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Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison.

Abstract
Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified as playing a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. The aim of the present study was to investigate other aspects of airway remodelling and to compare the effectiveness of tiotropium to the glucocorticosteroid budesonide. Ovalbumin-sensitised guinea pigs were challenged for 12 weeks with aerosolised ovalbumin. The ovalbumin induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet cell numbers and eosinophilia. It was reported previously that treatment with tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. This study demonstrates that tiotropium also fully prevented allergen-induced mucous gland hypertrophy, and partially reduced the increase in MUC5AC-positive goblet cell numbers and eosinophil infiltration. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell numbers and eosinophilia. This study demonstrates that tiotropium and budesonide are similarly effective in inhibiting several aspects of airway remodelling, providing further evidence that the beneficial effects of tiotropium bromide might exceed those of bronchodilation.
AuthorsI S T Bos, R Gosens, A B Zuidhof, D Schaafsma, A J Halayko, H Meurs, J Zaagsma
JournalThe European respiratory journal (Eur Respir J) Vol. 30 Issue 4 Pg. 653-61 (Oct 2007) ISSN: 0903-1936 [Print] England
PMID17537779 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenal Cortex Hormones
  • Allergens
  • Bronchodilator Agents
  • Cholinergic Antagonists
  • Glucocorticoids
  • Scopolamine Derivatives
  • Budesonide
  • Ovalbumin
  • Tiotropium Bromide
Topics
  • Adrenal Cortex Hormones (metabolism)
  • Allergens (chemistry)
  • Animals
  • Bronchodilator Agents (pharmacology)
  • Budesonide (chemistry, therapeutic use)
  • Cholinergic Antagonists (pharmacology)
  • Eosinophilia
  • Extracellular Matrix (metabolism)
  • Glucocorticoids (chemistry)
  • Guinea Pigs
  • Humans
  • Hypersensitivity (drug therapy)
  • Inflammation
  • Male
  • Muscle, Smooth (metabolism)
  • Ovalbumin (chemistry)
  • Scopolamine Derivatives (therapeutic use)
  • Tiotropium Bromide
  • Trachea (pathology)

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