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

¹ Dept of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands
² Dept of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; and Dept of Physiology, University of Manitoba, Winnipeg, Canada
³ Dept of Physiology, University of Manitoba, Winnipeg, Canada

^* To whom correspondence should be addressed. E-mail: r.gosens{at}rug.nl.

	Abstract

Chronic inflammation in asthma and COPD drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified by us to play a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. We now aimed to investigate other aspects of airway remodelling and to compare the effectiveness of tiotropium to the glucocorticosteroid budesonide.

Ovalbumin-sensitized guinea pigs were challenged for twelve weeks with aerosolized ovalbumin, which induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (sm-myosin) abundance, mucus gland hypertrophy, an increase in MUC5AC positive goblet cells and eosinophilia. We reported previously that treatment with tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. Our current studies demonstrate that tiotropium also fully prevented allergen-induced mucus gland hypertrophy, and partially reduced the increase in MUC5AC positive goblet cells and infiltrated eosinophils. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucus gland hypertrophy, and partially reduced MUC5AC positive goblet cells 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 bronchodilation.

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