No abstract

Dehydration of the upper airways increases risks of respiratory diseases from COVID-19 to asthma and COPD. We find in human volunteer studies involving 464 human subjects in Germany, the US, and India that respiratory droplet generation increases by up to 4 orders of magnitude in dehydration-associated states of advanced age (n = 357), elevated BMI-age (n = 148), strenuous exercise (n = 20) and SARS-CoV-2 infection (n = 87), and falls with hydration of the nose, larynx and trachea by calcium-rich hypertonic salts. We also find in a protocol of exercise-induced airway dehydration that hydration of the airways by calcium-rich salts increases oxygenation relative to a non-treatment control (P < 0.05). In a random control study of COVID-19 positive subjects (n = 40), thrice-a-day delivery of the calcium-rich hypertonic salts (active) suppressed respiratory droplet generation by 51% ± 11% and increased oxygen saturation over three days of treatment by 48.08% ± 9.61% (P < 0.001), while no changes were observed in the nasal-saline control group. Self-reported symptoms significantly declined in the active group and did not decline in the control group. Hydration of the upper airways appears promising as a non-drug approach for reducing risks of respiratory diseases such as COVID-19.

Dry air alters salt and water balance in the upper airways and increases the risks of COVID-19 among other respiratory diseases. We explored whether such upper airway variations in salt and water balance might alter respiratory droplet generation and potentially contribute to observed impacts of airway hydration on respiratory disease. In a randomized 4-arm study of 21 healthy human subjects we found that the breathing of humid air, the wearing of cotton masks, and the delivery of (sodium, calcium, and magnesium chloride) salt droplets sized to deposit in the nose, trachea, and main bronchi similarly reduce the exhalation of respiratory droplets by approximately 50% ([Formula: see text] ¡ 0.05) within 10 minutes following hydration. Respiratory droplet generation returns to relatively high baseline levels within 60–90 minutes on return to dry air in all cases other than on exposure to divalent (calcium and magnesium) salts, where suppression continues for 4–5 hours. We also found via a preliminary ecological regression analysis of COVID-19 cases in the United States between January 2020 and March 2021 that exposure to elevated airborne salt on (Gulf and Pacific) US coastlines appears to suppress by approximately 25%–30% ([Formula: see text] ¡ 0.05) COVID-19 incidence and deaths per capita relative to inland counties — accounting for ten potential confounding environmental, physiological, and behavioral variables including humidity. We conclude that the hydration of the upper airways by exposure to humidity, the wearing of masks, or the breathing of airborne salts that deposit in the upper airways diminish respiratory droplet generation and may reduce the risks of COVID-19 incidence and symptoms.

Traditional implanted drug delivery systems cannot easily change their release profile in real time to respond to physiological changes. Here we present a microfluidic aqueous two-phase system to generate microcapsules that can release drugs on demand as triggered by focused ultrasound (FUS). The biphasic microcapsules are made of hydrogels with an outer phase of mixed molecular weight (MW) poly(ethylene glycol) diacrylate that mitigates premature payload release and an inner phase of high MW dextran with payload that breaks down in response to FUS. Compound release from microcapsules could be triggered as desired; 0.4 μg of payload was released across 16 ondemand steps over days. We detected broadband acoustic signals amidst low heating, suggesting inertial cavitation as a key mechanism for payload release. Overall, FUS-responsive microcapsules are a biocompatible and wirelessly triggerable structure for on-demand drug delivery over days to weeks.Localized drug delivery can target intended sites in the body while reducing adverse off-target effects. [1] Many implanted drug-delivery systems, such as nanoparticles, hydrogels, and microdevices, work via passive release or exhibit a pre-programmed drug-release profile, [2] in contrast to localized drug-delivery systems that are externally triggerable for on-demand release. [2a, 3] These remotely-activated

Traditional implanted drug delivery systems cannot easily change their release profile in real time to respond to physiological changes. Here we present a microfluidic aqueous two‐phase system to generate microcapsules that can release drugs on demand as triggered by focused ultrasound (FUS). The biphasic microcapsules are made of hydrogels with an outer phase of mixed molecular weight (MW) poly(ethylene glycol) diacrylate that mitigates premature payload release and an inner phase of high MW dextran with payload that breaks down in response to FUS. Compound release from microcapsules could be triggered as desired; 0.4 μg of payload was released across 16 on‐demand steps over days. We detected broadband acoustic signals amidst low heating, suggesting inertial cavitation as a key mechanism for payload release. Overall, FUS‐responsive microcapsules are a biocompatible and wirelessly triggerable structure for on‐demand drug delivery over days to weeks.

Dr. Reuther's interests lie in the development and translation of early-stage medical technologies and discoveries and is an experienced educator in this area. She is currently a Senior Lecturer in Design, Innovation, and Entrepreneurship in the Department of Biomedical Engineering at Columbia University, with additional appointments as the Director of the Columbia Biomedical Technology Accelerator (BiomedX) Program and the Director of Master's Studies. The BiomedX program provides funding, education, and support to students and faculty interested in commercializing their biomedical inventions. She has advised and educated numerous student and faculty teams and start-ups in developing and commercializing medical technologies. Her current educational work focuses on developing new instructional tools and programs to enhance graduate education in the Department of Biomedical Engineering. Prior to joining Columbia and while pursuing her PhD, Reuther served as a Research Assistant at the McKay Orthopaedic Research Laboratory. Her dissertation researched focused on determining fundamental relationships and mechanisms of tendon and ligament injury and repair, with a particular emphasis on tissue mechanics and the shoulder. She continues to apply her research expertise through collaborations with the Department of Orthopaedic Surgery at Columbia University, with a specific focus on translational orthopaedic clinical research. The goal of her current work is to optimize surgical and non-surgical treatment strategies for shoulder injury. Reuther received a BS in Biomedical Engineering (with an emphasis in Mechanical Engineering) from The College of New Jersey and a PhD in Bioengineering from the University of Pennsylvania. She is currently pursuing an Executive MBA at Columbia Business School.

Dirty air and poor access to healthcare threatens the lives of billions of people in low-income regions of the world. We investigated whether upper-airway hydration might alter two-phase flow in the airways on normal tidal breathing and be a useful, safe, easily distributed non-drug intervention for limiting risks of COVID-19. In observational human volunteer studies involving 464 human subjects in Marburg, Germany (357 normal subjects), Boston, US (20 healthy subjects), and Bangalore, India (87 subjects recently tested positive for COVID-19), we find that respiratory droplet generation increases by up to 4 orders of magnitude with up to 1% total body mass dehydration (n=20), and in dehydration-associated states of advanced age (n=357), elevated BMI-age (n=148), and SARS-CoV-2 infection (n=87). Hydration of the nose, larynx and trachea in a protocol of exercise-induced dehydration by the nasal inhalation of calcium-rich hypertonic salt droplets of mean diameter 8-12 µm diminished respiratory droplet numbers and increased oxygenation relative to a non-treatment control (P<0.05). In a randomized double-blinded nasal-saline control study, thrice-a-day delivery of the calcium-rich hypertonic salts (active) over three days suppressed respiratory droplet generation by 51% +/- 11% and increased oxygen saturation by 48.08% ± 9.61% (P<0.001) in COVID-19 positive subjects (n=20), while no changes in exhaled aerosol (P=0.235) or oxygen saturation (P=0.533) were observed in the nasal-saline control group (n=20). In the active group 47% of patients discharged with no self-reported symptoms while all of the subjects in the nasal saline group discharged with lingering symptoms. Hydration of the upper airways appears promising as a non-drug approach for reducing risks of lower respiratory-tract infections such as COVID-19.