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Maged Hassan,1 Shefaly Patel,2 Ahmed S Sadaka,1 Eihab O Bedawi,2 John P Corcoran,3 José M Porcel4 1Chest Diseases Department, Alexandria University Faculty of Medicine, Alexandria, Egypt; 2Oxford Centre for Respiratory Medicine, Oxford University Hospitals, Oxford, UK; 3Department of Respiratory Medicine, University Hospitals Plymouth NHS Trust, Plymouth, UK; 4Department of Internal Medicine, Arnau de Vilanova University Hospital, Lleida, SpainCorrespondence: Maged HassanChest Diseases Department, Alexandria University Faculty of Medicine, Alexandria, EgyptTel +20 3 591-8662Email magedhmf@gmail.comAbstract: Pleural infection in adults has considerable morbidity and continues to be a life-threatening condition. The term “pleural infection” encompasses complicated parapneumonic effusions and primary pleural infections, and includes but is not limited to empyema, which refers to collection of pus in the pleural cavity. The incidence of pleural infection in adults has been continuously increasing over the past two decades, particularly in older adults, and most of such patients have comorbidities. Management of pleural infection requires prolonged duration of hospitalization (average 14 days). There are recognized differences in microbial etiology of pleural infection depending on whether the infection was acquired in the community or in a health-care setting. Anaerobic bacteria are acknowledged as a major cause of pleural infection, and thus anaerobic coverage in antibiotic regimens for pleural infection is mandatory. The key components of managing pleural infection are appropriate antimicrobial therapy and chest-tube drainage. In patients who fail medical therapy by manifesting persistent sepsis despite standard measures, surgical intervention to clear the infected space or intrapleural fibrinolytic therapy (in poor surgical candidates) are recommended. Recent studies have explored the role of early intrapleural fibrinolytics or first-line surgery, but due to considerable costs of such interventions and the lack of convincing evidence of improved outcomes with early use, early intervention cannot be recommended, and further evidence is awaited from ongoing studies. Other areas of research include the role of routine molecular testing of infected pleural fluid in improving the rate of identification of causative organisms. Other research topics include the benefit of such interventions as medical thoracoscopy, high-volume pleural irrigation with saline/antiseptic solution, and repeated thoracentesis (as opposed to chest-tube drainage) in reducing morbidity and improving outcomes of pleural infection. This review summarizes current knowledge and practice in managing pleural infection and future research directions.Keywords: pleural infection, empyema, respiratory infections, pneumonia

The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing seven clinically relevant PICO (Patient, Intervention, Comparison and Outcome) questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these seven PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and informing future research., Competing Interests: Conflict of interest: Y.C.G. Lee receives drainage kits without charge for participants of a clinical trial he leads. J.S. Reisenauer has a research grant with Intuitive Surgical and is an educational consultant for Vergent, Isola, Medview and Imvaria, outside the submitted work. M.M. DeCamp is an educational consultant for PulmonX and is on the scientific advisory board for Pleural Dynamics. D.J. Feller-Kopman is an educational consultant for AstraZeneca, Noah Medical and Boston Scientific, outside the submitted work. H. Grosu has a sponsored research agreement with Known Medicine. J.F.B. Chick is an educational consultant and speaker for Inari Medical, Guerbet, C. R. Bard, Argon Medical Devices, Boston Scientific, NXT Biomedical and AiDoc, outside the submitted work. F. Maldonado received research funding from Medtronic and personal consulting fees from J&J and Intuitive, outside of the submitted work. The remaining authors do not have any disclosures or conflicts of interest to report., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Management of complicated pleural infections (CPIs) had historically been surgical; however, following the publication of the second multicenter intrapleural sepsis trial (MIST-2), combination tissue plasminogen (tPA) and dornase (DNase) offers a less invasive and effective treatment. Our aim was to assess the quality of life (QOL) and functional ability of patients' recovery from a CPI managed with either intrapleural fibrinolytic therapy (IPFT) or surgery., Methods: We identified 565 patients managed for a CPI between January 1, 2013 and March 31, 2018. There were 460 patients eligible for contact, attempted through 2 phone calls and one mailer. Two questionnaires were administered: the Short Form 36-Item Health Survey (SF-36) and a functional ability questionnaire., Results: Contact was made in 35% (159/460) of patients, and 57% (90/159) completed the survey. Patients had lower QOL scores compared to average US citizens; those managed with surgery had higher scores in physical functioning (surgery: 80, IPFT: 70, P=0.040) but lower pain scores (surgery: 58, IPFT: 68, P=0.045). Of 52 patients who returned to work, 48% (25) reported an impact on their work effectiveness during recovery, similarly between management strategies (IPFT: 50%, 13/26 vs. surgery: 46%, 12/26; P=0.781)., Conclusion: Patients with a CPI had a lower QOL compared with average US citizens. Surgically managed patients reported improved physical functioning but worse pain compared with patients managed with IPFT. Patients returned to work within 4 weeks of discharge, and nearly half reported their ability to work effectively was impacted by their recovery. With further research into recovery timelines, patients may be appropriately counselled for expectations., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aims to correlate the RAPID score with the 3-month survival and surgical results of patients undergoing lung decortication with stage III pleural empyema., Methods: This was a retrospective study with the population of patients with pleural empyema who underwent pulmonary decortication between January 2019 and June 2022. Data were collected from the institution's database, and patients were classified as low, medium, and high risk according to the RAPID score. The primary outcome was 3-month mortality. Secondary outcomes were the length of hospital stay, readmission rate, and the need for pleural re-intervention., Results: Of the 34 patients with pleural empyema, according to the RAPID score, patients were stratified into low risk (23.5 %), medium risk (47.1 %), and high risk (29.4 %). The high-risk group had a 3-month mortality of 40 %, while the moderate-risk group had a 6.25 % and the low-risk group had no deaths within 90 days, confirming a good correlation with the RAPID score (p < 0.05). Sensitivity and specificity for the primary outcome in the high-risk score were 80.0 % and 79.3 %, respectively. The secondary outcomes did not reach statistical significance., Conclusions: In this retrospective series, the RAPID score had a good correlation with 3-month mortality in patients undergoing lung decortication. The morbidity indicators did not reach statistical significance. The present data justifies further studies to explore the capacity of the RAPID score to be used as a selection tool for treatment modality in patients with stage III pleural empyema., Competing Interests: Declaration of competing interests The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE., (© 2024. The Author(s).)

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively ( P  = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) ( P  = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) ( P  = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).

Competing Interests: Competing interests: Declarations of interest were completed in line with the BTS Policy and are available from the BTS Office on request

Background: Pleural biopsy findings offer greater diagnostic sensitivity in malignant pleural effusions compared with pleural fluid. The adequacy of pleural biopsy techniques in achieving molecular marker status has not been studied, and such information (termed "actionable" histology) is critical in providing a rational, efficient, and evidence-based approach to diagnostic investigation., Research Question: What is the adequacy of various pleural biopsy techniques at providing adequate molecular diagnostic information to guide treatment in malignant pleural effusions?, Study Design and Methods: This study analyzed anonymized data on 183 patients from four sites across three countries in whom pleural biopsy results had confirmed a malignant diagnosis and molecular profiling was relevant for the diagnosed cancer type. The primary outcome measure was adequacy of pleural biopsy for achieving molecular marker status. Secondary outcomes included clinical factors predictive of achieving a molecular diagnosis., Results: The median age of patients was 71 years (interquartile range, 63-78 years), with 92 of 183 (50%) male. Of the 183 procedures, 105 (57%) were local anesthetic thoracoscopies (LAT), 12 (7%) were CT scan guided, and 66 (36%) were ultrasound guided. Successful molecular marker analysis was associated with mode of biopsy, with LAT having the highest yield and ultrasound-guided biopsy the lowest (LAT vs CT scan guided vs ultrasound guided: LAT yield, 95%; CT scan guided, 86%; and ultrasound guided, 77% [P = .004]). Biopsy technique and size of biopsy sample were independently associated with successful molecular marker analysis. LAT had an adjusted OR for successful diagnosis of 30.16 (95% CI, 3.15-288.56; P = .003) and biopsy sample size an OR of 1.18 (95% CI, 1.02-1.37) per millimeter increase in tissue sample size (P < .03)., Interpretation: Although previous studies have shown comparable overall diagnostic yields, in the modern era of targeted therapies, this study found that LAT offers far superior results to image-guided techniques at achieving molecular profiling and remains the optimal diagnostic tool., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Rationale: Sonographic septations are assumed to be important clinical predictors of outcome in pleural infection, but the evidence for this is sparse. The inflammatory and fibrinolysis-associated intrapleural pathway(s) leading to septation formation have not been studied in a large cohort of pleural fluid (PF) samples with confirmed pleural infection matched with ultrasound and clinical outcome data. Objectives: To assess the presence and severity of septations against baseline PF PAI-1 (Plasminogen-Activator Inhibitor-1) and other inflammatory and fibrinolysis-associated proteins as well as to correlate these with clinically important outcomes. Methods: We analyzed 214 pleural fluid samples from PILOT (Pleural Infection Longitudinal Outcome Study), a prospective observational pleural infection study, for inflammatory and fibrinolysis-associated proteins using the Luminex platform. Multivariate regression analyses were used to assess the association of pleural biological markers with septation presence and severity (on ultrasound) and clinical outcomes. Measurements and Main Results: PF PAI-1 was the only protein independently associated with septation presence ( P  < 0.001) and septation severity ( P  = 0.003). PF PAI-1 concentrations were associated with increased length of stay ( P  = 0.048) and increased 12-month mortality ( P  = 0.003). Sonographic septations alone had no relation to clinical outcomes. Conclusions: In a large and well-characterized cohort, this is the first study to associate pleural biological parameters with a validated sonographic septation outcome in pleural infection. PF PAI-1 is the first biomarker to demonstrate an independent association with mortality. Although PF PAI-1 plays an integral role in driving septation formation, septations themselves are not associated with clinically important outcomes. These novel findings now require prospective validation.

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to disclose., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Objective: To investigate the effect of early diagnosis and intervention in adult patients with complicated parapneumonic pleural effusion or pleural empyema and the impact on outcomes., Methods: A systematic review based on a literature search of the PubMed database was performed., Results: Eleven eligible studies were included; nine observational studies and two randomised controlled trials totalling a study population of 10,717 patients. The studies were conducted from 1992 to 2018, all in Europe and Northern America except one. Results varied between studies, but a trend towards better outcome in patients with shorter duration of symptoms and quicker initiation of treatment was found. We found that duration of symptoms before treatment may affect length of hospital stay, rate of conversion to open surgery, and frequency of complications., Conclusion: We found that an earlier intervention in adults suffering from complicated parapneumonic pleural effusion and pleural empyema may potentially improve the outcome of patients in terms of length of stay, conversion to open surgery, and general complications following treatment, but not regarding mortality. Further studies are required to specify the timing of each intervention, and direct comparison in early management of interventions., Competing Interests: Thomas Decker Christensen has been on the speaker bureaus for AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche Diagnostics, Takeda, Merck Sharp & Dohme (MSD) and Bristol-Myers Squibb and has been in an Advisory Board for Bayer, Merck Sharp & Dohme (MSD), Sanofi and AstraZeneca. Christian B. Laursen has received a speaker’s fee from AstraZeneca. Morten Bendixen has received a teaching fee from Pulmonx Corporation. Najib M Rahman is a consultant for Rocket Medical and Lung Therapeutics, USA. Other authors: None declared., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined., Research Question: What is the bleeding complication risk associated with IET use in pleural infection?, Study Design and Methods: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria., Results: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 10 9 /L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare., Interpretation: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Malignant pleural effusion (MPE) is a common condition which often causes significant symptoms to patients and costs to healthcare systems. Over the past decade, the management of MPE has progressed enormously with large scale, randomised trials answering key questions regarding optimal diagnostic strategies and effective management strategies. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. The future goals for providing improved care for patients lies in changing the treatment paradigm from a generic pathway to personalised care, based on probability of malignancy type and survival. This article reviews the current evidence base, new discoveries and future directions in the diagnosis and management of MPE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Addala, Kanellakis, Bedawi, Dong and Rahman.)

There was a significant reduction in pleural infection incidence, by almost a third, in the year following the start of the #COVID19 pandemic. Public health measures enforced during this period are likely to have played a significant role. https://bit.ly/3QAPPR9., Competing Interests: Conflict of interest: The authors have no conflicts of interest to disclose., (Copyright ©The authors 2022.)

Objectives: Focused thoracic ultrasound (TUS) provides an increased safety profile when undertaking invasive pleural procedures. This has led to the requirement for defined curricula, high quality teaching and robust, validated assessment tools among physicians to ensure patient safety and clinical excellence. Current UK practice is based almost exclusively on expert consensus, but assessment methods employed have been shown to have low reliability and validity and are potentially open to bias. As a result, several assessment tools have been developed, although each has its own limitations., Methods: This study aimed to develop and validate an assessment tool corresponding to those skills associated with the most basic level of practice, defined recently as an emergency level operator in the British Thoracic Society Training Standards for Thoracic Ultrasound., Results: A total of 27 candidates were enrolled by two examiners based in Belfast and Oxford over a 10-month period between February and November 2019. Mean score of the inexperienced group was 44.3 (95% CI 39.2-49.4, range 28-54) compared with 74.9 (95% CI 72.8-77, range 64-80) in the experienced group providing an estimated mean difference of 30.7 between the two groups (95% CI 24.7-36.7; p < .001)., Conclusions: This tool appears to discriminate between trainees with limited experience of TUS performance and those with no experience. It has the potential to form part of the assessment strategy for trainees in the United Kingdom and beyond, alongside well established assessment tools in postgraduate training., (© 2022 Wiley Periodicals LLC.)

Competing Interests: Competing interests: None declared.

Pleural disease is a common presentation and spans a heterogeneous population across broad disease entities; a common feature is the requirement for interventional procedures. Despite the frequency of such procedures, there is little consensus on rates of complications and risk factors associated with such complications. This narrative review was based on a structured search of the literature. Searches were limited to 2010 onward, in recognition of the transformation in procedural complications following the mainstream use of thoracic ultrasound. Procedures of interest were limited to thoracocentesis, intercostal drains, indwelling pleural catheters (IPCs), and local anesthetic thoracoscopy. A total of 4,308 studies were screened, and 48 studies were identified for inclusion. Iatrogenic pneumothorax remains the most common complication following thoracocentesis (3.3%; 95% CI, 3.2-3.4), although pneumothorax requiring intervention was rare (0.3%; 95% CI, 0.2-0.4) when the procedure was ultrasound guided. Drain blockage and displacement were the most common complications following intercostal drain insertion (6.3% and 6.8%, respectively). IPC-related infections can be a significant problem (5.8%; 95% CI, 5.1-6.7). However, most cases can be managed without removal of the IPC. Local anesthetic thoracoscopy has an overall mortality of 0.1% (95% CI, 0.03-0.3). Data on safety and complication rates in procedural interventions are limited by methodologic problems, and novel methods to study this topic should be considered. Although complications remain rare events, once encountered, they have the potential to rapidly escalate. It is of paramount importance for operators to prepare and have in place plans for such events to ensure high quality and, above all, safe care., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients., Methods: We assessed 243 pleural fluid samples from the PILOT study, a prospective observational study on pleural infection, with 16S rRNA next generation sequencing. 20 pleural fluid samples from patients with pleural effusion due to a non-infectious cause and ten PCR-grade water samples were used as controls. Downstream analysis was done with the DADA2 pipeline. We applied multivariate Cox regression analyses to investigate the association between bacterial patterns and 1-year survival of patients with pleural infection., Findings: Pleural infection was predominately polymicrobial (192 [79%] of 243 samples), with diverse bacterial frequencies observed in monomicrobial and polymicrobial disease and in both community-acquired and hospital-acquired infection. Mixed anaerobes and other Gram-negative bacteria predominated in community-acquired polymicrobial infection whereas Streptococcus pneumoniae prevailed in monomicrobial cases. The presence of anaerobes (hazard ratio 0·46, 95% CI 0·24-0·86, p=0·015) or bacteria of the Streptococcus anginosus group (0·43, 0·19-0·97, p=0·043) was associated with better patient survival, whereas the presence (5·80, 2·37-14·21, p<0·0001) or dominance (3·97, 1·20-13·08, p=0·024) of Staphylococcus aureus was linked with lower survival. Moreover, dominance of Enterobacteriaceae was associated with higher risk of death (2·26, 1·03-4·93, p=0·041)., Interpretation: Pleural infection is a predominantly polymicrobial infection, explaining the requirement for broad spectrum antibiotic cover in most individuals. High mortality infection associated with S aureus and Enterobacteriaceae favours more aggressive, with a narrower spectrum, antibiotic strategies., Funding: UK Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, Wellcome Trust, Oxfordshire Health Services Research Committee, Chinese Academy of Medical Sciences, and John Fell Fund., Competing Interests: Declaration of interests IP works for AstraZeneca in a non-related field. TSCH reports grants from the Wellcome Trust and The Guardians of the Beit Fellowship, during the conduct of the study; personal fees from AstraZeneca, TEVA, and Peer Voice; grants from Pfizer, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Sensyne Health, and Kymab, outside the submitted work. RFM reports personal fees from Gilead, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment., Methods and Analysis: A national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life., Ethics and Dissemination: All patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www., Clinicaltrials: gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences., Trial Registration Number: NCT04095676., Competing Interests: Competing interests: TDC has been on the speaker bureaus for AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche Diagnostics, Takeda, Merck Sharp and Dohme (MSD) and Bristol-Myers Squibb and has been in an Advisory Board for Bayer and Merck Sharp and Dohme (MSD). RHP has received a speaker’s fee from Medtronic and on the advisory board for AstraZeneca. CBL has received a speaker’s fee from AstraZeneca. MB has received a teaching fee from Pulmonx Corporation. PL has received a speaker’s fee from Johnson & Johnson., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pleurodesis is done as an in-patient procedure to control symptomatic recurrent malignant pleural effusion (MPE) and has a success rate of 75-80%. Thoracic ultrasonography has been shown in a small study to predict pleurodesis success early by demonstrating cessation of lung sliding (a normal sign seen in healthy patients, lung sliding indicates normal movement of the lung inside the thorax). We aimed to investigate whether the use of thoracic ultrasonography in pleurodesis pathways could shorten hospital stay in patients with MPE undergoing pleurodesis., Methods: The Efficacy of Sonographic and Biological Pleurodesis Indicators of Malignant Pleural Effusion (SIMPLE) trial was an open-label, randomised controlled trial done in ten respiratory centres in the UK and one respiratory centre in the Netherlands. Adult patients (aged ≥18 years) with confirmed MPE who required talc pleurodesis via either a chest tube or as poudrage during medical thorascopy were eligible. Patients were randomly assigned (1:1) to thoracic ultrasonography-guided care or standard care via an online platform using a minimisation algorithm. In the intervention group, daily thoracic ultrasonography examination for lung sliding in nine regions was done to derive an adherence score: present (1 point), questionable (2 points), or absent (3 points), with a lowest possible score of 9 (preserved sliding) and a highest possible score of 27 (complete absence of sliding); the chest tube was removed if the score was more than 20. In the standard care group, tube removal was based on daily output volume (per British Thoracic Society Guidelines). The primary outcome was length of hospital stay, and secondary outcomes were pleurodesis failure at 3 months, time to tube removal, all-cause mortality, symptoms and quality-of-life scores, and cost-effectiveness of thoracic ultrasonography-guided care. All outcomes were assessed in the modified intention-to-treat population (patients with missing data excluded), and a non-inferiority analysis of pleurodesis failure was done in the per-protocol population. This trial was registered with ISRCTN, ISRCTN16441661., Findings: Between Dec 31, 2015, and Dec 17, 2019, 778 patients were assessed for eligibility and 313 participants (165 [53%] male) were recruited and randomly assigned to thoracic ultrasonography-guided care (n=159) or standard care (n=154). In the modified intention-to-treat population, the median length of hospital stay was significantly shorter in the intervention group (2 days [IQR 2-4]) than in the standard care group (3 days [2-5]; difference 1 day [95% CI 1-1]; p<0·0001). In the per-protocol analysis, thoracic ultrasonography-guided care was non-inferior to standard care in terms of pleurodesis failure at 3 months, which occurred in 27 (29·7%) of 91 patients in the intervention group versus 34 (31·2%) of 109 patients in the standard care group (risk difference -1·5% [95% CI -10·2% to 7·2%]; non-inferiority margin 15%). Mean time to chest tube removal in the intervention group was 2·4 days (SD 2·5) versus 3·1 days (2·0) in the standard care group (mean difference -0·72 days [95% CI -1·22 to -0·21]; p=0·0057). There were no significant between-group differences in all-cause mortality, symptom scores, or quality-of-life scores, except on the EQ-5D visual analogue scale, which was significantly lower in the standard care group at 3 months. Although costs were similar between the groups, thoracic ultrasonography-guided care was cost-effective compared with standard care., Interpretation: Thoracic ultrasonography-guided care for pleurodesis in patients with MPE results in shorter hospital stay (compared with the British Thoracic Society recommendation for pleurodesis) without reducing the success rate of the procedure at 3 months. The data support consideration of standard use of thoracic ultrasonography in patients undergoing MPE-related pleurodesis., Funding: Marie Curie Cancer Care Committee., Competing Interests: Declaration of interests MH reports support by a long-term research fellowship from the European Respiratory Society (LTRF 2016-7333) during the conduct of the study. KGB reports grants from Rocket Medical UK, outside the submitted work. RK reports grants from the Marie Curie Institute during the conduct of the study. RFM reports personal fees from Gilead, outside the submitted work. NMR reports grants from Rocket Medical outside the submitted work. All the other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The rising incidence and high morbidity of pleural infection remain a significant challenge to health care systems worldwide. With distinct microbiology and treatment paradigms from pneumonia, pleural infection is an area in which the evidence base has been rapidly evolving. Progress in recent years has revolved around characterizing the microbiome of pleural infection and the addition of new strategies such as intrapleural enzyme therapy to the established treatment pathway of drainage and antibiotics. The future of improving outcomes lies with personalizing treatment, establishing optimal timing of intrapleural agents and surgery, alongside wider use of risk stratification to guide treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although our understanding of the pathogenesis of empyema has grown tremendously over the past few decades, questions still remain on how to optimally manage this condition. It has been almost a decade since the publication of the MIST2 trial, but there is still an extensive debate on the appropriate use of intrapleural fibrinolytic and deoxyribonuclease therapy in patients with empyema. Given the scarcity of overall guidance on this subject, we convened an international group of 22 experts from 20 institutions across five countries with experience and expertise in managing adult patients with empyema. We did a literature and internet search for reports addressing 11 clinically relevant questions pertaining to the use of intrapleural fibrinolytic and deoxyribonuclease therapy in adult patients with bacterial empyema. This Position Paper, consisting of seven graded and four ungraded recommendations, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience when necessary. Panel members participated in the development of the final recommendations using the modified Delphi technique. Our Position Paper aims to address the existing gap in knowledge and to provide consensus-based recommendations to offer guidance in clinical decision making when considering the use of intrapleural therapy in adult patients with bacterial empyema., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: Competing interests: None declared.

Objectives: Patients with malignant pleural mesothelioma (MPM) or pleural metastases often present with malignant pleural effusion (MPE). This study aimed to analyze the effect of pleural fluid on cancer cells., Materials and Methods: Established patient-derived cancer cell cultures derived from MPE (MPM, breast carcinoma, lung adenocarcinoma) were seeded in 100% pleural fluid (exudate MPM MPE, transudate MPE, non-MPE transudate fluid) and proliferation was monitored. In addition, the establishment of new MPM cell cultures, derived from MPE specimens, was attempted by seeding the cells in 100% MPE fluid., Results: All established cancer cell cultures proliferated with similar growth rates in the different types of pleural fluid. Primary MPM cell culture success was similar with MPE fluid as with full culture medium., Conclusions: Pleural fluid alone is adequate for cancer cell proliferation in vitro , regardless of the source of pleural fluid. These results support the hypothesis that pleural fluid has important pro-growth biological properties, but the mechanisms for this effect are unclear and likely not malignant effusion specific., Competing Interests: IP was employed by AstraZeneca in a non-related field. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Asciak, Kanellakis, Yao, Abd Hamid, Mercer, Hassan, Bedawi, Dobson, Fsadni, Montefort, Dong, Rahman and Psallidas.)

Thoracic ultrasound is increasingly considered to be an essential tool for the pulmonologist. It is used in diverse clinical scenarios, including as an adjunct to clinical decision making for diagnosis, a real-time guide to procedures and a predictor or measurement of treatment response. The aim of this European Respiratory Society task force was to produce a statement on thoracic ultrasound for pulmonologists using thoracic ultrasound within the field of respiratory medicine. The multidisciplinary panel performed a review of the literature, addressing major areas of thoracic ultrasound practice and application. The selected major areas include equipment and technique, assessment of the chest wall, parietal pleura, pleural effusion, pneumothorax, interstitial syndrome, lung consolidation, diaphragm assessment, intervention guidance, training and the patient perspective. Despite the growing evidence supporting the use of thoracic ultrasound, the published literature still contains a paucity of data in some important fields. Key research questions for each of the major areas were identified, which serve to facilitate future multicentre collaborations and research to further consolidate an evidence-based use of thoracic ultrasound, for the benefit of the many patients being exposed to clinicians using thoracic ultrasound., Competing Interests: Conflict of interest: C.B. Laursen has nothing to disclose. Conflict of interest: A. Clive has nothing to disclose. Conflict of interest: R. Hallifax has nothing to disclose. Conflict of interest: P.I. Pietersen has nothing to disclose. Conflict of interest: R. Asciak has nothing to disclose. Conflict of interest: J.R. Davidsen has nothing to disclose. Conflict of interest: R. Bhatnagar has nothing to disclose. Conflict of interest: E.O. Bedawi has nothing to disclose. Conflict of interest: N. Jacobsen has nothing to disclose. Conflict of interest: C. Coleman is an employee of the European Lung Foundation. Conflict of interest: A. Edey has nothing to disclose. Conflict of interest: G. Via has nothing to disclose. Conflict of interest: G. Volpicelli has nothing to disclose. Conflict of interest: G. Massard has nothing to disclose. Conflict of interest: F. Raimondi has nothing to disclose. Conflict of interest: M. Evison has nothing to disclose. Conflict of interest: L. Konge has nothing to disclose. Conflict of interest: J. Annema has nothing to disclose. Conflict of interest: N.M. Rahman reports equipment provision from Esaote, Italy, outside the submitted work. Conflict of interest: N. Maskell has nothing to disclose., (Copyright ©ERS 2021.)

Pleural infection and malignancy are among the most common causes of pleural disease and form the mainstay of pleural practice. There has been significant research and increase in scientific understanding in these areas in the past decade. With regard to pleural infection, the rising incidence remains worrying. An increased awareness allowing earlier diagnosis, earlier escalation of therapy and the use of validated risk stratification measures may improve outcomes. In pleural malignancy, research has enabled clinicians to streamline patient pathways with focus on reducing time to diagnosis, definitive management of malignant pleural effusion and achieving these with the minimum number of pleural interventions. Trials comparing treatment modalities of malignant pleural effusion continue to highlight the importance of patient choice in clinical decision-making. This article aims to summarise some of the most recent literature informing current practice in these two areas., Competing Interests: Conflict of interest: E.O. Bedawi has nothing to disclose. Conflict of interest: J. Guinde has nothing to disclose. Conflict of interest: N.M. Rahman reports grants from Roche and Genentech, and grants and personal fees from LTI USA, outside the submitted work. Conflict of interest: P. Astoul has nothing to disclose., (Copyright ©ERS 2021.)

Background: Diagnostic yield (DY) and safety of computed tomography (CT)- and thoracic ultrasound (TUS)-guided biopsies in the diagnosis of pleural lesions have been investigated in a number of studies, but no synthesis of data from the literature has ever been performed., Objectives: We aimed to provide the first systematic review and meta-analysis on the DY and safety of CT- versus TUS-guided biopsy in the diagnosis of pleural lesions., Method: We searched MEDLINE and EMBASE for all studies reporting outcomes of interest published up to April 2018. Two authors reviewed all titles/abstracts and retrieved selected full text to identify studies according to predefined selection criteria. Summary estimates were derived using the random-effects model. Cumulative meta-analysis assessed the influence of increasing adoption of the procedures over time., Results: Thirty original studies were included in the present review; the number of studies on TUS-guided biopsy was almost three-fold higher than those on CT-guided biopsy. The pooled DYs of the 2 procedures were overall excellent and differed <10%, being 84% for TUS-guided biopsy and 93% for CT-guided biopsy. Safety profiles were reassuring for both the techniques, being 7 and 3% for CT- and TUS-guided biopsy, respectively. DY of ultrasound technique significantly improved over time, while no time effect was observed for CT-guided biopsy., Conclusions: Data show that CT- and TUS-guided biopsies in the diagnosis of pleural lesions are both excellent procedures, without meaningful differences in DYs and safety. Considering that TUS is non-ionizing and easily performed at the bedside, it should be the preferred approach in presence of adequate skills., (© 2020 S. Karger AG, Basel.)

Pleural disease diagnostics represent a sprawling topic that has enjoyed a renaissance in recent years from humble beginnings. Whilst pleural patients are heterogeneous as a population and in the aetiology of the disease with which they present, we provide an overview of the typical diagnostic approach. Pleural fluid analysis is the cornerstone of the diagnostic pathway; however, it has many shortcomings. Strong cases have been made for more invasive upfront investigations, including image-guided biopsies or local anaesthetic thoracoscopy, in selected populations. Imaging can guide the diagnostic process as well as act as a vehicle to facilitate therapies, and this is never truer than with the recent advances in thoracic ultrasound.

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM., Competing Interests: Competing interests: IP works for AstraZeneca in a non-related field., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Current guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a 'real world' population., Methods: A retrospective analysis was conducted of all patients who underwent pleural fluid (PF) sampling, in a single centre, over 3 years to determine the utility of the initial aspiration., Results: A diagnosis of MPE was confirmed in 230/998 (23%) cases, a further 95/998 (9.5%) were presumed to represent MPE. Transudative biochemistry was found in 3% of cases of confirmed MPE. Positive PF cytology was only sufficient to guide management in 45/140 (32%) cases. Evidence of pleural thickening on CT was associated with both negative cytology (χ 2 1df=26.27, p<0.001) and insufficient samples (χ 2 1df=10.39, p=0.001). In NEL 44.4% of patients did not require further procedures after pleurodesis compared with 72.7% of those with expansile lung (χ 2 1df=5.49, p=0.019). In patients who required a combined diagnostic and therapeutic aspiration 106/113 (93.8%) required further pleural procedures., Conclusions: An initial pleural aspiration does not achieve either definitive diagnosis or therapy in the majority of patients. A new pathway prioritising symptom management while reducing procedures should be considered., Competing Interests: Competing interests: NMR reports grants and personal fees from Rocket Medical UK, grants from BD USA, personal fees from Lung therapeutics USA, outside the submitted work. VG reports personal fees from Teva UK Ltd/Haymarket Media Group, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Solitary fibrous tumours of the pleura (SFTP), or pleural fibromas, are rare tumours that generally, but not universally, follow a benign course. Surgical resection is the standard treatment, but there are no evidence-based guidelines regarding the management of these tumours., Methods: Five databases were searched from inception to April 1, 2019 for studies reporting on SFTP management., Results: Twenty-seven studies met the inclusion criteria (1542 patients, all non-comparative case series); 98% of these patients underwent resection and all SFTP included were pathologically diagnosed. 394 out of 1299 cases (30.5%, 95% CI 27.8-32.8%) were malignant with recurrence rates of between 0% and 42.9%. A pleural effusion was always associated with a negative outcome, but no other features were consistently reported to have negative associations. Preoperative biopsies incorrectly reported malignant histology in two studies. Over 25% of cases of recurrence occurred when a complete (R0) resection had been achieved. The first recurrence occurred >5 years after the initial resection in at least 23% of cases., Conclusions: There is strong evidence to support long-term surveillance after surgical resection of SFTP, even where a complete (R0) resection has been achieved; however, there is no clear evidence to inform clinicians regarding the selection of patients who should undergo resection. The rates of malignant SFTP and SFTP recurrence are higher than previously reported. Only those that were pathologically diagnosed or resected were included, which may bias the data towards more aggressive tumours. Data collection on radiologically diagnosed SFTP is required to draw conclusions regarding the timing and need for intervention., Competing Interests: Conflict of interest: R.M. Mercer has nothing to disclose. Conflict of interest: C. Wigston has nothing to disclose. Conflict of interest: R. Banka has nothing to disclose. Conflict of interest: G. Cardillo has nothing to disclose. Conflict of interest: R. Benamore has nothing to disclose. Conflict of interest: G. Cardillo has nothing to disclose. Conflict of interest: R. Asciak has nothing to disclose. Conflict of interest: M. Hassan has nothing to disclose. Conflict of interest: R.J. Hallifax has nothing to disclose. Conflict of interest: L. Wing has nothing to disclose. Conflict of interest: E.O. Bedawi has nothing to disclose. Conflict of interest: N.A. Maskell reports an unrestricted research grant from Rocket and Becton Dickinson for IPC plus HiSPEC and REDUCE studies, and sat on the advisory board for cook medical. Conflict of interest: E. Harriss has nothing to disclose. Conflict of interest: R.F. Miller reports personal fees for a nonpromotional lecture on clinical aspects of HIV infection from Gilead outside the submitted work. Conflict of interest: N.J. Rahman reports grants and personal fees from Rocket Medical UK, grants from BD USA, and personal fees from Lung therapeutics USA, outside the submitted work., (Copyright ©ERS 2020.)

Introduction: The rising incidence of pleural disease is seeing an international growth of pleural services, with physicians performing an ever-increasing volume of pleural interventions. These are frequently conducted at sites without immediate access to thoracic surgery or interventional radiology and serious complications such as pleural bleeding are likely to be under-reported., Aim: To assess whether intercostal vessel screening can be performed by respiratory physicians at the time of pleural intervention, as an additional step that could potentially enhance safe practice., Methods: This was a prospective, observational study of 596 ultrasound-guided pleural procedures conducted by respiratory physicians and trainees in a tertiary centre. Operators did not have additional formal radiology training. Intercostal vessel screening was performed using a low frequency probe and the colour Doppler feature., Results: The intercostal vessels were screened in 95% of procedures and the intercostal artery (ICA) was successfully identified in 53% of cases. Screening resulted in an overall site alteration rate of 16% in all procedures, which increased to 30% when the ICA was successfully identified. This resulted in procedure abandonment in 2% of cases due to absence of a suitable entry site. Intercostal vessel screening was shown to be of particular value in the context of image-guided pleural biopsy., Conclusion: Intercostal vessel screening is a simple and potentially important additional step that can be performed by respiratory physicians at the time of pleural intervention without advanced ultrasound expertise. Whether the widespread use of this technique can improve safety requires further evaluation in a multi-centre setting with a robust prospective study., Competing Interests: Conflict of interest: E.O. Bedawi has nothing to disclose. Conflict of interest: A. Talwar has nothing to disclose. Conflict of interest: M. Hassan has nothing to disclose. Conflict of interest: D.J. McCracken has nothing to disclose. Conflict of interest: R. Asciak has nothing to disclose. Conflict of interest: R.M. Mercer has nothing to disclose. Conflict of interest: N.I. Kanellakis has nothing to disclose. Conflict of interest: F.V. Gleeson has nothing to disclose. Conflict of interest: R.J. Hallifax has nothing to disclose. Conflict of interest: J.M. Wrightson has nothing to disclose. Conflict of interest: N.M. Rahman has nothing to disclose., (Copyright ©ERS 2020.)

Objectives: Recent observations indicate a potential survival benefit in patients with malignant pleural effusion (MPE) who achieve successful pleurodesis in comparison to patients who experience effusion recurrence post pleurodesis. This study aimed to explore this observation using two datasets of patients with MPE undergoing talc pleurodesis., Materials and Methods: Dataset 1 comprised patients who underwent talc pleurodesis at Oxford Pleural Unit for MPE. Dataset 2 comprised patients enrolled in the TIME1 clinical trial. Pleurodesis success was defined as absence of need for further therapeutic procedures for MPE in the three months following pleurodesis. Data on various clinical, laboratory and radiological parameters were collected and survival was compared according to pleurodesis outcome (success vs. failure) after adjusting for the aforementioned parameters., Results: Dataset 1 comprised 60 patients with mean age 74.1±10.3 years. The most common primary malignancies were mesothelioma, breast and lung cancer. 29 patients (48.3%) achieved pleurodesis. The adjusted odds ratio (aOR) for poor survival with pleurodesis failure was 2.85 (95% CI 1.08-7.50, =p 0.034). Dataset 2 comprised 259 patients from the TIME1 trial. The mean age was 70.8±10.3 and the most common primary malignancies were mesothelioma, lung and breast cancer. Pleurodesis was successful in 205 patients (79%). aOR for poor survival was 1.62 (95% CI 1.09-2.39, p = 0.015)., Conclusion: Achieving pleurodesis seems to impart a survival benefit in patients with MPE. Further studies are required to explore factors that may contribute to this phenomenon and to address the difference in survival between pleurodesis and indwelling pleural catheter interventions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Objectives: Pleural infection is a major cause of morbidity and mortality among adults. Identification of the offending organism is key to appropriate antimicrobial therapy. It is not known whether the microbiological pattern of pleural infection is variable temporally or geographically. This systematic review aimed to investigate available literature to understand the worldwide pattern of microbiology and the factors that might affect such pattern., Data Sources and Eligibility Criteria: Ovid MEDLINE and Embase were searched between 2000 and 2018 for publications that reported on the microbiology of pleural infection in adults. Both observational and interventional studies were included. Studies were excluded if the main focus of the report was paediatric population, tuberculous empyema or post-operative empyema., Study Appraisal and Synthesis Methods: Studies of ≥20 patients with clear reporting of microbial isolates were included. The numbers of isolates of each specific organism/group were collated from the included studies. Besides the overall presentation of data, subgroup analyses by geographical distribution, infection setting (community versus hospital) and time of the report were performed., Results: From 20 980 reports returned by the initial search, 75 articles reporting on 10 241 patients were included in the data synthesis. The most common organism reported worldwide was Staphylococcus aureus . Geographically, pneumococci and viridans streptococci were the most commonly reported isolates from tropical and temperate regions, respectively. The microbiological pattern was considerably different between community- and hospital-acquired infections, where more Gram-negative and drug-resistant isolates were reported in the hospital-acquired infections. The main limitations of this systematic review were the heterogeneity in the method of reporting of certain bacteria and the predominance of reports from Europe and South East Asia., Conclusions: In pleural infection, the geographical location and the setting of infection have considerable bearing on the expected causative organisms. This should be reflected in the choice of empirical antimicrobial treatment., Competing Interests: Conflict of interest: M. Hassan has nothing to disclose. Conflict of interest: T. Cargill has nothing to disclose. Conflict of interest: E. Harriss has nothing to disclose. Conflict of interest: R. Asciak has nothing to disclose. Conflict of interest: R.M. Mercer has nothing to disclose. Conflict of interest: E.O. Bedawi has nothing to disclose. Conflict of interest: D.J. McCracken has nothing to disclose. Conflict of interest: I. Psallidas has nothing to disclose. Conflict of interest: J.P. Corcoran has nothing to disclose. Conflict of interest: N.M. Rahman has nothing to disclose., (Copyright ©ERS 2019.)

Background: Pleural infection (PI) is a major global disease with an increasing incidence, and pleural fluid (PF) drainage is essential for the successful treatment. The MIST2 study demonstrated that intrapleural administration of tissue plasminogen activator (t-PA) and DNase, or t-PA alone increased the volume of drained PF. Mouse model studies have suggested that the volume increase is due to the interaction of the pleura with the t-PA via the monocyte chemoattractant protein 1 (MCP-1) pathway. We designed a study to determine the time frame of drained PF volume induction on intrapleural delivery of t-PA±DNase in humans, and to test the hypothesis that the induction is mediated by the MCP-1 pathway., Methods: Data and samples from the MIST2 study were used (210 PI patients randomised to receive for 3 days either: t-PA and DNase, t-PA and placebo, DNase and placebo or double placebo). PF MCP-1 levels were measured by ELISA. One-way and two-way analysis of variance (ANOVA) with Tukey's post hoc tests were used to estimate statistical significance. Pearson's correlation coefficient was used to assess linear correlation., Results: Intrapleural administration of t-PA±DNase stimulated a statistically significant rise in the volume of drained PF during the treatment period (days 1-3). No significant difference was detected between any groups during the post-treatment period (days 5-7). Intrapleural administration of t-PA increased MCP-1 PF levels during treatment; however, no statistically significant difference was detected between patients who received t-PA and those who did not. PF MCP-1 expression was not correlated to the drug given nor the volume of drained PF., Conclusions: We conclude that the PF volume drainage increment seen with the administration of t-PA does not appear to act solely via activation of the MCP-1 pathway., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Pleural infection is a condition that continues to pose a significant challenge to respiratory physicians. We hypothesize that the main barriers to progress include limited understanding of the etiopathogenesis, microbiology,and role of antibiotics in the pleural space. Areas covered: PubMed was searched for articles related to adult pleural infection using the terms 'pleural infection', 'empyema' and 'parapneumonic'. The search focused on relevant literature within the last 10 years, with any older citations used only to display context or lack of progress. Tuberculous pleural infection was excluded. We chose to give specific attention to the etiopathogenesis of pleural infection, including recent advances in diagnostics and biomarkers. We discuss our understanding of the pleural microbiome and rationalize the current use of antibiotics in treating this condition. Expert commentary: Understanding of key events in the development of this condition remains limited. The microbiology is unique compared to the lung, and highly variable. Higher culture yields from pleural biopsy may add new insights into the etiopathogenesis. There is little evidence into achievable effective antibiotic concentration within the pleura. Research into issues including the relevance of biofilm formation and significance of pleural thickening is necessary for treatment progress.

Pneumothorax is a well-recognised complication of end-stage COPD, but the management is often complex and may be complicated by other sequelae of advanced respiratory disease including the requirement for NIV http://ow.ly/vkoJ30mB4nZ., Competing Interests: Conflict of interest: D.J. McCracken has nothing to disclose. Conflict of interest: E.O. Bedawi has nothing to disclose. Conflict of interest: M. Hassan has nothing to disclose. Conflict of interest: D. Stavroulias has nothing to disclose. Conflict of interest: N.M. Rahman has nothing to disclose.