(L-470) Aerosol Lung Deposition Characteristics of Isotonic and Hypertonic Solutions in a Stochastic Lung Model

Nebulizers are drug-delivery devices that generate aerosol particles composed of medicine and other solutions for treating patients through inhalation. Nebulizers deliver medication into the lung and are utilized to help patients with allergies, COPD, cystic fibrosis, and other respiratory illnesses. The current issue with these devices is that most nebulizer companies do not advertise the effectiveness of their products and where the particles deposit in a patient's airway. For medical treatment, it is not desirable for the aerosol particles of a nebulizer to deposit in the oropharyngeal region of the airway, and the medicine must reach the deep lung, such as the tracheobronchial and pulmonary regions. To properly deposit in the deep lung, nebulizers must produce small enough particles (< 5 μm). There is a lack of current information from manufacturing companies on the size of particles produced by commercial nebulizers. 

This research project aims to measure the particle characteristics produced by a jet compression nebulizer and where these particles deposit in the lung. The jet nebulizer is one of the most commonly used nebulizer forms (Ari, 2014). A jet nebulizer utilizes a baffle to introduce compressed air into a medication reservoir, producing aerosol particles to be delivered into the lung through the flow of the provided compressed air. The size of the particles produced by the nebulizer will be analyzed through an experimental airway system and a stochastic lung model to understand where these particles deposit in the lung.

This experiment used a standard jet nebulizer (Compressor Nebulizer Model A500, SWE Plastic & Metal Manufactory Limited). A series of tests with deionized water, 0.9% saline, and 7% saline, commonly used with nebulizers, were performed. 7% saline is only prescribed in specific circumstances with illnesses such as cystic fibrosis and bronchiectasis. The Optical Particle Sizer (OPS) Spectrometer (3300, TSI), which measures particles ranging from 0.3-10 micrometers, was used in this study. 

The setup can be seen in Figure 1 below. The nebulizer was attached with tubes to the system. The particle concentration was lowered by adding a settling chamber and compressed air.  The OPS could not easily handle particle concentrations above 1000 particles per cm3. A vacuum controlled the airflow rate through the respiratory model. The airflow through the system was 6 L/min, which matches the tidal volume of a resting adult (Pleil et al., 2021). The particles traveled through a chamber containing a 3D model of human lungs composed of resin. The size and number of particles were recorded before they entered and exited the chamber. 

The information from the OPS was placed through the Aerosol Instrument Manager, which formats the data to be placed into the Multiple-Path Particle Dosimetry Model (MPPD). This program takes the information gathered by the OPS and simulates a stochastic lung model to calculate the particle deposition in different airway regions. The data analyzed for this project from MPPD was the deposition mass rates for each major airway region.

The results of this experiment focus on analyzing the particle characteristics produced by the jet nebulizer. In Figure 2, the particle concentration and diameter of the particles are compared. The graph displays that water produced the highest concentration of the smallest particles (0.337-1.007 μm). In contrast, 7% saline had larger particles than the other solutions ranging from 2.3 to 4 micrometers, and produced the least amount of particles overall. Finally, the 0.9% saline produced the highest particle concentration and most particles between 1.007 and 2.3 micrometers. The higher water and 0.9% saline concentrations are attributed to the solutions having lower viscosities. Generally, the particle size decreases as the viscosity increases (McCallion et al., 1996); however, the massive cooling effect of the baffle and reservoir in the jet nebulizer is likely attributed to the lower concentration of 7% saline.
Figure 3 compares the Deposition Fractions for each solution given different regions of the lung airway. MPPD provided the fractions, which were converted into percentages for display for the head, tracheobronchial, and pulmonary regions. The 7% saline deposited the most particles in all regions, while water deposited the least. The largest total deposition percentage was 36%, meaning that most of the aerosol particles were exhaled rather than deposited or would continue deeper into the lung than the simulation could process. 

Based on the particle depositions calculated by MPPD and the data analysis, there appears to be a correlation between particle size and the amount of deposition. For 7% saline, the particles were larger and deposited in higher percentages in the lung regions. Smaller particles are able to travel further into the lung, so water particles were deposited in smaller amounts in the evaluated areas compared to the saline. 

The jet nebulizers produced the highest concentration of particles with solutions of lower viscosity. In contrast, solutions with higher viscosity produced the highest depositions. In the future, the results of this study will be evaluated experimentally using a 3D-printed porous lung model up to the 7th generation of the lung.

Ari, A. (2014). Jet, Ultrasonic, and Mesh Nebulizers: An Evaluation of Nebulizers for Better Clinical Outcomes. https://scholarworks.gsu.edu/cgi/viewcontent.cgi?article=1001&context=rt_facpub 

McCallion, O. N. M., Taylor, K. M. G., Bridges, P. A., Thomas, M., & Taylor, A. J. (1996). Jet nebulisers for Pulmonary Drug Delivery. International Journal of Pharmaceutics, 130(1), 1–11. https://doi.org/10.1016/0378-5173(95)04233-4 

Pleil, J. D., Ariel Geer Wallace, M., Davis, M. D., & Matty, C. M. (2021). The physics of human breathing: Flow, timing, volume, and pressure parameters for normal, on-demand, and ventilator respiration. Journal of Breath Research, 15(4), 042002. https://doi.org/10.1088/1752-7163/ac2589