The Research
My research over the years has spanned from applied math (my work on interfacial dynamics and transport in complex media, including my two textbooks in these fields) to art and design research at Le Laboratoire in Paris, to my lifelong work on aerosols and breathing. Below is the relevant trail of this latter research, my work on the air we breathe.
The 2024 European Respiratory Journal Open Research Article
Led by the team of Professor Kian Fan Chung at Imperial College London, the ERJOR paper summarizes the results from an exploratory human clinical trial in refractory chronic cough patients to assess the treatment potential of targeted hydration of the larynx by alkaline hypertonic divalent salts — as a function of pH. We had reached a conclusion that alkalinity might be the difference between hydration as hygienic intervention and hydration as treatment. The results of this study are the first indication that this may be true. The treatment efficacy of 33-35% relative to placebo 2 days post treatment with a pH 9 aerosol is the first evidence that a purely endogenous aerosol might treat refractory chronic cough as effectively as the drugs most advanced in clinical testing.
Abubakar-Waziri H, Edwards DA, Bhatta DB, et al. Inhaled alkaline hypertonic divalent salts reduce refractory chronic cough frequency.
ERJ Open Res 2024; 10: 00241-2024 [DOI: 10.1183/23120541.00241-2024]
The 2024 Journal of Aerosols in Medicine Paper
Led by Professor Ana Flavia Zuim at New York University, the JAM article summarizes the results of an exploratory, randomized, double blinded, placebo-controlled study of exploring the laryngeal hydration potential of the 4 endogenous salts at identical concentrations by measuring the quality of one’s voice. Phonation threshold pressure is the most reliable measure of phonation quality currently used today — and the results of this study show that magnesium chloride lasts longer and is more effective at hydration than any other salt. The study also shows why calcium or magnesium chloride avoid the cough provocation common with sodium chloride and mannitol — and led to the composition of the therapeutic aerosol that is now advancing in clinical testing.
Zuim, A-F, Edwards, A, Ausiello DA, Bhatta, D Edwards DA Hypertonic aerosols hydrate airways longer and reduce acidification risk with non-permeating cation and permeating anion salts. 2024. Journal Aerosols Medicine Pulmonary Drug Delivery. DOI10.1089/jamp.2023.0039
The 2023 Invited Review in LUNG
This review, written with my colleague Fan Chung at Imperial College London, provides an overview of our discovery of mucus transpiration and the modality of treatment of chronic cough inherent in targeted hydration of the larynx. The review captures understanding at the moment of publication — in a field of inquiry that is rapidly expanding.
Edwards DA, Chung KF. Mucus Transpiration as the Basis for Chronic Cough and Cough Hypersensitivity. Lung. 2023 Dec 22. doi: 10.1007/s00408-023-00664-0. Epub ahead of print. PMID: 38135857.
The 2023 QRB Discovery Article
We find that the breathing of dry air leads to evaporative stresses on mucus in the upper airways, and notably in the larynx and trachea, which press mucus onto underlying cilia, promoting inflammation, and cough reflex. This is a first paper that points out how mucus in the upper airways appears to be an example of a transpiring hydrogel, like the hydrogel on the surface of a leaf, which pulls by osmosis water from the roots toward the sky. The weight of the water head in a tree is an illustration of the inflammatory force that can act in the upper airways, leading to dysfunction that includes loss of cilia clearance and amplified respiratory droplet generation. The article also indicates how such dehydration stresses can be reduced by targeted hydration using hypertonic salts.
The 2022 Scientific Reports Article
This is the first article to point to the commonality of dry airways to multiple normal/infected human conditions as a likely cause of elevated respiratory droplet generation — and that drying out of the larynx may also be responsible for diminished oxygen saturation in invected and normal human subjects. The article communicates the results of a multisite human clinical trial involving 464 human subjects in Germany, the US, and India. It is found that 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) far more respiratory droplets are produced in the airways (up to 4 orders of magnitude) than in relatively hydrated (the young, the low BMI, the non-infected). In a random control study of COVID-19 positive subjects (n=40), thrice-a-day delivery of calcium-rich hypertonic salts (FEND) targeting the upper airways suppressed respiratory droplet generation by 51% +/- 11%. No changes were observed in the nasal saline control group. Oxygen saturation rose significantly over the course of the airway hygiene treatment in the active group and did not change in the nasal saline control group. Self-reported symptom scores fell in the active group from Day 2 with 86% of all subjects discharged without symptoms. In the control, 0% of the group ended their stay in the hospital without symptoms. Additionally, in the exercise-induced dehydration study, exhaled aerosol increased around 15 fold following one hour of exercise (between 0.5 to 1.0% whole body weight loss). Drying out of the upper airways may be a significant cause of the high rates of respiratory infection illness among high-endurance athletes.
The 2022 Molecular Frontiers Journal Editorial
This editorial is an outcome of the Next Breath Symposium in Lausanne in November 2021. It is a call for improving access to hydration in those parts of the world least developed and where respiratory disease is the number one killer. The editorial makes the case that getting water where it is needed most, to those who lack access to water, as well as to the region of our bodies (the upper airways) most in need of water to keep our airways clean, should be a global humanitarian and scientific priority. Billions of life years on the planet are at risk today owing to the scourge of dirty air and the lack of hydrated airways to clean it.
The 2021 Molecular Frontiers Journal Article
This article is the first to show that hydration of the upper airways, as occurs when we breathe humid air, diminishes respiratory droplet generation in our upper airways. This suppression lasts for about an hour on return to a dry room. Wearing a cotton face mask accomplishes the same thing — humidifying our upper airways with our own moist air. Delivering sodium chloride salt droplets sized to land in the upper airways mimics the suppression effects of the humid room and the face mask. Replacing sodium chloride by calcium chloride prolongs the cleansing effect for 4-5 hours. Upper airway hydration appears to equivalently occur by water and salt exposure, as water and salt balance to hydrate the upper airways. Previous peer-reviewed research, cited in the article, shows that sustained breathing of humid air reduces risks of COVID-19. Our article is the first to show from public county-level data in the US a preliminary correlation between 25-30% suppression of COVID-19 incidence and death rates and residency in (Pacific and Gulf) coastal US counties where wind blows off the sea. Among the roles of upper airway hydration in reducing risks of lower-respiratory-tract disease may be the suppression of respiratory droplet generation — which lowers traffic of inhaled contaminants to the lower respiratory tract.
A most recent 2021 PNAS article
A most recent 2021 PNAS article begins to explore the connection between respiratory droplets and COVID-19 self-infection and transmission via human and non-human primate exhaled aerosol data. The article reports a “super spreading” distribution of exhaled aerosol in the human population — 20% of the subjects exhaled 80% of the aerosol of the group. Consistent with earlier research, the finding suggests that super spreading of airborne infectious disease may be an inherency in the nature of respiratory droplet heterogeneity, ie that in any group of individuals some people exhale many more droplets than others. The article reports a strong correlation between high respiratory droplet generation and old age and high BMI — and with nonhuman primates a correlation between exhaled aerosol and degree of pathogen (SARS-CoV-2 and TB) proliferation in the airways.
In a pair of articles in the 2020 Molecular Frontiers Journal human volunteer data are reported in over 100 individuals confirming the effect seen on n=10 people in the QRBD article. See Airway Hygiene in Children and Adults for lowering Respiratory Droplet Exposure in Clean and Dirty Air and https://www.worldscientific.com/doi/abs/10.1142/S2529732520400040. The findings that FEND administration suppresses respiratory droplet generation by up to 99% (notably in those airways that have the highest numbers of respiratory droplets) and for up to 6 hours and generally across a broad population of ages and BMI indicate the key efficacy property of airway hygiene.
2020 Molecular Frontiers Journal
In a pair of articles in the 2020 Molecular Frontiers Journal human volunteer data are reported in over 100 individuals confirming the effect seen on n=10 people in the QRBD article. See Airway Hygiene in Children and Adults for lowering Respiratory Droplet Exposure in Clean and Dirty Air and Nasal Calcium-Rich Salts for Cleaning Airborne Particles from the Airways of Essential Workers, Students, and a Family in Quarantine.The findings that FEND administration suppresses respiratory droplet generation by up to 99% (notably in those airways that have the highest numbers of respiratory droplets) and for up to 6 hours and generally across a broad population of ages and BMI indicate the key efficacy property of airway hygiene.
2020 Quarterly Reviews Biophysics Discovery article
The 2020 Quarterly Reviews Biophysics Discovery article shares much of the research of the period 2008–2012 as well as the new insight that for the purposes of airway hygiene (cleansing of the airways of respiratory droplets) it is unnecessary to deliver salt aerosol to the entire lungs. It is more efficient to deliver salts through the nose to the upper airways only. The observation that the upper airways are the principal site of respiratory droplet generation is a key finding of this paper. Delivering salts via the nose to the upper airways for airway cleansing leads to faster delivery (seconds not minutes) and non-drug effects. Link to article
2007 JCIS Article
The 2007 JCIS article explores the role of mucus surface properties in the generation of respiratory droplets. The “cough machine” used in this article reproduces air flows along mucus surfaces that are characteristic of air speeds encountered on normal breathing through the “laryngeal jet” that forms when air passes on inhalation past the larynx — notably on mucus surfaces in the trachea and main bronchi. Increasing surface elasticity (the mucus surface becomes easier to stretch) leads to more droplets forming. Lowering surface tension has a minor contribution to droplet breakup — more importantly lower surface tension leads to smaller droplets. Both of these effects occur on adding surfactant to mucus surfaces. The addition of salts meanwhile alters electrostatic interactions between surfactants (and mucus proteins ie mucin molecules) at or near mucus surfaces promoting a less elastic surface and therefore reducing droplet generation.
2004 PNAS Article
The 2004 PNAS article reports the first observation of salt reduction of respiratory droplet generation. The article also reveals the contrary effect of surfactants on respiratory droplet generation — an effect that eventually underlies variations in respiratory droplet generation (reported in more recent articles) with changes in viral load and airway lining fluid volume given the presence of lung surfactant in the upper airways — Link to article
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