Validation of Noninvasive Remote Dielectric Sensing System to Quantify Lung Fluid Levels

Background: The accuracy of the remote dielectric sensing (ReDSTM) system, which is a noninvasive electromagnetic-based technology to quantify lung fluid levels, particularly among those with small body size, remains uncertain. Methods: Hospitalized patients with and without heart failure underwent assessment of lung fluid levels with ReDS and successive chest computed tomography imaging. We performed a correlation analysis of the ReDS measurement, representing lung fluid levels, and computed tomography-derived high attenuation area percentage, which also provides a spatial quantification of lung fluid level. Results: A total of 46 patients (median 76 years old, 28 men), including 28 patients with heart failure, were included. The median ReDS value was 28% (interquartile: 23%, 33%), and the median percentage of high attenuation area was 21.6% (14.4%, 28.5%). ReDS values and percentage of high attenuation area were moderately correlated (r = 0.65, p < 0.001), irrespective of the existence of heart failure. ReDS value independently predicted the percentage of high attenuation area seen on computed tomography (p < 0.001). Conclusions: The ReDS system may be a promising, noninvasive tool to quantify fluid lung levels, as validated by comparison with chest computed tomography imaging. Further studies are warranted to validate the utility and applicability of this technology to a variety of clinical scenarios.

Pulmonary Interstitial Matrix and Lung Fluid Balance From Normal to the Acutely Injured Lung

This review analyses the mechanisms by which lung fluid balance is strictly controlled in the air-blood barrier (ABB). Relatively large trans-endothelial and trans-epithelial Starling pressure gradients result in a minimal flow across the ABB thanks to low microvascular permeability aided by the macromolecular structure of the interstitial matrix. These edema safety factors are lost when the integrity of the interstitial matrix is damaged. The result is that small Starling pressure gradients, acting on a progressively expanding alveolar barrier with high permeability, generate a high transvascular flow that causes alveolar flooding in minutes. We modeled the trans-endothelial and trans-epithelial Starling pressure gradients under control conditions, as well as under increasing alveolar pressure (Palv) conditions of up to 25 cmH2O. We referred to the wet-to-dry weight (W/D) ratio, a specific index of lung water balance, to be correlated with the functional state of the interstitial structure. W/D averages ∼5 in control and might increase by up to ∼9 in severe edema, corresponding to ∼70% loss in the integrity of the native matrix. Factors buffering edemagenic conditions include: (i) an interstitial capacity for fluid accumulation located in the thick portion of ABB, (ii) the increase in interstitial pressure due to water binding by hyaluronan (the “safety factor” opposing the filtration gradient), and (iii) increased lymphatic flow. Inflammatory factors causing lung tissue damage include those of bacterial/viral and those of sterile nature. Production of reactive oxygen species (ROS) during hypoxia or hyperoxia, or excessive parenchymal stress/strain [lung overdistension caused by patient self-induced lung injury (P-SILI)] can all cause excessive inflammation. We discuss the heterogeneity of intrapulmonary distribution of W/D ratios. A W/D ∼6.5 has been identified as being critical for the transition to severe edema formation. Increasing Palv for W/D &gt; 6.5, both trans-endothelial and trans-epithelial gradients favor filtration leading to alveolar flooding. Neither CT scan nor ultrasound can identify this initial level of lung fluid balance perturbation. A suggestion is put forward to identify a non-invasive tool to detect the earliest stages of perturbation of lung fluid balance before the condition becomes life-threatening.

In Search of Clinical Impact: Advanced Monitoring Technologies in Daily Heart Failure Care

Despite significant advances in the management of heart failure (HF), further improvement in the outcome of this chronic and progressive disease is still considered a major unmet need. Recurrent hospitalizations due to decompensated HF frequently occur, resulting in increased morbidity and mortality rates. Past attempts at early detection of clinical deterioration were mainly based on monitoring of signs and symptoms of HF exacerbation, which have mostly given disappointing results. Extensive research of the pathophysiology of HF decompensation has indicated that hemodynamic alterations start days prior to clinical manifestation. Novel technologies aim to monitor these minute hemodynamic changes, allowing time for therapeutic interventions to prevent hemodynamic derangement and HF exacerbation. The latest noticeable advancements include assessment of lung fluid volume, wearable devices with integrated sensors, and microelectromechanical systems-based implantable devices for continuous measurement of cardiac filling pressures. This manuscript will review the rationale for monitoring HF patients and discuss previous and ongoing attempts to develop clinically meaningful monitoring devices to improve daily HF health care, with particular emphasis on the recent advances and clinical trials relevant to this evolving field.

Perioperative Pulmonary Atelectasis: Part I. Biology and Mechanisms

Pulmonary atelectasis is common in the perioperative period. Physiologically, it is produced when collapsing forces derived from positive pleural pressure and surface tension overcome expanding forces from alveolar pressure and parenchymal tethering. Atelectasis impairs blood oxygenation and reduces lung compliance. It is increasingly recognized that it can also induce local tissue biologic responses, such as inflammation, local immune dysfunction, and damage of the alveolar–capillary barrier, with potential loss of lung fluid clearance, increased lung protein permeability, and susceptibility to infection, factors that can initiate or exaggerate lung injury. Mechanical ventilation of a heterogeneously aerated lung (e.g., in the presence of atelectatic lung tissue) involves biomechanical processes that may precipitate further lung damage: concentration of mechanical forces, propagation of gas–liquid interfaces, and remote overdistension. Knowledge of such pathophysiologic mechanisms of atelectasis and their consequences in the healthy and diseased lung should guide optimal clinical management.

Validation of Remote Dielectric Sensing (ReDS) in Monitoring Adult Patients Affected by COVID-19 Pneumonia

Remote dielectric sensing (ReDS) is a non-invasive electromagnetic wave technology which provides an accurate reading of lung fluid content, and it has been reported as a valid tool in monitoring heart failure patients. Considering that morphological alterations in COVID-19 include pulmonary edema, the purpose of the present study was to evaluate the reliability of ReDS technology in assessing the excess of lung fluid status in COVID-19 pneumonia, as compared to CT scans. In this pilot single center study, confirmed COVID-19 patients were enrolled on admission to an intermediate care unit. Measurements with the ReDS system and CT scans were performed on admission and at weeks 1 and 2. Eleven patients were recruited. The average change in ReDS was −3.1 ± 1.7 after one week (p = 0.001) and −4.6 ± 2.9 after two weeks (p = 0.006). A similar trend was seen in total CT score (−3.3 ± 2.1, p = 0.001). The level of agreement between ReDS and CT changes yielded a perfect result. Statistically significant changes were observed in lactate dehydrogenase, lymphocytes, and c-reactive protein over 2 weeks. This pilot study shows that ReDS can track changes in lung involvement according to the severity of COVID-19. Further studies to detect early clinical deterioration are needed.

Aerosolized nanoliposomal carrier of remdesivir: an effective alternative for COVID-19 treatment in vitro

Aim: To formulate an aerosolized nanoliposomal carrier for remdesivir (AL-Rem) against coronavirus disease 2019. Methods: AL-Rem was prepared using modified hydration technique. Cytotoxicity in lung adenocarcinoma cells, stability and aerodynamic characteristics of developed liposomes were evaluated. Results: AL-Rem showed high encapsulation efficiency of 99.79%, with hydrodynamic diameter of 71.46 ± 1.35 nm and surface charge of -32 mV. AL-Rem demonstrated minimal cytotoxicity in A549 cells and retained monolayer integrity of Calu-3 cells. AL-Rem showed sustained release, with complete drug release obtained within 50 h in simulated lung fluid. Long-term stability indicated >90% drug recovery at 4°C. Desirable aerosol performance, with mass median aerodynamic diameter of 4.56 ± 0.55 and fine particle fraction of 74.40 ± 2.96%, confirmed successful nebulization of AL-Rem. Conclusion: AL-Rem represents an effective alternative for coronavirus disease 2019 treatment.