Randomised trial of indwelling pleural catheters for refractory transudative pleural effusions.

OBJECTIVE: Refractory symptomatic transudative pleural effusions are an indication for pleural drainage. There has been supportive observational evidence for the use of indwelling pleural catheters (IPCs) for transudative effusions, but no randomised trials. We aimed to investigate the effect of IPCs on breathlessness in patients with transudative pleural effusions when compared with standard care. METHODS: A multicentre randomised controlled trial, in which patients with transudative pleural effusions were randomly assigned to either an IPC (intervention) or therapeutic thoracentesis (TT; standard care). The primary outcome was mean daily breathlessness score over 12 weeks from randomisation. RESULTS: 220 patients were screened from April 2015 to August 2019 across 13 centres, with 33 randomised to intervention (IPC) and 35 to standard care (TT). Underlying aetiology was heart failure in 46 patients, liver failure in 16 and renal failure in six. In primary outcome analysis, the mean±sd breathlessness score over the 12-week study period was 39.7±29.4 mm in the IPC group and 45.0±26.1 mm in the TT group (p=0.67). Secondary outcomes analysis demonstrated that mean±sd drainage was 17 412±17 936 mL and 2901±2416 mL in the IPC and TT groups, respectively. A greater proportion of patients had at least one adverse event in the IPC group (p=0.04). CONCLUSION: We found no significant difference in breathlessness over 12 weeks between IPCs or TT. TT is associated with fewer complications and IPCs reduced the number of invasive pleural procedures required. Patient preference and circumstances should be considered in selecting the intervention in this cohort.

Ambulatory management of secondary spontaneous pneumothorax: a randomised controlled trial.

Secondary spontaneous pneumothorax (SSP) is traditionally managed with an intercostal chest tube attached to an underwater seal. We investigated whether use of a one-way flutter valve shortened patients' length of stay (LoS).This open-label randomised controlled trial enrolled patients presenting with SSP and randomised to either a chest tube and underwater seal (standard care: SC) or ambulatory care (AC) with a flutter valve. The type of flutter valve used depended on whether at randomisation the patient already had a chest tube in place: in those without a chest tube a pleural vent (PV) was used; in those with a chest tube in situ, an Atrium Pneumostat (AP) valve was attached. The primary end-point was LoS.Between March 2017 and March 2020, 41 patients underwent randomisation: 20 to SC and 21 to AC (13=PV, 8=AP). There was no difference in LoS in the first 30 days following treatment intervention: AC (median=6 days, IQR 14.5) and SC (median=6 days, IQR 13.3). In patients treated with PV there was a high rate of early treatment failure (6/13; 46%), compared to patients receiving SC (3/20; 15%) (p=0.11) Patients treated with AP had no (0/8 0%) early treatment failures and a median LoS of 1.5 days (IQR 23.8).There was no difference in LoS between ambulatory and standard care. Pleural Vents had high rates of treatment failure and should not be used in SSP. Atrium Pneumostats are a safer alternative, with a trend towards lower LoS.

The role of serum procalcitonin in establishing the diagnosis and prognosis of pleural infection.

BACKGROUND: Bacterial pleural infection requires prompt identification to enable appropriate investigation and treatment. In contrast to commonly used biomarkers such as C-reactive protein (CRP) and white cell count (WCC), which can be raised due to non-infective inflammatory processes, procalcitonin (PCT) has been proposed as a specific biomarker of bacterial infection. The utility of PCT in this role is yet to be validated in a large prospective trial. This study aimed to identify whether serum PCT is superior to CRP and WCC in establishing the diagnosis of bacterial pleural infection. METHODS: Consecutive patients presenting to a tertiary pleural service between 2008 and 2013 were recruited to a well-established pleural disease study. Consent was obtained to store pleural fluid and relevant clinical information. Serum CRP, WCC and PCT were measured. A diagnosis was agreed upon by two independent consultants after a minimum of 12 months. The study was performed and reported according to the STARD reporting guidelines. RESULTS: 80/425 patients enrolled in the trial had a unilateral pleural effusion secondary to infection. 10/80 (12.5%) patients had positive pleural fluid microbiology. Investigations for viral causes of effusion were not performed. ROC curve analysis of 425 adult patients with unilateral undiagnosed pleural effusions showed no statistically significant difference in the diagnostic utility of PCT (AUC 0.77), WCC (AUC 0.77) or CRP (AUC 0.85) for the identification of bacterial pleural infection. Serum procalcitonin >0.085 µg/l has a sensitivity, specificity, negative predictive value and positive predictive value of 0.69, 0.80, 0.46 and 0.91 respectively for the identification of pleural infection. The diagnostic utility of procalcitonin was not affected by prior antibiotic use (p = 0.80). CONCLUSIONS: The study presents evidence that serum procalcitonin is not superior to CRP and WCC for the diagnosis of bacterial pleural infection. The study suggests routine procalcitonin testing in all patients with unilateral pleural effusion is not beneficial however further investigation may identify specific patient subsets that may benefit. TRIAL REGISTRATION: The trial was registered with the UK Clinical Research Network ( UKCRN ID 8960 ). The trial was approved by the South West Regional Ethics Committee (Ethical approval number 08/H0102/11).

Primary spontaneous pneumothorax: a cohort study of VATS with talc poudrage.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is an increasingly common treatment for recurrent or persistent primary spontaneous pneumothorax (PSP). Surgery usually involves diffuse treatment of the pleura and possible targeted therapy to areas of bullous disease. The purpose of this large cohort study was to examine incidence of recurrence after VATS and identify predictors of outcome. METHODS: Patients undergoing VATS for PSP at a single centre between 2000 and 2012 were prospectively enrolled. All patients underwent talc poudrage. Targeted surgical techniques were used based on presence of air leak and Vanderschueren's stage. Patients had clinical and radiological follow-up for at least 2 years (median 8.5 years). RESULTS: 1415 patients with PSP underwent VATS with talc poudrage. The most frequent indications were recurrent pneumothorax (92.2%) and persistent air leak (6.5%). The complication rate was 2.0% of which 1.7% was prolonged air leak. There was no mortality. Median length of stay was 5 days. Recurrent pneumothorax occurred in 26 patients (1.9%). At the time of surgery, 592 patients smoked (43%) and they had a significantly higher incidence of recurrence (24/575, 4.2%) than non-smokers (2/805, 0.2%), p<0.001. The incidence of recurrence in those undergoing bullae suturing (3.8%, n=260) was significant higher than those undergoing poudrage alone (0.3%, p=0.036). CONCLUSION: The marked difference in recurrence between smokers and non-smokers suggests this as an important predictor of outcome. This study demonstrates a low incidence of recurrence and complications for patients with PSP undergoing VATS with talc poudrage. Talc poudrage requires prospective comparison with pleurectomy and mechanical abrasion.

ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax.

Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research.The European Respiratory Society's Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence.Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach.In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required.

Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score.

BACKGROUND: Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system. METHODS: Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated. RESULTS: Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228-549; n=43), 130 days (47-467; n=129) and 44 days (22-77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, p<0.01), 3 months (0.84 vs 0.75, p<0.01) and 6 months (0.85 vs 0.76, p<0.01). CONCLUSIONS: The LENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population.

Training opportunities in thoracic ultrasound for respiratory trainees: are current guidelines practical?

Introduction: Respiratory trainees in the UK face challenges in meeting current Royal College of Radiologists (RCR) Level 1 training requirements for thoracic ultrasound (TUS) competence, specified as attending 'at least one session per week over a period of no less than 3 months, with approximately five scans per session performed by the trainee (under supervision of an experienced practitioner)'. We aimed to clarify where TUS training opportunities currently exist for respiratory registrars. Methods: Data were collected (over a 4-week period) to clarify the number of scans (and therefore volume of training opportunities) within radiology departments and respiratory services in hospitals in the South West, North West deaneries and Oxford. Results: 14 hospitals (including three tertiary pleural centres) provided data. Of 964 scans, 793 (82.3%) were conducted by respiratory teams who performed a mean of 17.7 scans per week, versus 3.1 TUS/week in radiology departments. There was no radiology session in any hospital with ≥5 TUS performed, whereas 8/14 (86%) of respiratory departments conducted such sessions. Almost half (6/14) of radiology departments conducted no TUS scans in the period surveyed. Conclusions: The currently recommended exposure of regularly attending a list or session to undertake five TUS is not achievable in radiology departments. The greatest volume of training opportunities exists within respiratory departments in a variety of scheduled and unscheduled settings. Revision of the competency framework in TUS, and where this is delivered, is required.

Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project.

RATIONALE: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. OBJECTIVES: To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. METHODS: Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. RESULTS: We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22-58] to 16% [8-31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247-2,984] over 72 h of therapy; P < 0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent surgery. Three patients (4.9%) received blood transfusions for gradual pleural blood loss; none were hemodynamically compromised. Pain requiring escalation of analgesia affected 36% of patients; none required cessation of therapy. CONCLUSIONS: These pilot data suggest that a starting dose of 5 mg of tPA administered intrapleurally twice daily in combination with 5 mg of DNase for the treatment of pleural infection is safe and effective. This regimen should be tested in future randomized controlled trials.

The management of benign non-infective pleural effusions.

The evidence base concerning the management of benign pleural effusions has lagged behind that of malignant pleural effusions in which recent randomised trials are now informing current clinical practice and international guidelines.The causes of benign pleural effusions are broad, heterogenous and patients may benefit from individualised management targeted at both treating the underlying disease process and direct management of the fluid. Pleural effusions are very common in a number of non-malignant pathologies, such as decompensated heart failure, and following coronary artery bypass grafting. Pleural fluid analysis forms an important basis of the diagnostic evaluation, and more specific assays and imaging modalities are helpful in specific subpopulations.Options for management beyond treatment of the underlying disorder, whenever possible, include therapeutically aspirating the fluid, talc pleurodesis and insertion of an indwelling pleural catheter. Randomised trials will inform clinicians in the future as to the risks and benefits of these options providing a guide as to how best to manage patient symptoms in this challenging clinical setting.

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.

Unilateral Pleural Effusions with More Than One Apparent Etiology. A Prospective Observational Study.

RATIONALE: Evaluation of a pleural effusion has historically focused on establishing a single etiology. Pleural fluid may accumulate through multiple pathophysiological processes. The prevalence of multiple causes for pleural effusions has not been established. The identification of contributing processes may improve clinical outcomes. OBJECTIVES: The objective of this prospectively collected case series was to establish the prevalence and nature of multiple etiologies for a unilateral pleural effusion. METHODS: Consecutive patients presenting with an undiagnosed unilateral pleural effusion were recruited at a tertiary pleural center. Patients underwent a comprehensive structured diagnostic clinical evaluation and were followed up for a minimum of 12 months, after which one or more diagnoses were recorded independently by two experienced clinicians. MEASUREMENTS AND MAIN RESULTS: One hundred thirty patients were recruited to the study over a 24-month period, and 126 patients completed follow up. Altogether, 88 patients (70%) had a single cause for their pleural effusion, and 38 (30%) had multiple causes. Serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) greater than or equal to 1,500 pg/ml was predictive of multiple etiologies. NT-pro BNP had a sensitivity and specificity of 79 and 88%, respectively, for establishing heart failure as a primary or contributory cause. Thirteen patients with a malignant pleural effusion also had an NT-pro BNP greater than or equal to 1,500 pg/ml. CONCLUSIONS: This study is the first to estimate the prevalence of more than one identifiable cause for a unilateral pleural effusion. Out of 130 study subjects, 38 (30%) had multiple causes for an effusion. The identification of multiple pathologies underlying an accumulation of fluid in the pleural space may be important in determining optimum treatment and improving patients' symptoms.

Spontaneous pneumothorax: time to rethink management?

There are substantial differences in international guidelines for the management of pneumothorax and much geographical variation in clinical practice. These discrepancies have, in part, been driven by a paucity of high-quality evidence. Advances in diagnostic techniques have increasingly allowed the identification of lung abnormalities in patients previously labelled as having primary spontaneous pneumothorax, a group in whom recommended management differs from those with clinically apparent lung disease. Pathophysiological mechanisms underlying pneumothorax are now better understood and this may have implications for clinical management. Risk stratification of patients at baseline could help to identify subgroups at higher risk of recurrent pneumothorax who would benefit from early intervention to prevent recurrence. Further research into the roles of conservative management, Heimlich valves, digital air-leak monitoring, and pleurodesis at first presentation might lead to an increase in their use in the future.