title: Computational Models of Inhalation Therapy in Early Childhood: Therapeutic Aerosols in the Developing Acinus.
abstract: Inhalation therapy targeted to the deep alveolated regions holds great promise, specifically in pediatric populations. Yet, inhalation devices and medical protocols are overwhelmingly derived from adult guidelines, with very low therapeutic efficiency in young children. During the first years of life, airway remodeling and changing ventilation patterns are anticipated to alter aerosol deposition with underachieving outcomes in infants. As past research is still overwhelmingly focused on adults or limited to models of upper airways, a fundamental understanding of inhaled therapeutic transport and deposition in the acinar regions is needed to shed light on delivering medication to the developing alveoli.
  
  
  
  Using computational fluid dynamics (CFD), we simulated inhalation maneuvers in anatomically-inspired models of developing acinar airways, covering the distinct phases of lung development, from underdeveloped, saccular pulmonary architectures in infants, to structural changes in toddlers, ultimately mimicking space-filling morphologies of a young child, representing scaled-down adult lungs. We model aerosols whose diameters span the range of sizes acknowledged to reach the alveolar regions and examine the coupling between morphological changes, varying ventilation patterns and particle characteristics on deposition outcomes.
  
  
  
  Spatial distributions of deposited particles point to noticeable changes in the patterns of aerosol deposition with age, in particular in the youngest age group examined (3 month). Total deposition efficiency, as well as deposition dispersion, vary not only with the phases of lung development but also and critically with aerosol diameter.
  
  
  
  Given the various challenges when prescribing inhalation therapy to a young infant, our findings underline some mechanistic aspects to consider when targeting medication to the developing alveoli. Not only does the intricate coupling between acinar morphology and ventilation patterns need to be considered, but the physical properties (i.e., aerodynamic size) of therapeutic aerosols also closely affect the anticipated success rates of the inhaled medication.
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology , Haifa, Israel .
authors.forename: Janna Tenenbaum
authors.initials: JT
authors.lastname: Katan
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology , Haifa, Israel .
authors.forename: Philipp
authors.initials: P
authors.lastname: Hofemeier
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology , Haifa, Israel .
authors.forename: Josué
authors.initials: J
authors.lastname: Sznitman
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000367:Age Factors; D001830:Body Surface Area; D001835:Body Weight; D002675:Child, Preschool; D003198:Computer Simulation; D054796:Drug Dosage Calculations; D006801:Humans; D007223:Infant; D008953:Models, Anatomic; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D011650:Pulmonary Alveoli / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D012123:Pulmonary Ventilation; D015656:Respiratory Mechanics
chemical_list: D000336:Aerosols; D004364:Pharmaceutical Preparations
keywords: CFD; infants; inhalation therapy; lung development; systemic delivery