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.
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.
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.
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 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. Link to article
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.
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.
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
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.
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