Reconciling Oxygen and Aerosol Delivery with a Hood on In Vitro Infant and Paediatric Models

This study aimed to evaluate optimal aerosol and oxygen delivery with a hood on an infant model and a paediatric model. A facemask and a hood with three inlets, with or without a front cover, were used. A small-volume nebuliser with a unit-dose of salbutamol was used for drug delivery and an air entrainment nebuliser was used to deliver oxygen at 35%. Infant and paediatric breathing patterns were mimicked; a bacterial filter was connected to the end of a manikin trachea for aerosol drug collection, and an oxygen analyser was used to measure the oxygen concentration. For the infant model, inhaled drug dose was significantly higher when the nebuliser was placed in the back of the hood and with a front cover. This was verified by complementary computational simulations in a comparable infant-hood model. For the paediatric model, the inhaled dose was greater with a facemask than with a hood. Oxygen delivery with a facemask and a hood with a front cover achieved a set concentration in both models, yet a hood without a front cover delivered oxygen at far lower concentrations than the set concentration.

The Impact of Head Model Choice on the In Vitro Evaluation of Aerosol Drug Delivery

There are variations in the values reported for aerosol drug delivery across in vitro experiments throughout the published literature, and often with the same devices or similar experimental setups. Factors contributing to this variability include, but are not limited to device type, equipment settings, drug type and quantification methods. This study assessed the impact of head model choice on aerosol drug delivery using six different adults and three different paediatric head models in combination with a facemask, mouthpiece, and high-flow nasal cannula. Under controlled test conditions, the quantity of drug collected varied depending on the choice of head model. Head models vary depending on a combination of structural design differences, facial features (size and structure), internal volume measurements and airway geometries and these variations result in the differences in aerosol delivery. Of the widely available head models used in this study, only three were seen to closely predict in vivo aerosol delivery performance in adults compared with published scintigraphy data. Further, this testing identified the limited utility of some head models under certain test conditions, for example, the range reported across head models was aerosol drug delivery of 2.62 ± 2.86% to 37.79 ± 1.55% when used with a facemask. For the first time, this study highlights the impact of head model choice on reported aerosol drug delivery within a laboratory setting and contributes to explaining the differences in values reported within the literature.

Fabrication and Validation of an Economical, Programmable, Dual-Channel, Electronic Cigarette Aerosol Generator

Vaping (inhalation of electronic cigarette-generated aerosol) is a public health concern. Due to recent spikes in adolescent use of electronic cigarettes (ECIGs) and vaping-induced illnesses, demand for scientific inquiry into the physiological effects of electronic cigarette (ECIG) aerosol has increased. For such studies, standardized and consistent aerosol production is required. Many labs generate aerosol by manually activating peristaltic pumps and ECIG devices simultaneously in a predefined manner. The tedium involved with this process (large puff number over time) and risk of error in keeping with puff topography (puff number, duration, interval) are less than optimal. Furthermore, excess puffing on an ECIG device results in battery depletion, reducing aerosol production, and ultimately, its chemical and physical nature. While commercial vaping machines are available, the cost of these machines is prohibitive to many labs. For these reasons, an economical and programmable ECIG aerosol generator, capable of generating aerosol from two atomizers simultaneously, was fabricated, and subsequently validated. Validation determinants include measurements of atomizer temperatures (inside and outside), electrical parameters (current, resistance and power) of the circuitry, aerosol particle distribution (particle counts and mass concentrations) and aerosol delivery (indexed by nicotine recovery), all during stressed conditions of four puffs/minute for 75 min (i.e., 300 puffs). Validation results indicate that the ECIG aerosol generator is better suited for experiments involving ≤ 100 puffs. Over 100 puffs, the amount of variation in the parameters measured tends to increase. Variations between channels are generally higher than variations within a channel. Despite significant variations in temperatures, electrical parameters, and aerosol particle distributions, both within and between channels, aerosol delivery remains remarkably stable for up to 300 puffs, yielding over 25% nicotine recovery for both channels. In conclusion, this programmable, dual-channel ECIG aerosol generator is not only affordable, but also allows the user to control puff topography and eliminate battery drain of ECIG devices. Consequently, this aerosol generator is valid, reliable, economical, capable of using a variety of E-liquids and amenable for use in a vast number of studies investigating the effects of ECIG-generated aerosol while utilizing a multitude of puffing regimens in a standardized manner.

Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study

The nasal olfactory region is a potential route for non-invasive delivery of drugs directly from the nasal epithelium to the brain, bypassing the often impermeable blood-brain barrier. However, efficient aerosol delivery to the olfactory region is challenging due to its location in the nose. Here we explore aerosol delivery with bi-directional pulsatile flow conditions for targeted drug delivery to the olfactory region using a computational fluid dynamics (CFD) model on the patient-specific nasal geometry. Aerosols with aerodynamic diameter of 1 µm, which is large enough for delivery of large enough drug doses and yet potentially small enough for non-inertial aerosol deposition due to, e.g., particle diffusion and flow oscillations, is inhaled for 1.98 s through one nostril and exhaled through the other one. The bi-directional aerosol delivery with steady flow rate of 4 L/min results in deposition efficiencies (DEs) of 50.9 and 0.48% in the nasal cavity and olfactory region, respectively. Pulsatile flow with average flow rate of 4 L/min (frequency: 45 Hz) reduces these values to 34.4 and 0.12%, respectively, and it mitigates the non-uniformity of right-left deposition in both the cavity (from 1.77- to 1.33-fold) and the olfactory region (from 624- to 53.2-fold). The average drug dose deposited in the nasal cavity and the olfactory epithelium region is very similar in the right nasal cavity independent of pulsation conditions (inhalation side). In contrast, the local aerosol dose in the olfactory region of the left side is at least 100-fold lower than that in the nasal cavity independent of pulsation condition. Hence, while pulsatile flow reduces the right-left (inhalation-exhalation) imbalance, it is not able to overcome it. However, the inhalation side (even with pulsation) allows for relatively high olfactory epithelium drug doses per area reaching the same level as in the total nasal cavity. Due to the relatively low drug deposition in olfactory region on the exhalation side, this allows either very efficient targeting of the inhalation side, or uniform drug delivery by performing bidirectional flow first from the one and then from the other side of the nose.

Aerosol delivery through high flow nasal cannula compared to biphasic positive airway pressure, at two different pressure: an in-vitro study

Background Both non-invasive ventilation and high flow oxygen therapy are preferred over low flow oxygen therapy in many conditions. Nebulizers, for aerosol delivery, can be used within them without interrupting the circuit. The present study aimed to compare the efficiency of drug delivery within high flow nasal cannula (HFNC) and biphasic positive airway pressure (BiPAP) ventilation mode using two different inspiratory positive airway pressures. The aerosol delivery was examined in HFNC system at low flow, 5 L min−1, and BiPAP non-invasive ventilation under 2 different pressures [high pressure; inspiratory positive airway pressure/expiratory positive airway pressure (IPAP/EPAP) of 20/5 cm water, and low pressure; IPAP/EPAP of 10/5 cm water]. The total inhalable dose (TID) was measured by inserting an Aerogen Solo nebulizer installed with 1 mL salbutamol respiratory solution (5000 μg mL−1) within the circuit, and the salbutamol was collected on an inhalation filter placed in a filter holder connected to a breathing simulator. The breathing simulator was adjusted at a tidal volume of 500 mL, respiratory rate of 15 breaths min−1, and inhalation to exhalation (I:E) ratio of 1:1 for the adult setting. In each technique of the three (HFNC, and low, and high-pressures BiPAP), TID was determined 5 times (n = 5). For particle size characterization, cooled Anderson Cascade Impactor (ACI) was inserted instead of the inhalation filter and the breathing simulator with the same scheme. In each technique of the three, particle size characterization was determined 3 times (n = 3). Results The BiPAP mode at low inspiratory pressure had the highest TID, followed by HFNC at flow 5 L min−1, then BiPAP mode at high inspiratory pressure. There was a significant difference only between low and high inspiratory pressure modes of BiPAP mode. Low-inspiratory pressure BiPAP delivered the highest mean ± SD fine particle dose (FPD). It was significantly higher than that delivered in high inspiratory pressure BiPAP, and HFNC. Also, FPD in HFNC was significantly higher than that in high inspiratory pressure BiPAP. HFNC system had the smallest mass median aerodynamic diameter (MMAD) and the highest FPF followed by low then high inspiratory pressure BiPAP. Conclusions Increasing the inspiratory positive airway pressure in BiPAP, from 10 to 20 cm water, decreased the total inhalable dose and FPF nearly by half. Low inspiratory pressure BiPAP delivered the highest TID and FPD. The HFNC system at low oxygen flow resulted in the least MMAD, and the highest FPF. Using HFNC delivered a TID that was non-significant from that delivered by low inspiratory pressure BiPAP. Graphical Abstract