Lucía Ferreiro

Background and Objective: Pleural effusion (PLE) is a common clinical condition with a broad spectrum of underlying etiologies. Accurate estimation of pleural fluid (PF) volume can support clinical decision-making, particularly in critically ill patients, by guiding invasive procedures, monitoring treatment response, and informing prognosis. This review aims to provide an overview of the main ultrasound (US) techniques for estimating PLE volume and to discuss their limitations in routine practice. Methods: A narrative review of the literature was conducted, synthesizing the most relevant evidence identified through structured manual searches and consultation of authoritative sources Key Content and Findings: Computed tomography (CT) is considered the reference standard for volumetric assessment, but it is costly, exposes patients to ionizing radiation, and often requires transfer, which may carry additional risks. Thoracic US has emerged as a reliable bedside alternative, offering high sensitivity and specificity for the detection of even small effusions and showing good correlation with CT measurements. Multiple sonographic approaches are available for estimating PLE volume, including linear methods based on interpleural distances and more complex multiplanar models. Linear formulas are rapid and easy to apply at the bedside, with reported correlation coefficients (R²) ranging from 0.68 to 0.90 when compared with drained volumes, whereas multiplanar models achieve higher precision (R² up to 0.98 versus CT) but require greater technical expertise. Accuracy is influenced by patient-related factors, including body position and mechanical ventilation, as well as operator experience and the presence of associated lung pathology such as consolidations or loculated effusions, which may lead to underestimation of true volume. Standardized protocols and adequate training are therefore essential to improve reproducibility. Conclusions: Although US does not replace CT or other imaging modalities, it provides a non-invasive, rapid, and generally reliable estimate of PF volume that complements bedside clinical judgment.

Background: Intrapleural enzyme therapy (IET) is widely used for pleural infections, including complicated parapneumonic effusions and empyema; however, the role of saline lavage alone or in combination with IET remains uncertain. Methods: The SCOPE trial was a two-centre, prospective, randomised superiority study designed to determine whether saline lavage alone or combined with IET was superior to IET alone in adults with pleural infection. Patients were randomised in a 1:1:1 ratio to saline lavage alone, saline lavage plus IET (urokinase and DNase) or IET alone. Patients and outcome assessors were blinded to the treatment allocation. The primary end-point was the duration of pleural drainage. Secondary end-points included radiographic resolution, need for additional interventions, length of hospital stay, mortality and adverse events. Results: 89 patients were analysed in three groups (saline lavage, n=30; saline+IET, n=30; IET, n=29). Baseline characteristics were broadly similar across the groups. The median (interquartile range) drainage duration was longer with saline lavage alone (4.0 (3.0–6.75) days) than with IET alone (3.0 (2.0–4.0) days; p=0.01) or saline lavage plus IET (3.0 (3.0–3.75) days; p=0.01). No significant difference was observed between the two IET-containing regimens (p=0.24). Secondary outcomes showed no clear advantage for saline lavage alone or in combination with IET. Conclusions: In pleural infection, saline lavage alone results in a longer drainage duration than IET. In this small superiority trial, adding saline lavage to IET did not demonstrate a clinically meaningful advantage over IET alone.

Letter to the Editor Paradigm shift in the diagnosis of tuberculous pleural effusion: impact of epidemiology Lucía Ferreiro, María E. Toubes, Luis Valdés

Background: Cryptococcus neoformans infection occurs more frequently in immunocompromised individuals, with pulmonary and cerebral forms being the most common. Among pulmonary manifestations, pleural effusion in cryptococcosis is an exceptional presentation. Methods: We present a series of four cases of cryptococcosis with empyema caused by Cryptococcus neoformans diagnosed at a single centre and we conducted a systematic review of the literature on cases of cryptococcal pleural effusion. 32 were selected for data extraction and analysis. Results: The median patient age was 59 years, with 72% over 50 years old. The infection was more common in males (72%). 62% cases were disseminated infection and 34% localized. Cryptococcus neoformans was the most frequent species (90%). Common predisposing factors included cirrhosis (22%), solid organ transplantation (12.5%), and malignancy (19%). HIV infection was infrequent (6%). Pleural effusions were unilateral in 67% of cases and bilateral in 32%. Radiological findings included consolidations (25%), ground-glass opacities, nodules and pleural thickening (15%). Cryptococcal serum antigen was positive in 64% of tested cases, and blood cultures were positive in 57% as well. Lumbar puncture detected Cryptococcus in 7 of 20 cases tested. Microbiological confirmation from pleural fluid was achieved in 75% of cases, with antigen testing aiding diagnosis when cultures were negative. Additional methods included pleural biopsy (positive in 8 cases), bronchoalveolar lavage, EBUS-TBNA, and lung tissue staining. Pleural fluid analysis revealed mostly exudates with lymphocytic predominance (67%). Adenosine deaminase levels were below 35 UI/L in 90% of the tested cases. Glucose and pH values were generally normal. Mortality was documented in 37% of cases. Conclusions: Cryptococcal pleural infection is rare and mainly affects immunocompromised, older males, often with disseminated disease. Pleural effusions are typically lymphocyte-predominant and unilateral. Cryptococcal antigen detection in pleural fluid improves diagnosis, especially when cultures fail. Despite treatment, mortality rates remain notably high.

Background: The characteristics of pleural fluid (PF) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are poorly understood. During the pandemic, several cases of pleural effusion (PE) have been reported, but no clear conclusions have been reached regarding the features of this fluid. This systematic review aimed to analyze and summarize the available evidence on PF attributes in patients with SARS-CoV-2 infection. Methods: Systematic literature search using the PRISMA methodology of studies describing PF characteristics of SARS-CoV-2 patients and treatment of PE. Results: Eighteen articles (32 patients and 37 PF samples) were included. Median age was 61 years (range, 25–81 years), male/female ratio 5.4:1. PE was predominantly unilateral (71.4%), with no distinction between one side and the other; it usually extended over 2/3 of the hemithorax (50%) and its appearance was variable [serous (50%), hematic or serohematic (28.1%) and purulent (21.9%)]. PF was exudative in 88.9% of cases, but with PF protein and PF/serum protein ratio values less than 3 g/dL and 0.5 in 36.7% and 54.5%, respectively. The pH and glucose values were less than 7.20 and 60 mg/dL in 28.6% and 24% of cases, respectively. The percentage of neutrophils (≥50%) was higher than that of lymphocytes/monocytes [12/26 (46.2%) vs. 7/26 (26.9%), respectively]. Polymerase chain reaction (PCR) on PF was positive for SARS-CoV-2 in 6/23 cases (26.1%) and for other pathogens in 8 (5 bacteria and 3 fungi). Almost all patients underwent thoracentesis and the medical treatment received by the cases with positive PCR for SARS-CoV-2 on PF varied. Patient follow-up was provided in 25 cases and 10 cases died (40%). Conclusions: PE from coronavirus disease 2019 (COVID-19) infection is more frequent among males aged 50–80 years, generally unilateral and large. Its appearance is variable, with features of lactate dehydrogenase (LDH)-discordant exudate, usually predominantly neutrophilic, with treatment like that of any other PE. PE from COVID-19 infection is a poor prognostic sign and associated with worse mortality.

Pleural effusion induces an increase in pleural pressure, resulting in a cascade of changes in the physiological parameters of the thoracic cavity. These changes include increased volume of the rib cage, abnormal gas exchange, impaired respiratory mechanics, and abnormal diaphragmatic movements. Such alterations have a significant clinical impact, including the development of specific symptoms such as dyspnoea. Dyspnoea secondary to pleural effusion has a complex physiopathology. Notably, the severity of dyspnoea often shows a poor correlation with effusion size and may not improve after fluid drainage. The symptomatic relief experienced by patients after fluid drainage is largely attributed to improvements in the length–tension relationship of the respiratory muscles. Importantly, dyspnoea in these cases results from the abnormal shape and restricted motion of the ipsilateral hemidiaphragm, coupled with an increased compensatory respiratory drive aimed at preserving adequate ventilation. Fluid drainage reduces diaphragmatic distension, restoring diaphragmatic mobility, reducing inspiratory neural drive, and enhancing the neuromechanical coupling of the diaphragm, all of which contribute to dyspnoea relief. This review explores current evidence regarding the pathophysiological mechanisms underlying dyspnoea in pleural effusion and the therapeutic effects of thoracentesis.

Nocardia spp. are a pathogen that can cause both localized infection in different organs and disseminated infection. Although it is not always associated with immunosuppression situations, the increase in these conditions, along with the development of novel diagnostic methods, makes this diagnosis increasingly common. In this manuscript, we describe three cases of pleural infection caused by different species of Nocardia. The lesson learned is that when faced with pleural infection, Nocardia infection should be ruled out, and if confirmed, performing an imaging study of the central nervous system is mandatory to exclude a brain abscess. Close monitoring is required to control the clinical course and prevent drug-induced toxicity.