title: Assessment of in vitro COPD models for tobacco regulatory science: Workshop proceedings, conclusions and paths forward for in vitro model use.
abstract: The Family Smoking Prevention and Tobacco Control Act of 2009 established the Food and Drug Administration Center for Tobacco Products (FDA-CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 8-10 December 2014, IIVS organised a workshop conference, entitled Assessment of In Vitro COPD Models for Tobacco Regulatory Science, to bring together stakeholders representing regulatory agencies, academia, industry and animal protection, to address the research priorities articulated by the FDA-CTP. Specific topics were covered to assess the status of current in vitro technologies as they are applied to understanding the adverse pulmonary events resulting from tobacco product exposure, and in particular, the progression of chronic obstructive pulmonary disease (COPD). The four topics covered were: a) Inflammation and Oxidative Stress; b) Ciliary Dysfunction and Ion Transport; c) Goblet Cell Hyperplasia and Mucus Production; and d) Parenchymal/Bronchial Tissue Destruction and Remodelling. The 2.5 day workshop included 18 expert speakers, plus poster sessions, networking and breakout sessions, which identified key findings and provided recommendations to advance the in vitro technologies and assays used to evaluate tobacco-induced disease etiologies. The workshop summary was reported at the 2015 Society of Toxicology Annual Meeting, and the recommendations led to an IIVS-organised technical workshop in June 2015, entitled Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays, to assess these assays and to conduct a proof-of-principle multi-laboratory exercise to determine their suitability for standardisation. Here, we report on the proceedings, recommendations and outcomes of the December 2014 workshop, including paths forward to continue the development of non-animal methods to evaluate tissue responses that model the disease processes that may lead to COPD, a major cause of mortality worldwide.
authors.affiliation: Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA.
authors.forename: Holger
authors.initials: H
authors.lastname: Behrsing
authors.affiliation: Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Raabe
authors.affiliation: PETA International Science Consortium, Ltd, London, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Manuppello
authors.affiliation: R.J. Reynolds Tobacco Company, Winston-Salem, NC, USA.
authors.forename: Betsy
authors.initials: B
authors.lastname: Bombick
authors.affiliation: Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA.
authors.forename: Rodger
authors.initials: R
authors.lastname: Curren
authors.affiliation: Physicians Committee for Responsible Medicine, Washington, DC, USA.
authors.forename: Kristie
authors.initials: K
authors.lastname: Sullivan
authors.affiliation: University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
authors.affiliation: University of Rochester, Rochester, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Phipps
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.affiliation: Lorillard Tobacco Company, Greensboro, NC, USA.
authors.forename: Sherwin
authors.initials: S
authors.lastname: Yan
authors.affiliation: Lorillard Tobacco Company, Greensboro, NC, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: D'Ruiz
authors.affiliation: University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Tarran
authors.affiliation: Epithelix Sàrl, Geneva, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Constant
authors.affiliation: British American Tobacco (Investments) Ltd, Southampton, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
authors.affiliation: British American Tobacco (Investments) Ltd, Southampton, UK.
authors.forename: Marianna
authors.initials: M
authors.lastname: Gaça
authors.affiliation: MatTek Corporation, Ashland, MA, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hayden
authors.affiliation: FDA-National Center for Toxicological Research, Jefferson, AR, USA.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Cao
authors.affiliation: Philip Morris Product SA, Neuchâtel, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Mathis
authors.affiliation: Philip Morris Product SA, Neuchâtel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
authors.affiliation: Institute for In Vitro Sciences, Inc., Gaithersburg, MD, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Hill
mesh_terms: D032761:Animal Experimentation; D000818:Animals; D020397:Goblet Cells / Q000473:pathology; D033161:Government Regulation; D006801:Humans; D009079:Mucociliary Clearance / Q000502:physiology; D009093:Mucus / Q000378:metabolism; D009538:Nicotine / Q000009:adverse effects; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology*; D062789:Tobacco Products / Q000009:adverse effects* / Q000592:standards; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D009538:Nicotine