Pneumologie

Thrombospondin (TSP) signals focal adhesion disassembly (the intermediate adhesive state) through interactions with cell surface calreticulin (CRT). TSP or a peptide (hep I) of the active site induces focal adhesion disassembly through binding to CRT, which activates phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinase (ERK) through Galphai2 proteins. Because CRT is not a transmembrane protein, it is likely that CRT signals as part of a coreceptor complex. We now show that low density lipoprotein receptor-related protein (LRP) mediates focal adhesion disassembly initiated by TSP binding to CRT. LRP antagonists (antibodies, receptor-associated protein) block hep I/TSP-induced focal adhesion disassembly. LRP is necessary for TSP/hep I signaling because TSP/hep I is unable to stimulate focal adhesion disassembly or ERK or PI3K signaling in fibroblasts deficient in LRP. LRP is important in TSP-CRT signaling, as shown by the ability of hep I to stimulate association o...

In a pilot project we examined whether an improvement of oxygen saturation (SPO (2)) can be established by applying a modified respiratory intervention technique (bagging) for patients in early neurorehabilitation. The "bagging" method involves adding air into the lungs during the inspiration phase by using a resuscitation bag. Subsequently, the patient is requested to cough, and is given manual support on the chest by the therapist. We examined a group of 11 patients who received 1 - 2 bagging interventions per day over a period of 12 days. By applying the bagging method, a continuous and stable improvement of oxygen saturation could be accomplished for all patients. A single case analysis confirmed this effect for each patient. Furthermore, we observed an improvement of the patients' vigilance, improved quality of bronchial secretion and marked improvements in swallowing and phonation. The bagging method is an easy-to-learn and inexpensive method that leads to a stab...

Diagnosis and treatment of sleep disordered breathing (SDB) undergo substantial changes, both in terms of increasing scientific knowledge and also in terms of patient provision and socio-economic aspects. Increasing evidence shows the relevance of SDB on morbidity and mortality of affected patients. The precise differentiation of different phenotypes of SDBs has improved substantially in recent years. These proceedings influence the approach to the patients suspected of suffering from SDB. The scientific advances on the one hand are facing intentions to simplify diagnostical processes and treatment initiation and intentions to translate duties of physicians to non-medical personnel on the other hand. This consensus paper presents the principals of diagnosis, treatment initiation and provision, including the role of different participants of the healthcare system, and compares different treatment options. Major aspects include the differentiation of the diagnostical process in screen...

This is an updated overview of indications, contraindications, performance and interpretation of bronchial challenge tests. As speciality, the diagnostic step by step scheme comprises in addition to the clinical case history a detailed exposure (occupational) history, lung function testing, assessment of nonspecific bronchial hyperresponsiveness, allergological diagnostics (skin prick test, measurement of specific IgE antibodies), privation and reexposure test and as gold standard specific bronchial challenge tests. The last mentioned tests are of particular importance in the framework of a diagnostic backup with regard to specific therapeutic and preventive measures and insurance regulations (occupational disease?). Specific bronchial challenge tests and their variant, the workplace-related challenge test, serve to objectify or exclude the clinical relevance and the current state of a respiratory sensitization. They require a comprehensive experience of the physician performing the...

Spirometry is a simple test and considered the gold standard in lung function. An obstructive ventilatory defect is a disproportionate reduction of maximal airflow from the lung in relation to the maximal volume that can be displaced from the lung. It implies airway narrowing and is defined by a reduced FEV1/FVC ratio below the 5th percentile of the predicted value (lower limit of normal, LLN). A restrictive disorder may be suspected when vital capacity (FVC) is reduced and FEV1/FVC is normal. It is definitely proven, however, only by a decrease in TLC below the 5th percentile of predicted value (LLN). The measurement of TLC by body plethysmography is necessary to confirm or exclude a restrictive defect or hyperinflation of the lung when FVC is below the LLN.2012 a task force of the ERS published new reference values based on 74 187 records from healthy non-smoking males and females from 26 countries. The new reference equations for the 3-95 age range are now available that include ...

Central nervous system tuberculosis remains a clinical diagnostic challenge. The ex vivo Mycobacterium tuberculosis-specific enzyme-linked immunospot assay (ELISPOT) is a novel assay for the rapid detection of M. tuberculosis-specific T-lymphocytes in the peripheral blood. However, when performed on peripheral blood, this assay cannot distinguish between active tuberculosis or latent tuberculosis infection. On the assumption that M. tuberculosis-specific T-lymphocytes migrate to sites of infection, we were able to demonstrate high levels of M. tuberculosis-specific cells by ELISPOT in the cerebrospinal fluid of a patient with tuberculous meningitis and intracerebral tuberculoma four weeks before cerebrospinal fluid culture became positive for M. tuberculosis by culture.

We report on a 73-year-old man, who developed chronical bronchitis after 15 years of working as a coal miner. About 3 decades later a manifest COPD, and additionally a silicosis, were diagnosed. The silicosis was rated as an accepted case for the hazard insurance, but not as a reason for pension. The reasoning for the declining of pension for the applicant is refuted by the literature which defines occupational diseases and is generally accepted by the legislation. In this case the insurance argued that in low- to medium-grade spread of silicosis functional deficits of the lung and/or the cardio-vascular system are not to be expected. Thus the recognition and recompensation of a BK 4101 (grinders' disease, silicosis) was proposed, in contrast to the social court which demanded an expert's opinion on causality.

Blood pressure measurement is performed either invasively by an intra arterial catheter or noninvasively by cuff sphygmomanometry. The invasive method is continuous and accurate but has increased risk; the cuff is safe but less reliable and infrequent. A reliable continuous noninvasive blood pressure measurement is highly desirable. While the possibility of using pulse transit time to monitor blood pressure has previously been investigated, most studies were limited to calculating the correlation of the pulse transit time and blood pressure under rather static conditions. The relationship between the pulse transit time and blood pressure is yet to be clearly identified. This paper focuses on the modeling between the two values and presents results on cases where dramatic variation in blood pressure of the patient was induced by drug administration or surgical stimulation.

COPD is a heterogenous disease caused by the interaction of genetic susceptibility and environmental influences. The best example to support this is tobacco smoke. Although cigarette smoking is the most important aetiological factor, only up to half of chronic smokers develop significant COPD. There are three main themes within the pathogenesis of COPD: 1) imbalance between proteases and anti-proteases, 2) oxidative stress, 3) inflammation. Disparity between levels of exogeneous oxidants, e. g., tobacco smoke, and endogeneous antioxidants leads to oxidative stress which, in turn, causes an inflammatory response involving pro-inflammatory mediators. The activated inflammatory cells release further proteases and oxidants, leading to chronic inflammation and irreversible destruction of connective tissue in the lung. Individual genetic variations influence these processes in many ways. This article summarises the results of recent candidate gene studies for COPD.

Isocyanates are extensively used for the production of different foams and elastomers. They also serve as glues, lacquer hardeners, inks, adhesives, fillers, finishes, sealants, coating and insulation materials. Usually, their application results in inhalative, partly also in cutaneous uptake. This review describes occupational exposures to isocyanates as well as hazardous effects. Isocyanates are used in the automotive/mechanical engineering/building and construction/mining/casting/electricity and electronic/plastics/printing/timber and furniture/white goods and textile industry, partly also in medicine. Hazardous exposures to thermal degradation products of isocyanate-based polyurethanes and other materials have also be taken into consideration. Obstructive airway diseases are the major disorder caused by isocyanates. Rare cases suffer from extrinsic allergic alveolitis or eczema. In addition to regulation-based primary prevention qualitative medical surveillance mostly prevents d...

ZusammenfassungMukoviszidose (Cystic Fibrosis, CF) ist die häufigste, autosomal-rezessiv vererbte Multisystemerkrankung. In Deutschland sind ca. 8000 Menschen betroffen. Die Erkrankung wird durch Mutationen im Cystic Fibrosis Transmembrane Conductance Regulator (CFTR-) Gen verursacht; diese führen zu einer Fehlfunktion des Chloridkanals CFTR. Dadurch kommt es in den Atemwegen zu einer unzureichenden Hydrierung des epithelialen Flüssigkeitsfilms und somit zu einer chronischen Inflammation. Rezidivierende Infektionen der Atemwege sowie pulmonale Exazerbationen der Lunge führen im Verlauf zu zunehmender Inflammation, pulmonaler Fibrose und fortschreitender Lungendestruktion bis hin zur respiratorischen Globalinsuffizienz, die für über 90 % der Mortalität verantwortlich ist. Das Ziel der medikamentösen Therapie ist die pulmonale Inflammation und v. a. die Infektion der Atemwege zu reduzieren. Der Kolonisation und chronischen Infektion mit Pseudomonas aeruginosa (Pa) kommt die größte Bed...

Diagnosis and treatment of sleep disordered breathing (SDB) undergo substantial changes, both in terms of increasing scientific knowledge and also in terms of patient provision and socio-economic aspects. Increasing evidence shows the relevance of SDB on morbidity and mortality of affected patients. The precise differentiation of different phenotypes of SDBs has improved substantially in recent years. These proceedings influence the approach to the patients suspected of suffering from SDB. The scientific advances on the one hand are facing intentions to simplify diagnostical processes and treatment initiation and intentions to translate duties of physicians to non-medical personnel on the other hand. This consensus paper presents the principals of diagnosis, treatment initiation and provision, including the role of different participants of the healthcare system, and compares different treatment options. Major aspects include the differentiation of the diagnostical process in screen...

Anticholinergics are agents of first choice for the symptomatic treatment of patients with COPD. Tiotropium (Ba 679 BR, Spiriva) is a long-acting inhaled anticholinergic designed for once-daily bronchodilator treatment of COPD. Tiotropium is a selective antagonist of pulmonary M1 and M3 muscarinic receptor subtypes, that produces a long-lasting (24 hours), dose-dependent bronchodilation and bronchoprotection against constrictive stimuli, e. g. methacholine, following inhalation of single doses. Clinical trials with tiotropium in COPD patients over a maximum treatment duration of one year have confirmed a persisting bronchodilator effect of tiotropium compared with placebo and ipratropium, as well as meaningful clinical improvements in lung function, hyperinflation, exercise tolerance, symptom control and quality of life. Moreover, recent trials indicate that treatment with tiotropium also reduces the frequency of COPD exacerbations and hospitalizations. Comparative trials further su...

Infections are frequent and important causes of exacerbations in patients with COPD. This article reviews underlying mechanisms and therapeutic consequences. A complex interaction exists between COPD, co-morbidities, physical inactivity and systemic inflammation. The components of the postulated chronic inflammatory systemic syndrome need to be identified in more detail; physical inactivity seems to be the least common denominator. The patient's adaptive and innate immune systems play a role for the pathogenesis of infections. When interpreting positive bacterial cultures, it is important to differentiate between colonisation and infection. The impact of viral infections in COPD exacerbation needs further clarification, including the task to distinguish acute infection from viral persistence. Community acquired pneumonias pose a special risk for patients with COPD. Clinical scores and procalcitonin serum concentrations can support decisions on whether or not to start antibiotic ...

With beginning of the year 2004 a new documentation sheet for occupational preventive medical examinations according to exposures to mineral dust (quartz, asbestos, ceramic fibres) will replace the existing sheet. The new investigation sheet is presented in this publication and changes are described.

Cryptococcus is a leading mycological cause of morbidity among HIV-infected patients. In many patients, cryptococcosis is the first indication of AIDS. The lung is invariably the portal of entry and initial site of infection for C.neoformans. In immunosuppressed patients all areas of the body can be infected, and central nervous sistem involvement is the most severe complication. Cryptococcosis is an important fungal infection that should be considered in the differential diagnosis of the pulmonary infiltrates in the immunosuppressed patient. The purpose of this paper is to review the current knowledge of the management and treatment strategies of cryptococcosis.