In Vitro Determination of the Main Effects in the Design of High-Flow Nasal Therapy Systems with Respect to Aerosol Performance

Bennett, Gavin; Joyce, Mary; Sweeney, Louise; MacLoughlin, Ronan

doi:10.1007/s41030-018-0054-x

Cited by 23 publications

(37 citation statements)

References 29 publications

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“…Previously our group reported a systematic approach to determine the conditions required to yield an optimal emitted dose, thus becoming available for inhalation during HFNT [20]. The findings in that study clearly indicate that in order to optimize the amount of aerosol exiting the nasal cannula interface during HFNT, it is necessary for gas flow to be low and the input droplet size to be small, while the nebulizer should be positioned immediately after the humidification chamber [18].…”

Section: Introductionmentioning

confidence: 89%

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

et al. 2019

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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.

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Section: Introductionmentioning

confidence: 89%

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

et al. 2019

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“…Non-invasive Nasal High Flow therapy is increasingly used across a variety of patient populations and so it may be beneficial to combine this intervention with inhaled drug therapy including biomolecules [28]. Investigations by Branconnier and colleagues [29] determining non-invasive nasal high flow therapy-nebulizer compatibility employed albuterol sulphate as an exemplar drug, as have studies by Diaz and colleagues [25], and our own colleagues [30]. We chose to use albuterol as a tracer aerosol (see study limitations).…”

Section: Methodsmentioning

confidence: 99%

“…An adult high flow nasal therapy system (Optiflow™, Fisher and Paykel) was attached to a humidifier (MR850™, Fisher and Paykel) set at 37 °C. The nebulizers were placed at the humidifier, in line with previous findings for maximal aerosol delivery during high flow therapy [30]. 2 ml of 2 mg/ml Albuterol sulphate solution was nebulized by both the Aerogen Solo and PDAP mesh devices.…”

Section: Methodsmentioning

confidence: 99%

Effective nebulization of interferon-γ using a novel vibrating mesh

et al. 2019

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Background Interferon gamma (IFN-γ) is a clinically relevant immunomodulatory cytokine that has demonstrated significant potential in the treatment and management of respiratory diseases such as tuberculosis and pulmonary fibrosis. As with all large biomolecules, clinical translation is dependent on effective delivery to the disease site and delivery of IFN-γ as an aerosol offers a logical means of drug targeting. Effective localization is often hampered by instability and a lack of safe and efficient delivery systems. The present study sought to determine how effectively IFN-γ can be nebulized using two types of vibrating mesh nebulizer, each with differing mesh architectures, and to investigate the comparative efficiency of delivery of therapeutically active IFN-γ to the lungs. Methods Nebulization of IFN-γ was carried out using two different Aerogen vibrating mesh technologies with differing mesh architectures. These technologies represent both a standard commercially available mesh type (Aerogen Solo®) and a new iteration mesh (Photo-defined aperture plate (PDAP®). Extensive aerosol studies (aerosol output and droplet analysis, non-invasive and invasive aerosol therapy) were conducted in line with regulatory requirements and characterization of the stability and bioactivity of the IFN-γ post-nebulization was confirmed using SDS-PAGE and stimulation of Human C-X-C motif chemokine 10 (CXCL 10) also known as IFN-γ-induced protein 10KDa (IP 10) expression from THP-1 derived macrophages (THP-1 cells). Results Aerosol characterization studies indicated that a significant and reproducible dose of aerosolized IFN-γ can be delivered using both vibrating mesh technologies. Nebulization using both devices resulted in an emitted dose of at least 93% (100% dose minus residual volume) for IFN-γ. Characterization of aerosolized IFN-γ indicated that the PDAP was capable of generating droplets with a significantly lower mass median aerodynamic diameter (MMAD) with values of 2.79 ± 0.29 μm and 4.39 ± 0.25 μm for the PDAP and Solo respectively. The volume median diameters (VMD) of aerosolized IFN-γ corroborated this with VMDs of 2.33 ± 0.02 μm for the PDAP and 4.30 ± 0.02 μm for the Solo. SDS-PAGE gels indicated that IFN-γ remains stable after nebulization by both devices and this was confirmed by bioactivity studies using a THP-1 cell model in which an alveolar macrophage response to IFN-γ was determined. IFN-γ nebulized by the PDAP and Solo devices had no significant effect on the key inflammatory biomarker cytokine IP-10 release from this model in comparison to non-nebulized controls. Here we demonstrate that it is possible to combine IFN-γ with vibrating mesh nebulizer devices and facilitate effective aerosolisation with minimal impact on IFN-γ structure or bioactivity. Conclusions It is possible to nebulize IFN-γ effectively with vibrating mesh nebulizer devices without compromising its stability. The PDAP allows for ge...

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“…Previously, our group reported a systematic approach to determine the conditions required to yield an optimal emitted dose, thus becoming available for inhalation during HFNT. The findings in that study clearly indicate that in order to optimize the amount of aerosol exiting the nasal prongs during HFNT, it is necessary for the gas flow rate to be low and the input droplet size to be small, while the nebulizer should be positioned immediately after the humidification chamber [13]. In a recent scintigraphy study, Dugernier et al demonstrated in vivo that lung deposition was significantly greater while using a vibrating mesh nebulizer (VMN), in comparison with a jet nebulizer (JN) during adult HFNT [14].…”

Section: Introductionmentioning

confidence: 99%

Comparison of aerosol delivery across combinations of drug delivery interfaces with and without concurrent high-flow nasal therapy

Bennett

Joyce

Fernández

et al. 2019

ICMx

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Background Current clinical practice during high-flow nasal therapy (HFNT) involves utilization of a nasal cannula to provide humidification, with a facemask placed over the cannula to deliver aerosol. Few studies have compared aerosol delivery across various delivery interfaces during HFNT. The objective of this study was to address this gap in the literature and evaluate aerosol delivery using two nebulizer types across different drug delivery interfaces, nasal cannula, facemask, and mouthpiece, during simulated adult HFNT. Methods A facemask or mouthpiece and/or a nasal cannula were positioned on an anatomically correct adult head model. The head model was connected to a breathing simulator via a collection filter. Both healthy breathing pattern and distressed breathing patterns were utilized. Aerosol dose was determined by quantifying the mass of drug captured on a filter positioned distal to the trachea. Results During simulated healthy breathing, a significantly greater aerosol dose was observed when the vibrating mesh nebulizer (VMN) was integrated with HFNT alone, supplying aerosol and humidified air simultaneously (2.88 ± 0.15%), as opposed to using with a facemask (0.33 ± 0.07%, 1.62 ± 0.46%, and 1.07 ± 0.25% at 0 L/min (LPM), 2LPM, and 6LPM, respectively) or mouthpiece (0.56 ± 0.13%, 2.16 ± 0.06%, and 1.82 ± 0.41% at 0LPM, 2LPM, and 6LPM). In addition, aerosol delivery was also significantly greater when the VMN was integrated into simulated HFNT (2.88 ± 0.15%), in comparison with using the jet nebulizer (JN) with a facemask (0.82 ± 0.16%) or a mouthpiece (0.86 ± 0.11%). During simulated distressed breathing, a significantly greater aerosol dose was observed when the VMN was integrated with HFNT, supplying aerosol and humidified air simultaneously (6.81 ± 0.45%), compared with using a facemask (0.86 ± 0.04%, 2.96 ± 0.26%, and 4.23 ± 0.93% at 0LPM, 2LPM, and 6LPM) or mouthpiece (0.73 ± 0.37%, 0.97 ± 0.20%, and 3.11 ± 0.53% at 0LPM, 2LPM, and 6LPM, respectively). Aerosol delivery was also greater when the VMN was integrated into HFNT (6.81 ± 0.45%), in comparison with using the JN with a facemask (5.72 ± 0.71%) or a mouthpiece (0.69 ± 0.53%). Furthermore, across all drug delivery interfaces, and in line with previous reports, aerosol delivery was greater during simulated distressed breathing, in comparison with simulated healthy adult breathing. Conclusions This article will be of considerable benefit in enhancing the understanding of aerosol delivery during HFNT, an increasingly adopted therapeutic intervention by healthcare professionals.

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In Vitro Determination of the Main Effects in the Design of High-Flow Nasal Therapy Systems with Respect to Aerosol Performance

Cited by 23 publications

References 29 publications

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

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

Effective nebulization of interferon-γ using a novel vibrating mesh

Comparison of aerosol delivery across combinations of drug delivery interfaces with and without concurrent high-flow nasal therapy

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