Nasal hygiene compositions, antimicrobial treatments, devices, and articles for delivery of same to the nose, trachea and main bronchi
Patent Information
- Application Number
- AU2021306236
- Authority / Receiving Office
- AU · AU
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2020-12-31
- Filing Date
- 2021-07-02
- Publication Date
- 2026-09-17
- Estimated Expiration
- 2041-07-02
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Abstract
Description
Field 5 This disclosure generally relates to suppression of exhaled aerosol particles from the upper airways ( / .e., nose, pharynx, larynx, trachea and / or main bronchi) of the human respiratory tract via nasally administered salt-based formulations or compositions, for example calcium rich salt-based formulation and / or compositions with a mass median diameter ranging from approximately 7 microns to 10 approximately 15 microns and preferably around 10 microns, and treatment protocols, devices, and articles suitable for the delivery of salt-based compositions as aerosols to the nose, trachea and / or main bronchi of a respiratory tract of a subject. BACKGROUND 15 Description of the Related Art Various illnesses are caused by viruses, bacteria and other inhaled foreign particles. At least some viruses, for example various variations of the flu viruses and variations of corona viruses are communicated, at least in part, via respiratory transmission. Examples of airborne bacterial infections include 20 tuberculosis. In one mechanism, an individual inflected with the microbe may shed the microbe through breakup of airway lining fluid during respiration, coughing, sneezing, talking or even singing, subjecting others to the airborne microbe. The shed microbes may also be drawn inwardly, deeper into the respiratory tract, of the subject, for example into the lungs. Inhaled particles from the environment, for 25 instance soot particles, may land on the upper airway lining mucus. Breakup of the mucus into respiratory droplets can carry these particles deeper into the lungs, promoting allergic responses or other respiratory ailments. Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2) transmits through the air by a combination of the large droplets exhaled when people cough or This data, for application number 2021306236, is current as of 2026-08-26 22:42 AEST 2021306236 27 Aug 2026 sneeze, and by the very small droplets people generate in their airways when they naturally breathe. How exhaled respiratory droplets vary between individuals, evolves over time within individuals, and changes with the onset and progression of COVID-19 infection is critical to clarifying the nature of COVID-19 transmission—and other highly-5 communicable airborne respiratory diseases, such as influenza and tuberculosis. The delivery of therapeutic substances to the nasal epithelium and other portions of the upper airways to modulate human health, as in the delivery of active substances for relieving congestion, or symptoms related to asthma, generally involves the active (forced) delivery of dry or liquid formulations to the nose via a 10 spray, metered dose inhaler, or dry powder inhaler. The use of these substances to fight against infectious diseases is generally limited to antibiotic or anti-viral drugs. The delivery of purely nasal hygiene substances, as in sodium chloride, for cleaning mucus is also common. Applicant is unaware of any nasal hygiene specifically targeted against infectious diseases, in the way that the washing of hands or the 15 wearing of masks provides protection against infection. The ability to return to normal activities in the face of an airborne infectious disease pandemic of the kind posed by COVID-19 may hinge on the ability to provide hygienic protection against airborne infection in the vicinity of the nose, trachea and main bronchi where infection often begins and where considerable 20 bioaerosol shedding occurs. Such may be important on an individual basis, as well as in crowds, for instance where social distancing cannot be ensured. This same hygienic protection might be beneficial for other airborne infectious diseases, such as influenza, and also useful to promoting respiratory health for individuals exposed to high levels of air pollution. 25 BRIEF SUMMARY Given the potential for widespread illness via the inhalation of foreign particles, as evidenced by the ongoing COVID-19 pandemic, new approaches that effectively deliver hygienic and therapeutic substances in order to reduce the generation of respiratory droplets in the upper airways, and therefore the 30 suppression of exhaled droplets or bioaerosols, are desirable. 2021306236 27 Aug 2026 Generation of respiratory droplets in exhaled breath can occur by the force of the fast air flows that occur in the upper airways when we breathe, talk, cough and sneeze. At peak inspiratory flows during normal breathing, air speeds in the trachea and main bronchi can reach turbulent velocities. The rush of air over the 5 thin (5 pm to 10 pm) mucus layer lining the upper airways can break up the mucus surface into small droplets in the way strong winds produce breakup and spray on the surface of the ocean. The nature and extent of this droplet breakup is dependent on the surface properties of the mucus itself. Among properties most influencing droplet generation and droplet size are surface viscoelasticity (which resists the 10 stretching of mucus surface on breakup) and surface tension (which lowers the energy expended in small droplet creation). In airway lining mucus, both properties vary with lung surfactant type and concentration, surface particulate concentration, as well as with composition and structure of mucus in close proximity to air surfaces. Particulate accumulation, e.g., by breathing polluted air or pathogen proliferation, or 15 surfactant and mucin compositional and structural changes, driven in part by physiological alterations of the human condition — including diet, aging, and COVID19 infection itself — may therefore be anticipated to alter droplet generation and droplet size during acts of breathing. The scientific response to the COVID-19 pandemic has largely focused 20 on the development of curative drugs and preventive vaccines. In the wait for a cure or collective immunity, it may be advisable for the scientific community to additionally focus on management of COVID-19; in part through the diminution of respiratory droplet generation as reflected in the numbers of exhaled breath particles. Notably, typical masks do not stop submicron particles, which are the most numerous of all in 25 air expelled by an infected individual. For example, it is believed that approximately 85% of (inhaled and exhaled) respiratory particles are in the submicron size range. Beyond more effective masks and more sophisticated social distancing rules, approaches to stabilize airway lining mucus and retain mucus clearance function might be particularly useful. 30 Notably, exhaled aerosol numbers appear to be not only an indicator of disease progression, but a marker of disease risk in non-infected individuals. Monitoring as a diagnostic might also be an important strategy to consider in the 2021306236 27 Aug 2026 control of transmission and infection of COVID-19 and other respiratory infectious diseases, including influenza. The nasal administration of physiological salts appears particularly effective at reducing airborne particles from exhaled breath including the sub-micron 5 aerosolized particles that are ineffectively filtered by cloth face masks. For example, nasal application of a drug-free calcium-enriched nasal salt interacts with airway lining mucus to cleanse the airways of bioaerosols which may reduce exhaled aerosol particles up to 99%, with an overall reduction of exhaled particles in a large cohort of human subjects of around 75%. The cleansing may not only reduce the 10 exhalation of particles, but may also reduce the inhalation of particles further into the airways (e.g., lower respiratory tract). The nasal administration of physiological salts can be an important addition to current COVID-19 hygiene protocols of mask wearing, hand washing, and social distancing. The nasal administration of physiological salts adds to the efficacy of masks at reducing the penetration of 15 respiratory droplets into the lungs or back into the environment; and provides an added layer of defense for when mask wearing is not possible. The global crisis caused by the rapid and tenacious spread of COVID-19 points to the inadequacy of current defenses against airborne infectious diseases. Nasal administration of physiological salts, and in particular, calcium-enriched 20 physiological salts may be employed to address the challenge that the air route of infection and transmission presents to public health. There is a particular need for purely hygienic compositions and methods for cleaning the airways of droplets of airway lining fluid, as are generated during natural breathing, talking, coughing and sneezing. In a study of 10 human volunteers (5 younger than 65, 5 older than 65), 25 the 5 to 15 second delivery of a nasal saline comprising calcium and sodium salts with a 9-10 pm mean diameter quickly (e.g., within 15 minutes) and durably (e.g., up to at least 6 hours) diminishes exhaled particles from the human airways without appreciably penetrating the lower airways ( / .e., secondary bronchi, tertiary bronchi, bronchiole, terminal bronchiole of the lungs) beyond the trachea and primary or main 30 bronchi. Being predominantly smaller than 1 pm, these exhaled particles are largely below the size effectively filtered by conventional masks. By contrast, in the same study, the delivery of a similar calcium-enriched nasal saline with 2-4 pm mean 2021306236 27 Aug 2026 diameter droplets required several minutes to administer and led to less uniform suppression of exhaled particles from the human airways while also penetrating the lungs beyond the trachea and main bronchi. The delivery of isotonic normal saline (sodium chloride) by small aerosol (2-4 pm droplets) to the lungs has a more modest 5 effect on suppression, as shown in the same study as well as in a 2004 study. Delivering isotonic normal saline to the nose by large droplets ranging between approximately 10 pm and 300 pm, with a mean diameter of around 40 to 50 pm, in the same study of 10 human volunteers, led to no effect on exhaled aerosol. However, in a recent study, delivery of this same aerosol with similar large droplet 10 diameter, tilting of the head to permit post-nasal drip showed significant suppression of exhaled aerosol. These results are consistent with the known deposition patterns of inhaled aerosols. Particularly, droplets in the range of 1 to 5 pm tend to penetrate and deposit throughout the respiratory tract including in the alveolar region of the lungs. The generation of a given mass for deep lung delivery with small droplets in 15 this size range requires more energy than the generation of the same mass for delivery within droplets of say 10 pm in size, and therefore requires, for a given energy input, more time. Inhaled droplets of around 10 pm in diameter predominantly deposit in the nasal pharynx and in the trachea and main bronchi. On the other hand droplets of 15 to 300 pm can be sprayed into the nose but tend to 20 land in the nose and do not penetrate the trachea. Solution deposited in the nose can drip into the trachea and main bronchi via post-nasal drip. While other divalent cations can be delivered to the airways with an aim to suppress respiratory droplet formation, calcium is particularly desirable in that it is present in the body at a relatively high concentration. Magnesium is also in the body while at lower 25 concentrations (roughly 5 to 10 times lower than calcium concentrations) and also acts on negatively charged molecules such as mucins and alginates more slowly than calcium. Other divalent and multivalent cations may be effective but are either foreign to the body, as in the case of chitosan, or present in the body, as in the case of iron, while introducing other complex biochemical consequences. 30 The suppression of exhaled droplets by the nasal delivery of calcium- rich salines — with and without sodium chloride, and other additives including lavender, cinnamon, lemongrass, and alcohol —with aerosol droplet median 2021306236 27 Aug 2026 diameter of between around 7 pm to around 15 pm, and preferably around 10 pm (e.g., 9 pm -10 pm) suggests the upper airways ( / .e., the nose, pharynx, larynx, trachea and main bronchi) as a primary source of bioaerosol generation. The suppression effect is especially pronounced (99%) among those who exhale large 5 numbers of particles. High particle exhalation appears to correlate with advanced age and body mass index (BMI) as well as with lung infection and prolonged exposure to high fine particle aerosol burden in the atmosphere. A new hygienic practice of “airway hygiene” using a calcium-rich saline nasally-administered solution is proposed, to complement the widely-recommended 10 washing of hands with ordinary soap, use of a face mask, and social distancing. Airway hygiene might be immediately introduced next to these other hygienic measures. The combination of hygiene and therapy, whether through combinations of salts that have been shown to produce antimicrobial effects or 15 through other therapeutically active substances, is also desirable. There is also a need for therapeutic compositions and methods for treating the airways of individuals who are known or suspected of having an airborne illness (e.g., infection of COVID-19 and other respiratory infectious diseases, including influenza), or who have been exposed to other individuals who are known 20 or suspected of having an airborne illness. A new therapeutic practice of nasal application of a calcium-rich saline aerosol, with or without other salts that have been shown to produce antimicrobial effects or with or without other therapeutically active substances, to the upper respiratory tract is described. Nasal application of physiological salts, and in 25 particular application of an aerosol of droplets containing calcium rich salts (e.g., calcium chloride) in sizes that constrain the aerosol predominately in the upper respiratory tract may advantageously produce antimicrobial and / or anti- pathogen effects. In particular, a mister or nebulizer that targets deliver of an aerosol that 30 has a high concentration of calcium to the upper airway site of respiratory droplet formation may be particularly effective. The ions of the calcium rich salt may associate with mucins on the surface of the airway lining mucus, strengthening 2021306236 27 Aug 2026 resistance to the breakup of mucus. This may advantageously clean the airways of the respiratory droplets that can carry infection and insoluble environmental contaminants. Otherwise a calcium rich salt solution applied to the nose by a spray, 5 combined with a leaning back of the head or reclined position that promotes postnasal drip, is another method to deliver to the upper airway site of respiratory droplet formation a high concentration of calcium or other multi-valent cationic molecule. Hygienically and therapeutically active substances deposit in the nose, depending on the nature of the delivery system and technique, with some associated 10 degree of efficiency. This efficiency can be measured as a fraction of "delivered dose" to "nominal dose." Delivery of substances to the nasal epithelium occurs in two ways. The first, ortho-nasal scent delivery, occurs by sniffing substances in the atmosphere, e.g., directly via the nostrils or nasal vestibule. The second, retronasal scent delivery, occurs by the natural diffusion and convection of substances in 15 the mouth into the nasal passages via the oropharynx. This latter delivery is referred to as retro-nasal olfaction, and is promoted by exhalation. Described herein are new salt-based hygienic and / or antimicrobial formulations or compositions that are effective against airborne pathogens and other airborne contaminants, and associated apparatus, methods and articles for delivery 20 of salt-based antimicrobial and / or anti-contagion formulations or compositions. The described salt-based hygienic and / or antimicrobial formulations or compositions, apparatus, methods and articles can advantageously be employed to suppress or otherwise reduce the shedding of aerosol particles of airway lining fluid (bioaerosol), either on an individual basis, or in groups or crowds of individuals. The described 25 approaches employ a combination of ortho-nasal and retro-nasal delivery, the former occurring on inspiration of the physiological salt solutions, and the latter on exhalation of these same salt solutions. The salt-based formulations or compositions are formulated in readily-soluble solutions applied to the nose as an installation or a spray, or in the form of aerosolized water droplets that have a mass 30 median droplet diameter range of approximately 7 microns to approximately 15 microns, with a standard deviation of less than 5 microns; alternatively the mass median droplet diameter is approximately 9 to approximately 10 microns, 2021306236 27 Aug 2026 approximately 9.5 microns, or approximately 10 microns, with a standard deviation of less than 1 micron. These droplet diameter ranges are advantageously too large for significant penetration into the lungs, while small enough to be carried into the trachea and main bronchi of the respiratory tract via the nose. 5 The salt-based hygienic and / or antimicrobial formulations or compositions may preferably be rich in calcium or magnesium (e.g., calcium or magnesium chloride). Suitable salt-based hygienic and / or antimicrobial formulations or compositions rich in calcium or magnesium may, for example, include: salt solutions containing 1%, 2%, 3%, 4%, 5%, 6%, 7% or 8% CaCl2or MgCh; 10 alternatively about 1 to about 10%, about 4% to about 10%, 1.0-8.0%, 1.0-6.0%, 1.02.0%, or 4.0-6.0% CaCh or MgCh. These CaCh or MgCh solutions might additionally contain NaCI, and may, for example, include: solutions containing 0.1%, 0.5%, 1.0%, or 1.5% NaCI; alternatively 0.1-1.5%, 0.5-1.5%, or 0.1-0.5% NaCI. In another embodiment, the salt-based compositions are devoid of any NaCI in the 15 compositions. In another embodiment, the salt-based compositions have 0.1% or less by weight of NaCI in the compositions. The percentages may be wt% based on the total amount of the salt-based composition in a droplet or other quantity of a solution (e.g., water, other solvent) containing the salt. As the examples demonstrate, the salt-based composition may comprise 4.72% CaCh and 0.31% 20 NaCI, or 1.29% CaCI2 and 0.9% NaCI. The salt-based solution may also optionally contain one or more preservatives. The preservatives may include any preservative that would not otherwise interfere with the chemistry of the salts in the salt-based formulation. As one skilled in the art would appreciate, preservatives are on the FDA list of non- 25 active agents. Suitable preservatives include benzalkonium chloride, benzyl alcohol, and benzoic acid. The preservative can be added in amounts known to those of skill in the art, for instance, 0.05-0.2 wt%, or about 0.1 wt%. Alternatively or additionally, the salt-based solution might also have low pH, through the addition of HCI or by some other means, e.g., pH in the range of about 2 to about 6; alternatively, about 2 30 to about 5; about 2 to about 3; or about 2.5. The HCI acid may be added with a citric acid buffer. 2021306236 27 Aug 2026 Alternatively, compositions of CaCb, with or without NaCI, containing lavender, cinnamon, lemongrass, and ethanol, among other essential oils and flavor extracts, are all effective. Essential oil, fragrance oil, and flavor extract compositions can take any of a large variety of forms, and may be mixed with water (e.g., distilled 5 or sterilized water). For example, begin with a vial of water 25 milliliters. Add 0.025 to 1 milliliter of essential oil, fragrance oil or flavor extract, as in cacao oil, caramel oil, cinnamon bark oil, coffee oil, eucalyptus oil, palm oil, fig oil, grapefruit oil, hazelnut oil, honeydew melon oil, lavender or spike lavender oil, lemongrass oil, lime oil, black or green pepper oil, peppermint oil, rosemary oil, strawberry oil, smoke oil, 10 tobacco vanilla oil, vanilla oil, chocolate extract, anise extract, and / or linalool or linalool containing essential oil. As an example, where the mass of cloud dispersed before the nose is less than 100 milligram total mass, the total quantity of ginger may be less than approximately 100 micrograms. Application may be simple, for example one or more deep nasal 15 inspirations may diminish exhaled aerosol by up to 75% or even 99% for up to six hours after administration. A protocol for administration may, for example include application on arrival at a location (e.g., worksite) prior to masking up. An initial application (e.g., two deep nasal inspirations) may be administered by a staff member or other personal assigned to the specific task. A second application (e.g., 20 two deep nasal inspirations) may follow, for example during a meal (e.g. lunch) break. The second application may, for example, be self-administered. Selfadministration may be performed from freely-accessible wall and / or table mounted nebulizers or misters, which may advantageously include hand sanitizer dispensers attached or positioned proximate to the nebulizers or misters. Alternatively, each 25 individual (e.g., employee) may be supplied with a personal nebulizer or mister and an adequate supply of calcium rich solution or dry powder to allow the individual to self-administerthe calcium rich airway hygiene, for example three times a day. Training may advantageously be provided, particularly where self-administration is employed. 30 Various apparatus are also describe herein which allow the portable, discrete delivery of salt-based hygienic and / or antimicrobial formulations or compositions, enhancing efficiency of delivery to humans and other animals on an 2021306236 27 Aug 2026 individual basis. Advantageously, the apparatus is configured to be portable, allowing the user to have the benefit of on demand delivery, in a wide variety of environments, for example to suppress virus shedding and / or to limit exposure (e.g., deep lung) to undesirable airborne contaminants (e.g., smoke and other airborne 5 toxins). Various apparatus are also described herein which allow the mass delivery of salt-based formulations or compositions to groups (e.g., two or more individuals, crowds, lines of individuals), enhancing efficiency of delivery to humans and other animals on a group basis. Such may be fixed devices, or portable 10 devices. Such may be suitable for use with crowds at stadiums, other venues, and / or at various events. Further, there is a need for diagnostic methods and apparatus that monitor respiratory droplet shedding from individuals, for example individuals who are known or suspected of having an airborne illness (e.g., infection of COVID-19 15 and other respiratory infectious diseases, including influenza), or who have been exposed to other individuals who are known or suspected of having an airborne illness, or who breathe for long durations polluted air. A diagnostic method may include: sampling exhaled breath for a subject, determining a metric that characterizes an amount of exhaled respiratory droplets shed in the exhaled breath, 20 and correlating the metric with a category that indicates at least one of: a level of illness risk and / or a level of transmission or transmissibility risk or a level of suggested quarantine precautions to be taken. The metric may, for example, take the form of a count or approximate count of exhaled respiratory droplets and / or pathogen presence, or another representation of an aerosol number. Sampling the 25 exhaled breath may be performed over a defined number of breathes or over a defined period of time. Correlation may be performed with respect to a representative sampling of breath samples taken from a representative sample of a population. Accordingly, one implementation may be summarized as a composition 30 of aerosol droplets comprising a salt-based composition comprising: (a) from about 1% to about 10% by weight calcium chloride and / or magnesium chloride in water (e.g., percentages per droplet). The droplets have a mass median droplet diameter 2021306236 27 Aug 2026 ranging from approximately 7 microns to approximately 15 microns. In some implementations the composition of aerosol droplets may include (b1) a preservative selected from the group consisting of benzalkonium chloride, benzoic acid, and benzoyl alcohol, or (b2) an acid in an amount sufficient to reduce the pH of the salt- 5 based composition to about 2 to about 6. Either the (b1) preservative or the (b2) acid may be present in some implementations. Another implementation may be summarized as a composition comprising (a) a dry powder containing calcium and / or magnesium chloride; and (b) a sterile solution. The sterile solution may comprise of consist of water (e.g., sterile 10 water). In some implementations, a water-based composition may comprise: (1) a preservative selected from the group consisting of benzalkonium chloride, benzoic acid, and benzoyl alcohol, or (2) an acid in an amount sufficient to reduce the pH of the salt-based composition to about 2 to about 6. The dry powder can be mixed with the water or water-based composition to form a salt-based composition. 15 Another implementation may be summarized as a method of administering a formulation or composition to the nose, trachea, and main bronchi of a respiratory tract of a subject. The method comprises generating an aerosol of droplets in a space from which the aerosol is naturally inspirable by the subject, in the nose, trachea, and main bronchi of the respiratory tract of the subject, without 20 any application of force. The aerosol of droplets comprises a salt-based composition comprising calcium chloride and / or magnesium chloride in water, and the droplets have a mass median droplet diameter ranging from approximate 7 microns to approximately 15 microns. Another implementation may be summarized as a method of 25 suppressing the exhalation of particles in an upper airway of a respiratory tract of a subject. The method comprises generating an aerosol of droplets, and administering the aerosol of droplets to the airway lining fluid in the nose, trachea, and main bronchi of the subject, thereby suppressing the exhalation of particles in the upper respiratory tract of the subject. The aerosol of droplets comprise a salt-based 30 composition comprising calcium chloride and / or magnesium chloride in water droplets, the droplets have a mass median droplet diameter ranging from 2021306236 27 Aug 2026 approximately 7 microns to approximately 15 microns, and the droplets are suspended in a standing cloud. Another implementation may be summarized as a delivery system operable to delivery of a purely hygienic or antimicrobial formulation or composition 5 to the nose, trachea and main bronchi of a respiratory tract of a subject. The delivery system comprises a reservoir having at least one wall which at least partially delimits an interior of the reservoir from an exterior thereof, the reservoir having a port that provides a fluidly communicative path between the interior of the reservoir and an exterior thereof, the reservoir which at least in use holds the hygienic or 10 antimicrobial formulation or composition comprising a quantity of water and at least calcium chloride and / or magnesium chloride dissolved in the water. The delivery system also includes at least one nebulizer delivery device, the at least one nebulizer delivery device comprising a reservoir and an actuator, and the actuator controllably operable on the active substance media to cause formation of an aerosol 15 comprising readily-soluble droplets that have a mass median diameter range of approximately 7 microns to approximately 15 microns and comprising at least the calcium chloride dissolved in the quantity of water. Another implementation may be summarized as a kit to suppress the exhalation of particles in an upper airway of a respiratory tract of subjects. The kit 20 comprises a measured quantity of calcium chloride and / or magnesium chloride; a container sized to receive a defined quantity of water to dissolve the calcium chloride therein; and instructions. Another implementation may be summarized as a method of administering a formulation or composition to the nose, trachea, and main bronchi of 25 a respiratory tract of a subject. The method comprises generating an aerosol of droplets in a space from which the aerosol is naturally inspirable by the subject, in the nose, trachea, and main bronchi of the respiratory tract of the subject, without any application of force. The aerosol of droplets comprises a salt-based composition comprising calcium chloride and / or magnesium chloride in water. The method of 30 administering the formulation or composition to the nose, trachea, and main bronchi of a respiratory tract of the subject is achieved by spraying the salt-based 2021306236 27 Aug 2026 composition in the nose of the subject while the subject has their head leaning back or is in a reclined position that promotes post-nasal drop. Another implementation may be summarized as a composition of aerosol droplets comprising a salt-based composition, comprising (a) from about 1% 5 to about 5% by weight calcium chloride in water; and (b1) a benzalkonium chloride preservative, or (b2) an acid in an amount sufficient to reduce the pH of the saltbased composition to about 2 to about 3. Advantageously, this method is not limited by the droplet size, although the ranges described can still be effectively used with the method, for instance in a 20-30 mg dosage range. 10 Salt-based non-therapeutic hygienic formulations or compositions or therapeutic formulations or compositions, for example those rich in calcium, are effective against airborne pathogens and toxins, suppressing shedding, for instance by increasing a surface viscoealasticity of airway lining fluid. Associated apparatus, methods and articles are used to deliver salt-based non-therapeutic hygienic 15 formulations or compositions as hygienic treatments to the upper respiratory tract. Associated apparatus, methods and articles are used to deliver salt-based therapeutic antimicrobial formulations or compositions to the upper respiratory tract. For example, nasal delivery of calcium-rich salines with aerosol droplet size of around 10 pm (e.g., 7 pm -15 pm, or more preferably 9 pm -10 pm) may 20 advantageously limit distribution to the nose and upper airways of the respiratory tract, suppressing bioaerosol generation / shedding of pathogens and toxins. A nebulizer or pump with micron scale orifice() may deliver the aerosol into free space, or into a partially enclosed volume, and the composition inspired (e.g., naturally inspired by normal breathing) by one or more subjects. 25 BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS In the drawings, identical reference numbers identify similar elements or acts. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes of various elements and angles are not drawn to scale, and some of these elements are arbitrarily enlarged 30 and positioned to improve drawing legibility. Further, the particular shapes of the elements as drawn, are not intended to convey any information regarding the actual 2021306236 27 Aug 2026 shape of the particular elements, and have been solely selected for ease of recognition in the drawings. Figure 1A is an isometric view of a delivery device delivering an aerosol of a salt-based hygienic and / or antimicrobial formulation or composition into 5 an unconfined space or volume to be inspired by a subject, according to at least one illustrated implementation. Figure 1B is an illustrative diagram of various sequential acts performed in using a delivery device to deliver an aerosol of a salt-based hygienic and / or antimicrobial formulation or into either a unconfined or free space or volume, 10 or into a confined space or volume (e.g., mask, tumbler, glass, vial beaker or other container), to be inspired by a subject, according to at least one illustrated implementation. Figure 2A is a bar graph showing particles exhaled from two human volunteers prior to dosing with a salt-based hygienic and / or antimicrobial formulation 15 or composition who exhibited relatively high virus shedding, according to at least one illustrated implementation. Figure 2B is a bar graph showing particles exhaled from eight human volunteers prior to dosing with a salt-based hygienic and / or antimicrobial formulation or composition who exhibited relatively average virus shedding, according to at least 20 one illustrated implementation. Figure 3 is a line graph showing particles exhaled from the ten human volunteers after dosing with a salt-based hygienic and / or antimicrobial formulation or composition, according to at least one illustrated implementation. Figure 4A is a graph showing particles exhaled per subject following 25 dosing with a salt-based hygienic and / or antimicrobial formulation or composition in comparison to a placebo control, according to at least one illustrated implementation. Figure 4B is a graph showing particles exhaled per subject following dosing with a salt-based hygienic and / or antimicrobial formulation or composition in comparison to a placebo control, according to at least one illustrated implementation. 30 Figure 4C is a graph showing particles exhaled per subject following dosing with a salt-based hygienic and / or antimicrobial formulation or composition in comparison to a placebo control, according to at least one illustrated implementation. 2021306236 27 Aug 2026 Figure 4D is a graph showing particles exhaled per subject following dosing with salt-based hygienic and / or antimicrobial formulation or composition in comparison to a placebo control, according to at least one illustrated implementation. Figure 4E is a graph showing particles exhaled per subject following 5 dosing with a salt-based hygienic and / or antimicrobial formulation or composition in comparison to a placebo control, according to at least one illustrated implementation. Figure 4F is a graph showing particles exhaled per subject following dosing with a salt-based hygienic and / or antimicrobial formulation or composition in comparison to a placebo control, according to at least one illustrated implementation. 10 Figure 4G is a graph showing particles exhaled per subject following dosing with a salt-based hygienic and / or antimicrobial formulation or composition in comparison to a placebo control, according to at least one illustrated implementation. Figure 4H is a graph showing particles exhaled per subject following dosing with a salt-based hygienic and / or antimicrobial formulation or composition in 15 comparison to a placebo control, according to at least one illustrated implementation. Figure 41 is a graph showing particles exhaled per subject following dosing with salt-based hygienic and / or antimicrobial formulation or composition in comparison to a placebo control, according to at least one illustrated implementation. Figure 5 is schematic view of a portion of a delivery device, including a 20 nebulizer which can include a screen and at least one of a piezo-electric element, solenoid or electric motor physically coupled to move the screen, the device also including one or more of a radio, a transducer or sensor and a switch communicatively coupled to a control system, for example a microcontroller and memory, and operably coupled to control operation of the nebulizer, according to at 25 least one illustrated implementation. Figure 6A is an exploded view of a delivery device of Figure 5 to deliver a mist, a cloud, or an aerosol comprising a salt-based hygienic and / or antimicrobial formulation or composition that is effective against airborne pathogens, according to at least one illustrated embodiment. 30 Figure 6B is a perspective view of the delivery device to deliver a mist, a cloud, or an aerosol comprising a salt-based hygienic and / or antimicrobial 2021306236 27 Aug 2026 formulation or composition that is effective against airborne pathogens of Figure 6A, according to at least one illustrated embodiment. Figure 6C is a side view of the delivery device to deliver a mist, a cloud, or an aerosol comprising a salt-based hygienic and / or antimicrobial and / or 5 formulation or composition that is effective against airborne pathogens of Figures 6A and 6B, according to at least one illustrated embodiment. Figure 6D is a cross-sectional side view of the delivery device to deliver a mist, a cloud, or an aerosol comprising a salt-based hygienic and / or antimicrobial formulation or composition that is effective against airborne pathogens of Figures 10 6A-6C, according to at least one illustrated embodiment. Figure 6E is a side view of components of the delivery device to deliver a mist, a cloud, or an aerosol comprising a salt-based hygienic and / or antimicrobial formulation or composition that is effective against airborne pathogens of Figures 6A-6D, according to at least one illustrated embodiment. 15 Figure 6F is another side view of components of the delivery device to deliver a mist, a cloud, or an aerosol comprising a salt-based hygienic and / or antimicrobial formulation or composition that is effective against airborne pathogens of Figures 6A-6D, according to at least one illustrated embodiment. Figure 7A is a rear view of a printed circuit board and associated 20 components coupled thereto for use in the delivery device to deliver a mist, a cloud, or an aerosol comprising a salt-based hygienic and / or antimicrobial formulation or composition that is effective against airborne pathogens of Figures 6A-6F, according to at least one illustrated embodiment. Figure 7B is a side view of the printed circuit board and associated 25 components of Figure 7A, according to at least one illustrated embodiment. Figure 7C is a front view of the printed circuit board and associated components of Figures 7A and 7B, according to at least one illustrated embodiment. Figure 7D is a perspective view of the printed circuit board and associated components of Figures 7A-7C, according to at least one illustrated 30 embodiment. 2021306236 27 Aug 2026 Figure 7E is a rear view of the printed circuit board of Figures 7A-7D, without the associated components coupled thereto of Figures 7A-7D, according to at least one illustrated embodiment. Figure 7F is a side view of the printed circuit board of Figures 7A-7D, 5 without the associated components coupled thereto of Figures 7A-7D, according to at least one illustrated embodiment. Figure 7G is a front view of the printed circuit board of Figures 7A-7D, without the associated components coupled thereto of Figures 7A-7D, according to at least one illustrated embodiment. 10 Figure 7H is a front view of an alternative configuration of the printed circuit board of Figures 7A-7D, without the associated components coupled thereto of Figures 7A-7D, according to at least one illustrated embodiment. Figure 8 illustrates the general design of the protocol for the three study sites, specifically the GRCC study site, discussed in the experimental section. 15 Figures 9A, 9B and 9C show the results, in terms of exhaled aerosol particle numbers and sizes, for the 40 human subject volunteers in Bangalore (Figure (A), 120 human volunteers in Grand Rapids (Figure 9B), and 93 human volunteers on Cape Cod (Figure 9C). Figures 10Aand 10B show the exhaled aerosol numbers for 20 20 subjects 15 minutes after being administered Composition A (Figure 10A), and several hours after being administered Composition A. Figures 10C and 10D show the suppression effect following a Composition A administration, versus the nasal saline control on overall exhaled aerosol of all 40 subjects at two hours post dosing. 25 Figures 11 A, 11B, and 11C compare the effectiveness of nasal saline airway hygiene versus Composition A, shown in exhaled aerosol from all subjects before and 15 to 30 minutes post administration of Composition A or Simply Saline. The results for the 20% highest emitting aerosol subjects are shown in Figures 11A-C (Composition A). 30 Figures 12A, 12B and 12C present the overall degree of suppression of exhaled aerosol at each site for both Composition A and Simply Saline at 15 to 20 minutes post administration. Overall airway cleansing by the Simply Saline control is 2021306236 27 Aug 2026 insignificant in every case (BBH p<0.94, GRCC p<0.83, CCA p<0.65), while the overall Composition A airway cleansing effect is marginally significant at each site of the study (BBH p<0.169, GRCC p<0.124, CCA p<0.098). Figure 13A is a bar graph showing exhaled particle counts from a study 5 of a set of human subjects who presented with mild COVID-19 symptoms prior to treatment, according to at least one illustrated implementation. Figure 13B is a bar graph showing baseline values for the human subjects as a function of time period of infection, according to at least one illustrated implementation. 10 Figure 13C is a scatter plot showing baseline values for the human subjects as a function of age, according to at least one illustrated implementation. Figure 13D is a scatter plot showing C-Reactive Protein values for the human subjects as a function of age, according to at least one illustrated implementation. 15 Figure 14A is a line graph showing a percentage (%) change in average exhaled particle counts from corresponding base line measurements against time following the base line measurement for a subset of human subjects following administration of a hypertonic calcium-rich salts targeting the upper airways of the respiratory tract (FEND), according to at least one illustrated implementation. 20 Figure 14B is a line graph showing a percentage (%) change in average exhaled particle counts from corresponding base line measurements against time following the base line measurement for a subset of human subjects following administration of a nasal saline spray (simply saline), according to at least one illustrated implementation. 25 Figure 14C is a line graph showing a percentage (%) change in average exhaled particle counts from corresponding base line measurements against time following the base line measurement for a subset of human subjects who comprise a non-treated control group, according to at least one illustrated implementation. 30 Figure 15A is a bar graph showing a percentage (%) of study subjects which required intravenous antibiotic or steroid intervention among those study subjects with high inflammation in a first cohort which were administered the 2021306236 27 Aug 2026 hypertonic calcium-rich salts targeting the upper airways of the respiratory tract (FEND) and a second cohort which was administered the simple saline, according to at least one illustrated implementation. Figure 15B is a bar graph showing an oxygen saturation percentage 5 over a first day, a second day, and a third day for each of: i) a population that administered a calcium chloride hygienic and / or antimicrobial formulation or composition; ii) a population that administered a sodium chloride (saline) hygienic and / or antimicrobial formulation or composition; and iii) a human control group population who were not treated with a salt-based hygienic and / or antimicrobial 10 formulation or composition, according to at least one illustrated implementation. Figure 16A is a bar graph showing self-reported symptom scores as a function of days of hospitalization and administration over the first three days of FEND, according to at least one illustrated implementation. Figure 16B is a bar graph showing self-reported symptom scores as a 15 function of days of hospitalization and administration over the first three days of simply saline as one control, according to at least one illustrated implementation. Figure 16C is a bar graph showing self-reported symptom scores as a function of days of hospitalization and without administration of nasal salt, according to at least one illustrated implementation, according to at least one illustrated 20 implementation. DETAILED DESCRIPTION In the following description, certain specific details are set forth in order to provide a thorough understanding of various disclosed embodiments. However, one skilled in the relevant art will recognize that embodiments may be practiced 25 without one or more of these specific details, or with other methods, components, materials, etc. In other instances, well-known structures associated with microcontrollers, piezo-electric devices, Peltier devices, power supplies such as DC / DC converters, wireless radios ( / .e., transmitters, receivers or transceivers), computing systems including client and server computing systems, and networks 30 (e.g., cellular, packet switched), as well as other communications channels, have not 2021306236 27 Aug 2026 been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments. Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” 5 and “comprising” are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the 10 appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. As used in this specification and the appended claims, the singular 15 forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. It should also be noted that the term “or” is generally employed in its sense including “and / or” unless the content clearly dictates otherwise. The headings and Abstract of the Disclosure provided herein are for convenience only and do not interpret the scope or meaning of the embodiments. 20 In particular, described herein are new compositions, systems, methods, and articles of manufacture to advantageously delivery of one or more saltbased formulations or compositions, and in particular physiological salt formulations or compositions that are rich in calcium, to the upper airways of a respiratory tract via a nose to reduce virus shedding and / or as an antimicrobial and / or anti-contagion that 25 is effective against airborne pathogens, for instance to limit exposure (e.g., deep lung) to undesirable airborne contaminants (e.g., smoke and other airborne toxins). The nasal administration of physiological salts appears particularly effective at reducing airborne particles from exhaled breath including the sub-micron aerosolized particles that are ineffectively filtered by cloth face masks. For example, 30 nasal application of a drug-free, calcium-enriched nasal salt, interacts with airway lining mucus to cleanse the airways of bioaerosols which may reduce exhaled aerosol particles up to 99%, with an overall reduction of exhaled particles in a largest 2021306236 27 Aug 2026 cohort of human subjects of around 75%. Nasal application of physiological salts (e.g., calcium chloride; combinations of calcium chloride and sodium chloride) may, for example, restore the natural surface viscoelasticity of airway lining mucus, reducing the breakup of mucus caused by airflow during natural breathing. As most 5 of these airway droplets are submicron, and as acknowledged by WHO and CDC as potential carriers of SARS CoV-2, their reduction lowers risk of deep lung infection and spread of disease. The nasal administration of physiological salts can be an important addition to current COVID-19 hygiene protocols of mask wearing, hand washing, and social distancing. The nasal administration of physiological salts adds 10 to the efficacy of masks at reducing the penetration of respiratory droplets into the lungs or back into the environment; and provides an added layer of defense for when mask wearing is not a possible. In particular, a mister or nebulizer that delivers to the site of respiratory droplet formation an aerosol that has a high concentration of calcium may be 15 particularly effective. The ions of the calcium rich salt may associate with mucins on the surface of the airway lining mucus, strengthening resistance to the breakup of mucus. This may advantageously clean the airways of the respiratory droplets that can carry infection and insoluble environmental contaminants. A new therapeutic practice of nasal application of a calcium-rich saline 20 aerosol to the upper respiratory tract is proposed. Nasal application of physiological salts, and in particular application of an aerosol of droplets containing calcium rich salts (e.g., calcium chloride; combinations of calcium chloride and magnesium chloride, and combinations of calcium chloride and relative small concentrations of sodium chloride, e.g., 0.1% or less by weight of sodium chloride or completely 25 omitting sodium chloride) in sizes that constrain the aerosol predominately in the upper respiratory tract may produce advantageous antimicrobial effects. In particular, a mister or nebulizer that delivers to the upper respiratory tract an aerosol that has a high concentration of calcium may be particularly effective. The mister or nebulizer may deliver the calcium rich aerosol with or 30 without other salts that are effective antimicrobials and / or with or without other antimicrobial substances. 2021306236 27 Aug 2026 These salt-based hygienic and / or antimicrobial formulations or compositions are advantageously formulated as or in readily-soluble water droplets. The readily-soluble water droplets have a median size range of approximately 7 microns to approximately 15 microns, and preferably approximately 10 microns. 5 Thus, the readily-soluble water droplets are too large for significant penetration into the lungs, while being small enough to be carried into the nose and the upper airway of the respiratory tract. Advantageously, such can cause the salt-based hygienic and / or antimicrobial formulations or compositions to be delivered to the upper respiratory track without any appreciable delivery to the lower respiratory track, 10 unexpectedly successfully suppressing or otherwise significantly reducing the shedding of virus. Such can be employed to suppress virus shedding in humans and other animals. Such can additionally or alternatively be employed to produce other beneficial physiological effects, for instance limiting exposure (e.g., deep lung) to undesirable airborne contaminants (e.g., smoke and other airborne toxins). 15 The droplets are delivered as aerosol, and for instance taken in by the subject through the act of inspiration. The aerosol can be dispensed in an unenclosed volume for instance the open air (e.g., in a room, out of doors), preferably reasonably proximate to a location of one or more individual’s faces (e.g., positioned relatively in front of a nose of one or more subjects), without the use of an 20 enclosed volume (e.g., mask, chimney, tumbler, vial, beaker or other container or vessel). Alternatively, the aerosol may be dispensed in an enclosed or partially enclosed volume (e.g., mask, chimney, tumbler, vial, beaker or other container or vessel). The individual(s) draw the salt-based hygienic and / or antimicrobial active substances into the upper respiratory tract via the nose, for instance ortho-nasally 25 and / or retro-nasally, and possibly exhale the hygienic and / or antimicrobial active substances retro-nasally. Open air dispensing may be particularly suitable for treating large crowds, for example crowds entering a stadium or other venue, for instance without the individuals in the crowd touching any objects (e.g., delivery devices or dispensers). 30 The salt-based hygienic and / or antimicrobial active substance loaded droplets described here may for example, be produced from a small reservoir of less than 100 ML, for instance for individual treatment of subjects. Alternatively, larger 2021306236 27 Aug 2026 reservoirs may be employed, for instance when treating crowds of individuals entering a stadium or other venue or event location. The salt-based hygienic and / or antimicrobial compositions and formulations may comprise one, two, or more forms of physiological salts, at least 5 one of which is calcium chloride, which are dissolved in water. The salt-based hygienic and / or antimicrobial compositions and formulations may, for example comprise a combination of calcium chloride and sodium chloride, for example in ratio: a 4 x isotonic composition (4.72% CaCl2 in 0.31% NaCI) [0.43M CaCh, 0.05M NaCI]; ora 2 x isotonic composition (1.29 CaCh in 0.9% NaCI) [0.12M CaCh, 0.15M 10 NaCI], The salt-based hygienic and / or antimicrobial compositions and formulations may include one or more other salts, for instance potassium chloride and / or magnesium chloride. The salt-based hygienic and / or antimicrobial compositions and formulations may include one or more essential oil, fragrance oil or 15 flavor extract (e.g., cacao oil, caramel oil, cinnamon bark oil, coffee oil, eucalyptus oil, palm oil, fig oil, grapefruit oil, hazelnut oil, honeydew melon oil, lavender or spike lavender oil, lemongrass oil, lime oil, black or green pepper oil, peppermint oil, rosemary oil, strawberry oil, smoke oil, tobacco vanilla oil, vanilla oil, chocolate extract, anise extract, rose oil, and / or linalool containing oil) and / or solvents (e.g., 20 ethanol) in addition to water. Exhaled aerosol numbers appear to be not only an indicator of disease progression, but a marker of disease risk in non-infected individuals. Monitoring exhaled aerosol may be performed as a diagnostic technique in the identification and control of transmission and infection of COVID-19 and other respiratory infectious 25 diseases, including influenza. A NEW NATURAL DEFENSE AGAINST AIRBORNE PATHOGENS INTRODUCTION Airborne transmission of infectious disease by the very small droplets emitted from human airways on natural breathing, and that accumulate in poorly 30 ventilated indoor environments, has been observed for a range of respiratory 2021306236 27 Aug 2026 diseases, including tuberculosis, measles, chicken pox, influenza and SARS (Yi et al 2007). Recent observations place the novel coronavirus SARS-CoV-2 — carried by the small airborne droplets exhaled by COVID-19 infected individuals and reported stable in aerosol form for beyond 3 hours — in the family of airborne transmitted 5 infectious diseases as well. The assessment of SARS-CoV-2 as an airborne pathogen clarifies the nature of the fight against the COVID-19 pandemic. While major international scientific efforts advance toward the development of drugs and vaccines in response to the COVID-19 pandemic, less attention has been given to new ways to prophylactically combat airborne viral and 10 bacterial threats. Social distancing, the washing of hands and the wearing of face masks, while each effective and necessary, do not prevent the transmission of pathogens that travel through the air within droplets smaller than 1 pm in diameter. Such small particles are not only too small to be filtered effectively by conventional masks, they are also too small to settle by gravity within the 2 meter threshold of 15 social distancing. Sub-micron droplets happen to be the majority of particles emit from mouths and noses when breathing naturally. The sub-micron particles emerge from the respiratory system either by the necking of airway lining fluid that occurs with the expansion and contraction of the lungs, or by the rapid movement of air through 20 upper airways, as occurs during natural breathing, coughing, sneezing, and speaking. Whether high or low in the airways, shedding of small droplets from infected lungs can carry viral and bacterial pathogens and / or toxins into the environment, promoting disease spread. When this shedding of droplets occurs in the upper airways, it can promote movement of pathogen or toxins deeper into the 25 lungs, and, for instance self-infection. The delivery of saline to the respiratory system has been observed to diminish the exhalation of these very small particles. This diminution is due to electrostatic interactions between salt cations and mucin and mucin-like proteins on the surface of airway lining fluid. These increase the viscoelasticity of the surface of 30 airway lining fluids, reducing the formation of airborne droplets. Calcium chloride, far more than sodium chloride, has been found to increase the surface elasticity of airway lining fluid, potentially promoting even more substantial suppression of 2021306236 27 Aug 2026 airborne particle generation in the airways, while enhanced surface plasticization also further resists pathogen penetration through the mucus layer, strengthening its biophysical barrier to infection. Calcium and sodium salts appear to have antimicrobial properties as 5 well. High concentrations of extracellular calcium, as can be achieved by the aerosol delivery of calcium salts, promote the secretion of p-defensin 2 from nasal epithelial cells. Human p-defensin 2 is an endogenous antimicrobial peptide that conjugates with receptor-binding domains of many viruses, including coronaviruses, to promote expression of antiviral and immune-inducing molecules as well as 10 chemokine recruiters of leukocytes. Human p-defensin 2 has been shown to be effective as an antiviral adjuvant due to its binding to the spike protein of MERS CoV, and mouse beta defensin 4 derived peptide has shown activity against SARS CoV-1. Chloride salts have been shown to diminish viral replication as far back as the 1960s. Chloride ions promote antiviral activity by the induction within cells of 15 hypochlorous acid, the active constituent of bleach. Chloride salts induce innate immune response of epithelial cells in the presence of sodium chloride. Sodium hypochlorite, the sodium salt of hypochlorous acid, has particularly demonstrated effectiveness as a disinfectant against coronavirus. High concentrations of chloride, delivered via hypertonic saline to nasal epithelial tissues, have been found to 20 diminish viral infections associated with the common cold. In an open-labeled randomized controlled human study of 68 subjects with common cold infections including rhinoviruses and coronaviruses, as well as enterovirus, influenza A virus, nasal delivery of 2-3% hypertonic saline 2-8 times a day (median thrice-a-day) significantly lowered duration of illness, as well as use of over-the-counter 25 medications, household transmissions, and viral shedding. Nasal administration of 3.5% hypertonic seawater has similarly shown indications of efficacy against common cold symptoms in other human clinical trials. Described herein are various salt compositions incorporating at least two ions that are abundant in human tissues: calcium, and chloride, and optional a 30 third ion sodium, which may be used for hygienic applications, for example to address the need for a broad prophylactic and anti-contagion defense against respiratory viral and bacterial infections. Without being bound by theory, the 2021306236 27 Aug 2026 inventor(s) hypothesized that an aerosol combining calcium and optionally sodium salts would improve the barrier function of the mucus lining to protect against infection while diminishing bioaerosol formation in the lungs and nasal passages. Given the hygienic practice of nasal saline flushing, the nasal delivery of these 5 physiological salines were evaluated with a specially designed nasal mist, as a practical, efficacious and safe personal hygiene intervention, complementary to masks. This might prove of particular utility to the immediate fight against the current COVID-19 pandemic, but would also potentially be useful against other airborne pathogens and / or toxins. 10 RESULTS NASAL DELIVERY DEVICE A hand-held nebulizer (Nimbus™) device was designed capable of delivering salt-based hygienic and / or antimicrobial formulations or compositions nasal doses of around 1-2 mg CalCh. The nebulizer device employed integrated 15 vibrating meshes with a 6 pm pore size to produce, on tipping of the device, an aerosol cloud with a particle size distribution optimal for delivery within the nose through natural nasal inspiration. The particle size distribution of the aerosol cloud reveals a median volume particle diameter of 9-10 pm, an optimal size for nasal and upper airway deposition of aerosol following a natural tidal inspiration through the 20 nose and with relatively uniform distribution of deposition from the anterior to the posterior of the nose (Calmet et al 2019). The particle size distribution is significantly smaller than that produced from a standard nasal pump spray (Figure 6B). On tipping (Figure 1A), Nimbus™ nebulizer device produces 57 mg + / 2 mg within a 10 second actuation, after which power ceases until tipped back 25 upright and again overturned. The Nimbus™ nebulizer device is designed to deliver a controlled dose of approximately 33 mg (i.e., 1.56 mg CalCh or 0.43 mg CalCh) by filling an empty 6 oz. glass with the cloud for the internally programmed 10 second actuation of the device and then inspiring the cloud directly from the glass into the nose (Figure 1B). Uncontrolled dosing can also be achieved by creating the cloud 30 before the nose and direct natural deep nasal inspiration (Figure 1B). 2021306236 27 Aug 2026 It was decided to pursue a human volunteer study with Nimbus™ nebulizer device to evaluate the effectiveness of salt-based hygienic and / or antimicrobial formulations or compositions for suppressing exhaled aerosol particles following nasal administration in comparison to our observation of the effectiveness 5 of the salt-based hygienic and / or antimicrobial formulations or compositions on pulmonary delivery. HUMAN EXHALED BIOAEROSOL STUDIES: NASAL ADMINISTRATION Ten healthy volunteers were recruited in St Augustine, Florida and 10 Boston, Massachusetts. Each signed informed consent to participate in the several-hour nasal saline hygiene study. Five of these subjects were older than 65 (70, 75, 82, 83, 88) and five younger than 65 (30, 40, 59, 60, 63). Subjects with severe respiratory illnesses were excluded from the study, while two of the subjects (ages 30 and 63) were cigarette smokers. 15 All subjects began the study by breathing into an apparatus that measured expired aerosols. Following a baseline assessment of exhaled aerosol particle count subjects drew two deep nasal inspirations of an 4 x isotonic composition of 1.29% CaCh and 0.31% NaCI dissolved in water via Nimbus™ nebulizer device. Subsequent to administration, subjects breathed into the airborne 20 particle detector at intervals for up to 6 hours post-dosing. Subjects also selfadministered a commercial (isotonic sodium chloride) simple saline cleansing spray (CVS Nasal Saline). Subsequent to nasal administration of the placebo control, subjects breathed into the airborne particle detector at intervals for up to 2 hours. Baseline exhaled particles per liter per subject age are shown in 25 Figures 2A and 2B. Two of the ten subjects in the older age (>65) group exhaled very high numbers of particles per liter of air (24,088 + / - 9,413 and 7,180 + / - 1250) (Figure 2A) while the other eight (Figure 2B) exhaled between approximately 10 and 1200 particles per liter. In the latter group two individuals (ages 30 and 63), were smokers. There is a strong correlation between high numbers of exhaled particles 30 and age, with the group older than 65 exhaling on average 6,641 particles per liter while the group younger than 65 on average 440 particles per liter. In ail subjects 2021306236 27 Aug 2026 over 95% of the baseline exhaled particles were less than 1 micrometer in size, with most smalier than 500 nm. Following administration of the salt-based hygienic and / or antimicrobial formulation or composition, exhaled particle numbers diminished for up to several 5 hours as shown in Figure 3. This diminution relative to baseline is statistically significant (p<0.05) for all 10 subjects. Duration of effect continued up to the last data point several (2-6) hours after administration for ail of the subjects other than subjects B and E, each of whom were very small producers of particles. Administration of the simple saline control has a minor suppressive effect on exhaled 10 particles for 2 of the subjects in the first hour following administration while in the other subjects we observed no suppressive effect (Figures 4A-4I). Using the lowest exhaled particle number following administration as a measure of suppression effect, diminution of bioaerosol ranged from a low of 45% (subject age 75) to a high of 99% (subject ages 83 and 70), with overall suppression 15 of aerosol for the group (99%) predominantly related to the dramatic effect of aerosolized salt-based hygienic and / or antimicrobial formulations or compositions on suppression amongst super producing individuals (subject ages 83 and 70). DISCUSSION Hypertonic calcium chloride and sodium chloride solution delivered to 20 the respiratory system appears to have potential as both hygienic and therapeutic biodefense against airborne pathogens. Hygienically, these physiological salts coat the surfaces of airway lining fluid to diminish breakup and clear away the sub-micron bioaerosol droplets that are not effectively captured by masks. By potentially boosting natural immunological defenses — strengthening the barrier function of the 25 airway lining fluid and promoting the secretion of p-defensin 2 from nasal and bronchial epithelial tissues— these salts may also act therapeutically for antimicrobial prophylaxis or treatment. While these results suggest that calcium and sodium chloride salt combinations may be therapeutically useful against bacterial and viral infections 30 including influenza, rhinovirus and pneumonia, these results point to an immediate hygienic value in the use of calcium chloride salt formulations and compositions in 2021306236 27 Aug 2026 the fight against any airborne infectious disease, including COVID-19, by cleaning the airways of the small airborne droplets that carry airborne infection. The finding that nasal inspiration of salt-based hygienic and / or antimicrobial formulation or composition of 1.29% CaCh and 0.31% NaCI dissolved 5 in water in a group of 10 healthy human subjects reduces exhaled particles between 45% and 99% by way of an aerosol too large to penetrate the lower airways (Figures 8 and 4A-4I), suggests that the upper airways are a primary source of expired bioaerosol. The high velocity airstreams created during natural breathing (often reaching turbulent airflow conditions) in the trachea and main bronchi disturb the 10 surfaces of airway lining fluid in the way of wind passing over the sea to generate sea mist. Such phenomena are highly sensitive to compositional variations in the underlying fluid, making exhaled bioaerosol a sensitive measure of airway lining fluid and introducing variability within and between subjects. In the study the application of the salt-based hygienic and / or 15 antimicrobial formulation or composition substantially cleared away exhaled particles, most being less than 1 pm in size. That particles in the range of 300 to 500 nm were the most predominant observed in the exhaled breath of subjects can be explained by the fact that such particles are both too small to deposit in the lungs by gravity or inertia, once generated, and too large to be deposit by diffusion. These 20 are the submicron particles most likely to remain suspended in the atmosphere essentially indefinitely. Possibly most important in terms of their ability to transmit infection — and deposit on surfaces including airways of the infected or naive individuals — are those particles in the 500 to 1000 nm range, a significant fraction of the exhaled particles of the super spreader individuals. These particles are also 25 substantially eliminated by the salt-based hygienic and / or antimicrobial formulation or composition treatment. In the study most of the airborne particles were exhaled from two of ten “super producing” individuals. This super production of bioaerosol promotes the phenomenon of super spreaders (Stein 2015). Super spreading events for COVID-30 19 have been reported in China (so-called patient 31), India (the Punjab outbreak), South Korea, and many other regions, and are suspected to be a primary mode of transmission of the disease. Among key correlates of super spreading are 2021306236 27 Aug 2026 suppressed immunity and infected lungs—two particular vulnerabilities of the most aged. Indeed older subjects in our study exhaled many more particles than younger subjects — suggesting the possibility that seniors, while among the most vulnerable to COVID-19 infection, may also be those most likely to spread the disease, and 5 underscoring the extreme risk seniors face today in nursing homes. As nasal hygiene, a salt-based hygienic and / or antimicrobial formulation or composition is easy to administer (Figure 1B), rapid (one or two deep nasal inspirations) and lasts long (at least 6 hours in those expiring the largest numbers of particles). It might be easily administered to individuals on entering 10 environments where they are likely to encounter others, including hospitals, nursing homes, prisons, schools, offices, factories, stadia, restaurants, and museums. The use of salt-based hygienic and / or antimicrobial formulations or compositions as an “invisible mask” supplement to traditional masks administered prior to close encounters with others in public and private spaces in order to clean the air of the 15 small particles that masks do not block appears a prudent addition to current hygienic practices in the face of the COVID-19 pandemic. More research may be performed to assess the consequences of calcium-enriched physiological salt nasal hygiene on airborne infection and transmission rates within environments at high-risk of COVID-19 and other airborne 20 infectious diseases. The therapeutic potential of these nasally and pulmonary delivery salts should also be explored beyond the scope of the in vitro and animal a studies reported here. Figure 1A is an isometric view of a delivery device 100 delivering an aerosol 102 of a salt-based hygienic and / or antimicrobial formulation or composition 25 into an unconfined space or volume to be inspired by a subject, according to at least one illustrated implementation. Tipping of a Nimbus™ nebulizer device with respect to a gravitational axis of the Earth actuated an actuator to cause a mesh to vibrate, thereby generating an aerosol cloud for dosing. Figure 1B is an illustrative diagram of various sequential acts 30 performed in using a delivery device to deliver an aerosol of a salt-based hygienic and / or antimicrobial formulation or into either a unconfined or free space or volume, or into a confined space or volume (e.g., mask, chimney, tumbler, vial, beaker or 2021306236 27 Aug 2026 other container or vessel), to be inspired by a subject, according to at least one illustrated implementation. A salt-based hygienic and / or antimicrobial formulation or composition can be administered by a Nimbus™ nebulizer device with a deep nasal inspiration either in an unconstrained environment, for instance before the nose of a 5 subject, or in a constrained environment (e.g., by containing the aerosol cloud in a partially enclosed environment such as a mask, chimney, tumbler, vial, beaker or other container or vessel). As illustrated in Figure 1B, a reservoir 104 containing the salt-based hygienic and / or antimicrobial formulation or composition 106 (e.g., CaCl2) dissolved 10 in water (e.g., distilled water) is provided at 1. At 2, the reservoir 104 is then coupled to a dispenser portion 108 of the Nimbus™ nebulizer device in a generally upright (with respect to the gravitational axis) orientation. The dispenser portion 108 of Nimbus™ nebulizer device 100 may include a housing, a mesh, an actuator coupled to drivingly oscillate the mesh at a desired frequency, and / or drive circuitry. The 15 drive circuitry may, for example, include an accelerometer, geomagnetic field sensor, level sensor, and / or gyroscope, which activate the actuator on sensing a tipping of the Nimbus™ nebulizer device relative to the gravitational axis. The drive circuitry may include a timer, that deactivate the actuator after a defined period of time, for example, to control the dosage of the salt-based hygienic and / or antimicrobial 20 formulation or composition dispensed. At 3, the Nimbus™ nebulizer device 100 is positioned proximate the face and / or nose 110 of a subject, and tipped relative to the gravitational axis to dispense a salt-based hygienic and / or antimicrobial formulation or composition as an aerosol 102 into an unconstrained or free space or volume 112, not contained by an 25 enclosure. In response, the drive circuitry activates the actuator to vibrate the mesh, causing the salt-based hygienic and / or antimicrobial formulation or composition to be dispensed as an aerosol proximate the nose 110 of the subject, for inspiration by the subject via the nose 110 (e.g., ortho-nasally) and into the upper airways of the respiratory tract. 30 Alternatively, at 4 the Nimbus™ nebulizer device 100 is positioned proximate an opening of a container or vessel 114, and tipped relative to the gravitational axis to dispense a salt-based hygienic and / or antimicrobial formulation 2021306236 27 Aug 2026 or composition as an aerosol 102 into a constrained or at least partially enclosed space or volume, at least partially contained by an enclosure (e.g., mask, chimney, tumbler, vial, beaker or other container or vessel 114). In response, the drive circuitry activates the actuator to vibrate the mesh, causing the salt-based hygienic 5 and / or antimicrobial formulation or composition to be dispensed as an aerosol 102 into the container or vessel 114. At 5, the container or vessel 114 is positioned proximate the face and / or nose 110 of a subject, for inspiration by the subject via the nose 110 (e.g., ortho-nasally and / or retro-nasally) and into the upper airways of the respiratory tract. 10 As used herein a confined or partially confined or constrained volume refers to a vessel sized volume (e.g., on the order of 1 foot3 or approximately 28316 cm3) as compared unconfined or unconstrained volumes (e.g., room sized volumes on the order of 100 foot3 or approximately 2.8 m3). Figures 2A and 2B show a measure of exhaled particles from ten (10) 15 human volunteers prior to salt-based hygienic and / or antimicrobial dosing. The exhaled particles per liter of air are shown within three size distributions, between 300 and 500 nm, between 500 nm and 1000 nm, and between 1000 nm and 5000 nm. In particular, Figure 2A shows results from two (2) of the human subjects (ages 63 and 70) who exhaled greater than 25,000 and 7000 particle per liter respectively, 20 the majority of these particles between 300 and 500 nm, and a large minority of the particles between 500 nm and 1000 nm. Figure 2B shows the results from the other eight (8) individuals who breathed out on average several hundred particles per liter. Figure 3 shows the measure of exhaled particles from each of the ten (10) human volunteers following salt-based hygienic and / or antimicrobial dosing. In 25 all cases statistically significant suppression of exhaled aerosol is observed while the effect is dramatically significant for the largest “super producing” subjects (ages 63 and 70), whose overall exhaled particle counts diminish more than 99% for 6 h following salt-based hygienic and / or antimicrobial nasal inspiration. Figures 4A-4I are graphs showing measures of exhaled particles per 30 subject following salt-based hygienic and / or antimicrobial dosing in comparison to the placebo control. All exhaled particles per liter (all sizes) are shown with standard error bars up to one hour post dosing comparing the effects of salt-based hygienic 2021306236 27 Aug 2026 and / or antimicrobial formulation or composition and isotonic saline (CVS Saline Spray) dosing on expired aerosol numbers In particular, for the subjects represented in Figures 4D and 4G, the saline control shows significant suppression, while for the subject represented in Figure 4F, it shows significant amplification. In all cases, 5 aerosolized treatment with a salt-based hygienic and / or antimicrobial formulation or composition suppresses exhaled aerosol counts relative to the control (p<.05) when comparisons are made between the closest time points of counts measured. The ages of the human subjects shown are: (A) 83 (B) 40 (C) 70 D) 88 (E) 76 (F) 59 (G) 63 (H) 75 (I) 30. 10 Figure 5 is a schematic diagram that shows a portion of a nebulizer delivery device 1000 according to at least one illustrated implementation. The nebulizer delivery device 1000 may take the form of, or otherwise include , a nebulizer 1002, with one or more actuators 1004, and a control subsystem 1006 and, or other electronics, according to at least one illustrated implementation. 15 The nebulizer 1002 can include one or more mesh screens 1008, for example a metal mesh screen, which is supported by a frame 1010 for movement, for example for oscillation or rotation The nebulizer 1002 can include one or more of a piezo-electric element 1012, solenoid 1014 or electric motor 1016 physically coupled to move the mesh screen(s) 1008 along at least one axis in response to 20 signals from the microcontroller to dispense aerosol into the chamber. In some implementations, the actuator is physically coupled to the mesh screen 1008 via one or more mechanical transmissions (e.g., elliptical gear) or magnetic transmissions. The nebulizer may, for example, oscillate the screen at ultrasonic frequencies to cause a dispersion of the scent media. The transducer may oscillate at a frequency 25 of about 112 KHz ± 10 kHz that is sufficient to atomize the fluid held in the fluid reservoir. As one of skill in the art will appreciate, the oscillation frequency may be geometry dependent, and may be tuned to the harmonic of each piezo element design that is employed as a actuator. The frequency of oscillation of such a transducer may be increased or decreased depending up on the properties of the 30 fluid or other materials held within the fluid reservoir. The fluid can, for example, have viscosity of around 1.25 mPa at room temperature. In at least some implementations, the transducer may form an annular ring with a metal-mesh 2021306236 27 Aug 2026 included within a center portion of the transducer. The metal-mesh screen 1008 may take the form of various metals, for example stainless steel or 304 or 316 grade, with the 316 grade being particularly resistant to corrosion. The metal-mesh screen 1008 may be provided as a foil. In some implementations, the metal-mesh screen 1008 5 may be fluidly coupled to the fluid reservoir via capillaries, thereby providing a fluid path that enables a low flow of the fluid from the fluid reservoir to the metal-mesh screen 1008. As such, the fluid may be transported to the metal mesh, via, for example, capillary action, where it is atomized into the vapor or, more preferably, an aerosol as a result of the oscillation of the transducer. In some implementations, the 10 metal-mesh screen 1008 may provide a filter that prevents large sized molecules from being emitted as part of the vapor or, more preferably, the aerosol that exits the dispenser. As such, the metal-mesh screen 1008 may have mesh openings that are approximately 6 microns in size. In some implementations, the mesh openings may be less than 6 microns in width (e.g., 5 microns, 4 microns, 3 microns, or 2 microns). 15 In some implementations, the mesh openings may be greater than 6 microns in width (e.g., 7 microns, 8 microns, 9 microns, or 10 microns). Preventing the larger molecules from being dispensed may provide for a better user experience by reducing the possibility that the vapor or, more preferably, the aerosol will irritate the user. 20 The nebulizer 1002 may include one or more of radios 1018, transducers or sensors 1020 and, or, switches 1022 communicatively coupled to the control subsystem 1006. The control subsystem 1006 may, for example, include one or more microcontrollers 1024, microprocessors, field programmable gate arrays, and, or 25 application specific integrated circuits. The control subsystem 1006 may, for example, include one or more nontransitory storage media 1026 that stores at least one of processor-executable instructions or data, which when executed by the microcontroller 1024 causes the microcontroller 1024 to control operation of the device 900, for example in response to one or more inputs. For example, the 30 microcontroller may receive signals from one or more of radios 1018, transducers or sensors 1020 and, or, switches 1022, and control operation of the nebulizer 1002 in response to same. For instance, the control subsystem may cause the nebulizer to 2021306236 27 Aug 2026 dispense or disperse scent media in response to a first input, and to stop the nebulizer 1002 from dispensing or dispersing salt-based antimicrobial and / or anticontagion formulations or compositions in response to a second input. Input can include user manipulation of a switch, positioning or orientation of the vessel by the 5 user, or wireless commands from a radio or remote controller. The nebulizer delivery device 1000 may, for example, include one or more switches and / or sensors. The switch(es) and / or sensor(s) may be communicatively coupled to the microcontroller and operable to produce a signal that causes the microcontroller to operate the actuator accordingly. The switches may, 10 for instance, include one or more of any of the following: a contact switch, a momentary contact switch, a rocker switch, etc. The sensors may, for instance, include one or more of any of the following: The device may, for example, include one or more sensors, for instance a one-, two- or three-axis accelerometer, a PIR motion sensor, an inductive sensor, a capacitive sensor, and, or Reed switches. The 15 switch(es) and / or sensor(s) may, for example, be operable to produce a signal that causes the microcontroller to operate the actuator in response to the at least one nebulizer delivery device 106 being coupled to at least one of the docks. The switch(nebulizer) and / or sensor(s) may, for example, be responsive to a presence or an absence of the vessel with respect to a base and operable to produce a signal 20 that causes the microcontroller to operate the actuator according to the presence or an absence of the vessel with respect to the base. The switch(es) and / or sensor(s) may, for example, be responsive to a position or orientation of the vessel and operable to produce a signal that causes the microcontroller to operate the actuator according to the orientation of the vessel. The switch(es) and / or sensor(s) may, for 25 example, be part of the at least one nebulizer delivery device. The nebulizer delivery device 1000 may include a transducer communicatively coupled to operate the nebulizer. The transducer may, for example, include one or more radios (e.g., cellular transceiver, WI-FI transceiver, Bluetooth transceiver) which receives wireless signals for instance RF or microwave 30 signals for one or more wireless communications devices (e.g., smartphones) or remote controllers. The transducer may, for example, include one or more receivers, 2021306236 27 Aug 2026 for instance an infrared receiver that receivers infrared light signals from a remote controller. Activation may be synchronized with the delivery of audio, video, or audiovisual media. For example, a smartphone or digital assistance (e.g., Amazon 5 Alexa®, Google Home®, Apple HomePod®) can cause activation of nebulizer 1002. A suitable microcontroller may take the form of an 8-bit microcontroller with in-system programmable flash memory, such as the microcontroller commercially available from Atmel Corporation under designation ATMEGA48 / 88 / 168-AU. The microcontroller executes a program stored in its 10 memory, and sends signals to control the various other components, such as, for example, the valves. Control signals may, for instance be pulse width modulated (PWM) control signal, particularly where controlling an active power supply device. Otherwise, control signals may take on any of a large variety of forms. For instance, the microcontroller may operate valves or the actuator 1004 simply by completing a 15 circuit that powers the respective value or actuator 1004. The nebulizer delivery device 1000 may optionally include a visual indicator (not illustrated) to indicate when the nebulizer delivery device 1000 is operating or turned ON. Although a single light emitting diode (LED) may be employed, the visual indicator may take any of a large variety of forms. The LED 20 may be capable of emitting one, two or more nebulizer colors. The visual indicator may also indicate other information or conditions, for instance the visual indicator may flash in response to an occurrence of an error condition. A pattern of flashes (e.g., number of sequential flashes, color of flashes, number and color of sequential flashes) may be used to indicate which of a number of possible error conditions has 25 occurred. In some implementations, the nebulizer delivery device 1000 is electrically powered by one or more batteries that may provide a power source for the oscillation of the actuator 1004. The battery may be small and lightweight, such as the batteries used for small electronic devices (e.g., hearing aids). In some 30 implementations, the battery is at least partially embedded within the nebulizer delivery device. In some implementations, the battery is selectively removable and replaceable, such as when the battery can no longer provide sufficient charge to 2021306236 27 Aug 2026 operate the nebulizer delivery device 106. Other types of power sources may be provided, such as a power source comprised of one or more photovoltaic panels and associated components that may convert light into energy that can be used to operate the nebulizer delivery device 106, an array of super- or ultra-capacitor cells, 5 or an array of fuel cells. While not illustrated, one or more cartridges may carry the salt-based antimicrobial and / or anti-contagion formulation or composition to be dispensed. The cartridges are sized and dimensioned to be removably receivable by a scent media reservoir of a nebulizer delivery device, to supply a solution of the salt-based 10 antimicrobial and / or anti-contagion formulation or composition to the nebulizer for dispersion, for example as a spray of droplets or an aerosol. The cartridges may be made of plastic. Single use cartridges may, for example contain a single dose of the substance to be dispensed, stored in a liquid form. Alternatively, large reservoirs may employed at large venues and events. 15 The cartridges may form a fluid reservoir and may be comprised of a polymer, elastomer, or other light-weight, durable material that may be used to hold a liquid. The cartridges may be formed of one or more plastics, for example an ABS or polycarbonate plastic. The plastic may be injection molded or vacuum molded to form the cartridges. The type of material or process employed to form the cartridges 20 from the material should not be considered limiting. In some implementations, the cartridges may include an interior cavity that forms the fluid reservoir that may be used to hold and contain one or more salt-based antimicrobial and / or anti-contagion formulations or compositions as a fluid or other material (e.g., powder, gel, colloidal suspension) that carries active substances (e.g., calcium chloride and sodium 25 chloride). In some implementations, for example, the fluid reservoir may be sized and dimensioned to hold up to 100 mL of the fluid. In some implementations, the fluid reservoir may be sized and dimensioned to hold a maximum amount of the fluid that used to form a single dose, which may, for example, hold less than 100 mL (e.g., 5 mL, 10 mL, 20 mL, 40 mL, or 50 mL). The fluid may be any liquid or other 30 material that is, or that carries, the salt-based antimicrobial and / or anti-contagion formulation or composition that are released when the fluid transitions to a vapor or, more preferably, an aerosol and is released. The cartridges may include an aperture 2021306236 27 Aug 2026 that forms part of the fluidly communicative path for the fluid to be transferred from the fluid reservoir to the a nebulizer to be converted into a vapor or, more preferably, an aerosol. The vapor or, more preferably, the aerosol may advantageously comprise readily-soluble water droplets have a median size range of approximately 7 5 microns to approximately 15 microns, and more preferably about 10 microns. Thus, the readily-soluble water droplets are too large for significant penetration into the lungs, while being small enough to be carried into the upper airways of the respiratory tract via the nose. Figures 6A-6F illustrate various views of a handheld Nimbus™ 10 nebulizer delivery device 2100 for producing and delivering a cloud of aerosolized salt-based antimicrobial and / or anti-contagion formulation or composition in aerosol form (e.g.^ suspension of droplets in air, for instance a suspension of small water droplets each comprising CaCh and / or MgCl2 salts in the water of the droplets in the recited concentrations, with or without NaCI). 15 The hand-held nebulizer (Nimbus™) operates on the basis of a vibrating mesh activated by two replaceable AAA batteries. The device is comprised of a head, which contains the piezoelectric vibrating mesh and on / off trigger, and a base or 1 oz. (30 mL) vial into which the salt-based hygienic and / or antimicrobial formulation or composition solution can be filled. The Nimbus™ vial is detachable 20 and made either of glass or plastic, full of sterile solution and discarded once empty. To evaluate delivered dose a 4-place balance (0.1 mg precision) was used along with the hand-held nebulizer. Nimbus™ was inverted and cloud dispensed into a 6 ounce jar covered by a disk with a hole for cloud emission into the glass container. After ten seconds the cloud ceased to form, the Nimbus™ was removed, the disk 25 removed, and the weight of the glass determined. The “Discharged Dose” (n=5) results comprise measuring the entire 10-second emission into the jar through the coaster, and capping the coaster hole immediately after. The total emitted mass from the device was determined to be 57.0 ± 2.1 mg. Approximately 22.1 ±1.5 of the dose deposited on the walls of the glass or ~39% of the emitted dose. Nasally 30 delivered dose was assessed by two users affecting a single nasal inhalation from the glass post filling (n=5). The results 22.6 mg and 23.4 mg, respectively suggest a reproducible delivery of the solution and in the range of the target nasal dose. 2021306236 27 Aug 2026 The device 2100 can include any of the features of any of the other devices described herein, and can be used in combination with any of the other devices described herein. As illustrated in Figure 6A, delivery device 2100 includes a base 2102, which can be transparent and which includes a hollow container or 5 tank or vial, in some cases having a volume or capacity of less than 100 mL, for holding salt-based antimicrobial and / or anti-contagion formulation or composition in a liquid form. The base 2102 also includes an upwardly-extending hollow conduit, tube, or pipe 2116, through which the salt-based antimicrobial and / or anti-contagion formulation or composition can be poured out of the base 2102 in a liquid form. An 10 exterior surface of the conduit 2116 includes a set of threads. The delivery device 2100 also includes a top or upper portion or main body 2104, which includes a hollow housing and the electronic and mechanical components of the delivery device 2100. Such components include a printed circuit board 2200 and associated components coupled thereto, a pair of batteries 2106, a 15 hollow conduit, tube, or pipe 2108, a piezo-electric device 2110, which can include or be physically coupled to a mesh screen having a mesh size of 3 microns, of 4 microns, of 6 microns, of 20 microns, or of between 3 and 20 microns, as well as an internal cover 2112, and an external cover 2114, which can be transparent or translucent. The housing of the main body 2104 can be opaque or translucent, and 20 can have a specific color such as red, orange, yellow, green, blue, purple, brown, black, or white. The internal cover 2112 can have an appearance matching that of the housing of the main body 2104. In particular, the internal cover 2112 can be opaque if the housing of the main body 2104 is opaque or translucent if the housing of the main body 2104 is translucent, and can have a specific color matching that of 25 the housing of the main body 2104, such as red, orange, yellow, green, blue, purple, brown, black, or white. The conduit 2108 includes a relatively wide top end portion, a relatively narrow middle portion and a relatively wide bottom end portion sized to extend around the conduit 2116 of the base 2102. An inner surface of the bottom end 30 portion of the conduit 2108 includes threads complementary to the threads of the conduit 2116 so that the conduits 2108 and 2116 can be threadedly engaged and thereby coupled to one another. When the conduits 2108 and 2116 are coupled to 2021306236 27 Aug 2026 one another, liquid salt-based antimicrobial and / or anti-contagion formulation or composition can be poured out of the base 2102 through the conduit 2116 and into the conduit 2108. The relatively wide top end portion of the conduit 2108 is sized and configured to house the piezo-electric device 2110 at the top end of the conduit 5 2108, so that the liquid salt-based antimicrobial and / or anti-contagion formulation or composition can flow through the conduit 2108 from the bottom end portion thereof to the piezo-electric device housed at the top end portion thereof. The conduit 2108 also includes a pair of flanges 2118 that are coupled to opposing outer side surfaces of the middle portion of the conduit 2108, and that 10 extend laterally outward from the respective side surfaces as well as in a direction aligned with the overall length of the conduit 2108. The flanges 2118 each include a recess or cradle that is shaped and configured to cradle a portion of one of the batteries 2106, to partially restrain the batteries 2106 when the device 2100 is assembled. The internal cover 2112 includes a generally circular or disk-shaped 15 main body portion and a hollow and truncated cone-shaped portion 2120 that extends upward from the main body portion. The main body portion of the internal cover 2112 includes a pair of openings or apertures 2122 that extend through the main body portion. Each of the apertures 2122 is sized and configured to cradle a portion of one of the batteries 2106, to partially restrain the batteries 2106 when the 20 device 2100 is assembled. The external cover 2114 includes a generally circular or disk-shaped main body portion and an opening or aperture 2124 that extends through the main body portion. The aperture 2124 is sized and configured to fit snugly around a portion of the outer surface of the cone-shaped portion 2120 of the internal cover 2112 when the device 2100 is assembled. 25 Figures 6B, 6C, and 6D illustrate perspective, side, and cross-sectional side views, respectively, of the delivery device 2100. Figures 6E and 6F illustrate two different side views of the delivery device 2100 with the housing of the main body 2104 removed to reveal internal components of the main body 2104. Figures 7A-7D illustrate the printed circuit board 2200 of the delivery 30 device 2100 with associated components coupled thereto. Figure 7A is a rear view of the printed circuit board 2200 and illustrates that the printed circuit board 2200 includes an LED 2202 physically and electrically coupled to the rear surface thereof, 2021306236 27 Aug 2026 which can be operable to light up or turn on when the delivery device 2100 is generating a cloud of aerosolized salt-based antimicrobial and / or anti-contagion formulation or composition or salt-based antimicrobial and / or anti-contagion formulation or composition in aerosol form, and to turn off when the delivery device 5 2100 is not generating a cloud of aerosolized salt-based antimicrobial and / or anti contagion formulation or composition or salt-based antimicrobial and / or anticontagion formulation or composition in aerosol form. The LED can be useful to a user of the device 2100 because when the LED lights up, the user can be confident that power is being supplied to the printed circuit board 2200. Figure 22A also 10 illustrates that the rear surface of the printed circuit board 2200 is physically and electrically coupled to two metallic springs 2204, each of which is positioned and configured to act as a contact for, and to partially support or cradle, one of the batteries 2106. One of the springs 2204 can act as a positive contact, while the other of the springs 2204 can act as a negative contact, for the batteries 2106, such 15 that the batteries 2016 will be installed within the device 2100 with their polarities reversed with respect to one another. Figure 7B is a side view of the printed circuit board 2200 and illustrates that the rear surface of the printed circuit board 2200 is also physically and electrically coupled to a plurality of gold pins 2208 to which a fluid sensor can be 20 physically and electrically coupled. Figure 7C is a front view of the printed circuit board 2200 and illustrates that the front surface of the printed circuit board 2200 can include an electrical connector 2212, which can be a JST connector, to allow an operator to physically and electrically couple other electronic devices, such as the piezo-electric device 2110, to the printed circuit board 2200 and to allow the printed 25 circuit board and other associated components coupled thereto to communicate with (e.g., transmit signals to or receive signals from) such other electronic devices including the piezo-electric device 2110. Figure 7C also illustrates that the front surface of the printed circuit board 2200 is physically and electrically coupled to a tilt sensor 2206, which can include an accelerometer or a ball tilt switch in which a ball 30 moves and connects pins to complete an electrical circuit when the device 2100 is tilted, and to a plurality of capacitors 2210 for storing electrical energy. Figure 7D is a perspective view of the printed circuit board 2200 and illustrates a perspective view 2021306236 27 Aug 2026 of the printed circuit board 2200 with the associated components coupled thereto. Figures 7E-7G illustrate the printed circuit board 2200 without the associated components coupled thereto. As illustrated in Figures 6A-6F, the rear of the printed circuit board 5 2200, illustrated directly in Figure 7A, faces toward the conduit 2108 and the center of the delivery device 2100, while the front of the printed circuit board 2200, illustrated directly in Figure 7C, faces away from the conduit 2108 and the center of the delivery device 2100. In some implementations, the printed circuit board 2200 receives power from a source at between 2.0 and 3.4 Volts DC, and provides power 10 to a load at 140 KHz and at 65 Volts peak-to-peak. Figure 7H illustrates a front view of an alternative shape and configuration for the printed circuit board 2200. Figures 7A-7H illustrate some examples of possible dimensions of the printed circuit board 22, with the numbers used in millimeters. It will be understood that the specific dimensions provided in these Figures are merely examples of possible suitable 15 dimensions. To operate the delivery device 2100, a user can fill the base 2102 with salt-based antimicrobial and / or anti-contagion formulation or composition in a liquid form and assemble the device 2100 except for the batteries 2106 and the external cover 2114, such as by screwing or threading the base 2102 onto the main body 20 2104. The user can then insert the batteries 2106 into the device 2100 through the apertures 2122 in the internal cover 2112, such that the batteries are partially cradled by the recesses of the flanges 2118, and such that bottom terminals of the batteries 2106 are in electrical contact with the springs 2204. The user can then couple the external cover 2114 to the rest of the device 2100, such as by threading 25 or press-fitting the external cover into a top end of the main body 2104. An underside of the external cover 2114 can include a strip of electrically-conductive material, such as metal, which can engage the top terminals of the batteries 2106 and electrically couple the upper terminal of one of the batteries 2106 to the upper terminal of the other one of the batteries 2106. 30 The user can then lift and tilt the device 2100, such that the fluid flows, under the force of gravity, from the base 2102, through the conduit 2108, to the piezo-electric device 2110. Once the user tilts the device 2100, for example to dock 2021306236 27 Aug 2026 with the primary vessel, the tilt sensor 2206 can generate and transmit a signal indicating that the device 2100 has been tilted. Further, once the fluid flows to the piezo-electric device 2110, the fluid may come into contact with a fluid sensor coupled to the pins 2208 and generate and transmit a signal indicating that the fluid 5 has reached the fluid sensor. Further still, the device 2100 can include a pressure sensitive switch on a bottom surface thereof which, when the device 2100 is picked up off of a flat surface, can generate and transmit a signal that the device 2100 has been picked up. In some implementations, the device 2100 includes no manually-operated switches or buttons, and receives no input from the user, other than one, 10 two, or three of the signals described above. Upon receipt of any one, any two, or all three of such signals, the device 2100 can activate the piezo-electric device 2110 to begin generating a cloud of aerosolized salt-based antimicrobial and / or anti-contagion formulation or composition or salt-based antimicrobial and / or anti-contagion formulation or 15 composition in aerosol form from the scent media in liquid form. Because the device 2100 is tilted sideways or upside-down, the cloud of aerosolized salt-based antimicrobial and / or anti-contagion formulation or composition or salt-based antimicrobial and / or anti-contagion formulation or composition in aerosol form can flow out of the device 2100 through the hollow cone-shaped portion 2120, and can 20 be dispensed into free space to be consumed directly by the user or can be poured into another container or vessel for subsequent consumption by the user. In some implementations, the device 2100 includes an internal timer and automatically turns off or de-activates the piezo-electric device 2110 to stop generating the cloud of aerosolized salt-based antimicrobial and / or anti-contagion formulation or composition 25 or salt-based antimicrobial and / or anti-contagion formulation or composition in aerosol form after a time period of about 5, about 10, about 15, or about 20 seconds. In other implementations, the device 2100 continues to operate and generate the aerosolized salt-based antimicrobial and / or anti-contagion formulation or composition or salt-based antimicrobial and / or anti-contagion formulation or composition in 30 aerosol form until the device 2100 is once again oriented upright or placed back on a flat horizontal surface. 2021306236 27 Aug 2026 When the fluid within the base 2102 runs out, the user can unscrew or unthread of the base 2102 from the main body 2104 of the device 2100, refill the base 2102 with more of a salt-based antimicrobial and / or anti-contagion formulation or composition in a fluid form, screw or thread the base 2102 back on to the main 5 body 2104, and then resume using the device 100. When the batteries 2106 die, no longer power the device 2100, and need to be replaced, the user can remove the external cover 2114 from the rest of the device 2100, such as by unscrewing, unthreading, or turning the external cover 2114 with respect to the rest of the device 2100. The old batteries 2106 within the device 100 can then be removed and new 10 batteries 2106 can be installed in their place. The user can then re-install the external cover 2114 onto the rest of the device 2100 and resume using the device 2100. In some implementations, the external cover 2114, or a surface of the rest of the device 2100 that engages with the external cover 2114, includes a detent, 15 and the detent is engaged as the external cover 2114 is turned with respect to the rest of the device 2100 just before the external cover 2114 is released from the rest of the device 2100. Engagement of the detent can serve as a signal to the user that the external cover 2114 is about to be released from the rest of the device 2100. Once the user releases and removes the external cover 2114 from the rest of the 20 device 2100, the batteries are disconnected and the device is unable to operate. Thus, the external cover 2114 can act as a switch, where removing the external cover 2114 from the rest of the device 2100 switches the device 2100 off and engagement of the external cover 2114 with the rest of the device 2100 switches the device 2100 into an ON state. 25 Alternatively or additionally, a dispenser may employ a structure (e.g., substrate) with one or more nozzles, the nozzles having orifices in the micron size range (e.g., 1 micron-30 microns). Such nozzles may take advantage of the Raleigh effect, passage through the micron sized range orifice causing a jet or stream of fluid to separate into a mono-disperse spray of droplets. Desired droplet size can be 30 achieved by properly dimensioning the orifice(s), with the droplets generally being twice the size of the orifice. Thus, an orifice size in the range of 3.5 microns to 7.5 microns can achieve a median droplet size in the range of 7 microns to 15 microns, 2021306236 27 Aug 2026 while a 4.5 micron orifice or a 5.0 micron orifice can achieve a median droplet size of 9 microns or 10 microns, respectively. The use of nozzles with micron sized orifices may advantageously reduce the variation between droplet size in an aerosol, leading or more uniformity and / or predictability of the amounts (e.g., mass) of an active 5 substance (e.g., salt) delivered to a subject in a unit time. Multiple micron sized orifices may advantageously increase the number of droplets in an aerosol per unit of time. Nozzles with micron sized orifices can be obtained from Medspray of The Netherlands. The nozzle(s) be implemented as part of a mister with a reservoir and associated pump. Manual activation of the pump can drive fluid from the reservoir 10 through the micron sized orifices. Delivery of an aerosol, and particularly an aerosol with a fairly consistent droplet size, may be advantageous over other forms of delivery (e.g., vapor). Vapor tends to linger longer, tends to stick to surfaces, and is generally more difficult to delivery precise amounts as compared to an aerosol. Droplets are 15 also typically capable of holding more mass (e.g., more mass of calcium chloride and / or magnesium chloride) then can a vapor, allowing an effective amount to be delivered in a shorter period of time than via a vapor. For instance, exposure to an aerosol of droplets with median size in the range of 7 microns to 15 microns for less than a minute (e.g., 10 seconds) can deliver as much salt as exposure to a vapor of 20 smaller than 7 microns for several minutes (e.g., 6 minutes). As noted herein, control over droplet size can advantageously target the upper airways, allowing delivery of a small quantity of salt to be effective as compared to delivery that is not constrained to the upper airways. Targeted the droplet size in the range of 7 microns to 15 microns may advantageously facilitate or enhance retro-nasal delivery, 25 which may be more efficient that ortho-nasal delivery. EXPERIMENTAL It was recently observed that the delivery of a nasal saline comprised of a mist of 10 pm droplets containing a mixture of calcium and sodium chloride salts can 30 reduce respiratory droplets by up to 99% for up to 6 hours post administration. The salts (a hypertonic mixture called Composition A) associate with mucin macromolecules near the mucus surface, binding mucus molecules together, thereby increasing mucus surface tension and surface viscoelasticity. These effects 2021306236 27 Aug 2026 help mucus surfaces withstand the stresses that occur on air passing over mucus during normal breathing, resulting in fewer respiratory droplets in the airways, and fewer exhaled aerosol particles — a form of “airway hygiene.” Airway hygiene follows a millennia-long tradition of nasal saline administration 5 for cleaning mucus surfaces of foreign particulate matter. Salts ranging from pure sodium chloride (table salt) at physiological tonicity (0.9% by weight) to more complex mixtures of salts including calcium chloride, magnesium chloride and others, have long been commonly administered as gavages and nasal sprays. Hypertonic salt compositions can particularly increase cilia beat, facilitating the 10 clearance of mucus and associated particulate matter toward the mouth. The effects of airway hygiene were explored in learning establishments in the USA (Grand Rapids Michigan and Cape Cod Massachusetts) and in comparison with a setting (Bangalore India) of relatively high airborne particulate burden. Two kinds of nasal saline administration were examined — Composition A and Simply 15 Saline Nasal Spray. The findings are reported below. Methods Human volunteer studies were conducted at Bangalore Baptist Hospital (BBH), Grand Rapids Community College (GRCC), and Cape Cod Academy 20 (CCA). IRB approval was received for these (non-drug cosmetic) studies from the BBH Ethics Committee, the GRCC Ethics Committee, and for the CCA study a waiver of the need for IRB approval from E & I Review, an independent accredited ethics review board. Forty 40 human volunteers were recruited in Bangalore, ages 26 to 63; 120 human volunteers in Grand Rapids, ages 11 to 68; and 93 human 25 volunteers on Cape Cod, ages 10 to 70. Overall 126 females, 104 males, and 23 undeclared persons were recruited. Of the 253 human subjects, 82 were Caucasian, 15 were African American, 33 were Asian, 33 were Latino, 49 were Indian, and 41 were undeclared. Participants were not screened for SARS CoV-2 infection by serology or polymerase chain reaction (PCR) before enrollment. While none of the 30 subjects were known to be COVID-19 positive, two of the subjects in Grand Rapids, a brother (16 years of age) and a sister (19 years of age) living in the same household, were suspected to be asymptomatic carriers given an unusually high exhaled aerosol number and sibling relationship. All participants in all studies 2021306236 27 Aug 2026 provided written informed consent prior to enrollment. Figure 8 illustrates the general design of the protocol for the three study sites (specifically the GRCC study site). Exhaled particles were measured, before and after nasal saline administration, by a particle detector (Climet 4504) designed to count airborne 5 particles in the size range of 0.3 to 5 micrometers. The particle detector was connected to standard nebulizer tubing and mouthpiece that filters incoming air through a HEPA filter. Each standard nebulizer tubing and mouthpiece was removed from sealed packaging before each subject prior to the subject’s first exhaled particle detection. On subsequent counting maneuvers the same 10 mouthpiece, tubing and HEPA filter were replaced into the particle counter system by the participant to insure effective hygiene. Subjects performed normal tidal breathing through a mouthpiece while plugging their noses over 1 to 2 minutes — beginning with two deep breaths to empty their lungs of environmental particles. Over this time frame particle counts per liter diminished to a lower baseline number reflecting 15 particles emitted from breakup of airway lining fluid surfaces in the subject's airways. Once the lower plateau of particle counts was reached subjects continued to breathe normally. Three to eight particle counts (average values of particle counts assessed over six seconds) were then averaged to determine the mean exhaled particle count and standard deviation. Participants sat opposite to the study administrator with a 20 Plexiglas® barrier in between. Two nasal salines were used in the studies. Composition A is a drug-free nasal saline hygiene formulation comprised of calcium chloride and sodium chloride in distilled water. Overall salt composition (4 x isotonic composition) is in the range of sea water, specifically with 0.43M CaCI2, 0.05M NaCI (4.72% CaCI2, 0.31%NaCI). 25 Composition A compositions were manufactured at Pharmasol (MA) in a GMP mixing and filling facility and contained in sealed plastic bottles (0.5 ounces). Composition A bottles were opened and emptied into glass vials of the Mister device. The hand-held, vibrating-mesh nebulizer is produced at Perfect Electronics in Shenzhen, China, with a 6 pm pore size to produce, on tipping of the device, an 30 aerosol cloud with a particle size distribution optimal for delivery to the nose through natural nasal inspiration. Generating a median volume particle diameter of 9-10 pm (16), optimal for nasal and upper airway deposition of aerosol following a deep natural tidal inspiration through the nose and with relatively uniform distribution of 2021306236 27 Aug 2026 deposition from the anterior to the posterior of the nose, Nimbus produces on tipping 57 mg +1- 2 mg within a 10 second actuation, after which power ceases until tipped back upright and again overturned. The device delivers a dose of approximately 33 mg (1.56 mg CalCh) by filling an empty 6 oz glass with the cloud for the internally 5 programmed 10 s actuation of the device and then inspiring the cloud directly from the glass into the nose. Dosing can also be achieved by creating the cloud before the nose with deep nasal inspiration. Simply Saline by Arm & Hammer, a nasal spray of isotonic sodium chloride available on the market, was bought and used (one spray per nostril) as a control. 10 Results Total Exhaled Aerosol Versus Ambient Inhaled Particle Mass Exposure Exhaled aerosol particle numbers and sizes at the three sites were assessed, 15 including 40 human subject volunteers in Bangalore (Figure 9A), 120 human volunteers in Grand Rapids (Figure 9B), and 93 human volunteers on Cape Cod (Figure 9C). At each site a small group of subjects exhaled around 80% of the overall aerosol of the group, adhering to the classical 20:80 rule of “super spreading” of infectious disease. 20 “Super Spreaders” (of aerosol particles) are considered those individuals who exhale 80% of total aerosol particles of the group (while being less than 20% of all subjects). Classic super spreader distributions can be found at each US sites: in Grand Rapids 24 (20%) of the 120 subjects produce 79.5% of the exhaled aerosol of the group, while at the Cape Cod site 19 (20%) of the 93 subjects produce 79.7% of 25 the exhaled aerosol of the group. However, only 10% (4 of the 40) subjects in India produce 82.6% of the exhaled aerosol of the group, while 20% of all subjects (8 subjects) produce 95.1% of all exhaled aerosol. The skewing of the importance of high emitters in India reflects the fact that exhaled aerosol numbers are dramatically higher at the Indian relative to the US 30 sites. The top 20% aerosol emitting individuals in Bangalore had mean exhaled aerosol particle numbers of 30,585+ / -11,380. Mean exhaled aerosols were statistically lower (p < 0.0002) at the US sites, notably 532+ / -668 in Grand Rapids and 818+ / -722 on Cape Cod. These differences mirror the differences in burden of airborne particulate matter between the Indian and US sites. Reported particulate 2021306236 27 Aug 2026 mass (PM10) smaller than 10 pm over this same time frame in India (Bangalore) was 150 pg / m3 while for the USA sites it was an order of magnitude lower (17 pg / m3 in Grand Rapids and 7 pg / m3 on Cape Cod). No statistically significant differences were observed in our study across sites 5 between exhaled aerosols among Caucasian, African American, Asian, Hispanic or Indian subjects, nor were significant differences observed between subjects of varying age or BMI. Correlations between exhaled aerosol and BMI years (BMI multiplied by age) was observed, while differences in BMI years between the three study sites were not significant. 10 Exhaled Aerosol Versus Time Post Airway Hygiene Administration The effect of airway hygiene on exhaled aerosol in Bangalore was evaluated as a function of time post administration and in comparison to the saline nasal spray control. 15 In the case of those subjects who received Composition A (n=20), post administration, exhaled aerosol numbers fell within 15 minutes and remained suppressed for at least three to four hours (Figure 10A). In the case of those subjects who received the saline nasal spray control (n=20), post administration exhaled aerosol numbers fell to a lesser degree, and were mixed over the several 20 hours post administration (Figure 10B). Figures 10C and 10D present the suppression effect following Composition A versus the nasal saline control on overall exhaled aerosol of all 40 subjects at two hours post dosing. The large difference in overall exhaled aerosol relative to baseline (86%) was highly significant (p<0.011) for the Composition A airway 25 hygiene (n=20), while the diminution in overall exhaled aerosol (34%) was insignificant (p<0.62) for the Simply Saline control (n=20). Exhaled Aerosol Suppression by Airway Hygiene Administration The effectiveness of nasal saline airway hygiene was evaluated in Bangalore, 30 Grand Rapids and Cape Cod by evaluating exhaled aerosol from all subjects before and 15 to 30 minutes post administration of Composition A or Simply Saline. The results for the 20% highest emitting aerosol subjects are shown in Figures 11A-C (Composition A). 2021306236 27 Aug 2026 Composition A administration reduces exhaled aerosol most significantly in the airways of those exhaling the greatest numbers of aerosol particles at each site, with the most significant % reductions appearing in the dirtiest air environment, notably Bangalore, where exhaled aerosol is most significantly elevated. The less 5 significant individual subject Composition A suppression relative to baseline seen in Figure 11A relative to Figure 10C relates to the continued decline in exhaled aerosol with time post Composition A administration (Figure 10A). Figures 12A, 12B and 12C present the overall degree of suppression of exhaled aerosol at each site for both Composition A and Simply Saline at 15 to 20 10 minutes post administration. Overall airway cleansing by the Simply Saline control is insignificant in every case (BBH p<0.94, GRCC p<0.83, CCA p<0.65), while the overall Composition A airway cleansing effect is marginally significant at each site of the study (BBH p<0.169, GRCC p<0.124, CCA p<0.098), reflecting the large dispersion in exhaled aerosol numbers between Low Spreaders and Super 15 Spreaders (Figures 11A-C). Discussion The study of exhaled aerosol in India and the USA suggests that prolonged inhalation of high levels of micron- and submicron particulate matter may promote 20 the generation of large numbers of respiratory droplets, and skew these droplets to submicron size (Figure 9). These findings are consistent with the hypothesis that inhaled particles, by landing on mucus surfaces, lower surface tension and surface viscoelasticity, rendering airway lining mucus more prone to breakup into droplets of smaller size. 25 These same trends were observed elsewhere in exhaled aerosol following viral (COVID-19) and bacterial (tuberculosis) infection in nonhuman primates. Exhaled aerosol increases, and exhaled aerosol particle size decreases, in tandem with proliferation of viral and bacterial burden in lung tissues. Whether or not, in the development of respiratory diseases such as COVID-19 30 and tuberculosis, the accumulation of viral and bacterial particles at or near mucus surfaces has a similar surface property alteration effect as the accumulation of fine particles breathed in from the atmosphere — the findings of this study suggest that an abundance of respiratory droplets play a role in the spread of airborne infectious 2021306236 27 Aug 2026 disease in dirty air settings. This might also explain the trends that have been observed for heightened risk of COVID-19 death in polluted settings. Airway hygiene is a simple hygienic intervention that can allow people to meet the respiratory droplet carrier challenge wherever they live. Administration of the 5 calcium-enriched nasal saline, by increasing surface viscoelasticity via calcium-mucin interactions, suppresses droplet breakup, cleaning the upper airways of respiratory droplets by up to 99% in the dirtiest airways (Figure 9C) for several hours (Figure 9A). The effectiveness of airway hygiene obviously can be influenced on the success of the application (i.e. deep nasal inspiration) technique, while it appears 10 significant within 15 minutes of administration (Figure 12) and is remarkably consistent across all the sites of and all subjects. It is especially effective for those breathing dirty air (Figures 10A, 10C). By comparison the nasal saline spray control has little to modest effect — no overall effect was observed in the short-term (15-30 minute) time frame of Figures 15 12A-C while an indication of effect in Figure 10B overtime. This conclusion is consistent with the belief the inhalation of isotonic saline suppresses exhaled aerosol, and may suggest that post-nasal drip drainage of the saline solution from the nose can reach the trachea in some subjects. It has been found that children and young adults (under the age of 26) exhale 20 very few particles. In the 120 children and young adults assessed, only 6 of these young people were observed to exhale more than 150 particles per liter, while 89% of the young subjects exhaled between 1 and 50 particles per liter of air. Of these six individuals all of these exceptions exhaled aerosols exceeding 1000 particles per liter. In three of these cases, subjects 5, 8 and 39 from our Bangalore study, the 25 young subjects breathed into their airways highly polluted air. In two of the cases, the Grand Rapids siblings (16 and 19 years of age), the children were suspected to have been asymptomatic carriers of COVID-19, while in one case, a 17 year-old male on Cape Cod, there was no obvious airway particle burden causality. It appears that while young people as a rule have very few respiratory droplets, they 30 can become high producers of respiratory aerosols, and especially should their airways be overridden by foreign particles, whether inbound particulate matter, or — as in the case of infection — proliferating virus. While a combination of environmental and biological factors clearly renders certain people more vulnerable than others to respiratory disease, and more 2021306236 27 Aug 2026 susceptible than others to the communication of airborne infectious disease, including COVID-19, the results suggest that by weakening airway lining mucus, inhaled particles may themselves be at the origin of excessive respiratory droplet creation, and risk of infection and transmission. 5 Before 313+ / -145 After 15 + / - 27 These results show that before administering Composition B, the individual exhaled 313 +1-145 particles per liter and 30 minutes after the person exhaled 15 +1- 27 particles per liter, thus demonstrating the effectiveness of 10 Composition B. Bangalore Study Details A randomly controlled two-armed study was conducted in Bangalore, India to assess whether salt hydration of the upper airways reduces symptoms of the delta variant of COVID-19. 15 Salts delivered to the upper airways increase upper airway hydration and reduce the generation of respiratory droplets. It was hypothesized that such salt-mediated reduction in respiratory droplet generation might slow progression of pathogens such as SARS-CoV-2 into the lower airways and reduce symptoms in mildly symptomatic COVID-19 patients independently of pathogen nature. 20 Methods Evaluated were the effects of daily administration of calcium-rich hypertonic salts to the upper airways on exhaled breath aerosol and COVID-19 symptoms in a randomized single-blinded nasal saline controlled study at Bangalore Baptist Hospital over a period (December 2020 through June 2021) during which the delta 25 (B. 1.617.2) coronavirus variant emerged as the predominant cause of Bangalore infections. The study recruited 84 human subject volunteers among mildly symptomatic COVID-19 patients. Participants were screened for SARS CoV-2 infection by polymerase chain reaction (PCR) before enrollment. IRB approval for the study was obtained from the Ethics Committee at Bangalore Baptist Hospital. All 30 participants provided written informed consent prior to enrollment. The study assessed symptoms immediately after enrollment by blood analysis (C-Reactive Protein, d-dimer), lung X-Ray, oxygen saturation, temperature and self-reported symptoms (fever, cough, diarrhea, loss of taste / smell, breathing difficulty, body pain). 2021306236 27 Aug 2026 Exhaled particles of all participants were measured by a particle detector (Climet 450-t) designed to count airborne particles in the size range of 0.3 pm to greater than 5 pm. Among participating COVID-19 positive patients, all participated in the exhaled aerosol measurements, while 39 were randomly assigned to two multi-day treatment 5 cohorts. An active (FEND) cohort of 20 subjects received by nasal inhalation a calcium-rich hypertonic salt solution (0.43M CaCI2, 0.05M NaCI) (4.72% CaCI2, 0.31% NaCI) via a hand-held, vibrating-mesh nebulizer and with a median volume droplet diameter of 9-10 pm designed to target the nose, trachea and main bronchi. A (Simply Saline) control cohort of 19 subjects received by nasal spray an isotonic 10 saline (0.9% sodium chloride) three times a day over the first three days following admission into the study. Patients received the active and control treatments three times a day for the first three days following admission into the study and were blinded to the active and the control. Exhaled aerosol was evaluated of all active and control patients before and after salt administration and monitored exhaled 15 aerosol for two hours post-delivery. All patients were monitored each day for oxygen levels, body temperature, IV antibiotic and steroid treatment (where needed), and self-reported symptoms on a scale of 1-5 (increasing in scale from no symptoms to the most severe symptoms). Excluded from the study were those patients whose severity of symptoms required escalation to intensive care during the first three days 20 post admission. Statistical significance of differences of variables was calculated using a multiway analysis of variance (ANOVA) test and Student t-tests. Findings As the delta variant of the SARS-CoV-2 virus spread in Bangalore India to become the predominant sequenced strain, the study measured an increase in mean 25 exhaled respiratory droplet numbers among 83 COVID-19 positive patients from 1,468+ / -1,883 particles per liter of air in the period December 2020 through February 2021 to 8,234 +1- 4,315 particles per liter of air in early June 2021. Administration of hypertonic calcium and sodium salts (FEND) to the upper airways of 39 patients in a randomly-controlled two-arm study at Bangalore Baptist Hospital suppressed 30 respiratory droplet generation by 42.72% + / - 30.51% (P=0.014) while no diminution was observed (P=0.39) 60 minutes post baseline measurement for those patients who received the nasal saline control (Simply Saline). Over the course of three days of daily administration intravenous antibiotics or steroid intervention was required in 2021306236 27 Aug 2026 those participants exhibiting severe inflammation (CRP levels greater than 10 mg / L) for 93% of the Simply Saline group and 55% of the FEND group. Oxygen saturation increased significantly for the FEND group (P=1,86e-8) while no significant increase in oxygen saturation levels was observed in the Simply Saline group 5 (P=0.128). Self-reported symptom scores reduced by 55.44% ± 7.43% in the FEND group, while for those patients who received the nasal saline spray control, selfreported symptoms reduce by 32.18% ± 7.91%. Among the FEND group 61% of patients discharged with no symptoms while 0% of the nasal saline group discharged with no symptoms. 10 Interpretation Thrice-a-day delivery of calcium-rich salts to the upper airways lowers need for anti-inflammatory steroid and antibiotic treatment, increases oxygen saturation, and reduces symptoms of COVID-19 in mildly symptomatic patients predominantly infected by the delta variant relative to isotonic nasal saline control. The results 15 suggest that daily administration of the non-drug salt solution to the upper airways may be a useful hygienic means of reducing severity of symptoms of COVID-19 independently of the nature of the COVID-19 variant. Introduction The challenges of rapid mutation and access to vaccination are prolonging the 20 COVID-19 pandemic and threatening human populations in low-income regions of the world. A non-pathogen specific hygienic approach for airborne respiratory disease equivalent to hand hygiene for gastrointestinal infectious diseases might save lives in the present global pandemic and post-pandemic improve respiratory health in the light of worsening air quality. 25 Upper airway hydration appears to reduce risks of airborne infectious diseases through a variety of mechanisms, including the increasing of cilia beat frequency and the reducing of upper airway generation of the respiratory droplets that have been found to be a principal vector for SARS-CoV-2 transmission. Nasal administration of a hypertonic mist of divalent calcium and magnesium salts with 30 droplet size of 9-10 pm median diameter appears to be an especially effective means of upper airway hydration, reducing respiratory droplet generation for 4-6 hours post administration in comparison to around 1 hour post the breathing of humid air or the wearing of a mask. Inhalation of the mist of 9-10 pm droplets targets the hypertonic salts to the trachea and main bronchi, where principal 2021306236 27 Aug 2026 hydration of incoming air occurs, providing a non-drug hydration approach to clearing the airways of respiratory droplets, and potentially reducing the movement of upperairway deposited inhaled pathogens (and other contaminants) irrespective of pathogen type deeper into the lungs where they can promote severe symptoms. 5 Applicant hypothesized that a three-times per day nasal administration of a calcium-rich hypertonic saline to the upper airways in human subjects infected by COVID-19 might reduce symptoms notably among recently infected, mildly symptomatic subjects, and be an effective non-drug strategy against increasingly contagious variants of SARS-CoV-2 including the delta variant (B. 1.617.2) that first 10 appeared in India in October 2020. To explore this hypothesis the study recruited incoming COVID-19 positive patients at the Bangalore Baptist Hospital from December 2020 through June 2021 in parallel with the recent surge of infections promoted by the spread of the delta coronavirus variant. The study assessed exhaled aerosol of all volunteers and enrolled a subset of volunteers into a randomly 15 controlled two-armed study as reported here. Methods Study Design and Participants The study recruited 84 human subject volunteers ages 16-57 among mildly symptomatic COVID-19 patients at Bangalore Baptist Hospital (BBH) during a phase 20 of the Indian pandemic (December to June 2021) over which sequenced BBH infections of the delta (B.1.617.2) coronavirus variant increased from a small minority of cases to up to 70% of Indian infections (14). Participants were screened for SARS CoV-2 infection by polymerase chain reaction (PCR) before enrollment. IRB approval for the study was obtained from the Ethics Committee at Bangalore Baptist 25 Hospital. All participants provided written informed consent prior to enrollment. Symptoms of all 84 participants were assessed immediately after enrollment by analysis of blood markers of inflammation (CRP, d-dimer), lung X-Ray, pulse oximetry, temperature and self-reported symptoms (fever, cough, diarrhea, loss of taste / smell, breathing difficulty, body pain). Exhaled particles of all participants were 30 measured by a particle detector (Climet 450-t) designed to count airborne particles in the size range of 0.3 pm to greater than 5 pm. Among participants 39 were randomly assigned to two treatment cohorts. An active (FEND) cohort of 20 subjects received by nasal inhalation a calcium-rich hypertonic salt solution (0.43M CaCI2, 0.05M 2021306236 27 Aug 2026 NaCI) (4.72% CaCI2, 0.31% NaCI) via a hand-held, vibrating-mesh nebulizer and with a median volume droplet diameter of 9-10 pm designed to target the nose, trachea and main bronchi. A (Simply Saline) control cohort of 19 subjects received by nasal spray an isotonic saline (0.9% sodium chloride). All participants received the active 5 or the control three times a day over the first three days following the start of the study. Patients were blinded to whether they received the active or the control. The study evaluated exhaled aerosol of all active and control patients before and after salt administration and monitored exhaled aerosol for one to two hours post-delivery. All patients were monitored each day for oxygen saturation levels, body temperature, 10 IV antibiotic and steroid treatment (where needed), and self-reported symptoms on a scale of 1-5 (increasing in scale from no symptoms to the most severe symptoms). Excluded from the study were those patients who required supplemental oxygen prior to admission or during the first three days post admission (blood oxygen saturation below 95%). 15 Procedures Exhaled particles were measured before and after administration of the active or the control by a particle detector (Climet 450-t) designed to count airborne particles in the size range of 0.3 pm to greater than 5 pm. The particle detector air port was attached by a flexible plastic tube to the side (by a T connector) of a 1” 20 inner diameter tube into which subjects inhaled and exhaled. The 1 ” tube connected at one end a mouthpiece provided with standard nebulizer tubing and at the other end a portable HEPA filter. The entire tubing system facilitated the filtration of all environmental particles from the lungs of subjects over a period of about one minute of breathing with subjects’ lips tightly sealed around the mouthpiece and pinching 25 their noses. The rate of flow of the particle counter (50 L / min) was near the typical peak inspiratory / expiratory rate of flow of human subject breathing such that the direction of air flow remained into the particle counter. Each standard nebulizer tubing and mouthpiece were removed from sealed packaging before each subject prior to the subject’s first exhaled particle detection. On subsequent counting 30 maneuvers the same mouthpiece, tubing and HEPA filter were reattached by the participant to insure the absence of contamination from one subject to the next. Before each test, the mouthpiece was replaced by a stopper and the particle detector was turned on to verify the absence of leakage of particles from the 2021306236 27 Aug 2026 environment. Background of less than 10 particles per liter of air was deemed “well sealed.” With the mouthpiece placed back onto the tubing, subjects performed normal tidal breathing through the mouthpiece while plugging their noses with their fingers over 1 to 2 minutes — beginning with two deep breaths to empty their lungs 5 of environmental particles. Over this time frame particle counts per liter of air pulled from the exhaled breath into the particle counter diminished and subsequently fluctuated around a baseline number. Given the assurance of no leakage from the outside environment, the tight lip seal and the pinched nose, we assumed this baseline number to equate to the particles generated within the subject’s airways. 10 Once the lower plateau of particle counts was reached subjects continued to breathe normally for the determination of exhaled aerosol particle number. Participants sat opposite to the study administrator with a Plexiglas® barrier in between. The Climet 450-t particle counter reports particle counts as a function of aerodynamic particle size ranges for particles larger than 0.3 pm, particles larger than 0.5 pm, particles 15 larger than 1 pm, and all particles larger than 5 pm. The numbers reported represent average values of particle counts automatically measured by the light-scattering detector over six seconds. For determination of exhaled aerosol particle number the study averaged three to eight average particle counts (each integrating a six second interval) as reported by the particle detector to determine the mean exhaled particle 20 count and the standard deviation. Blood samples were drawn and tests (i.e., C-reactive protein (CRP), D-dimer) performed to detect Covid-19. Oxygen saturation levels were measured by pulse oximetry. Those with high levels of inflammation and associated symptoms received either IV antibiotics or IV steroids. Patients were escalated to intensive care when 25 oxygen levels fell below defined levels, and excluded from the study. Outcomes Primary outcomes were exhaled aerosol particle counts, need for intravenous antibiotic or anti-inflammatory steroid administration, and oxygen saturation. A secondary outcome was daily self-reported symptom scores. Data from this study 30 are presented in Figures 13A, 13B, 13C, 13D, 14A, 14B, 14C, 15A, 15B, 16A, 16B, and 16C. Statistical Analysis All error bars represent 95% confidence intervals based on standard deviation values. Significance of differences in individual and collective aerosol numbers were 2021306236 27 Aug 2026 determined by twin-tailed T Test. Statistical significance of differences were calculated using a multiway analysis of variance (ANOVA) test for each set of variables. This allowed for evaluating the influence of multiple factors on the mean within a 95% confidence interval. P-values were calculated for each unique set of 5 variables compared to baseline values. Each P-value below 0.05 was considered to be statistically different. Figure 13A shows as a bar graph of exhaled particle counts from a study of a set of human subjects who presented with mild COVID-19 symptoms prior to treatment, according to at least one illustrated implementation. In particular, the 10 exhaled particle counts where collected prior to application of a calcium chloride aerosol of droplets with median droplet size of around 10 microns for one cohort, and prior to application of a sodium chloride (saline) aerosol of droplets with median droplet size of around 10 microns for another cohort. Figure 13B shows as a bar graph of baseline values for average 15 exhaled particle counts for the human subjects of the study as a function of time period of infection, according to at least one illustrated implementation. The error bars represent standard errors of the mean. Figure 13C shows as a scatter plot of baseline values for average exhaled particle counts for the human subjects as a function of age, according to at 20 least one illustrated implementation. Figure 13D shows as a scatter plot of C-Reactive Protein values for the human subjects as a function of age, according to at least one illustrated implementation. Figure 14A shows as a line graph of a percentage (%) change in 25 average exhaled particle counts from corresponding base line measurements against time following the base line measurement for a subset of human subjects following administration of a hypertonic calcium-rich salts targeting the upper airways of the respiratory tract (FEND), according to at least one illustrated implementation. Figure 14B shows as a line graph of a percentage (%) change in 30 average exhaled particle counts from corresponding base line measurements against time following the base line measurement for a subset of human subjects 2021306236 27 Aug 2026 following administration of a nasal saline spray (simply saline), according to at least one illustrated implementation. Figure 14C shows as a line graph of a percentage (%) change in average exhaled particle counts from corresponding base line measurements 5 against time following the base line measurement for a subset of human subjects who comprise a non-treated control group, according to at least one illustrated implementation. The non-treated group were not treated with the hypertonic calcium-rich salts targeting the upper airways of the respiratory tract (FEND) nor with the nasal saline spray (simply saline). 10 Figure 15A shows as a bar graph a percentage (%) of study subjects which required intravenous antibiotic or steroid intervention among those study subjects with high inflammation in a first cohort which were administered the hypertonic calcium-rich salts targeting the upper airways of the respiratory tract (FEND) and a second cohort which was administered the simple saline, according to 15 at least one illustrated implementation. The first cohort, which were administered the hypertonic calcium-rich salts targeting the upper airways of the respiratory tract (FEND), included 9 of 20 subjects. The second cohort, which were administered the saline, included 9 of 19 subjects. Figure 15B shows as a bar graph of an oxygen saturation percentage 20 over a first day, a second day, and a third day for each of: i) a population that were administered a calcium chloride hygienic and / or antimicrobial formulation or composition; ii) a population that were administered a sodium chloride (saline) hygienic and / or antimicrobial formulation or composition; and iii) a human control group population who were not administered a salt-based hygienic and / or 25 antimicrobial formulation or composition, according to at least one illustrated implementation. The error bars represent standard errors of the mean. Figure 16A shows as a bar graph self-reported symptom scores as a function of days of hospitalization and administration over the first three days of FEND, according to at least one illustrated implementation. The self-reported 30 symptom scores are reported on a scale of 1 to 5, with 1 = no symptoms, and 5 = most severe symptoms. 2021306236 27 Aug 2026 Figure 16B shows as a bar graph self-reported symptom scores as a function of days of hospitalization and administration over the first three days of simply saline as one control, according to at least one illustrated implementation. The self-reported symptom scores are reported on a scale of 1 to 5, with 1 = no 5 symptoms, and 5 = most severe symptoms. Figure 16C shows as a bar graph self-reported symptom scores as a function of days of hospitalization and without administration of nasal salt, according to at least one illustrated implementation, according to at least one illustrated implementation. The self-reported symptom scores are reported on a scale of 1 to 5, 10 with 1 = no symptoms, and 5 = most severe symptoms. Examples: Example 1. A composition of an aerosol of droplets comprising a saltbased composition, each droplet comprising: 15 from about 1% to about 10% by weight calcium chloride and / or magnesium chloride in water; and wherein the droplets have a mass median droplet diameter ranging from approximately 7 microns to approximately 15 microns. Example 2. The composition of example 1, wherein the droplets 20 comprise greater than 1 % by weight calcium chloride and / or magnesium chloride. Example 3. The composition of example 1, wherein the salt-based composition does not contain sodium chloride or contains 0.1 % or less by weight of sodium chloride. Example 4. The composition of any of examples 1 through 3, wherein 25 the salt-based composition further comprises an essential oil, fragrance oil or flavor extract selected from the group consisting of cacao oil, caramel oil, cinnamon bark oil, coffee oil, eucalyptus oil, palm oil, fig oil, grapefruit oil, hazelnut oil, honeydew melon oil, lavender or spike lavender oil, lemongrass oil, lime oil, black or green pepper oil, peppermint oil, rosemary oil, strawberry oil, smoke oil, tobacco vanilla oil, 2021306236 27 Aug 2026 vanilla oil, chocolate extract, anise extract, rose oil, linalool containing oil, and combinations thereof. Example 5. The composition of any of examples 1 through 3, wherein the salt-based composition comprises calcium chloride and / or magnesium chloride 5 and at least 10% by weight ethyl alcohol. Example 6. The composition of any of examples 1 through 3, wherein the droplets comprise about 4% to about 10% by weight calcium chloride and / or magnesium chloride. Example 7. The composition of any of examples 1 through 3, wherein 10 the droplets comprise about 1 % to about 5% by weight calcium chloride and / or magnesium chloride. Example 8. The composition of any of examples 1 through 3, wherein the droplets have a mass median droplet diameter ranging from 9 microns to 10 microns. 15 Example 9. The composition of any of examples 1 through 3, wherein the droplets have a mass median droplet diameter of approximately 9.5 microns, with a standard deviation of less than 1 micron. Example 10. The composition of any of examples 1 through 3, wherein the droplets have a mass median droplet diameter ranging from 7 microns to 15 20 microns, with a standard deviation of less than 5 microns. Example 11. The composition of any of examples 1 through 3, wherein a majority of the droplets have a droplet size between 9 microns and 10 microns in diameter. 2021306236 27 Aug 2026 Example 12. The composition of example 11 wherein a majority of the droplets have a droplet size of approximately 9.5 microns in diameter. Example 13. The composition of any of examples 1 through 3, wherein the salt-based composition comprises a preservative selected from the group 5 consisting of benzalkonium chloride, benzoic acid, and benzoyl alcohol. Example 14. The composition of example 13, wherein the preservative is benzalkonium chloride. Example 15. The composition of example 14, wherein the benzalkonium chloride is present in an amount ranging from 0.05 wt% to about 0.2 10 wt%. Example 16. The composition of any of examples 1 through 3, wherein the salt-based composition comprises an acid in an amount sufficient to reduce the pH of the salt-based composition to about 2 to about 6. Example 17. The composition of example 16, wherein the pH ranges 15 from about 2 to about 3. Example 18. The composition of example 15, wherein the acid is citric acid, hydrochloric acid, or a combination thereof. Example 19. The composition of any of examples 1 or 2, wherein the salt-based composition comprises about 1.0 wt% to about 6.0 wt% calcium chloride 20 and about 0.1 to about 1.5 wt% sodium chloride. Example 20. The composition of example 19, wherein the salt-based composition comprises about 1.0 wt% to about 2.0 wt% calcium chloride and about 0.5 wt% to about 1.5 wt% sodium chloride. 2021306236 27 Aug 2026 Example 21. The composition of example 19, wherein the salt-based composition comprises about 4.0 wt% to about 6.0 wt% calcium chloride and about 0.1 wt% to about 0.5 wt% sodium chloride. Example 22. A composition comprising: 5 (a) a dry powder containing calcium and / or magnesium chloride; and (b) a sterile solution of a water-based composition comprising (1) a preservative selected from the group consisting of benzalkonium chloride, benzoic acid, and benzoyl alcohol, or 10 (2) an acid in an amount sufficient to reduce the pH of the salt-based composition to about 2 to about 6; wherein the dry powder can be mixed with the water-based composition to form a salt-based composition. Example 23. The composition of example 22, wherein the water-based 15 composition comprises the preservative selected from the group consisting of benzalkonium chloride, benzoic acid, and benzoyl alcohol. Example 24. The composition of example 23, wherein the preservative is benzalkonium chloride. Example 25. The composition of example 22, wherein the water-based 20 composition comprises the acid in an amount sufficient to reduce the pH of the saltbased composition to about 2 to about 4. Example 26. The composition of example 22, wherein the pH of the salt-based composition ranges from about 2 to about 6. Example 27. The composition of example 26, wherein the pH ranges 25 from about 2 to about 5. 2021306236 27 Aug 2026 Example 28. The composition of example 25, wherein the acid is citric acid, hydrochloric acid, or a combination thereof. Example 29. The composition of example 22, wherein the dry powder does not contain sodium chloride or contains 0.1% or less by weight of sodium 5 chloride. Example 30. The composition of example 22, wherein the dry powder is in a sachet. Example 31. A method of administering a formulation or composition to the nose, trachea, and main bronchi of a respiratory tract of a subject to suppress 10 viral shedding, method comprising: generating an aerosol of droplets in a space from which the aerosol is naturally inspirable by the subject, in the nose, trachea, and main bronchi of the respiratory tract of the subject, without any application of force; wherein the aerosol of droplets comprises a salt-based composition 15 comprising calcium chloride and / or magnesium chloride in water, and wherein the droplets have a mass median droplet diameter ranging from approximate 7 microns to approximately 15 microns. Example 32. The method of example 31, wherein generating an aerosol of droplets comprises generating an aerosol of droplets wherein the droplets 20 comprise greater than 1 % by weight calcium chloride and / or magnesium chloride. Example 33. The method of example 31, wherein generating an aerosol of droplets comprises generating an aerosol of droplets wherein the saltbased composition does not contain sodium chloride or contains 0.1% or less by weight of sodium chloride. 25 Example 34. The method of any of examples 31 through 33, wherein generating an aerosol of droplets comprises generating an aerosol of droplets 2021306236 27 Aug 2026 wherein the salt-based composition further comprises an essential oil, fragrance oil or flavor extract selected from the group consisting of cacao oil, caramel oil, cinnamon bark oil, coffee oil, eucalyptus oil, palm oil, fig oil, grapefruit oil, hazelnut oil, honeydew melon oil, lavender or spike lavender oil, lemongrass oil, lime oil, black 5 or green pepper oil, peppermint oil, rosemary oil, strawberry oil, smoke oil, tobacco vanilla oil, vanilla oil, chocolate extract, anise extract, rose oil, linalool containing oil, and combinations thereof. Example 35. The method of any of examples 31 through 33, wherein generating an aerosol of droplets comprises generating an aerosol of droplets 10 wherein the salt-based composition comprises calcium chloride and / or magnesium chloride and at least 10% by weight ethyl alcohol. Example 36. The method of example 32, wherein generating an aerosol of droplets comprises generating an aerosol of droplets wherein the droplets comprise greater than 4% by weight calcium chloride and / or magnesium chloride. 15 Example 37. The method of any of examples 31 through 33, wherein generating an aerosol of droplets comprises generating an aerosol of droplets wherein the droplets have a mass median droplet diameter ranging from 9 microns to 10 microns. Example 38. The method of any of examples 31 through 33, wherein 20 generating an aerosol of droplets comprises generating an aerosol of droplets wherein the droplets have a mass median droplet diameter of approximately 10 microns, with a standard deviation of less than 1 micron. Example 39. The method of any of examples 31 through 33, wherein generating an aerosol of droplets comprises generating an aerosol of droplets 25 wherein the droplets have a mass median droplet diameter ranging from 7 microns to 15 microns, with a standard deviation of less than 1 micron. 2021306236 27 Aug 2026 Example 40. The method of any of examples 31 through 33, wherein generating an aerosol of droplets comprises generating an aerosol of droplets wherein a majority of the droplets have a droplet size between 9 microns and 10 microns in diameter. 5 Example 41. The method of any of examples 31 through 33, wherein generating an aerosol of droplets comprises generating an aerosol of droplets wherein a majority of the droplets have a droplet size of approximately 9.5 microns in diameter. Example 42. The method of any of examples 31 through 33, further 10 comprising the subject inhaling an amount of aerosol droplets comprising between 0.5-4.0 mg calcium chloride and / or magnesium chloride. Example 43. The method of any of examples 31 through 33, wherein generating an aerosol of droplets comprises providing the aerosol of droplets into a free space from which the aerosol of droplets are inhaled. 15 Example 44. The method of example 43, further comprising slowing down a velocity of the aerosol relative to a velocity of the aerosol as it leaves a dispenser and from which the aerosol becomes relatively quiescent. Example 45. The method of any of examples 31 through 33, further comprising providing the aerosol in a range of 12 inches to 1 inch of a nose of the 20 subject. Example 46. The method of any of examples 31 through 33, wherein further comprising providing the aerosol in a range sufficient distant to a nose of the subject such that the aerosol has zero or negligible net velocity at least horizontally with respect to the earth. 2021306236 27 Aug 2026 Example 47. The method of any of examples 31 through 33, wherein the generating an aerosol of droplets includes providing the aerosol in an at least partially constrained space in the form of a vessel from which the aerosol is inspirable via an opening in the vessel. 5 Example 48. The method of any of examples 31 through 33, wherein the generating an aerosol of droplets comprises generating the aerosol for a defined period of time in response to an activation event, and ceasing the generating after the defined period of time until a subsequent activation event. Example 49. The method of any of examples 31 through 33, wherein 10 the generating an aerosol of droplets comprises repeatedly generating the aerosol for defined periods of time, the defined periods of time separated by periods of time during which the generating of the aerosol ceases, to deliver multiple doses over a period of time. Example 50. The method of any of examples 31 through 33, wherein 15 the generating an aerosol of droplets comprises providing the aerosol in a free space in a venue prior to and / or during an event. Example 51. The method of example 50, wherein providing the aerosol in a free space in a venue prior to and / or during an event includes providing the aerosol in a free space at an entrance to the venue. 20 Example 52. The method of example 50, wherein providing the aerosol in a free space in a venue prior to and / or during an event includes providing the aerosol in a free space at a queue for the event, through which subjects successively pass and the providing occurs continuously or periodically over an extended period of time during which access to the event is provided. 25 Example 53. The method of example 52, wherein providing the aerosol in a free space at a queue for the event, through which subjects successively pass 2021306236 27 Aug 2026 includes providing the aerosol at two or more locations along a length of a queue path used to access the event. Example 54. The method of example 52, wherein providing the aerosol in a free space at a queue for the event, through which subjects successively pass 5 includes providing the aerosol along an entire length of at least a defined portion of a queue path used to access the event, wherein the defined portion is sufficiently long to provide a measured dosage to each subject traversing the defined portion of the queue path at a walking speed. Example 55. The method of example 52, further comprising: 10 successively reading identification information from each subject passing through the aerosol; and storing the information that represents that each subject passed through the aerosol. Example 56. The method of example 54, further comprising: 15 successively reading identification information from each subject passing through the aerosol via at least one machine-readable symbol reader, radio frequency identification (RFID) interrogator, or via facial recognition based camera and processor-based computer system; and storing the information to at least one non-transitory processor- 20 readable media that represents an amount of time that each subject was subjected to the aerosol. Example 57. The method of example 50, wherein generating an aerosol of droplets includes generating an aerosol of droplets in which the salt-based composition is a purely hygienic composition. 25 Example 58. The method of example 50, wherein generating an aerosol of droplets includes generating an aerosol of droplets to administer the 2021306236 27 Aug 2026 subject a therapeutically effective amount of the salt-based composition to suppress viral shedding. Example 59. The method of example 31, wherein the method of administering the formulation or composition to the nose, trachea, and main bronchi 5 of a respiratory tract of the subject comprises administering the salt-based composition in the nose of the subject while the subject has their head leaning back or is in a reclined position that promotes post-nasal drop. Example 60. The method of example 59, wherein administering the salt-based composition in the nose of the subject includes administering the salt-10 based composition to the nose of the subject for 5-10 seconds while a head of the subject is leaning back. Example 61. The method of example 59, wherein administering the salt-based composition in the nose of the subject includes administering the saltbased composition to the nose of the subject for 30 seconds or more while the 15 subject is in a reclined position. Example 62. A method of suppressing the exhalation of particles in an upper airway of a respiratory tract of a subject, the method comprising: generating an aerosol of droplets of a salt-based composition comprising calcium chloride and / or magnesium chloride, the droplets have a mass 20 median droplet diameter ranging from approximately 7 microns to approximately 15 microns, and administering the aerosol of droplets to the airway lining fluid in the nose, trachea, and main bronchi of the subject, thereby suppressing the exhalation of particles in the upper respiratory tract of the subject. 25 Example 63. The method of example 62 wherein generating an aerosol of droplets includes generating an aerosol of droplets comprising calcium 2021306236 27 Aug 2026 chloride and / or magnesium chloride in water. Example 64. The method of any of examples 62 or 63 wherein administering the aerosol of droplets includes administering the aerosol of droplets as suspended in a standing cloud. 5 Example 65. A delivery system operable to delivery of a purely hygienic or antimicrobial formulation or composition to the nose, trachea and main bronchi of a respiratory tract of a subject, the delivery system comprising: a reservoir having at least one wall which at least partially delimits an interior of the reservoir from an exterior thereof, the reservoir having a port that 10 provides a fluidly communicative path between the interior of the reservoir and an exterior thereof, the reservoir which at least in use holds the hygienic or antimicrobial formulation or composition comprising a quantity of water and at least calcium chloride and / or magnesium chloride dissolved in the water; and at least one delivery device, the at least one delivery device operable 15 to cause formation of an aerosol comprising readily-soluble droplets that have a mass median diameter range of approximately 7 microns to approximately 15 microns and comprising at least the calcium chloride dissolved in the quantity of water. Example 66. The delivery system of example 65, wherein the at least 20 one delivery device comprises at least one orifice with a size in the range of 3.5 microns and 7.5 microns and at least one pump operable to dispense a jet from the at least one orifice. Example 67. The delivery system of example 65, wherein the at least one delivery device comprises: 25 at least one nebulizer delivery device, the at least one nebulizer delivery device comprising an actuator, and the actuator controllably operable on the active substance media to cause formation of an aerosol comprising readily-soluble droplets that have a mass median diameter range of approximately 7 microns to 2021306236 27 Aug 2026 approximately 15 microns and comprising at least the calcium chloride dissolved in the quantity of water. Example 68. The delivery system of example 67, wherein the at least one nebulizer delivery device is a nebulizer and further comprises a respective 5 control subsystem communicatively coupled to control the actuator. Example 69. The delivery system of example 67, wherein the at least one nebulizer delivery device is a nebulizer that includes a mesh screen mounted for oscillation, a microcontroller, and at least one of a piezoelectric transducer, a solenoid, or an electric motor drivingly coupled to oscillate the mesh screen along at 10 least one axis in response to signals from the microcontroller to dispense aerosol. Example 70. The delivery system of example 67, further comprising: at least one of a switch or a sensor communicatively coupled to the microcontroller and operable to produce a signal that causes the microcontroller to operate the actuator accordingly. 15 Example 71. The delivery system of example 67, further comprising: at least one of a switch or a sensor communicatively coupled to the microcontroller and operable to produce a signal that causes the microcontroller to operate the actuator in response to the at least one nebulizer delivery device being titled relative to a normal or upright position. 20 Example 72. The delivery system of example 67, further comprising: at least one of a switch or a sensor communicatively coupled to the microcontroller and responsive to a position or orientation of the vessel and operable to produce a signal that causes the microcontroller to operate the actuator according to the orientation of the vessel. 25 Example 73. The delivery device of example 67, wherein the at least 2021306236 27 Aug 2026 one nebulizer delivery device removably dockable to the reservoir. Example 74. A kit to suppress the exhalation of particles in an upper airway of a respiratory tract of subjects, the kit comprising: a measured quantity of calcium chloride and / or magnesium chloride; 5 a container sized to receive a defined quantity of water to dissolve the calcium chloride therein; and instructions. Example 75. The kit of example 74, wherein the quantity of calcium chloride and / or magnesium chloride is hermetically packaged by itself. 10 Example 76. The kit of example 74, further comprising: a measured quantity of at least one of distilled or sterilized water hermetically packaged by itself, separate from the measured quantity of calcium chloride. Example 77. A method of administering a formulation or composition to 15 the nose, trachea, and main bronchi of a respiratory tract of a subject, method comprising: generating an aerosol of droplets in a space from which the aerosol is inspirable by the subject, in the nose, trachea, and main bronchi of the respiratory tract of the subject, without any application of force; 20 wherein the aerosol of droplets comprises a salt-based composition comprising calcium chloride and / or magnesium chloride in water, and wherein the method of administering the formulation or composition to the nose, trachea, and main bronchi of a respiratory tract of the subject is achieved by spraying the salt-based composition in the nose of the subject while the subject 25 has their head leaning back or is in a reclined position that promotes post-nasal drop. 2021306236 27 Aug 2026 Example 78. A composition of aerosol droplets comprising a saltbased composition, comprising: from about 1% to about 5% by weight calcium chloride in water; and a benzalkonium chloride preservative, or 5 an acid in an amount sufficient to reduce the pH of the salt-based composition to about 2 to about 3. Example 79. The composition of example 78, wherein the salt-based composition further comprises magnesium chloride. Example 80. The composition of any of examples 78 or 79, wherein 10 the droplets have a mass median droplet diameter ranging from 7 microns to 15 microns. Example 81. The composition of example 80, wherein a majority of the droplets have a droplet size between 9 microns and 10 microns in diameter. Example 82. The composition of example 78, wherein the salt-based 15 composition comprises the benzalkonium chloride preservative, and wherein the benzalkonium chloride is present in an amount ranging from about 0.05 wt% to about 0.2 wt%. Example 83. The composition of example 78, wherein the salt-based composition comprises the acid, wherein the acid is citric acid, hydrochloric acid, or a 20 combination thereof. Example 84. The composition of example 78, wherein the composition is in the form a 20 mg to30 mg dosage. Example 85. The method of example 84, wherein a 20 mg to30 mg formulation dosage is administered into a nose of the subject. 25 2021306236 27 Aug 2026 Applicants incorporate by reference the following: U.S. provisional patent application Serial No. 62 / 687,970, filed June 21,2018; U.S. provisional patent application Serial No. 62 / 652,069, filed April 3, 2018; U.S. provisional patent application Serial No. 62 / 628,395, filed February 9, 2018; U.S. provisional patent 5 application Serial No. 62 / 556,974, filed September 11,2017; U.S. provisional patent application Serial No. 62 / 727,123, filed September 5, 2018; U.S. nonprovisional patent application Serial No. 16 / 122,673, filed Septembers, 2018 (published as US2019-0105460); U.S. provisional patent application Serial No. 63 / 048,421, filed July 6, 2020; U.S. provisional patent application Serial No. 63 / 121,448, filed 10 December 12, 2020; U.S. provisional patent application Serial No. 63 / 130,099, filed December 23, 2020; U.S. patent application Serial No. 17 / 139,401, filed December 31,2020; and International patent application Serial No. PCT / US2018 / 050250 (published as WO 2019 / 051403). 15 Adam P, Stiffman M, and Blake RL, Jr (1998) A clinical trial of hypertonic saline nasal spray in subjects with the common cold or rhinosinusitis. Arch Fam Med 7(1), 39-43; Alp S, et al (2005) Expression of beta-defensin 1 and 2 in nasal epithelial cells and alveolar macrophages from HIV-infected patients. EurJ Med Res 10(1), 1-6.; Bai, Y, et al (2020) Presumed Asymptomatic Carrier 20 Transmission of COVID-19. JAMA; Bastier (2015). Nasal irrigation: From empiricism to evidence-based medicine. A review; Bunyan D, et al (2013) Respiratory and facial protection: a critical review of recent literature. J Hosp Infect. 85(3), 165-169; Calmet H, et al (2019) Nasal sprayed particle deposition in a human nasal cavity under different inhalation conditions. PLOS ONE 14(9), e0221330; Choy et al (2020) 25 Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS- CoV-2 T replication in vitro. Antiviral Research 178, 104786; Dellanno C, Vega Q, and Boesenberg D (2009) The antiviral action of common household disinfectants and antiseptics against murine hepatitis virus, a potential surrogate for SARS coronavirus. American Journal of Infection Control 37(8), 649-652; Edwards DA, et al 30 (2004) Inhaling to mitigate exhaled bioaerosols. Proceedings of the National Academy of Sciences 101(50), 17383-17388; Fauci AS, Lane HC, and Redfield RR (2020) Covid-19 — Navigating the Uncharted. New England Journal of Medicine 382 2021306236 27 Aug 2026 (13), 1268-1269; Fulcher ML, et al (2005) Well-Differentiated Human Airway Epithelial Cell Cultures, (ed. Picot J) Human Cell Culture Protocols. Methods in Molecular MedicineTM, vol 107. Humana Press, 183-206. Geller C, Varbanov M, and Duval R (2012) Human Coronaviruses: Insights into Environmental Resistance 5 and Its Influence on the Development of New Antiseptic Strategies. Viruses 4 (11), 3044-3068; Head, K, Snidvongs, K, Glew, S., Scadding, G., Schiller, A., Philpot, C and C Hopkins (2018). Saline irrigation for allergic rhinitis. Cochrane Database Syst Rev. CD01259; Hou, Y.J et al (2020) SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell 182, 1-18; Kim J, et al 10 (2018) Human p-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity. Virology Journal 15(1); Krisanaprakornkit S, Jotikasthira D, and Dale BA (2003) Intracellular calcium in signaling human beta-defensin-2 expression in oral epithelial cells. J Dent Res 82(11), 877-82; Lescure, F-X, et al (2020) Clinical and virological data of the first 15 cases of COVID-19 in Europe: a case series. The Lancet Infectious Diseases; Leung NHL, et al (2020) Respiratory virus shedding in exhaled breath and efficacy of face masks. Nature Medicine; Ngaosuwankul N, et al (2010) Influenza A viral loads in respiratory samples collected from patients infected with pandemic H1N1, seasonal H1N1 and H3N2 viruses. Virology Journal 7(1), 75. Ramalingam S, et al (2018) 20 Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels. Scientific Reports 8(1); Ramalingam S, et al (2019) A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold. Scientific Reports 9(1); Schmittgen TD and Livak KJ (2008) Analyzing real-time PCR data by 25 the comparative C(T) method. Nat Protoc 3(6), 1101-8; Slapak I, et al (2008) Efficacy of Isotonic Nasal Wash (Seawater) in the Treatment and Prevention of Rhinitis in Children. Arch Otolaryngol Head Neck Surg 134(1), 67; Speir RW (1961) Effect of Several Inorganic Salts on Infectivity of Mengo Virus. Proceedings of the Society for Experimental Biology and Medicine 106(2), 402-404; Sweet C and Smith H (1980) 30 Pathogenicity of influenza virus. Microbiol Rev 44(2), 303-30; Van Doremalen N, et al (2020) Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. New England Journal of Medicine 382, 1564-1567; Wang J, and Du G (2020) 2021306236 27 Aug 2026 COVID-19 may transmit through aerosol. Irish Journal of Medical Science (1971 -); Watanabe W, et al (2007) Why inhaling salt water changes what we exhale. J Colloid Interface Sci 307(1), 71-8; WHO Guidelines on Hand Hygiene in Health Care: First Global Patient Safety Challenge Clean Care Is Safer Care. Geneva: World Health 5 Organization; 2009. 4, Historical perspective on hand hygiene in health care. Available from: https: / / www.ncbi.nlm.nih.ciov / books / NBK144018A Zhang, P.R. et al. (2020). Identifying airborne transmission as the dominant route for the spread of COVID-19. PNAS, 1-7; Zhao H, et al (2016) A novel peptide with potent and broadspectrum antiviral activities against multiple respiratory viruses. Scientific Reports 10 6(1), 22008; Zou L, et al (2020) SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. New England Journal of Medicine 382(12), 11771179. The various embodiments described above can be combined to 15 provide further embodiments. These and other changes can be made to the embodiments in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which 20 such claims are entitled. Accordingly, the claims are not limited by the disclosure.
Claims
1. A delivery system operable to deliver an aqueous salt-based composition to an upper airway of a subject, the delivery system comprising:a reservoir containing the aqueous salt-based composition, the composition comprising about 5% by weight, in total, of a salt selected from calcium chloride, magnesium chloride and combinations thereof in water, and no more than 0.1% by weight sodium chloride; and an aerosolisation device in fluid communication with the reservoir and operable to form the aqueous salt-based composition into an aerosol of readily soluble droplets for nasal inhalation by the subject,wherein the droplets have a mass median droplet diameter of approximately 10 micrometres and a standard deviation in droplet diameter of less than 1 micrometre, such that, upon nasal inhalation, the droplets are carried to upper-airway tissue comprising one or more of the pharynx, larynx, trachea and main bronchi while being too large for significant penetration into the lower airways.
2. The delivery system of claim 1, wherein the salt is calcium chloride.
3. The delivery system of claim 1, wherein the salt is magnesium chloride.
4. The delivery system of claim 1, wherein the salt comprises both calcium chloride andmagnesium chloride.
5. The delivery system of any one of claims 1 to 4, wherein the aqueous salt-based composition is devoid of sodium chloride.
6. The delivery system of any preceding claim, wherein the upper-airway tissue comprises the pharynx and larynx.
7. The delivery system of any preceding claim, wherein the aerosolisation device comprises at least one orifice having a size from 3.5 micrometres to 7.5 micrometres and at least one pump operable to dispense a jet through the at least one orifice.
8. The delivery system of any one of claims 1 to 6, wherein the aerosolisation device comprises a nebuliser having a mesh screen, an actuator and a control subsystem communicatively coupled to control the actuator.
9. The delivery system of any preceding claim, wherein the aerosolisation device is configured to dispense the aerosol into a free space in which a velocity of the aerosol decreases so that the aerosol becomes relatively quiescent and is naturally inspirable by the subject without force beyond inhalation by the subject.
10. The delivery system of any preceding claim, wherein the aerosolisation device is configured to deliver from 0.5 mg to 4.0 mg of the salt in one administration.2021306236 27 Aug 202611. A method of suppressing exhalation of aerosol particles from an upper airway of a subject, the method comprising:generating an aerosol of droplets from an aqueous salt-based composition comprising about 5% by weight, in total, of a salt selected from calcium chloride, magnesium chloride and combinations thereof in water, and no more than 0.1% by weight sodium chloride, wherein the droplets have a mass median droplet diameter of approximately 10 micrometres and a standard deviation in droplet diameter of less than 1 micrometre; andadministering the aerosol to airway-lining fluid of the subject by nasal inhalation so that the droplets are carried to upper-airway tissue comprising one or more of the pharynx, larynx, trachea and main bronchi without significant penetration into the lower airways, thereby suppressing exhalation of aerosol particles from the upper airway.
12. The method of claim 11, wherein the salt is calcium chloride.
13. The method of claim 11, wherein the salt is magnesium chloride.
14. The method of claim chloride. 11, wherein the salt comprises both calcium chloride and magnesium15. The method of any one of claims 11 to 14, wherein the aqueous salt-based composition is devoid of sodium chloride.
16. The method of any one of claims 11 to 15, comprising administering from 0.5 mg to 4.0 mg of the salt to the subject in one administration.
Citation Information
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