title: Assessing the potential to induce respiratory hypersensitivity.
abstract: Acute and repeat dose inhalation studies have been an important part of the safety assessment of drugs, chemicals, and other products throughout the world for many years. It is known that damage to the respiratory tract can be triggered either by nonspecific irritation or by specific immune-mediated pathogenesis, and it is acknowledged that traditional inhalation studies are not designed to address fully the impact of the latter. It is also recognized that different types of immune-mediated responses can be triggered by different classes of compounds and that some immune reactions in the lung are life threatening. As such, it is important to understand as fully as possible the basis for the immune-mediated damage to the lung in order to characterize adequately the risks of individual chemicals or proteins. It is against this background that a review of the methods used to assess the potential for immune-mediated respiratory hypersensitivity was conducted. The primary objectives of this review are to discuss appropriate methods for identifying and characterizing respiratory hypersensitivity hazards and risks; and to identify key data gaps and related research needs with respect to respiratory hypersensitivity testing. The following working definition of respiratory hypersensitivity was formulated: a hypersensitivity response in the respiratory tract precipitated by a specific immune response, mediated by multiple mechanisms, including IgE antibody. Because of the importance played by various classes of compounds, the subsequent sections of this review will consider protein-specific, chemical-specific, and drug-specific aspects of respiratory hypersensitivity.
authors.affiliation: ILSI Health and Environmental Sciences Institute, Washington, DC, USA. mholsapple@ilsi.org
authors.forename: Michael P
authors.initials: MP
authors.lastname: Holsapple
authors.forename: David
authors.initials: D
authors.lastname: Jones
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Kawabata
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.forename: Kathy
authors.initials: K
authors.lastname: Sarlo
authors.forename: MaryJane K
authors.initials: MK
authors.lastname: Selgrade
authors.forename: Jui
authors.initials: J
authors.lastname: Shah
authors.forename: Michael R
authors.initials: MR
authors.lastname: Woolhiser
mesh_terms: D004342:Drug Hypersensitivity / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D007073:Immunoglobulin E