The role of respiratory flow asynchrony on convective mixing in the pulmonary acinus

Hofemeier, Philipp; Fishler, Rami; Sznitman, Josué

doi:10.1088/0169-5983/46/4/041407

Cited by 17 publications

(29 citation statements)

References 34 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…II and Fig. 2(c)], experimentally resolved alveolar and ductal flow patterns are consistent with computational fluid dynamics (CFD) simulations conducted in more realistic space-filling 3D geometries 73,76 [Fig. 2(d)].…”

Section: Establishing Respiratory Flows In Vitrosupporting

confidence: 77%

Biomimetics of the pulmonary environment in vitro: A microfluidics perspective

et al. 2018

Self Cite

View full text Add to dashboard Cite

The entire luminal surface of the lungs is populated with a complex yet confluent, uninterrupted airway epithelium in conjunction with an extracellular liquid lining layer that creates the air-liquid interface (ALI), a critical feature of healthy lungs. Motivated by lung disease modelling, cytotoxicity studies, and drug delivery assessments amongst other, in vitro setups have been traditionally conducted using macroscopic cultures of isolated airway cells under submerged conditions or instead using transwell inserts with permeable membranes to model the ALI architecture. Yet, such strategies continue to fall short of delivering a sufficiently realistic physiological in vitro airway environment that cohesively integrates at true-scale three essential pillars: morphological constraints (i.e., airway anatomy), physiological conditions (e.g., respiratory airflows), and biological functionality (e.g., cellular makeup). With the advent of microfluidic lung-on-chips, there have been tremendous efforts towards designing biomimetic airway models of the epithelial barrier, including the ALI, and leveraging such in vitro scaffolds as a gateway for pulmonary disease modelling and drug screening assays. Here, we review in vitro platforms mimicking the pulmonary environment and identify ongoing challenges in reconstituting accurate biological airway barriers that still widely prevent microfluidic systems from delivering mainstream assays for the end-user, as compared to macroscale in vitro cell cultures. We further discuss existing hurdles in scaling up current lung-on-chip designs, from single airway models to more physiologically realistic airway environments that are anticipated to deliver increasingly meaningful whole-organ functions, with an outlook on translational and precision medicine.

show abstract

Section: Establishing Respiratory Flows In Vitrosupporting

confidence: 77%

Biomimetics of the pulmonary environment in vitro: A microfluidics perspective

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The uniform deposition pattern of PM 0.2 in the acinar region indicates that the gravitational force is not the main factor that influences the motion of the smaller particles. The kinetics of the PM 0.2 is largely affected by the local unsteady airflow patterns within alveolar cavities, where the particle is diverted from an escape zone to a capture zone (or vice versa) (13,(15)(16)(17). Additionally, the highest concentration of PM 0.2 is in the bronchiole region, a local area marked with the dash square (b2) is observed, and more particles are found on the surface of the bronchiole, as shown in Fig.…”

Section: Significancementioning

confidence: 92%

“…According to current understanding, kinematics of particles in the acinar region are dominated by the gravitational sedimentation for large particles (larger than 2.0 μm), while Brownian motion influences small ones (smaller than 0.1 μm) (13,14). For intermediate particles in the size range of 0.1-1 μm, transport is dependent on the local irreversible kinematics within the alveolar cavities (13,(15)(16)(17). Because of the different kinematics, the deposition process and patterns are more complicated than those predicted by the average model based on uniform deposition.…”

mentioning

confidence: 99%

Fluorescent reconstitution on deposition of PM _2.5 in lung and extrapulmonary organs

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

145

View full text Add to dashboard Cite

The deposition of PM2.5 (fine particulate matter in air with diameter smaller than 2.5 μm) in lungs is harmful to human health. However, real-time observation on the deposition of particles in the acinar area of the lung is still a challenge in experiments. Here, a fluorescent imaging method is developed to visualize the deposition process with a high temporal and spatial resolution. The observations reveal that the deposition pattern is nonuniform, and the maximum deposition rate in the acinar area differs significantly from the prediction of the widely used average deposition model. The method is also used to find single particles in the kidney and liver, though such particles are commonly believed to be too large to enter the extrapulmonary organs.

show abstract

“…Wall breathing expansions and contractions of the acinar domain are modeled with an idealized sinusoidal motion. While temporal asynchrony and heterogeneous wall motions as a result of a geometric hysteresis in lung expansion are known to exist (25,29,45), the principal mode of breathing is acknowledged to remain largely self-similar (2,17). Mathematically, the motion of the computational domain is thus mimicked with (26,35,59,60,64,70) x͑t͒…”

Section: Methodsmentioning

confidence: 99%

“…Whether two-dimensional (2D) or 3D geometries of single isolated alveoli (19,67,64), acinar ducts (8,21,26,35,36,63), or bifurcating acinar airways (6,10,43,60), numerical studies have largely focused on the kinematics of inhaled micrometersized particles predominantly governed by (26,31,43,60); yet, this range of sizes represents only a small fraction of the aerosols capable of reaching the acinus (23,24). For finer submicrometer particles, their motion has long been thought to follow convective airflows (65), and thus most studies have analyzed trajectories of passive tracer particles subject to acinar flows only (5,10,22,25,53,68,69). However, these fail to capture intrinsic particle diffusion (i.e., Brownian motion) that is anticipated to become a critical transport mechanism in the acinus (58), in particular for ultrafine particles (UFPs) with diameters Ͻ100 nm.…”

mentioning

confidence: 99%

Revisiting pulmonary acinar particle transport: convection, sedimentation, diffusion, and their interplay

Hofemeier

Sznitman

2015

Journal of Applied Physiology

Self Cite

View full text Add to dashboard Cite

It is largely acknowledged that inhaled particles ranging from 0.001 to 10 m are able to reach and deposit in the alveolated regions of the lungs. To date, however, the bulk of numerical studies have focused mainly on micrometer sized particles whose transport kinematics are governed by convection and sedimentation, thereby capturing only a small fraction of the wider range of aerosols leading to acinar deposition. Too little is still known about the local acinar transport dynamics of inhaled (ultra)fine particles affected by diffusion and convection. Our study aims to fill this gap by numerically simulating the transport characteristics of particle sizes spanning three orders of magnitude (0.01-5 m) covering diffusive, convective, and gravitational aerosol motion across a multigenerational acinar network. By characterizing the deposition patterns as a function of particle size, we find that submicrometer particles [formulae see text (0.1 m)] reach deep into the acinar structure and are prone to deposit near alveolar openings; meanwhile, other particle sizes are restricted to accessing alveolar cavities in proximal generations. Our findings underline that a precise understanding of acinar aerosol transport, and ultrafine particles in particular, is contingent upon resolving the complex convective-diffusive interplay in determining their irreversible kinematics and local deposition sites.

show abstract

The role of respiratory flow asynchrony on convective mixing in the pulmonary acinus

Cited by 17 publications

References 34 publications

Biomimetics of the pulmonary environment in vitro: A microfluidics perspective

Biomimetics of the pulmonary environment in vitro: A microfluidics perspective

Fluorescent reconstitution on deposition of PM _2.5 in lung and extrapulmonary organs

Revisiting pulmonary acinar particle transport: convection, sedimentation, diffusion, and their interplay

Contact Info

Product

Resources

About

The role of respiratory flow asynchrony on convective mixing in the pulmonary acinus

Cited by 17 publications

References 34 publications

Biomimetics of the pulmonary environment in vitro: A microfluidics perspective

Biomimetics of the pulmonary environment in vitro: A microfluidics perspective

Fluorescent reconstitution on deposition of PM 2.5 in lung and extrapulmonary organs

Revisiting pulmonary acinar particle transport: convection, sedimentation, diffusion, and their interplay

Contact Info

Product

Resources

About

Fluorescent reconstitution on deposition of PM _2.5 in lung and extrapulmonary organs