Maximizing Deep Lung Deposition in Healthy and Fibrotic Subjects During Jet Nebulization

In volunteers with idiopathic pulmonary fibrosis (IPF), inhaled Interferon-γ (IFN-γ) is safe and may improve pulmonary function. However, coughing, associated with upper airway deposition, is often reported. To address this problem, a small-particle, breath-enhanced jet nebulizer (i-NEB Mini; InspiRx, Inc., Somerset, NJ) was developed. Using gamma scintigraphy, this device was tested in healthy individuals and subjects with IPF to determine efficiency and regional deposition in lung and airways. Four healthy individuals and nine subjects with IPF were enrolled. The nebulizer was filled with 2 mL of saline with ^99m Tc bound to diethylenetriaminepentaacetic acid (DTPA) powered continuously with 3.4 L/min of compressed air. Mass median aerodynamic diameter (MMAD) was measured by cascade impactor. To maximize deposition in alveoli, inspiratory flow was limited by an inspiratory resistance incorporated into the nebulizer, resulting in a deep inspiration ∼6 seconds. The treatment was run to completion (10 minutes), and each subject underwent deposition imaging. Mass balance and regions of interest determined upper airway (measured by calibrated stomach activity) and regional lung deposition as a percent of pretreatment nebulizer charge. Subjects tolerated the device with no complaints. MMAD (mean [geometric standard deviation]) = 1.04 [1.92] μm. Lung deposition (mean ± standard error, % nebulizer charge) in healthy subjects was 26.2% ± 1.83 and in IPF individuals 23.4% ± 1.60 (p = 0.414). Upper airway deposition was 1.4% ± 0.83 and 2.3% ± 0.48, respectively (p = 0.351), and 20.1% was lost during expiration. Central/Peripheral ratios were consistent in both groups, showing high peripheral deposition (1.32 ± 0.050, vs. 1.28 ± 0.046, p = 0.912). The i-NEB Mini jet nebulizer with breath enhancement produced small particles, resulting in minimal upper airway deposition. Using slow and deep breathing, more than half of the emitted dose deposited in the peripheral lung in normal subjects and individuals with IPF. These data indicate that, for future clinical trials, controlled lung doses of small particles, designed to avoid coughing, are possible even in subjects with advanced disease.