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Calcium channel blocker reduces airway remodeling in severe asthma. A proof-of-concept study.
- Source :
-
American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2015 Apr 15; Vol. 191 (8), pp. 876-83. - Publication Year :
- 2015
-
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.<br />Objectives: We conducted a double-blind, randomized, placebo-controlled study to evaluate the effect of gallopamil on airway remodeling in patients with severe asthma.<br />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.<br />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.<br />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).
- Subjects :
- Asthma diagnostic imaging
Bronchography methods
Bronchoscopy methods
Double-Blind Method
Female
Fiber Optic Technology
Follow-Up Studies
Humans
Male
Middle Aged
Tomography, X-Ray Computed methods
Treatment Outcome
Airway Remodeling drug effects
Asthma drug therapy
Calcium Channel Blockers pharmacology
Gallopamil pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1535-4970
- Volume :
- 191
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- American journal of respiratory and critical care medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25633090
- Full Text :
- https://doi.org/10.1164/rccm.201410-1874OC