Inhaling to mitigate exhaled bioaerosols

Abstract

Humans commonly exhale aerosols comprised of small droplets of airway-lining fluid during normal breathing. These ''exhaled bioaerosols'' may carry airborne pathogens and thereby magnify the spread of certain infectious diseases, such as influenza, tuberculosis, and severe acute respiratory syndrome. We hypothesize that, by altering lung airway surface properties through an inhaled nontoxic aerosol, we might substantially diminish the number of exhaled bioaerosol droplets and thereby provide a simple means to potentially mitigate the spread of airborne infectious disease independently of the identity of the airborne pathogen or the nature of any specific therapy. We find that some normal human subjects expire many more bioaerosol particles than other individuals during quiet breathing and therefore bear the burden of production of exhaled bioaerosols. Administering nebulized isotonic saline to these ''high-producer'' individuals diminishes the number of exhaled bioaerosol particles expired by 72.10 ؎ 8.19% for up to 6 h. In vitro and in vivo experiments with saline and surfactants suggest that the mechanism of action of the nebulized saline relates to modification of the physical properties of the airway-lining fluid, notably surface tension.drug delivery ͉ lung ͉ infectious disease ͉ influenza I t has long been understood that exhaled bioaerosol particles provide an important vector for the spread of certain infectious diseases (1, 2). Viruses known to spread from humans and͞or animals through breathing, sneezing, and coughing include measles, influenza virus (3, 4), adenovirus (5), African swine fever virus (6), foot and mouth disease virus (7), varicellazoster virus (chicken pox) (8), infectious bronchitis virus (9), and smallpox, among others (10). Airborne bacteria include anthrax, Escherichia coli (11), Klebsiella pneumoniae (12), Francisella tularensis (13), and tuberculosis (14). Normal mouth breathing (more than coughing, nose breathing, or talking) has been observed to produce the largest number of airborne droplets (15,16). These droplets are primarily Ͻ1 m in size, because larger droplets tend to be filtered out of the expired air by the lungs (16). Given the variable dimensions of common viral and bacterial pathogens (Ϸ25 nm to 5 m), the ability of exhaled bioaerosol droplets of a given size to carry pathogen obviously varies with pathogen type. Bioaerosols seem to form by the passage of air, during inhalation and exhalation, over the mucus layer lining the lungs (17) or possibly through the reopening of closed small airways, destabilizing the mucus surface through an interplay of surface tension and viscous forces to form small airborne droplets, as has been simulated in vitro via ''cough machine '' experiments (18). In this study, we aimed to explore the ability to transiently diminish the number of exhaled bioaerosol droplets in normal human subjects by delivery of a simple, safe, liquid aerosol. We also aimed to understand the mechanism of the effect of the inhaled aerosol through in vitro cough...

Influenza virus aerosol exposure and analytical system for ferrets

“…Reduced virus shedding was also observed in ferrets inoculated IN with a low or intermediate dose of TH16 virus compared with similar AR inoculations. A possible explanation is that the 1-mL volume of inoculum alters the surface tension of the mucous layer lining the respiratory tract, and such alteration in surface tension has been shown to result in reduced virus shedding (25), although this effect seems to be overcome by increasing the viral load in the IN inoculum. Ferrets inoculated via AR with TH16 virus exhibited a broader spectrum of disease than IN-inoculated animals, but lethality was similar.…”

The Mechanism of Breath Aerosol Formation

“…It is worth noting that Edwards et al 7 showed that delivering an aerosolised surfactant solution to the lungs increases exhaled aerosol concentration during normal breathing 30 fold. Surfactants have a well known ability to increase aqueous film elasticity, thereby allowing bubbles to form readily and to achieve much larger diameters before bursting.…”

“…That model does not adequately explain the influence that respiratory activities exert on aerosol concentration: Experimental data do not show a clear increase in aerosol concentration with exhalation flow rate during breathing, as should occur if turbulent airflow is the dominant breath aerosol formation mechanism. In fact normal breathing can produce higher aerosol number concentrations than coughing 4,6,7 which involves far higher flow rates. Gebhart et al 8 found that these particles are expired from volumetric lung depths of more than 200 cm -3 implying that they occur beyond the conducting airways.…”

Clinical evaluation of a screen pneumotachograph as an in-line filter

“…Such variability has already been mentioned [11,23] and may be linked to high inter-subject variability in the number of small-size particles produced during mouth breathing [24], possibly relating to the physical properties of the lung lining fluid [25]. Several mechanisms have been described to explain the retention properties of filters in terms of particle size.…”

“…However, the measured resistance of such filters is found to be slightly higher [26] and the experimental design is far from the conditions of natural contamination occurring in pulmonary function testing. In particular, the droplets produced by this experimental condition (3-5 mm) are much larger than the droplets (,1 mm) produced by normal breathing [25] and even coughing [24]. During standard spirometry, the SensorMedics filter was considered no different from the Pall filter [27].…”