Clinical Trial: Effect of Montelukast on the Airway Remodeling

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effect of Montelukast on the Airway Remodeling in Asthma Patients: Physiological-radiological Correlation

Brief Summary: The distal lung contributes to asthmatic airway remodeling which is observed from early onset of the disease. Cysteinyl leukotrienes (CysLT) play important role in the pathogenesis of airway remodeling and antileukotrienes work to exert a certain degree of anti-inflammatory effect. The cysteinyl leukotriene antagonist Montelukast has been in vivo shown to significantly inhibit ovalbumin induced airway smooth muscle hyperplasia and subepithelial fibrosis in sensitized mice. This study aims to evaluate if Montelukast could reverse airway remodeling in asthma patients by a non-invasive approach-HRCT.

Detailed Summary:

Accumulated data have suggested that the distal lung, which includes airways of < 2mm in diameter and lung parenchyma, contribute to asthma pathogenesis and symptoms. In addition to persisting inflammation, distal lung undergoes remodeling, as demonstrated by the reduced elastic fiber content and abnormal alveolar attachments, with the latter thought to result in a loss of elastic recoil and a reduction in FEV1.0. Furthermore, recent studies have shown that airway remodeling is observed from early onset of the disease and may, therefore, be characteristic of asthma. Amounting evidence has revealed that airway remodeling of asthmatic airways accounts for a large component of airway hyperresponsiveness (AHR) and excessive airway narrowing.

Since remodeling processes occur in parallel to, or may even be obligatory for, the establishment of persistent inflammation, the pathogenesis of airway remodeling and the implications of therapeutic interventions that are designed to diminish airway remodeling remain important areas of both research and clinic. Inhale corticosteroid (ICS) is mainstay for the treatment of asthma, however, ICS provides very little benefit for airway remodeling.

Cysteinyl leukotrienes (CysLT) play important role in the pathogenesis of airway remodeling and antileukotrienes work to exert a certain degree of anti-inflammatory effect. The cysteinyl leukotriene antagonist Montelukast, for example, has been in vivo shown to significantly inhibit ovalbumin induced airway smooth muscle hyperplasia and subepithelial fibrosis in sensitized mice. Montelukast, a systemically delivered leukotriene receptor antagonist, has been strongly recommended to treat asthma by several guidelines. Clinically, the systemically acting oral agent montelukast has been shown to improve proximal and distal lung physiology. In particul
Sponsor: Chinese Academy of Medical Sciences

Current Primary Outcome: To evaluate distal airway function using high-resolution CT and lung function test [ Time Frame: 6 months ]

To demonstrate that the correlation between non-invisive chest HRCT and lung function test in patients moderate-to-severe asthma


Original Primary Outcome: Montelukast can improve lung function including proximal and distal airways and reverse airway remodeling in moderate to severe patients with asthma. [ Time Frame: 6 months ]

Current Secondary Outcome: Montelukast can bring additional benefit for lung function improvement in moderate to severe patients with asthma [ Time Frame: 6 months ]

To test whether montelukast can improve the distal airway function


Original Secondary Outcome: Montelukast can bring additional benefit for lung function improvement in moderate to severe patients with asthma [ Time Frame: 6 months ]

Information By: Chinese Academy of Medical Sciences

Dates:
Date Received: June 11, 2008
Date Started: January 2010
Date Completion:
Last Updated: January 3, 2012
Last Verified: January 2012