Performance and Feasibility of Therapeutic Vibrating Mesh Nebulizer for Ventilation Lung Scan

This study aimed to evaluate the performance of a therapeutic vibrating mesh-type nebulizer for the pulmonary delivery of radioaerosols for lung scintigraphy in healthy subjects. Six healthy subjects (mean age of 28.7 ± 6.2 y) inhaled 2 mL of Tc-99m diethylenetriaminepentaacetic acid (DTPA) and normal saline solution (20 mCi) via the therapeutic vibrating mesh nebulizer (DK010, DELBio, Taipei, Taiwan). The nebulizer’s mass median aerodynamic diameter (MMAD) is between 2.3 μm and 5.0 μm (3.47 ± 0.37 μm) and the nebulization rate is greater than 0.2 ml/min. Scintigraphy was performed to count radioaerosols in the regions of interest to determine the total and regional lung deposition and extrathoracic airway deposition of aerosols, penetration of aerosols, and radioactivity count balance. The total lung deposition of aerosols was 21.2 ± 5.2% (% ex-valve dose), 27.4 ± 8.0% (% ex-device dose) and 13.8 ± 4.1% (% initial dose) in nebulizer. The extrathoracic airway deposition was 4.8 ± 1.1%. The radioactivity count balance was 5.4 ± 3.0%. The ratio of outer vs inner lung deposition (O/I ratio, or penetration index) was 1.89 ± 0.55. The delivery efficiency and the penetration of aerosols to the peripheral lung achieved by the DELBio DK010 vibrating mesh-type nebulizer are similar to the commercialized jet-type nebulizers dedicated for radioaerosol lung scintigraphy nebulizer. The therapeutic vibrating mesh-type nebulizer (DELBio DK010) is feasible for radionuclide lung ventilation scintigraphy.

Patient-specific modeling of aerosol delivery in healthy and asthmatic adults

The magnitude and regional heterogeneity of airway obstructions in severe asthmatics is likely linked to insufficient drug delivery, as evidenced by the inability to mitigate exacerbations with inhaled aerosol medications. To understand the correlation between morphometric features, airflow distribution, and inhaled dosimetry, we perform dynamic computational simulations in two healthy and four asthmatic subjects. Models incorporate computed tomography-based and patient-specific central airway geometries and hyperpolarized 3He MRI-measured segmental ventilation defect percentages (SVDPs), implemented as resistance boundary conditions. Particles [diameters ( dp) = 1, 3, and 5 μm] are simulated throughout inhalation, and we record their initial conditions, both spatially and temporally, with their fate in the lung. Predictions highlight that total central airway deposition is the same between the healthy subjects (26.6%, dp = 3 μm) but variable among the asthmatic subjects (ranging from 5.9% to 59.3%, dp = 3 μm). We found that by preferentially releasing the particles during times of fast or slow inhalation rates we enhance either central airway deposition percentages or peripheral particle delivery, respectively. These predictions highlight the potential to identify with simulations patients who may not receive adequate therapeutic dosages with inhaled aerosol medication and therefore identify patients who may benefit from alternative treatment strategies. Furthermore, by improving regional dose levels, we may be able to preferentially deliver drugs to the airways in need, reducing associated adverse side effects. NEW & NOTEWORTHY Although it is evident that exacerbation mitigation is unsuccessful in some asthmatics, it remains unclear whether or not these patients receive adequate dosages of inhaled therapeutics. By coupling MRI and computed tomography data with patient-specific computational models, our predictions highlight the large intersubject variability, specifically in severe asthma.

Simulation of Airway Deposition of an Aerosol Drug in COPD Patients

Medical aerosols are key elements of current chronic obstructive pulmonary disease (COPD) therapy. Therapeutic effects are conditioned by the delivery of the right amount of medication to the right place within the airways, that is, to the drug receptors. Deposition of the inhaled drugs is sensitive to the breathing pattern of the patients which is also connected with the patient’s disease severity. The objective of this work was to measure the realistic inhalation profiles of mild, moderate, and severe COPD patients, simulate the deposition patterns of Symbicort® Turbuhaler® dry powder drug and compare them to similar patterns of healthy control subjects. For this purpose, a stochastic airway deposition model has been applied. Our results revealed that the amount of drug depositing within the lungs correlated with the degree of disease severity. While drug deposition fraction in the lungs of mild COPD patients compared with that of healthy subjects (28% versus 31%), lung deposition fraction characteristic of severe COPD patients was lower by a factor of almost two (about 17%). Deposition fraction of moderate COPD patients was in-between (23%). This implies that for the same inhaler dosage severe COPD patients receive a significantly lower lung dose, although, they would need more.