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Calcium channel blocker reduces airway remodeling in severe asthma. A proof-of-concept study.

Abstract：

RATIONALE: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. OBJECTIVES: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. MEASUREMENTS AND MAIN 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).

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Girodet PO,Dournes G,Thumerel M,Begueret H,Dos Santos P,Ozier A,Dupin I,Trian T,Montaudon M,Laurent F,Marthan R,Berger P

doi

10.1164/rccm.201410-1874OC

subject

Has Abstract

pub_date

2015-04-15 00:00:00

pages

876-83

issue

eissn

1073-449X

issn

1535-4970

journal_volume

191

pub_type

杂志文章,随机对照试验

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Calcium channel blocker reduces airway remodeling in severe asthma. A proof-of-concept study.