title: Impaired Bronchoprotection Is Not Induced by Increased Smooth Muscle Mass in Chronic Treatment In Vivo with Formoterol in Asthmatic Mouse Model.
abstract: OBJECTIVE
  Inhaling β2-adrenoceptor agonist is first-line asthma treatment, which is used for both acute relief of and prevention of bronchoconstriction. However, chronic use of β-agonists results in impaired bronchoprotection and increasing occurrences of severe asthma exacerbation, even death in clinical practice. The mechanism of β-adrenoceptor hyposensitivity has not been thoroughly elucidated thus far. Bronchial smooth muscle contraction induces airway narrowing and also mediates airway inflammation. Moreover, bronchial smooth muscle mass significantly increases in asthmatics. We aim to establish an asthmatic model that demonstrated that formoterol induced impaired bronchoprotection and to see whether increased smooth muscle mass play a role in it.
  
  
  METHODS
  We combined routine allergen challenging (seven weeks) with repeated application of formoterol, formoterol plus budesonide or physiological saline in allergen-sensitized BALB/c mouse. The bronchoprotection mediated by β-agonist was measured in five consecutive weeks. Smooth muscle mass was shown by morphometric analysis, and α-actin expression was detected by western blot.
  
  
  RESULTS
  The trend of bronchoprotection was wavy in drug interventional groups, which initially increased and then decreased. Chronic treatment with formoterol significantly impaired bronchoprotection. According to the morphometric analysis and α-actin expression, no significant difference was detected in smooth muscle mass in all groups.
  
  
  CONCLUSIONS
  This experiment successfully established that a chronic asthmatic mouse model, which manifested typical features of asthmatic patients, when treated chronically with formoterol, resulted in a loss of bronchoprotection. No significant difference was detected in smooth muscle mass in all groups, which implied some subcellular signalling changes may be the key points.
authors: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China. LuoBao97@163.com.
authors: W
authors: W
authors: Luo
authors: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors: C-T
authors: CT
authors: Liu
authors: Department of Respiratory Medicine, The 7th People's Hospital, Chengdu, Sichuan 610041, PR China.
authors: Q-H
authors: QH
authors: Yang
authors: Department of Functional Branch, The Leshan People's Hospital, Leshan, Sichuan 614000, PR China.
authors: Q
authors: Q
authors: Yu
authors: Laboratory of Pulmonary Disease, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors: T
authors: T
authors: Wang