Estimation of the transpulmonary pressure from the central venous pressure in mechanically ventilated patients.

Transpulmonary pressure (PL) calculation requires esophageal pressure (PES) as a surrogate of pleural pressure (Ppl), but its calibration is a cumbersome technique. Central venous pressure (CVP) swings may reflect tidal variations in Ppl and could be used instead of PES, but the interpretation of CVP waveforms could be difficult due to superposition of heartbeat-induced pressure changes. Thus, we developed a digital filter able to remove the cardiac noise to obtain a filtered CVP (f-CVP). The aim of the study was to evaluate the accuracy of CVP and filtered CVP swings (ΔCVP and Δf-CVP, respectively) in estimating esophageal respiratory swings (ΔPES) and compare PL calculated with CVP, f-CVP and PES; then we tested the diagnostic accuracy of the f-CVP method to identify unsafe high PL levels, defined as PL>10 cmH2O. Twenty patients with acute respiratory failure (defined as PaO2/FiO2 ratio below 200 mmHg) treated with invasive mechanical ventilation and monitored with an esophageal balloon and central venous catheter were enrolled prospectively. For each patient a recording session at baseline was performed, repeated if a modification in ventilatory settings occurred. PES, CVP and airway pressure during an end-inspiratory and -expiratory pause were simultaneously recorded; CVP, f-CVP and PES waveforms were analyzed off-line and used to calculate transpulmonary pressure (PLCVP, PLf-CVP, PLPES, respectively). Δf-CVP correlated better than ΔCVP with ΔPES (r = 0.8, p = 0.001 vs. r = 0.08, p = 0.73), with a lower bias in Bland Altman analysis in favor of PLf-CVP (mean bias - 0.16, Limits of Agreement (LoA) -1.31, 0.98 cmH2O vs. mean bias - 0.79, LoA - 3.14, 1.55 cmH2O). Both PLf-CVP and PLCVP correlated well with PLPES (r = 0.98, p < 0.001 vs. r = 0.94, p < 0.001), again with a lower bias in Bland Altman analysis in favor of PLf-CVP (0.15, LoA - 0.95, 1.26 cmH2O vs. 0.80, LoA - 1.51, 3.12, cmH2O). PLf-CVP discriminated high PL value with an area under the receiver operating characteristic curve 0.99 (standard deviation, SD, 0.02) (AUC difference = 0.01 [-0.024; 0.05], p = 0.48). In mechanically ventilated patients with acute respiratory failure, the digital filtered CVP estimated ΔPES and PL obtained from digital filtered CVP represented a reliable value of standard PL measured with the esophageal method and could identify patients with non-protective ventilation settings.

Pleural effusion osmolality correlation with pH and glucose level of pleural fluid and its effects on the pleural membrane permeability.

BACKGROUND AND AIM: Pleural effusions (PE) are a common clinical entity resulting from pathologies that affect the pleural space such as congestive heart failure, malignancy and pneumonia. The osmolality of the pleural fluid has never been studied as well as the effects of its changes on the pleural membrane. The purpose of this study was to identify the osmolality levels of PEs of different etiologies and to assess the potential effects of osmolality imbalance on the pleural permeability. MATERIALS AND METHODS: We measured the osmolality of the PEs of 64 consecutive patients (6 with transudative, 11 with parapneumonic and 47 with malignant pleural effusions) that were hospitalized in the University Hospital of Larissa. Subsequently, we selected clinically relevant hyper- and hypo- osmolality levels and performed assessment of the permeability of sheep parietal pleura by means of Ussing chamber experiments. RESULTS: The mean pleural fluid osmolality was 291.7 ± 24.89 mOms/Kg (95 % CI: 285.4-297.9), and it varied among the three groups of PEs (p = 0.05). Transformed osmolality values were associated with pH and glucose levels in the PEs. After exposure of the sheep parietal pleura to 240 mOsm/kg (hyposmolar) the transmesothelial resistance (RTM) significantly increased (p < 0.05) while at 340 mOsm/kg (hyperosmolar) the RTM was not significantly altered. CONCLUSIONS: PEs osmolality differs depending on the underlying pathology and is linked to PE pH and glucose. Hypo-osmotic PEs can lead to decreased pleural permeability. These results warrant further study of the PEs osmolality levels on the function of the pleural mesothelial cells.

High-grade myofibroblastic sarcoma of the pleura: A case report and literature review.

High-grade myofibroblastic sarcoma (HGMS) is a rare cancer that has high recurrence and metastatic rates. Here, we report the first case of HGMS originating from the pleura. Based on the findings of pleural biopsy, pathological examination and immunohistochemical staining, grade III myofibroblastic sarcoma (MS) was diagnosed. The patient underwent eight cycles of chemotherapy (epirubicin and ifosfamide), followed by radiotherapy. As of May 2020, the patient had been followed for six months and no tumor progression had occurred. KEY POINTS: This is the first report of high-grade myofibroblastic sarcoma originating from the pleura. The patient was treated via nonsurgical strategies, including chemotherapy and radiotherapy.

Intrapleural Impedance Sensor Real-Time Tracking of Pneumothorax in a Porcine Model of Air Leak.

In patients with alveolar-to-pleural air leak due to recent surgery or trauma, clinicians tend to manage chest tubes with suction therapy. Nonsuction therapy is associated with shorter chest tube duration but also a higher risk of pneumothorax. We sought to develop an intrapleural electrical impedance sensor for continuous, real-time monitoring of pneumothorax development in a porcine model of air leak as a means of promoting nonsuction therapy. Using thoracoscopy, 2 chest tubes and the pleural impedance sensor were introduced into the pleural space of 3 pigs. Continuous air leak was introduced through 1 chest tube by carbon dioxide insufflation. The second chest tube was placed to suction then transitioned to no suction at increasingly higher air leaks until pneumothorax developed. Simultaneously, real-time impedance measurements were obtained from the pleural sensor. Fluoroscopy spot images were captured to verify the presence or absence of pneumothorax. Statistical Analysis Software was used throughout. With the chest tube on suction, a fully expanded lung was identified by a distinct pleural electrical impedance respiratory waveform. With transition of the chest tube to water seal, loss of contact of the sensor with the lung resulted in an immediate measurement of infinite electrical impedance. Pneumothorax resolution by restoring suction therapy was detected in real time by a return of the normal respiratory impedance waveform. Pleural electrical impedance monitoring detected pneumothorax development and resolution in real time. This simple technology has the potential to improve the safety and quality of chest tube management.

The Relationship of Pleural Manometry With Postthoracentesis Chest Radiographic Findings in Malignant Pleural Effusion.

BACKGROUND: Both elevated pleural elastance (E-PEL) and radiographic evidence of incomplete lung expansion following thoracentesis have been used to exclude patients with a malignant pleural effusion (MPE) from undergoing pleurodesis. This article reports on a cohort of patients with MPE in whom complete drainage was attempted with pleural manometry to determine the frequency of E-PEL and its relation with postthoracentesis radiographic findings. METHODS: Seventy consecutive patients with MPE who underwent therapeutic pleural drainage with pleural manometry were identified. The pressure/volume curves were constructed and analyzed to determine the frequency of E-PEL and the relation of PEL to the postthoracentesis chest radiographic findings. RESULTS: E-PEL and incomplete lung expansion were identified in 36 of 70 (51.4%) and 38 of 70 (54%) patients, respectively. Patients with normal PEL had an OR of 6.3 of having complete lung expansion compared with those with E-PEL (P = .0006). However, 20 of 70 (29%) patients exhibited discordance between postprocedural chest radiographic findings and the pleural manometry results. Among patients who achieved complete lung expansion on the postdrainage chest radiograph, 9 of 32 (28%) had an E-PEL. In addition, PEL was normal in 11 of 38 (34%) patients who had incomplete lung expansion as detected according to the postthoracentesis chest radiograph. CONCLUSIONS: E-PEL and incomplete lung expansion postthoracentesis are frequently observed in patients with MPE. Nearly one-third of the cohort exhibited discordance between the postprocedural chest radiographic findings and pleural manometry results. These findings suggest that a prospective randomized trial should be performed to compare both modalities (chest radiograph and pleural manometry) in predicting pleurodesis outcome.

Assessment of Diaphragm Function and Pleural Pressures During Thoracentesis.

BACKGROUND: This prospective observational study reports on diaphragm excursion, velocity of diaphragm contraction, and changes in pleural pressure that occur with thoracentesis. METHODS: Twenty-eight patients with pleural effusion underwent therapeutic thoracentesis. Diaphragm excursion and velocity of diaphragm contraction were measured with M-mode ultrasonography of the affected hemidiaphragm. Pleural pressure was measured at each aliquot of 250 mL of fluid removal. Fluid removal was continued until no more fluid could be withdrawn, unless there was evidence of nonexpandable lung defined as a pleural elastance greater > 14.5 cm H2O/L and/or ipsilateral anterior chest discomfort. RESULTS: Twenty-three patients had expandable lung, and five patients had nonexpandable lung. Velocity of diaphragm contraction (mean ± SD) increased from 1.5 ± 0.4 cm/s to 2.8 ± 0.4 cm/s pre-thoracentesis and post-thoracentesis, respectively (CI, 0.93-1.61; P < .001) in subjects with expandable lung. Velocity of diaphragm contraction (mean ± SD) increased from 2.0 ± 0.4 cm/s to 2.3 ± 0.4 cm/s pre-thoracentesis and post-thoracentesis (P = .45) in subjects with nonexpandable lung. Diaphragm excursion was significantly increased in subjects with expandable lung at the end of thoracentesis; diaphragm excursion did not increase to a significant extent in patients with nonexpandable lung. CONCLUSIONS: The velocity of diaphragm contraction and diaphragm excursion increased in association with fluid removal with thoracentesis in patients with expandable lung, whereas it did not significantly change in patients with nonexpandable lung. This may derive from improvement in loading conditions of the diaphragm in patients with expandable lung related to its preload and length-tension characteristics.

In Silico Transcriptomic Analysis of Wound-Healing-Associated Genes in Malignant Pleural Mesothelioma.

Background and objectives: Malignant pleural mesothelioma (MPM) is a devastating malignancy with poor prognosis. Reliable biomarkers for MPM diagnosis, monitoring, and prognosis are needed. The aim of this study was to identify genes associated with wound healing processes whose expression could serve as a prognostic factor in MPM patients. Materials and Methods: We used data mining techniques and transcriptomic analysis so as to assess the differential transcriptional expression of wound-healing-associated genes in MPM. Moreover, we investigated the potential prognostic value as well as the functional enrichments of gene ontologies relative to microRNAs (miRNAs) of the significantly differentially expressed wound-healing-related genes in MPM. Results: Out of the 82 wound-healing-associated genes analyzed, 30 were found significantly deregulated in MPM. Kaplan-Meier analysis revealed that low ITGAV gene expression could serve as a prognostic factor favoring survival of MPM patients. Finally, gene ontology annotation enrichment analysis pointed to the members of the hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members as important regulators of the deregulated wound healing genes. Conclusions: 30 wound-healing-related genes were significantly deregulated in MPM, which are potential targets of hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members. Out of those genes, ITGAV gene expression was a prognostic factor of overall survival in MPM. Our results highlight the role of impaired tissue repair in MPM development and should be further validated experimentally.

Suppressive Effects of Aspirin for Postthoracotomy Pleural Adhesion in Rats.

BACKGROUND: Postoperative adhesion is one of major concerns at re-thoracotomy. Aspirin has both the anti-platelet and anti-inflammatory effects, and decreases several cytokines production. OBJECTIVE: We investigated that aspirin could reduce postoperative adhesion formation in a rat model. METHODS: We cauterised the lung visceral pleural to make postoperative adhesion in rats. The animals were allocated to a control group and an aspirin administration group (100 mg/kg/day for 14 days). We performed re-thoracotomy and evaluated the adhesion lengths on day 14. We also investigated the cytokine expression in the adhesion region and the peripheral tissue with platelet-derived growth factor (PDGF), platelet-derived growth factor receptor (PDGFR), alpha smooth muscle actin (α-SMA), transforming growth factor beta 1 (TGF-ß1), and vascular endothelial growth factor-A (VEGF-A), sequentially. RESULTS: The adhesion lengths were significantly shorter in the aspirin group than that in the control group (8.7±2.0 mm vs 11.2±1.1 mm, p=0.024). The expressions of PDGF and PDGFR were lower in the aspirin group than that in the control group on day 3. The expression of α-SMA on fibroblasts decreased in the aspirin group on day 3. There was no significant difference in the expressions of TGF-ß1 and VEGF-A with administration of aspirin. CONCLUSIONS: Aspirin could reduce postoperative pleural adhesion by inhibiting the expression of PDGF.

Pleura revisited: From histology and pathophysiology to pathology and molecular biology.

Pleural cavity has an interesting physiology that when impaired gives rise to pleural effusions a rather frequent problem in respiratory medicine practice. Their aetiology varies widely producing distinct pathological lesions with different prognosis and treatment. The basic morphological features of pleural diseases, neoplastic and non-neoplastic, will be analysed in this review with an emphasis to their pathophysiology, differential diagnosis and clinicopathological correlations.

In patients with unilateral pleural effusion, restricted lung inflation is the principal predictor of increased dyspnoea.

BACKGROUND AND OBJECTIVE: The mechanism of dyspnoea associated with pleural effusion is uncertain. A cohort of patients requiring thoracoscopy for unilateral exudative effusion were investigated for associations between dyspnoea and suggested predictors: impaired ipsilateral diaphragm movement, effusion volume and restricted lung inflation. METHODS: Baseline Dyspnoea Index, respiratory function, and ultrasound assessment of ipsilateral diaphragm movement were assessed prior to thoracoscopy, when effusion volume was measured. Transitional Dyspnoea Index (change from baseline) was assessed 4 and 8 weeks after thoracoscopy. Pearson product moment assessed bivariate correlations and a general linear model examined how well total lung capacity (measuring restricted lung inflation), effusion volume and impaired diaphragm movement predicted Baseline Dyspnoea Index. Un-paired t tests compared the groups with normal and impaired diaphragm movement. RESULTS: 19 patients were studied (14 malignant etiology). Total lung capacity was associated with Baseline Dyspnoea Index (r = 0.68, P = 0.003). Effusion volume (r = -0.138, P = 0.60) and diaphragm movement (P = 0.09) were not associated with Baseline Dyspnoea Index. Effusion volume was larger with impaired diaphragm movement compared to normal diaphragm movement (2.16 ±SD 0.95 vs.1.16 ±0.92 L, P = 0.009). Total lung capacity was lower with impaired diaphragm movement compared to normal diaphragm movement (65.4 ±10.3 vs 78.2 ±8.6% predicted, P = 0.011). The optimal general linear model to predict Baseline Dyspnoea Index used total lung capacity alone (adjusted R2 = 0.42, P = 0.003). In nine participants with controlled effusion, baseline effusion volume (r = 0.775, P = 0.014) and total lung capacity (r = -0.690, P = 0.040) were associated with Transitional Dyspnoea Index. CONCLUSIONS: Restricted lung inflation was the principal predictor of increased dyspnoea prior to thoracoscopic drainage of effusion, with no independent additional association with either effusion volume or impaired ipsilateral diaphragm movement. Restricted lung inflation may be an important determinant of the dyspnoea associated with pleural effusion.

Pressure-decay testing of pleural air leaks in intact murine lungs: evidence for peripheral airway regulation.

The critical care management of pleural air leaks can be challenging in all patients, but particularly in patients on mechanical ventilation. To investigate the effect of central airway pressure and pleural pressure on pulmonary air leaks, we studied orotracheally intubated mice with pleural injuries. We used clinically relevant variables - namely, airway pressure and pleural pressure - to investigate flow through peripheral air leaks. The model studied the pleural injuries using a pressure-decay maneuver. The pressure-decay maneuver involved a 3 sec ramp to 30 cmH2 0 followed by a 3 sec breath hold. After pleural injury, the pressure-decay maneuver demonstrated a distinctive airway pressure time history. Peak inflation was followed by a rapid decrease to a lower plateau phase. The decay phase of the inflation maneuver was influenced by the injury area. The rate of pressure decline with multiple injuries (28 ± 8 cmH2 0/sec) was significantly greater than a single injury (12 ± 3 cmH2 O/sec) (P < 0.05). In contrast, the plateau phase pressure was independent of injury surface area, but dependent upon transpulmonary pressure. The mean plateau transpulmonary pressure was 18 ± 0.7 cm H2 O. Finally, analysis of the inflation ramp demonstrated that nearly all volume loss occurred at the end of inflation (P < 0.001). We conclude that the air flow through peripheral lung injuries was greatest at increased lung volumes and limited by peripheral airway closure. In addition to suggesting an intrinsic mechanism for limiting flow through peripheral air leaks, these findings suggest the utility of positive end-expiratory pressure and negative pleural pressure to maintain lung volumes in patients with pleural injuries.

Pleural manometry in patients with pleural diseases - the usefulness in clinical practice.

Although pleural manometry is a relatively simple medical procedure it is only occasionally used to follow pleural pressure (Ppl) changes during a therapeutic thoracentesis and pneumothorax drainage. As some studies showed that pleural pressure monitoring might be associated with significant advantages, pleural manometry has been increasingly evaluated in the last decade. The major clinical applications of pleural pressure measurements include: the prevention of complications associated with large volume thoracentesis, diagnosis and differentiation between various types of an unexpandable lung and a possible prediction of the efficacy of chest tube drainage in patients with spontaneous pneumothorax. It is well known that the therapeutic thoracentesis might be complicated by cough, chest discomfort, and rarely, by a life threatening condition called reexpansion pulmonary edema (RPE). The serious adverse events of thoracentesis are related to pleural pressure drop rather than to the volume of removed pleural effusion. The use of pleural manometry during pleural fluid withdrawal enables the evaluation of the relationship between withdrawn pleural fluid volume, pleural pressure changes and procedure related complications. Pleural pressure measurement is also an important tool to study the different mechanism of pneumothorax complicating the thoracentesis. Pleural manometry is critical for measurement of pleural elastance, diagnosis of an unexpandable lung and differentiation between trapped lung and lung entrapment. This usually has significant clinical implications in terms of further management of patients with pleural effusion. The paper is a comprehensive review presenting different aspects of pleural pressure measurement in clinical practice.

Cryptococcal Pleuritis Presenting with Lymphocyte-predominant and High Levels of Adenosine Deaminase in Pleural Effusions Coincident with Pulmonary Tuberculosis.

Co-infection with cryptococcus and tuberculosis has rarely been reported. We herein report a case of an 80-year-old man with cryptococcal pleuritis concurrent with pulmonary tuberculosis. He was admitted for progression of left pleural effusion and consolidation in the left upper lobe. Culture for Mycobacterium tuberculosis was positive in sputum, and analyses of pleural effusion revealed lymphocyte-predominant high levels of adenosine deaminase (ADA). Medical thoracoscopy revealed massive infiltration of Cryptococcus neoformans in pleura without granuloma. This is the first case report of cryptococcal pleuritis coincident with pulmonary tuberculosis. Cryptococcal pleuritis should be ruled out when the adenosine deaminase levels are elevated in pleural effusion.