title: Calcium channel blocker reduces airway remodeling in severe asthma. A proof-of-concept study.
abstract: BACKGROUND
  Severe asthma is a major public health issue throughout the world. Increased bronchial smooth muscle (BSM) mass, a characteristic feature of airway remodeling in severe asthma, is associated with resistance to high-intensity treatment and poor prognosis. In vitro, the Ca(2+)-channel blocker gallopamil decreased the proliferation of BSM cells from patients with severe asthma.
  
  
  OBJECTIVE
  We conducted a double-blind, randomized, placebo-controlled study to evaluate the effect of gallopamil on airway remodeling in patients with severe asthma.
  
  
  METHODS
  Subjects received either gallopamil (n = 16) or placebo (n = 15) for 1 year and were monitored for an additional 3-month period. Airway remodeling was analyzed at baseline and after treatment phase using both fiberoptic bronchoscopy and computed tomography scan. The primary end point was the BSM area. Secondary end points included normalized BSM thickness and frequency of asthma exacerbations.
  
  
  RESULTS
  BSM area was reduced in the gallopamil group (baseline vs. end of treatment) but was unchanged in the placebo group. Between-group differences in BSM area were not significantly different in gallopamil versus placebo groups. By contrast, between-group differences in normalized BSM thickness were significantly different between the two groups. The mean number of exacerbations per month was not different during the treatment phase in gallopamil versus placebo group but was significantly lower in patients previously treated with gallopamil during the follow-up period. There were no differences between the groups with respect to overall side effects.
  
  
  CONCLUSIONS
  Gallopamil treatment for 12 months reduces BSM remodeling and prevents the occurrence of asthma exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT 00896428).
authors: 1 Université de Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, Département de Pharmacologie, CIC1401, Bordeaux, France;
authors: Pierre-Olivier
authors: PO
authors: Girodet
authors: Gaël
authors: G
authors: Dournes
authors: Matthieu
authors: M
authors: Thumerel
authors: Hugues
authors: H
authors: Begueret
authors: Pierre
authors: P
authors: Dos Santos
authors: Annaig
authors: A
authors: Ozier
authors: Isabelle
authors: I
authors: Dupin
authors: Thomas
authors: T
authors: Trian
authors: Michel
authors: M
authors: Montaudon
authors: François
authors: F
authors: Laurent
authors: Roger
authors: R
authors: Marthan
authors: Patrick
authors: P
authors: Berger
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D001249:Asthma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001995:Bronchography / Q000379:methods; D001999:Bronchoscopy / Q000379:methods; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005336:Fiber Optic Technology; D005500:Follow-Up Studies; D005711:Gallopamil / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome
chemical_list: D002121:Calcium Channel Blockers; D005711:Gallopamil
keywords: asthma; exacerbation; mitochondria; remodeling; smooth muscle