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Aerosol transport and liquid delivery through the lung airway system

par Hervé Henry - publié le

Due to the remarkable surface of the air-blood interface, lungs are a privileged path for systemic delivery using aerosols. Our group has studied the mechanisms of aerosol deposition in the lung, and shown that transport into the bronchial tree, for a large population of particles or droplets, can essentially be seen as a "multiplicative" process in which each successive bifurcation acts independently. In other words, the fraction of particles reaching a given generation can be computed by multiplying the escape probabilities at each bifurcation along the path. These probabilities only depend on the bifurcation morphology and the local "Stokes number" of the particles. This approach enables to compute in a very simple way the deposition rates in a complex tree, and to understand the role of bronchial morphology on aerosol capture.

We also address fluid transport into the lung airway system, especially surfactant delivery. Pulmonary alveoli are normally lined with a chemical called surfactant which enables their homogeneous dilation and contraction during the breathing cycle. Surfactant deficiency leads to Newborn Respiratory Distress Syndrom in premature babies (NRDS) and contributes to Acute Respiratory Distress Syndrom (ARDS) in adults. One recommended treatment consists in a direct instillation of surfactant inside the patient trachea. However, its efficacy remains limited. About 35% of premature babies do not respond to the surfactant replacement treatment, and this therapy has been discontinued in adults.

The first physico-mathematical model of surfactant replacement therapy, elaborated in our group, enables us today to understand the mechanisms governing the transport of a liquid plug into the tracheobronchial tree. Our works paves the way of a complete revision of past clinical trials, and of the possible reopening of therapeutic ways discontinued for wrong reasons. Thanks to our model which accounts for the 3D pulmonary structure (bronchi, bronchioles), the fluid properties (viscosity, density), the interaction between fluid and airway wall, and the splitting mechanism at each bifurcation (function of orientation and gravity), we have been able to show that the classical hypotheses underlying clinical trials are not always fulfilled. The pulmonary system is very complex and the trajectory of the surfactant depends on its physico-chemical properties, on the patient size, and on the delivery procedure. Thanks to this new modeling tool, physicians and pharmaceutical labs may envision improve the prediction of the therapeutic efficacy, and engineer patient specific treatments.

A few significant publications :

  1. T.F. de Vasconcelos, B. Sapoval, J.S. Andrade Jr., J.B. Grotberg, Y. Hu, M. Filoche, “Deposition of particles in the lung made simple ?”, J. Appl. Physiol. 110:1664-1673 (2011).
  2. J.R. Zierenberg, D. Halpern, M. Filoche, B. Sapoval, J.B. Grotberg, “An Asymptotic Model of Particle Deposition at an Airway Bifurcation”, Math. Med. & Biol. 102(30):131-156 (2013).
  3. P.-A. Muller, M. Pichelin, G. Apiou, B. Louis, I. Katz, G. Caillibotte, M. Filoche, D. Isabey, “Maximal efficiency of convective mixing occurs in mid acinus : a 3D-numerical analysis by an Eulerian approach”, J. Aerosol Sci. 76:163-174 (2014).
  4. M. Filoche, C.-F. Tai, J. B. Grotberg, “A three-dimensional model of surfactant delivery into the lung”, Proc. Natl. Acad. Sci. USA 112 (30) : 9287-9292 (2015).