Pulmonary delivery of anti-contagion aerosol to diminish exhaled bioaerosols and airborne infectious disease

BACKGROUND/OBJECTIVES: Many contagious diseases are transmitted by exhalation of infectious droplets. Airborne infectious disease (AID) spread via exhaled bioaerosols (EBs) is a significant public health risk. Altering biophysical surface properties of airway lining fluid (ALF) through an inhaled, safe anticontagion aerosol (ACA) of isotonic saline provides a novel mechanism to diminish EB. In a recent study in normal volunteers (Edwards et al., PNAS 101:17383-388, 2004), half the study population was found to expire many more bioaerosol particles during quiet breathing and therefore bear the burden of production of EB. Administering nebulized isotonic saline (6 minutes) to these high producers diminished EB expired by 72.1 ± 8.2% for up to 6 hours. A subsequent study in Holstein bulls (a relevant animal model of AID) investigated the role of ACA dose on EB over time. METHODS: Seven Holstein bull calves (75-140 kg) were anesthetized, intubated, and maintained under general anesthesia following Defense Department and university-approved protocols on a custom-designed closed circle anesthesia system modified to evaluate pulmonary function and sample the number and size of EB using an Optical Particle Counter (Climet Instrument Company, Redlands, California). Every animal received four different ACA (0.9% isotonic saline) doses by nebulization (sham, 1.8, 6, or 12 minutes; Pari Respiratory Equipment, Starnberg, Germany) through the intubation tube; a minimum of 1week separated dosing in individual animals and doses were randomized throughout the study. EB were measured pre-ACA treatment and at 5, 15, 30, 60, 90, 120, and 180 minutes post-ACA treatment. RESULTS: Substantial inter-subject variability was found in baseline values, which revealed two distinct populations, low producers and high producers similar to the human trial. Delivery of ACA showed a dose-responsive effect on EB; 6 minutes of ACA treatment resulted in >50% decrement in EB for at least 120 minutes compared to pre-treatment. CONCLUSIONS: These results suggest individual variability in EB production may contribute to infectivity and ACA offers a dose-sensitive, ubiquitous measure to limit EB. A clinical trial assessing the role of AID (influenza) on EB production with a follow-up study evaluating the role of ACA in limiting EB is ongoing. These studies provide the foundation for a strategy to mitigate transmission of AID. This work was partially funded by the Technical Support Working Group (TSWG).