title: Effects of corticosteroid treatment on airway inflammation, mechanics, and hyperpolarized ³He magnetic resonance imaging in an allergic mouse model.
abstract: The purpose of this study was to assess the effects of corticosteroid therapy on a murine model of allergic asthma using hyperpolarized (3)He magnetic resonance imaging (MRI) and respiratory mechanics measurements before, during, and after methacholine (MCh) challenge. Three groups of mice were prepared, consisting of ovalbumin sensitized/ovalbumin challenged (Ova/Ova, n = 5), Ova/Ova challenged but treated with the corticosteroid dexamethasone (Ova/Ova+Dex, n = 3), and ovalbumin-sensitized/saline-challenged (Ova/PBS, n = 4) control animals. All mice underwent baseline 3D (3)He MRI, then received a MCh challenge while 10 2D (3)He MR images were acquired for 2 min, followed by post-MCh 3D (3)He MRI. Identically treated groups underwent respiratory mechanics evaluation (n = 4/group) and inflammatory cell counts (n = 4/group). Ova/Ova animals exhibited predominantly large whole lobar defects at baseline, with significantly higher ventilation defect percentage (VDP = 19 ± 4%) than Ova/PBS (+2 ± 1%, P = 0.01) animals. Such baseline defects were suppressed by dexamethasone (0%, P = 0.009). In the Ova/Ova group, MCh challenge increased VDP on both 2D (+30 ± 8%) and 3D MRI scans (+14 ± 2%). MCh-induced VDP changes were diminished in Ova/Ova+Dex animals on both 2D (+21 ± 9%, P = 0.63) and 3D scans (+7 ± 2%, P = 0.11) and also in Ova/PBS animals on 2D (+6 ± 3%, P = 0.07) and 3D (+4 ± 1%, P = 0.01) scans. Because MCh challenge caused near complete cessation of ventilation in four of five Ova/Ova animals, even as large airways remained patent, this implies that small airway (<188 μm) obstruction predominates in this model. This corresponds with respiratory mechanics observations that MCh challenge significantly increases elastance and tissue damping but only modestly affects Newtonian airway resistance.
authors.affiliation: Center for In Vivo Microscopy, Box 3302, Duke Univ. Medical Center, Durham, NC 27710, USA.
authors.forename: Abraham C
authors.initials: AC
authors.lastname: Thomas
authors.forename: S Sivaram
authors.initials: SS
authors.lastname: Kaushik
authors.forename: John
authors.initials: J
authors.lastname: Nouls
authors.forename: Erin N
authors.initials: EN
authors.lastname: Potts
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Slipetz
authors.forename: W Michael
authors.initials: WM
authors.lastname: Foster
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Driehuys
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004548:Elasticity; D006371:Helium; D006967:Hypersensitivity / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007554:Isotopes; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D010047:Ovalbumin; D012123:Pulmonary Ventilation / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects*
chemical_list: D000305:Adrenal Cortex Hormones; D016085:Bronchoconstrictor Agents; D007554:Isotopes; D016210:Methacholine Chloride; D006371:Helium; D003907:Dexamethasone; D010047:Ovalbumin