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A Vibrating Mesh Nebulizer as an Alternative to the Collison Three-Jet Nebulizer for Infectious Disease Aerobiology.

ABSTRACT: Experimental infection of animals with aerosols containing pathogenic agents is essential for an understanding of the natural history and pathogenesis of infectious disease as well as evaluation of potential treatments. We evaluated whether the Aeroneb nebulizer, a vibrating mesh nebulizer, would serve as an alternative to the Collison nebulizer, the "gold standard" for generating infectious bioaerosols. While the Collison possesses desirable properties that have contributed to its longevity in infectious disease aerobiology, concerns have lingered about the liquid volume and concentration of the infectious agent required to cause disease and the damage that jet nebulization causes to the agent. Fluorescein salt was added to the nebulizer contents to assess pathogen loss during aerosolization. Relative to fluorescein salt, loss of influenza virus during aerosolization was worse with the Collison than with the Aeroneb. Four other viruses also had superior aerosol performance with the Aeroneb. The Aeroneb did not improve the aerosol performance for a vegetative bacterium, Francisella tularensis Environmental parameters collected during the aerosol challenges indicated that the Aeroneb generated a higher relative humidity in exposure chambers while not affecting other environmental parameters. The aerosol mass median aerodynamic diameter (MMAD) was generally larger and more disperse for aerosols generated by the Aeroneb than what is seen with the Collison, but ≥80% of particles were within the range that would reach the lower respiratory tract and alveolar regions. The improved aerosol performance and generated particle size range suggest that for viral pathogens, the Aeroneb is a suitable alternative to the Collison three-jet nebulizer for use in experimental infection of animals.IMPORTANCE Respiratory infection by pathogens via aerosol remains a major concern for both natural disease transmission as well as intentional release of biological weapons. Critical to understanding the disease course and pathogenesis of inhaled pathogens are studies in animal models conducted under tightly controlled experimental settings, including the inhaled dose. The route of administration, particle size, and dose can affect disease progression and outcome. Damage to or loss of pathogens during aerosolization could increase the dose required to cause disease and could stimulate innate immune responses, altering outcome. Aerosol generators that reduce pathogen loss would be ideal. This study compares two aerosol generators to determine which is superior for animal studies. Aerosol research methods and equipment need to be well characterized to optimize the development of animal models for respiratory pathogens, including bioterrorism agents. This information will be critical for pivotal efficacy studies in animals to evaluate potential vaccines or treatments against these agents.

SUBMITTER: Bowling JD

PROVIDER: S-EPMC6696971 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background:Allergen inhalation tests are a valuable research tool. The allergen dose producing an early asthmatic response (EAR) can be predicted from methacholine responsiveness and allergen skin test endpoint (STE). The Wright® jet nebulizer, which is both inefficient and increasingly difficult to obtain, has been used historically. We assessed the Solo® vibrating mesh nebulizer as an alternative for allergen and methacholine challenges. Methods:Eighteen mild atopic asthmatics completed the study. Doubling concentration allergen prick skin tests were performed to determine the STE in allergen units/mL. The Wright® protocol was used to measure the methacholine provocation dose causing a 20% forced expired volume in one second (FEV1) fall (PD20) (?g) and the allergen PD20 (units). The Solo® protocol (0.5 mL nebulized to completion, tidal breathing inhalation) was used to determine both methacholine PD20 and allergen PD20. The nebulizer order was randomized and separated by ??2 weeks. Results:All data were log transformed. The allergen PD20, predicted from the methacholine PD20 and the STE, was within 2 doubling doses of the PD20 measured with the Wright® and 2.64 doubling doses of that measured with Solo®. The Wright® allergen PD20 correlated with the Wright® methacholine PD20 (r?=?0.74) and the STE (r?=?0.78) and more strongly with the product of the two (Wright® methacholine PD20?×?STE, r?=?0.91, p?<?0.00001). The Solo® allergen PD20 showed similar relationships with the Solo® methacholine PD20 (r?=?0.61), the STE (r?=?0.75) and the product of the two (Solo® methacholine PD20?×?STE, r?=?0.83, p?<?0.00002). The Wright® and the Solo® methacholine geometric mean PD20s were not significantly different (49.3 and 54.5 ?g respectively, p?=?0.62). The Wright® allergen PD20 was slightly but significantly lower than the Solo® allergen PD20 (geometric means 6.7 and 10.5 units respectively, p?=?0.003). Conclusion:The Solo® allergen PD20 showed the same relationship with methacholine responsiveness and STE as did the Wright®. The Solo® allergen PD20 was slightly but significantly higher than the Wright® allergen PD20. The Solo® vibrating mesh nebulizer was well tolerated and is an acceptable alternative for allergen challenge.Trial registration clinicaltrials.gov: NCT03491358.

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A Vibrating Mesh Nebulizer as an Alternative to the Collison Three-Jet Nebulizer for Infectious Disease Aerobiology.

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