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Background: The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities., Methods: One thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1-4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up., Results: One thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year., Conclusion: These findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency., Trial Registration: Trial registration ClinicalTrials.gov, Identifier: NCT01245933. Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010-11, primary completion 2013-12, study completion 2023-09. https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3., (© 2024. The Author(s).)

The present guideline provides a new and updated concept of the management of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2016.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment.The recommendations aim at the same time at a structured assessment of risk for adverse outcome as well as an early determination of treatment goals in order to reduce mortality in patients with curative treatment goal and to provide palliation for patients with treatment restrictions., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 020-020., (Thieme. All rights reserved.)

Background: The COVID-19 pandemic has caused significant disruptions in the implementation of programs across educational institutions. Nursing students, being both young adults and by practical training, part of the health care system, may be particularly vulnerable during the COVID-19 pandemic. The purpose of this study was to explore the associations between self-reported fear of COVID-19, general health, psychological distress and overall quality of life (QoL) in a sample of Norwegian baccalaureate nursing students compared to reference data., Methods: The survey targeted baccalaureate nursing students from five universities in February 2021. An electronic questionnaire consisted of the Fear of COVID-19 Scale (FCV-19S), the Hopkins Symptom Checklist 5 (SCL-5), one general health and one overall QoL question. The respondents' mean scores were compared to reference data. Hierarchical regression analyses were conducted, and effect sizes (Cohen's d) were evaluated., Results: In total, 2605 out of 6088 (43%) students responded. Their FCV-19S scores (mean 2.45, CI 2.42, 2.48) were significantly higher than those of the reference population (mean 1.8, P < 0.001). Nursing students scores showed significantly lower general health (mean 3.50 ± 0.93 SD, population mean = 3.57, Cohen's d = 0.07), higher levels of psychological distress (mean 2.68 ± 1.03 SD, population mean = 2.12, Cohen's d = 0.55) and lower overall QoL (mean 5.50 ± 2.16 SD, population mean = 8.00, Cohen's d = 1.16) compared to pre-pandemic reference data. FCV-19S scores were significantly associated with levels of general health (Cohen's d = 0.26), psychological distress (Cohen's d = 0.76) and overall QoL (Cohen's d = 0.18)., Conclusions: Baccalaureate nursing students reported worse outcomes during the Covid-19 pandemic on general health, psychological distress and overall QoL compared to the reference population. Level of fear of Covid-19, however, accounted for few of these differences. Other factors related to the pandemic may have reduced nursing students' overall QoL., (© 2021. The Author(s).)

Aim:  Dyspnoea is a frequent and compromising symptom in patients with advanced and metastatic lung cancer. Exogenous as well as endogenous factors contribute to development of shortness of breath. Knowledge of these influences is essential for effective treatment of this important symptom. In our study, we evaluated the influence of cofactors and comorbidity on development of dyspnoea in lung cancer patients for the purpose of effective therapy of shortness of breath in this target group., Methods:  In this prospective monocentric study, we registered severity of dyspnoea in advanced lung cancer patients using the modified Medical Research Council-Scale (mMRC-scale). Patients' history of COPD and cardiopulmonary comorbidity was recorded using a standardized questionnaire. Moreover, cofactors such as pain or cancer-induced mental stress were documented by visual rating scale., Results:  25 (48,1 %) of 52 recruited lung cancer-patients reported moderate or severe dyspnoea. In logistic regression analysis history of COPD or cardiopulmonary comorbidity, severe pain, airway obstruction or pleural effusion were associated with severe dyspnoea (mMRC-scale ≥ 3). Furthermore, in our study cohort lower cancer level III UICC and absence of metastasis correlated with severe dyspnoea., Conclusions:  Our findings confirm the relevance of dyspnoea in patients with advanced lung cancer. Probability of occurrence is influenced by comorbidity and cofactors. The knowledge of these factors contributes to better understanding of occurrence and treatment of dyspnoea., Competing Interests: Prof. Rohde berichtet, Forschungsunterstützung von der DFG, der EU, dem BMBF und der Firma Gilead erhalten zu haben. Er hat von den Firmen AstraZeneca, Boehringer, Bayer, Berlin-Chemie, Grifols, Insmed, MSD, Novartis, Pfizer, GSK, Roche Honorare für Vorträge und von den Firmen Boehringer, GSK, Novartis, Pfizer, Roche, Sanofi und Insmed Honorare für Beratungstätigkeiten erhalten.Dr. Grünewaldt hat Vortrags- und Beraterhonorare folgender Firmen erhalten: Novartis, GSK, AstraZeneca, Boehringer, Sanofi, Roche; zudem Forschungsunterstützung der Firma TNI.Frau Lehn und Herr Sützle geben keine Interessenkonflikte an., (Thieme. All rights reserved.)

Impulsive optical excitation generally results in a complex nonequilibrium electron and lattice dynamics that involves multiple processes on distinct timescales, and a common conception is that for times shorter than about 100 fs the gap in the electronic spectrum is not seriously affected by lattice vibrations. Here, however, by directly monitoring the photoinduced collapse of the spectral gap in a canonical charge-density-wave material, the blue bronze Rb&#95;{0.3}MoO&#95;{3}, we find that ultrafast (∼60  fs) vibrational disordering due to efficient hot-electron energy dissipation quenches the gap significantly faster than the typical structural bottleneck time corresponding to one half-cycle oscillation (∼315  fs) of the coherent charge-density-wave amplitude mode. This result not only demonstrates the importance of incoherent lattice motion in the photoinduced quenching of electronic order, but also resolves the perennial debate about the nature of the spectral gap in a coupled electron-lattice system.

A significant proportion of the current technological developments in pneumology originate from the various areas of information technology. The spectrum ranges from smartphone apps to be used in daily life or in patient care to the use of artificial intelligence in screening and early detection of diseases. The diagnostic accuracy of apps for symptom analysis is currently very limited. Research projects are performed on the integration of symptoms and functional parameters into early detection, but also on mobility measurements as a prognostic marker in COPD. Lung cancer screening using computed tomography represents a major challenge. Here, artificial intelligence can help radiologists to cope with huge amounts of data. However, the quality of the software depends on the sufficient training of the system. Technological developments shape all fields of pneumology. For diagnostic and interventional endoscopy, they offer improved biopsy techniques and microstructural imaging. Advances in lung function measurements allow the differentiated analysis of respiratory mechanical disorders, and they could be transferred to ventilation technology. The translation of basic findings about the lung microbiome into patient care may perspectively help to better understand and treat COPD exacerbations., Competing Interests: Michael Dreher erhielt Honorare für Vorträge von Actelion, Astra Zeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Chiesi, GSK, Hamilton, Heinen und Löwenstein, Intermune, Linde, Novartis, Pfizer, Philips Respironics, ResMed, Roche, Weinmann. Beratungshonorare von Almirall, Boehringer Ingelheim, Hamilton, Linde, Novartis, Pfizer, Philips Respironics, ResMed, Roche. Research Grants von Linde, Philips Respironics, ResMedRembert Koczulla erhielt Honorare für Vorträge/Advisory Boards von Sanofi, Boehringer Ingelheim, Astra Zeneca, Chiesi, Novartis, Berlin Chemie, GSK, CSL Behring, Grifols, Streamed up, Schön Klinik, Produktunterstützung von Novotec, Berater bei KaiaGernot Rohde erhielt Honorare für Vorträge und Beratungstätigkeiten von Astra Zeneca, Boehringer Ingelheim, GSK, Novartis, Roche, Berlin Chemie, Grifols, Vertex, Pfizer, MSD, Chiesi, Bayer, Insmed, BMS, Sanofi, PulmonX.Winfried Randerath erhielt Honorare für Vorträge und Beratertätigkeit von Bayer, Berlin Chemie, Boehringer Ingelheim, Heinen und Löwenstein, Novartis, Philips Respironics, ResMed.Gratiana Steinkamp erhielt Honorare für medizinisch-wissenschaftliches Publizieren von Boehringer Ingelheim, InfectoPharm, Pari GmbH und Gilead.Julia Wälscher erhielt Vortragshonorare und Reisekostenunterstützungen von Boehringer Ingelheim und Roche.Henrik Watz erhielt Honorare für Vorträge oder Beratungstätigkeit der Firmen Astra Zeneca, Boehringer Ingelheim, Bayer, BerlinChemie, Chiesi, GSK, Novartis, Takeda., (© Georg Thieme Verlag KG Stuttgart · New York.)

We employ time- and angle-resolved photoemission spectroscopy to study the spin- and valley-selective photoexcitation and dynamics of free carriers at the K[over ¯] and K[over ¯]^{'} points in singly oriented single-layer WS&#95;{2}/Au(111). Our results reveal that in the valence band maximum an ultimate valley polarization of free holes of 84% can be achieved upon excitation with circularly polarized light at room temperature. Notably, we observe a significantly smaller valley polarization for the photoexcited free electrons in the conduction band minimum. Clear differences in the carrier dynamics between electrons and holes imply intervalley scattering processes into dark states being responsible for the efficient depolarization of the excited electron population.

Time- and angle-resolved photoelectron spectroscopy with 13 fs temporal resolution is used to follow the different stages in the formation of a Fermi-Dirac distributed electron gas in graphite after absorption of an intense 7 fs laser pulse. Within the first 50 fs after excitation, a sequence of time frames is resolved that are characterized by different energy and momentum exchange processes among the involved photonic, electronic, and phononic degrees of freedom. The results reveal experimentally the complexity of the transition from a nascent nonthermal towards a thermal electron distribution due to the different timescales associated with the involved interaction processes.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized., Competing Interests: Interessenkonflikt: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://www.awmf.org; AWMF-Registernummer 020-013., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To explore the relationship between demographic and disease-related variables and the perceived effect of health status on sexual activity in patients with axial spondyloarthritis (ax-SpA)., Method: The study assessed 379 ax-SpA patients consecutively recruited from two rheumatology outpatient clinics. Data collection included information on demographics, markers and measures of ax-SpA disease, treatment, comorbidity, and health-related quality of life (HRQoL) using the Short Form-36. The perceived effect of health status on sexual activity was assessed using question 15 in the HRQoL instrument 15D., Results: The mean age of the patients was 45.6 years, 66.5% were men, 87.3% were human leucocyte antigen-B27 positive, and mean disease duration was 13.9 years. A total of 312 patients (82.3%) reported their health status to have no/little effect and 17.7% patients reported their health status to have a large negative effect on their sexual activity. In univariate analysis, increased body mass index (BMI), smoking, alcohol consumption, unemployed status, low physical activity, comorbidities, and higher disease activity (Bath Ankylosing Spondylitis Questionnaire), impaired body movement and lower HRQoL were associated with a large effect on sexual activity. In adjusted analyses, only female gender, high BMI, current smoking, and low HRQoL showed significant associations., Conclusion: Approximately 20% of ax-SpA patients reported a large negative effect on their sexual activity. Female gender, high BMI, current smoking, and reduced HRQoL were associated with health status having a large effect on sexual activity, whereas no measures reflecting ax-SpA disease showed an independent association.

Study purpose  According to the Robert Koch Institute, 84,700 people in Germany suffer from HIV infection. One-third of the affected persons is over 50 years old. In Germany, community-acquired pneumonia (CAP) is a widespread disease with more than 250,000 cases per year. Incidence and mortality increase with the age of the affected individuals. For this reason, diagnostic and therapeutic strategies are needed to guide medical care of HIV-infected patients presenting with CAP. Methodology  HIV therapists were interviewed about their diagnostic approach, risk stratification strategy and therapeutic approach to HIV-associated community-acquired pneumonia (HIV  + /CAP) using a questionnaire. 56 completed questionnaires were analysed. Results  Half of the respondents reported that CAP occurred in 1 to 5 % of HIV-infected individuals per year. This indicates an estimated number of up to 4200 HIV  + /CAP cases per year in Germany - a much higher number than expected from the literature. 58.9 % of respondents considered that the pathogenic spectrum did not differ in HIV  + /CAP from non-HIV/CAP. 80.3 % of respondents applied the same antibiotic regimens in HIV  + /CAP as used in patients with non-HIV/CAP. Conclusion  Even though over 40 % of HIV therapists agree that the pathogenic spectrum of HIV  + /CAP differs from that of non-HIV/CAP, over 80 % of therapists managed these patients in accordance with the S3-guidelines for non-immunocompromised CAP-patients, because specific guidelines for the treatment of HIV  + /CAP are lacking. Since specific data on the aetiology and the clinical course of HIV  + /CAP depending, for instance, on CD4-count and antiretroviral therapy are missing, we feel that the clinical course of HIV  + /CAP should be further analysed in the context of prospective cohort studies., (© Georg Thieme Verlag KG Stuttgart · New York.)

An experimental setup for time- and angle-resolved photoelectron spectroscopy with sub-15 fs temporal resolution is presented. A hollow-fiber compressor is used for the generation of 6.5 fs white light pump pulses, and a high-harmonic-generation source delivers 11 fs probe pulses at a photon energy of 22.1 eV. A value of 13 fs full width at half-maximum of the pump-probe cross correlation signal is determined by analyzing a photoemission intensity transient probing a near-infrared interband transition in 1T-TiSe 2 . Notably, the energy resolution of the setup conforms to typical values reported in conventional time-resolved photoemission studies using high harmonics, and an ultimate resolution of 170 meV is feasible.

The aim of this study was to investigate the effects of vitamin C and E supplementation on changes in muscle mass (lean mass and muscle thickness) and strength during 12 weeks of strength training in elderly men. Thirty-four elderly males (60-81 years) were randomized to either an antioxidant group (500 mg of vitamin C and 117.5 mg vitamin E before and after training) or a placebo group following the same strength training program (three sessions per week). Body composition was assessed with dual-energy X-ray absorptiometry and muscle thickness by ultrasound imaging. Muscle strength was measured as one-repetition maximum (1RM). Total lean mass increased by 3.9% (95% confidence intervals: 3.0, 5.2) and 1.4% (0, 5.4) in the placebo and antioxidant groups, respectively, revealing larger gains in the placebo group (P = 0.04). Similarly, the thickness of m. rectus femoris increased more in the placebo group [16.2% (12.8, 24.1)] than in the antioxidant group [10.9% (9.8, 13.5); P = 0.01]. Increases of lean mass in trunk and arms, and muscle thickness of elbow flexors, did not differ significantly between groups. With no group differences, 1RM improved in the range of 15-21% (P < 0.001). In conclusion, high-dosage vitamin C and E supplementation blunted certain muscular adaptations to strength training in elderly men., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The present guideline provides a new and updated concept of treatment and prevention of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2009.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment as well as primary and secondary prevention., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Flexible, fibreoptic bronchoscopy (FFB) and bronchoalveolar lavage (BAL) have been used for diagnostic purposes in critically ill ventilated patients. The additional diagnostic value compared to tracheal aspirations in ventilator-associated pneumonia (VAP) has been questioned. Nevertheless, BAL can provide extra information for the differential diagnosis of respiratory disease and good antibiotic stewardship. These benefits should outweigh potential hazards caused by the invasiveness of this diagnostic technique. The focus of the present study was on the clinical course and complications of patients following BAL procedures up to 24 h., Methods: Hundred sixty-four FFB guided BAL procedures for suspected pneumonia were analysed in an observational study. The clinical course of patients was monitored by respiratory and haemodynamic data before BAL, 1 and 24 h after BAL. Complications were defined and registered. Factors associated with complications were analysed by logistic regression., Clinical Course: a decrease in average pO2/FiO2 ratio 1 h after BAL from 29 kPa (218 mmHg) to 25 kPa (189 mmHg) (p < 0.05) was observed which fully recovered within 24 h. Respiratory complications: the incidence of procedure related hypo-oxygenation (SaO2 ≤ 88 %) and/or bronchospasm was 9 %; a decrease of >25 % PaO2/FiO2 ratio 1 h after BAL was found in 29 % of patients; no bleeding or pneumothorax were registered. Haemodynamic complications: there were no cases of hypertension and cardiac rhythm disturbances; haemodynamic instability within the first 24 h after BAL was recorded in 22 %; this was correlated with a cardiovascular diagnosis at admission (OR 2.9; 95 % CI 1.2 - 6.7) and the presence of cardiovascular co-morbidity (OR 3.5; 95 % CI 1.5 - 8.3). The incidence of bacteraemia was 7 %. There was no case of procedure related death., Discussion: Frequently occurring haemodynamic and respiratory instability but no cases of cardiac rhythm disturbances, bleeding, pneumothorax or procedure related death were attributable to diagnostic FFB and BAL. The procedures should be conducted under careful supervision by experienced physicians. Only a randomized controlled trial that compares diagnostic FFB and BAL with a non-invasive strategy could ultimately establish the safety profile and clinical utility of these procedures in critically ill ventilated patients.

Background: Addition of assessment of comorbid diseases ('D') and oxygen saturation ('S') to the CRB-65 score has been recommended to improve its accuracy for risk stratification in community-acquired pneumonia (CAP). The aim of this study was to validate the resulting DS-CRB-65 score in a large cohort of patients with CAP., Methods: A total of 4432 patients prospectively enrolled in the CAPNETZ cohort were included in this study. Predefined end points were 28-day mortality, requirement for mechanical ventilation or vasopressors (MV/VS) and requirement for MV/VS or intensive care unit admission (MV/VS/ICU). Receiver operating characteristic curve analysis was used to determine the accuracy of the CRB-65 score and the addition of D (extra-pulmonary comorbidities) and S (oxygen saturation <90% or partial pressure of oxygen <8 kPa). Binary logistic regression and the method of Hanley and McNeil were used to compare the criteria., Results: The mortality rate was 4.0%, and 4.2% of patients required MV/VS and 6.6% required MV/VS/ICU. After multivariate analysis, D and S independently were added to the CRB-65 criteria for mortality prediction, but only S improved prediction of MV/VS and MV/VS/ICU (P < 0.001 for all). The area under the curve of the CRB-65 score was significantly improved by adding D and S for all end points (P < 0.02). Amongst patients who died or required MV/VS despite a CRB-65 score of 0, 64-80% would have been identified by the DS-CRB-65 score., Conclusions: The addition of assessment of oxygenation and comorbidities significantly improved the prognostic accuracy of the CRB-65 score. Consequently, the DS-CRB-65 score may have a useful role in risk stratification algorithms for CAP., (© 2015 The Association for the Publication of the Journal of Internal Medicine.)

Objective: To determine whether the sense of coherence (SOC) could predict the outcome of an 18-month lifestyle intervention program for subjects at risk of type 2 diabetes., Methods: Subjects at high risk of type 2 diabetes mellitus were recruited to a low-intensity lifestyle intervention program by their general practitioners. Weight reduction ≥ 5% and improvement in exercise capacity of ≥ 10% from baseline to follow-up indicated a clinically significant lifestyle change. SOC was measured using the 13-item SOC questionnaire., Results: The study involved 213 subjects with a mean body mass index of 37 (SD ± 6). Complete follow-up data were obtained for 131 (62%). Twenty-six participants had clinically significant lifestyle changes. There was a 21% increase in the odds of a clinically significant lifestyle change for each point increase in the baseline SOC score (odds ratio = 1.21; confidence interval = 1.11-1.32). The success rate was 14 times higher in the highest SOC score tertile group compared with the lowest., Conclusion: High SOC scores were good predictors of successful lifestyle change in subjects at risk of type 2 diabetes. SOC-13 can be used in daily practice to increase clinical awareness on the impact of mastery on the outcome of life-style intervention programs., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: Rhinoviruses (RVs) are the major triggers of asthma exacerbations. We have shown previously that lower respiratory tract symptoms, airflow obstruction, and neutrophilic airway inflammation were increased in experimental RV-induced asthma exacerbations., Objectives: We hypothesized that neutrophil-related CXC chemokines and antimicrobial peptides are increased and related to clinical, virologic, and pathologic outcomes in RV-induced exacerbations of asthma., Methods: Protein levels of antimicrobial peptides (SLPI, HNP 1-3, elafin, and LL-37) and neutrophil chemokines (CXCL1/GRO-α, CXCL2/GRO-β, CXCL5/ENA-78, CXCL6/GCP-2, CXCL7/NAP-2, and CXCL8/IL-8) were determined in bronchoalveolar lavage (BAL) fluid of 10 asthmatics and 15 normal controls taken before, at day four during and 6 weeks post-experimental infection., Results: BAL HNP 1-3 and Elafin were higher, CXCL7/NAP-2 was lower in asthmatics compared with controls at day 4 (P = 0.035, P = 0.048, and P = 0.025, respectively). BAL HNP 1-3 and CXCL8/IL-8 were increased during infection (P = 0.003 and P = 0.011, respectively). There was a trend to increased BAL neutrophils at day 4 compared with baseline (P = 0.076). BAL HNP 1-3 was positively correlated with BAL neutrophil numbers at day 4. There were no correlations between clinical parameters and HNP1-3 or IL-8 levels., Conclusions: We propose that RV infection in asthma leads to increased release of CXCL8/IL-8, attracting neutrophils into the airways where they release HNP 1-3, which further enhances airway neutrophilia. Strategies to inhibit CXCL8/IL-8 may be useful in treatment of virus-induced asthma exacerbations., (© 2014 John Wiley & Sons Ltd.)

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However infections on general wards are also increasing. A central issue are infections with multi drug resistant (MDR) pathogens which are difficult to treat particularly in the empirical setting potentially leading to inappropriate use of antimicrobial therapy. This guideline was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and therapy of HAP on the basis of quality of evidence and benefit/risk ratio. The guideline has two parts. First an update on epidemiology, spectrum of pathogens and antiinfectives is provided. In the second part recommendations for the management of diagnosis and treatment are given. Proper microbiologic work up is emphasized for knowledge of the local patterns of microbiology and drug susceptibility. Moreover this is the optimal basis for deescalation in the individual patient. The intensity of antimicrobial therapy is guided by the risk of infections with MDR. Structured deescalation concepts and strict limitation of treatment duration should lead to reduced selection pressure., (© Georg Thieme Verlag KG Stuttgart · New York.)

Symptoms of acute febrile respiratory tract infection are often unspecific, but the rapid identification of pathogens allows optimised patient management. The objective of this study was to evaluate a novel multiplex polymerase chain reaction (PCR) suspension microarray which detects 19 viral and four atypical bacterial targets. A comprehensive set of sensitive monoplex real-time PCR assays was used for each pathogen as the gold standard. A panel of archived as well as 300 prospectively collected clinical samples was analysed by both methods. At least one target was detected in 165/300 (55 %) samples by monoplex PCR and in 140/300 (46 %) samples by multiplex PCR, respectively. The positivity rate was significantly higher in paediatric patients compared to adults [126/154 (82 %) vs. 39/146 (27 %) by monoplex and 114/154 (74 %) vs. 26/146 (18 %) by multiplex PCR, respectively]. Among all samples, 17/300 (5.6 %) were positive for atypical bacteria by monoplex and 8/300 (2.6 %) by multiplex PCR, respectively. Multiple detections were recorded in 35/300 (11.6 %) samples by monoplex and 26/300 (8.7 %) by multiplex PCR. For the most common pathogens, the sensitivity ranged from 57 to 93 % and the specificity ranged from 95 to 100 %. The overall concordance between both methods was 77 % [95 % confidence interval (CI) 72-81 %]. False-negative results by multiplex PCR were mainly due to the low target concentration. Compared to monoplex PCR, the novel microarray assay proved its principle but displayed overall lower sensitivities, potentially restricting its use to paediatric patients. For some targets, only small numbers of positive samples were available, requiring larger studies to firmly assess the sensitivity and specificity.

Antimicrobial resistance is a serious threat and compromises the management of infectious disease. This has particular significance in relation to infections of the respiratory tract, which are the lead cause of antibiotic prescribing. Education is fundamental to the correct use of antibiotics. A novel open access curriculum has been developed in the context of a European Union funded research project Genomics to combat Resistance against Antibiotics in Community-acquired lower respiratory tract infections in Europe (GRACE http://www.grace-lrti.org). The curriculum was developed in modular format and populated with clinical and scientific topics relevant to community-acquired lower respiratory tract infections. This curriculum informed the content of a series of postgraduate courses and workshops and permitted the creation of an open access e-Learning portal. A total of 153 presentations matching the topics within the curriculum together with slide material and handouts and 104 webcasts are available through the GRACE e-Learning portal, which is fully searchable using a 'mindmap' to navigate the contents. Metrics of access provided a means for assessing usage. The GRACE project has permitted the development of a unique on-line open access curriculum that comprehensively addresses the issues relevant to community-acquired lower respiratory tract infections and has provided a resource not only for personal learning, but also to support independent teaching activities such as lectures, workshops, seminars and course work., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

Background: Pneumococcal pneumonia is still an important cause of mortality. The objective of this study was to compare frequency, clinical presentation, outcome and vaccination status of patients with pneumococcal community-acquired pneumonia (CAP) to CAP due to other or no detected pathogen based on data of the German Network for community-acquired pneumonia (CAPNETZ)., Methods: Demographic, clinical and diagnostic data were recorded using standardized web-based data acquisition. Standardized microbiological sampling and work-up were conducted in each patient., Results: 7400 patients with CAP from twelve clinical centers throughout Germany were included. In 2259 patients (32 %) a pathogen was identified, Streptococcus pneumonia being the most frequent (n = 676, 30 % of all patients with identified pathogens). Compared to those with non-pneumococcal pneumonia, patients with pneumococcal pneumonia were more frequently admitted to hospital (80 % vs. 66 %, p < 0.001), had higher CURB score values on admission, had more frequently pleural effusion (19 % vs. 14 %, p = 0.001) and needed more frequently oxygen insufflation (58 % vs. 44 %, p < 0.001). There was no relevant difference in overall mortality., Conclusions: Pneumococcal pneumonia was associated with a more severe clinical course demanding more medical resources as compared to non-pneumococcal pneumonia., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Persons with migration background exhibit higher smoking rates in comparison to the general population.These smokers often cannot be reached by prevention measures at the family doctor's office., Methods: In summer 2011 the health campaign "Smoke-free by Ramadan" was launched in 11 German cities. Measures included the training of doctors on smoking cessation methods, general bilingual information flyers, and in some cases lectures on smoking, specifically for imams. A number of local events, especially for individuals with Turkish migration background were initiated. For these health events a specially equipped health bus of the BKK-vor-Ort was used, in which visitors were offered following elements: systematic data collection about age, sex and smoking behavior, a test to determine of the severity of nicotine dependence (Fagerström test, FTNA), as well as spirometric lung function test. Smokers were generally motivated to stop smoking. Data were anonymously collected and analysed in a documentation and communication sheet in Turkish language, and test results were handed over to participants on a printed information sheet., Results: Data of 1012 people collected on 8 health days were analysed (70% men, mean age 46.5 years). The percentage of smokers was 41.5% (men) or 30% (women). Of 294 male smokers, according to FTNA 43.6% had low, 24.8% had moderate, and 31.6% strong nicotine dependence; in the 91 female smokers the corresponding rates were 54.9%, 30.8% and 14.3%. The distribution pattern of the dependency levels was statistically significantly different between genders (p = 0.006). Reduced lung function (FEV, < 80%) occurred in smokers more often than in nonsmokers (30% versus 21%)., Conclusions: These results reinforce the importance of low-threshold prevention measures. By screening, here shown by the example of individuals with Turkish migration background, a significant number of smokers was identified who had in addition to strong nicotine addiction also significantly impaired lung function. As the odds for successful cessation without support are below 5%, evidence-based smoking cessation was advised to all smokers.

Pneumococcal disease can be divided into invasive disease, i.e. when bacteria are detected in normally sterile body fluids, and noninvasive disease. Pneumococcal disease occurs more frequently in younger children and older adults. It is estimated that, in 2050, 30.3% of the European population will be ≥65 yrs old, compared with 15.7% in 2000. Preventive medicine, including vaccination, is essential for the promotion of healthy ageing. Uptake rates for influenza vaccination in the elderly are generally low, despite recommendations in many countries. In addition, it has been reported that influenza infections can make people more susceptible to pneumococcal infections. Despite pneumococcal vaccination, case fatality rates for patients hospitalised with invasive pneumococcal disease have remained at around 12% since the 1950s. Even when effective antibiotic therapy is administered, mortality can be high amongst immunocompetent patients in intensive care. Timely and accurate diagnosis of pneumococcal disease and identification of patients at high risk of poor outcome is essential to ensure that adequate treatment, including hospitalisation when necessary, is implemented as early as possible. Improved diagnostic techniques and more efficacious treatments may help to reduce the burden of pneumococcal disease, but preventive measures, such as influenza and pneumococcal vaccination, should be promoted in order to avoid preventable disease, particularly in the elderly.

We performed a Web-based survey on attitudes and uptake of H1N1 influenza vaccination among members of two European societies, namely the European Respiratory Society and the European Society of Clinical Microbiology and Infectious Diseases. A multidisciplinary panel developed a questionnaire that examined physicians' and members' knowledge, attitudes and practice about seasonal and pandemic (H1N1) influenza vaccination. In all, 1334 healthcare workers from 83 countries (785 men and 549 women, mean age 45 ± 7 years) accessed and completed the survey. Safety concerns about vaccines was the main reason reported by 451/1285 respondents for not being vaccinated. More than 30% of 1282 respondents considered the management of communication on the flu pandemic by health authorities to be insufficient. The results of this survey should help health authorities to better design future steps for the successful vaccination of healthcare workers., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors., (© 2010 John Wiley & Sons A/S.)

Community-acquired pneumonia is a frequent disease. Case-fatality rate and incidence are increasing with age. The German nation-wide competence network CAPNETZ presents reliable data on aetiology and course of the disease, based on more than 9000 prospectively observed patients. This review discusses current CAPNETZ-publication and their impact on daily clinical practice. The most frequent isolated pathogen isolated was STREPTOCOCCUS PNEUMONIAE. According to CAPNETZ results, the importance of atypical pathogens (i. e. Mycoplasma spp., Chlamydia spp., Legionella spp.) may have been overestimated in older studies: CHLAMYDIA PNEUMONIAE (< 1 %) are rarely found, and the most frequent atypical pathogen, Mycoplasma spp., causes only mild disease in younger patients resulting in a very low case-fatality-rate (0.7 %). Only hospitalized patients with legionella infections are at an increased risk to die. Gram-negative ENTEROBACTERIACEAE and PSEUDOMONAS AERUGINOSA are rare, restricted to high-risk patient groups (e. g. mulitmorbidity, enteral tube feeding), but are associated with an increased case-fatality rate., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Biomarkers have been intensively studied in community-acquired pneumonia (CAP) in recent years. In the context of the CAPNETZ study we had the unique opportunity to evaluate old and new biomarkers in a multicentre study with a high number of patients., Results: In several substudies we found the following results: procalcitonin, CRP and leukocytes show highest values in patients with typical bacterial etiology of CAP, but do not allow individual prediction of etiology. Patients without antibiotic pre-treatment show higher values of biomarkers compared to patients with antibiotic pre-treatment. New cardiovascular biomarkers are good predictors for short- and long-term mortality in CAP, superior to the inflammatory markers procalcitonin, CRP and leukocytes and at least comparable to the clinical CRB-65 score. Pro-Adrenomedullin is among the new biomarkers the one with the best prognostic value., Conclusions: Biomarkers correlate with the severity of CAP but do not allow individual prediction of etiology. New cardiovascular biomarkers are suitable for the evaluation of short- and long-term prognosis in CAP. The combination of several biomarkers reflecting different pathophysiological pathways has the potential to improve management of CAP in the future., (© Georg Thieme Verlag KG Stuttgart · New York.)

Lower respiratory tract infections and tuberculosis represent some of the top health priorities in Europe. In the present report, the most recent advances in the field of disease control, clinical research and basic science of lower respiratory tract infections and tuberculosis are presented through analysis of some of the best abstracts presented at the 19th European Respiratory Society Congress in Vienna (Austria). Pathogenesis, diagnosis, treatment, prognostic factors and novel diagnostic techniques relevant for bacterial and viral infections, as well as new tools for the diagnosis of latent and active tuberculosis in different sub-groups of patients, are discussed. The growing epidemiological threat represented by multidrug-resistant and extensively drug-resistant tuberculosis cases is presented and its impact analysed.

Lower respiratory tract infections play an important role in the ambulatory and hospital health-care sectors. State-of-the-art diagnoses of lower respiratory tract infections and methods to differentiate bacterial lower respiratory tract infections from colonisation have been described in the first two parts of this review series. The present article summarises current diagnostic methods and treatment indications for viral and fungal respiratory infections. These recommendations may guide clinicians in their decision to prescribe or withhold antibiotic therapies in daily clinical practice., (Georg Thieme Verlag KG Stuttgart. New York.)

This update summarized the hospital experience from the first wave of the new influenza A/H1/N1 pandemic., (Copyright Georg Thieme Verlag KG Stuttgart . New York.)

In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections affect the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series described frequent viral pathogens, pathogenesis of viral LRTI, and diagnostic procedures. In this 2 (nd) part the aetiological role of viruses in the most frequent forms of LRTI will be highlighted, and the third and last part will provide an overview of therapeutic and preventive options., (Georg Thieme Verlag KG Stuttgart New York.)

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., ((c) Georg Thieme Verlag KG Stuttgart-New York.)

Background: Respiratory viruses, predominantly rhinoviruses are the major cause of asthma exacerbations. Impaired production of interferon-beta in rhinovirus infected bronchial epithelial cells (BECs) and of the newly discovered interferon-lambdas in both BECs and bronchoalveolar lavage cells, is implicated in asthma exacerbation pathogenesis. Thus replacement of deficient interferon is a candidate new therapy for asthma exacerbations. Rhinoviruses and other respiratory viruses infect both BECs and macrophages, but their relative capacities for alpha-, beta- and lambda-interferon production are unknown., Methods: To provide guidance regarding which interferon type is the best candidate for development for treatment/prevention of asthma exacerbations we investigated respiratory virus induction of alpha-, beta- and lambda-interferons in BECs and peripheral blood mononuclear cells (PBMCs) by reverse transferase-polymerase chain reaction and enzyme-linked immunosorbent assay., Results: Rhinovirus infection of BEAS-2B BECs induced interferon-alpha mRNA expression transiently at 8 h and interferon-beta later at 24 h while induction of interferon-lambda was strongly induced at both time points. At 24 h, interferon-alpha protein was not detected, interferon-beta was weakly induced while interferon-lambda was strongly induced. Similar patterns of mRNA induction were observed in primary BECs, in response to both rhinovirus and influenza A virus infection, though protein levels were below assay detection limits. In PBMCs interferon-alpha, interferon-beta and interferon-lambda mRNAs were all strongly induced by rhinovirus at both 8 and 24 h and proteins were induced: interferon-alpha>-beta>-lambda. Thus respiratory viruses induced expression of alpha-, beta- and lambda-interferons in BECs and PBMCs. In PBMCs interferon-alpha>-beta>-lambda while in BECs, interferon-lambda>-beta>-alpha., Conclusions: We conclude that interferon-lambdas are likely the principal interferons produced during innate responses to respiratory viruses in BECs and interferon-alphas in PBMCs, while interferon-beta is produced by both cell types.

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.

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.

Bcl-2-associated athanogene-1 (BAG1) binds heat-shock protein 70 (Hsp70)/Hsc70, increases intracellular chaperone activity in neurons and proved to be protective in several models for neurodegeneration. Mutations in the superoxide dismutase 1 (SOD1) gene account for approximately 20% of familial amyotrophic lateral sclerosis (ALS) cases. A common property shared by all mutant SOD1 (mtSOD1) species is abnormal protein folding and the propensity to form aggregates. Toxicity and aggregate formation of mutant SOD1 can be overcome by enhanced chaperone function in vitro. Moreover, expression of mtSOD1 decreases BAG1 levels in a motoneuronal cell line. Thus, several lines of evidence suggested a protective role of BAG1 in mtSOD1-mediated motoneuron degeneration. To explore the therapeutic potential of BAG1 in a model for ALS, we generated SOD1G93A/BAG1 double transgenic mice expressing BAG1 in a neuron-specific pattern. Surprisingly, substantially increased BAG1 protein levels in spinal cord neurons did not significantly alter the phenotype of SOD1G93A-transgenic mice. Hence, expression of BAG1 is not sufficient to protect against mtSOD1-induced motor dysfunction in vivo. Our work shows that, in contrast to the in vitro situation, modulation of multiple cellular functions in addition to enhanced expression of a single chaperone is required to protect against SOD1 toxicity, highlighting the necessity of combined treatment strategies for ALS.

Asthma is a chronic inflammatory disorder of the airways. Allergen-induced airway inflammation plays a central role in the pathogenesis of the disease whereas infections are known to be important triggers of acute exacerbations. Chronic or latent infections may also influence and enhance the local inflammation. The aim of this review is to give an overview of the different pathogens and to present the current understanding of the role of respiratory viruses and atypical bacteria in the pathogenesis of the disease.