Protocol for bacterial filtration efficiency evaluations of facemask materials using viable bacteria-laden aerosol droplets.

Here, we present a protocol for determining the bacterial filtration efficiencies of facemask materials according to the American Society for Testing and Materials (ASTM) standard F2101-19. We describe steps for reproducibly generating, collecting, and enumerating viable bacteria-laden aerosols containing the bacterial pathogen Staphylococcus aureus. The optimized operating parameters generate 1,700 to 3,000 viable bacteria-laden aerosol droplets between 2.

Unraveling the impact of operational parameters and environmental conditions on the quality of viable bacterial aerosols.

Viable pathogen-laden droplets of consistent quality are essential for reliably assessing the protection offered by facemasks against airborne infections. We identified a significant gap in guidance within standardized tests for evaluating the filtration efficiencies of facemask materials using viable bacteria-laden aerosol droplets. An aerosol platform, built according to the American Society for Testing and Materials standard F2101-19, was used to validate and standardize facemask filtration test procedures.

Design Considerations for Intratracheal Delivery Devices to Achieve Proof-of-Concept Dry Powder Biopharmaceutical Delivery in Mice.

Purpose: Intratracheal delivery and consistent dosing of dry powder vaccines is especially challenging in mice. To address this issue, device design of positive pressure dosators and actuation parameters were assessed for their impacts on powder flowability and in vivo dry powder delivery.

Methods: A chamber-loading dosator assembled with stainless-steel, polypropylene or polytetrafluoroethylene needle-tips was used to determine optimal actuation parameters.

Dextran Mass Ratio Controls Particle Drying Dynamics in a Thermally Stable Dry Powder Vaccine for Pulmonary Delivery.

Purpose: Thermally stable, spray dried vaccines targeting respiratory diseases are promising candidates for pulmonary delivery, requiring careful excipient formulation to effectively encapsulate and protect labile biologics. This study investigates the impact of dextran mass ratio and molecular weight on activity retention, thermal stability and aerosol behaviour of a labile adenoviral vector (AdHu5) encapsulated within a spray dried mannitol-dextran blend.

Methods: Comparing formulations using 40 kDa or 500 kDa dextran at mass ratios of 1:3 and 3:1 mannitol to dextran, in vitro quantification of activity losses and powder flowability was used to assess suitability for inhalation.

Radiolabeling Methods.

measurements of the deposition of an inhaled radiolabeled pharmaceutic have provided useful information related to the inhaler efficiency for depositing drug in the lung. A number of labeling techniques have been developed and applied to pharmaceutical aerosols delivered by pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs) and nebulizers; the choice of radiotracer depends on the type of imaging study being performed and the equipment used to image the lung. Preparation, validation and calibration of the radiolabeled pharmaceutical product is key to successful interpretation of the imaging study.

Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans.

BackgroundAdenovirus-vectored (Ad-vectored) vaccines are typically administered via i.m. injection to humans and are incapable of inducing respiratory mucosal immunity.

Forgotten Technology in the COVID-19 Pandemic: Filtration Properties of Cloth and Cloth Masks-A Narrative Review.

Management of the global crisis of the coronavirus disease 2019 pandemic requires detailed appraisal of evidence to support clear, actionable, and consistent public health messaging. The use of cloth masks for general public use is being debated, and is in flux. We searched the MEDLINE and EMBASE databases and Google for articles reporting the filtration properties of flat cloth or cloth masks.

Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach.

As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors of this article suggest that there is convincing evidence to support this recommendation.

Biophysical model to predict lung delivery from a dual bronchodilator dry-powder inhaler.

A biophysical lung model was designed to predict inhaled drug deposition in patients with obstructive airway disease, and quantitatively investigate sources of deposition variability. Different mouth-throat anatomies at varying simulated inhalation flows were used to calculate the lung dose of indacaterol/glycopyrronium [IND/GLY] 110/50 µg (QVA149) from the dry-powder inhaler Breezhaler. Sources of variability in lung dose were studied using computational fluid dynamics, supported by aerosol particle sizing measurements, particle image velocimetry and computed tomography.

Studies of Radioaerosol Deposition in the Respiratory Tract.

Deposition of aerosols in the respiratory tract can be quantitatively and qualitatively studied by scintigraphy. The most commonly used radionuclide for this purpose is technetium-99m. The effects of various factors on particle deposition have been investigated by using radiolabeled aerosols in the past decade.

Relationship of Inhaled Corticosteroid Adherence to Asthma Exacerbations in Patients with Moderate-to-Severe Asthma.

Background: Patients with asthma and elevated blood eosinophils are at increased risk of severe exacerbations. Management of these patients should consider nonadherence to inhaled corticosteroid (ICS) therapy as a factor for increased exacerbation risk.

Objective: The objective of this study was to investigate whether poor adherence to ICS therapy explains the occurrence of asthma exacerbations in patients with elevated blood eosinophil levels.

Errors in the Use of Inhalers by Health Care Professionals: A Systematic Review.

Background: Inefficient inhaler technique (IT) compromises the optimal delivery of medication. However, the IT knowledge of health care professionals (HCPs) has received scant attention.

Objective: The objective of this study was to perform a systematic review of published reports assessing the IT proficiency of HCPs in using pressurized metered dose (pMDI) and dry powder (DPI) inhalers.

Real-Life Outcomes for Patients with Asthma Prescribed Spacers for Use with Either Extrafine- or Fine-Particle Inhaled Corticosteroids.

Background: Spacers are often used with pressurized metered-dose inhalers (pMDIs) to eliminate the need for coordinating inhalation with actuation.

Objective: To investigate the real-life effectiveness of spacers prescribed for use with either extrafine- or fine-particle inhaled corticosteroids (ICSs).

Methods: This historical matched cohort study examined anonymous medical record data over 2 years (1-year baseline, 1-year outcome) for patients with asthma aged 12 to 80 years initiating ICSs by pMDI with or without prescribed spacer.

The use of multiple respiratory inhalers requiring different inhalation techniques has an adverse effect on COPD outcomes.

Background: Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques. Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique. Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known.

Airway Epithelial Cell Cilia and Obstructive Lung Disease.

Airway epithelium is the first line of defense against exposure of the airway and lung to various inflammatory stimuli. Ciliary beating of airway epithelial cells constitutes an important part of the mucociliary transport apparatus. To be effective in transporting secretions out of the lung, the mucociliary transport apparatus must exhibit a cohesive beating of all ciliated epithelial cells that line the upper and lower respiratory tract.

Patient Focus and Regulatory Considerations for Inhalation Device Design: Report from the 2015 IPAC-RS/ISAM Workshop.

This article reports on discussions at the 2015 workshop cosponsored by the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) and the International Society for Aerosols in Medicine (ISAM), entitled "Regulatory and Patient Considerations for Inhalation Device Design, Development and Use." Key topics addressed at the workshop and presented here include patient-focused device design for orally inhaled products (OIPs), instructions for use (IFU), human factors, regulatory considerations in the United States and Europe, development of generic inhalers, quality-by-design, and change management of OIP devices. Workshop participants also identified several areas for further consideration and emphasized the need for increased focus on the patient to create therapeutic products (inclusive of device design, IFU, education, training) that support adherence with an individual patient's treatment regimen.

Positron emission tomography (PET) for assessing aerosol deposition of orally inhaled drug products.

The topical distribution of inhaled therapies in the lung can be viewed using radionuclides and imaging. Positron emission tomography (PET) is a three-dimensional functional imaging technique providing quantitatively accurate localization of the quantity and distribution of an inhaled or injected PET radiotracer in the lung. A series of transaxial slices through the lungs are obtained, comparable to an X-ray computed tomography (CT) scan.

Standardization of techniques for using planar (2D) imaging for aerosol deposition assessment of orally inhaled products.

Two-dimensional (2D or planar) imaging with (99m)Tc radiolabels enables quantification of whole-lung and regional lung depositions for orally inhaled drug products. This article recommends standardized methodology for 2D imaging studies. Simultaneous anterior and posterior imaging with a dual-headed gamma camera is preferred, but imaging with a single-headed gamma camera is also acceptable.

Clinically relevant test methods to establish in vitro equivalence for spacers and valved holding chambers used with pressurized metered dose inhalers (pMDIs).

Regulatory guidance in Canada and Europe recommends that the manufacturer of an inhaled drug product delivered by pressurized metered-dose inhaler (pMDI) identify a spacer (S) or valved holding chamber (VHC) to be used with their designated product. It therefore becomes necessary to include the S/VHC in the process of establishing bioequivalence (BE) to the reference pMDI product for both new-entry generic and subsequent market entry products (SMEPs). S/VHCs substantially modify the aerodynamic particle size distribution (APSD) of the inhaled medication, and potentially the spatial distribution of the mass of active pharmaceutical ingredient(s) [API(s)] depositing in the respiratory tract.

Ciliary beating is depressed in nasal cilia from chronic obstructive pulmonary disease subjects.

Unlabelled: COPD is characterized by increased cough, mucus production, and airway inflammation. Beating epithelial cell cilia contribute to mucociliary clearance with ciliary beat frequency (CBF) an important measure of cilia function. However, whether CBF varies with COPD severity is unknown.

The direct effect of hyperosmolar agents on ciliary beating of human bronchial epithelial cells.

Background: Inhalation of hypertonic saline and mannitol improve mucociliary clearance in patients with bronchiectasis, but little is known about how the relative osmotic strengths of these compounds affect ciliary beat frequency (CBF) of ciliated human bronchial epithelial cells (HBEC). Our aim was to compare in vitro the direct effects of osmotically equivalent solutions on CBF of HBEC.

Methods: HBEC were acutely (10, 30 min) exposed to comparable osmolar solutions of saline (0.