title: Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung.
abstract: Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participated in a workshop aiming at bridging the gap between basic research and clinical efficacy of inhaled drugs. This publication summarizes the current consensus on the topic. It begins with a short description of basic concepts of aerosol transport and a discussion on targeting strategies of inhaled aerosols to the lungs. It is followed by a description of both computational and biological lung models, and the use of imaging techniques to determine aerosol deposition distribution (ADD) in the lung. Finally, the importance of ADD to clinical efficacy is discussed. Several gaps were identified between basic science and clinical efficacy. One gap between scientific research aimed at predicting, controlling, and measuring ADD and the clinical use of inhaled aerosols is the considerable challenge of obtaining, in a single study, accurate information describing the optimal lung regions to be targeted, the effectiveness of targeting determined from ADD, and some measure of the drug's effectiveness. Other identified gaps were the language and methodology barriers that exist among disciplines, along with the significant regulatory hurdles that need to be overcome for novel drugs and/or therapies to reach the marketplace and benefit the patient. Despite these gaps, much progress has been made in recent years to improve clinical efficacy of inhaled drugs. Also, the recent efforts by many funding agencies and industry to support multidisciplinary networks including basic science researchers, R&D scientists, and clinicians will go a long way to further reduce the gap between science and clinical efficacy.
authors.affiliation: 1 Department of Medicine, University of California , San Diego, La Jolla, California.
authors.forename: Chantal
authors.initials: C
authors.lastname: Darquenne
authors.affiliation: 2 National Institute of Health Research Biomedical Research Unit in Respiratory Disease , Southampton, United Kingdom .|3 Department of Medical Physics and Bioengineering, University Hospital Southampton NHS Foundation Trust , Southampton, United Kingdom .
authors.forename: John S
authors.initials: JS
authors.lastname: Fleming
authors.affiliation: 4 Medical R&D, Air Liquide Santé International, Centre de Recherche Paris-Saclay , Jouy-en-Josas, France .|5 Department of Mechanical Engineering, Lafayette College , Easton, Pennsylvania.
authors.forename: Ira
authors.initials: I
authors.lastname: Katz
authors.affiliation: 6 Department of Mechanical Engineering, University of Alberta , Edmonton, Alberta, Canada .
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Martin
authors.affiliation: 7 Applied Research Associates, Inc. , Raleigh, North Carolina.
authors.forename: Jeffry
authors.initials: J
authors.lastname: Schroeter
authors.affiliation: 8 Airway Disease Section, National Heart and Lung Institute , Imperial College London and Royal Brompton Hospital, London, United Kingdom .
authors.forename: Omar S
authors.initials: OS
authors.lastname: Usmani
authors.affiliation: 9 Department of Anesthesia (Bioengineering), MGH/Harvard, Boston, Massachusetts.
authors.forename: Jose
authors.initials: J
authors.lastname: Venegas
authors.affiliation: 10 Comprehensive Pneumology Center (CPC), Member of the German Center for Lung Research , Munich, Germany .|11 Institute of Lung Biology and Disease, Helmholtz Zentrum München-German Research Center for Environmental Health , Neuherberg, Germany .
authors.forename: Otmar
authors.initials: O
authors.lastname: Schmid
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D035843:Biomedical Research / Q000592:standards*; D032921:Consensus; D004339:Drug Compounding; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008168:Lung / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000502:physiology*; D008953:Models, Anatomic; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D012119:Respiration
chemical_list: D000336:Aerosols; D004364:Pharmaceutical Preparations
keywords: PET; SPECT; aerosol deposition distribution; biological lung models; in-silico lung modeling
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