title: Glucocorticoids may not inhibit plasma exudation by direct vascular antipermeability effects in human airways.
abstract: In animal airways, single topical treatment with glucocorticoids produces a prompt vascular anti-permeability effect that may last for several hours. This has been considered a potentially important anti-inflammatory action in human airways. The present study, involving nine healthy subjects, examines whether nasal budesonide application affects histamine-induced mucosal exudation of plasma and plasma-derived mediators in human airways. A selected low concentration (40 micrograms.ml-1) of the vascular permeability-inducing agent histamine was kept in one of the nasal cavities for 10 min, and this challenge was repeated at 50 min intervals over 4 h. Ten minutes after the first histamine-challenge, a clinical dose of budesonide (100 micrograms) was sprayed into the same nasal cavity. Nasal lavage fluid levels of albumin and fibrinogen were measured as indices of mucosal exudation of bulk plasma, and bradykinins were analysed to indicate generation of plasma-derived mediators. The baseline levels of albumin and fibrinogen were evaluated in 24 healthy control subjects by means of a 10 min saline lavage. Histamine produced significant mucosal exudation of albumin and fibrinogen, compared to control subjects. Topical budesonide treatment did not affect the histamine-induced mucosal exudation of albumin or fibrinogen, nor did budesonide affect the mucosal output of bradykinins. The present human airway data do not support the view, based on animal findings, that airway glucocorticoids reduce mucosal exudation of plasma by direct vascular effects. We suggest that anti-exudative effects of topical glucocorticoids in airway diseases indirectly reflect the inhibition of cellular inflammatory processes by these drugs, rather than any direct effects on the airway microcirculation.
authors.affiliation: Dept of Otorhinolaryngology, Lund University Hospital, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Greiff
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: C
authors.initials: C
authors.lastname: Svensson
authors.forename: U
authors.initials: U
authors.lastname: Alkner
authors.forename: C G
authors.initials: CG
authors.lastname: Persson
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000418:Albumins / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001920:Bradykinin / Q000378:metabolism; D019819:Budesonide; D002199:Capillary Permeability / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005340:Fibrinogen / Q000378:metabolism; D005938:Glucocorticoids; D006632:Histamine; D006801:Humans; D011282:Pregnenediones / Q000494:pharmacology*; D011863:Radioimmunoassay
chemical_list: D000418:Albumins; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011282:Pregnenediones; D019819:Budesonide; D006632:Histamine; D005340:Fibrinogen; D001920:Bradykinin