Pharmacokinetics of vancomycin in sputum of intubated patients: Optimized intravenous delivery vs. inhaled therapy.

Aims: Intubated patients with methicillin-resistant Staphylococcus aureus pneumonia, fail optimized treatment with intravenous (IV) vancomycin (serum trough 15-20 μg/mL) in 38-79% of cases. Airway blood flow is diminished compared to alveoli and we hypothesized that vancomycin concentrations achieved in airway secretions are suboptimal and nonbactericidal. Targeted therapy by inhalation may overcome this deficit.

External Jet Nebulization and Measured Ventilator Performance.

Background: During invasive ventilation, external flow jet nebulization results in increases in displayed exhaled tidal volumes (V). We hypothesized that the magnitude of the increase is inaccurate. An ASL 5000 simulator measured ventilatory parameters over a wide range of adult settings: actual V, peak inspiratory pressure (PIP), and time to minimum pressure.

In Vivo Deposition of High-Flow Nasal Aerosols Using Breath-Enhanced Nebulization.

Aerosol delivery using conventional nebulizers with fixed maximal output rates is limited and unpredictable under high-flow conditions. This study measured regulated aerosol delivery to the lungs of normal volunteers using a nebulizer designed to overcome the limitations of HFNC therapy ( (InspiRx, Inc., Somerset, NJ, USA)).

Multidrug Aerosol Delivery During Mechanical Ventilation.

In the critically ill, pulmonary vasodilators are often provided off label to intubated patients using continuous nebulization. If additional aerosol therapies such as bronchodilators or antibiotics are needed, vasodilator therapy may be interrupted. This study assesses aerosol systems designed for simultaneous delivery of two aerosols using continuous nebulization and bolus injection without interruption or circuit disconnection.

In Vitro Model for Analysis of High-Flow Aerosol Delivery During Continuous Nebulization.

Background: To understand the fate of aerosols delivered by high-flow nasal cannula using continuous nebulization, an open-source anatomical model was developed and validated with a modified real-time gamma ratemeter technique. Mass balance defined circuit losses. Responsiveness to infusion rate and device technology were tested.

Real-Time Analysis of Dry-Side Nebulization With Heated Wire Humidification During Mechanical Ventilation.

Background: Recent observational studies of nebulizers placed on the wet side of the humidifier suggest that, after some time, considerable condensation can form, which triggers an occlusion alarm. In the current study, an inline breath-enhanced jet nebulizer was tested and compared in vitro with a vibrating mesh nebulizer on the humidifier dry-inlet side of the ventilator circuit.

Methods: Two duty cycle breathing patterns were tested during continuous infusion (5 or 10 mL/h) with and without dynamic changes in infusion flow and duty cycle, or bolus delivery (3 or 6 mL) of radiolabeled saline solution.

Continuous infusion aerosol delivery of prostacyclins during mechanical ventilation: challenges, limitations, and recent advances.

Introduction: Critically ill mechanically ventilated patients routinely receive aerosol delivery of epoprostenol by continuous infusion of the nebulizer by syringe pump. This procedure is 'off-label' as no FDA approved drug presently exists. Without standardized protocols, therapy is based on prior experience with bronchodilators, limited studies of delivery systems and anecdotal clinical trials.

The Unfulfilled Promise of Inhaled Therapy in Ventilator-Associated Infections: Where Do We Go from Here?

Respiratory infection is common in intubated/tracheotomized patients and systemic antibiotic therapy is often unrewarding. In 1967, the difficulty in treating Gram-negative respiratory infections led to the use of inhaled gentamicin, targeting therapy directly to the lungs. Fifty-three years later, the effects of topical therapy in the intubated patient remain undefined.

Real-Time Assessment of Aerosol Delivery During Mechanical Ventilation.

A new real-time method for assessing factors determining aerosol delivery is described. A breath-enhanced jet nebulizer operated in a ventilator/heated humidifier system was tested during bolus and continuous infusion aerosol delivery. Tc (technetium)/saline was either injected (3 or 6 mL) or infused over time into the nebulizer.

Control de la fuente respiratoria mediante el uso de una mascarilla quirúrgica: un estudio .

RESUMENLa etiqueta para la tos y la higiene respiratoria son formas de control de la fuente de emisión cuyo uso se alienta para evitar la propagación de infecciones respiratorias. El uso de mascarillas quirúrgicas como medio de control de la fuente en términos de reducción de la exposición de terceros no se ha investigado. En este estudio diseñamos un modelo utilizando varias mascarillas faciales con el fin de evaluar su aporte a la reducción de la exposición cuando son utilizadas en la fuente infecciosa (Fuente) en comparación con la reducción proporcionada por las mascarillas usadas para la protección primaria (Receptor), así como los factores que contribuyen a cada una.

Factors Determining Continuous Infusion Aerosol Delivery During Mechanical Ventilation.

Background: Continuous nebulization of prostacyclins and albuterol by infusion pump during mechanical ventilation evolved as a popular off-label treatment for severe hypoxemic respiratory failure and asthma. Most institutions use a vibrating mesh nebulizer. A new breath-enhanced jet nebulizer is a potential alternative.

Face Mask Leak Determines Aerosol Delivery in Noninvasive Ventilation.

Background: Aerosol transport during noninvasive ventilation follows the flow of pressurized gas through the noninvasive ventilation circuit, vented via leak port and face mask, and inhaled by the patient. Recommendations for nebulizer placement are based on in vitro models that have focused primarily on aerosol losses via the leak port; face mask leaks have been avoided. This study tested aerosol delivery in the setting of controlled face mask leak.

Reducing Aerosol-Related Risk of Transmission in the Era of COVID-19: An Interim Guidance Endorsed by the International Society of Aerosols in Medicine.

National and international guidelines recommend droplet/airborne transmission and contact precautions for those caring for coronavirus disease 2019 (COVID-19) patients in ambulatory and acute care settings. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, an acute respiratory infectious agent, is primarily transmitted between people through respiratory droplets and contact routes. A recognized key to transmission of COVID-19, and droplet infections generally, is the dispersion of bioaerosols from the patient.

Wet-Side Breath-Enhanced Jet Nebulization: Controlling Drug Delivery During Mechanical Ventilation.

Background: The present study tested a novel nebulizer and circuit that use breath enhancement and breath actuation to minimize ventilator influences. The unique circuit design incorporates "wet-side" jet nebulization (the nebulizer connected to the humidifier outlet port) to prevent unpredictable aerosol losses with active humidification. The system was studied using several ventilator brands over a wide range of settings, with and without humidification.

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.

Interferon-γ enhances the antifibrotic effects of pirfenidone by attenuating IPF lung fibroblast activation and differentiation.

Background: Idiopathic pulmonary fibrosis (IPF) pathogenesis involves multiple pathways, and combined antifibrotic therapy is needed for future IPF therapy. Inhaled interferon-γ (IFN-γ) was recently shown to be safe and without systemic effects in patients with IPF.

Aim: To examine the in vitro effects of individual and combined treatment with IFN-γ and pirfenidone (PFD) on normal and IPF fibroblast activation and extracellular matrix remodeling after TGF-β1 and PDGF-BB stimulation.

Nebulized Mannitol, Particle Distribution, and Cough in Idiopathic Pulmonary Fibrosis.

Background: Inhaled interferon, a potential treatment for idiopathic pulmonary fibrosis, must be formulated with mannitol, which can cause bronchospasm and cough. Coughing during drug inhalation can be affected by many factors, but some factors are fixed by the needs of the formulation and inflammatory disease in the airways. A component of the cough response may be related to sites of deposition, particularly upper and central airways.

Repurposing of gamma interferon via inhalation delivery.

Pulmonary diseases frequently involve imbalances in immunity. The inability to control bacteria in tuberculosis is a failed response to a pathogen. Idiopathic pulmonary fibrosis (IPF), a progressive fibrotic lung disease, can lead to respiratory failure and death within 3 years of diagnosis.

Faraday Waves-Based Integrated Ultrasonic Micro-Droplet Generator and Applications.

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.

Lung microbiome and host immune tone in subjects with idiopathic pulmonary fibrosis treated with inhaled interferon-γ.

Therapies targeting inflammation reveal inconsistent results in idiopathic pulmonary fibrosis (IPF). Aerosolised interferon (IFN)-γ has been proposed as a novel therapy. Changes in the host airway microbiome are associated with the inflammatory milieu and may be associated with disease progression.