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ObjectivesSpontaneous pneumothorax is a common pathology. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second occurrence. This study comprehensively reviews the existing literature regarding chemical pleurodesis efficacy.DesignWe systematically reviewed the literature to identify relevant randomised controlled trials (RCTs), case–control studies and case series. We described the findings of these studies and tabulated relative recurrence rates or ORs (in studies with control groups). Meta-analysis was not performed due to substantial clinical heterogeneity.ResultsOf 560 abstracts identified by our search strategy, 50 were included in our systematic review following screening. Recurrence rates in patients with chest tube drainage only were between 26.1% and 50.1%. Thoracoscopic talc poudrage (four studies (n=249)) provided recurrence rates of between 2.5% and 10.2% with the only RCT suggesting an OR of 0.10 compared with drainage alone. In comparison, talc administration during video-assisted thoracic surgery (VATS) from eight studies (n=2324) recurrence was between 0.0% and 3.2%, but the RCT did not demonstrate a significant difference compared with bleb/bullectomy alone. Minocycline appears similarly effective post-VATS (recurrence rates 0.0–2.9%). Prolonged air leak and recurrence prevention using tetracycline via chest drain (n=726) is likely to provide recurrence rates between 13.0% and 33.3% and autologous blood patch pleurodesis (n=270) between 15.6% and 18.2%.ConclusionsChemical pleurodesis postsurgical treatment or via thoracoscopy appears to be most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised trials or other comparative studies.

BackgroundPleural infection is a common complication of pneumonia associated with high mortality and poor clinical outcome. Treatment of pleural infection relies on the use of broad-spectrum antibiotics, since reliable pathogen identification occurs infrequently. We performed a feasibility interventional clinical trial assessing the safety and significance of ultrasound (US)-guided pleural biopsy culture to increase the microbiological yield.Methods20 patients with clinically established pleural infection were recruited. Participants underwent a detailed US scan and US-guided pleural biopsies before chest drain insertion, alongside standard clinical management. Pleural biopsies and routine clinical samples (pleural fluid and blood) were submitted for microbiological analysis. In an exploratory sub-study, the 16S rRNA technique was applied on pleural biopsy samples, to investigate its’ utility on increasing speed and accuracy versus standard microbiological diagnosis. This trials is registered with ClinicalTrials.gov, number NCT02608814FindingsUS-guided were safe with no adverse events observed in this study. Pleural biopsies increased microbiological yield by 30% in addition to pleural fluid and blood samples (combined diagnostic sensitivity 55%). US characteristics at baseline were not statistically associated with survival, fluid volume drainage, radiological improvement or need for surgery. The 16S rRNA technique was successfully applied to pleural biopsy samples, demonstrating high sensitivity (93%) and specificity (89·5%).ConclusionOur findings demonstrate safety of conducting US guided biopsies in patients with pleural infection and a substantial increase in microbiological diagnosis. qPCR primer assessment of pleural fluid and biopsy appears to have excellent sensitivity and specificity.FundingOxfordshire Health Services Research Committee[Figure]

AimTo audit the pleural on-call service referrals and outcome.MethodOur unit instituted the provision of a “pleural phone” and pleural email service as a central point of contact for pleural related questions, both internally for our large Trust, and externally including local GPs, to facilitate a more open model of care, increase efficiency of the diagnostic pathway and prevent unnecessary admissions or procedures. All documented pleural phone (9 am-5 pm,Monday-Friday) and email (any time) referrals between March 2016-February 2017 were analysed.Results506 cases were discussed via email (n=257) or via phone calls (n=249), and this only included logged phone calls (mean 1.9 referrals per working day). This is an underestimation of the number of calls received because phone calls documented on the electronic patient record were not accessible and therefore not included. The number of cases discussed via email is not a reflection of the number of emails, as each case may have involved several emails. Table 1shows the reasons for referral. The outcome of the referrals included advice (33.6%,n=170), advice and pleural clinic follow up (23.7%,n=120), advice and scheduling for a pleural procedure (42.7%,n=216). Of the 216 scheduled for procedures, 49.1% (n=106) were scheduled for a procedure by the pleural team (n=29 pleural one-stop-shop appointments for procedure and review), 49.1% (n=106) were scheduled for a procedure by the radiology team, 1.4% (n=3) were scheduled for an initial procedure by the radiology team (pleural fluid aspiration) then a further procedure by the pleural team (indwelling pleural catheter insertion(n=2), medical thoracoscopy(n=1)), 0.5% (n=1) were scheduled for bronchoscopy. An analysis of the referrals revealed that 22 unnecessary procedures and clinic appointments were avoided after discussion with the pleural team including new pleural outpatient referrals (n=4), follow up pleural outpatient appointment(n=10), pleural procedure appointment (n=5), referral to another clinic(n=2), CT scan(n=1). Advice given on the most appropriate investigation, such as advising large volume aspiration rather than chest drain insertion and hospital admission for a new undiagnosed pleural effusion, was not quantifiable in this retrospective study.Abstract P239 Table 1Shows the reasons for referral to the pleural phone and email serviceReason for referralPercentage of total referrals (number)Pleural effusion (new, previously known, hydropneumothorax)66.8% (n=338)Empyema (diagnosed or clinically/radiologically suspected)8.3% (n=42)Pneumothorax6.5% (n=33)Indwelling pleural catheter-related queries5.1% (n=26)Other (eg pleurodesis-related, pleural thickening)13.2% (n=67)DiscussionPleural on-call service is beneficial and can help avoid unnecessary clinic and procedure list appointments.

IntroductionTIME3, a randomised controlled trial of intrapleural urokinase versus placebo for patients with non-draining malignant pleural effusion (MPE), demonstrated that these patients appear to be a distinct subgroup of patients with a poor prognosis (median survival 58 days). The aim of this study was to identify patient and fluid characteristics associated with this subgroup, to enable further understanding of why patients with non-draining effusion may have poor prognosis.MethodsBaseline demographics and pleural fluid (PF) characteristics of patients enrolled in TIME3 were compared to patients enrolled in TIME2,2a randomised controlled trial of indwelling pleural catheter versus chest drain and pleurodesis for patients with recurrent MPE. Demographic characteristics compared were: age, sex, histological type of cancer and ECOG performance status (PS). Pleural fluid characteristics compared were: total protein, glucose, cytology (positive or negative), pH, lactate dehydrogenase (LDH) and presence of septations on ultrasound. These characteristics were compared using t test for linear variables and chi squared for categorical variables.ResultsThe median survival was 58 days (IQR 27–123) in TIME3 versus 187 days (IQR 48–358) in TIME2. Patients with non-draining effusions had a significantly higher PF LDH (mean 1900 (SD 3100) versus 660 (SD 840), p<0.001) and CRP (mean 117 (SD 80) versus 62 (SD 55), p<0.001). Patients in TIME3 were on average 4 years older (mean 71 years in TIME3 versus 67 in TIME2, p=0.01) and less likely to be cytology positive (24% versus 51%, p=0.021).ConclusionNon draining MPEs have a higher LDH than those without. There was a large difference in mortality between groups, but despite this no identifiable differences in baseline ECOG, PS or tumour type, despite these variables being associated with a poor prognosis in unselected cohorts of patients with MPE.1We postulate that survival in MPE may be associated with septations and the intrapleural inflammatory milieu. Further study of the association between PF LDH, septations and survival is warranted.Abstract P234 Table 1VariableTIME2TIME3Difference (p)Number of patients10671-Mean age (years) (SD)67 (11)71 (9.4)0.013Male:female (% male)46:60 (43)41:30 (58)0.06Median time to death (days) (IQR)187 (48–358)58 (27–123)Type of cancer (%)- breast27 (25)12 (17)0.47- lung25 (24)22 (31)- mesothelioma11 (10)9 (13)- other43 (41)28 (39)ECOG PS 0–2:3–4 (% 0–2)60:46 (57)42:29 (59)0.11Bloods White cell count9.8 (5.4)11.0 (5.4)0.15CRP62 (55)117 (80)<0.001Pleural fluid characteristics:- Cytology positive: negative (% positive)54:48 (51)17:34 (24)0.021- pH (SD)7.4 (0.24)7.4 (0.34)1.0- mean glucose (mmol/L) (SD)5.4 (2.8)4.6 (3.6)0.13- LDH (U/L) (SD)660 (840)1900 (3100)<0.001- Total protein (g/dL) (SD)43 (8.1)41 (10)0.18Septated on ultrasound (yes:no)Not recorded59:7-ReferencesClive, A. O. Predicting survival in malignant pleural effusion: Development and validation of the LENT prognostic score. Thorax2014;69(12):1098–104.Davies HE, M. E. TIME2 randomised controlled trial. Journal of the American Medical Association2012;2383–9.

IntroductionMalignant pleural effusions are a common complication of advanced malignancy, have a poor prognosis and have a significant impact on quality of life. Treatment strategies include chest drain and pleurodesis, or insertion of an indwelling pleural catheter. Successful pleurodesis is thought to be due to the body’s inflammatory response resulting in pleural symphysis. This post hoc analysis of data from the TIME 1 was conducted to address assess whether there is a correlation between the pleurodesis and a systemic inflammatory response.MethodsA total of 282 patients from the TIME 1 trial had data on pleurodesis success, which was defined as no further pleural procedures for up to 3 months after pleurodesis. Patients who had undergone thoracosopy and poudrage as well as those who had undergone chest drain with pleurodesis were included. Sterile talc was used in all patients. The difference in the white cell count (WCC) and C-reactive protein (CRP) levels was calculated between the day of pleurodesis (Day 0) and Day 1. The data are normally distributed thus independent t test was used for analysis. The CRP Day 0 and 1 data were not normally distributed, and therefore were log transformed to produce a normal distribution.ResultsTwo hundred and eighty two patients were included in the analysis with a mean age of 71 in both groups. 229 had a successful pleurodesis and 53 patients required a further pleural procedure on the ipsilateral side signifying failed pleurodesis. 193 patients had CRP levels and 220 patients had WCC levels recorded on both Day 0 and Day 1.Patients who had a successful pleurodesis had a significantly greater rise in CRP than those who failed pleurodesis. There was no significant difference in the change in WCC between the groups. There was also no significant difference in Day 0 and Day 1 WCC or CRP levels between the two groups.ConclusionsThis analysis demonstrates that systemic rise in CRP as an indicator of inflammation is a better predictor of pleurodesis success than the WCC. These data support the hypothesis that higher levels of inflammation are associated with pleurodesis success.Abstract S129 Table 1Pleurodesis SuccessPleurodesis FailureSignificanceWCC Day 08.84 (SD 4.00, n=213)9.12 (SD – 3.14, n=46)p=0.582WCC Day 111.14 (SD 3.78, n=191)10.71 (SD 4.01, n=42)p=0.525WCC Change2.30 (SD 3.07, n=180)1.55 (SD 2.82, n=40)p=0.140CRP Day 0 (log)1.46 (SD 0.58, n=181)1.45 (SD 0.58, n=42)p=0.900CRP Day 1 (log)1.92 (SD 0.34, n=179)1.83 (SD 0.33, n=41)p=0.123CRP Change47.81 (SD 52.08, n=154)27.05 (SD 32.47, n=39)p=0.003SD=Standard Deviation and n=number of patients

BackgroundOver 50 000 patients with malignant pleural effusion (MPE) are seen annually in the UK. The majority develop recurrent symptomatic disease requiring definitive treatment. MPE is most frequently managed with talc slurry pleurodesis via intercostal chest drain. This involves a lengthy inpatient stay and has a success rate of around 70%, with no means of predicting which patients will suffer pleurodesis failure. Thoracic ultrasound (TUS) is widely used by respiratory physicians, and data from animal and human studies suggest it can identify pleural adhesions (through the absence of normal lung sliding) in a range of conditions. By extension, TUS may allow clinicians to diagnose the presence or absence of adhesions post-pleurodesis in MPE, identifying patients suitable for discharge or needing further intervention.Abstract P233 Table 1Ultrasonographic pleurodesis score at day 0 (pre-pleurodesis) and day 1 (24 hours post-pleurodesis) in patients being treated for malignant pleural effusionSuccessful pleurodesisn=11/15 (73.3%) patientsFailed pleurodesisn=4/15 (26.7%) patientspvalue unpaired t-testDay 0 pleurodesis score(mean±SD, total out of 18)10.89±3.986.50±1.290.054Difference=4.39 (95%CI −0.09 to 8.86)Day 1 pleurodesis score(mean±SD, total out of 18)13.45±2.636.75±2.940.002Difference=6.70 (95%CI 3.08 to 10.33)Change from day 0 to 1(mean±SD)2.57±3.980.25±3.590.326Difference=2.32 (95%CI −2.59 to 7.23)MethodWe recruited 18 adult patients with MPE undergoing drainage and talc slurry pleurodesis to a prospective single-centre cohort study. Patients underwent standardised TUS assessment pre- and post-pleurodesis, evaluating pleural sliding and adhesions at nine points (three anterior, three lateral, three posterior) across the affected hemithorax. Lung sliding was graded as per Zhu et al.,1creating a total pleurodesis score out of 18. Pleurodesis failure was defined as radiological and symptomatic fluid recurrence in the same hemithorax requiring further intervention at any point up to 3 months post-pleurodesis. Patients also completed a questionnaire addressing satisfaction with TUS assessment.Results3/18 patients (16.7%) died before 1 month follow-up. Of 15 patients seen at one month, 11 (73.3%) had successful pleurodesis and 4 (26.7%) had failed. No patient had delayed pleurodesis failure between 1 and 3 month follow-up. There was a significant difference observed in the day 1 TUS pleurodesis score between patients who went on to have successful pleurodesis and those who failed during follow-up (table 1). TUS assessment was acceptable to patients, with none considering it either time-consuming or unwilling to have it again if needed.ConclusionOur data suggest TUS assessment 24 hours post-pleurodesis for MPE predicts success or failure of this intervention, with significant implications for clinical care. A larger randomised study is now underway to further evaluate this hypothesis.ReferenceChest2005;128(2):934–9.

IntroductionMalignant Pleural Mesothelioma (MPM) is the only malignancy which develops primarily in the pleural space and is a common cause of a malignant pleural effusion (MPE). MPE associated with MPM is managed similarly to any other malignancy, but it is unclear if the underlying mechanisms of fluid accumulation are the same and whether different treatment strategies should therefore be employed. The TIME 1 trial enrolled patients with MPE who underwent pleurodesis. This post hoc analysis compares the outcomes of patients with MPM to the rest of the trial population.Methods298 patients had available data on their final diagnosis. A number of different variables were compared, including pleurodesis success, systemic inflammation, the prevalence of trapped lung, total fluid volume drained and baseline pain Visual Analogue Score (VAS).ResultsOf the 298 patients included in the analysis 110 patients had mesothelioma (36.9%). Post pleurodesis, MPM patients had a significantly greater rise in CRP than those with other underlying pathologies but had a significantly lower rate of successful pleurodesis. Patients with MPM had a lower pain VAS score on enrolment. There was no significant difference in the rates of trapped lung, the total volume of pleural fluid drained or the change in White Cell Count (WCC) between the groups.ConclusionThere are significant differences in the outcomes of patients with MPM and those with other MPE. Patients with MPM had a lower pleurodesis rate but a significantly greater change in C-reactive protein levels post pleurodesis, signifying a higher inflammatory response to pleurodesis, which has been assumed to associate with pleurodesis success. The mechanisms causing the increased inflammatory response in MPM are unclear. The basis for the lower rates of pleurodesis is unexplained, especially as there was no significant different in the rates of trapped lung. Patients with MPM had a lower level of pain VAS scores on enrolment but further analyses are needed to determine whether this is clinically relevant and reproducible. These data indicate that MPM behaves differently to other forms of MPE and treatment strategies should be tailored towards MPM as a separate entity.Abstract S128 Table 1MesotheliomaOtherSignificancePleurodesis Success77/107 (72.0%)142/173 (82.1%)chi2=3.97, 1 df, p=0.046Trapped lung19/91 (20.9%)26/177 (14.7%)chi2=1.65, 1 df p=0.199Mean total fluid drained (95% CI)2208 (1917–2498)2345 (2119–2570)p=0.621Mean change in CRP (Day 0–1)58 (SD 43)32 (SD 50)p=<0.001Mean change in WCC (Day 0–1)2.53 (SD 2.83)1.89 (SD 3.31)p=0.13Median enrolment pain VAS4 (IQR 6)5 (IQR 15)p=0.016SD=Standard Deviation, df=degrees of freedom, CI=confidence interval, and IQR=Interquartile Range