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Simple observation of chest radiograph quadrant involvement in ARDS could improve the prediction of mortality. Patients needing mechanical ventilation with unilateral and two quadrants chest radiograph involvement should receive protective ventilation.https://bit.ly/2KqwqVO

Preventing cardiovascular events after pneumonia by aspirin: another step forward, but questions remainhttps://bit.ly/2H5z4OB

Introduction Efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, was demonstrated in randomised controlled trials; data on its real-world impact in routine clinical practice are starting to emerge. We assessed the effectiveness and safety of mepolizumab prescribed for patients in the real world. Methods REALITI-A is a global, prospective, observational cohort study, collecting data from routine healthcare visits from patients with asthma. Patients newly prescribed mepolizumab for severe asthma with 12 months of relevant medical history pre-mepolizumab (collected retrospectively) were enrolled. An initial analysis of data from early initiators who had completed 1 year of follow-up (as of February 28, 2019) was conducted. The primary objective was to compare the rate of clinically significant exacerbations (requiring oral corticosteroids (OCS) and/or hospitalisation and/or emergency department visit) before and after mepolizumab; exacerbations requiring hospitalisation and/or emergency department visit and change in maintenance OCS use were secondary objectives. Treatment-related adverse events were reported. Results Overall, 368 mepolizumab-treated patients were included. Rates of clinically significant exacerbations were reduced by 69% from 4.63 per person per year pre-treatment to 1.43 per person per year during follow-up (p, Mepolizumab has demonstrated efficacy in patients with severe eosinophilic asthma in the controlled environment of clinical trials. These initial data from the prospective REALITI-A study show that similar results are obtained in a real-world setting. https://bit.ly/3hINnFO

The European Respiratory Society now issues short official scientific documentshttps://bit.ly/3brN9jO

The ERS fellowship portfolio continues to be refined, to respond to the changing needs of our Society. Under the 2016–2019 Fellowship strategy, a wide range of programmes is available, reflecting the diversity and global dimension of the ERS membership.http://bit.ly/2YEpOnv

BackgroundThe role of macrolide/β-lactam combination therapy in community-acquired pneumonia (CAP) of moderate severity is a matter of debate. Macrolides expand the coverage to atypical pathogens and attenuate pulmonary inflammation, but have been associated with cardiovascular toxicity and drug interactions. We developed a decision tree based on aetiological and clinical parameters, which are available ex ante to support a personalised decision for or against macrolides for the best clinical outcome of the individual patient.MethodsWe employed machine learning in a cross-validation scheme based on a well-balanced selection of 4898 patients after propensity score matching to data available on admission of 6440 hospitalised patients with moderate severity (non-intensive care unit patients) from the observational, prospective, multinational CAPNETZ study. We aimed to improve the primary outcome of 180-day survival.ResultsWe found a simple decision tree of patient characteristics comprising chronic cardiovascular and chronic respiratory comorbidities as well as leukocyte counts in the respiratory secretion at enrolment. Specifically, we found that patients without cardiovascular or patients with respiratory comorbidities and high leukocyte counts in the respiratory secretion benefit from macrolide treatment. Patients identified to be treated in compliance with our treatment suggestion had a lower mortality of 27% (OR 1.83, 95% CI 1.48–2.27; pConclusionStratifying macrolide treatment in patients following a simple treatment rule may lead to considerably reduced mortality in CAP. A future randomised controlled trial confirming our result is necessary before implementing this rule into the clinical routine.

Patients with clinically significant bronchiectasis featuring an eosinophilic inflammatory endotype who were treated with add-on mepolizumab or benralizumab showed a significant improvement of FEV1, symptom burden and quality of lifehttp://bit.ly/2AZvBLm

Hyaluronic acid (HA) and its degradation products play an important role in lung pathophysiology and airway remodelling in chronic obstructive pulmonary disease (COPD). We investigated if HA and its degrading enzyme hyaluronidase (HYAL)-1 are associated with COPD severity and outcome. Serum HA was assessed in a discovery cohort of 80 COPD patients at stable state and exacerbations. HA, HYAL-1 and HYAL-1 enzymatic activity were evaluated at stable state, exacerbations and 4 weeks after exacerbations in 638 COPD patients from the PROMISE validation cohort. In the discovery cohort, serum HA was higher at exacerbations compared with the stable state (p=0.015). In the validation cohort, HA was higher at moderate and severe exacerbations than at baseline (p

The “dead-space” concept: bronchoscope size and instillation protocol significantly alter BAL cellular composition http://ow.ly/ZEaj30be7HV

This phase II, randomised, double-blind, multicentre study (NCT00930982) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis. Adults who were culture positive for pre-defined potential respiratory pathogens (including Pseudomonas aeruginosa and Haemophilus influenzae) were randomised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days (with 56 days of follow-up). Bacterial density in sputum (primary end-point), pulmonary function tests, health-related quality of life and safety were monitored throughout the study. 60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo. Subjects on ciprofloxacin DPI had a significant reduction (p0.001) in total sputum bacterial load at the end of treatment (-3.62 log10 CFU·g(-1) (range -9.78-5.02 log10 CFU·g(-1))) compared with placebo (-0.27 log10 CFU·g(-1) (range -7.96-5.25 log10 CFU·g(-1))); the counts increased thereafter. In the ciprofloxacin DPI group, 14 (35%) out of 40 subjects reported pathogen eradication at end of treatment versus four (8%) out of 49 in the placebo group (p=0.001). No abnormal safety results were reported and rates of bronchospasm were low. Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis.

The disease caused by nontuberculous mycobacteria (NTM) forms a broad clinical spectrum from asymptomatic infection to fatal disseminated disease in humans. While many NTM patients have underlying pulmonary diseases, NTM symptoms are undifferentiated from symptoms of patients with chronic pulmonary structural diseases [1]. Not all CF patients with MAC detected in respiratory samples require anti-mycobacterial treatment

ENaC polymorphism p.W493R is associated with bronchiectasis but does not necessarily lead to aberrant ion conductance http://ow.ly/S5Mwj

Increased awareness of the role of adult vaccination is needed to reduce pneumococcal pneumonia rates http://ow.ly/M3pqj

Guidelines indicate that pharmacological treatment of chronic obstructive pulmonary disease (COPD) is based on bronchodilators with the addition of inhaled corticosteroids (ICS) in frequent exacerbators [1]. Although this recommendation is in accordance with the best evidence available, it does not take into account that more than half of the exacerbations are infective and infections are not adequately prevented or treated by ICS. In fact, no pharmacological treatment has been able to suppress all exacerbations and, on the contrary, the long-term use of ICS has been associated with higher airway bacterial load in stable COPD [2], and increased risk of pneumonia [3] and tuberculosis [4]. Clinicians have always been aware that not all exacerbations of COPD are alike. Some must be treated with anti-infective agents while others respond better to systemic corticosteroids. Markers such as sputum colour and C-reactive protein levels are useful to differentiate exacerbations and guide therapy [5, 6]. Recent studies have further characterised these different types of exacerbations, and identified bacterial, viral, inflammatory (eosinophilic) and pauci-inflammatory phenotypes of exacerbations, with the majority (59%) of exacerbations being bacterial or viral. Interestingly, the phenotype of the exacerbation remains constant in a given patient [7]. However, despite these different phenotypes of exacerbations, no studies have attempted to investigate whether different treatments would be more effective in preventing one type of exacerbation or another. Both the high bacterial load in the airways in stable COPD and an increased frequency of exacerbations have been associated with a more rapid decline in lung function and an impairment in quality of life [8–10]. More recently, the presence of bronchiectasis in patients with COPD [11] and the persistent colonisation by unusual microorganisms [12] have also …

During the past decades, the incidence of tuberculosis (TB) has steadily declined in most west European countries, and many physicians will no longer encounter TB in their patients. Along with the declining practical experience of physicians, the chance for delay in diagnosing TB increases. An delayed diagnosis of TB index cases is the most important risk factor for the nosocomial transmission of Mycobacterium tuberculosis (MTB) [1], as numerous unprotected contacts among healthcare workers and inpatients may result before the diagnosis of TB is established and respiratory isolation is applied [2, 3]. The clean-up after such a mishap can be complicated and time-consuming, as the individuals concerned need to be identified and contacted. Patients might have been already discharged, or healthcare workers may not be aware of exposure to a TB index case for days or even weeks [4]. However, the difficulty is not over, even when the respective contacts have been identified. As there is no perfect test for the diagnosis of TB infection, the question arises of which test should be used and who should be tested with this assay in order to obtain optimal results. Only close contacts should be tested in order to improve the positive predictive value of …

The BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index is well-validated for mortality prediction in chronic obstructive pulmonary disease (COPD). Concentrations of plasma pro-adrenomedullin, a surrogate for mature adrenomedullin, independently predicted 2-year mortality among inpatients with COPD exacerbation. We compared accuracy of initial pro-adrenomedullin level, BODE and BODE components, alone or combined, in predicting 1-year or 2-year all-cause mortality in a multicentre, multinational observational cohort with stable, moderate to very severe COPD. Pro-adrenomedullin was significantly associated (p

This multicentre, blinded, sham-controlled study was performed to assess the safety and effectiveness of bronchial valve therapy using a bilateral upper lobe treatment approach without the goal of lobar atelectasis. Patients with upper lobe predominant severe emphysema were randomised to bronchoscopy with (n = 37) or without (n = 36) IBV Valves for a 3-month blinded phase. A positive responder was defined as having both a ≥ 4-point improvement in St George's Respiratory Questionnaire (SGRQ) and a lobar volume shift as measured by quantitative computed tomography. At 3 months, there were eight (24%) positive responders in the treated group versus none (0%) in the control group (p = 0.002). Also, there was a significant shift in volume in the treated group from the upper lobes (mean ± SD -7.3 ± 9.0%) to the non-treated lobes (6.7 ± 14.5%), with minimal change in the control group (p0.05). Mean SGRQ total score improved in both groups (treatment: -4.3 ± 16.2; control: -3.6 ± 10.7). The procedure and devices were well tolerated and there were no differences in adverse events reported in the treatment and control groups. Treatment with bronchial valves without complete lobar occlusion in both upper lobes was safe, but not effective in the majority of patients.

Increasing worldwide development of antimicrobial resistance and the association of resistance development and antibiotic overuse make it necessary to seek strategies for safely reducing antibiotic use and selection pressure. In a first step, in a non-interventional study, the antibiotic prescription rates, initial procalcitonin (PCT) levels and outcome of 702 patients presenting with acute respiratory infection at 45 primary care physicians were observed. The second part was a randomised controlled non-inferiority trial comparing standard care with PCT-guided antimicrobial treatment in 550 patients in the same setting. Antibiotics were recommended at a PCT threshold of 0.25 ng·mL −1 . Clinical overruling was permitted. The primary end-point for non-inferiority was number of days with significant health impairment after 14 days. Antibiotics were prescribed in 30.3% of enrolled patients in the non-interventional study. In the interventional study, 36.7% of patients in the control group received antibiotics as compared to 21.5% in the PCT-guided group (41.6% reduction). In the modified intention-to-treat analysis, the numbers of days with significant health impairment were similar (mean 9.04 versus 9.00 for PCT-guided and control group, respectively; difference 0.04; 95% confidence interval -0.73–0.81). This was also true after adjusting for the most important confounders. In the PCT group, advice was overruled in 36 cases. There was no significant difference in primary end-point when comparing the PCT group treated as advised, the overruled PCT group and the control group (9.008 versus 9.250 versus 9.000 days; p = 0.9605). A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to standard treatment in terms of safety, and effectively reduced the antibiotic treatment rate by 41.6%.

This report concerns the development and validation of two patient-reported outcomes questionnaires developed to assess chronic obstructive pulmonary disease (COPD) patients' ability to perform morning activities and to evaluate their morning symptoms. Based on interviews with COPD patients, the Capacity of Daily Living during the Morning (CDLM) questionnaire and the Global Chest Symptoms Questionnaire (GCSQ) were developed, linguistically validated and incorporated into two multicentre, randomised trials involving a total of 1,100 COPD patients; those trials were registered at ClinicalTrials.gov (NCT00496470 and NCT00542880). Data from these trials were used to determine the reliability, validity and responsiveness of the questionnaires and to derive estimates of minimal important differences (MIDs). Both questionnaires displayed good-to-high reliability (Cronbach's alpha 0.75-0.93). Analysis of convergent validity showed that CDLM and GCSQ scores correlated significantly (p

The aim of the present study was to determine the relevance of the presence of Enterobacteriaceae (EB) and Pseudomonas aeruginosa (PA) in patients with community-acquired pneumonia (CAP) and how the true incidence of these pathogens can be assessed. Based on prospective data from 5,130 patients with CAP included in the German Competence Network for Community-Acquired Pneumonia (CAPNETZ), the incidence, clinical characteristics, outcome and predictors of patients with CAP due to EB and PA were studied applying strict case definitions. The incidence of EB was 67 (1.3%) out of 5,130, including 27 patients with bacteraemia. PA was found in 22 (0.4%) out of 5,130 patients. These microorganisms were judged to be indeterminate pathogens in an additional 172 and 27 isolates, respectively. Patients with indeterminate pathogens differed considerably from those with definite isolates in terms of clinical presentation, comorbidity, pneumonia severity and outcome. Independent risk factors for EB included cardiac and cerebrovascular disease, and for PA chronic respiratory disease and enteral tube feeding. The 30-day mortality was significantly higher in patients with definite pathogens. In the present large population, the incidence of CAP due to EB/ PA was low. The risk of the presence of these pathogens can be assessed using several predictors, which may identify those patients in need of an extended diagnostic work-up and initial antimicrobial treatment.

Airway complications affect 20% of all lung transplant recipients. Self-expandable metallic stents (SEMS) are one treatment option but their use in benign airway disorders is controversial. We studies the long-term safety of SEMS in lung transplant recipients. Between January 1998 and February 2008, all lung transplant recipients with SEMS were analysed retrospectively at a single centre. Complications were recorded until September 2008. In 65 (9.2%) out of 706 recipients, 111 (91% noncovered) bronchial SEMS were implanted a median (range) 133 (55-903) days after lung transplantation; follow-up was 777 (7-3.655) days. Clinical improvement was noted in 80% of recipients. The forced expiratory volume in 1 s increased by (mean+/-SD) 21+/-33%. Most frequent early complications were migration (3%) and mucus plugging (11%). No procedure-related deaths were noted. Re-stenosis occurred in 34 (52%) out of 65 recipients 85 (7-629) days after insertion. In multivariate analysis, stent insertion before post-operative day 90 was independently associated with an increased risk of re-stenosis (HR 3.29, 95% CI 1.50-7.18; p = 0.003). In 40% of recipients, new bacterial airway colonisation occurred after SEMS insertion. In SEMS patients, 5-yr survival was significantly lower than in the total cohort (60% versus 76%; p = 0.02). Late complications in lung transplant recipients treated with SEMS are frequent. The major problems are re-stenosis and airway colonisation.

Up to now, the history of extracorporeal lung support has been a tale of great expectations and even greater disappointments. In 1972, Hill et al. 1 published the first case report on the use of extracorporeal membrane oxygenation (ECMO) in a young patient who suffered from acute respiratory distress syndrome (ARDS) after trauma. At that time, mortality rates from ARDS were extremely high and thus this report was embraced with great enthusiasm. However, only 2 yrs later reality caught up when the results of a randomised controlled trial using ECMO in ARDS were published showing mortality rates of >90% in both treatment arms 2. Despite these sobering results, several groups of investigators continued to work on extracorporeal devices. Gattinoni and co-workers 3, 4 were the first to introduce the use of extracorporeal CO2 removal to support protective ventilation strategies, now with survival rates of ∼50% among patients with ARDS. However, once again a randomised controlled trial failed to show a survival benefit in ARDS patients treated with extracorporeal CO2 removal 5 although the survival rates (33% in the extracorporeal group versus 42% in the conventional ventilation group) were now substantially better than in the 1970s. The reasons for the failure to demonstrate a survival benefit with extracorporeal lung support were certainly manifold. The study by Morris et al. 5 included only 40 patients and was gravely underpowered (for comparison, the ARDS Network trial on low tidal volumes recruited >800 patients before a survival difference of 22% became statistically significant 6). More importantly, the …

Weaning covers the entire process of liberating the patient from mechanical support and from the endotracheal tube. Many controversial questions remain concerning the best methods for conducting this process. An International Consensus Conference was held in April 2005 to provide recommendations regarding the management of this process. An 11-member international jury answered five pre-defined questions. 1) What is known about the epidemiology of weaning problems? 2) What is the pathophysiology of weaning failure? 3) What is the usual process of initial weaning from the ventilator? 4) Is there a role for different ventilator modes in more difficult weaning? 5) How should patients with prolonged weaning failure be managed? The main recommendations were as follows. 1) Patients should be categorised into three groups based on the difficulty and duration of the weaning process. 2) Weaning should be considered as early as possible. 3) A spontaneous breathing trial is the major diagnostic test to determine whether patients can be successfully extubated. 4) The initial trial should last 30 min and consist of either T-tube breathing or low levels of pressure support. 5) Pressure support or assist-control ventilation modes should be favoured in patients failing an initial trial/trials. 6) Noninvasive ventilation techniques should be considered in selected patients to shorten the duration of intubation but should not be routinely used as a tool for extubation failure.

Blood gas abnormalities in patients with idiopathic pulmonary arterial hypertension (IPAH) may be related to disease severity and prognosis. The present authors performed a 12-yr retrospective analysis assessing arterialised capillary blood gases, haemodynamics, exercise variables and survival in 101 patients with IPAH. At baseline, arterial oxygen tension (P(a,O(2))) and carbon dioxide arterial tension (P(a,CO(2))) were 9.17+/-1.86 and 4.25+/-0.532 kPa, respectively. While P(a,O(2) )was not associated with survival, a low P(a,CO(2 ))was a strong and independent prognostic marker. When patients were divided according to a baseline P(a,CO(2 ))value above or below 4.25 kPa, a cut-off value determined by receiver operating characteristics analysis, survival rates were 98 and 86% at 1 yr, 82 and 69% at 2 years, 80 and 51% at 3 yrs, 77 and 41% at 5 yrs, and 65 and 12% at 8 yrs, respectively. P(a,CO(2 ))after 3 months of medical therapy was strongly associated with survival. Hypocapnia at rest and during exercise correlated with low cardiac output, low peak oxygen uptake and reduced ventilatory efficacy. Multiple regression analysis revealed that 6-min walking distance, right atrial pressure and P(a,CO(2 ))were independently associated with survival. In patients with idiopathic pulmonary arterial hypertension, hypocapnia (carbon dioxide arterial tension4.25 kPa) is an independent marker of mortality.

This paper reports on a patient with diffuse pulmonary infiltrates directly related to Costello Syndrome. This congenital disorder is characterised by multiple congenital abnormalities, such as psychomotor retardation, short stature, redundant skin, papillomata, curly hair, relative macroencephaly, distinctive face and various defects of internal organs. This study is the first to document the histopathological findings in the lungs. Most conspicuous was the depositing of abnormal collagen and elastic fibres and the development of endogenous lipid pneumonia.

Patients with chronic congestive cardiac failure (CCF) frequently suffer from central sleep apnoea syndrome (CSAS). Continuous positive airway pressure (CPAP) has been suggested as a treatment. The authors hypothesised that bilevel ventilation might be easier to initiate and superior to CPAP at correcting the sleep-related abnormality of breathing in patients with CCF. After excluding those with a history suggestive of obstructive sleep apnoea, 35 patients with CCF (left ventricular ejection fraction