Search

Maged Hassan,1 Shefaly Patel,2 Ahmed S Sadaka,1 Eihab O Bedawi,2 John P Corcoran,3 José M Porcel4 1Chest Diseases Department, Alexandria University Faculty of Medicine, Alexandria, Egypt; 2Oxford Centre for Respiratory Medicine, Oxford University Hospitals, Oxford, UK; 3Department of Respiratory Medicine, University Hospitals Plymouth NHS Trust, Plymouth, UK; 4Department of Internal Medicine, Arnau de Vilanova University Hospital, Lleida, SpainCorrespondence: Maged HassanChest Diseases Department, Alexandria University Faculty of Medicine, Alexandria, EgyptTel +20 3 591-8662Email magedhmf@gmail.comAbstract: Pleural infection in adults has considerable morbidity and continues to be a life-threatening condition. The term “pleural infection” encompasses complicated parapneumonic effusions and primary pleural infections, and includes but is not limited to empyema, which refers to collection of pus in the pleural cavity. The incidence of pleural infection in adults has been continuously increasing over the past two decades, particularly in older adults, and most of such patients have comorbidities. Management of pleural infection requires prolonged duration of hospitalization (average 14 days). There are recognized differences in microbial etiology of pleural infection depending on whether the infection was acquired in the community or in a health-care setting. Anaerobic bacteria are acknowledged as a major cause of pleural infection, and thus anaerobic coverage in antibiotic regimens for pleural infection is mandatory. The key components of managing pleural infection are appropriate antimicrobial therapy and chest-tube drainage. In patients who fail medical therapy by manifesting persistent sepsis despite standard measures, surgical intervention to clear the infected space or intrapleural fibrinolytic therapy (in poor surgical candidates) are recommended. Recent studies have explored the role of early intrapleural fibrinolytics or first-line surgery, but due to considerable costs of such interventions and the lack of convincing evidence of improved outcomes with early use, early intervention cannot be recommended, and further evidence is awaited from ongoing studies. Other areas of research include the role of routine molecular testing of infected pleural fluid in improving the rate of identification of causative organisms. Other research topics include the benefit of such interventions as medical thoracoscopy, high-volume pleural irrigation with saline/antiseptic solution, and repeated thoracentesis (as opposed to chest-tube drainage) in reducing morbidity and improving outcomes of pleural infection. This review summarizes current knowledge and practice in managing pleural infection and future research directions.Keywords: pleural infection, empyema, respiratory infections, pneumonia

Background: Lung ultrasound (LUS) is increasingly used as an extension of physical examination, informing clinical diagnosis, and decision making. There is particular interest in the assessment of patients with pulmonary congestion and extravascular lung water, although gaps remain in the evidence base underpinning this practice as a result of the limited evaluation of its inter-rater reliability and comparison with more established radiologic tests., Methods: 30 patients undergoing haemodialysis were prospectively recruited to an observational cohort study (NCT01949402). Patients underwent standardised LUS assessment before, during and after haemodialysis; their total LUS B-line score was generated, alongside a binary label of whether appearances were consistent with an interstitial syndrome. LUS video clips were recorded and independently scored by two blinded expert clinician sonographers. Low-dose non-contrast thoracic CT, pre- and post dialysis, was used as a "gold standard" radiologic comparison., Results: LUS detected a progressive reduction in B-line scores in almost all patients undergoing haemodialysis, correlating with the volume of fluid removed once individuals with no or minimal B-lines upon pre-dialysis examination were discounted. When comparing CT scans pre- and post dialysis, radiologic evidence of the change in fluid status was only identified in a single patient., Conclusions: This is the first study to demonstrate that LUS detects changes in extravascular lung water caused by changing fluid status during haemodialysis using a blinded outcome assessment and that LUS appears to be more sensitive than CT for this purpose. Further research is needed to better understand the role of LUS in this and similar patient populations, with the aim of improving clinical care and outcomes.

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively ( P  = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) ( P  = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) ( P  = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).

Competing Interests: Competing interests: None declared. BTS Declarations of Interest forms have been completed by all members for each year they were part of the GDG. Details of these forms can be obtained from BTS Head Office. 'Declarations of Interests' was a standing item at each GDG meeting.

Rationale: Sonographic septations are assumed to be important clinical predictors of outcome in pleural infection, but the evidence for this is sparse. The inflammatory and fibrinolysis-associated intrapleural pathway(s) leading to septation formation have not been studied in a large cohort of pleural fluid (PF) samples with confirmed pleural infection matched with ultrasound and clinical outcome data. Objectives: To assess the presence and severity of septations against baseline PF PAI-1 (Plasminogen-Activator Inhibitor-1) and other inflammatory and fibrinolysis-associated proteins as well as to correlate these with clinically important outcomes. Methods: We analyzed 214 pleural fluid samples from PILOT (Pleural Infection Longitudinal Outcome Study), a prospective observational pleural infection study, for inflammatory and fibrinolysis-associated proteins using the Luminex platform. Multivariate regression analyses were used to assess the association of pleural biological markers with septation presence and severity (on ultrasound) and clinical outcomes. Measurements and Main Results: PF PAI-1 was the only protein independently associated with septation presence ( P  < 0.001) and septation severity ( P  = 0.003). PF PAI-1 concentrations were associated with increased length of stay ( P  = 0.048) and increased 12-month mortality ( P  = 0.003). Sonographic septations alone had no relation to clinical outcomes. Conclusions: In a large and well-characterized cohort, this is the first study to associate pleural biological parameters with a validated sonographic septation outcome in pleural infection. PF PAI-1 is the first biomarker to demonstrate an independent association with mortality. Although PF PAI-1 plays an integral role in driving septation formation, septations themselves are not associated with clinically important outcomes. These novel findings now require prospective validation.