In Vitro Study of the Effect of Breathing Pattern on Aerosol Delivery During High-Flow Nasal Therapy

Abstract

Introduction: The use of concurrent aerosol delivery during high-flow nasal therapy (HFNT) may be exploited to facilitate delivery of a variety of prescribed medications for inhalation. The study assessed the effect of tidal volume, breath rate, and inspiratory:expiratory (I:E) ratio on the quantity of aerosol captured at the level of the trachea during simulated HFNT. Methods: Testing was completed according to a factorial statistical design of experiments (DOE) approach. Tracheal dose was characterized with a vibrating mesh nebulizer (Aerogen Solo, Aerogen Ltd) using simulated adult, small child, and infant HFNT models. Furthermore, aerosol delivery was evaluated across a range of adult patient profiles with clinically representative test setups. Results: Aerosol delivery increased with a large tidal volume, a rapid breath rate, and a long inspiratory time. Tidal volume, breath rate, and I:E ratio each had a significant effect on tracheal dose across simulated adult, small child, and infant breathing. Conclusion: The main trends that were identified in the statistical DOE predicted aerosol delivery across adult patient breathing profiles, in terms of tidal volume, breath rate, and I:E ratio. Therefore, patients with distressed breathing profiles may be expected to receive a larger aerosol dose than those with normal breathing rates. Funding: Aerogen Limited.

In vitro comparison of unit dose vs infusion pump administration of albuterol via high‐flow nasal cannula in toddlers

“…With unit dose administration, the inhaled dose was 10% to 15% in similar pediatric models, which was consistent with our findings using unit dose delivery. Interestingly, at low administered gas flow setting (4‐5 L/min), inhaled dose in Ari's recent study that used albuterol with concentration of 2.5 mg/3 mL was only 3.27% ± 0.4%, in contrast to 13.84% ± 0.42% in Bennett et al's study, which utilized a higher concentration (2 mg/mL) with similar anatomical models and gas flow settings. Besides the slight difference between the tidal volumes (100 vs 150 mL), the low vs high concentrations in two studies may partially contribute to the different inhaled doses, which supports our finding that high‐concentrated albuterol had higher delivery efficiency than low concentration.…”

“…Previous in vitro and in vivo studies on aerosol delivery via HFNC all utilized unit dose with a single concentration . With unit dose administration, the inhaled dose was 10% to 15% in similar pediatric models, which was consistent with our findings using unit dose delivery.…”

“…Previous in vitro and in vivo studies on aerosol delivery via HFNC all utilized unit dose with a single concentration . With unit dose administration, the inhaled dose was 10% to 15% in similar pediatric models, which was consistent with our findings using unit dose delivery. Interestingly, at low administered gas flow setting (4‐5 L/min), inhaled dose in Ari's recent study that used albuterol with concentration of 2.5 mg/3 mL was only 3.27% ± 0.4%, in contrast to 13.84% ± 0.42% in Bennett et al's study, which utilized a higher concentration (2 mg/mL) with similar anatomical models and gas flow settings.…”

“…Similar to other in vitro studies, the manikin did not simulate microstructures or complexity of human airways and use of collecting filters that do not represent aerosol exhaled in vivo, tend to overestimate inhaled dose. However, the proportional changes of inhaled dose between parameters tested should be representative.…”

Investigation of Fugitive Aerosols Released into the Environment during High-Flow Therapy

“…Several factors influence aerosol drug delivery to the lungs, including the aerosol-generating device, the size distribution of the inhaled aerosol, the gas-flow rate, the inhalation pattern and the type of interface [5][6][7][8][9].Dysart et al [10] reported that the use of high-flow nasal therapy (HFNT) devices is rapidly growing in the clinical setting, for different age groups with a range of disease conditions. High-flow nasal therapy studies have reported gas-flow rates of 3 to 20 L/min for paediatrics, and 5 to 60 L/min for adults [11][12][13][14]. Studies have reported that several factors influence the quantity of aerosol available for inhalation, including the rate of gas flow delivered, the size of the nasal prongs, humidification, the size of the aerosol droplets and the aerosol generator type and position [11,13,15].…”