Background: Inhaled interferon-γ aerosol (aINF-γ) may be effective treatment for idiopathic pulmonary fibrosis (IPF). We evaluated safety and delivery of aIFN-γ (100 μg 3 times/week) in 10 IPF patients using the I-neb (Philips Respironics, Parsippany, NJ). Methods: IFN-γ activity in the aerosol was confirmed by viral inhibition. Ten patients with an average age of 68 diagnosed with IPF (American Thoracic Society/European Respiratory Society consensus guidelines) were enrolled. In vivo deposition was measured via a gamma camera. The nebulizer recorded patient adherence to therapy. Pulmonary function tests [PFTs, forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DLCO)] and the 6-min walk test were measured at baseline, and every 12–14 weeks for 80 weeks. Bronchoalveolar lavage (BAL) of the middle lobe was performed at baseline and 28 weeks. BAL and plasma samples were analyzed for chemokines and cytokines, including INF-γ. Results: All 10 patients tolerated 80 weeks of inhaled IFN-γ well, with no systemic side effects. True adherence with aerosol treatment averaged 96.7±4.81% (±SEM). In vivo lung deposition averaged 65.4±4.8μg and oropharyngeal deposition 12.6±3.0 μg. BAL IFN-γ increased 60-fold and profibrotic cytokines (FGP-2, Flt-3 ligand, IL-5) were significantly decreased; IFN-γ plasma levels were unchanged. PFTs showed minimal change in FVC. Post hoc analysis indicated that the slope of decline in TLC and DLCO reversed after beginning therapy. The 6-min walk was unchanged. Conclusions: IFN-γ is safe in IPF and can be effectively delivered to lung parenchyma. PFTs remained stable throughout the trial. Reversal of pretherapy PFT decline may define an end-point for future clinical trials.

Potentially infected individuals (‘source’) are sometimes encouraged to use face masks to reduce exposure of their infectious aerosols to others (‘receiver’). To improve compliance with Respiratory Source Control via face mask and therefore reduce receiver exposure, a mask should be comfortable and effective. We tested a novel face mask designed to improve breathability and filtration using nanofiber filtration. Using radiolabeled test aerosols and a calibrated exposure chamber simulating source to receiver interaction, facepiece function was measured with a life-like ventilated manikin model. Measurements included mask airflow resistance (pressure difference during breathing), filtration, (mask capture of exhaled radiolabeled test aerosols), and exposure (the transfer of ‘infectious’ aerosols from the ‘source’ to a ‘receiver’). Polydisperse aerosols were measured at the source with a mass median aerodynamic diameter of 0.95 µm. Approximately 90% of the particles were <2.0 µm. Tested facepieces included nanofiber prototype surgical masks, conventional surgical masks, and for comparison, an N95-class filtering facepiece respirator (commonly known as an ‘N95 respirator’). Airflow through and around conventional surgical face mask and nanofiber prototype face mask was visualized using Schlieren optical imaging. Airflow resistance [ΔP, cmH₂O] across sealed surgical masks (means: 0.1865 and 0.1791 cmH₂O) approached that of the N95 (mean: 0.2664 cmH₂O). The airflow resistance across the nanofiber face mask whether sealed or not sealed (0.0504 and 0.0311 cmH₂O) was significantly reduced in comparison. In addition, ‘infected’ source airflow filtration and receiver exposure levels for nanofiber face masks placed on the source were comparable to that achieved with N95 placed on the source; 98.98% versus 82.68% and 0.0194 versus 0.0557, respectively. Compared to deflection within and around the conventional face masks, Schlieren optical imaging demonstrated enhanced airflow through the nanofiber mask. Substituting nanofiber for conventional filter media significantly reduced face mask airflow resistance directing more airflow through the face mask resulting in enhanced filtration. Respiratory source control efficacy similar to that achieved through the use of an N95 respirator worn by the source and decreased airflow resistance using nanofiber masks may improve compliance and reduce receiver exposure.

Background: Placing a surgical mask on an infected patient (respiratory source control) may offer a health-care worker (HCW) more protection than donning an N95 respirator (receiver protection). This observation was made in an in vitro study that used hard, nondeformable faces, and the lack of proper N95 fit may have accounted for the observed results. In the present study, we test the effects of fit on respiratory source control protection, using a soft, deformable mannequin head. Methods: Resusci Anne CPR mannequin heads were placed in a chamber allowing 6 air exchanges/hr (14 cubic feet per minute), to simulate an infected patient (source) and an HCW (receiver). The heads were ventilated with a tidal breathing pattern. The source exhaled radioactive aerosols, and a filter was attached to the receiver to quantify inhaled exposure. N95 respirators and surgical masks were tested on both heads. The degree of protection was expressed by calculating the reduction in exposure expressed as a simulated workplace protection factor (sWPF; the ratio of exposure with mask to exposure without mask) compared statistically using confidence intervals. Results: Use of the Resusci Anne heads resulted in improved fit, with higher sWPF than previously reported, for example, for source N95 mask combinations (7,174 vs. 317) as well as receiver (7.53 vs. 1.37). Masks placed on the receiver provided minimal exposure protection (sWPF range 0.99–7.53), except when sealed with Vaseline (sWPF 63.1). Any mask applied to the source mannequin resulted in significant reductions in exposure (sWPF range 214–17,038). Conclusion: Improved fit significantly enhanced the effects of source control protection. A Vaseline-sealed N95 respirator on the receiver offered less protection when compared with any mask on the source. Respiratory source control can offer more protection to HCW and potentially decrease the spread of aerosolized infections.

An in-depth review on a new ultrasonic micro-droplet generator which utilizes megahertz (MHz) Faraday waves excited by silicon-based multiple Fourier horn ultrasonic nozzles (MFHUNs) and its potential applications is presented. The new droplet generator has demonstrated capability for producing micro droplets of controllable size and size distribution and desirable throughput at very low electrical drive power. For comparison, the serious deficiencies of current commercial droplet generators (nebulizers) and the other ultrasonic droplet generators explored in recent years are first discussed. The architecture, working principle, simulation, and design of the multiple Fourier horns (MFH) in resonance aimed at the amplified longitudinal vibration amplitude on the end face of nozzle tip, and the fabrication and characterization of the nozzles are then described in detail. Subsequently, a linear theory on the temporal instability of Faraday waves on a liquid layer resting on the planar end face of the MFHUN and the detailed experimental verifications are presented. The linear theory serves to elucidate the dynamics of droplet ejection from the free liquid surface and predict the vibration amplitude onset threshold for droplet ejection and the droplet diameters. A battery-run pocket-size clogging-free integrated micro droplet generator realized using the MFHUN is then described. The subsequent report on the successful nebulization of a variety of commercial pulmonary medicines against common diseases and on the experimental antidote solutions to cyanide poisoning using the new droplet generator serves to support its imminent application to inhalation drug delivery.

Background: 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. Methods: 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. Results: 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 25.7%±1.72 and in IPF individuals 23.5%±1.59 ( p = 0.604). Upper airway deposition was 1.45% ± 0.786 and 2.3% ± 0.48, respectively ( p = 0.386), 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). Conclusion: 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.