title: Do airway clearance mechanisms influence the local and systemic effects of inhaled corticosteroids?
abstract: The role of airway clearance in inhaled drug therapy is complex. Disease-induced bronchoconstriction results in a central drug-deposition pattern where mucociliary clearance is most efficient. When drug-induced bronchodilation is achieved, deposition and uptake becomes more peripheral, and because there is less mucociliary clearance in the periphery, this will lead to an unintentional increase in lung exposure and enhance the risk of systemic side effects. In addition, mucociliary clearance is pathologically reduced in both asthma and chronic obstructive pulmonary disease. Among inhaled corticosteroids, rate of dissolution and lung uptake differs considerably. For the slowly dissolving, lipophilic steroids, the contribution of mucociliary clearance to these findings appears significant, and variability in lung and systemic exposure resulting from variable mucociliary function appears to be amplified. In addition, dose optimisation of non-stable asthma becomes more complex. The present review highlights the impact of mucociliary clearance on inhaled corticosteroid disposition and identifies critical areas where more research is needed.
authors.affiliation: AstraZeneca R&D Lund, Clinical Pharmacology, S-221 87 Lund, Sweden. Staffan.Edsbacker@astrazeneca.com
authors.forename: Staffan
authors.initials: S
authors.lastname: Edsbäcker
authors.forename: Per
authors.initials: P
authors.lastname: Wollmer
authors.forename: Olof
authors.initials: O
authors.lastname: Selroos
authors.forename: Lars
authors.initials: L
authors.lastname: Borgström
authors.forename: Bo
authors.initials: B
authors.lastname: Olsson
authors.forename: Jarl
authors.initials: J
authors.lastname: Ingelf
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D016084:Bronchoconstriction; D003371:Cough / Q000503:physiopathology; D006801:Humans; D009079:Mucociliary Clearance / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000305:Adrenal Cortex Hormones