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BackgroundPleural infection is a condition associated with significant morbidity and burden on healthcare resources. This study aimed to investigate whether the rate of pleural infection diagnosis in a tertiary hospital varies with time and whether it is related to the national burden of hospitalisations due to influenza.MethodsThe reporting database of our pleural unit was searched for cases of pleural infection defined by the presence of frank pus or a pleural fluid pH <7.2 in the absence of other causes. Exponential smoothing was used to inspect for variations in pleural infection diagnosis and to forecast volume of referrals in the following two years. The monthly rates of influenza hospitalisations in England were retrieved from the website of Public Health England.ResultsBetween Jan 2016 and May 2019, 121 patients with pleural infection were diagnosed, of which 70 (57.8%) were males. The mean age was 69±13.8 years. In 106/121(88%) of the cases a low pleural fluid pH was noted while 15/121 (12%) had frank empyema. The rates of pleural infection varied by month, but overall a trend was observed for an increase over time (R square of the model 0.311) (Panel A). The log rates of influenza hospitalisations superimposed on pleural infection data did not show a clear direct correlation, but suggests possible peaks of pleural infection diagnosed following seasons of high national influenza rates (Panel B). However, the median (IQR) rate of infection per month during flu and non-flu season were 3 (2–4) and 3 (1–5) respectively.ConclusionThe rate of diagnosis of pleural infection appears to be rising over time, with a degree of temporal variation that could be related to influenza activity.Abstract P100 Figure 1

Background and ObjectivesWays to assess and track progress of new EBUS operators and trainees is desirable to ensure training goals and procedural competence are achieved and maintained. While important, relying on the diagnostic yield or on question-based assessments alone is not sufficient.MethodsThis study examined the longitudinal change in times taken between needle passes (needle pass time; NPT) during EBUS lymph node sampling as a metric to monitor progress. The EBUS database of a tertiary hospital that employs 1–2 lung cancer fellow per year was accessed to extract data on the first 50 EBUS procedures for three trainees were collected. The NPT was derived using PACS images that are stored to document every needle pass during an EBUS procedure and an average NPT per procedure was calculated.ResultsBetween the three trainees 157 procedures were carried out within the study period with 302 LN stations sampled. Station 7 was the most commonly sampled (36.9%). The mean NPT (n=204 stations) was 2:49±0:49 mins. The mean lymph node short axis diameter (n=210) was 15.5±8.7 mm. There was a negative correlation between node size and time per pass (r -0.146, p=0.045).The change in average NPT and time between passes during the study period for the trainees is plotted in figure 1 showing a consistent decrease in average times between passes during the first 50 procedures. A point of ‘convergence’ around the 30th procedure with less variation between procedures was noted (red vertical lines) for the three trainees. On multivariate regression, NPT was significantly associated with procedure order and type of station sampled but not lymph node diameter.Abstract P224 Figure 1ConclusionNPT and time between stations are easy metrics that can potentially help ensure EBUS trainees are advancing in a given training programme.

BackgroundRecurrent pleural intervention may complicate the pleural space by inducing pleural inflammation with subsequent septation formation. We evaluated our five year experience in the incidence of pleural septations in patients undergoing pleural interventions.MethodWe retrospectively identified patients who underwent thoracic ultrasound (TUS) in our pleural service from our reporting database between August 2015 and February 2021. Categorical reporting of the presence of septations was used, reporting septations as either present or absent. Repeated TUS, types of pleural interventions, and time between these interventions were analysed.ResultsOf the 2737 index TUS performed, we recorded whether septations were present or not in 2684 (98%) patients. Of these, septations were present in 715/2684 (26.6%: 95% CI 25–28.3%) cases.In 297 patients with >1 TUS reports, 187 underwent an intervention at the index visit. At baseline, septations were present in 39/187 (20.9%) of these patients. Of the remaining 148/187 (79.1%) patients without septations on index scan, 24/148 (16.2%; 95% CI 10.7–23.2) reported the formation of new septations at the second TUS visit at a median [interquartile range] time interval of 21 [9–63] days.No association was seen between the type of intervention and development of septations [chest drain 14.2% (1/7), diagnostic aspiration only 22.2% (6/27), therapeutic aspiration 15.3%( 17/111) p=0.68].No difference was observed in those patients with serial scans, not undergoing intervention, with new septations reported in 15/75 (20%) (p=0.48), while a shorter time interval between scans reporting conversion to septations (median [IQR] 7 [2.25–57] days (p=0.04)) was noted.ConclusionOverall, in this large cohort of patients seen through our pleural service, septations were present in a quarter of baseline thoracic ultrasound examinations. Septations formed with or without intervention in around 1 in 5 patients. Understanding this further has significant implications for diagnostic and management pathways.

BackgroundPleurodesis is an important method for palliating malignant pleural effusion (MPE). Recent observations show difference in survival among patients who achieve successful pleurodesis.1 MethodsA literature search of Medline, Embase and Cochrane databases for studies in English was carried using relevant keywords. Studies were included if reported patients were adults undergoing chemical pleurodesis for MPE and pleurodesis success was clearly defined. (Protocol CRD42018115874)ResultsFrom 972 titles the search returned, 13 studies (on 1976 patients) were included. The majority of studies were retrospective in design. The weighted mean age of studied patients was 68.45 (95% CI 67.7–69.1) years and the most common primaries were lung, breast and mesothelioma. Table 1 summarises the details of the included studies. Ten of the included studies showed difference in survival in favour of patients achieving successful pleurodesis.ConclusionPleurodesis success seems to be associated with a survival benefit in MPE patients, but most of the available data comes from retrospective series. The noticed survival difference could reflect a beneficial effect of the pleurodesis process. Conversely, this difference might only stem from the poorer response to pleurodesis in patients with heavier pleural disease burden and hence worse outcomes. More prospective studies are needed to explore this further.ReferenceHassan, et al. British Thoracic Winter Meeting 2018, London. Abstract S132.Abstract S48 Table 1

BackgroundThe British Thoracic Society Pleural guidelines recommend attempting pleurodesis in patients with malignant pleural effusion (MPE) whose chest X-rays show evidence of less than 50% lung entrapment,1 suggesting that more extensive entrapment would predict pleurodesis failure. It is not clear, however, how far the extent of pleural involvement by malignancy affects pleurodesis outcome.MethodsA systematic review of papers available on PubMed, Embase and Cochrane databases published in English on the subject of pleurodesis was carried out(protocol CRD42018115874). Only papers with clear definition of pleurodesis success with 20 or more patients were included.ResultsThe search returned 972 titles. Six papers (reporting on 1155 patients) studying MPE due to different primaries contained data on the relation between tumour burden assessed during thoracoscopic examination of the pleural cavity. Five of the included papers utilised a score developed previously.2Table 1 summarises the included studies and the effect measures reported. There was no uniform way of interpreting the results of the pleural burden score.ConclusionOnly papers of retrospective design linked higher pleural tumour burden with pleurodesis failure. More robust evidence is required from prospectively designed studies.ReferencesRoberts, et al. Thorax 2010;65:ii32–40.Sanchez-Armengol A, et al. Chest 1993;104:1482–5.Abstract P105 Table 1

IntroductionThe National Optimal Lung Cancer Pathway (NOLCP) aims for CT imaging within 72 hrs. In our centre, increased referral rates and significant variations in weekly numbers can saturate our pathway. We aimed to scope whether the process could be refined.MethodsSet up in 2018, patients with suspected lung cancer without a chest radiograph (CXR) could be referred directly for a CXR followed by a CT scan if indicated. A patient navigator collected a standardised symptom questionnaire. Symptoms, alone and in combination were assessed pre and post CXR, and outcomes recorded. In addition, a patient with an abnormal CXR could be entered into the pathway to expedite a CT scan. A normal CXR was defined as no radiographical evidence of lung pathology or cancer. The positive and negative predictive values were calculated pre and post the finding of a normal CXR.ResultsOver 18 months 1081/1100 patients entering the pathway had complete data. Primary referrals (CXR naive) accounted for 677, while 404 patients were pulled into the pathway following an abnormal CXR. Overall 154 cancers were diagnosed, of which 126 were of thoracic origin. Of the primary referrals 51/677(7.5%) were subsequently diagnosed with cancer, 40 of which were thoracic.Pre-CXR, the symptoms with the highest positive predictive values (PPV) were haemoptysis (12.1%) and loss of weight (LOW) (11.7%) dropping to 5.1% and 6.5% respectively following a normal CXR. Patients with a normal CXR and cough, chest pain, breathless or fatigue all had a PPV <4%. Thrombocytosis was present in 29/620(5%) patients referred pre-CXR, and in no patients with a normal CXR and susbsequent diagnosis of cancer.Symptom combinations showed a PPV of >10% in those with Loss of appetite+haemptysis, LOW+ haemoptysis and LOW+hoarse voice after a normal CXR, while a PPV <4% was seen in those with cough plus either haemoptysis, chest pain, breathlessness or fatigue, SOB+chest pain, fatigue+chest pain, and SOB+fatigue – with the PPV ranging from 2.7–3.5%.ConclusionThe use of symptom combinations in the context of a normal CXR may help streamlining CT resources to ensure that those with the greatest risk have immediate access. However, given the overall relative high pre-test probability most patients will require a CT scan.

Introduction and ObjectivesThe relationship between symptoms, pleural effusion size and the diaphragm is unclear. We conducted a pilot study to understand the role of diaphragm shape and movement in patients with unilateral pleural effusions.MethodWe prospectively recruited patients with unilateral pleural effusions. Routine investigations were collected. Study-specific thoracic ultrasounds (TUS) were performed at baseline, post intervention, and at day 7. A seven-day visual analogue score (VAS) diary was completed for breathlessness, starting at baseline, immediately post aspiration and then daily thereafter.ResultsOf the 45 patients recruited, 17/45(38%) were female. The median [interquartile] age was 71[66–77] years. The most common reported symptom was breathlessness in 43/45(96%). At baseline, the medial effusion depth was 100[80–126]mm over 4[3–5] rib spaces. Procedures were performed in 40/45(89%), including 32 therapeutic-interventions and 8 diagnostic aspirations. A median of 1,000 [481–1,500]mls of pleural fluid was aspirated. Malignancy was diagnosed in 20/45(44%) patients.A diaphragm abnormality (abnormal shape, movement or both) was seen in 22/45(49%) with a flattened diaphragm in 7/45(16%), an inverted diaphragm in 2/45(4%), paradoxical movement in 13/45(29%) and no movement in 8/45(36%). A malignant diagnosis was found in 14/22(64%) of those with a diaphragm abnormality at baseline, compared to 6/23(35%) with normal diaphragm (p<0.05). Of those undergoing a therapeutic intervention diaphragm abnormalities persisted in 4/21(19%) with improvement in 15/21(71%) (two were unreported). Diaphragm shape improved in all patients, however two patients had a persistent paradoxically moving diaphragm and two had no movement.In 27 patients undergoing therapeutic intervention and completing follow up, 19/27(70%) had a diaphragm abnormality at baseline, 4/27(15%) post intervention and 11/27(41%) at day 7. VAS scores at baseline, post aspiration and day 7 were 44[27–53.5]mm, 25[13–44]mm and 36[13.5–58.5]mm in those with a diaphragm abnormality compared with 46.5[34.25–72.5]mm, 34.5[18.5–54.75]mm and 22.5[14.25–32.25]mm in those with an normal diaphragm. In those with an abnormal diaphragm at day 7, the change in VAS was -4[-11.5–1] in the abnormal diaphragm group and -23[-31- -10.25] in the normal diaphragm group (p<0.05).ConclusionA diaphragm abnormality was common, demonstrated reversibility, but recurrence by day 7 was associated with loss of therapeutic benefit.

Pleural infection in adults has considerable morbidity and continues to be a lifethreatening 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

IntroductionPlasminogen Activator Inhibitor-1 (PAI-1) plays an essential role in the pathogenesis of lung and pleural injury. PAI-1 levels in pleural infection have been shown to be significantly elevated compared to malignant pleural effusions and heart failure. A significant variation was seen in levels of PAI-1 protein and activity in the pleural fluid from participants with pleural infection recruited to the MIST-2 study. Rabbit models of pleural injury have demonstrated that, along with other pro-inflammatory cytokines, PAI-1 is an important contributor to impaired fibrin clearance and subsequent pleural loculation. To date, this has not been studied in the context of prospectively collected pleural fluid samples from patients with confirmed pleural infection and documented baseline ultrasound septation status.MethodsPleural fluid samples (n=214) prospectively collected from patients recruited to the Pleural Infection Longitudinal OuTcomes study (PILOT) were analysed. Protein measurement assays were performed using a commercial Luminex assay for Serpin E1/PAI-1 (Luminex high performance assay, R&D) as analyte of interest in addition to TNF-alpha, MCP-1/CCL-2, IFN-gamma, urokinase plasminogen activator (uPA) and D-dimer. The independent samples T-test was used to compare mean values for each protein between two groups (septated vs non-septated). A multinomial regression model was performed to assess the independent predictive ability for each protein to septation status as an outcome.ResultsComplete ultrasound data was available for 166 cases, and these were used in the final analysis. There was a significant difference in the PAI-1 levels between the septated group (n=122; mean=1790.59 ng/mL, SD=2027.28) and non-septated group (n=44; mean=948.82ng/mL, SD=911.41); t(166)=2.65, p=0.009 (Normal ref 2–46 ng/mL). In the multinomial regression model, PAI-1 was the only significant independent predictor of septation status (ß=0.000, p=0.003).Abstract S12 Figure 1ConclusionThese data confirm that whilst several biological factors may contribute to impaired fibrinolysis and subsequent septation formation in pleural infection, PAI-1 appears to be the most important. These data imply that PAI-1 is likely to be the most useful target for further studies involving intrapleural fibrinolytic therapy in pleural infection. Further work assessing the effect of baseline PAI-1 levels on clinical outcomes in this dataset is ongoing.

BackgroundPleural infection (PI) is a common and complicated disease. Empirical antibiotic usage has been correlated to poor clinical outcomes. Although the identification of the pathogen is essential for successful treatment, conventional culture-based pathogen detection techniques fail in approximately 40% of cases. Therefore, the bacteriology of PI remains incomplete. Next generation sequencing (NGS) is a molecular-based methodology which could be applied to metagenomics studies and improve pathogen recognition.AimTo investigate and characterise the bacterial patterns of PI.MethodsPleural fluid specimens from the ‘Pleural Infection Longitudinal Outcome Study’1 (PILOT, n=243) were subjected to bacterial DNA extraction followed by 16S rRNA NGS. The DADA2 and Phyloseq R packages were used for the analysis of the data.ResultsWe identified 363 distinct species of bacteria, with various abundances among the samples. Diverse patterns between monomicrobial and polymicrobial PI were detected. 131 (54%) samples had one pathogen with abundance over 50% and 89 (36%) samples had at least three pathogens with relative abundance over 10%, suggesting a polymicrobial infection.DiscussionWe developed a methodology to extract bacterial DNA from pleural fluid specimens derived from patients with PI and the quality was satisfactory to be used for NGS. 16S rRNA gene NGS has the potential to detect the total microbiome of pleural fluid samples1 from complex PI.FundingNational Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC).ReferenceCorcoran, J.P., et al. Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study. Eur Respir J ( 2020).