Effects of physical property changes of expelled respiratory liquid on atomization morphology

A better understanding of the fluid dynamics of disease transmission by disintegrated respiratory droplets has been the focus of great attention since the recent outbreak of COVID-19. In particular, human respiratory activities such as coughing, sneezing and even talking and eating expel a large amount of pathogen-laden droplets. Particularly, during eating or drinking, the physical properties of saliva can be changed. In this study, we investigate the atomization morphology of expelled artificial saliva mixtures from the perspective of varying fluid physical properties, specifically surface tension and dynamic viscosity. Using high-speed shadowgraph experiments on artificial saliva, we visualize and analyse the disintegration of saliva liquid sheets into ligaments and droplets. We find that the viscosity and surface tension affect the droplet size formed from expelled saliva and follow scaling laws that have been previously observed and predicted for constant shear viscosity. We conclude that the changes in physical properties of saliva induced by eating and drinking tend to favour the formation of smaller droplets during sneezing or coughing, which could drive the airborne transmission pathway of pathogens. Furthermore, we derive a theoretical model based on scaling arguments that shows the breakup time of ligaments produced from the artificial saliva mixtures is dependent on the capillary number.

Toward unraveling the mechanisms of aerosol generation during phonation

Aerosol droplets made from respiratory liquid are of fundamental importance for airborne transmission of several virus-based diseases, such as COVID-19. While the transmission route in the air has been intensively studied in the last two years, only few papers deal with the formation of these droplets. It seems to be accepted that such droplets are generated by upper airway activity such as talking, sneezing, or coughing. Especially talking is associated with disease transmission, although the droplet formation mechanisms have not been fully resolved yet. Thus, we focus on the investigation of the atomization process of respiratory liquid attached to the vocal folds. A new experimental setup has been installed that emulates the vocal folds and their oscillating movement in a simplified manner. A model liquid mimicking the respiratory mucus is dispersed at the vocal folds. The primary atomization of the model liquid into an air stream is observed qualitatively. This new insight shows that in contrast to the typical assumption that only liquid bridges form between the vocal folds and breakup into droplets, rather bubbles are generated, which can breakup into much smaller particles than filaments. Furthermore, droplet size distributions downstream of the vocal folds are evaluated. The influence of the oscillation frequency and amplitude as well as air flow rate on the droplet size distributions are analyzed. It is found that an increase in both frequency and amplitude leads to smaller particle sizes, while raising the air flow rate results in a higher proportion of larger particles. (C) 2022 Author(s).

Pulmonary Surfactant: A Unique Biomaterial with Life-saving Therapeutic Applications.

Pulmonary surfactant is a complex lipoprotein mixture secreted into the alveolar lumen by type 2 pneumocytes, which is composed by tens of different lipids (approximately 90% of its entire mass) and surfactant proteins (approximately 10% of the mass). It is crucially involved in maintaining lung homeostasis by reducing the values of alveolar liquid surface tension close to zero at end-expiration, thereby avoiding the alveolar collapse, and assembling a chemical and physical barrier against inhaled pathogens. A deficient amount of surfactant or its functional inactivation is directly linked to a wide range of lung pathologies, including the neonatal respiratory distress syndrome. This paper reviews the main biophysical concepts of surfactant activity and its inactivation mechanisms, and describes the past, present and future roles of surfactant replacement therapy, focusing on the exogenous surfactant preparations marketed worldwide and new formulations under development. The closing section describes the pulmonary surfactant in the context of drug delivery. Thanks to its peculiar composition, biocompatibility, and alveolar spreading capability, the surfactant may work not only as a shuttle to the branched anatomy of the lung for other drugs but also as a modulator for their release, leading to innovative therapeutic avenues for the treatment of several respiratory diseases.

Surface tension effects on flow dynamics and alveolar mechanics in the acinar region of human lung.

Background: Computational fluid dynamics (CFD) simulations, in-vitro setups, and experimental ex-vivo approaches have been applied to numerous alveolar geometries over the past years. They aimed to study and examine airflow patterns, particle transport, particle propagation depth, particle residence times, and particle-alveolar wall deposition fractions. These studies are imperative to both pharmaceutical and toxicological studies, especially nowadays with the escalation of the menacing COVID-19 virus. However, most of these studies ignored the surfactant layer that covers the alveoli and the effect of the air-surfactant surface tension on flow dynamics and air-alveolar surface mechanics. Methods: The present study employs a realistic human breathing profile of 4.75s for one complete breathing cycle to emphasize the importance of the surfactant layer by numerically comparing airflow phenomena between a surfactant-enriched and surfactant-deficient model. The acinar model exhibits physiologically accurate alveolar and duct dimensions extending from lung generations 18 to 23. Airflow patterns in the surfactant-enriched model support previous findings that the recirculation of the flow is affected by its propagation depth. Proximal lung generations experience dominant recirculating flow while farther generations in the distal alveolar region exhibit dominant radial flows. In the surfactant-enriched model, surface tension values alternate during inhalation and exhalation, with values increasing to 25 mN/m at the inhalation and decreasing to 1 mN/m at the end of the exhalation. In the surfactant-deficient model, only water coats the alveolar walls with a high surface tension value of 70 mN/m. Results: Results showed that surfactant deficiency in the alveoli adversely alters airflow behavior and generates unsteady chaotic breathing through the production of vorticities, accompanied by higher vorticity magnitudes (100% increase at the end of exhalation) and higher velocity magnitudes (8.69% increase during inhalation and 11.9% increase during exhalation). In addition, high air-water surface tension in the surfactant-deficient case was found to induce higher shear stress values (by around a factor of 10) on the alveolar walls than that of the surfactant-enriched case. Conclusion: Overall, it was concluded that the presence of the surfactant improves respiratory mechanics and allows for smooth breathing and normal respiration.

SURFACE TENSION-MEDIATED PROCESSING OF WASTEWATER SAMPLES FOR SARS-CoV-2

Wastewater testing for SARS-CoV-2 has emerged as a promising tool for disease surveillance in aggregate populations. We present a novel method to rapidly extract, concentrate, and amplify viral RNA from wastewater using Exclusion-based Sample Preparation (ESP) and RT-PCR. This technology identified potential outbreaks of SARS-CoV-2 at University of Kentucky dormitories, resulting in targeted clinical testing and quarantine procedures. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

Changes in surfactant lipid composition 6 months after severe Covid-19

Background: SARS-CoV-2 displays high affinity for ACE2 receptors as a vector of pathogenesis. ACE2 receptors are highly expressed on surfactant producing type 2 alveolar cells. These cells produce pulmonary surfactant - a crucial thin layer of surface-active fluid mainly composed of lipids, lining the alveolar epithelial surface. The main function, to reduce the surface tension, is fundamental for proper gas exchange. Aims and Objectives: To investigate changes in surfactant lipid composition and the relationship to longstanding symptoms of post Covid-19 among patients treated in intensive care for Covid-19 infection. Methods: We recruited 43 patients (17 women, aged 44-80 years) who had previously been treated in ICU in a major Swedish hospital, in average 6 months before inclusion. The participants answered a questionnaire regarding symptoms, we collected particles in exhaled air with PExA-instrument (PExA AB) and conducted pulmonary function tests, body plethysmography, and diffusion capacity of the lungs for carbon monoxide. Twenty-two healthy, non-infected, ageand gender-matched controls were enrolled. Lipids were analysed using liquid chromatography with a triple quadrupole mass spectrometer. Statistical analyses were performed with Qlucore. Results: Early results suggest a significant change in the composition of surfactant lipids among post-Covid -19 patients treated in intensive care compared to controls. Early analysis show significant reductions of all measured phosphatidyl-glycerols (PG, n = 14) an increase of all measured phosphatidyl-inositols (PI, n = 4), for example were PG 18:1-18:1 22% lower (p < 0.001, q = 0.04) and PI:16:0:18:1 67% higher (p < 0.001, q = 0.0003) in subjects post-Covid compared to controls. Conclusions: Our findings suggest that surfactant composition is altered also in the recovery after Covid-19 infection, which could be a key component in the post-Covid syndrome and the lingering effects on the respiratory system.

Physicochemical indicators of dental patient saliva who have undergone an uncomplicated coronavirus infection

Today, it has been proven that saliva is the main medium through which the new COVID-19 coronavirus infection spreads. Since the oral cavity is the gateway for the SARS-CoV-2 virus, the degree of change in the physicochemical parameters of the saliva of people who have had coronavirus infection compared to people who have not had COVID-19 is of interest. This study involved dental patients of the first and second health groups with a history of chronic generalized periodontitis of moderate degree in the stage of remission. We studied physicochemical parameters of saliva such as pH, surface tension and base buffering capacity. The results of this stage of the study showed saliva acidification, that is a decrease in pH in people who had had a new coronavirus infection compared to the indicators of people from the control group. The average values of the surface tension of saliva in patients of the control group are 30% less than in those who have had COVID-19. This indicates that the saliva of people who have not been sick with the new coronavirus contains more surface-active agents (surfactants). Surfactants provide rinsing and disinfecting functions of saliva, therefore, it can be concluded that these functions are less pronounced in patients who have recovered from COVID-19. The base buffering capacity of the saliva of patients who have had COVID-19 is, on average, 35% higher than that of people from the control group. Thus, the pH and the base buffering capacity are in correlation: the lower the pH value, the higher the acidity of the saliva and the higher the base buffering capacity is. At the second stage of the study, similar physicochemical parameters of patients’ saliva were measured after the application of an oral spray containing a synthetic peptide (ZP2) of the active center of granulo-cyte-macrophage colony-stimulating factor. This spray was used as an antibacterial therapy for the oral cavity after professional hygiene of patients. In 5 minutes after spray irrigation, an increase in saliva pH was observed in all test subjects within the physiological norm. In patients, regardless of their anamnesis, the surface tension of saliva changed in different ways. In a number of people, it increased, which indicates an increase in the concentration of surfactants in saliva, while in others it decreased, which can be explained by the high rate of penetration of surfactants from saliva through the gums into the blood. After the application of the ZP-2 peptide, the base buffering capacity of saliva decreases or remains unchanged. In patients of the control group, the indicators of the base buffering capacity of saliva change less than in patients who have undergone COVID-19. All the studied physicochemical parameters of saliva in patients who had had uncomplicated COVID-19, three months after receiving two negative results for the SARS-CoV-2 virus, remained within the physiological norm.

QSPR Modeling with Topological Indices of Some Potential Drug Candidates against COVID-19

COVID-19, which has spread all over the world and was declared as a pandemic, is a new disease caused by the coronavirus family. There is no medicine yet to prevent or end this pandemic. Even if existing drugs are used to alleviate the pandemic, this is not enough. Therefore, combinations of existing drugs and their analogs are being studied. Vaccines produced for COVID-19 may not be effective for new variants of this virus. Therefore, it is necessary to find the drugs for this disease as soon as possible. Topological indices are the numerical descriptors of a molecular structure obtained by the molecular graph. Topological indices can provide information about the physicochemical properties and biological properties of molecules in the quantitative structure-property relationship (QSPR) and quantitative structure-activity relationship (QSAR) studies. In this paper, some analogs of lopinavir, favipiravir, and ritonavir drugs that have the property of being potential drugs against COVID-19 are studied. QSPR models are studied using linear and quadratic regression analysis with topological indices for enthalpy of vaporization, flash point, molar refractivity, polarizability, surface tension, and molar volume properties of these analogs.

A graphene-printed paper electrode for determination of H2O2in municipal wastewater during the COVID-19 pandemic

Recently, hydrogen peroxide (H2O2) has been used as a disinfectant in sanitizers for cleaning hands, and solid surfaces of hospitals, offices and homes to prevent the spread of the COVID-19 virus. The effluents from domestic, hospital and municipal waste should be monitored for their H2O2 content to avoid the entry of this toxic pollutant into the ecosystem. Therefore, we developed a low-cost graphene (Gr)-printed paper electrode for determination of H2O2 using cyclic voltammetry (CV). An office inkjet-printer and Gr nano-ink stabilized with ethyl cellulose (EC) were used for the fabrication of printed paper electrodes (PPEs) to determine H2O2 quantitatively. A stable Gr-EC nano-ink (2%) with viscosity and surface tension values of 12 mPa S-1 and 35 mN M-1, respectively, was formulated to obtain conductive electrodes. A wide linear range (2 μM-25 mM) with a better limit of detection (0.28 μM) for the determination of H2O2 was obtained when the Gr-EC/PPE was used as a working electrode. Further, the Gr-EC/PPE was successfully employed for analysis of H2O2 in wastewater. The electrochemical determination of H2O2 using the Gr-EC/PPE as an electrode in CV is rapid, economical, flexible and eco-friendly when compared with previously reported methods.

Evaluation of Viscosity Dependence of the Critical Meniscus Height with Optical Fiber Sensors.

Conventional means of data extraction using optical fiber interrogators are not adequate for fast-paced detection of a target parameter. In this instance, the relationship between the critical meniscus heights (CMH) of several liquids to the extraction speed of a rod submerged in them, have been analyzed. A limitation of a previous interrogator used for the purpose had been light absorption by the liquid due to the used bandwidth of the readily-available light source, i.e., C-band. The newly proposed technique addresses this limitation by utilizing a broadband light source instead, with a Si-photodetector and an Arduino. In addition, the Arduino is capable of extracting data at a relatively faster rate with respect to the conventional optical interrogator. The use of a different operational wavelength (850 nm instead of 1550 nm) increased the r2 and the sensitivity of the sensor. The new setup can measure surface chemistry properties, with the advantage of being comparatively cheaper than the conventionally available interrogator units, thereby providing a suitable alternative to conventional measurement techniques of liquid surface properties, while reducing material waste, i.e., in terms of the required volume for detection of a target parameter, through the use of optical fiber.

Intravenous sulforhodamine B reduces alveolar surface tension, improves oxygenation, and reduces ventilation injury in a respiratory distress model.

In the neonatal respiratory distress syndrome (NRDS) and acute respiratory distress syndrome (ARDS), mechanical ventilation supports gas exchange but can cause ventilation-induced lung injury (VILI) that contributes to high mortality. Further, surface tension, T, should be elevated and VILI is proportional to T. Surfactant therapy is effective in NRDS but not ARDS. Sulforhodamine B (SRB) is a potential alternative T-lowering therapeutic. In anesthetized male rats, we injure the lungs with 15 min of 42 mL/kg tidal volume, VT, and zero end-expiratory pressure ventilation. Then, over 4 h, we support the rats with protective ventilation-VT of 6 mL/kg with positive end-expiratory pressure. At the start of the support period, we administer intravenous non-T-altering fluorescein (targeting 27 µM in plasma) without or with therapeutic SRB (10 nM). Throughout the support period, we increase inspired oxygen fraction, as necessary, to maintain >90% arterial oxygen saturation. At the end of the support period, we euthanize the rat; sample systemic venous blood for injury marker ELISAs; excise the lungs; combine confocal microscopy and servo-nulling pressure measurement to determine T in situ in the lungs; image fluorescein in alveolar liquid to assess local permeability; and determine lavage protein content and wet-to-dry ratio (W/D) to assess global permeability. Lungs exhibit focal injury. Surface tension is elevated 72% throughout control lungs and in uninjured regions of SRB-treated lungs, but normal in injured regions of treated lungs. SRB administration improves oxygenation, reduces W/D, and reduces plasma injury markers. Intravenous SRB holds promise as a therapy for respiratory distress.NEW & NOTEWORTHY Sulforhodmaine B lowers T in alveolar edema liquid. Given the problematic intratracheal delivery of surfactant therapy for ARDS, intravenous SRB might constitute an alternative therapeutic. In a lung injury model, we find that intravenously administered SRB crosses the injured alveolar-capillary barrier thus reduces T specifically in injured lung regions; improves oxygenation; and reduces the degree of further lung injury. Intravenous SRB administration might help respiratory distress patients, including those with the novel coronavirus, avoid mechanical ventilation or, once ventilated, survive.

Lipid-Protein and Protein-Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis.

Pulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air-liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid-protein and protein-protein interactions contribute to the proper maintenance of an operative respiratory surface.