Convective flow dominates aerosol delivery to the lung segments

Abstract

Most previous computational studies on aerosol transport in models of the central airways of the human lung have focused on deposition, rather than transport of particles through these airways to the subtended lung regions. Using a model of the bronchial tree extending from the trachea to the segmental bronchi (J Appl Physiol 98: 970-980, 2005), we predicted aerosol delivery to the lung segments. Transport of 0.5- to 10-μm-diameter particles was computed at various gravity levels (0-1.6 G) during steady inspiration (100-500 ml/s). For each condition, the normalized aerosol distribution among the lung segments was compared with the normalized flow distribution by calculating the ratio (R(i)) of the number of particles exiting each segmental bronchus i to the flow. When R(i) = 1, particle transport was directly proportional to segmental flow. Flow and particle characteristics were represented by the Stokes number (Stk) in the trachea. For Stk < 0.01, R(i) values were close to 1 and were unaffected by gravity. For Stk > 0.01, R(i) varied greatly among the different outlets (R(i) = 0.30-1.93 in normal gravity for 10-μm particles at 500 ml/s) and was affected by gravity and inertia. These data suggest that, for Stk < 0.01, ventilation defines the delivery of aerosol to lung segments and that the use of aerosol tracers is a valid technique to visualize ventilation in different parts of the lung. At higher Stokes numbers, inertia, but not gravitational sedimentation, is the second major factor affecting the transport of large particles in the lung.

What Causes Uneven Aerosol Deposition in the Bronchoconstricted Lung? A Quantitative Imaging Study

“…This result is qualitatively consistent with the predictions of a recent CFD model by Darquenne et al (9) using an idealized geometry of the human central airway tree and uniform specific ventilation among lung segments. Their results showed that the distal delivery of aerosol from the trachea to the lung segments was largely determined by the distribution on ventilation for Stokes numbers in the trachea less than 0.01.…”

“…We then collect all sources of variability into a single expression that describes lobar deposition in Equation (6). To better compare these sources of variability across different subjects, we account for differences in overall dosing, lung size, centrality of deposition, and restate the expression in nondimensional, normalized form in Equation (9). After several simplifications, we decouple the sources of variability in Equation (15).…”

“…(9) When diseased regions are less ventilated than the rest of the lung, delivery of inhaled aerosol therapy may be reduced to areas where it may be most needed. For example, bronchoconstricted subjects with asthma might expect to receive lower local doses of inhaled bronchodilator or anti-inflammatory agents in ventilation defective regions.…”

“…(9) These concentration differences may develop by two distinct factors. One factor emerges at bifurcations when air and aerosol divide between daughter branches in unequal fractions.…”

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

“…Based on what is known about the physics of aerosol deposition, it is likely that most of the variability in peripheral aerosol deposition among lobes, sub-lobes, or any set of peripheral lung regions, can be attributed to one of four distinct factors: 1) differences in regional ventilation; (1,137,138) 2) differences in how the aerosol and air distribute between branches in the series of bifurcations along the pathway feeding the region; (138) 3) variability in the amount of the aerosol that escapes the series of airways along that pathway; (139)(140)(141) and 4) variability in the amount of aerosol that reaches the periphery and is not exhaled. (142) Using the concept of aerosol concentration as the average mass in suspension crossing any point of the bronchial tree, a theoretical framework can be defined to quantify each of the factors that lead to heterogeneous aerosol deposition among lobes: (143) differences in lobar ventilation per unit volume (specific ventilation), uneven splitting of aerosol and air at bifurcations (bifurcation factor), differences in the fraction of aerosol deposited along the feeding airways (escape factor), and differences in the fraction of aerosol that reaches the periphery but escapes via exhalation (retention factor).…”