Early Video-assisted Thoracoscopic Surgery or Intrapleural Enzyme Therapy in Pleural Infection: A Feasibility Randomized Controlled Trial. The Third Multicenter Intrapleural Sepsis Trial-MIST-3.

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).

ERS International Congress 2022: highlights from the Thoracic Oncology Assembly.

Thoracic malignancies are associated with a substantial public health burden. Lung cancer is the leading cause of cancer-related mortality worldwide, with significant impact on patients' quality of life. Following 2 years of virtual European Respiratory Society (ERS) Congresses due to the COVID-19 pandemic, the 2022 hybrid ERS Congress in Barcelona, Spain allowed peers from all over the world to meet again and present their work. Thoracic oncology experts presented best practices and latest developments in lung cancer screening, lung cancer diagnosis and management. Early lung cancer diagnosis, subsequent pros and cons of aggressive management, identification and management of systemic treatments' side-effects, and the application of artificial intelligence and biomarkers across all aspects of the thoracic oncology pathway were among the areas that triggered specific interest and will be summarised here.

Breathlessness Predicts Mortality in Adults: A Systematic Review and Meta-Analysis.

Breathlessness is a commonly encountered symptom, and although its relationship with mortality is well established for many conditions, less clear is this relationship in healthy adults. This systematic review and meta-analysis examines whether breathlessness is associated with mortality in a general population. This is important in understanding the impact of this common symptom on a patient's prognosis. This review was registered with PROSPERO (CRD42023394104). Medline, EMBASE, CINAHL and EMCARE were searched for the terms 'breathlessness' and 'survival' or 'mortality' on January 24, 2023. Longitudinal studies of >1,000 healthy adults comparing mortality between breathless and non-breathless controls were eligible for inclusion. If an estimate of effect size was provided, studies were included in the meta-analysis. Eligible studies underwent critical appraisal, data extraction and risk of bias assessment. A pooled effect size was estimated for the relationship between the presence of breathlessness and mortality and levels of severity of breathlessness and mortality. Of 1,993 studies identified, 21 were eligible for inclusion in the systematic review and 19 for the meta-analysis. Studies were of good quality with a low risk of bias, and the majority controlled for important confounders. Most studies identified a significant relationship between the presence of breathlessness and increased mortality. A pooled effect size was estimated, with the presence of breathlessness increasing the risk of mortality by 43% (risk ratio (RR): 1.43, 95% confidence interval (CI): 1.28-1.61). As breathlessness severity increased from mild to severe, mortality increased by 30% (RR: 1.30, 95% CI: 1.21-1.38) and 103%, respectively (RR: 2.03, 95% CI: 1.75-2.35). The same trend was seen when breathlessness was measured using the modified Medical Research Council (mMRC) Dyspnoea Scale: mMRC grade 1 conferred a 26% increased mortality risk (RR: 1.26, 95% CI: 1.16-1.37) compared with 155% for grade 4 (RR: 2.55, 95% CI: 1.86-3.50). We conclude that mortality is associated with the presence of breathlessness and its severity. The mechanism underlying this is unclear and may reflect the ubiquity of breathlessness as a symptom of many diseases.

ERS International Congress 2022: highlights from the Respiratory Infections Assembly.

The European Respiratory Society International Congress took place both in person, in Barcelona, Spain, and online in 2022. The congress welcomed over 19 000 attendees on this hybrid platform, bringing together exciting updates in respiratory science and medicine from around the world. In this article, Early Career Members of the Respiratory Infections Assembly (Assembly 10) summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, nontuberculous mycobacteria, tuberculosis, cystic fibrosis and coronavirus disease 2019.

Achieving Molecular Profiling in Pleural Biopsies: A Multicenter, Retrospective Cohort Study.

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.

A 58-Year-Old Man With Hemoptysis After COVID-19 Infection.

CASE PRESENTATION: A 58-year-old man presented to us with a 1-week history of high-grade fever and progressive dry cough. Four weeks before his presentation, he was diagnosed with COVID-19 infection and needed non-ICU hospital admission with no supplemental oxygen requirements for 6 days and was treated with a 5-day course of remdesivir and 3 weeks of dexamethasone. His steroid dose was commenced on dexamethasone 12 mg bid (four times the recommended dose) for 14 days and then gradually tapered over the remaining 7 days. His history was unremarkable, except for well-controlled asthma. He did not complain of any shortness of breath, weight loss, or loss of appetite. He was never a smoker and denied any alcohol use.

Objective Thoracoscopic Criteria in Differentiation between Benign and Malignant Pleural Effusions.

BACKGROUND: Thoracoscopy is the "gold standard" diagnostic modality for investigation of suspected pleural malignancy. It is postulated that meticulous assessment of the pleural cavity may be adequate to indicate malignancy through the macroscopic findings of nodules, pleural thickening, and lymphangitis. We attempted to critically assess this practice, by precisely defining objective macroscopic criteria which might differentiate benign from malignant pleural diseases according to intrapleural pattern and anatomical location, and thereby to explore the predilection of abnormalities to specific sites on pleural surfaces. METHODS: A structured review of recorded video footage from medical thoracoscopy procedures in 96 patients was conducted by 2 independent assessors. Abnormalities were scored on agreed, objective criteria for the presence of nodules, lymphangitis and inflammation on each of the costoparietal, visceral and diaphragmatic surfaces. The costoparietal pleura was divided into 6 levels (apical, middle, and inferior surfaces of the lateral and posterior parietal pleura). The anterior surface of the costoparietal pleura was excluded from analysis after interim review as this surface was rarely seen. RESULTS: In the benign group, inflammation was the predominant finding in 65% (n = 33; costoparietal), 44% (n = 21; visceral), and 42% (n = 15; diaphragmatic). Nodules were detected in 24% (n = 12; costoparietal), 8% (n = 4; visceral), and 8% (n = 3; diaphragmatic). The most affected surfaces with inflammation were the middle lateral (60%) and the inferior lateral (57.8%) parts of the costoparietal pleura. In the malignant group, nodules were the predominant finding according to surface in 73% (n = 33; costoparietal), 32% (n = 13; visceral) and 48% (n = 17; diaphragmatic). Inflammation was detected in 44% (n = 20; costoparietal), 25% (n = 10; visceral), and 29% (n = 10; diaphragmatic). The most affected surfaces with nodules were the middle lateral (67.4%) and inferior lateral (66.7%) costoparietal pleural surfaces. CONCLUSION: This is the first detailed, anatomical description of abnormalities in the pleural space during thoracoscopy. While nodules were the predominant pattern in malignant pleural effusion, they were detected in 24% of benign diagnoses. Detection of nodules in >1 area of the costoparietal pleura was in favor of a malignant diagnosis. Inflammation was the predominant pattern in benign pleural effusion. Our results suggest that macroscopic nodules in malignant diagnoses have a predilection for the middle and inferior surfaces of the lateral costoparietal pleura.

A randomised controlled trial of intrapleural balloon intercostal chest drains to prevent drain displacement.

BACKGROUND: Chest drain displacement is a common clinical problem that occurs in 9-42% of cases and results in treatment failure or additional pleural procedures conferring unnecessary risk. A novel chest drain with an integrated intrapleural balloon may reduce the risk of displacement. METHODS: A prospective randomised controlled trial comparing the balloon drain to standard care (12 F chest drain with no balloon) with the primary outcome of objectively defined unintentional or accidental chest drain displacement. RESULTS: 267 patients were randomised (primary outcome data available in 257, 96.2%). Displacement occurred less frequently using the balloon drain (displacement 5 of 128, 3.9%; standard care displacement 13 of 129, 10.1%) but this was not statistically significant (OR for drain displacement 0.36, 95% CI 0.13-1.0, Chi-squared 1 degree of freedom (df)=2.87, p=0.09). Adjusted analysis to account for minimisation factors and use of drain sutures demonstrated balloon drains were independently associated with reduced drain fall-out rate (adjusted OR 0.27, 95% CI 0.08-0.87, p=0.028). Adverse events were higher in the balloon arm than the standard care arm (balloon drain 59 of 131, 45.0%; standard care 18 of 132, 13.6%; Chi-squared 1 df=31.3, p<0.0001). CONCLUSION: Balloon drains reduce displacement compared with standard drains independent of the use of sutures but are associated with increased adverse events specifically during drain removal. The potential benefits of the novel drain should be weighed against the risks, but may be considered in practices where sutures are not routinely used.

Management of Pleural Infection.

Pleural infection is a millennia-spanning condition that has proved challenging to treat over many years. Fourteen percent of cases of pneumonia are reported to present with a pleural effusion on chest X-ray (CXR), which rises to 44% on ultrasound but many will resolve with prompt antibiotic therapy. To guide treatment, parapneumonic effusions have been separated into distinct categories according to their biochemical, microbiological and radiological characteristics. There is wide variation in causative organisms according to geographical location and healthcare setting. Positive cultures are only obtained in 56% of cases; therefore, empirical antibiotics should provide Gram-positive, Gram-negative and anaerobic cover whilst providing adequate pleural penetrance. With the advent of next-generation sequencing techniques, yields are expected to improve. Complicated parapneumonic effusions and empyema necessitate prompt tube thoracostomy. It is reported that 16-27% treated in this way will fail on this therapy and require some form of escalation. The now seminal Multi-centre Intrapleural Sepsis Trials (MIST) demonstrated the use of combination fibrinolysin and DNase as more effective in the treatment of empyema compared to either agent alone or placebo, and success rates of 90% are reported with this technique. The focus is now on dose adjustments according to the patient's specific 'fibrinolytic potential', in order to deliver personalised therapy. Surgery has remained a cornerstone in the management of pleural infection and is certainly required in late-stage manifestations of the disease. However, its role in early-stage disease and optimal patient selection is being re-explored. A number of adjunct and exploratory therapies are also discussed in this review, including the use of local anaesthetic thoracoscopy, indwelling pleural catheters, intrapleural antibiotics, pleural irrigation and steroid therapy.

Critical analysis of the utility of initial pleural aspiration in the diagnosis and management of suspected malignant pleural effusion.

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 (χ2 1df=26.27, p<0.001) and insufficient samples (χ2 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 (χ2 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.

Management of solitary fibrous tumours of the pleura: a systematic review and meta-analysis.

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.

Multidisciplinary approaches to the management of malignant pleural effusions: a guide for the clinician.

INTRODUCTION: Malignant pleural effusion (MPE) is a complication of advanced cancer, associated with significant mortality and morbidity. This entity is commonly treated by respiratory physicians, oncologists, and thoracic surgeons. There have been various randomized clinical trials assessing the relative merits of chest drain pleurodesis, indwelling pleural catheters, treatment of septated MPEs, the use of thoracoscopy and pleurodesis and pleurodesis through IPCs in the past decade which have addressed some key areas in the management of MPEs, with an increasing focus on patient related outcome. AREAS COVERED: In this review, we examine and review the literature for management strategies for MPEs and discuss future directions. A detailed search of scientific literature and clinical trial registries published in the past two decades was undertaken. EXPERT OPINION: Tremendous progress has been made in management of MPE in the past decade and current strategy involves patient preference along with local expertise that is available.

Catastrophic costs of treating drug resistant TB patients in a tertiary care hospital in India.

BACKGROUND: Private healthcare is choice of point of care for 70% of Indians. Multidrug resistant tuberculosis (MDR-TB) treatment is costly and involves duration as long as 2 years. AIM: To estimate costs to patients undergoing treatment for MDR-TB. METHODS: A health-economics questionnaire was administered to 50 consecutive patients who successfully completed ambulatory private treatment for MDR-TB. Direct costs included drug costs, investigations, consultation fees, travel costs, hospitalisation and invasive procedures and cost prior to presentation to us. Indirect costs included loss of income. RESULTS: Of our cohort of 50 patients, 36 had pulmonary TB while 14 had extra-pulmonary TB (EPTB). 40 had MDR-TB and 10 had XDR-TB. There were 15 males and 35 females. Mean age was 30 years (range 16-61 years). Treatment cost for pulmonary MDR-TB averaged $5723 while it averaged $8401 for pulmonary XDR-TB and $5609 for EPTB. The major expense was due to drug costs (37%) while consultation fees were only 5%. Annual individual income for the cohort ranged from $0 to $63,000 (mean $11,430). On average, the cost of treatment ranged from 2.56% to 180.34% of the annual family income. 34/50 (68%) had total costs greater than 20% of annual family income and 39/50 (78%) had total costs greater than 10% of annual family income. The number of patients with total costs >40% of total family income was 22. CONCLUSION: MDR-TB in the private sector results in "catastrophic health costs". Financial and social support is essential for patients undergoing treatment for MDR-TB.

A 31-year-old female with a rare cause of recurrent lower lobar collapses.

Can you diagnose this patient presenting to the emergency department with a short history of productive cough and breathlessness and a history of recurrent admission for chest infections? http://ow.ly/PoHQ30kmGPi.