Fate of inhaled aerosols under the influence of glottal motion in a realistic in silico human tracheobronchial tree model.

Despite the prevalence of inhalation therapy in the treatment of various respiratory diseases, predicting and optimizing lung deposition fractions of inhaled drugs for maximal efficacy remains challenging due to the complex anatomical structures of the extra-thoracic airways, notably the glottal region. One of the widespread speculations in current insilico simulations lies in assuming a static glottis during inhalation, while in reality inhalation leads to significant glottis cross-sectional area expansion. The present work attempts to explore, insilico, the influence of transient movement of the glottal structures on inhalation therapy outcomes.

Anatomical variability in the upper tracheobronchial tree: sex-based differences and implications for personalized inhalation therapies.

The morphometry of the large conducting airways is presumed to have a strong effect on the regional deposition of inhaled aerosol particles. Nevertheless, sex-based differences have not been fully quantified and are still largely ignored in designing inhalation therapies. To this end, we retrospectively analyzed high-resolution computed tomography scans for 185 individuals (90 women, 95 men) in the age range of 12-89 yr to determine airway luminal areas, airway lengths, and bifurcation angles.

In silico optimization of targeted aerosol delivery in upper airways via Inhaled Volume Tracking.

Background: Despite the widespread use of aerosol inhalation as a drug delivery method, targeted delivery to the upper airways remains an ongoing challenge in the quest for improved clinical response in respiratory disease.

Methods: Here, we examine in silico flow and particle dynamics when using an oral Inhaled Volume Tracking manoeuvre. A short pulsed aerosol bolus is injected during slow inhalation flow rates followed by clean air, and a breath-hold is initiated once it reaches the desired depth.

On the Validation of Generational Lung Deposition Computer Models Using Planar Scintigraphic Images: The Case of Mimetikos Preludium.

Mechanistic computer models for calculation of total and regional deposition of aerosols in the lungs are important tools for predicting or understanding clinical studies and for facilitating development of pharmaceutical inhalation products. Validation of such models must be indirect since generational data are lacking. Planar scintigraphy is probably the most common method addressing regional lung deposition in humans.

Multiscale lung modeling strategies for aerosol inhalation therapy and drug delivery.

Inhalation therapy is a hallmark of modern respiratory medicine. Over recent years, computational fluid-particle dynamics (CFPD) simulations of respiratory airflows and aerosol deposition in the lungs have rapidly developed into an increasingly mature research field in the biomedical engineering realm, owing, among others, to tremendous advances in computational capabilities and available resources. Despite such progress, the intrinsic anatomical and physiological complexity of the lungs prevents the straightforward implementation of 'brute force' simulation strategies applied across the entire pulmonary tract.

Targeting inhaled fibers to the pulmonary acinus: Opportunities for augmented delivery from in silico simulations.

Non-spherical particles, and fibers in particular, are potentially attractive airborne carriers for pulmonary drug delivery. Not only do they exhibit a high surface-to-volume ratio relative to spherical aerosols, but their aerodynamic properties also enable them to reach deep into the lungs. Until present, however, our understanding of the deposition characteristics of inhaled aerosols in the distal acinar lung regions has been mostly limited to spheres.

Targeting inhaled aerosol delivery to upper airways in children: Insight from computational fluid dynamics (CFD).

Despite the prevalence of inhalation therapy in the treatment of pediatric respiratory disorders, most prominently asthma, the fraction of inhaled drugs reaching the lungs for maximal efficacy remains adversely low. By and large drug delivery devices and their inhalation guidelines are typically derived from adult studies with child dosages adapted according to body weight. While it has long been recognized that physiological (e.