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BackgroundIdentifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India.MethodsThe European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s.Results1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39–7.50), severe exacerbations (HR 2.71, 95% CI 1.92–3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36–4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantlyKlebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62–6.06), whilePseudomonas aeruginosainfection was associated with severe exacerbations (HR 1.41, 95% CI 1.01–1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13–1.91).ConclusionsThis study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

ObjectiveThere is a paucity of observational data on antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). We aimed to assess the course of disease of IPF patients with and without antifibrotic therapy under real-life conditions.MethodsWe analysed data from a non-interventional, prospective cohort study of consecutively enrolled IPF patients from 20 interstitial lung disease expert centres in Germany. Data quality was ensured by automated plausibility checks, on-site monitoring, and source data verification. Propensity scores were applied to account for known differences in baseline characteristics between patients with and without antifibrotic therapy.ResultsAmong the 588 patients suitable for analysis, the mean±sd age was 69.8±9.1 years, and 81.0% were male. The mean±sd duration of disease since diagnosis was 1.8±3.4 years. The mean±sd value at baseline for forced vital capacity (FVC) and diffusion capacity (DLCO) were 68.6±18.8% predicted and 37.8±18.5% predicted, respectively. During a mean±sd follow-up of 1.2±0.7 years, 194 (33.0%) patients died. The 1-year and 2-year survival rates were 87% versus 46% and 62% versus 21%, respectively, for patients with versus without antifibrotic therapy. The risk of death was 37% lower in patients with antifibrotic therapy (hazard ratio 0.63, 95% CI 0.45; 0.87; p=0.005). The results were robust (and remained statistically significant) on multivariable analysis. Overall decline of FVC and DLCO was slow and did not differ significantly between patients with or without antifibrotic therapy.ConclusionsSurvival was significantly higher in IPF patients with antifibrotic therapy, but the course of lung function parameters was similar in patients with and without antifibrotic therapy. This suggests that in clinical practice, premature mortality of IPF patients eventually occurs despite stable measurements for FVC and DLCO.

Sarcoidosis is a disease characterised by granuloma formation. There is an unmet need for new treatment strategies beyond corticosteroids. The NLRP3 inflammasome pathway is expressed in innate immune cells and senses danger signals to elicit inflammatory interleukin (IL)-1β; it has recently become a druggable target. This prompted us to test the role of the NLRP3 inflammasome and IL-1β pathway in granuloma formation and sarcoidosis.19 sarcoid patients and 19 healthy volunteers were recruited into this pilot study. NLRP3 inflammasome activity was measured in bronchoalveolar lavage (BAL) cells and lung and skin biopsies using immunohistochemistry, Western blot, reverse-transcriptase PCR and ELISA. For in vivo experiments we used the trehalose 6,6′-dimycolate-granuloma mouse model and evaluated lung granuloma burden in miR-223 knockout and NLRP3 knockout mice, as well as the treatment effects of MCC950 and anti-IL-1β antibody therapy.We found strong upregulation of the NLRP3 inflammasome pathway, evidenced by expression of activated NLRP3 inflammasome components, including cleaved caspase-1 and IL-1β in lung granuloma, and increased IL-1β release of BAL cells from sarcoid patients compared to healthy volunteers (p=0.006). mRNA levels of miR-223, a micro-RNA downregulating NLRP3, were decreased and NLRP3 mRNA correspondingly increased in alveolar macrophages from sarcoid patients (pIn conclusion, our data provide evidence of upregulated inflammasome and IL-1β pathway activation in sarcoidosis and suggest both as valid therapeutic targets.

Few women are still promoted to leadership positions and there seems to be an unconscious bias that must be changedhttp://bit.ly/2mET3t6

Clinical practice guidelines have to respond to the needs of users http://ow.ly/Vui330iwPbY

The ERS Clinical Research Collaborations (CRCs) programme provides support to projects in different areas of respiratory medicine, to build and maintain pan-European and/or global collaborations. CRC applications can be submitted annually by October 15. http://ow.ly/34s730lxgnw

“… especially about the future.” This frequently used Yogi Berra quote also holds true for the paper by Mangen et al. [1] from the Netherlands, which modelled the cost-effectiveness of a potential vaccination programme for elderly adults using the 13-valent pneumococcal conjugate vaccine. Do the results of the CAPITA study justify the general vaccination of adults with PCV13? We would like to thank Alexander Kuhlmann (Centre for Health Economics, Hannover, Germany) for intense and fruitful discussions.

Task forces use rigorous methodology, and the ERS will not tolerate interference with the processes by outsiders http://ow.ly/WwIe30cyhDO

The pathogenetic role of angiogenesis in interstitial lung diseases (ILDs) is controversial. This study represents the first investigation of the spatial complexity and molecular motifs of microvascular architecture in important subsets of human ILD. The aim of our study was to identify specific variants of neoangiogenesis in three common pulmonary injury patterns in human ILD.We performed comprehensive and compartment-specific analysis of 24 human lung explants with usual intersitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and alveolar fibroelastosis (AFE) using histopathology, microvascular corrosion casting, micro-comupted tomography based volumetry and gene expression analysis using Nanostring as well as immunohistochemistry to assess remodelling-associated angiogenesis.Morphometrical assessment of vessel diameters and intervascular distances showed significant differences in neoangiogenesis in characteristically remodelled areas of UIP, NSIP and AFE lungs. Likewise, gene expression analysis revealed distinct and specific angiogenic profiles in UIP, NSIP and AFE lungs.Whereas UIP lungs showed a higher density of upstream vascularity and lower density in perifocal blood vessels, NSIP and AFE lungs revealed densely packed alveolar septal blood vessels. Vascular remodelling in NSIP and AFE is characterised by a prominent intussusceptive neoangiogenesis, in contrast to UIP, in which sprouting of new vessels into the fibrotic areas is characteristic. The molecular analyses of the gene expression provide a foundation for understanding these fundamental differences between AFE and UIP and give insight into the cellular functions involved.

Bronchiectasis is a chronic airway disease with often disabling symptoms, which is associated with excess mortality and a substantial economic burden for healthcare systems [1]. Although considered to be one of the most neglected diseases in respiratory medicine [2], bronchiectasis is apparently more common than previously thought [3, 4]. While trends regarding its epidemiology have been published for the UK and the US, with marked increases in prevalence rates reported [5–7], such studies are missing for most countries including Germany. However, these basic epidemiologic data are needed in order to inform healthcare authorities and policy makers regarding resource allocation and requirements planning. Thus, the objective of the present study was to provide insights into the trends of bronchiectasis prevalence in Germany. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Ringshausen reports grants, personal fees and other from Bayer HealthCare, grants, personal fees and other from Grifols Germany, grants, personal fees and other from Insmed Germany, personal fees from Astra Zeneca, personal fees and other from Chiesi, grants, personal fees and other from Novartis, grants and other from InfectoPharm, other from Vertex, other from Parion, other from Celtaxsys, other from Corbus, other from GSK, grants from Polyphor, personal fees and other from Boehringer Ingelheim, personal fees and other from Zambon, grants from Baslilea, other from Algipharma, outside the submitted work. Conflict of interest: Dr. Rademacher reports grants and personal fees from Bayer Health care, grants and personal fees from Insmed, grants and personal fees from Grifols, personal fees from MSD Sharp & Dohme, personal fees from Astra Zeneca, personal fees from Chiesi, outside the submitted work; . Conflict of interest: Dr. Pink reports grants from PROGNOSIS, during the conduct of the study; grants from Infectopharm, from Bayer , from Insmed, from Grifols, during the conduct of the study; personal fees and non-financial support from Berlin Chemie, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Chiesi , outside the submitted work. Conflict of interest: Dr. de Roux has nothing to disclose. Conflict of interest: Lennart Hickstein has nothing to disclose. Conflict of interest: Tina Ploner has nothing to disclose. Conflict of interest: Dr. Welte reports grants from Grifols, Insmed, Novartis, personal fees from Grifols, Insmed, Novartis, outside the submitted work. Conflict of interest: Dr. Diel reports grants and personal fees from Bayer Vital, personal fees from Insmed Inc., outside the submitted work.

Pneumocystis jirovecii pneumonia (PcP) occurs exclusively in immunocompromised patients. About 50% of PcP is HIV-related, the other half associated with immunosuppression for other reasons [1]. If PcP progresses to an acute respiratory distress syndrome (ARDS) requiring intensive care and invasive mechanical ventilation, the prognosis is generally poor [1] and mortality is about 80% if additional veno-venous extracorporeal membrane oxygenation (VV-ECMO) support is necessary [1]. Despite lack of clear evidence [2], VV-ECMO has become an integral part in the rescue therapy of severe ARDS. Moreover, some centers start VV-ECMO at early time-points in order to rigorously follow (ultra-) protective ventilation strategies [3]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Stahl has nothing to disclose. Conflict of interest: Dr. Schenk has nothing to disclose. Conflict of interest: Dr. Seeliger has nothing to disclose. Conflict of interest: Dr. Wiesner has nothing to disclose. Conflict of interest: Dr. Schmidt has nothing to disclose. Conflict of interest: Dr. Bauersachs has nothing to disclose. Conflict of interest: Dr. Welte reports personal fees from AstraZeneca, Boehringer, Berlin Chemie, Chiesi, GSK, Novartis, grants from AstraZeneca, Novartis, outside the submitted work. Conflict of interest: Dr. Kuhn has nothing to disclose. Conflict of interest: Dr. Haverich has nothing to disclose. Conflict of interest: Dr. Hoeper reports personal fees from Actelion, personal fees from Bayer, personal fees from MSD, personal fees from Pfizer, outside the submitted work. Conflict of interest: Dr. David has nothing to disclose.

This study suggests that the risk of cross-infection with P. aeruginosa in bronchiectasis is smallhttp://ow.ly/itUa30nrgET

Robust evidence for the prevalence of bronchiectasis in Germany and its association with chronic airflow obstruction http://ow.ly/QvSBo

C(U)RB-65 (confusion, (urea7 mol · L(-1),) respiratory frequency ≥ 30 breaths · min(-1), systolic blood pressure90 mmHg or diastolic blood pressure ≤60 mmHg and age ≥ 65 years) is now the generally accepted severity score for patients with community-acquired pneumonia (CAP) in Europe. In an observational study based on the large database from the German nationwide performance measurement programme in healthcare quality, including data from all hospitalised patients with CAP during 2008-2010, different CRB-age groups (≥ 50 and ≥ 60 years) across the total CAP population and three entities of CAP (younger population aged65 years, patients aged ≥ 65 years not residing in nursing homes and those with nursing home-acquired pneumonia (NHAP)) were validated for their potential to predict in-hospital death. 660 594 patients were investigated. Mortality was n=93 958 (14.0%). In the total population, CRB-80 had the optimal area under the curve (0.690, 95% CI 0.688-0.691). However, in the younger cohort, CRB-50 performed best (0.730, 95% CI 0.724-0.736), with good identification of low-risk patients (CRB-50 risk class 1: 1.28% deaths, negative predictive value 98.7%). In the elderly, CRB-80 as the optimal age group performed worse (0.663, 95% CI 0.660-0.655 in patients not residing in nursing homes; 0.608, 95% CI 0.605-0.611 in those with NHAP). In the latter group, all CRB-age groups failed to identify low-risk patients (CRB-80 risk class 1: 22.75% deaths, negative predictive value 81.8%). Patients with hospitalised CAP aged65 years may be assessed by the CRB-50 score. In those aged ≥65 years (not NHAP) assessed by the CRB-65 score, low-risk patients are already are at an increased risk of death. In NHAP patients, even the use of CRB-80 does not identify low-risk patients and should be accompanied by the evaluation of functional status and comorbidity.

Community-acquired pneumonia (CAP) is now most frequent in elderly patients. CAP in the younger patient has attracted much less attention. Therefore, we compared patients with CAP aged 18 to65 yrs with those aged ≥ 65 yrs. Data from the prospective multicentre Competence Network for Community Acquired Pneumonia Study Group (CAPNETZ) database were analysed for potential differences in baseline characteristics, comorbidities, clinical presentation, microbial investigations, aetiologies, antimicrobial treatment and outcomes. Overall, 7,803 patients were studied. The proportion of younger patients (aged65 yrs) was 52.3% (18 to30 yrs 6.4%;40 yrs 17.1%;50 yrs 29.4%). Comorbidity was present in only half of the younger patients (46.6% versus 88.2%). Fever and chest pain were more common. Most younger patients presented with mild CAP (74.0% had a CRB-65 [corrected] score of 0 (confusion of new onset, [corrected] respiratory rate of ≥ 30 breaths · min(-1), blood pressure90 mmHg or diastolic blood pressure ≤ 60 mmHg, age ≥ 65 yrs)). Overall, Streptococcus pneumoniae and Mycoplasma pneumoniae were the most frequent pathogens in the younger patients. Short-term mortality was very low (1.7% versus 8.2%) and even lower in patients without comorbidity (0.3% versus 2.4%). Long-term mortality was 3.2% versus 15.9%, also lower in patients without comorbidity (0.8% versus 6.1%). Most of the differences found clearly arise after the fifth or within the middle of the sixth decade. CAP in the younger patient is a clinically distinct entity.

The aim of this study was to investigate treatment failure (TF) in hospitalised community-acquired pneumonia (CAP) patients with regard to initial antibiotic treatment and economic impact. CAP patients were included in two open, prospective multicentre studies assessing the direct costs for in-patient treatment. Patients received treatment either with moxifloxacin (MFX) or a nonstandardised antibiotic therapy. Any change in antibiotic therapy after >72 h of treatment to a broadened antibiotic spectrum was considered as TF. Overall, 1,236 patients (mean ± SD age 69.6 ± 16.8 yrs, 691 (55.9%) male) were included. TF occurred in 197 (15.9%) subjects and led to longer hospital stay (15.4 ± 7.3 days versus 9.8 ± 4.2 days; p < 0.001) and increased median treatment costs (€2,206 versus €1,284; p

Current guidelines for the treatment of patients with idiopathic pulmonary arterial hypertension (IPAH) recommend basing therapeutic decision-making on haemodynamic, functional and biochemical variables. Most of these parameters have been evaluated as risk predictors at the time of diagnosis. The aim of the present study was to assess the prognostic impact of changes in these parameters after initiation of targeted therapy. A cohort of 109 patients with IPAH who had undergone haemodynamic, functional and biochemical assessments at baseline and 3-12 months after initiation of pulmonary arterial hypertension (PAH)-targeted therapy, were followed for a median 38 months in order to determine predictors of mortality at baseline and during the course of their disease. Within the observation period, 53 (48.6%) patients died and four (3.7%) underwent lung transplantation. Kaplan-Meier estimates for transplantation-free survival were 92%, 67%, and 51% at 1, 3, and 5 yrs, respectively. Among baseline variables, 6-min walk distance, right atrial pressure, cardiac index, mixed-venous oxygen saturation (S(v,O(2))) and N-terminal-pro brain natriuretic peptide (NT-proBNP) were independent predictors of survival. During follow-up, changes in World Health Organization functional class, cardiac index, S(v,O(2)) and NT-proBNP proved significant predictors of outcome. When assigned to prognostic groups, improvements as well as deteriorations in these parameters after initiation of PAH-targeted therapy had a strong impact on survival. Measurements obtained at follow-up had a higher predictive value than variables obtained at baseline. Changes in established predictors of outcome during the course of the disease provide important prognostic information in patients with IPAH.

Pneumonia is an important cause of influenza-associated morbidity and mortality. Influenza vaccination has been shown to reduce morbidity and mortality during influenza seasons. Protection from severe pneumonia may contribute to the beneficial effect of influenza vaccination. Therefore, we investigated the impact of prior influenza vaccination on disease severity and mortality in patients with community-acquired pneumonia (CAP). Analysis from an observational, multicentre cohort study initiated by the German competence network for CAP was performed. Patients were analysed separately as an influenza season and off-season cohort. Associations between vaccination status and outcome parameters were evaluated by multivariate analyses. In the season cohort (2,368 patients) CAP in vaccinated patients was significantly less severe according to most analysed parameters (CURB index ≥ 1: OR 0.76, 95% CI 0.60-0.98; procalcitonin ≥ 2.0 ng·mL(-1): OR 0.53, 95% CI 0.35-0.81; procalcitonin ≥ 0.5 ng·mL(-1): OR 0.71, 95% CI 0.51-0.99) and these patients showed a significantly better overall survival within the 6-month follow-up period (HR 0.63, 95% CI 0.45-0.89). Within the off-season cohort (2,632 patients) there was no significant influence of vaccination status on CAP severity or disease outcome. In conclusion, prior influenza vaccination was associated with less severe clinical course and improved overall long-term survival in patients with CAP during influenza seasons.

By following education best practices, using available technology to remove barriers and continuing to ensure content remains free from bias, @ERStalk is committed to guiding respiratory health professionals along the path of lifelong learninghttp://ow.ly/4uUa30leLMb

The aim of the present study was to investigate the prognostic value, in patients with community-acquired pneumonia (CAP), of procalcitonin (PCT) compared with the established inflammatory markers C-reactive protein (CRP) and leukocyte (WBC) count alone or in combination with the CRB-65 (confusion, respiratory rateor=30 breaths x min(-1), low blood pressure (systolic value90 mmHg or diastolic valueor=60 mmHg) and ageor=65 yrs) score. In total, 1,671 patients with proven CAP were enrolled in the study. PCT, CRP, WBC and CRB-65 score were all determined on admission and patients were followed-up for 28 days for survival. In contrast to CRP and WBC, PCT levels markedly increased with the severity of CAP, as measured by the CRB-65 score. In 70 patients who died during follow-up, PCT levels on admission were significantly higher compared with levels in survivors. In receiver operating characteristic analysis for survival, the area under the curve (95% confidence interval) for PCT and CRB-65 was comparable (0.80 (0.75-0.84) versus 0.79 (0.74-0.84)), but each significantly higher compared with CRP (0.62 (0.54-0.68)) and WBC (0.61 (0.54-0.68)). PCT identified low-risk patients across CRB classes 0-4. In conclusion, procalcitonin levels on admission predict the severity and outcome of community-acquired pneumonia with a similar prognostic accuracy as the CRB-65 score and a higher prognostic accuracy compared with C-reactive protein and leukocyte count. Procalcitonin levels can provide independent identification of patients at low risk of death within CRB-65 (confusion, respiratory rateor=30 breaths x min(-1), low blood pressure (systolic value90 mmHg or diastolic valueor=60 mmHg) and ageor=65 yrs) risk classes.

Novel treatments, such as prostanoids or endothelin receptor antagonists, have been introduced for various forms of pulmonary arterial hypertension, but the long-term effects of these treatments on portopulmonary hypertension (PPHT) are unknown. In a retrospective analysis, the present authors assessed the safety and efficacy of inhaled iloprost, a prostacyclin analogue, and bosentan, an endothelin receptor antagonist, in patients with PPHT. In total, 31 consecutive patients with Child class A or B cirrhosis and severe PPHT were treated for up to 3 yrs with either inhaled iloprost (n = 13) or bosentan (n = 18), and the effects on exercise capacity, haemodynamics and survival were evaluated. In the iloprost group, the survival rates at 1, 2 and 3 yrs were 77, 62 and 46%, respectively. In the bosentan group, the respective survival rates were 94, 89 and 89%. Event-free survival rates, i.e. survival without transplantation, right heart failure or clinical worsening requiring the introduction of a new treatment for pulmonary hypertension, was also significantly better in the bosentan group. Bosentan had significantly better effects than inhaled iloprost on exercise capacity, as determined by the 6-min walk test, as well as on haemodynamics. Both treatments proved to be safe, especially in regards of liver function. In the present series of patients with well-preserved liver function and severe portopulmonary hypertension, treatment with both inhaled iloprost and bosentan appeared to be safe. Patients treated with bosentan had higher survival rates, but prospective controlled studies are required to confirm these findings.

Combination therapy may improve outcome in patients with severe pulmonary arterial hypertension (PAH). PAH patients were treated according to a goal-oriented therapeutic strategy. Patients who did not reach the treatment goals with monotherapy received combination treatment according to a predefined strategy, including bosentan, sildenafil and inhaled iloprost. Intravenous iloprost and lung transplantation were reserved for treatment failures. End points were overall survival, transplantation-free survival, and survival free from transplantation and intravenous prostanoid treatment. Between January 2002 and December 2004, 123 consecutive patients with PAH were treated according to the novel approach. Survival at 1, 2 and 3 yrs was 93.0, 83.1 and 79.9%, respectively, which was significantly better than the survival of a historical control group, as well as the expected survival. Compared to the historical control group, the use of combination treatment also significantly improved the combined end point of death, lung transplantation and need for intravenous iloprost treatment. In conclusion, a therapeutic approach utilising combinations of bosentan, sildenafil and inhaled iloprost in conjunction with a goal-oriented treatment strategy provides acceptable long-term results in patients with severe pulmonary arterial hypertension, and reduces the need for intravenous prostaglandin treatment and lung transplantation.

To the Editor: Respiratory tract infections due to viral, bacterial or even fungal pathogens are common after lung transplantation [1]. Previous studies demonstrated increased hospitalisation rates and a greater risk of chronic lung allograft dysfunction in colonised patients with cystic fibrosis (CF) [2]. Positive effects of inhaled antibiotics have been demonstrated for pneumonia in non-transplant patients with improvements of lung function, hospitalisation rates and need for i.v. antibiotics [3, 4]. Inhaled colistin is known to provide high drug concentrations in sputum while low systemic concentrations occur and treatment is well tolerated [5]. Here, the impact of inhaled colistin, both in reducing bacterial load in previously colonised patients and as a preventive therapy in non-colonised CF patients, after lung transplantation, was studied in a retrospective single-centre study (Hanover Medical School, Hanover, Germany). CF patients who underwent lung transplantation between January 1, 2005 and May 1, 2011 were included and follow-up continued until June 6, 2011. Perioperative antibiotics were continued for 2 weeks after lung transplantation, consisting of combination therapy based on previous microbiological findings. A routine surveillance programme at 1, 3, 6, 9 and 12 months after transplantation included pulmonary function testing, blood gas analysis and bronchoscopy with bronchoalveolar …

It has been proposed that targeted treatments should be combined for patients with idiopathic pulmonary arterial hypertension (IPAH) responding insufficiently to monotherapy. This study followed the clinical course of nine patients with severe IPAH, in whom the endothelin receptor antagonist bosentan caused transient clinical improvement, eventually followed by a decline in exercise tolerance, who received adjunct treatment with the phospodiesterase-5-inhibitor sildenafil. Measurements included the 6-min walk distance (6MWD) and cardiopulmonary exercise testing (CPET). The 6MWD at baseline was 346+/-66 m and improved to 403+/-80 m 3 months after introduction of bosentan treatment. However, this effect was not sustained and, after an interval of 11+/-5 months, the walk distance had declined to 277+/-80 m. At this point, sildenafil was added to bosentan. Three months later, the 6MWD had increased to 392+/-61 m and the patients remained stable throughout the median follow-up of 9 months (range 6-12). Measurement of the maximum oxygen uptake during CPET confirmed these results. The combination of bosentan and sildenafil was well tolerated by all patients. These preliminary data suggest that combining bosentan and sildenafil may be safe and effective in patients with idiopathic pulmonary arterial hypertension.

Proteasome inhibition has become a target for antitumour and anti-inflammatory therapy. The present study investigated the influence of cysteine proteinase and proteasome inhibitors on chemokine production in lung epithelial cells and monocytic cells. The lung carcinoma cell lines A549, SK-MES, NCI-H727, virus-transformed bronchial epithelial cell line BEAS-2B, primary lung epithelial cells, and the acute monocytic leukaemia cell lines Mono-Mac-6 and THP-1 were incubated with proteasome (N-acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN), beta-lactone) or cysteine proteinase inhibitor (L-trans-Epoxysuccinyl-Leu-3-methylbutylamide-ethyl ester) and the influence on chemokine production (interleukin-8: IL-8, monocyte chemoattractant protein-1, RANTES) was quantified at protein and mRNA levels. Inhibition of proteasome activity by ALLN and beta-lactone resulted in significantly increased IL-8 secretion (5- to 22-fold). Cysteine proteinase inhibitors did not influence chemokine production. The simultaneous rise in IL-8 mRNA was caused by an increased half-life of mRNA and increased RNA synthesis. Moreover, analysis of transcription factor activation revealed induction of activator protein-1 (c-Jun) activity by proteasome inhibition, whereas nuclear factor-kappaB (p50 and p65) was not activated. The significant increase in IL-8 production after proteasome inhibition was also observed in primary lung epithelial cells and in monocytic cells. In addition, the secreted IL-8 was biologically active as shown by the neutrophil chemotaxis assay. In conclusion, it was shown that proteasome inhibitors stimulate interleukin-8 secretion in lung epithelial cells and monocytic cells, thus recruiting neutrophils.

Lysosomal cysteine proteases are a family comprising > 10 enzymes. For many years it was believed that these enzymes catalyse protein breakdown unselectively, are highly redundant in their substrate specificity and are also expressed ubiquitously. This view has changed dramatically since a number of new lysosomal cysteine proteases with restricted expression and outstanding enzymatic activity have been described. In addition, knockout mice and selective protease inhibitors have been used to characterise specific functions of single proteases. In this review, some of these functions are discussed in relation to the lungs, especially the role of lysosomal cysteine proteases in matrix remodelling, immunoregulation and surfactant protein processing.

Readers of scientific and medical journals will be familiar with the annual editorial from the chief editor(s) or editorial team, highlighting the aims for the year, interesting upcoming review series, statistics on submissions and impact factors, positioning alongside the competition (and what makes that journal better!), and new features and developments [1–4]. So, in keeping with tradition, the European Respiratory Journal ( ERJ ) brings you its yearly offering with everything that you would expect… but with a couple of twists. The first twist is that we are bringing this to you later than usual, more than mid-way through the year to coincide with the European Respiratory Society (ERS)'s congress in Vienna, Austria, from September 1 to 5, 2012. This gives us an opportunity to reflect on what has happened this year and check that the editorial aims that were set at the start of the year are being met. The second twist is that we will be introducing to you (or reminding you about, for those already familiar with the Society) the other publications in the ERS portfolio. The publications are central to the aims of the ERS, being one of the society's “pillars”, in that they are a forum for sharing and disseminating knowledge, and ultimately alleviating suffering from respiratory disease and promoting lung health. If the ERJ is considered as the official scientific journal of the ERS – one might say a flagship – then what of the rest of the fleet? Looking first at the ERJ , we are pleased to be able to announce the 2011 impact factor is 5.895, which means that the journal has regained the bronze medal position of third in the respiratory systems journals list. The ERJ attracts increasingly high-quality science and this reputation manifests itself in the number …

To the Editors: Endotracheal intubation and mechanical ventilation are mainstays in the management of patients with acute respiratory distress syndrome (ARDS), but this treatment strategy exposes the patient to several risks and complications. A small number of ARDS patients can be treated with noninvasive ventilation and these patients have less ventilator-associated pneumonia and a lower mortality rate [1]. However, failure to improve oxygenation with noninvasive ventilation indicates the need for endotracheal intubation [1]. In patients with severe respiratory failure, extracorporeal membrane oxygenation (ECMO) is increasingly being used on top of mechanical ventilation to facilitate oxygenation and protective ventilation [2]. A novel concept is the use of ECMO in awake, spontaneously breathing patients to avoid the complications of invasive ventilation. So far, “awake ECMO” has been used predominantly in patients with end-stage lung disease as bridge to lung transplantation [3, 4]. The use of awake ECMO as …

Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes.

The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent. The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited. A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink). Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population–intervention–comparison–outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.

Pulmonary arterial hypertension (PAH) is defined by the presence of pre-capillary pulmonary hypertension (PH) in the absence of underlying causes such as lung diseases, chronic thromboembolic pulmonary hypertension (CTEPH) or other rare conditions [1, 2]. While the idiopathic form of PAH (IPAH) was originally described as a disease affecting primarily younger women [3, 4], it is now increasingly being diagnosed in elderly patients, many of whom present with cardiopulmonary comorbidities, which can make the exact diagnostic classification of such patients difficult [5–8]., Elderly patients with IPAH, a smoking history and a low DLCO may suffer from a distinct pulmonary vasculopathy http://ow.ly/sdGh30dxd0G

If one asks medical students which emergencies they hold as especially important in internal medicine, more than 90% first mention myocardial infarction and stroke. This is not surprising, because these diseases occupy the first places in the mortality statistics contained in the Global Burden of Disease report [1]. Nevertheless, respiratory failure is only described as rare, despite the fact that chronic obstructive pulmonary disease (COPD) is ranked fifth and pneumonia seventh in the same report. While the high hospital mortality rate of myocardial infarction and stroke is well known, the risk of acute exacerbation of COPD and of pneumonia is often underestimated. COPD audit: COPD exacerbation and pneumonia are internal medicine emergencies needing treatment in specialist units

To the Editors: At least two clinical rules for predicting short- and long-term mortality in patients with community-acquired pneumonia (CAP) have been successfully validated: the Pneumonia Severity Index (PSI), and the CURB-65 score (confusion, urea >7 mmol·L−1, respiratory frequency ≥30 breaths·min−1, systolic blood pressure

S treptococcus pneumoniae is a major bacterial pathogen and a predominant cause of community-acquired pneumonia, acute exacerbations of chronic bronchitis, meningitis, sinusitis and bacteraemia in both developed and developing countries. Each year millions of people die from pneumococcal diseases. Even in developed countries, the case-fatality rate of pneumococcal pneumonia is still high 1. This is in contrast to the fact that 1) appropriate antibiotic treatment is available, and 2) to date, antimicrobial resistance rates of pneumococci for non-meningeal infections are still low in most countries or antimicrobial resistance ( e.g. penicillin-resistance) is not related to treatment failure in pneumococcal pneumonia 2. A considerable number of patients die within the first 48 h and these early deaths have not been prevented by antibiotic treatment 3. Brueggemann et al. 4 investigated the risk of different pneumococcal serotypes to cause invasive disease. Invasive pneumococcal disease is defined as the isolation of S. pneumoniae from a normally sterile site, e.g. blood, cerebrospinal fluid or pleural fluid. The polysaccharide capsule protects pneumococci from phagocytosis and also may determine affinity to respiratory epithelium. Therefore, it seems reasonable that different pneumococcal …

New antifibrotic therapies do not impair the clinical course and survival in patients with ILD who underwent DLuTX