[Guideline for the Diagnosis and Treatment of COPD Patients - Issued by the German Respiratory Society and the German Atemwegsliga in Cooperation with the Austrian Society of Pneumology]. / Leitlinie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD).

This document is a revision of the guideline for diagnosis and treatment of COPD that replaces the version from 2007. A multitude of recent reports regarding risk factors, diagnosis, assessment, prevention and pharmacological as well as non-pharmacological treatment options made a major revision mandatory. The new guideline is based on the GOLD document taking into account specifics in Germany and Austria.

[The Austrian LEAD (Lung hEart sociAL boDy) Study: Background of the Austrian Longitudinal Cohort Study]. / The Austrian LEAD (Lung hEart sociAL boDy) Study: Die Hintergründe der österreichischen longitudinalen Kohortenstudie.

More research is needed to elucidate natural history and underlying pathomechanisms of the most common airway diseases, Asthma and COPD. In the last decade risk factors affecting the natural history of lung function, defined by the decline of lung function over time, have been evaluated. Moreover, scientific methods have been extended and novel biomarkers, genetics, metabolomics, and epidemiology are dominant tools for investigating the natural history of lung function and potential risk factors. Evidence shows that lung function in childhood is a predictor for lung function in adulthood and risk factors starting in utero contribute to lung function decline during life. Therefore, recently it has been hypothesized that COPD begins in childhood. Thus, prospective investigation of lung function changes including novel scientific methodology has been advocated. The Austrian LEAD  study has been initiated in the general population 2012 to investigate the natural history of obstructive airway diseases.

A case of tracheobronchial amyloidosis treated with endoscopic debulking and external beam radiation therapy.

We report on a 55-year-old patient who was admitted to hospital because of recurrent pneumonia. CT imaging provided airway narrowing and mural thickening of the distal trachea and mainstem bronchi, compatible with endobronchial polypoid, toric-shaped changes of the distal tracheal wall spreading into both the left and right bronchial system. Bronchoscopy was performed and biopsies revealed the diagnosis of tracheobronchial amyloidosis. We performed a combination of bronchoscopic debulking and consecutive external beam radiation therapy with the result of no further progression of the disease, stable endobronchial situation, and functional improvements at a follow up at 6 months.

[A leak in the lung: endobronchial one-way valve placement as treatment for a persistent bronchopleural fistula]. / Das Leck in der Lunge: Bronchoskopische Ventilimplantation zur Behandlung einer persistierenden bronchopleuralen Fistel.

Patients with bronchopleural fistula are at an increased risk of morbidity and mortality. Treatment of the air leak includes intrathoracic drainage, antibiotic therapy and closure of the fistula, which conventionally has been performed via surgical means. In patients with limited respiratory capacity, less-invasive alternatives are required. Here we report on a 62-year-old patient with underlying severe COPD, who was admitted with a lung abscess and consecutively developed a persistent bronchopleural fistula. Treatment involved antibiotic therapy and endobronchial one-way valve placement, which resulted in termination of the air leak and full recovery.

Distribution of chronic cough phenotypes in the general population: A cross-sectional analysis of the LEAD cohort in Austria.

RATIONALE: Recent guidelines consider chronic cough to be a unique clinical entity with different phenotypes. We aimed to investigate them in a general population and to describe prevalence, distribution, and characteristics of these phenotypes within the Austrian general population. METHODS: From the LEAD study, a longitudinal observational population-based cohort, data from questionnaires and spirometry of 10,057 adult participants was analysed. Chronic cough was defined as coughing nearly every day during the last 12 months for at least 3 months (>12 weeks). RESULTS: The prevalence of chronic cough was 9% and increased with age. We found no sex predominance but a female preponderance (68%) in never smokers. A presumable cause was identified in 85% of which more than half (53.9%) had two phenotypes, 36.9% belonged to one only and 9.2% to three or more. Regarding the distribution of phenotypes, 40.8% were current smokers, 32.6% had an ACE inhibitor intake, 18.2% GERD, 17.6% asthmatic cough, 9.7% UACS and 28.3% other diseases associated with chronic cough. 15% had unexplained chronic cough with no identifiable phenotype. Current smoking, low socioeconomic status, obesity, COPD and obstructive sleep apnea were associated factors with chronic cough. CONCLUSION: Chronic cough is common among adults in Austria and highly prevalent in the older population. Most participants can be phenotyped with simple questionnaire-based assessment and can therefore potentially receive specific treatment without intensive clinical workup.

Incidence and outcome of weaning from mechanical ventilation according to new categories.

Weaning from mechanical ventilation was categorised as simple, difficult or prolonged by an international task force of the American Thoracic Society/European Respiratory Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine/Sociéte de Réanimation de Langue Française in 2007. This new classification has not been tested in clinical practice. The objective of the present study was to determine the incidence and outcome of weaning according to the new categories. We included medical and surgical patients who required mechanical ventilation in a prospective, multicentre, 6-month cohort study. From an initial cohort of 510 patients, 257 intubated patients started weaning. Of these patients, the cumulative incidences of simple, difficult, and prolonged weaning were 152 (59%), 68 (26%) and 37 (14%), respectively. Hospital mortality was increased in patients with prolonged (32%) but not difficult (9%) weaning in comparison with those with simple weaning (13%), overall p = 0.0205. In a multivariate logistic regression model, prolonged but not difficult weaning was associated with an increased risk of death. Ventilator-free days and intensive care unit (ICU)-free days were decreased in both difficult and prolonged weaning. In conclusion, the new weaning category prolonged weaning is associated with increased mortality and morbidity in the ICU. The new category difficult to wean was associated with increased morbidity, but not mortality.

Recruitment of Mycobacterium tuberculosis specific CD4+ T cells to the site of infection for diagnosis of active tuberculosis.

UNLABELLED: Accurate and early diagnosis of active tuberculosis (TB) is problematic as current diagnostic methods show low sensitivity (acid-fast bacilli smears), are time-consuming (culture of biological samples) or show variable results [Mycobacterium tuberculosis (MTB)-specific PCR]. OBJECTIVES: In the course of infection, MTB-specific T cells clonally expand at the site of infection and may thus be used as diagnostic marker for active disease. DESIGN: In this cohort study, the frequency of MTB-specific, interferon (IFN)-gamma expressing CD4(+) T cells obtained from peripheral blood and the site of disease in 25 patients with suspected TB was assessed (n = 11, bronchoalveolar lavage; n = 7, pleural fluid; n = 1, ascites; n = 1, joint fluid; n = 5, cerebrospinal fluid). RESULTS: Amongst 15 patients who showed proven active TB infection, a striking increase of MTB-specific T cells was detected at the site of infection compared with peripheral blood (median increase: 28.5-fold, range: 7.25-531 fold; median of IFN-gamma-producing CD4(+) T cells from blood: 0.02%, range: 0-0.52%; median of IFN-gamma-producing CD4(+) T cells from the site of infection: 1.81%, range: 0.29-6.55%, P < 0.001). MAIN OUTCOME MEASURE: Recruitment of MTB-specific T cells to the site of infection yielded a sensitivity of 100% and specificity of 90%, irrespective of the compartment affected. CONCLUSIONS: The accumulation of MTB-specific T cells at the site of infection may prove as useful diagnostic marker for an accurate and rapid diagnosis of active TB.

Measuring FEV(6) for detecting early airway obstruction in the primary care setting. Quality and utility of the new PiKo-6 device.

BACKGROUND: The prevalence of asthma and chronic obstructive pulmonary disease (COPD) is high ( approximately 7.4-18%) in the general population, but less than half are diagnosed. Several studies have shown FEV(6) as a good surrogate marker for forced vital capacity (FVC) to detect airflow limitations. OBJECTIVES: The aim of this study was to evaluate if it is possible to simplify and improve the diagnosis of so far undiagnosed asthma or COPD in the primary care setting by measuring FEV(6) with a new simple screening device (PiKo-6). METHODS: 507 patients were recruited from three general practices from May to June 2005. Patients with any known pulmonary disease were excluded by questionnaire. FEV(1), FEV(6) and FEV(1)/FEV(6) were determined using a PiKo-6 device. Patients with an FEV(1)/FEV(6) <80% (PiKo positive) were invited to a standardized pulmonary function test to confirm or rule out airflow limitation. RESULTS: 401 (79.1%) patients showed FEV(1)/FEV(6) > or =80% (PiKo negative), and 106 (20.9%) patients were PiKo positive. Of the 106 PiKo-positive patients, 74 patients (14.7% of total) agreed to further studies and 18 patients (3.6%) of them suffered from COPD [COPD 0: 5 (1.0%); COPD I: 9 (1.8%); COPD II: 4 (0.8%), and none with COPD III or IV] and 14 patients (2.8%) suffered from bronchial hyperresponsiveness or asthma. In 42 patients (8.3%), the pulmonary function test was normal. CONCLUSIONS: Measurement of FEV(6) using a new simple screening device (PiKo-6) may improve the detection rate of undiagnosed airflow limitation in the primary care setting. However, patients should be carefully selected.

Human atrial natriuretic peptide secretion in precapillary pulmonary hypertension. Clinical study in patients with COPD and interstitial fibrosis.

Human atrial natriuretic peptide (hANP) is stored by granules of both human atria. Atrial distension appears to be a major stimulus for hANP secretion. Precapillary pulmonary hypertension increases right ventricular afterload and may thus cause right atrial distension. We therefore hypothesized that hANP plasma concentrations (1) are higher in the right atrium than in the peripheral vein, (2) are increased in patients with precapillary pulmonary hypertension, and (3) correlate with right atrial pressure. Thirty-three adult patients with chronic obstructive pulmonary disease (COPD) or interstitial fibrosis were examined by right heart catheterization. Mean pressures were measured in the right atrium, pulmonary artery, and pulmonary capillary wedge position, and blood was drawn from the right atrium and from a peripheral vein for determination of hANP levels. In general, hANP plasma levels in the right atrium were significantly higher than in a peripheral vein. Seventeen out of 33 patients had pulmonary hypertension, whereas 16 patients exhibited normal pulmonary artery mean pressures. In all patients, pulmonary arterial wedge pressure was normal. Plasma hANP concentrations were significantly higher in patients with pulmonary hypertension than in patients with normal pulmonary artery pressure. A strong correlation between central or peripheral hANP plasma levels (or both) and mean right atrial pressure could be observed (r = 0.75; p less than 0.001). From these data, we conclude that the increased secretion of hANP in our patients with precapillary pulmonary hypertension appears to be mediated by right atrial distension.

Platelet sensitivity to prostacyclin in smokers and non-smokers.

Platelet activating effect of cigarette smoking appears to be important in the development of atherosclerosis. We previously demonstrated a reduced sensitivity of platelets to exogenous prostacyclin (PGI2) in vitro from patients with proven atherosclerotic disease, indicating a possible role of altered platelet function in the development of atherosclerosis. We now hypothesize that cigarette smoking might be an important cause of altered platelet sensitivity to PGI2 observed in patients with atherosclerosis. To test this hypothesis, the response of platelets to exogenous PGI2 was tested in chronic smokers and non-smokers, prior to and after smoking two cigarettes (active smoking) and prior to and after exposure to a tobacco smoke-contaminated atmosphere (passive smoking). This study indicates that platelets of chronic smokers are less sensitive to exogenous PGI2 than platelets of non-smokers. In addition, active as well as passive smoking decreases platelet sensitivity to PGI2 in non-smokers, whereas chronic smokers exhibit no further decline. We conclude that decreased platelet sensitivity to PGI2 might be an important contributing factor to the altered platelet function observed in patients with atherosclerosis.

Aerobic endurance training program improves exercise performance in lung transplant recipients.

STUDY OBJECTIVE: To determine whether an aerobic endurance training program (AET) in comparison to normal daily activities improves exercise capacity in lung transplant recipients. PATIENTS AND STUDY DESIGN: Nine lung transplant recipients (12+/-6 months after transplant) were examined. All patients underwent incremental bicycle ergometry with the work rate increased in increments of 20 W every 3 min. Identical exercise tests were performed after 11+/-5 weeks of normal daily activities and then after a 6-week AET. The weekly aerobic training time increased from 60 min at the beginning to 120 min during the last week. Training intensity ranged from 30 to 60% of the maximum heart rate reserve. RESULTS: Normal daily activities had no effect on exercise performance. The AET induced a significant decrease in resting minute ventilation from 14+/-5 to 11+/-3 L/min. At an identical, submaximal level of exercise, a significant decrease in minute ventilation from 47+/-14 L/min to 39+/-13 L/min and heart rate from 144+/-12 to 133+/-17 beats/min, before and after the AET, was noted. The increase in peak oxygen uptake after AET was statistically significant (1.13+/-0.32 to 1.26+/-0.27 L/min). CONCLUSIONS: These data demonstrate that normal daily activities do not affect exercise performance in lung transplant recipients > or = 6 months after lung transplantation. An AET improves submaximal and peak exercise performance significantly.

Early experience with sequential bilateral lung transplantation.

We performed 20 sequential bilateral lung transplantation in 19 consecutive patients from April 1990 to May 1992. Perioperative mortality was low (2 patients). One-year actuarial survival was 70%. All survivors had normal blood oxygen tension (82 mm Hg, mean) while breathing room air and continuing improvement of pulmonary function. Bronchial dehiscence did not occur. Stents were implanted in 7 patients to control bronchial stenosis. Aggressive treatment of graft rejection has been effective in preventing obliterative bronchiolitis.

Accuracy of echocardiographic right ventricular parameters in patients with different end-stage lung diseases prior to lung transplantation.

BACKGROUND: Because there are few data available on the accuracy of 2D-echocardiography to assess right ventricular (RV) size and function in patients with far-advanced lung disease, in this prospective study, we compared various echocardiographic RV parameters with RV volumes derived from magnetic resonance imaging (MRI). METHODS: In 32 patients (18 male, 17 female) presenting for lung transplantation, we measured RV end-diastolic and end-systolic area as well as derived RV fractional area change, long-axis diameter, short-axis diameter, tricuspid valve anulus diameter (using 2D apical or sub-costal 4-chamber view), and RV end-diastolic diameter (using M-mode in the parasternal short-axis view). These values were compared with RV end-diastolic and end-systolic volumes derived by MRI, serving as the gold standard. RESULTS: Right ventricular end-diastolic area was the most accurate echocardiographic parameter of RV size (correlation to MRI: r = 0.88, p < 0.001), followed by RV end-diastolic short-axis diameter (r = 0.75, p < 0.001), long axis diameter (r = 0.66, p < 0.001), and tricuspid valve anulus diameter (r = 0.63, p < 0.001). In contrast, M-mode measurement of RV end-diastolic diameter was possible in only 24/35 (68%) patients and showed a weak correlation to MRI-derived RV end-diastolic volume (r = 0.56, p = 0.004). Right ventricular fractional area change correlated well with MRI-derived RV ejection fraction (r = 0.84, p < 0.0001). In a sub-group analysis, patients with vascular lung disease showed best agreement between both methods for RV end-diastolic area and RV fractional area change compared with patients with restrictive or obstructive lung disease. CONCLUSION: This study shows that in patients with far-advanced lung diseases, RV end-diastolic area demonstrated the best correlation with MRI-derived measurement of RV end-diastolic volume, and RV fractional area change compared favorably with MRI-derived ejection fraction. Despite reduced image quality, especially in patients with obstructive lung disease, these parameters can yield clinically valuable information.

Clinical biochemistry of neuron specific enolase.

The soluble brain protein 14-3-2 first described by Moore and McGregor in 1965 is now known to be a cell specific isoenzyme of the glycolytic enzyme enolase (EC 4.2.1.11), designated neuron specific enolase (NSE). It is not only a marker for all types of neurons, but also for all neuroendocrine or paraneuronal cells. The appearance of NSE is a late event in neural differentiation, thus making NSE a useful index of neural maturation. The demonstration that tumors of the nervous system and of neuroendocrine origin contain NSE has promoted the study of NSE as a possible tumor marker. Immunocytochemistry has been used to identify NSE in cytologic preparations from several types of tumors, offering useful indications for differential diagnosis. NSE levels in serum from tumor patients are not useful in the diagnosis of early stage disease. However, serum NSE levels have been shown to be helpful in the identification of advanced small cell lung cancer, neuroblastoma and several other neoplasms. The main use of serum NSE is the monitoring of chemotherapy and the detection of a relapse in these cases.

Efficacy of cyclosporin A in systemic sclerosis.

In this open pilot study, the potential therapeutic efficacy of Cyclosporin A (CsA) in systemic sclerosis (scleroderma) was investigated. Eight patients with severe scleroderma (skin manifestation and at least three organ manifestations such as pulmonary, intestinal, cardiac, renal, and severe hypertension) were included in the study. CsA administration was started at a dose of 5 mg per kg body weight per day and then, to obtain whole blood levels of 300-500 ng/ml, adjusted to a mean dosage of 4.3 mg/kg/day. Therapeutic effects were evaluated by monitoring the measures of cutaneous, pulmonary, cardiac, gastrointestinal, and renal involvement as well as laboratory parameters. After 6 to 12 months of CsA-administration, cutaneous abnormalities improved in seven, arterial oxygen tension slightly increased in four, pulmonary hypertension decreased in five, and smooth muscle esophageal contraction amplitudes improved in three patients. However, the disease progressed in one patient. No serious side effects were observed, and occurring renal side effects were mild. Taken together, these observations indicate that CsA administration may be effective mainly in the skin involvement, but also in some organ manifestations of scleroderma. The results of this pilot investigation therefore indicate that a controlled study of the efficacy of CsA in scleroderma is needed and ought to be performed.

[Effects of experimental hypovolaemic shock on platelets in the pig (author's transl)]. / Zur Frage des Verhaltens der Thrombozyten bei experimentellem Volumenmangelschock

The effects of standardized blood loss on the platelets, as well as on coagulation, fibrinolysis and complement parameters were studied in the pig. A simultaneous fall in arterial and venous platelet counts was demonstrated during the initial phase of blood loss, with a concomitat rise in pulmonary vascular resistance. After exsanguination to the extent of about 40% of the blood volume, the arterial platelet counts increased significantly, whilst the pulmonary vascular resistance, which was negatively correlated with the arterial platelet counts throughout the experiment, fell. Venous platelet counts, on the other hand, remained low during this experimental period and were correlated with cardiac output, but not with pulmonary vascular resistance.