Impact of montelukast on symptoms in mild-to-moderate persistent asthma and exercise-induced asthma: results of the ASTHMA survey. Adding Singulair Treatment to Handle symptoms in Mild to moderate Asthmatics

A nation-wide survey was undertaken in Belgium among general practitioners (GPs) to evaluate the impact of the leukotriene receptor antagonist (LTRA) montelukast on the control of asthma symptoms, after at least 4 weeks of treatment. Patients from 6 years of age were eligible if they were suffering from mild-to-moderate persistent asthma which was still symptomatic despite inhaled corticosteroids (ICS) treatment, or from exercise-induced asthma. Patient general satisfaction was evaluated by recording the willingness to continue the treatment. A total of 1360 GPs took part in the study and more than 11000 patients were included in the survey. Of the included patients, 85% were receiving inhaled corticosteroids, 60% of whom were also on long-acting beta2-agonists (LABA). However, despite the use of daily controller medication, 92% of the patients still reported limitation of activities, 49% difficulties with sleep and 45% early morning awakening due to asthma. Moreover, 78% of the patients used rescue medication more than twice a week. At the end of the survey, 90% of the patients expressed their willingness to continue montelukast therapy. Of the patients having symptoms at the start of the study, 87% reported amelioration in sleep while on montelukast therapy, 80% less frequent early morning awakening, 85% better ability to perform daily activities and 77% decreased need for rescue medication.     

Montelukast: a review of its therapeutic potential in persistent asthma

Montelukast is a cysteinyl leukotriene receptor antagonist used to treat persistent asthma in patients aged > or = 6 years. The drug has a rapid onset of action. Improvements in lung function and reductions in as-needed beta2-agonist usage are apparent within 1 day of initiating montelukast treatment in adults and adolescents (aged > or = 15 years treated with 10 mg/day) or children (aged 6 to 14 years treated with 5 mg/day) with persistent asthma as shown in clinical trials. In two 12-week, multicentre, randomised, double-blind studies in adults and adolescents aged > or = 15 years with persistent asthma [forced expiratory volume in 1 second (FEV1) = 50 to 85% predicted] there was significantly (p < 0.05) greater improvement in FEV1, symptom scores, peak expiratory flow (PEF), as-needed beta2-agonist use, peripheral eosinophil counts and health-related quality of life (QOL) in patients treated with montelukast 10 mg/day than in recipients of placebo. Improvements were significantly greater in patients treated with inhaled beclomethasone 400 microg/day than in recipients of montelukast 10 mg/day in 1 of these studies. Nonetheless, 42% of montelukast recipients experienced > or = 11% improvement in FEV1, the median improvement in this parameter in beclomethasone-treated patients. In an 8-week multicentre, randomised, double-blind, study in children aged 6 to 14 years with persistent asthma (FEV1 50 to 85% predicted), montelukast 5 mg/day produced significantly greater improvements in FEV1, clinic PEF, as-needed beta2-agonist use, peripheral eosinophil counts, asthma exacerbations and QOL scores than placebo. The combination of montelukast 10 mg/day plus inhaled beclomethasone 200 microg twice daily provided significantly better asthma control than inhaled beclomethasone 200 microg twice daily in adults with poorly controlled asthma (mean FEV1 = 72% predicted) despite 4 weeks treatment with inhaled beclomethasone. Patients receiving the combination experienced significant improvements in FEV1 and morning PEF, significant reductions in daytime symptom scores, as-needed beta2 agonist usage and night-time awakenings with asthma, and had significantly lower peripheral blood eosinophil counts after 16 weeks in this multicentre, randomised, double-blind, placebo-controlled study. Among adults (FEV1 > or = 70%) treated with montelukast 10 mg/day for 12 weeks, inhaled corticosteroid dosages were titrated downward by 47% (vs 30% in placebo recipients), 40% of patients were tapered off of inhaled corticosteroids (vs 29%), and significantly fewer patients (16 vs 30%) experienced failed corticosteroid rescues in a multicentre, randomised, double-blind study. During clinical studies, the frequency of adverse events in montelukast-treated adults, adolescents and children was similar to that in placebo recipients. In conclusion, montelukast is well tolerated and effective in adults and children aged > or = 6 years with persistent asthma including those with exercise-induced bronchoconstriction and/or aspirin sensitivity. Furthermore, montelukast has glucocorticoid sparing properties. Hence, montelukast, as monotherapy in patients with mild persistent asthma, or as an adjunct to inhaled corticosteroids is useful across a broad spectrum of patients with persistent asthma.     

Comparison of the effects of tulobuterol patch and salmeterol in moderate to severe asthma

1. Although the clinical effects of the tulobuterol patch have been reported to include an increase in morning peak expiratory flow (PEF) values and a decrease of symptoms and the frequency of the rescue use of inhaled short-acting beta2-adrenoceptor agonists, no trials comparing the efficacy of the tulobuterol patch to other standard inhaled long-acting beta2-adrenoceptor agonists have yet been conducted. The aim of the present study was to compare the clinical effects of the patch formulation of tulobuterol with those of inhaled salmeterol in moderate to severe asthma. 2. Fifty-four patients with moderate to severe asthma, whose conditions were suboptimally controlled despite receiving inhaled corticosteroids, were recruited. The study was a prospective, randomized trial of cross-over design comparing the effects of 4 weeks treatment with tulobuterol patch, 2 mg once daily, and salmeterol, 50 mg twice daily. The mean prebronchodilator morning PEF during the last 14 days of each treatment period and health-related quality of life (HRQoL) were the primary outcome variables. The HRQoL was assessed using the St George's Respiratory Questionnaire. 3. Forty-four patients (81.5%) completed the trial and were included in the analysis. The mean morning PEF and HRQoL score were significantly improved in both the salmeterol (P < 0.0001 and P < 0.05, respectively) and the tulobuterol patch (P < 0.01 and P < 0.05, respectively) treatment periods compared with the run-in period. Although the mean morning PEF was significantly higher in the salmeterol-treated group than in the tulobuterol-treated group (P < 0.001), the HRQoL scores were comparable. 4. The tulobuterol patch may be useful as a controller medication in addition to inhaled corticosteroids in moderate to severe asthma.     

Asthma control in Switzerland: a general practitioner based survey

ABSTRACT

Background: Achievement of optimal asthma control is the goal of the Global Initiative for Asthma (GINA) guidelines.

Methods: In a survey involving 281 physicians, asthma control was assessed using the Juniper asthma control questionnaire (ACQ); physicians were also asked to judge patients’ asthma control subjectively.

Results: In total, 2127 patients were included. Follow-up was available in 1893 (89%) patients (885 females). The mean time between visits was 62 ± 29.3 days; mean age was 45 years (± 19 years) and 30% were smokers. Well-controlled asthma was found in 298 patients (16%). Smokers were less likely to have well-controlled asthma (smokers 12% vs. non-smokers 18%). Physicians assessed asthma control to be good in 292 patients (15%), sufficient in 504 (27%), insufficient in 954 (50%) and poor in 137 (7%) patients. Of the 292 patients assessed by their physicians as ‘good asthma control’, only 142 (49%) were confirmed as ‘well-controlled’ by the ACQ. At the first visit, 1308 (69%) patients were pre-treated with any inhaled corticosteroids (ICS). Pre-treatment with leukotriene receptor antagonists (LTRAs) was reported in 127 patients (7%). Add-on therapy with the LTRA montelukast was the most frequent treatment adjustment at the first visit. Out of 1893 patients who had a follow-up visit, 298 (16%) were well controlled at the first visit and 1170 (62%) at the follow-up visit.

Conclusion: Asthma control is insufficient in the majority of patients. Improvement of asthma control can be achieved by using objective measures such as the ACQ in regular clinical practice and adapting therapy.     

Improving asthma control in patients suboptimally controlled on inhaled steroids and long-acting β2‐agonists: addition of montelukast in an open-label pilot study

ABSTRACT

Background: Airway inflammation and symptoms often persist in asthma patients despite treatment with inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA). It is hypothesized that the leukotriene receptor antagonist montelukast, treating a pathway of inflammation distinct from that of ICS, might confer additional benefit.

Objective: To evaluate the efficacy of montelukast in improving asthma control in patients symptomatic on a fixed-association (FA) medium dose of ICS and LABA.

Methods: A 2-month, open-label, real-life observational study was undertaken by 131 Belgian pulmonologists. Patients (≥ 15 years old) suffering from persistent asthma (pre-bronchodilator FEV₁ ≥ 60% of predicted value) and insufficiently controlled on a FA therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10?mg daily as add-on therapy. Asthma control was assessed by the standardized Juniper asthma control questionnaire (ACQ) at baseline and after a 2-month treatment with montelukast. Global evaluation of therapy was made both by the patients and physicians.

Results: A total of 313 patients were eligible for analysis. Forty-nine per cent received inhaled fluticasone/salmeterol and the rest budesonide/formoterol. Mean ACQ score decreased significantly on montelukast (13.9 ± 5.1 at baseline versus 7.4 ± 4.7 on montelukast, p < 0.001), with a significant improvement in all individual symptom scores (?p < 0.001) and in pre-bronchodilator FEV₁ score (from 2.2 ± 1.5 to 1.6 ± 1.4; p < 0.001). Parallel to these results, 78.6% of the patients reported a global improvement of their asthma. The same proportion of improvement was observed in the global evaluation made by the physicians (κ = 0.66).

Conclusion: This pilot study suggests that addition of montelukast in patients symptomatic on a FA of ICS and LABA may result in significant improvements in asthma control. A randomised, placebo-controlled clinical trial seems warranted.     

Asthma control in patients with asthma and allergic rhinitis receiving add-on montelukast therapy for 12 months: a retrospective observational study

ABSTRACT

Background: Montelukast, a potent leukotriene receptor antagonist, is approved for treatment of both asthma and allergic rhinitis (AR). No studies to date have examined whether montelukast can improve asthma control over a long period of time in patients with seasonal AR and asthma.

Objective: To evaluate asthma control and use of asthma-related medical resources by patients with inadequately controlled mild to moderate persistent asthma and seasonal AR who required addition of montelukast as part of routine care.

Methods: This multicenter, 24?month, pre–post retrospective observational study included patients receiving current inhaled corticosteroid (ICS) therapy (alone or in combination with long-acting β-agonist [LABA]), who received add-on treatment with montelukast for 12 consecutive months. The incidence of asthma attacks, defined as emergency department visit, hospitalization, or oral corticosteroid use for asthma, was compared for the year before and the year after addition of montelukast to therapy.

Results: For the 696 patients from Italy, Poland, and Spain who were included in the analyses, the proportion of patients experiencing an asthma attack declined from 31.5% in the year before to 10.1% (?p < 0.001) the year after addition of montelukast to therapy. Proportions of patients with an asthma-related emergency room visit, hospitalization, and oral corticosteroid use declined from 18.7% to 3.9%, from 5.2% to 1.4%, and from 17.5% to 5.9% (all p < 0.01), respectively. The incidence of these outcomes declined in all three countries, regardless of baseline asthma severity or asthma therapy (ICS alone or ICS + LABA). Important study limitations include the possibility of selection bias or missing medical chart data in this retrospective study design. Also noteworthy is the inclusion of only those patients who remained persistent with montelukast therapy. Therefore, the results of the study are relevant for patients who remain persistent with montelukast therapy.

Conclusions: Addition of montelukast to current ICS therapy improved long-term asthma control and resulted in substantial reductions in asthma-related resource use by patients with mild or moderate persistent asthma and concomitant seasonal AR who were persistent with montelukast therapy in this retrospective observational study.     

Oral Montelukast Versus Inhaled Beclomethasone in 6- to 11-year-old Children with Asthma: Results of an Open-label Extension Study Evaluating Long-term Safety,Satisfaction, and Adherence with Therapy

SUMMARY

This 6-month, open-label extension study of a previously described base study compared oral montelukast with inhaled beclomethasone in terms of safety, forced expiratory volume in one second (FEV1) measurements, parent and patient satisfaction with treatment, asthma-related medical resource utilization, school absenteeism, and parental work loss in children with asthma. A total of 124 of 266 asthmatic children, 6 to 11 years of age, who enrolled in the base study entered a 6-month open-label extension study (74 boys, 50 girls) and were re-randomized (2:1 ratio) to receive once-daily oral montelukast (n?=?83) or inhaled beclomethasone 100?mcg three times daily

(n?=?41). Children were evaluated in the clinic prior to re-randomization (Month 0) and at regular visits at 1, 3, and 6 months. Children and their parents showed a significantly higher overall satisfaction for montelukast at 6 months than for inhaled beclomethasone (p?=?0.001 and p?<?0.05, respectively). According to parents, montelukast was more convenient (p?<?0.001), less difficult to use (p?=?0.005), and was used as instructed more of the time (p?=?0.006) compared with beclomethasone. Oral corticosteroid use was similar in the montelukast (13% of patients) and beclomethasone (17%) treatment groups. The montelukast treatment group was more adherent with their regimen than the inhaled beclomethasone treatment group; almost twice as many children on montelukast compared with inhaled beclomethasone were highly compliant (82% versus 45%). The two study groups were similar with respect to overall safety, change in FEV1, asthma-related medical i resource utilization, school absenteeism, and parental work loss. Montelukast represents a safe and effective asthma treatment regimen to which children with asthma are more likely to adhere.     

吸入糖皮质激素联合小剂量茶碱与联合白三烯调节剂治疗5岁以下儿童哮喘的效果比较

目的比较吸入糖皮质激素（ics）联合小剂量茶碱与联合白三烯调节剂治疗5岁以下儿童哮喘的临床效果。方法将90例中度持续性哮喘患者按照随机原则分为ICS＋茶碱组和ICS＋孟鲁司特钠组,每组各45例。两组均常规吸人丙酸氟替卡松,ICS＋茶碱组加用口服缓释茶碱片6mg／（kg·d）,分两次服;ICS＋孟鲁司特组加用口服孟鲁司特钠,1次／d,4mg／次,两组疗程均为6个月。结果治疗3个月及6个月后,两组的H间症状评分、夜间症状评分、ACT评分与治疗前比较,差异有统计学意义（P〈0．05）,两组的上述指标比较,差异无统计学意义（P〉0．05）。结论吸人丙酸氟替卡松联合小剂量茶碱与联合白三烯调节剂治疗5岁以下儿童哮喘的效果相当。     

The pharmacists’ potential to provide targets for interventions to optimize pharmacotherapy in patients with asthma

Background Despite of pharmacists’ specialized knowledge of medication and his/her regular contact with patients, the expertise of the pharmacist may not be used enough yet. Furthermore, the potential of pharmacy dispensing data is underestimated. Objective To provide targets for tailored interventions in asthma patients and to illustrate the potential value of pharmacists in the identification of these targets using individual pharmacy dispensing data. Setting We performed a cross sectional retrospective analysis assessing the quality of asthma patients’ pharmacotherapeutic treatment. Method Drug dispensing data from 2008 to 2009 were retrieved from a Dutch pharmacy database. All asthma patients were screened for potential suboptimal pharmacotherapy in 2009. Results were projected to a single community pharmacy to provide an estimate of the number of patients eligible for potential interventions. Main outcome measures (1) frequent use of short-acting β-agonists without preventive medication, (2) concomitant use of β-blockers, (3) multiple short courses of oral corticosteroids without using inhaled corticosteroids and 4) use of long-acting β-agonist without inhaled corticosteroids. Results A total of 8,504 patients were eligible for analysis of the quality of their asthma treatment. 20.9 % of all asthma patients used >100 DDD short-acting β-agonists per year, whereas between 21.2 % (≥400 DDD) and 31.4 % (100–199 DDD) of these patients did not receive preventive medication. Approximately 5.2 % of the asthma patients are using β-blockers concomitantly and 21.8 % of them received non-cardioselective β-blockers. 6.3 % of the asthma patients received two or more oral courses of corticosteroids in 2008 and 17.4 % of these patients did not receive inhaled corticosteroids in 2009. 2.9 % of the patients used a long-acting β-agonists without inhaled corticosteroids. 8.4 % of the asthma patients using both long-acting β-agonists and inhaled corticosteroids received these drugs in two separate inhalers. We estimated that about 400 asthma patients could be identified in an average pharmacy population (8,000 patients) and 33 (95 % CI 22–44) of these patients would be eligible for interventions. Conclusion This study shows the potential for pharmacists to use their own pharmacy records to identify suboptimal therapy of asthma patients, who may be targets for tailored interventions.     

Systematic literature review of the clinical,humanistic, and economic burden associated with asthma uncontrolled by GINA Steps 4 or 5 treatment

Objective: This study sought to characterize the epidemiologic, clinical, humanistic, and economic burden of patients with asthma uncontrolled by GINA Steps 4 or 5 treatment (severe, uncontrolled asthma [SUA]).

Methods: A systematic literature review adhering to PRISMA guidelines was performed. Relevant publications were searched for in MEDLINE and EMBASE from January 2004 to September 2016 and in a conference proceedings database from January 2012 to October 2016. Studies were screened using the Population, Intervention, Comparator, Outcomes, Study Design, and Time (PICOS-T) framework. Studies of SUA with observational (prospective and retrospective), randomized, or nonrandomized study designs; adult patient populations; sample sizes ≥20 patients; epidemiologic or clinical outcomes, patient-reported outcomes (PROs), or economic outcomes were included. For our analysis, SUA was defined as inadequate control of asthma, despite the use of medium- to high-dosage inhaled corticosteroids and at least one additional treatment.

Results: A total of 195 articles reporting unique study populations were included. Prevalence of SUA was as great as 87.4% for patients with severe asthma, although values varied depending on the criteria used to define asthma control. Compared with patients with severe asthma who were controlled, patients with SUA experienced more symptoms, night-time awakenings, rescue medication use, and worse PROs. SUA-associated costs were 3-times greater than costs for patients with severe, controlled disease.

Conclusion: Despite the availability of approved asthma treatments, this literature analysis confirms that SUA poses a substantial epidemiologic, clinical, humanistic, and economic burden. Published data are limited for certain aspects of SUA, highlighting a need for further research.     

Pranlukast: a review of its use in the management of asthma

Pranlukast (Onon, Azlaire), is an orally administered, selective, competitive antagonist of the cysteinyl leukotrienes (LT) C(4), LTD(4) and LTE(4). It is indicated for the prophylactic treatment of chronic bronchial asthma in paediatric and adult patients. The efficacy of pranlukast 225mg twice daily in adults with mild to moderate asthma was demonstrated in double-blind, placebo- or azelastine-controlled studies of 4 or 8 weeks' duration. The drug at this dosage was superior to both comparators in improving mean attack scores and morning and/or evening peak expiratory flow rates, and decreasing the use of rescue bronchodilators (p < 0.05). In limited clinical studies, pranlukast 225mg twice daily appeared to be as effective as montelukast 10mg once daily and zafirlukast 40mg twice daily in adults with mild to moderate asthma. Tachyphylaxis was absent when the drug was administered for up to 4 years. In patients requiring high-dose inhaled corticosteroid therapy, pranlukast 225 mg twice daily plus a halved dosage of inhaled corticosteroid was as effective as the original dosage of inhaled corticosteroid. Pranlukast was also effective in patients with mild to severe asthma in a clinical practice setting. In a double-blind trial, greater improvements in most outcome measures were observed with pranlukast than with oxatomide in children and adolescents with asthma. In clinical trials, pranlukast was well tolerated in adult and paediatric patients with asthma, with an adverse event profile similar to that of placebo. Gastrointestinal events and hepatic function abnormalities were the most commonly reported adverse events. No clinically significant differences in adverse event profiles between pranlukast, zafirlukast or montelukast were shown in limited comparisons. Although Churg-Strauss syndrome has been noted in pranlukast recipients, a direct causal relationship is unlikely. CONCLUSIONS: Pranlukast is a well tolerated and effective preventative treatment in adult and paediatric patients with persistent asthma of all severities. In some patients, pranlukast may be beneficial when added to low-dose inhaled corticosteroids; it may also be a viable alternative to increasing inhaled corticosteroid dosages. The efficacy of pranlukast relative to placebo has been confirmed; its efficacy relative to other therapy awaits further investigation. Nonetheless, pranlukast is a useful therapeutic option (with as-required short-acting beta(2)-agonists), either as preventative monotherapy for the treatment of mild persistent asthma or in conjunction with inhaled corticosteroids in the management of moderate or severe persistent asthma.     

Mometasone furoate dry powder inhaler: a once-daily inhaled corticosteroid for the treatment of persistent asthma

ABSTRACT

Background: Mometasone furoate (MF), a potent synthetic inhaled corticosteroid (ICS) with a high affinity for the glucocorticoid receptor, is approved for use in the treatment of asthma.

Scope: Publications reviewed in this article were identified via searches of MEDLINE and EMBASE databases using the terms ‘mometasone furoate AND pharmacology’ and ‘mometasone furoate AND asthma AND clinical trial’. Data from abstracts presented at respiratory society meetings, and relevant background information, are also reviewed.

Findings: In clinical studies, MF, administered by dry powder inhaler (MF-DPI), was effective in treating all severities of persistent asthma, improving pulmonary function, reducing asthma symptoms, and reducing or eliminating the need for oral corticosteroids. Once-daily dosing of MF-DPI was effective in patients with mild or moderate persistent asthma previously taking twice-daily regimens of inhaled corticosteroids (ICSs), and in patients taking only inhaled β₂?agonists for symptom relief. Once-daily dosing in the evening with MF-DPI 200?µg conferred a greater benefit than morning dosing with MF-DPI 200?µg. Patients with severe asthma who were dependent on oral corticosteroids (OCSs) and high doses of ICSs were able to achieve greater asthma control and reduce or even eliminate OCSs when switched to MF-DPI. In trials of up to 1 year in duration, MF-DPI was well tolerated, with the majority of adverse events considered mild or moderate in intensity. MF had low systemic bioavailability and no clinically significant hypothalamic–pituitary–adrenal-axis suppression at therapeutic doses. The DPI device is a multiple-dose inhaler with a counter containing agglomerates of MF and lactose. Patients of all severities of persistent asthma were able to generate and maintain airflow profiles necessary to provide a uniform and accurate dose.

Limitations: Only one study evaluated both morning and evening administration of once-daily doses, and one of the comparative clinical trials was an open-label study.

Conclusion: Once-daily administration of MF-DPI 200–400?µg in patients with mild to moderate persistent asthma effectively improved lung function and asthma control. In patients with severe persistent asthma dependent on oral corticosteroids, treatment with MF-DPI 400?µg BID permitted substantial reduction of oral corticosteroid use. All MF-DPI treatments were well tolerated and had minimal systemic effects.     

Efficacy of add-on montelukast in patients with non-controlled asthma: a Belgian open-label study*

ABSTRACT

Objective: To evaluate the efficacy of add-on montelukast on asthma control and allergic rhinitis symptoms in asthmatic patients still symptomatic with chronic treatment with inhaled corticosteroid and long-acting β₂ agonist (ICS/LABA), irrespective of the dose.

Research design and methods: This 2-month, open-label, real-life, multicentre, observational study was undertaken by 499 general practitioners in Belgium. Patients (≥?4?years old) with uncontrolled asthma despite fluticasone/salmeterol or budesonide/formoterol therapy had oral montelukast 4, 5, or 10?mg daily added to their therapy, depending on the registered dose for their age. Asthma control, assessed by the 6-item Juniper Asthma Control Questionnaire (ACQ) was recorded at baseline and after 2?months of treatment with montelukast and the patients’ global evaluation of asthma was also recorded at the end of the study. Concomitant allergic rhinitis symptoms were evaluated according to the patients’ perception.

Results: A total of 5769 patients were eligible for analysis. Addition of montelukast was associated with significant decrease in mean (SD) ACQ score (from 1.97 [0.77] at baseline to 1.05 [0.69] after add-on treatment, p?<?0.001). There was also a significant improvement in all individual symptoms of the ACQ score (p?<?0.001). After 2?months, 89% of the patients reported global improvement of their asthma, with a good correlation between patients’ global evaluation and change in ACQ scores. Of the 2442 patients who reported allergic rhinitis symptoms at baseline, 91% showed a global improvement of their asthma symptoms and 82% in their rhinitis symptoms after adding montelukast.

Conclusion: This open-label observational study showed an improvement, after 2?months of add-on therapy with montelukast, in both asthma and allergic rhinitis symptoms in patients not adequately controlled on a fixed association of ICS/LABA.     

Assessment of various second‐line medications in addition to inhaled corticosteroid in asthma patients: a randomized controlled trial

Many patients with persistent asthma cannot achieve the treatment goal for asthma with a single controller medication. The aim of the present study was to assess lung function and rescue medication use in asthma patients receiving four different categories of drugs in combination with an inhaled corticosteroid. Patients recruited to the study were randomized into four groups to receive budesonide with either formoterol, doxofylline, montelukast or tiotropium for a period of 3 months. Lung function (i.e. forced expiratory volume in 1 s (FEV₁)) and rescue medication use were determined at baseline and on Day 15, 30, 45, 60 and 90 of treatment. A total of 297 patients completed the study. At baseline, no significant differences (P > 0.05) were observed in any of the outcome measures. Significant within‐group improvement in FEV₁ was observed in all groups. On Day 90, between‐group differences showed that the improvement in FEV₁ was significantly (P < 0.05) higher for patients receiving budesonide + formoterol, followed by budesonide + montelukast and budesonide + doxofylline, and least for those receiving budesonide + tiotropium. Similarly, within‐ and between‐group comparisons showed significant (P < 0.05) reductions in rescue medication use in all groups. However, the magnitude of the decrease was greater in the budesonide + formoterol group, followed by the budesonide + montelukast, budesonide + doxofylline and budesonide + tiotropium groups. Based on our findings, among the second‐line treatment regimens, budesonide with either montelukast or doxofylline was found to be better than budesonide + tiotropium in patients with mild‐to‐moderate persistent asthma. Further studies with a longer duration are likely to be useful.     

Improving asthma control in patients suboptimally controlled on inhaled steroids and long-acting beta2-agonists: addition of montelukast in an open-label pilot study

BACKGROUND: Airway inflammation and symptoms often persist in asthma patients despite treatment with inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA). It is hypothesized that the leukotriene receptor antagonist montelukast, treating a pathway of inflammation distinct from that of ICS, might confer additional benefit. OBJECTIVE: To evaluate the efficacy of montelukast in improving asthma control in patients symptomatic on a fixed-association (FA) medium dose of ICS and LABA. METHODS: A 2-month, open-label, real-life observational study was undertaken by 131 Belgian pulmonologists. Patients (> or = 15 years old) suffering from persistent asthma (pre-bronchodilator FEV1 > or = 60% of predicted value) and insufficiently controlled on a FA therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg daily as add-on therapy. Asthma control was assessed by the standardized Juniper asthma control questionnaire (ACQ) at baseline and after a 2-month treatment with montelukast. Global evaluation of therapy was made both by the patients and physicians. RESULTS: A total of 313 patients were eligible for analysis. Forty-nine per cent received inhaled fluticasone/salmeterol and the rest budesonide/formoterol. Mean ACQ score decreased significantly on montelukast (13.9 +/- 5.1 at baseline versus 7.4 +/- 4.7 on montelukast, p < 0.001), with a significant improvement in all individual symptom scores (p < 0.001) and in pre-bronchodilator FEV1 score (from 2.2 +/- 1.5 to 1.6 +/- 1.4; p < 0.001). Parallel to these results, 78.6% of the patients reported a global improvement of their asthma. The same proportion of improvement was observed in the global evaluation made by the physicians (kappa = 0.66). CONCLUSION: This pilot study suggests that addition of montelukast in patients symptomatic on a FA of ICS and LABA may result in significant improvements in asthma control. A randomised, placebo-controlled clinical trial seems warranted.     

白三烯受体拮抗剂治疗儿童哮喘的疗效观察

目的探讨孟鲁司特在儿童哮喘中的应用及疗效。方法将97例哮喘患儿随机分为常规治疗组48例和常规治疗加用孟鲁司特组49例,观察患儿急性期症状消失的时间及最大呼气流量(PEF)升高的幅度及各级哮喘患儿6个月内累积吸入糖皮质激素的总量及速效受体激动剂的总量,并比较两组患儿升降级治疗的例数。结果两组哮喘患儿急性期临床症状、体征消失时间比较差异无显著性(P>0.05),两组间PEF的改善幅度比较在一级哮喘患儿差异无显著性(P>0.05),而在二、三级哮喘患儿差异有显著性(P<0.05),对于吸入糖皮质激素和吸入速效受体激动剂用量的比较,同样在一级哮喘患儿差异无显著性(P>0.05),而在二、三级哮喘患儿孟鲁司特组用量明显少于对照组(P<0.05)。同时在对照组的二、三级患儿分别有35.3%(6/18)和25.0%(3/12)降级治疗,而在孟鲁司特组的数据为57.9%(11/19)和53.8%(7/13)。结论对于轻度持续和中度持续的哮喘患儿,加用孟鲁司特有助于缓解病情,减少糖皮质激素和β2受体激动剂的用量,而对于轻度间歇的哮喘患儿无明显帮助     

Inhaled salmeterol/fluticasone propionate: a review of its use in asthma

Salmeterol/fluticasone propionate, administered twice daily via a multidose dry powder inhaler (Seretide/Advair Diskus), Seretide Accuhaler or metered-dose hydrofluoroalkane (chlorofluorocarbon-free) inhaler (Seretide Evohaler), is a combination of the long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) [LABA] salmeterol and the corticosteroid fluticasone propionate.Maintenance therapy with combined salmeterol/fluticasone propionate is at least as effective in improving lung function and symptoms and is as well tolerated in patients with asthma as concurrent salmeterol plus fluticasone propionate. In patients previously receiving as-required short-acting beta(2)-agonists (SABAs) or inhaled corticosteroids, salmeterol/fluticasone propionate was significantly more effective in providing asthma control than fluticasone propionate and in improving lung function and asthma symptoms than inhaled corticosteroids (at equivalent or higher dosages), salmeterol or montelukast (as monotherapy or in combination with fluticasone propionate). Salmeterol/fluticasone propionate was more effective in improving asthma symptoms than adjusted-dose budesonide/formoterol in patients with uncontrolled asthma despite treatment with inhaled corticosteroids with or without a LABA in a well designed 1-year study. In pharmacoeconomic analyses, salmeterol/fluticasone propionate compared favourably with inhaled corticosteroids and mono- or combination therapy with oral montelukast. Salmeterol/fluticasone propionate is, therefore, an effective, well tolerated and cost-effective option for the maintenance treatment of patients with asthma.     

孟鲁司特治疗儿童变应性鼻炎合并支气管哮喘的临床研究

目的:研究孟鲁司特治疗儿童变应性鼻炎合并支气管哮喘的疗效。方法:120例变应性鼻炎合并支气管哮喘患儿随机分为治疗组与干预组,分别采用糖皮质激素及加用孟鲁司特治疗,总疗程3个月。观察2组临床症状及肺功能改善情况。结果:干预组在改善变应性鼻炎症状方面较治疗组有效,在哮喘症状和肺功能改善上较治疗组显著(P<0.05)。结论:孟鲁司特能有效缓解变应性鼻炎症状,在治疗哮喘方面与吸入性糖皮质激素药物联用优于单纯使用吸入激素。     

Salmeterol decreases eosinophilic cationic protein and rescue medication in patients inhaling beclomethasone dipropionate: preliminary study in mild and moderate asthma in Trinidad, West Indies

Activated eosinophils play a critical role in asthma pathogenesis, and eosinophil cationic protein (ECP) is a useful indicator of inflammation. Inhaled corticosteroids and long-acting beta2-agonists (LABA) effectively control asthma symptoms and improve airway function. Salmeterol's anti-inflammatory efficacy as add-on therapy to inhaled corticosteroids has not been evaluated in Caribbean populations. We investigated nine non-smoking subjects (three men and six women; mean age: +/- SE, 50.7 +/- 3.82 years) with stable mild and moderate persistent asthma who were inhaling > or = 500 microg beclomethasone dipropionate (BDP) daily. This was a with-in-patient controlled laboratory blind study performed over 8 weeks. Patients received BDP for 2 weeks, add-on salmeterol 100 microg in weeks 3-6 and BDP alone in weeks 7-8. Patients recorded daily morning and night symptoms. Morning peak expiratory flow rate was measured on entry to the study and with sputum ECP at the end of weeks 2, 4, 6 and 8. Salmeterol together with BDP decreased sputum ECP from a pretreatment median value of 897.84 microg/l to 628.38 microg/l after 4 weeks, and ECP continued to decrease even after salmeterol withdrawal. Both drugs decreased the frequency of rescue medication use by approximately 50% and increased the median number of days per week without rescue salbutamol from 0 to 3 days. Salmeterol's bronchoprotective effect was maximal after 4 weeks and was sustained after its withdrawal. In conclusion, this study, performed in Trinidadian asthmatics, used ECP as a surrogate marker of bronchial inflammation and supports the recent Salmeterol Multi-center Asthma Research Trial (SMART) data recommending add-on salmeterol therapy to adequate anti-inflammatory medication such as inhaled corticosteroids for optimal asthma management. Further studies are required to evaluate the anti-inflammatory efficacy and possible tolerance to salmeterol in Caribbean patients.