BACKGROUND:Patients with suspected malignant pleural effusions (MPE) are often in need of both a confirmatory diagnosis and symptom control. Therapeutic options include talc pleurodesis via chest drain, poudrage during medical thoracoscopy, or alternatively an indwelling pleural catheter (IPC). Combining the diagnostic and therapeutic efficacy of medical thoracoscopy and poudrage with the ambulatory benefits of an IPC has not been studied within a randomised controlled trial. The aim of the TACTIC trial was to determine whether this approach resulted in a reduced length of hospital stay and improvements in dyspnoea. METHODS:This unblinded, phase 3, randomised controlled trial was undertaken in 11 UK hospitals. Patients with MPE and confirmed malignancy (during medical thoracoscopy or beforehand) received talc poudrage and were randomly assigned by a centralised web-based system to an IPC at the time of medical thoracoscopy or usual care (ie, medical thoracoscopy, poudrage, and admission with large bore tube). Co-primary outcomes were time in hospital (including initial admission for trial procedure and any subsequent readmissions over 4 weeks post procedure) and average breathlessness assessed with visual analogue scale dyspnoea scores, measuring severity of dyspnoea from 0 mm to 100 mm, over a 4-week period. All randomised patients in whom an outcome was available were included in the analysis on a modified intention-to-treat basis. TACTIC was registered with ISRCTN on Aug 8, 2021 (ISRCTN11058680). FINDINGS:Participants were recruited from between Dec 15, 2021, and Jan 3, 2024. 124 participants were randomised: 62 to the intervention and 62 to standard care. Leading diagnoses were pleural mesothelioma (46%), lung cancer (28%), and breast cancer (10%). Co-primary outcome data were available for 102 patients for total length of hospital stay (52 in intervention group vs 50 in standard care group) and 108 patients for breathlessness (57 vs 51). Median time in hospital was 1 day (IQR 1-3, 95% CI 1-2) in the intervention group versus 2 days (IQR 1-3, 95% CI 1-2) in standard care group (p=0·26). Median visual analogue scale dyspnoea scores did not differ between groups: 14·0 mm (IQR 8·8-32·4) in the intervention group versus 19·6 mm (8·1-38·7) in standard care group (p=0·26). Participants in the intervention group required fewer additional invasive pleural procedures by 12 weeks (two [3%] of 60 vs 19 [34%] of 56, p<0·0001) Trial related adverse events rates were similar in both groups (46 [74%] of 62 vs 44 [71%] of 62, p=0·84). Three related serious adverse events were recorded, all occurring in the intervention group. INTERPRETATION:The combination of medical thoracoscopy, poudrage, and IPC did not result in shorter hospital stay but was safe and resulted in similar dyspnoea control compared with standard care. For patients with symptomatic MPE undergoing medical thoracoscopy for pleurodesis who prioritise minimising the length of hospital stay or the need for further invasive pleural procedures, the addition of an IPC alongside poudrage might help to achieve this goal. FUNDING:National Institute of Health Research, Research for Patient Benefit.
Background: Nontraumatic chylothorax is an uncommon cause of pleural effusion and a challenge to manage. Several radiological tests have been recommended for evaluation of chylothorax, but there is little evidence to guide clinicians on the utility, yield and optimal order of these diagnostic modalities. We aimed to evaluate the clinical utility of radiological tests including computed tomography (CT), positron emission tomography-CT (PET-CT) and lymphatic imaging such as magnetic resonance (MR) lymphangiogram in the management of nontraumatic chylothorax. Methods: A retrospective single-centre study of patients with nontraumatic chylothorax from January 2019 to December 2023. Radiological tests were classified based on their utility in supporting a specific diagnosis or guiding a diagnostic or therapeutic intervention. Results: Twenty patients with a median age of 66 [interquartile range (IQR), 56-75] years were included. The median pleural fluid triglyceride level was 5.04 (IQR, 2.82-18.32) mmol/L. Malignancy accounted for the majority (40.0%) of causes, of which lymphoma was the most common. High output or persistent chyle leak requiring >_2 therapeutic interventions were seen in 90% of patients, and 75% of patients had a large pleural effusion on ultrasonography (>_4 rib spaces). CT or PET-CT imaging was useful in 75% of patients, supporting a specific diagnosis in 8 (40.0%) patients and detecting abnormalities that guided tissue biopsy in 7 (35.0%) patients. Lymphatic imaging was performed in 12 (60.0%) patients, all of whom underwent MR lymphangiogram. An additional lymphoscintigraphy was performed in two patients and lymphangiography in one patient. Thoracic duct ligation was attempted in one patient after a small volume lymphatic leak was visualised on MR lymphangiogram. No significant abnormalities to direct lymphatic intervention were found on lymphatic imaging in the remaining 11 patients. Conclusions: In most patients with nontraumatic chylothorax, CT imaging provides specific diagnostic value and guides further evaluation such as tissue biopsy. Larger prospective studies are required to evaluate the utility of routine lymphatic imaging.
BACKGROUND:Light's criteria use pleural fluid protein and lactate dehydrogenase (LDH) to differentiate pleural effusions as exudative or transudative. In a subset of exudative pleural effusions, discordance occurs between LDH and protein (ie, protein high, LDH low, or vice versa). RESEARCH QUESTION:What incidence and diagnostic profile are associated with discordant pleural fluid biochemistry? STUDY DESIGN AND METHODS:We conducted a retrospective analysis of 995 pleural fluid samples between 2015 and 2017 from a UK tertiary center. Exudates were subdivided into concordant or discordant, with low protein defined as < 30 g/L and low LDH as < 170 IU/L. Demographic characteristics and diagnostic patterns were assessed in both groups. A χ2 test and ORs (± 95% CI) were calculated for each diagnosis between discordant and concordant pleural effusions, and adjusted ORs were calculated by using multivariable logistic regression. RESULTS:In 715 exudative pleural fluid samples, 229 (32%) were discordant. Eighty-five (37%) of these displayed low protein, with high LDH, and 144 (63%) displayed low LDH with high protein. The median age was higher in the discordant group than in the concordant group (75 years vs 70 years; P = .01). The proportion of patients with the following diagnoses were significantly higher in the discordant group compared with the concordant group: fluid overload (10% [24 of 229] discordant vs 2% [10 of 486] concordant; P < .0001), benign asbestos-related pleural effusion (14% [33 of 229] vs 9% [44 of 486]; P = .031), and ICU-associated effusion (9% [20 of 229] vs 3% [15 of 486]; P = .001). The following were less frequent in the discordant group: pleural infection (6% [14 of 229] vs 16% [79 of 486]; P < .0001) and malignant pleural effusion (34% [77 of 229] vs 42% [206 of 486]; P = .025). These patterns were maintained when adjusting for age and sex. INTERPRETATION:Our results indicate that discordant pleural effusions are common and represent a biologically distinct entity with different diagnostic patterns compared with concordant effusions. Clinicians should assess for discordance early and tailor investigations accordingly.
Introduction:Pleural effusions caused by organ dysfunction are the commonest pleural disease and account for a huge healthcare burden. Previous work has demonstrated poor survival rates, but there is still uncertainty about determinants of prognosis. This study describes the characteristics and risk factors for poor outcomes in patients with pleural effusion secondary to organ failure in an international cohort. Methods:The European Respiratory Society International Multicentre Pleural Research Collaborative (IMPACT) registry includes an international retrospective study of patients with effusions secondary to heart, liver or renal failure, collected from 10 countries in Europe and North and South America between 2019 and 2021. The data were analysed for associations between baseline patient characteristics and key clinical outcomes. Descriptive data were collected on treatments and complications. Results:A total of 755 patients contributed data. Overall, 85.2% of effusions were classified as transudates by Light's criteria. 42% of effusions were bilateral. One-year mortality rates were 46% in renal, 35% in hepatic and 33% in cardiac effusions. Increased mortality was observed in neutrophil-predominant effusions (HR 2.001, 95% CI 1.202-3.349, p=0.008), with age (HR 1.013, 95 CI 1.002-1.024, p=0.02) and with N-terminal pro-brain natriuretic peptide >450 pg·mL-1 (HR 1.508, 95% CI 1.191-1.911) in patients with cardiac failure. Therapeutic thoracentesis was the most frequently employed pleural intervention; indwelling pleural catheter use was rare and associated with higher pleural infection rates than thoracentesis. Conclusion:This study identifies prognostic factors in an international cohort of patients with transudative pleural effusions. Identification of these risk factors may support treatment approaches in a global population.
Background Artificial intelligence (AI)-assisted image interpretation is a fast-developing area of clinical innovation. Most research to date has focused on the performance of AI-assisted algorithms in comparison with that of radiologists rather than evaluating the algorithms' impact on the clinicians who often undertake initial image interpretation in routine clinical practice. This study assessed the impact of AI-assisted image interpretation on the diagnostic performance of frontline acute care clinicians for the detection of pneumothoraces (PTX). Methods A multicentre blinded multi-case multi-reader study was conducted between October 2021 and January 2022. The online study recruited 18 clinician readers from six different clinical specialties, with differing levels of seniority, across four English hospitals. The study included 395 plain CXR images, 189 positive for PTX and 206 negative. The reference standard was the consensus opinion of two thoracic radiologists with a third acting as arbitrator. General Electric Healthcare Critical Care Suite (GEHC CCS) PTX algorithm was applied to the final dataset. Readers individually interpreted the dataset without AI assistance, recording the presence or absence of a PTX and a confidence rating. Following a 'washout' period, this process was repeated including the AI output. Results Analysis of the performance of the algorithm for detecting or ruling out a PTX revealed an overall AUROC of 0.939. Overall reader sensitivity increased by 11.4% (95% CI 4.8, 18.0, p=0.002) from 66.8% (95% CI 57.3, 76.2) unaided to 78.1% aided (95% CI 72.2, 84.0, p=0.002), specificity 93.9% (95% CI 90.9, 97.0) without AI to 95.8% (95% CI 93.7, 97.9, p=0.247). The junior reader subgroup showed the largest improvement at 21.7% (95% CI 10.9, 32.6), increasing from 56.0% (95% CI 37.7, 74.3) to 77.7% (95% CI 65.8, 89.7, p<0.01). Conclusion The study indicates that AI-assisted image interpretation significantly enhances the diagnostic accuracy of clinicians in detecting PTX, particularly benefiting less experienced practitioners. While overall interpretation time remained unchanged, the use of AI improved diagnostic confidence and sensitivity, especially among junior clinicians. These findings underscore the potential of AI to support less skilled clinicians in acute care settings.
We present the initial results of analysis of patients diagnosed and treated for mesothelioma at a tertiary cancer centre (Oxford University Hospitals NHS Foundation Trust, OUH).
Introduction: The current pathway in suspected malignant pleural effusion involves multiple procedures to achieve diagnosis and fluid control, typically 1)pleural aspiration 2)biopsy and 3)Indwelling pleural catheter. The patient experience of this pathway is unexplored. Methods: Patient records were reviewed to establish pathway duration. Semi structured qualitative interviews were undertaken with 17 patients at IPC insertion. Results: 56 patient records were reviewed. Median time to 1)diagnosis was 46 days (IQR:28-54) and 2)time to fluid control was 70 days (IQR:45-84). 17 patients (10 male, 7 female) were interviewed. Breathlessness 9limiting daily activities9 was a common complaint. 65% (11/17) of patients reported ≥1 month of breathlessness, with 88% (15/17) stating impact on daily activity. 35% (6/17) reported an 9unacceptable9 duration of breathlessness. 60% (11/17) of patients reported making ≥1 emergency call for fluid drainage or admission, with comments pertaining to 'being too breathless to wait'. 76% (13/17) had undergone ≥2 pleural procedures prior to IPC insertion. 70% of patients (12/17) reported a preference for earlier IPC and all patients provided input on a proposed feasibility study of early pleural biopsy+IPC. Conclusions: The current MPE pathway is lengthy with multiple procedures. Using this study we have designed the STREAMLINE trial to assess pleural biopsy + IPC as a 1st procedure vs standard care in suspected MPE.
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).
Background Chylothorax is an uncommon medical condition for which limited data are available regarding the contemporary aetiology, management and outcomes. The goal of this study was to better define these poorly characterised features. Methods The medical records of adult patients diagnosed with chylothorax at 12 centres across Europe, America and South Africa from 2009–2021 were retrospectively reviewed. Descriptive and inferential statistics were performed. Results 77 patients (median age 69 years, male to female ratio 1.5) were included. Subacute dyspnoea was the most typical presenting symptom (66%). The commonest cause of chylothorax was malignancy (68.8%), with lymphoma accounting for 62% of these cases. Other aetiologies were trauma (13%), inflammatory/miscellaneous conditions (11.7%) and idiopathic cases (6.5%). At the initial thoracentesis, the pleural fluid appeared milky in 73%, was exudative in 89% and exhibited triglyceride concentrations >100 mg·dL−1 in 88%. Lymphangiography/lymphoscintigraphy were rarely ordered (3%), and demonstration of chylomicrons in pleural fluid was never ascertained. 67% of patients required interventional pleural procedures. Dietary measures were infrequently followed (36%). No patient underwent thoracic duct ligation or embolisation. Morbidity included infections (18%), and thrombosis in malignant aetiologies (16%). The 1-year mortality was 47%. Pleural fluid protein >3.5 mg·dL−1 (sub-distribution hazard ratio (SHR) 4.346) or lactate dehydrogenase <500 U·L−1 (SHR 10.21) increased the likelihood of effusion resolution. Pleural fluid protein ≤3.5 mg·dL−1 (HR 4.047), bilateral effusions (HR 2.749) and a history of respiratory disease (HR 2.428) negatively influenced survival. Conclusion Chylothoraces have a poor prognosis and most require pleural interventions. Despite the standard recommendations, lymphatic imaging is seldom used, nor are dietary restrictions followed.
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.
Radiofrequency, microwave and thermal ablation is increasingly used for treatment of primary lung tumours and oligometastatic disease in non-surgical candidates. Pleural complications of ablation, especially pneumothorax and effusion, are common1. We sought to explore identification, investigation and management of pleural complications of ablation in all patients treated at a tertiary UK hospital over 4-years. Methods: Consecutive lung ablation procedures between Jan2018-Dec2022 were captured retrospectively by interrogating the[BI1] radiology database (CRIS). Two independent physicians reviewed e-records for pleural complications and management of each case. Complications were graded using standard CTEP-AERS criteria. Results: 244 ablation procedures were conducted; 81 for primary malignancy and 163 for metastases. There were 138 males, median age 71years (IQR63-79).. Treatment with ablation was decided for all patients by radiology, surgery and oncology colleagues in the lung cancer meeting. 153(63%) patients had no or minor (Grade1) pleural complications post ablation. 76 (31%) patients had moderate (Grade2) effects. 15 (6%) patients had severe (Grade3) pleural complications requiring prolonged hospital admission or readmission or multiple pleural interventions as summarised in Table 1. Discussion This case series highlights the burden of pleural complications following ablation and the management requiring close working relationships with pleural and radiology colleagues. Future research would likely help determine optimal management of pleural complications post ablation treatment.
Thoracic ultrasound has developed into an integral part of the respiratory physician's diagnostic and therapeutic toolbox, with high diagnostic accuracy for many diseases causing acute or chronic respiratory symptoms. However, it is vitally important that the operator has received the appropriate education and training to ensure a systematic and thorough examination, correct image interpretation, and that they then have the appropriate skills to integrate all the findings for patient benefit.In this review, we present the new European Respiratory Society thoracic ultrasound training programme, including a discussion of curriculum development, its implementation, and trainee evaluation. This programme enables participants to gain competence in thoracic ultrasound through structured, evidence-based training with robustly validated assessments and certification. The training programme consists of three components: an online, theoretical part (part 1), which is accessible all year; a practical course (part 2), with four courses held each year (two online courses and two on-site courses); and an examination (part 3) comprising an objective structured clinical examination (OSCE), which is hosted each year at the European Respiratory Society Congress.
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. 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. What is the adequacy of various pleural biopsy techniques at providing adequate molecular diagnostic information to guide treatment in malignant pleural effusions? 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. 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). 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.