title: Three-dimensional model of surfactant replacement therapy.
abstract: Surfactant replacement therapy (SRT) involves instillation of a liquid-surfactant mixture directly into the lung airway tree. It is widely successful for treating surfactant deficiency in premature neonates who develop neonatal respiratory distress syndrome (NRDS). However, when applied to adults with acute respiratory distress syndrome (ARDS), early successes were followed by failures. This unexpected and puzzling situation is a vexing issue in the pulmonary community. A pressing question is whether the instilled surfactant mixture actually reaches the adult alveoli/acinus in therapeutic amounts. In this study, to our knowledge, we present the first mathematical model of SRT in a 3D lung structure to provide insight into answering this and other questions. The delivery is computed from fluid mechanical principals for 3D models of the lung airway tree for neonates and adults. A liquid plug propagates through the tree from forced inspiration. In two separate modeling steps, the plug deposits a coating film on the airway wall and then splits unevenly at the bifurcation due to gravity. The model generates 3D images of the resulting acinar distribution and calculates two global indexes, efficiency and homogeneity. Simulating published procedural methods, we show the neonatal lung is a well-mixed compartment, whereas the adult lung is not. The earlier, successful adult SRT studies show comparatively good index values implying adequate delivery. The later, failed studies used different protocols resulting in very low values of both indexes, consistent with inadequate acinar delivery. Reasons for these differences and the evolution of failure from success are outlined and potential remedies discussed.
authors.affiliation: INSERM, U955 (Equipe 13) and CNRS Équipe de Recherche Labellisée 7240, Cell and Respiratory Biomechanics, Université Paris-Est, 94010 Créteil, France; Physique de la Matière Condensée, Ecole Polytechnique, CNRS, 91128 Palaiseau, France;
authors.forename: Marcel
authors.initials: M
authors.lastname: Filoche
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Tai
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 grotberg@umich.edu.
authors.forename: James B
authors.initials: JB
authors.lastname: Grotberg
mesh_terms: D000328:Adult; D001999:Bronchoscopy / Q000379:methods; D003198:Computer Simulation; D006801:Humans; D021621:Imaging, Three-Dimensional; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000187:drug effects* / Q000254:growth & development*; D008953:Models, Anatomic; D008962:Models, Theoretical; D011650:Pulmonary Alveoli / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D012119:Respiration / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000378:metabolism; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000378:metabolism; D014132:Trachea / Q000473:pathology; D014481:United States; D014783:Viscosity
chemical_list: D011663:Pulmonary Surfactants
keywords: biological fluid mechanics; biological transport processes; pulmonary drug delivery; respiratory distress syndrome; surfactant replacement therapy