Maximizing Deep Lung Deposition in Healthy and Fibrotic Subjects

Abstract

Background:

Inhaled Interferon-gamma (IFN-g) may improve pulmonary function in idiopathic pulmonary fibrosis (IPF). However, the main reported side effect was coughing associated with upper and central airway deposition. To address this problem, our group developed an efficient, small particle breath enhanced jet nebulizer, designed to bypass upper and central airways on inspiration and maximize alveolar deposition on expiration. We tested this device by gamma scintigraphy in healthy individuals and subjects with IPF to determine device efficiency, upper and central airway, and lung deposition.

Methods:

Six healthy individuals and nine subjects with IPF were enrolled. Following background and transmission images, aerosol inhalation was performed. The I-neb Mini is a breath-enhanced jet nebulizer, that is, the majority of aerosol is generated during inspiration. The nebulizer was filled with 2mL of saline radiolabeled with 99m Tc bound to DTPA, and operated continuously via 3.5L/min of compressed air. MMAD measured by cascade impactor was (mean ± SE) 1.08 µm ± 0.04. In addition, to maximize deposition in alveoli, patients were encouraged to inhale slowly via an audible inspiratory resistance (over approx 6 s). The treatment was run to completion (10 min) 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 pre treatment nebulizer charge. Each individual signed a consent form approved by the University IRB.

Results:

Subjects tolerated the aerosol and device with no complaints. Lung deposition (%neb charge, mean ± SE) in healthy subjects was 26. 1% ± 1.36 and in IPF individuals 21.4% ± 1.6 (pNS). Upper airway deposition was 2.83% ± 1.11 (normal) and 3. 3% ± 0.48 (IPF) (pNS). Deposition fraction averaged 0.57 ± 0.05 (normal), 0.52 ± 0.02 (IPF) (P=0.0004). Central/Peripheral ratios were consistent with peripheral deposition in both groups (1.27 ± 0.05, vs 1.28 ± 0.05, pNS).

Conclusions:

The I-neb Mini jet nebulizer with breath enhancement produces small particles resulting in minimal upper airway deposition. Using slow and deep breathing, approximately 55 % of the inhaled particles deposited in the peripheral lung in both normal subjects and in 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.