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.