Comparison of montelukast and budesonide on bronchial reactivity in subjects with mild-moderate persistent asthma

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Abstract

We studied 51 atopic non-smoking subjects who were divided to four treatments groups: (A) montelukast 10 mg daily, (B) budesonide 400 μg twice a day (bid), (C) montelukast 10 mg daily plus budesonide 400 μg bid and (D) budesonide 800 μg bid. Bronchial responsiveness was assessed before and after 12 weeks of treatment. The bronchial responsiveness, evaluated by means of PC20 values, showed a strong significant increase in groups B, C and D, and a weak but significant rise in group A, when compared to basal data. Regarding other pulmonary parameters (FEV1, PEF) there were no significant differences among the groups after 12 weeks of therapy. A statistical significance was founded after therapy between group A and C (p<0.05), but not between the group B and D treated with only budesonide at different doses. No significant differences was observed in the side effect pattern among the various treatments.

The study data demonstrated that administration of montelukast provided an important and additional effect on bronchial hyperresponsiveness. Oral administration represents a significant advantage over the majority of other anti-asthmatic drugs. Our results confirm the anti-inflammatory properties of both the inhaled corticosteroid (ICS) and montelukast and the possible role of these drugs can have on airway remodelling. While currently low dose ICS remains the reference drug as a controller in mild-moderate persistent asthma, montelukast may be viewed as a possible option, either in monotherapy or in association.

Introduction

Bronchial asthma is a chronic inflammatory disease of the airways involving many cells and mediators which determine recurrent episodes of pharmacologically reversible bronchoconstriction. The inflammatory nature of the disease is supported by a large amount of data from biochemical and cytological studies on induced sputum, bronchoalveolar lavage and bronchial biopsy [1]. Chronic inflammation constitutes an important predisposing condition for airway remodelling with secondary irreversible airflow obstruction. To avoid this evolution it is important to follow an adequate treatment aimed at interacting and modifying the inflammatory process [2], [3]. Current approach for asthma treatment involves many classes of drugs, adequate patient education for their correct use, environmental exposure control and daily monitoring of pulmonary function [4]. Unfortunately, the use of multiple therapies complicates treatment regimens, thus leading to less compliance to therapy [5]. The goals of asthma therapy are absence of asthma symptoms, no activity limitation, no episodes of asthma worsening and an acceptable tolerability profile [6]. Asthma therapy is based on daily administration of many drugs by means of specific inhaler devices. An incorrect use of the inhaler device is very frequent: 50% of patients do not use it in a satisfactory way and this percentage increases to 70% in elderly [6], [7], [8]. Non-observation of the therapeutic program is responsible for about half of drug failure. This degree of compliance reveal little faith in inhalatory treatment with consequent withdrawal of therapy [9]. In addition, many patients with persistent asthma cannot reach these treatment goals with a single controller even at high dosages. The addition of a second drug with a complementary anti-inflammatory action may provide more complete asthma control [10]. A previous report indicated that compliance with inhaled medications was inferior to that with oral medication; multiple daily administration of any therapy also contributes to poor compliance [5].

An oral therapy administered once daily could potentially provide the clinical efficacy requested in common clinical practice. Montelukast, a new specific leukotriene receptor antagonist (LTRA) provides benefit to patients with chronic asthma by means of once daily oral administration [11], [12]; for this reason the recent GINA guidelines allocate this drug to step 2 and 3 of asthma treatment [4].

The aim of the present study was to evaluate the efficacy and tolerability of montelukast versus budesonide in different doses on bronchial reactivity in atopic subjects, with mild-moderate persistent asthma.

Section snippets

Patients

Between March and July 2000 we enrolled 51 atopic (Dermatophagoides Pteronyssinus) non-smoking subjects (29 males, 22 females) with at least 1 year of mild-persistent bronchial asthma at our Respiratory Pathophysiology Center. The diagnosis of asthma was based on typical symptoms and on improvement in pre-bronchodilator forced expiratory volume in one second (FEV1)±15% after salbutamol (200 μg). Their asthma was classified as mild-moderate based on FEV1 between 60 and 85% of predicted value,

Airway responsiveness

Baseline characteristics of the study population do not show significant differences among the four treatment groups for gender, age, FEV1 and PEF (Table 1). After 12 weeks of treatment, the bronchial responsiveness evaluated by PC20 values showed a strong significant increase among groups B (p<0.001), C (p<0.001) and D (p<0.001), and a weak but significant rise among group A (p<0.02), when compared to basal data (Table 2). We founded a statistical significance after therapy between group A

Discussion

The study data demonstrated that montelukast provided an important effect on bronchial responsiveness in patients with mild-moderate persistent asthma. Oral administration represents a significant advantage over the majority of other anti-asthmatics drugs. Montelukast may be considered as alternative to or in association with low-doses of ICS in patients with mild-moderate persistent asthma, on account of their documented clinical efficacy [15], [16], [17], [18], [19], of the reduced airway

References (27)

  • Guidelines for the Diagnosis and Management of Asthma. Expert Panel Report II

    (1997)
  • J.A Coutts et al.

    Measuring compliance with inhaled medication in asthma

    Arch Dis Child

    (1992)
  • J.M Armitage et al.

    Inhaled technique in the elderly

    Age ageing

    (1998)
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