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Background: Fifty years since its inception, Light's criteria have aided in classifying pleural effusions (PEs) as exudates if 1 or more criteria are met. Thoracic ultrasound (US) emerges as a non‐invasive technique for point of care use especially if pleural procedures are contemplated. Objective: We aimed to develop a score based on radiological and US features that could separate exudates from transudates without serum and pleural fluid biochemical tests necessary for Light's criteria. Methods: A prospective review of consecutive patients with PE who underwent thoracocentesis was performed. CXRs were evaluated for laterality followed by US for echogenicity, pleural nodularity, thickening and septations. PE was classified as exudate or transudate according to Light's criteria and corroborated with albumin gradient. A score combining radiological and US features was developed. Results: We recruited 201 patients with PE requiring thoracocentesis. Mean age was 64 years, 51% were females, 164 (81.6%) were exudates, and 37 (18.4%) were transudates. Assigning 1‐point for Diaphragmatic nodularity, Unilateral, Echogenicity, Pleural Thickening and Septations, DUETS ranged from 1 to 5. DUETS ≥2 indicated high likelihood for exudate (PPV 98.8%, NPV 100%) with 1% misclassification versus 6.9% using Light's criteria (p < 0.001). Conclusion: DUETS separated exudates from transudates with good accuracy, and could obviate paired serum and pleural fluid tests necessary for Light's criteria computation. Our study reflected real world practice where DUETS performed better than Light's criteria for PE that arose from more than one disease processes, and in the evaluation of patients with PE who have received diuretics. This study aimed to develop an accurate pleural ultrasound based composite score to accurately distinguish between transudates and exudates for clinical use, in evaluation of pleural effusions. The DUETS score was shown to accurately identify exudative effusions and would be particularly useful in clinical scenarios where there are dual pathologies. See relatededitorial [ABSTRACT FROM AUTHOR]

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Background and Objective: Device‐assessed activity behaviours are a novel measure for comparing intervention outcomes in patients with malignant pleural effusion (MPE). Australasian Malignant PLeural Effusion (AMPLE)‐2 was a multi‐centre clinical trial where participants with MPE treated with an indwelling pleural catheter were randomized to daily (DD) or symptom‐guided (SGD) drainage for 60‐days. Our aim was to describe activity behaviour patterns in MPE patients, explore the impact of drainage regimen on activity behaviours and examine associations between activity behaviours and quality of life (QoL). Methods: Following randomization to DD or SGD, participants enrolled at the lead site (Perth) completed accelerometry assessment. This was repeated monthly for 5‐months. Activity behaviour outcomes were calculated as percent of daily waking‐wear time and compared between groups (Mann–Whitney U test; Median [IQR]). Correlations between activity behaviour outcomes and QoL were examined. Results: Forty‐one (91%) participants provided ≥1 valid accelerometry assessment (DDn = 20, SGD n = 21). Participants spent a large proportion of waking hours sedentary (72%–74% across timepoints), and very little time in moderate‐to‐vigorous physical activity (<1% across timepoints). Compared to SGD group, DD group had a more favourable sedentary‐to‐light ratio in the week following randomization (2.4 [2.0–3.4] vs. 3.2 [2.4–6.1]; p = 0.047) and at 60‐days (2.0 [1.9–2.9] vs. 2.9 [2.8–6.0]; p = 0.016). Sedentary‐to‐light ratio was correlated with multiple QoL domains at multiple timepoints. Conclusion: Patients with MPE are largely sedentary. Preliminary results suggest that even modest differences in activity behaviours favouring the DD group could be meaningful for this clinical population. Accelerometry reflects QoL and is a useful outcome measure in MPE populations. Accelerometry is a novel patient‐centred outcome measure. Malignant pleural effusion patients are mostly sedentary. Those undergoing daily drainages of indwelling pleural catheter could have a better activity behaviour profile compared to those doing symptom guided drainages. A lower proportion of sedentary time was associated with better quality of life. [ABSTRACT FROM AUTHOR]

Background and objective: The pathophysiology of breathlessness in pleural effusion is unclear. In the PLEASE‐1 study, abnormal ipsilateral hemidiaphragm shape and movement, assessed qualitatively, were independently associated with breathlessness relief after pleural drainage. Effects of pleural effusion on contralateral hemidiaphragm function are unknown. PLEASE‐2, a prospective exploratory pilot study, assessed the effects of unilateral effusion and drainage on both hemidiaphragms using advanced quantitative bedside ultrasonography. Methods: Individuals with symptomatic unilateral pleural effusion undergoing therapeutic drainage were included. Measurements pre‐ and post‐drainage included severity of breathlessness (visual analogue scale) and ultrasound measurements of diaphragm excursion and thickness, in addition to shape and movement. Diaphragm measurements were compared to published reference values. Results: Twenty participants were recruited (mean age 68.9 [SD 12.8] years, 12 females). During tidal breathing, contralateral hemidiaphragm excursion exceeded ipsilateral excursion and reference values (all p ≤ 0.001). Contralateral excursion was greatest in participants with abnormal ipsilateral hemidiaphragm movement and was inversely correlated with ipsilateral tidal excursion (r = −0.676, p = 0.001). Following drainage (mean volume 2121 [SD = 1206] ml), abnormal shape (n = 12) and paradoxical movement (n = 9) of the ipsilateral hemidiaphragm resolved in all participants, and tidal excursion of the contralateral hemidiaphragm normalized. Relief of breathlessness post‐drainage correlated with improvement in ipsilateral hemidiaphragm excursion (r = 0.556, p = 0.031). Conclusion: This pilot study suggests, for the first time, that unilateral pleural effusion not only impairs ipsilateral hemidiaphragm function but also causes compensatory hyperactivity of the contralateral hemidiaphragm, which resolves post‐drainage. These findings provide a basis for detailed studies of diaphragmatic function and ventilatory drive in patients with symptomatic pleural effusion. [ABSTRACT FROM AUTHOR]

This study, notwithstanding limitations of its approach, provides the first comprehensive evaluation of adult patients at least 12 months following tPA/DNase treatment for pleural infection. Without a comparison group (e.g. those successfully treated without tPA/DNase or those treated with surgery only), it is difficult to determine if residual symptoms or defects are related to tPA/DNase.5,8 Patient recall biases are inevitable in cross-sectional studies. This cross-sectional multicentre cohort study reports, for the first time, long-term clinical, respiratory and functional outcomes >=12 months following tPA/DNase treatment for pleural infection. Keywords: deoxyribonuclease; intrapleural; pleural effusion; respiratory infection; tissue plasminogen activator EN deoxyribonuclease intrapleural pleural effusion respiratory infection tissue plasminogen activator 388 391 4 03/22/21 20210401 NES 210401 Abbreviations CP loss obliteration of costophrenic angle CXR chest radiograph DNase deoxyribonuclease FEV 1 forced expiratory volume in 1 s FVC forced vital capacity IQR interquartile range mMRC modified Medical Research Council QoL quality of life SF-36v2 36-item short form health survey TLC total lung capacity tPA tissue plasminogen activator Intrapleural tissue plasminogen activator/deoxyribonuclease (tPA/DNase) therapy has been rapidly adopted worldwide for treating pleural infection. [Extracted from the article]

Background and objective: IPC in patients with MPE are removed within 3 months in 30–58% of cases, usually due to decreased pleural fluid output as a result of pleurodesis. Disease control can also account for the lack of fluid output, potentially explaining why 4–14% of patients undergo repeat pleural intervention for fluid re‐accumulation (at the time of disease recurrence or progression). The aim of our pilot study is to determine the accuracy of thoracic ultrasound (TUS) in predicting pleurodesis success in patients with MPE at the time of IPC removal. Methods: This is a single‐centre, prospective observational cohort study that enrolled consecutive patients with confirmed MPE treated with IPC at the time of IPC removal. TUS was performed to calculate a PAS. Patients were followed up for a minimum of 3 months. Failure was defined as pleural fluid recurrence within 3 months. Results: Twenty‐seven patients were screened and 25 were included in the final analysis. Pleurodesis success was observed in 88% (n = 22) and failure in 12% (n = 3) of patients. The mean PAS was higher in patients with pleurodesis success (22.0 vs 9.3, P = 0.01). A PAS greater than 10 predicted pleurodesis success with a sensitivity of 100% and specificity of 86%. Conclusion: This pilot study suggests that TUS at the time of IPC removal accurately identifies patients who have achieved pleurodesis and therefore will not have re‐accumulation of pleural effusion or require an ipsilateral pleural intervention for at least 3 months post‐IPC removal. [ABSTRACT FROM AUTHOR]

Background and objective: Analysis of programmed death ligand‐1 (PD‐L1) in tumour samples is necessary to identify candidates for anti‐PD‐L1/PD‐L1 therapy. Because PD‐L1 is evaluated by immunohistochemistry (IHC), an adequate amount of tumour tissue is a prerequisite for PD‐L1 testing. To examine whether pleural fluid might be an alternative to biopsy/resection specimens for IHC evaluation of PD‐L1 in patients with non‐small cell lung carcinoma (NSCLC), we compared PD‐L1 by IHC between histological specimens and matched pleural fluid. Methods: A retrospective cohort study of patients with NSCLC who underwent core biopsy of a lung mass/surgical resection with PD‐L1 IHC and had a pleural fluid cell block (CB) available for PD‐L1 staining was conducted. PD‐L1 was categorized as negative (PD‐L1 in <1% of tumour cells), moderately positive (PD‐L1 in ≥1% to <50%), strongly positive (PD‐L1 ≥ 50) or inadequate for PD‐L1 testing (<100 tumour cells in the CB). Weighted Cohen's kappa was calculated to evaluate the agreement between PD‐L1 on biopsy/resection specimen and pleural fluid for variables with more than two categories. Results: Of the 115 patients included in this study, 82 (71.3%) had at least 100 tumour cells and were included in the analysis. Of these, 80 (97.6%) had adenocarcinoma. For PD‐L1 of histological specimens versus pleural fluid categorized as negative, moderately positive or strongly positive, the weighted kappa statistic was 0.76 (95% CI: 0.64–0.88), and the concordance was 0.78 (95% CI: 0.68–0.86). Conclusion: Correlation and concordance are high between PD‐L1 in histological specimens and matched pleural fluid. Evaluation of PD‐L1 in pleural fluid should be considered in patients unable to undergo histological biopsies. Programmed death ligand‐1 (PD‐L1) expression in pleural fluid is reliable with fairly good correlation and concordance with PD‐L1 expression in surgical biopsy/resection specimens and should be considered in patients who are unable to undergo histological biopsies. [ABSTRACT FROM AUTHOR]

Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion with loculations, pleural thickening and even frank empyema, all of which may have a lasting effect on lung function. The pathogenesis is a combination of true pleural infection and an effusive hypersensitivity reaction, compartmentalized within the pleural space. Diagnostic thoracentesis with thorough pleural fluid analysis including biomarkers such as adenosine deaminase and gamma interferon achieves high accuracy in the correct clinical context. Definitive diagnosis may require invasive procedures to demonstrate histological evidence of caseating granulomas or microbiological evidence of the organism on smear or culture. Drug resistance is an emerging problem that requires vigilance and extra effort to acquire a complete drug sensitivity profile for each tuberculous effusion treated. Nucleic acid amplification tests such as Xpert MTB/RIF can be invaluable in this instance; however, the yield is low in pleural fluid. Treatment consists of standard anti‐tuberculous therapy or a guideline‐based individualized regimen in the case of drug resistance. There is low‐quality evidence that suggests possible benefit from corticosteroids; however, they are not currently recommended due to concomitant increased risk of adverse effects. Small studies report some short‐ and long‐term benefit from interventions such as therapeutic thoracentesis, intrapleural fibrinolytics and surgery but many questions remain to be answered. [ABSTRACT FROM AUTHOR]

Background and objective: The discovery of highly accurate pleural fluid (PF) biomarkers of malignancy remains elusive. We assessed the operating characteristics of the PF epithelial cell adhesion molecule (EpCAM), claudin 4 (CL4) and human epididymis protein 4 (HE4) as potential markers of epithelial malignancies. Methods: The three markers were quantified by immunoassays in the supernatants (s) and cell lysates (cl) of 175 PF samples. The cut‐off values with 100% specificity were selected for malignant–benign discrimination. An immunocytochemical staining index score for each marker was also evaluated on PF cell blocks. The resulting best biomarker was further validated in two independent populations of 73 and 48 patients with pleural effusions (PE). Results: An EpCAM(cl) >98 pg/g total lysate protein yielded 75% sensitivity, 100% specificity, negative likelihood ratio of 0.25 and area under the curve of 0.94 for labelling adenocarcinomatous effusions. Sensitivity reached 88% if EpCAM(cl) was combined with EpCAM immunostaining. One‐third or more of the malignant effusions exhibiting a false‐negative cytological fluid examination were correctly classified by EpCAM(cl) concentrations. Immunoassays for CL4 and HE4 were diagnostically useless. Conclusion: EpCAM(cl) is a new biomarker of adenocarcinomatous PE with meaningful discriminating properties. [ABSTRACT FROM AUTHOR]

The article offers information on the accurate diagnosis and staging for optimal management of patients with lung cancer and pleural disease. Topics discussed include challenges faced by the respiratory community and patients, and the developments in interventional pulmonology and surgery that are aimed at overcoming these challenges; role of navigational bronchoscopy in obtaining histological specimens in peripheral lung lesions; and the role of endobronchial ultrasound.

Background and objective: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. Methods: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause‐specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine–Gray subdistribution hazard model, and externally validated the model. Results: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X‐ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21–2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43–3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04–1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004–1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43–0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. Conclusion: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence. Factors such as larger pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for pleural fluid recurrence. Knowing what risk factors are associated with recurrence of pleural effusion would allow physicians to identify patients who are more likely to recur. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background and objective: Extrapulmonary tuberculosis (EPTB) accounts for ~15% of all TB patients, and TB pleural effusion is the second most common site of EPTB. The diagnosis of pleural TB is challenging due to the pauci‐bacillary nature of the disease. Histopathology of thoracoscopically obtained pleural biopsy provides the highest diagnostic yield. The Xpert MTB/RIF assay (Xpert) is a PCR test that can identify both Mycobacterium tuberculosis (MTB) and rifampicin resistance. Currently, there is a lack of clarity regarding the value of Xpert on pleural tissue. We report our experience of using Xpert on thoracoscopic pleural biopsy samples. Methods: We retrospectively reviewed the records of patients who underwent thoracoscopy in our institution over a 1‐year period. Relevant clinical details; indications; and results of tests on pleural tissue and fluid, including histopathology, mycobacterial cultures and Xpert, were extracted. Results: Of the 156 patients who underwent thoracoscopy, 73 (47%) had TB, 66 (42%) malignancy and 17 (11%) other conditions. Histopathology was diagnostic in all the 73 TB patients (100%). The yields of the microbiological tests against histopathology on thoracoscopic biopsy sample and pleural fluid were: pleural tissue Xpert 45%, pleural tissue culture 39%, pleural fluid culture 17% and pleural fluid Xpert 14%. Pleural tissue provided higher yields than fluid in both Xpert and culture (P < 0.05). Pleural tissue Xpert provided a higher yield than culture and substantially improved yield compared with closed pleural biopsy as we previously reported. Conclusion: Thoracoscopic pleural biopsy results in increased sensitivity on Xpert testing. [ABSTRACT FROM AUTHOR]

ABSTRACT: Unexpandable lung is a common complication of malignant pleural effusions and inflammatory pleural diseases, such as pleural infection (e.g. empyema and complicated parapneumonic effusion) and noninfectious fibrinous pleuritis. Unexpandable lung due to pleural disease may be because of an active pleural process, and is referred to as malignant or inflammatory lung entrapment. An unexpandable lung may also be encountered in the setting of remote pleural inflammation resulting in a mature fibrous membrane overlying the visceral pleura preventing full expansion of the lung. This condition is termed trapped lung and may be understood as a form of defective healing of the pleural space. Trapped lung typically presents as a chronic, stable pleural effusion without evidence of active pleural disease. An unexpandable lung most often manifests itself as an inability of fully expanding the lung with pleural space drainage. Patients will either develop chest pain preventing complete drainage of the pleural space or develop a post‐procedure pneumothorax. Pleural manometry and radiological imaging are useful in the assessment of an unexpandable lung. Pleural manometry can demonstrate abnormal lung expansion during drainage and imaging will demonstrate abnormal visceral pleural thickening found in trapped lung or malignant and inflammatory lung entrapment. [ABSTRACT FROM AUTHOR]

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ABSTRACT Background and objective Exudative pleural effusions affect over 1500 patients per million population each year. The pathobiology of pleural exudate formation remains unclear. Our recent study revealed monocyte chemotactic protein-1 ( MCP-1) as a key driver of fibrinolytic-induced exudate effusion while another study found a role for MCP-1 in malignant effusion formation. In the present study, we further evaluated the role of MCP-1 in the development of pleural effusion in a mouse model of acute pleural inflammation. Methods λ-Carrageenan ( CAR) was injected into the pleural cavity of CD1 mice and pleural effusion volume measured up to 16 h post-injection. Pleural effusion and serum protein and MCP-1 concentrations were measured and differential cell counts performed in fluids. Mice were also treated with either intraperitoneal (i) anti- MCP-1 antibody or isotype control or (ii) an MCP-1 receptor ( CCR2) antagonist or vehicle control 12 h prior to and at the time of CAR injection. Results Intrapleural CAR induced significant pleural fluid accumulation (300.0 ± 49.9 μL) in mice after 4 h. Pleural fluid MCP-1 concentrations were significantly higher than corresponding serum MCP-1 (144 603 ± 23 204 pg/ mL vs 3703 ± 801 pg/ mL, P < 0.0001). A significant decrease in pleural fluid formation was seen both with anti- MCP-1 antibody (median (interquartile range, IQR): 36 (0-168) μL vs controls 290 (70-436) μL; P = 0.02) or CCR2 antagonist (153 (30-222) μL vs controls 240 (151-331) μL, P = 0.0049). Conclusions Blockade of MCP-1 activity significantly reduced inflammatory pleural effusion formation in a CAR model. Together with recent successes in MCP-1 blockade in other effusion formation models, our data strongly support clinical evaluation of MCP-1 antagonists as a novel approach to pleural fluid management. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective Ultrasound has been shown to improve the accuracy and safety of pleural procedures. Studies to date have been performed in large, specialized units, where pleural procedures are performed by a small number of highly specialized physicians. There are no studies examining the safety and accuracy of ultrasound in the Australian healthcare system where procedures are performed by junior doctors with a high staff turnover. Methods We performed a retrospective review of the ultrasound database in the Respiratory Department at the Royal Melbourne Hospital to determine accuracy and complications associated pleural procedures. Results A total of 357 ultrasounds were performed between October 2010 and June 2013. Accuracy of pleural procedures was 350 of 356 (98.3%). Aspiration of pleural fluid was successful in 121 of 126 (96%) of patients. Two (0.9%) patients required chest tube insertion for management of pneumothorax. There were no recorded pleural infections, haemorrhage or viscera puncture. Conclusion Ward-based ultrasound for pleural procedures is safe and accurate when performed by appropriately trained and supported junior medical officers. Our findings support this model of pleural service care in the Australian healthcare system. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective Yellow nail syndrome ( YNS) is a rare and poorly described disease process. In this case-control study, clinical features and findings on HRCT were compared with idiopathic bronchiectasis ( IBx). Methods A review of all patients attending an adult bronchiectasis clinic between 2007 and 2013 identified 25 YNS patients. IBx patients were matched in a 2:1 ratio for age, duration of symptoms and gender. Results Median age of onset was 53 years. There were 12 male and 23 Caucasian YNS patients. Respiratory manifestations included chronic productive cough (100%), chronic rhinosinusitis (88%), pleural effusions (20%) and lymphoedema (12%). Chest symptoms preceded yellow nails in the majority (68%). Abnormal nails persisted at follow-up in 23 of 25 patients but improved in 14. In both disorders, there was symmetrical, predominantly lower lobe bronchiectasis on HRCT. Extent ( P = 0.04), severity ( P = 0.03) and bronchial wall thickness ( P = 0.05) scores were lower in YNS, with less upper and middle lobe disease. Multivariate analysis showed an independent association with increased mucus plugging in YNS. There was a similar prevalence of Pseudomonas aeruginosa infection and mild lung function abnormalities. Conclusion Bronchiectasis in YNS is less severe than IBx but is associated with increased mucus plugging, onset is in middle age and there is no female predominance. Treatment targeted at improved secretion clearance may improve both chest and nail symptoms, with consideration of long-term macrolide antibiotics. [ABSTRACT FROM AUTHOR]

Patients with an unexplained pleural effusion often require urgent investigation. Clinical practice varies due to uncertainty as to whether an effusion should be drained completely before diagnostic imaging. We performed a retrospective study of patients undergoing medical thoracoscopy for an unexplained effusion. In 110 patients with paired (pre- and post-drainage) chest X-rays and 32 patients with paired computed tomography scans, post-drainage imaging did not provide additional information that would have influenced the clinical decision-making process. [ABSTRACT FROM AUTHOR]

Background and objective Development of CPE in CAP is associated with prolonged hospital stay and it may increase the morbidity and mortality. We aimed to identify microbiological and clinical factors that predicate a prolonged hospital admission in patients treated with a tube thoracostomy to control CPE. Methods This retrospective cohort included patients with CPE requiring chest tube drainage in a tertiary referral Korean hospital from 1 January 2004 to 30 July 2012. After dichotomous grouping according to the mean duration of hospital stay, clinical, laboratory and microbiological parameters were compared. Results The final analysis included 158 patients with CPE. The majority were male (130, 85.0%), and the mean age was 62.8 years. The mean duration of hospital stay was 17.7 (±10.2) days. The mean duration of chest tube drainage was 9.6 (±6.7) days. Streptococcus viridans (48.4%) was the most common pathogen. Intrapleural fibrinolysis was performed in 85 (53.8%); additional tube insertion was needed in 40 (25.3%) patients. In the multivariate analysis after adjusting for covariates, a prolonged hospital stay was associated with fever (aOR: 3.42, P = 0.02), lower PaO2 (a OR: 4.89, P = 0.007) and haemoglobin (aOR: 4.90, P = 0.003) levels, and an increased blood neutrophil fraction (a OR: 3.83, P = 0.01) on admission as well as the identification of microbes in CPE (a OR: 4.14, P = 0.03), and ineffective pleural drainage (a OR: 3.28, P = 0.03). Conclusions This study suggests that physicians should note the clinical symptoms and laboratory findings of severe infection and effectiveness of pleural drainage to predicate which patients with a CAP needing thoracostomy for CPE will have a prolonged hospital stay. [ABSTRACT FROM AUTHOR]

Background and objective The mechanistic target of rapamycin ( mTOR) promotes cancer cell proliferation and survival, transduces pro-angiogenic signals and regulates immune cell differentiation and function. We hypothesized that temsirolimus, an mTOR inhibitor, would curtail experimental mesothelioma progression in vivo by limiting tumour cell growth, abrogating tumour angiogenesis and modulating immune/inflammatory tumour milieu. Methods We produced flank and pleural syngeneic murine mesotheliomas by delivering AE17 and AB1 murine mesothelioma cells into the right flank or the pleural space of C57BL/6 and BALB/c mice, respectively. Animals were given five times/week intraperitoneal injections of 20 mg/kg temsirolimus or vehicle and were sacrificed on day 26 (flank) or on day 15 (pleural) post-tumour cell propagation. Results Temsirolimus limited mesothelioma growth in vivo by stimulating tumour cell apoptosis, inhibiting tumour angiogenesis, enhancing tumour lymphocyte abundance and blocking pro-tumour myeloid cell recruitment. Pleural fluid accumulation was significantly mitigated in AE17 but not in AB1 mesotheliomas. In vitro, temsirolimus hindered mesothelioma cell growth, NF- kappaB activation and macrophage migration. Conclusions In conclusion, temsirolimus apart from inducing tumour cell apoptosis, targets tumour angiogenesis and influences inflammatory tumour microenvironment to halt experimental mesothelioma growth in vivo. [ABSTRACT FROM AUTHOR]

Background and objective The clinical relevance of pleural effusions in lung cancer has seldom been approached systematically. The aim of this study was to determine the prevalence, causes and natural history of lung cancer-associated pleural effusions, as well as their influence on survival. Methods Retrospective review of clinical records and imaging of 556 consecutive patients with a newly diagnosed lung cancer over a 4-year period at our institution. Results Lung cancer comprised 490 non-small cell and 66 small cell types. About 40% of patients with lung cancer developed pleural effusions at some time during the course of their disease. In half the patients, the effusions were too small to be tapped. These effusions did not progress to require a pleural intervention. Patients with minimal effusions had a worse prognosis compared to patients without pleural effusions (median survival of 7.49 vs 12.65 months, P < 0.001). Less than 20% of the 113 patients subjected to a diagnostic thoracentesis had benign causes for their effusions. Palliative pleural procedures (like therapeutic thoracenteses, pleurodesis or tunnelled pleural catheters) were conducted in 79 (84%) of the 94 malignant effusions. An effusion's size equal to or greater than half of the hemithorax was a strong predictor of the need for a palliative procedure. Overall survival of patients with malignant effusions was 5.49 months. Conclusions Malignant pleural effusions are a poor prognostic factor in the setting of lung cancer, which includes minimal effusions not amenable to tapping. [ABSTRACT FROM AUTHOR]

Yellow nail syndrome ( YNS) can be associated with a pleural effusion ( PE) but the characteristics of these patients are not well defined. We performed a systematic review across four electronic databases for studies reporting clinical findings, PE characteristics, and most effective treatment of YNS. Case descriptions and retrospective studies were included, unrestricted by year of publication. We reviewed 112 studies (150 patients), spanning a period of nearly 50 years. The male/female ratio was 1.2/1. The median age was 60 years (range: 0-88). Seventy-eight percent were between 41-80 years old. All cases had lymphoedema and 85.6% had yellow nails. PEs were bilateral in 68.3%. The appearance of the fluid was serous in 75.3%, milky in 22.3% and purulent in 3.5%. The PE was an exudate in 94.7% with lymphocytic predominance in 96% with a low count of nucleated cells. In 61 of 66 (92.4%) of patients, pleural fluid protein values were >3 g/dL, and typically higher than pleural fluid LDH. Pleurodesis and decortication/pleurectomy were effective in 81.8% and 88.9% of cases, respectively, in the treatment of symptomatic PEs. The development of YNS and PE occurs between the fifth to eighth decade of life and is associated with lymphoedema. The PE is usually bilateral and behaves as a lymphocyte-predominant exudate. The most effective treatments appear to be pleurodesis and decortication/pleurectomy. [ABSTRACT FROM AUTHOR]

The approach to management of malignant pleural effusions ( MPE) has changed over the past few decades. The key goals of MPE management are to relieve patient symptoms using the least invasive means and in the most cost-effective manner. There is now a realization that patient-reported outcome measures should be the primary goal of MPE treatment, and this now is the focus in most clinical trials. Efforts to minimize patient morbidity are complemented by development of less invasive treatments that have mostly replaced the more aggressive surgical approaches of the past. Therapeutic thoracentesis is simple, effective and generally safe, although its benefits may only be temporary. Pleurodesis is the conventional and for a long time the only definitive therapy available. However, the efficacy and safety of talc pleurodesis has been challenged. Indwelling pleural catheter ( IPC) drainage is increasingly accepted worldwide and represents a new concept to improve symptoms without necessarily generating pleural symphysis. Recent studies support the effectiveness of IPC treatment and provide reassurance regarding its safety. An unprecedented number of clinical trials are now underway to improve various aspects of MPE care. However, choosing an optimal intervention for MPE in an individual patient remains a challenge due to our limited understanding of the underlying pathophysiology of breathlessness in MPE and a lack of predictors of survival and pleurodesis outcome. This review provides an overview of common pleural interventional procedures used for MPE management, controversies and limitations of current practice, and areas of research most needed to improve practice in future. [ABSTRACT FROM AUTHOR]

Background and objective Laceration of the intercostal artery during pleural procedures is a rare but serious complication. This study evaluates the utility of thoracic ultrasound ( US) to screen for a vulnerable vessel compared with the gold standard computed tomography ( CT). Methods Before undergoing contrast-enhanced CT chest, thoracic US was performed on 50 patients with a high-end and portable machine, and an attempt made to visualize the vessel at three positions across the back to the axilla. These positions were labelled with radio-opaque fiducial markers. On both US and CT images, the location of the vessel at each position, relative to the overlying rib, was calculated and compared. Results The vessel was unshielded by a rib according to CT in 114 of the 133 positions. The sensitivity, specificity and negative predictive value of portable US to image the vessel, when it was within the intercostal space on CT, was 0.86, 0.30 and 0.27 respectively. The performance of a high-end machine was not significantly different. The median time required for a pulmonologist to locate the vessel was 42 s and 18 s for the portable and high-end US respectively. Conclusions US can be used to screen for a vulnerable vessel prior to pleural procedures, in a time amenable to use in clinical practice. Further, it is achievable by a pulmonologist using a portable US machine. If thoracentesis or chest tube insertion is being performed on a patient at increased risk of bleeding, screening for a vulnerable vessel with US prior to beginning the procedure is recommended. [ABSTRACT FROM AUTHOR]

Background and objective Thoracoscopy with a semi-rigid instrument is a recent technique successfully used for diagnosing pleural diseases. However, there are concerns about the diagnostic adequacy of biopsy samples obtained by semi-rigid procedures when compared with rigid thoracoscopy. The purpose of this study was to compare the size, quality and diagnostic adequacy of biopsy specimens obtained at semi-rigid and rigid thoracoscopy in a prospective, randomized fashion. Methods Patients with pleural effusion of unknown origin and/or pleural irregularities suspicious for pleural malignancy were included after less invasive means of diagnosis had failed. All procedures were performed under local anaesthesia with intravenous sedation/analgesia with a single point of entry. Patients were randomly assigned to a rigid instrument procedure ( Olympus Endo EYE WA50120A, forceps) or semi-rigid instrument procedure ( Olympus LTF-160, FB- 55CR-1 forceps). Results Eighty-four patients were randomized. Five of them were excluded because of lack of pleural space. Thirty-eight patients were assigned to a rigid and 41 to a semi-rigid procedure, with mean follow up 24.1 (±8.1) months after the procedure. The average size of the sample obtained by rigid thoracoscopy was 24.7 mm2 (±12.9), and 11.7 mm2 (±7.6) by semi-rigid thoracoscopy. There were no differences in the quality and interpretability of the specimens assessed by the pathologist. The diagnostic accuracy was 100% for the rigid procedure and 97.6% for the semi-rigid procedure. Conclusions The samples obtained by semi-rigid thoracoscopy were smaller, but of adequate quality. The diagnostic accuracy was comparable with that of rigid thoracoscopy in the evaluation of pleural disease. [ABSTRACT FROM AUTHOR]

Background and objective The purpose of this study was to compare the diagnostic utility of pleural fluid N-terminal pro- B-type natriuretic peptide ( NT-pro BNP), midregion pro-atrial natriuretic peptide ( MR-pro ANP) and midregion pro-adrenomedullin ( MR-pro ADM) for discriminating heart failure ( HF)-associated effusions. Methods NT-pro BNP, MR-pro ANP and MR-pro ADM were measured by commercially available methodologies in the pleural fluid of a retrospective cohort of 185 consecutive patients with pleural effusions, of whom 95 had acute decompensated HF. Receiver-operating characteristic and area under the curve ( AUC) analyses allowed comparisons of the discriminative properties of these biomarkers to be made at their optimal cut-off points. Results The diagnostic accuracy of NT-pro BNP and MR-pro ANP for HF as quantified by the AUC was 0.935 and 0.918, respectively, whereas MR-pro ADM was of limited value ( AUC = 0.62). A pleural fluid MR-pro ANP >260 pmol/ L or NT-pro BNP >1700 pg/ mL argues for HF (likelihood ratio ( LR) positive >5), while levels below these cut-off values significantly decrease the probability of having the disease (respective LR negative 0.19 and 0.10). The optimal cut-off points for natriuretic peptides were influenced by age, renal function and body mass index. Finally, both NT-pro BNP and the albumin gradient correctly identified more than 80% of those cardiac effusions misclassified as exudates by standard criteria. Conclusions MR-pro ANP is as valuable a diagnostic tool as NT-pro BNP for diagnosing or excluding HF as the cause of pleural effusion. [ABSTRACT FROM AUTHOR]

ABSTRACT Despite 50-60% of intensive care patients demonstrating evidence of pleural effusions, there has been little emphasis placed on the role of effusions in the aetiology of weaning failure. Critical illness and mechanical ventilation lead to multiple perturbations of the normal physiological processes regulating pleural fluid homeostasis, and consequently, failure of normal pleural function occurs. Effusions can lead to deleterious effects on respiratory mechanics and gas exchange, and when extensive, may lead to haemodynamic compromise. The widespread availability of bedside ultrasound has not only facilitated earlier detection of pleural effusions but also safer fluid sampling and drainage. In the majority of patients, pleural drainage leads to improvements in lung function, with data from spontaneously breathing individuals demonstrating a consistent symptomatic improvement, while a meta-analysis in critically ill patients shows an improvement in oxygenation. The effects on respiratory mechanics are less clear, possibly reflecting heterogeneity of underlying pathology. Limited data on clinical outcome from pleural fluid drainage exist; however, it appears to be a safe procedure with a low risk of major complications. The current level of evidence would support a clinical trial to determine whether the systematic detection and drainage of pleural effusions improve clinical outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Pleural transudates are most commonly due to heart failure (HF) or hepatic hydrothorax (HH), but a number of these effusions are misclassified as exudates by standard (Light's) criteria. The aim of this study was to determine the prevalence of mislabelled transudates and to establish simple alternative parameters to correctly identify them. Methods: We retrospectively analysed the pleural fluid and serum protein, lactate dehydrogenase and albumin concentrations from 364 cardiac effusions and 102 HH. The serum-to-pleural fluid protein and albumin gradients (serum concentration minus pleural fluid concentration), as well as the pleural fluid-to-serum albumin ratio (pleural fluid concentration divided by the serum concentration) were calculated for the mislabelled transudates. Results: Light's criteria had misclassified more HF-associated effusions than HH (29% vs 18%, P = 0.002). A serum-to-pleural fluid protein gradient >3.1 g/dL correctly identified 55% and 61% of the HF and HH false exudates, respectively. The figures for an albumin gradient >1.2 g/dL were 83% and 62%. Finally, a pleural fluid-to-serum albumin ratio <0.6 had identical accuracy for labelling miscategorized cardiac and liver-related effusions (78% and 77%, respectively). Conclusions: If the clinical picture is consistent with HF but the pleural fluid meets Light's exudative criteria, the measurement of the albumin rather than the protein gradient is recommended. In the context of cirrhosis, a potentially 'false' exudate is identified better by the pleural fluid-to-serum albumin ratio. [ABSTRACT FROM AUTHOR]

BSTRACT The most efficient and cost-effective approach to the diagnosis of pleural exudates remains controversial. Important considerations include the respective diagnostic yields of thoracocentesis, closed pleural biopsy and thoracoscopy; the incremental gain in diagnostic yield when sequentially combining these investigations; and the role of various image modalities. The diagnostic yield of thoracocentesis is in the order of 60% for malignancy and >90% for tuberculosis. A second aspiration may increase the yield for malignancy, but a third is generally superfluous. Many authorities consider thoracoscopy the investigation of choice in exudative pleural effusions where a thoracocentesis was nondiagnostic and particularly when malignancy is suspected. It allows for the direct inspection of the pleura and for talc poudrage. Thoracoscopy has a diagnostic yield of 91-95% for malignant disease and as high as 100% for pleural tuberculosis. Access to thoracoscopy is, however, limited in many parts of the world, as significant resources and expertise are required. Blind closed pleural biopsy has a yield of 80% for tuberculosis and <60% for pleural malignancy. Recent studies suggest that CT and/or ultrasound guidance may improve the yield, particularly for malignancy, where it may be as high as 88% and 83%, respectively. A second thoracocentesis combined with an image-assisted pleural biopsy with either an Abrams needle or cutting needle, depending on the setting, may therefore be an acceptable alternative to thoracoscopy. With such an approach, thoracoscopy may potentially be reserved for cases not diagnosed by means of closed pleural biopsy. [ABSTRACT FROM AUTHOR]

Image-guided pleural procedures are important in both the diagnosis and management of pleural disease. Pleural aspiration, biopsy and drainage are all proven to be safer and more efficacious using image guidance. The aim of this article is to review common image-guided pleural techniques and the evidence base for their application in clinical practice. [ABSTRACT FROM AUTHOR]

In recent years, a higher and higher percentage of patients with pleural effusions or pneumothorax are being treated with small-bore (10-14 F) chest tubes rather than large-bore (>20 F). However, there are very few randomized controlled studies comparing the efficacy and complication rates with the small- and large-bore catheters. Moreover, the randomized trials that are available have flaws in their design. The advantages of the small-bore catheters are that they are easier to insert and there is less pain with their insertion while they are in place. The placement of the small-bore catheters is probably more optimal when placement is done with ultrasound guidance. Small-bore chest tubes are recommended when pleurodesis is performed. The success of the small-bore indwelling tunnelled catheters that are left in place for weeks documents that the small-bore tubes do not commonly become obstructed with fibrin. Patients with complicated parapneumonic effusions are probably best managed with small-bore catheters even when the pleural fluid is purulent. Patients with haemothorax are best managed with large-bore catheters because of blood clots and the high volume of pleural fluid. Most patients with pneumothorax can be managed with aspiration or small-bore chest tubes. If these fail, a large-bore chest tube may be necessary. Patients on mechanical ventilation with barotrauma induced pneumothoraces are best managed with large-bore chest tubes. [ABSTRACT FROM AUTHOR]

Virtually all patients with a newly discovered pleural effusion should undergo thoracentesis to aid in diagnosis and management. The routine pleural fluid (PF) evaluation usually includes the following: cell count and differential; tests for protein, LDH, glucose, adenosine deaminase, cytology and, if infection is a concern, pH and bacterial and mycobacterial cultures. Distinguishing transudates from exudates with Light's criteria is a pragmatic first step. If the effusion is an exudate, various PF tests have proven diagnostic utility: adenosine deaminase levels >35 IU/L usually indicate tuberculosis in lymphocyte-predominant PF; pH < 7.2 or glucose less than 60 mg/dL allow the clinician to identify complicated parapneumonic effusions; and conventional cytology may reveal malignant cells in 60% of the patients with malignant effusions. A number of optional PF tests may complement the diagnostic approach to an undiagnosed pleural effusion. For example, natriuretic peptide assays significantly improve the accuracy of a diagnosis of cardiac pleural effusion, whereas PF mesothelin levels greater than 20 nmol/L are highly suggestive of mesothelioma. [ABSTRACT FROM AUTHOR]

The possibility of tuberculous pleuritis should be considered in every patient with an undiagnosed pleural effusion, for if this diagnosis is not made the patient will recover only to have a high likelihood of subsequently developing pulmonary or extrapulmonary tuberculosis Between 3% and 25% of patients with tuberculosis will have tuberculous pleuritis. The incidence of pleural tuberculosis is higher in patients who are HIV positive. Tuberculous pleuritis usually presents as an acute illness with fever, cough and pleuritic chest pain. The pleural fluid is an exudate that usually has predominantly lymphocytes. Pleural fluid cultures are positive for Mycobacterium tuberculosis in less than 40% and smears are virtually always negative. The easiest way to establish the diagnosis of tuberculous pleuritis in a patient with a lymphocytic pleural effusion is to generally demonstrate a pleural fluid adenosine deaminase level above 40 U/L. Lymphocytic exudates not due to tuberculosis almost always have adenosine deaminase levels below 40 U/L. Elevated pleural fluid levels of γ-interferon also are virtually diagnostic of tuberculous pleuritis in patients with lymphocytic exudates. In questionable cases the diagnosis can be established by demonstrating granulomas or organisms on tissue specimens obtained via needle biopsy of the pleura or thoracoscopy. The chemotherapy for tuberculous pleuritis is the same as that for pulmonary tuberculosis. [ABSTRACT FROM AUTHOR]

Background and objective: Binding of Toll-like receptors (TLRs) to microbial or endogenous ligands activates and triggers the associated signalling pathway, which leads to the production of inflammatory cytokines and type I interferons. The extent of TLR pathway activation may vary with the ligands present in different pleural diseases. Methods: The relative mRNA expression levels of TLRs and their adaptors in pleural fluid were determined by PCR and gel electrophoresis in 36 transudative, 25 infectious and 39 malignant pleural effusions. Results: The relative mRNA expression levels of TLR8 and myeloid differentiation factor 88 were low in infectious effusions and that of ras-related C3 botulinum toxin substrate 1 was low in malignant pleural effusions. Different cellular components correlated significantly with the relative mRNA expression of TLRs or their adaptors in pleural effusions with different aetiologies. Conclusions: The relative mRNA expression profiles of TLRs and their adaptors in pleural fluid differ among transudative, infectious and malignant pleural effusions. [ABSTRACT FROM AUTHOR]

Background and objective: Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions. Methods: A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables β coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases). Results: Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models. Conclusions: The proposed models were effective in suggesting pleural tuberculosis or cancer. [ABSTRACT FROM AUTHOR]

Background and objective: Both talc and 0.5% silver nitrate have been shown to induce effective pleurodesis. However, acute adverse systemic inflammatory effects have been described with both agents. The aim of this study was to assess in rabbits the systemic effects associated with a new technique of pleurodesis using repeated low doses of 0.1% silver nitrate. Methods: Rabbits were injected intrapleurally through a chest tube with 0.1% silver nitrate at 0, 24 and 48 h. Other groups received a single injection of 0.5% silver nitrate or 400 mg/kg of talc. Blood samples were collected at 24, 48 and 72 h, and at 7 days, and cytological and biochemical measurements were performed. After 28 days, the presence of macroscopic pleural adhesions and microscopic pleural fibrosis in the pleural cavity were evaluated. Results: Both talc and 0.5% silver nitrate caused significant increases in blood neutrophils, serum LDH, IL-8, transforming growth factor-β and CRP in comparison with control at almost all time points, whereas sequential doses of 0.1% silver nitrate only increased LDH and CRP in the first 24 h and transforming growth factor-β at all time points. All groups showed efficient pleurodesis, with no differences in pleural adhesions or fibrosis. Conclusions: Sequential doses of 0.1% silver nitrate produced efficient pleurodesis in rabbits, with a low systemic inflammatory response in comparison with 400 mg/kg of talc or 0.5% silver nitrate. [ABSTRACT FROM AUTHOR]

Pleural procedures are commonly performed by physicians from a range of specialities. These procedures vary in complexity, from relatively straightforward pleural aspiration to more challenging procedures such as pleuroscopy. After appropriate training, even complex pleural procedures have a low risk of complications. Nevertheless, an appreciation of procedural risks is essential for physician training and forms the crux of a valid patient consent process. This review presents a systematic evaluation of the potential complications of common pleural procedures. [ABSTRACT FROM AUTHOR]

Background and objective: It has been suggested that pulmonary embolism (PE) is an under-recognized cause of pleural effusion. This study aimed to (i) establish the incidence and clinical relevance of pleural effusion in patients with pulmonary emboli; and (ii) determine if there is a relationship between development of pleural effusions and the location of emboli and number of pulmonary arteries involved. Methods: A retrospective analysis of all CT pulmonary angiograms (CTPA) performed over 12 months on adult patients with clinically suspected PE in a hospital which used CTPA as first-line imaging investigation for PE. Results: Of 285 CTPA, 60 patients (21%) had evidence of pulmonary emboli (38 had both central and peripheral clots and 22 peripheral emboli only). Emboli were bilateral in 39 cases and unilateral in 21 cases. Pleural effusion was present in almost one half ( n = 29, 48%) of the patients with pulmonary emboli. Patients with pulmonary emboli were more likely to have a pleural effusion (OR 2.2 (95% CI: 1.1–4.7), P < 0.05) than patients without PE; however, the effusions were generally very small. Most (86%) of the effusions were present on the same side as the emboli. The location of emboli and number of arteries involved did not predict the presence of pleural effusions. Conclusions: Pleural effusion is common in patients with pulmonary emboli demonstrated on CTPA. These effusions are small and seldom alter clinical management. Clinicians should therefore have a high threshold of suspicion in attributing large or contralateral pleural effusions to embolic diseases without excluding alternative diagnoses. [ABSTRACT FROM AUTHOR]

Sjogren's syndrome can cause many organic changes, but is rarely accompanied by pleuritis. We report a 65-year-old patient with primary Sjogren's syndrome who developed bilateral pleuritis with moderately large effusions. He was diagnosed as having Sjogren's syndrome, based on xerophthalmia, xerostomia, positive results for anti-Sjogren's syndrome (anti-SS-A/SS-B) antibodies, the Schirmer test and biopsy findings in the minor salivary glands. The pleural fluid was lymphocyte rich and contained high levels of anti-SS-A/SS-B antibodies. There was no evidence of infection, malignancy or other collagen diseases which cause pleuritis. We conclude that this case adds to the eight previously published reports of primary Sjogren's syndrome complicated by pleural effusion. [ABSTRACT FROM AUTHOR]