[COPD and Clinical Trials. Results of an expert meeting "Castles in the Air" 2010]. / COPD und Studien. Ergebnisse des Expertentreffens Luftschlösser 2010, Mainz, 3.­4. Dezember 2010 (Sponsor: Boehringer Ingelheim Pharma GmbH & Co KG).

Clinical trials in COPD patients aim at achieving progress in diagnosis and treatment. Study results should be applicable to a large number of patients. However, an analysis of the methods and design of current and previous trials reveals considerable room for improvement. COPD is a complex disease with different clinical phenotypes. Genetic factors need to be evaluated systematically to allow appropriate stratification of patients. Frequently used endpoints such as the FEV1 that had previously been considered reliable have shown limitations in recent trials. Thus, researchers now aim to identify new surrogate parameters that are related to the prognosis of the disease, e. g., composite endpoints and biomarkers. Physical activity and capacity are becoming increasingly important for the evaluation of disease progression. The focus of pharmaceutical development is long acting bronchodilators and new anti-inflammatory drugs. The value of non-drug interventions will also be evaluated.

[Paraganglioma--a rare cause of mediastinal lesions]. / Das Paragangliom--seltene Ursache einer mediastinalen Raumforderung.

A 73-year-old female patient was admitted to our clinic for further clarification of a suspicious mediastinal lesion. Endosonographically, we performed a fine-needle aspiration biopsy. Clinical and radiological findings as well as cytology hardened the suspicion of a paraganglioma as being the cause of the mediastinal lesion. Finally, this diagnosis was confirmed histologically after complete surgical resection of the lesion. This case report on a mediastinal paraganglioma includes a concise summary of diagnostic procedures and therapeutic options for this rare disease.

Guidelines of the German Respiratory Society for diagnosis and treatment of adults suffering from acute or chronic cough.

The first set of German guidelines for diagnosis and treatment of patients suffering from acute or chronic cough was published in 2004. Scientific developments over the past five years necessitate an update. The purpose of this document is to assist in ascertaining underlying causes and treating cough, in order to eliminate or minimize impairments of patients' health. The guidelines aim to introduce scientifically founded, evidence-based steps for the diagnosis and treatment of cough and optimize cost-effectiveness. Recommendations are assessed through the GRADE system (The Grades of Recommendation, Assessment, Development and Evaluation). Cough as a symptom is categorized as either acute (lasting up to 8 weeks) or chronic (lasting more than 8 weeks) and attributed to distinct diseases. For acute and chronic cough the diagnostic algorithms are updated; cost effectiveness is also taken into account. Additionally, the most frequent diagnostic errors are highlighted. Finally, available therapeutic options are discussed.

[COPD and infection]. / COPD und Infektion.

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 treatment. Antibiotics probably do not need to be taken for longer than 5 days, since their efficacy does not increase after longer treatment, while adverse events rise in frequency. Hospitalisations for respiratory exacerbations are associated with increased mortality in COPD.

Comparison of wheat and rye flour solutions for skin prick testing: a multi-centre study (Stad 1).

BACKGROUND: Skin prick testing (SPT) is the basic method for diagnosing IgE-mediated allergies. However, skin reactivity is related to the quality of allergen extracts, which are often poorly defined for occupational allergens. OBJECTIVE: To compare wheat and rye flour SPT solutions from different producers. MATERIALS AND METHODS: Standardized SPTs were performed in seven allergy centres with wheat and rye flour solutions from four producers in 125 symptomatic bakers. Optimal cut-off levels for weal sizes were assessed with the Youden Index. Comparisons between SPT results of different solutions were made with flour-specific IgE (sIgE) as the gold standard. Sensitivities, specificities, positive and negative predictive values, and test efficiencies were calculated and compared with McNemar and chi(2)-tests. The influence of the choice of the gold standard (sIgE or challenge) test was examined for 95 subjects. Additionally, SPT solutions were analysed for protein and antigen content. RESULTS: The optimal cut-off level for all SPT solutions was a weal size of >or=1.5 mm. While differences between wheat and rye flours were small, differences between producers were important. Variability of sensitivities (0.31-0.96), negative predictive values (0.42-0.91), and test efficiencies (0.54-0.90) were higher than variations of specificities (0.74-1.00) and positive predictive values (0.88-1.00). Similar results were obtained when using challenge test results as the gold standard. Variability could be explained by the different antigen contents of the SPT solutions. CONCLUSION: There is a wide variability of SPT solutions for wheat and rye flour from different producers, mainly with respect to sensitivities, negative predictive values, and test efficiencies. Improvement and standardization of SPT solutions used for the diagnosis of baker's asthma are highly recommended.

[Cheyne-Stokes respiration and cardiovascular risk]. / Cheyne-Stokes-Atmung und kardiovaskuläres Risiko.

Due to its high prevalence in patients with heart failure and its negative predictive value concerning morbidity and mortality, Cheyne-Stokes respiration (CSR) is a sleep disorders of major interest. CSR correlates with the degree of heart failure and is characterised by a typical crescendo/decrescendo breathing pattern combined with phases of central sleep apnoea, caused by pulmonary oedema and oscillation of ventilatory control. Thus, CSR is a marker of the severity of heart failure. Treatment of CSR first involves optimisation of heart failure therapy by cardiologists and then application of non-invasive means of ventilatory support. Treatment of patients with severe heart failure with non-invasive positive pressure ventilatory support leads to a significant reduction of CSR, sympathetic activity, and daytime sleepiness and improves cardiac output and 6-minute walking distance. At present, a prospective randomised, controlled intervention-study (Serve-HF study) is being conducted in order to show if therapy of CSR can improve patient survival. This review describes the pathophysiology, epidemiology, and therapeutic options of CSR with a special focus on the elevated cardiovascular risk of patients with CSR.

[The genetics of chronic obstructive pulmonary disease]. / Zur Genetik der chronisch-obstruktiven Lungenerkrankung.

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.

[Lung impairment in systemic sclerosis]. / Lungenbeteiligung bei systemischer Sklerodermie.

Scleroderma is a generic term for autoimmunological diseases having thickened sclerotic skin lesions in common. Scleroderma belongs to a group of connective tissue diseases. The systemic form of scleroderma is called progressive systemic sclerosis (PSS) or systemic sclerosis (SSc). Lung impairments, namely interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), are one of the most common manifestations in SSc. This article summarises the forms of lung impairment in SSc with special emphasis on interstitial lung diseases and draws attention to the so far identified pathogenetic mechanisms and the presently accepted therapeutic options.

[Detection of respiratory viruses--how, when, where and why?]. / Nachweis von Atemwegsviren--Wie, warum, wann und wo?

Respiratory viruses trigger the majority of common colds, acute respiratory illnesses in children during the cold season as well as acute exacerbations of asthma and chronic obstructive pulmonary disease. They also play a role in community acquired pneumonia. Unfortunately their detection is still difficult. The aim of this review is therefore to introduce the methods of detection and to present the current knowledge of the clinical role of respiratory viruses in different diseases.

[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.

[Health effects of particulate matter exposure: current scientific knowledge]. / Gesundheitliche Effekte der Feinstaubbelastung - aktueller wissenschaftlicher Kenntnisstand.

INTRODUCTION: Air quality is not only important for respiratory health but it also influences the homeostasis of the whole human organism. In the past years numerous violations of European Union particulate matter thresholds have been recorded. METHODS: The present study is a selective literature analysis encompassing the epidemiology and pathophysiological effects of particulate matter. RESULTS: Epidemiological studies point to an association between chronic particulate matter exposure and mortality. The most prominent effects on the human body are present in subjects with cardiovascular or respiratory conditions. However, the effects of air pollutants need to be examined critically and the plausibility of thresholds should be evaluated in detail. DISCUSSION: The negative influences of chronic particulate matter exposure have been proven by a multitude of epidemiological and experimental studies. From the viewpoint of primary prevention, air quality plays a crucial role. This encompasses both the outdoor compartment with particulate matter and other pollutants and the indoor compartment with tobacco smoke.

Prediction of challenge test results by flour-specific IgE and skin prick test in symptomatic bakers.

BACKGROUND: Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker's asthma is based on inhalation challenge tests with flours. AIMS OF THE STUDY: To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker's asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing. METHODS: Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard. RESULTS: Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74-100% (74-100%) for wheat and 82-100% (91-100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour. CONCLUSION: High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.

[Effects of high altitude on bronchial asthma]. / Asthmatherapie im Hochgebirgsklima.

Sojourns in the high mountains have been recommended to patients with asthma for many decades. It is the aim of this contribution to summarise the published studies about the effects of a stay at > 1500 m above sea level on asthmatic patients. These data from 428 adolescent and adult patients indicate an improvement of asthma symptoms and lung function during sojourns at high altitude. In many patients a reduction of the steroid therapy was achievable. Profound changes in the immune system have been demonstrated at high altitude, with a reduction of B- and T-helper cell activation. Total and mite-specific immunoglobulin E antibodies decrease significantly during longer sojourns. These changes are associated with a reduction of airway inflammation (e. g., reduction of eosinophil activation, NO exhalation and bronchial hyper-responsiveness). The fact that also patients with non-allergic asthma demonstrate a reduction of their airway inflammation at high altitude suggests that the high altitude climate has beneficial effects on asthma beyond the effects of allergen avoidance. High UV exposure and low humidity could be important additional factors, to explain the reductions in asthma severity in the high mountain climate. Larger controlled studies should be performed to prove the positive effects of the high altitude climate on asthma.

[Acute effects of cardiac resynchronization therapy on breathing during sleep in patients with severe chronic heart failure--a pilot study]. / Akuteffekte einer kardialen Resynchronisationstherapie auf die Atmung im Schlaf bei Patienten mit fortgeschrittener Herzinsuffizienz--Eine Pilotstudie.

BACKGROUND: Sleep-related breathing disorders (SDB), especially Cheyne-Stokes respiration (CSR), have prognostic relevance in patients with chronic heart failure (CHF). Thus, we investigated acute effects of cardiac resynchronization therapy on breathing during sleep. METHODS: Beside a cardiopulmonary investigation, breathing during sleep was analysed polygraphically/polysomnographically on the night before and during the second night after implantation of a biventricular pacemaker for cardiac resynchronization. PATIENTS: We investigated 16 consecutive patients with severe CHF (NYHA class III-IV) and widened QRS complexes (QRS > 150 ms) with the indication for cardiac resynchronization therapy independent of this study. RESULTS: Cardiac resynchronization therapy shortened the QRS time in each and every patient (QRS: 167.3 +/- 21.7 ms to 113.0 +/- 19.0 ms; p < 0.001) as a marker for successful resynchronization. Initially, SDB were diagnosed in 11 of the 16 patients studied (69 %), with 7 patients having CSR (44 %) and 4 patients (25 %) having CSR and obstructive sleep apnoea. With cardiac resynchronization therapy, no significant acute changes were seen regarding nocturnal breathing/breathing disorder, heart frequency, or oxygen saturation. CONCLUSIONS: The established positive effects of cardiac resynchronization therapy are rather due to a chronic improvement of cardiopulmonary interactions (remodelling, circulatory time, or chemosensitivity) than to acute effects, as investigated in this study.

[Influence of nocturnal oxygen therapy on quality of life in patients with COPD and isolated sleep-related hypoxemia: a prospective, placebo-controlled cross-over trial]. / Einfluss der nächtlichen Sauerstofftherapie auf die Lebensqualität bei Patienten mit COPD und isolierter schlafbezogener Hypoxämie: Eine prospektive, plazebokontrollierte cross-over Studie.

BACKGROUND: In patients with COPD and isolated night time hypoxemia, oxygen administration has not shown any effects on life expectancy and the development of pulmonal arterial hypertension. The aim of the present pilot study was to investigate the influence of nocturnal oxygen therapy on the quality of life in daytime normoxemic COPD patients with nocturnal oxygen desaturations. PATIENTS AND METHODS: 19 patients with COPD, in a stable phase of the disease without need for oxygen supplementation under rest (PaO2 62.7 +/- 4.9 mmHg) and nocturnal hypoxemia (t90 = 55.5 +/- 33.4 % of registration time, mean SaO2 89.8 +/- 1.9 %, minimal SaO2 81.1 +/- 4.8 %) were randomly assigned to either oxygen or placebo treatment, both generated by identical concentrator devices. Each treatment period lasted 6 weeks, after six weeks a cross-over was performed by a technician. Quality of life was assessed before and at the end of each treatment period by the SF-36, Nottingham Health Profile and Saint George's Respiratory Questionnaire. RESULTS: Significant differences for the comparison of placebo and verum were only seen for the dimension sleep (NHP), all other dimensions showed no differences between placebo and oxygen. However, both placebo and oxygen improved the majority of the quality of life items significantly. CONCLUSIONS: The prescription of supplemental oxygen in COPD patients with isolated nocturnal hypoxemia in the present pilot study is not able to improve the quality of life within 6 weeks after initiation of therapy. It cannot, therefore, be generally recommended, but may be indicated in patients with a documented improvement of sleep quality.

[Daytime ventilatory efficiency in obstructive sleep apnea syndrome--influence of CPAP-therapy]. / Einfluss der CPAP-Therapie auf die ventilatorische Effizienz am Tage bei Patienten mit obstruktivem Schlafapnoe-Syndrom.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a nocturnal breathing disorder with possibly negative consequences on daytime control of ventilatory drive. We therefore investigated ventilatory efficiency, defined as the ventilatory equivalent for CO2 (VaE/VaCO2), in patients with OSAS during exercise before and under treatment with continuous positive airway pressure (CPAP). PATIENTS AND METHODS: In 21 patients with untreated OSAS, ventilatory efficiency, described as the slope (DeltaVaE vs. VaCO2) and the lowest ratio (VaE/VaCO2 min) of the ventilatory equivalent for CO2, was determined below the anaerobic threshold using spiroergometry. A follow-up after at least 6 months of CPAP therapy was performed in 16 of these patients and in 5 CPAP-neglecting patients with OSAS, who served as controls. RESULTS: In 21 patients with untreated OSAS, DeltaVaE vs. VaCO2 was significantly and VaE/VaCO2 min non-significantly lower, revealing better ventilatory efficiency, compared to normal values. In 16 patients, ventilatory efficiency did not change after on average 305.7 +/- 104.8 nights of CPAP-therapy, compared to 5 controls. CONCLUSIONS: OSAS is not associated with a disturbed ventilatory efficiency during exercise. Long-term CPAP-therapy does not change ventilatory efficiency during exercise in patients with OSAS. The improved ventilatory efficiency during exercise compared to normal controls may be due to differences concerning anthropometric data (e. g., obesity, hypertension) and cardiopulmonary exercise-test (45 degrees lying position).

[Sleep apnoea in women?--The forgotten gender]. / Schlafapnoe bei Frauen?--Das vergessene Geschlecht.

The prevalence of clinically relevant, obstructive sleep apnoea syndrome (OSAS) in the general population is 2% in women and 4% in men. With increasing age and onset of postmenopausal status, the prevalence of OSAS in women becomes comparable to that of males. However, compared to prevalence data, women are under-represented in clinical sleep laboratories. The present overview deals with the potential reasons for clinical under-recognition of OSAS in women. The fact that OSAS frequency is underestimated in women probably derives from the atypical clinical symptoms, dominated by difficulties of initiating and maintaining sleep and by a depressive mood. There are several protecting mechanisms in women that prevent or postpone OSAS development to higher age groups or until the onset of menopause. These factors include craniofacial morphology and function, gender-specific body-fat distribution and hormonal influences on ventilation and dilating muscles in the oropharynx. Physicians should be aware of the presence of sleep-disordered breathing in women and of their special features.

[Locus of control belief is a predictor of CPAP-compliance in patients with obstructive sleep apnea syndrome]. / Die Kontrollüberzeugung ist ein Prädiktor für CPAP-Compliance bei obstruktivem Schlafapnoesyndrom1.

Approximately 25 % of all patients suffering from obstructive sleep apnea syndrome (OSAS) discontinue CPAP-therapy in long-term follow-up. This study was conducted to investigate if there are any predictors signaling low compliance prior to initiation of CPAP-therapy. We used an open label longitudinal cohort study at an University hospital in-patient Sleep laboratory setting. In 85 consecutive patients with a diagnosis of OSAS confirmed by polysomnography a CPAP-therapy was initiated. Prior to CPAP-titration the subjects were interviewed using standardized, validated questionnaires (Nottingham Health Profile, von Zerssen's Depression Scale, State Trait Anxiety Inventory, IPC-Scale). On follow up (mean 16 +/- 8 month) 66 patients were still using CPAP regularly, 19 individuals had discontinued the therapy. Data of both groups were compared. There were no significant differences in polysomnographic parameters before CPAP except apnea-hypopnea-index (users: 30.72 +/- 20.68, rejecters: 18.43 +/- 10.43) and mean oxygen saturation (users: 91.65 +/- 3.32, rejecters 93.63 +/- 1.86). Depression and anxiety levels were normal in both groups. The subjects who discontinued CPAP had a significantly less external control belief. Internal control belief was normal in all patients. It is suggested that individuals who discontinued CPAP could not be convinced of the necessity of CPAP by physicians or nurses due to their reduced external control belief. Identifying patients with diminished external control belief prior to prescription of a device might be useful. In selected subgroups, different methods of motivation to maintain long-term acceptance for CPAP-therapy seems to be necessary.

[Treatment of bronchial asthma with consideration also of the upper airway]. / Gemeinsame Therapiestrategie für obere und untere Luftwege. Denken Sie bei Asthma auch an Rhinitis?

Asthma is chronic inflammatory disease of the lower airway. In many cases, it is accompanied by allergic or non-allergic upper airway disease. While the treatment of the lower airway in bronchial asthma has been largely standardized based on diverse guidelines, for the simultaneous treatment of the upper airway, different strategies are in use. On the basis of collected study data, it has been shown that simultaneous pharmacotherapy of the upper airway comorbidities also has a positive effect on asthma. It has been shown that, when applied in good time, specific immunotherapy can prevent the development of asthma in some cases. This means that in patients with airway pathology, simultaneous treatment of the other level (upper or lower) should be considered.

Relevance of human metapneumovirus in exacerbations of COPD.

BACKGROUND AND METHODS: Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR. RESULTS: We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 x 10(5) viral copies/ml in nasal lavage and 1.88 x 10(5) viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD. CONCLUSION: HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.