Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial.

Importance: Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. Objective: To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. Interventions: Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. Main Outcomes and Measures: The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. Results: Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, -1.8% [95% CI, -10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. Conclusions and Relevance: Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences. Trial Registration: ISRCTN Identifier: ISRCTN47845793.

A Pilot Feasibility Study in Establishing the Role of Ultrasound-Guided Pleural Biopsies in Pleural Infection (The AUDIO Study).

BACKGROUND: Pleural infection is a common complication of pneumonia associated with high mortality and poor clinical outcome. Treatment of pleural infection relies on the use of broad-spectrum antibiotics because reliable pathogen identification occurs infrequently. We performed a feasibility interventional clinical study assessing the safety and significance of ultrasound (US)-guided pleural biopsy culture to increase microbiological yield. In an exploratory investigation, the 16S ribosomal RNA technique was applied to assess its utility on increasing speed and accuracy vs standard microbiological diagnosis. METHODS: Twenty patients with clinically established pleural infection were recruited. Participants underwent a detailed US scan and US-guided pleural biopsies before chest drain insertion, alongside standard clinical management. Pleural biopsies and routine clinical samples (pleural fluid and blood) were submitted for microbiological analysis. RESULTS: US-guided pleural biopsies were safe with no adverse events. US-guided pleural biopsies increased microbiological yield by 25% in addition to pleural fluid and blood samples. The technique provided a substantially higher microbiological yield compared with pleural fluid and blood culture samples (45% compared with 20% and 10%, respectively). The 16S ribosomal RNA technique was successfully applied to pleural biopsy samples, demonstrating high sensitivity (93%) and specificity (89.5%). CONCLUSIONS: Our findings demonstrate the safety of US-guided pleural biopsies in patients with pleural infection and a substantial increase in microbiological diagnosis, suggesting potential niche of infection in this disease. Quantitative polymerase chain reaction primer assessment of pleural fluid and biopsy appears to have excellent sensitivity and specificity.

Exploring the characteristics of patients with mesothelioma who chose active symptom control over chemotherapy as first-line treatment: a prospective, observational, single centre study.

BACKGROUND: Mesothelioma is an aggressive thoracic tumour with a poor prognosis. The only treatment that extends survival is chemotherapy. However, in the UK, up to 50% of patients who are suitable for chemotherapy choose not to receive it, opting for active symptom control instead. The aim of this prospective, single-centre observational study was to describe the characteristics of patients who chose active symptom control over chemotherapy and explore their reasons for doing so. METHODS: Two hundred consecutive patients with mesothelioma from one UK centre were included. Eligibility for chemotherapy and choice of first-line treatment were recorded prospectively. Patient characteristics and outcomes were compared using descriptive statistics, regression analysis and survival analysis. Reasons for choosing active symptom control over chemotherapy were extracted, retrospectively. RESULTS: People who chose active symptom control were older, more likely to be female and had worse performance statuses than patients who received front-line chemotherapy. Concern over side effects, the modest survival benefit and previous adverse experiences with chemotherapy were reported as reasons for the decision. Median survival was 13.9 months in the chemotherapy group compared with 6.7 months in the active symptom control group. CONCLUSIONS: This is the first study to describe the characteristics of patients with mesothelioma who chose active symptom control over chemotherapy, in the front-line setting. Important differences were seen between this group and patients who received chemotherapy, although confounding is likely to have affected some outcomes. Future research could use qualitative methods to explore patients' reasons for choosing active symptom control, and to further elucidate the decision-making process.

Lung Parenchymal Assessment in Primary and Secondary Pneumothorax.

RATIONALE: The definition of primary spontaneous pneumothorax excludes patients with known lung disease; however, the assumption that the underlying lung is normal in these patients is increasingly contentious. OBJECTIVES: The purpose of this study was to assess lung structure and compare the extent of emphysema in patients with primary versus secondary spontaneous pneumothorax and to patients with no pneumothorax in an otherwise comparable control group. METHODS: We identified patients treated for pneumothorax by screening inpatient and outpatient medical records at one medical center in the United Kingdom. From this group, 20 patients had no clinically apparent underlying lung disease and were classified as having a primary spontaneous pneumothorax, and 20 patients were classified as having a secondary spontaneous pneumothorax. We assembled a control group composed of 40 subjects matched for age and smoking history who had a unilateral pleural effusion or were suspected to have a thoracic malignancy and had a chest computed tomography scan suitable for quantitative analysis. Demographics and smoking histories were collected. Quantitative evaluation of low-attenuation areas of the lung on computed tomography imaging was performed using semiautomated software, and the extent of emphysema-like destruction was assessed visually. MEASUREMENTS AND MAIN RESULTS: The extent of emphysema and percentage of low-attenuation areas was greater for patients with primary spontaneous pneumothorax than for control subjects matched for age and smoking history (median, 0.25 vs. 0.00%; P = 0.019) and was also higher for patients with secondary pneumothorax than those with primary spontaneous pneumothorax (16.15 vs. 0.25%, P < 0.001). Patients with primary pneumothorax who smoked had significantly greater low-attenuation area than patients with primary pneumothorax who were nonsmokers (0.7 vs. 0.1%, P = 0.034). CONCLUSIONS: The majority of patients with primary spontaneous pneumothorax had quantifiable evidence of parenchymal destruction and emphysema. The exclusion of patients with underlying lung disease from the definition of primary spontaneous pneumothorax should be reappraised.

Pleural irrigation trial (PIT): a randomised controlled trial of pleural irrigation with normal saline versus standard care in patients with pleural infection.

Pleural infection is increasing in incidence. Despite optimal medical management, up to 30% of patients will die or require surgery. Case reports suggest that irrigation of the pleural space with saline may be beneficial.A randomised controlled pilot study in which saline pleural irrigation (three times per day for 3 days) plus best-practice management was compared with best-practice management alone was performed in patients with pleural infection requiring chest-tube drainage. The primary outcome was percentage change in computed tomography pleural fluid volume from day 0 to day 3. Secondary outcomes included surgical referral rate, hospital stay and adverse events.35 patients were randomised. Patients receiving saline irrigation had a significantly greater reduction in pleural collection volume on computed tomography compared to those receiving standard care (median (interquartile range) 32.3% (19.6-43.7%) reduction versus 15.3% (-5.5-28%) reduction) (p<0.04). Significantly fewer patients in the irrigation group were referred for surgery (OR 7.1, 95% CI 1.23-41.0; p=0.03). There was no difference in length of hospital stay, fall in C-reactive protein, white cell count or procalcitonin or adverse events between the treatment groups, and no serious complications were documented.Saline irrigation improves pleural fluid drainage and reduces referrals for surgery in pleural infection. A large multicentre randomised controlled trial is now warranted to evaluate its effects further.

A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: a proof of principle pilot study.

INTRODUCTION: Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. METHODS: We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. RESULTS: Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. CONCLUSIONS: This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. TRIAL REGISTRATION: UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

Differentiating benign from malignant mediastinal lymph nodes visible at EBUS using grey-scale textural analysis.

BACKGROUND AND OBJECTIVE: Recent data suggest that grey-scale textural analysis on endobronchial ultrasound (EBUS) imaging can differentiate benign from malignant lymphadenopathy. The objective of studies was to evaluate grey-scale textural analysis and examine its clinical utility. METHODS: Images from 135 consecutive clinically indicated EBUS procedures were evaluated retrospectively using MATLAB software (MathWorks, Natick, MA, USA). Manual node mapping was performed to obtain a region of interest and grey-scale textural features (range of pixel values and entropy) were analysed. The initial analysis involved 94 subjects and receiver operating characteristic (ROC) curves were generated. The ROC thresholds were then applied on a second cohort (41 subjects) to validate the earlier findings. RESULTS: A total of 371 images were evaluated. There was no difference in proportions of malignant disease (56% vs 53%, P = 0.66) in the prediction (group 1) and validation (group 2) sets. There was no difference in range of pixel values in group 1 but entropy was significantly higher in the malignant group (5.95 vs 5.77, P = 0.03). Higher entropy was seen in adenocarcinoma versus lymphoma (6.00 vs 5.50, P < 0.05). An ROC curve for entropy gave an area under the curve of 0.58 with 51% sensitivity and 71% specificity for entropy greater than 5.94 for malignancy. In group 2, the entropy threshold phenotyped only 47% of benign cases and 20% of malignant cases correctly. CONCLUSIONS: These findings suggest that use of EBUS grey-scale textural analysis for differentiation of malignant from benign lymphadenopathy may not be accurate. Further studies are required.

Morphologic predictors of a microbiological yield in patients with a tree-in-bud pattern on computed tomography.

PURPOSE: To evaluate the computed tomographic (CT) predictors of a clinically significant yield from microbiological tests in patients with a tree-in-bud pattern. MATERIALS AND METHODS: CT examinations in 53 patients (male=34; mean age=52.9 ± 17.3 y) with a tree-in-bud pattern in whom a diagnostic test (sputum analysis, bronchoalveolar lavage or nasopharyngeal aspirates) had been performed within 2 weeks were identified. The following CT patterns were independently quantified by 2 thoracic radiologists: tree-in-bud, bronchiectasis, bronchial wall thickening, consolidation, ground-glass opacification, and nodules. The presence of cavitation (in nodules and/or consolidation) was recorded. Patient charts were reviewed for the presence of a clinically significant positive microbiological result. RESULTS: A clinically significant causal organism was present in 25/53 (47%) patients. The median extent of a tree-in-bud pattern was 5 [range=1 to 16 (maximum range=0 to 18)], and cavitation was present in 14/53 (26%) patients (cavitating nodules=8, cavitation in consolidation=3, and cavitation in consolidation and nodules=3). There was no independent linkage between the extent of a tree-in-bud pattern and the identification of a clinically significant organism. The microbiological yield was significantly higher if there was coexistent cavitation in nodules or consolidation [11/14 (79%) vs. 14/39 (39%); P=0.005]. On stepwise logistic regression, the only CT predictor of a clinically significant microbiological yield was cavitation on CT (odds ratio=9.7; 95% confidence interval=1.9, 49.9; P<0.01); the extent of a tree-in-bud pattern, concurrent use of antibiotics, age, and sex were not independently linked to a significant microbiological yield. CONCLUSIONS: A specific clinically significant microbiological diagnosis was obtained in approximately 50% of patients with a tree-in-bud pattern. The microbiological yield rises strikingly when a tree-in-bud pattern coexists with cavitation (in nodules or consolidation) but is not predicted by ancillary CT signs or clinical parameters.

Lung clearance index and high-resolution computed tomography scores in primary ciliary dyskinesia.

RATIONALE: Lung clearance index (LCI) is a more sensitive measure of lung function than spirometry in cystic fibrosis (CF) and correlates well with abnormalities in high-resolution computed tomography (HRCT) scanning. We hypothesized LCI would be equally sensitive to lung disease in primary ciliary dyskinesia (PCD). OBJECTIVES: To test the relationships between LCI, spirometry, and HRCT in PCD and to compare them to the established relationships in CF. METHODS: Cross-sectional study of 127 patients with CF and 33 patients with PCD, all of whom had spirometry and LCI, of which a subset of 21 of each had HRCT performed. HRCT was scored for individual features and these features compared with physiological parameters. MEASUREMENTS AND MAIN RESULTS: Unlike in CF, and contrary to our hypothesis, there was no correlation between spirometry and LCI in PCD and no correlation between HRCT features and LCI or spirometry in PCD. CONCLUSIONS: We show for the first time that HRCT, spirometry, and LCI have different relationships in different airway diseases and that LCI does not appear to be a sensitive test of airway disease in advanced PCD. We hypothesize that this results from dissimilarities between the components of large and small airway disease in CF and PCD. These differences may in part lead to the different prognosis in these two neutrophilic airway diseases.

The role of thoracic imaging in the intensive care unit.

Radiology is critical in managing patients on intensive care units. The portable chest X-ray is widely used, but ultrasound and computed tomography are of diagnostic value in selected cases. This article discusses the role of thoracic imaging in the intensive care unit.

Imaging incidental pulmonary nodules.

The incidental nodule is an increasingly common clinical conundrum. This article outlines the characteristics that allow differentiation of benign and malignant pathologies and discusses strategies for their follow up and management.

Imaging the pleura.

Pleural disease is now recognized as an important subspecialty of pulmonary medicine, with increasing provision being made for specialist services and procedures. In response, the field of pleural imaging has advanced in recent years, especially with regard to ultrasound. Salient multimodality imaging techniques are discussed.

Fibrotic idiopathic interstitial pneumonias: HRCT findings that predict mortality.

OBJECTIVES: The study aims were to identify CT features that predict outcome of fibrotic idiopathic interstitial pneumonia (IIP) when information from lung biopsy data is unavailable. METHODS: HRCTs of 146 consecutive patients presenting with fibrotic IIP were studied. Visual estimates were made of the extent of abnormal lung and proportional contribution of fine and coarse reticulation, microcystic (cysts ≤4 mm) and macrocystic honeycombing. A score for severity of traction bronchiectasis was also assigned. Using death as our primary outcome measure, variables were analysed using the Cox proportional hazards model. RESULTS: CT features predictive of a worse outcome were coarse reticulation, microcystic and macrocystic honeycombing, as well as overall extent of lung abnormality (p < 0.001). Importantly, increased severity of traction bronchiectasis, corrected for extent of parenchymal abnormality, was predictive of poor prognosis regardless of the background pattern of abnormal lung (HR = 1.04, CI = 1.03-1.06, p < 0.001). On bivariate Cox analysis microcystic honeycombing was a more powerful determinant of a poor prognosis than macrocystic honeycombing. CONCLUSIONS: In fibrotic IIPs we have shown that increasingly severe traction bronchiectasis is indicative of higher mortality irrespective of the HRCT pattern and extent of disease. Extent of microcystic honeycombing is a more powerful determinant of outcome than macrocystic honeycombing.