy--the endoscopic picture is transformed already in the tip of the endoscope into electronic signals which can be guided through electrical wire nearly free from losses. This results in an enormous improvement of the image quality. Some problems arise from the adjustment of the light intensity yielding too much brightness in the short-distance and darkness in the depth. Furthermore, the work channel of the prototype we used is still too small. The investigation with this new technique requires an increased coordinative effort between the handling of the instrument and the picture on the monitor; but with some practice one becomes familiar with it. The pictures of the bronchial wall are extremely brilliant. Unusual structures of bronchial mucosa can be analyzed. Microscopic endoscopy seems to be only a short step away. Digital processing of the electronic image offers extraordinary perspectives for the future.

[Lung changes caused by Mycobacterium xenopi infection in a patient with bone marrow transplantation: problems in differential diagnosis]. / Lungenveränderungen durch Infektion mit Mycobacterium xenopi bei einem Patienten nach Knochenmarktransplantation: Differentialdiagnostische Probleme.

Pulmonary affections caused by atypical mycobacteria are an increasingly common problem particularly in patients with immune deficiency disorders. We here report a case of pulmonary infiltrates due to Mycobacterium xenopi in a patient after allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission and under immunosuppressive treatment with prednisolone and Cyclosporin A. While sputum cultures, serology as well as bronchial lavage and transbronchial biopsy remained inconclusive, diagnosis could only be established by open lung biopsy. We suggest that particularly in immunocompromised patients unclear pulmonary infiltrates require rapid and possibly invasive diagnostic procedures.