1. Impact of Montelukast on Symptoms of Mild-to-Moderate Persistent Asthma and Exercise-Induced Asthma: The ASTHMA Survey
The ASTHMA* survey was supported by an educational grant from MSD Belgium. *Adding Singulair™ Treatment to Handle symptoms in Mild-to-moderate Asthmatics
Contents
Slide 1 Title Slide
Slide 2 Background: Using Montelukast with an ICS Improved Asthma Control in Clinical Studies
Slide 3 Why Conduct the ASTHMA Survey?
Slide 4 ASTHMA Survey: Patients and Methods
Slide 5 Assessments
Slide 6 Patient Demographics and Characteristics
Slide 7 Pre-study Medications
Slide 8 Pre-study Medications by Age
Slide 9 ‘Other’ Pre-study Medications by Age
Slide 10 Pre-study Symptoms (Total Study Group)
Slide 11 Pre-study Symptoms by Age
Slide 12 Asthma Symptoms Persisted Despite Treatment
Slide 13 Results: Montelukast Improved Symptoms and Activities
Slide 14 Results: Treatment Effect Was Even More Pronounced in Children
Slide 15 Results: Symptom Improvements Were Greatest When Adding Montelukast to ICS
Slide 16 Results: Global Evaluations of Well Being Were Favourable After Treatment with Montelukast
Slide 17 Results: 90% of Patients Were Willing to Continue Montelukast
Slide 18 Results: 92% of Children Were Willing to Continue Montelukast
Slide 19 The ASTHMA Survey: Summary
Slide 20 The ASTHMA Survey: Conclusions
References
SINGULAIR (montelukast sodium) is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

2. Background: Using Montelukast with an ICS Improved Asthma Control in Clinical Studies
In clinical studies involving symptomatic asthma patients on inhaled corticosteroids (ICS), adding montelukast:
Improved asthma control compared with adding placebo to beclomethasone 400 mg/day
Fewer days with asthma exacerbations (CASIOPEA study: Vaquerizo MJ et al Thorax 2003;58: )
Was as effective as doubling the dose of budesonide from 800 mg/day to 1600 mg/day
With a faster onset of action, shown by a greater increase in morning PEF and reduced beta-agonist use compared with baseline over days 1-3
Similar reduction in inflammatory cells (eosinophils) (COMPACT study: Price DB et al Thorax 2003;58: )
Was as effective as adding a long-acting beta-agonist (LABA), salmeterol 100 mg/day, to fluticasone 200 mg/day
With a greater reduction in inflammatory cells (eosinophils) (IMPACT study: Bjermer L et al BMJ 2003;327: )
Slide 2
Several randomised, double-blind clinical studies have demonstrated the efficacy of adding montelukast to ICS therapy in asthmatic patients who remain symptomatic on an ICS.
In a 20-week study, 642 adult patients used beclomethasone 400 mg/day plus placebo tablet for a 4-week run-in period before being randomised to receive beclomethasone 400 mg + montelukast 10 mg, beclomethasone 400 mg + placebo tablet, montelukast 10 mg + inhaled placebo or placebo tablet + inhaled placebo. During 16 weeks of treatment, montelukast provided significant clinical benefit in addition to inhaled beclomethasone by improving forced expiratory volume in one second (FEV1), while reducing exacerbation days, daytime asthma symptom scores and nocturnal awakenings (p<0.05).1
In a study involving 36 children aged 6–14 years with mild-to-moderate persistent asthma, the addition of montelukast 5 mg to a stable low-to-moderate dose of ICS for 4 weeks resulted in significantly more rescue-free days (p=0.0001) and a greater number of rescue-free days per week (p=0.002) compared with adding placebo.2
The 18-week CASIOPEA (CApacidad de SIngulair™ Oral en la Prevencion de Exacerbaciones Asthmaticas) study involved 639 adult patients. Following a 2-week single-blind run-in period, during which patients continued on a dose of budesonide (400–1600 mg/day) equivalent to the regimen they had used prior to the study, patients were randomised to receive montelukast 10 mg (n=326) or placebo (n=313) once daily in addition to budesonide for 16 weeks. Compared with budesonide alone, treatment with montelukast plus budesonide produced a 35% reduction in the median percentage of asthma exacerbation days (p=0.03) and a 56% increase in the median percentage of asthma-free days (p=0.001).3
The 16-week COMPACT (Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy) study enrolled 889 adult patients. Following a 1-month single-blind run-in period, during which patients received inhaled budesonide 800 mg/day, patients were randomised to treatment with montelukast 10 mg once daily plus budesonide 800 mg/day (n=448) or to have their dose of budesonide doubled to 1600 mg/day (n=441) for 12 weeks. While there was an improvement in asthma control in both treatment groups, montelukast plus budesonide 800 mg/day showed a faster onset of action compared with budesonide 1600 mg/day, as evidenced by a significantly greater increase in morning peak expiratory flow (PEF; p<0.001) and reduced beta-agonist use (p<0.05) over days 1-3 compared with baseline. Daytime symptom score followed a similar pattern (p>0.05). Both treatments reduced blood eosinophil counts (p=0.387)4
The 52-week IMPACT (Investigation of Montelukast as a Partner Agent for Complementary Therapy) study involved 1490 adult patients with chronic asthma. During the 4-week run-in period, patients received fluticasone 200 mg/day, and were then randomised to receive montelukast 10 mg or salmeterol 100 mg/day in addition to fluticasone 200 mg/day for 48 weeks. Both treatments provided similar asthma control, but montelukast plus fluticasone produced a significant reduction in blood and sputum eosinophils (p0.001 and p<0.005, respectively), while salmeterol plus fluticasone did not.5

3. Why Conduct the ASTHMA Survey?
For many patients, asthma symptoms persist despite controller therapy
Limitation of daily activities
Sleep disturbance
Frequent use of reliever medication
Contributing factors may include:
Compliance – Low adherence to inhaled therapy and incorrect inhaler technique
Concomitant conditions – Up to 80% of patients with asthma suffer from comorbid allergic rhinitis
Slide 3
Asthma treatment guidelines, such as the Global Initiative for Asthma (GINA) Guidelines state that the goals of asthma therapy should include freedom from daytime and night-time symptoms, no restriction of activities, and minimal need for beta-agonist reliever therapy.6 However, the multinational Asthma Insights and Reality in Europe (AIRE) survey highlighted the gap between these goals and the reality for asthma patients.7 Only 5% of the 2803 patients who completed the survey met all of the criteria for asthma control, with 46% reporting daytime symptoms and 30% experiencing asthma-related sleep disturbance at least once a week. Nearly two-thirds had used reliever medication in the past month and many experienced limitations to their normal daily activities.7 Likewise, the UK Asthma in Real Life (AIR) study found that three-quarters of the 2232 patients surveyed used reliever medication twice or more the previous day, and one-third experienced symptoms at least once a week.8 Patients commonly reported inability to undertake certain activities on a ‘bad asthma day.’8
Various factors may contribute to the lack of success of existing asthma therapies. Non-compliance with medication is a major problem in asthma management, with various studies highlighting the low adherence to inhaled therapies in real-life conditions, particularly in children with asthma.9-13
Even when a patient is fully compliant with the prescribed regimen of inhaled medication, incorrect inhalation technique can impair the effectiveness of therapy. In a systematic literature review, it was estimated that up to 40% of patients do not use an efficient inhalation technique.14
Finally, up to 80% of patients with asthma suffer from concomitant allergic rhinitis.15 This comorbidity confounds the treatment of asthma, as a treatment which does not address the symptoms of allergic rhinitis could leave the patient still suffering from respiratory symptoms and resulting impairment.
The ASTHMA Survey sought to determine the effectiveness of montelukast, a once-daily oral medication, with ICS in alleviating the symptoms and limitations caused by asthma in a real-life setting, and also assessed patients’ satisfaction and willingness to continue therapy.16
Rabe KF et al Eur Respir J 2000;16: ; Price D et al Asthma J 1999;4:74-78; Milgrom H et al J Allergy Clin Immunol 1996;98: ; Cochrane MG et al Chest 2000;117: ; Leynaert B et al J Allergy Clin Immunol 2000;106(Suppl 5):S201-S205.

4. ASTHMA Survey: Patients and Methods
A large-scale Belgian survey conducted among > 11,000 GP-treated symptomatic patients with mild-to-moderate persistent asthma despite treatment with ICS or with exercise-induced asthma (EIA)
Questionnaire given before and at least 4 weeks after starting treatment with montelukast once daily at bedtime
Montelukast 5 mg for patients aged 6–14 years
Montelukast 10 mg for patients aged  15 years
Slide 4
Numerous clinical trials have demonstrated the efficacy of montelukast added to ICS therapy. Clinical trials, however, are limited since many factors, including patient preference and compliance, will impact the real-world effectiveness of any drug. To evaluate effectiveness, pragmatic trials based in the clinical practice setting are needed.
The ASTHMA survey was a large-scale Belgian clinical practice survey conducted among GP-treated patients aged 6 years with mild-to-moderate persistent asthma despite treatment with ICS or with EIA. Patients already on leukotriene receptor antagonists (LTRA) therapy were excluded from the study. A total of 11,054 patients were enrolled.
A questionnaire was administered at enrollment and following a minimum of 4 weeks of montelukast therapy. The survey assessed the level of symptoms experienced by patients despite their current medication and determined the efficacy of montelukast, administered orally once daily, in alleviating these symptoms in real-life conditions. Montelukast was taken once daily at bedtime – 5 mg tablet for children aged 6–14 years and 10 mg tablet for patients aged 15 years. Each patient’s concurrent medication could be continued or modified as determined by his/her physician.
Patient-relevant outcomes, such as limitation of activities, were incorporated into this survey and general satisfaction was evaluated through patients’ willingness to continue treatment with montelukast.16
Malonne H et al Curr Med Res Opin 2002;18:

5. Assessments Symptoms Satisfaction Global evaluation of well being
Difficulty with sleep
Early morning awakening
Limitation of activities
Short-acting beta-agonist use (SABA)  twice per week
Satisfaction
Willingness to continue montelukast treatment
Global evaluation of well being
Patient (or parent of young children)
Physician
Slide 5
At enrollment, patients reported whether they experienced the following symptoms:
Difficulty in sleeping due to asthma
Early morning awakening due to asthma
Limitation of activities due to asthma
Use of SABA  twice per week
After 4 weeks of treatment, patients who had experienced symptoms at baseline recorded whether those symptoms were improved, unchanged or worse.
At the end of the study, patients were asked whether they were willing to continue treatment with montelukast.
Patients (or parents of young children) and physicians also gave a global evaluation of the patient’s well being on a scale ranging from 1 (very bad) to 6 (very good).16
Malonne H et al Curr Med Res Opin 2002;18:

6. Patient Demographics and Characteristics
1360 GP participants (~10% of Belgian GPs)
Patients
11,054 patients recruited
9082 patients included in analysis (after exclusion of incorrectly completed questionnaires and those already on LTRAs)
51% male, 45% female (4% sex not mentioned)
13% aged 6–14 years, 87% aged  15 years
Slide 6
A total of 1360 GPs took part in the survey, representing almost 10% of Belgian-registered GPs.
Patients were recruited between May and August 2001, with a median interval between administration of the two questionnaires of 31 days.
A total of 11,054 patients were recruited, representing an average of 8 patients per GP. After exclusion of 1807 incorrectly completed questionnaires and 165 patients already receiving LTRAs, data from 9082 patients were included in the final analysis.
About half of the study population were male and 13% were children aged 6–14 years.16
Malonne H et al Curr Med Res Opin 2002;18:

7. Pre-study Medications
LABA
(+ Other, No ICS) 4%
No Medication
mentioned 4%
Other 8%
ICS (+ Other, No LABA) 24%
ICS + LABA (+ Other) 60%
Slide 7
In total, almost 85% of patients were using an ICS, with 60% using a combination of ICS and LABA. Of the 15% of patients who had not used an ICS, less than 4% reported LABA use, about 7% various other anti-asthma medications and 4% did not report their current anti-asthma medication.16
Other = anticholinergics, theophylline, antihistamine, cromoglycate, oral corticosteroids, ketotifen
Malonne H et al Curr Med Res Opin 2002;18:

8. Pre-study Medications by Age
Children were more likely to be using medications other than ICS or LABA
Patients
(%) 75
6–14 years (n = 1184)
64%
 15 years (n = 7898) 60 45
40%
33% 30
22%
15% 15 8% 6% 3% 4% 4%
Slide 8
This slide shows the pre-study medications used by children aged 6–14 years and adults and adolescents aged 15 years. The combination of ICS and LABA was the most frequent medication prescribed to adults (64%), whereas only one-third of children received this combination. For children, there was a clear trend towards prescribing alternative medications other than ICS or LABA.16
ICS (+ other, no LABA)
LABA (+ other, no ICS)
ICS + LABA (+ other)
Other
None mentioned
Other = anticholinergics, theophylline, antihistamine, cromoglycate, oral corticosteroids, ketotifen
Malonne H et al Curr Med Res Opin 2002;18:

9. ‘Other’ Pre-study Medications by Age
Percentage of patients
Other therapies
Anticholinergics
Theophylline
Oral corticosteroids
Antihistamine
Cromoglycate
Ketotifen
Bromhexine HCl, acetylcysteine
Total
n = 9082
14.0
6.2
2.1
2.0
1.4
0.4
6–14 years
n = 1184
8.8
0.4
5.0
6.3
4.5
0.2
 15 years
n = 7898
14.8
7.1
2.3
1.6
1.5
1.0
0.4
Slide 9
This slide details the ‘other’ asthma medications used by patients prior to entry into the study. Antihistamine, cromoglycate and ketotifen were prescribed more frequently in children (5.0%, 6.3% and 4.5%, respectively) than in adults (1.6%, 1.5% and 1.0%, respectively). Theophylline was primarily prescribed to adults (7.1% compared with 0.4% of children).16
Malonne H et al Curr Med Res Opin 2002;18:

10. Pre-study Symptoms (Total Study Group)
Most patients suffered asthma-related limitations
Patients
(%)
100
92%
78% 80 60
48%
45% 40
Slide 10
Based on the inclusion criteria, all patients reported symptoms at enrollment. Despite most patients being on daily controller therapy, 92% reported limitation of activities, 48% asthma-related difficulty with sleep, 45% had early morning awakening due to asthma, and 78% use of rescue SABA  twice per week.16 20
Difficulty with
sleep
Early morning
awakening
Limitation of
activities
SABA use  twice a week
Malonne H et al Curr Med Res Opin 2002;18:

11. Pre-study Symptoms by Age
More adults and adolescents reported symptoms compared with children
p<0.05
Patients
(%)
100
Aged 6–14 years
Aged  15 years
p<0.001 80
p<0.001
p<0.001 60 40
Slide 11
While most patients experienced asthma-related limitations on their activities of daily life, a significantly greater percentage of adults compared with children reported each individual symptom at enrollment (p<0.05).16 20
Difficulty with
sleep
Early morning
awakening
Limitation of
activities
SABA use  twice a week
Malonne H et al Curr Med Res Opin 2002;18:

12. Asthma Symptoms Persisted Despite Treatment
Patients using ICS + LABA reported more symptoms than those using other treatments (*p<0.001 vs. all other subgroups)
Patients
(%)
100 *
ICS + LABA (+ other) (n=5472)
LABA (+ other) (n=341) * 80
ICS (+ other) (n=2213)
Other (n=1056) 60 * * 40
Slide 12
Notably, significantly more patients using ICS plus LABA therapies reported symptoms compared with those using other medications (p<0.001).16 20
Difficulty with
sleep
Early morning
awakening
Limitation of
activities
SABA use  twice a week
Other = anticholinergics, theophylline, antihistamine, cromoglycate, oral corticosteroids, ketotifen
Malonne H et al Curr Med Res Opin 2002;18:

13. Results: Montelukast Improved Symptoms and Activities
Treatment with montelukast afforded patients less symptoms, better sleep and less limitation of activities
Patients
(%)
100
Less
87%
85%
Unchanged
80% 80
77%
More 60 40
21%
19%
Slide 13
Most patients who had symptoms at the start of the study experienced improvement after treatment with montelukast. Of those patients experiencing limitation of activities at enrollment (n=8363), 85% reported fewer limitations after montelukast therapy. In patients who had difficulty with sleep (n=4403), 87% reported better sleep after treatment with montelukast, and 80% of the 4096 patients who experienced early morning awakenings due to asthma reported a reduction in that symptom. Improvement in symptoms was confirmed by a decrease in SABA use. Of the 7117 patients using their SABA  twice per week at enrollment, 77% reported reduced need for rescue medication. Worsening of any symptom was reported by less than 1% of patients.16 20
12%
14%
0.5%
0.6%
0.6%
0.8%
Difficulty with
sleep
(n=4403)
Early morning
awakening
(n=4096)
Limitation of
activities
(n=8363)
SABA use  twice a week
(n=7117)
Malonne H et al Curr Med Res Opin 2002;18:

14. Results: Treatment Effect Was Even More Pronounced in Children
More children compared with adults showed improvement with montelukast
6–14 years
 15 years
Patients
(%)
p<0.001
100
p<0.001
p<0.001
p<0.001 80 60 40
Slide 14
While patients in all age groups responded well to treatment with montelukast, for all symptoms, more children compared with adults showed improvement after treatment with montelukast (p<0.001).
For patients aged 6–14 years, the child or the parent (for young children) evaluated the effect of treatment. The preference and satisfaction of both parents and children with a prescribed asthma medication represent a critical component in maintaining adherence and achieving optimal therapeutic outcomes.16 20
Less difficulty with sleep
Less early
awakening
Less limitation of activities
Decrease in SABA use
Malonne H et al Curr Med Res Opin 2002;18:

15. Less difficulty with sleep Less limitation of activities
Results: Symptom Improvements Were Greatest When Adding Montelukast to ICS
Among patients using ICS, symptom improvement was slightly, but significantly, less pronounced in patients using concomitant LABA
No ICS
ICS (+ other)
Patients
(%)
p<0.05
p<0.05
100
ICS+LABA (+ other)
p <0.05
p<0.05
90% 90
87%
87%
88%
88%
83%
84%
82%
83%
80%
81% 80
76% 70
Slide 15
Among patients using an ICS, symptom improvement rates were slightly, but significantly, less pronounced in patients using concomitant LABA (p<0.05). In contrast, for patients who did not receive the ICS + LABA combination, the improvement rates were independent of ICS use.
Improvement rates were independent of ICS use, but slightly dependent on LABA association with ICS. This observation may reflect the more serious profile of these patients, as confirmed by their particularly high level of symptoms at enrollment, and may also suggest the benefit of using montelukast as the first choice of add-on therapy to ICS.16 60
Less difficulty with sleep
Less early
awakening
Less limitation of activities
Decrease in SABA use
Other = anticholinergics, theophylline, antihistamine, cromoglycate, oral corticosteroids, ketotifen
Malonne H et al Curr Med Res Opin 2002;18:

16. Results: Global Evaluations of Well Being Were Favourable After Treatment with Montelukast
After treatment with montelukast, patient well being was rated as high by patients, parents and doctors
Very Bad
Very Good 1 2 3 4 5 6
Patient
(n=8672)
4.53
Parent (if child)
(n=972)
4.88
Slide 16
The global evaluation scores of patient well being recorded by patients (n=8672), parents (n=972) and doctors (n=8592) after treatment with montelukast were high, ranging from 4.5 to 4.9 on a 1–6 scale.16
Doctor
(n=8592)
4.57
Malonne H et al Curr Med Res Opin 2002;18:

17. Results: 90% of Patients Were Willing to Continue Montelukast
Most patients were willing to continue montelukast, regardless of age
No answer 2% No 8%
Slide 17
As an indicator of satisfaction, 90% of patients expressed willingness to continue montelukast therapy.16
Compliance with treatment regimens is an important determinant of the effectiveness of therapy in the ‘real world.’ Thus, satisfaction and willingness to use a drug is as important as clinical efficacy in the success of therapy. The poor compliance and subsequent treatment failure with inhaled asthma therapies was highlighted in a study by Milgrom et al.9 A sample of 24 children aged 8–12 years had their use of ICS and beta agonists electronically monitored by the metered dose inhaler (MDI) Chronolog device over a 13-week period. Both treatments had been prescribed as fixed-dose regimens, and children and parents demonstrated their knowledge on the correct use of the inhalers by passing a quiz. However, monitoring of MDI use revealed that median compliance was only 58.4% (n=24) and 62.1% (n=16) of prescribed doses for ICS and beta agonist, respectively. During the study, 8 children had an asthma exacerbation requiring a course of oral steroids. These children had a significantly lower compliance with prescribed ICS (13.7%) compared with children who did not have an exacerbation (68.2%; p=0.008).9
Other studies have highlighted the low adherence to inhaled therapies compared with oral therapies in real-life conditions. In a study of 276 patients using concurrent ICS or inhaled cromolyn and oral theophylline, medical records and delivered medication data revealed that patients were significantly more compliant with oral theophylline than inhaled steroids or cromolyn (p=0.0001).10 In well-controlled double-blind studies, compliance is optimised, which may not reflect the situation during chronic treatment in real life.16
Yes
90%
Malonne H et al Curr Med Res Opin 2002;18:

18. Results: 92% of Children Were Willing to Continue Montelukast
Most children aged 6–14 years were willing to continue montelukast therapy
No answer 2% No 6%
Yes
92%
Slide 18
92% of children expressed willingness to continue treatment with montelukast.16
Problems with compliance are particularly pronounced in children, with the preferences of children and parents playing a part. A 3-month study assessing compliance with inhaled beta agonists and ICS in 24 children with asthma demonstrated that patients seldom took all of their medications as prescribed.12 Despite the fact that daily medication was prescribed, the children did not use ICS on 41.8% of days and failed to use beta agonists on 28.1% of days. In a 6-month study of 124 children aged 6–11 years, 82% were compliant with montelukast 10 mg once daily compared with 45% who were compliant with a regimen of inhaled beclomethasone 100 mg three times daily (i.e., a full dose of therapy was taken for >95% of days). Parents reported that montelukast was more convenient (p<0.001) and easier to get their children to take (p=0.005) compared with the ICS.13 Likewise, in a crossover study comparing 4 weeks of treatment with montelukast 5 mg tablet or inhaled cromolyn 8 mg/day in 23 children aged 6–11 years, 82% of parents and 76% of the children expressed a preference for montelukast.17 While there were no asthma exacerbations during treatment with montelukast, two children withdrew from the study due to asthma exacerbations during cromolyn treatment.17
Malonne H et al Curr Med Res Opin 2002;18:

19. The ASTHMA Survey: Summary
At enrollment, asthma symptoms persisted, despite the use of daily controller medication (60% of patients were using ICS + LABA)
Montelukast reduced asthma symptoms and improved activities for most patients
90% of patients were willing to continue montelukast therapy, regardless of age
Slide 19
At enrollment into the study, patients were experiencing symptoms such as limitations of daily activities and difficultly sleeping despite the use of daily controller medication. Notably, 60% of patients were using ICS and LABA (plus other medications, such as anticholinergics, theophylline, antihistamine, cromoglycate, oral corticosteroids, or ketotifen).
After 4 weeks of treatment with montelukast in addition to their usual therapy, most patients reported improved asthma symptoms, less limitation of activities and reduced need for rescue medication.
Overall, 90% of patients expressed willingness to continue treatment with montelukast.16
Malonne H et al Curr Med Res Opin 2002;18:

20. The ASTHMA Survey: Conclusions
In previous studies, montelukast added to ICS provided additional clinical benefits
Complementary benefit of montelukast may be due to blockade of the leukotriene pathway – key mediators in asthmatic inflammation not blocked by steroids
In this survey of 9082 patients with persistent asthma symptoms despite ICS, better control of asthmatic inflammation with montelukast led to better patient outcomes and willingness to continue therapy
90% of patients wished to continue taking montelukast
Slide 20
Data from randomised controlled clinical trials has demonstrated the efficacy of using montelukast with an ICS in patients who remain symptomatic despite treatment with ICS.1-5 Montelukast blocks a key pathway of asthmatic inflammation not controlled by ICS, and so montelukast and ICS may have complementary actions.1, The ASTHMA survey has extended findings from previous clinical trials in a ‘real-life’ setting, by showing that most patients who were symptomatic despite daily controller therapy reported an improvement in life-limiting symptoms after the addition of montelukast, irrespective of their concurrent medication. Importantly, patients reported a high level of satisfaction with montelukast and were willing to continue treatment.16
Laviolette M et al Am J Respir Crit Care Med 1999;160: ; Phipatanakul W et al Ann Allergy Asthma Immunol 2002;91:49-54; Vaquerizo MJ et al Thorax 2003;58: ; Price DB et al Thorax 2003;58: ; Bjermer L et al BMJ 2003;327: ; Malonne H et al Curr Med Res Opin 2002;18:

21. See notes page for references.
LaViolette M, Malmstrom K, Lu S et al. Montelukast added to inhaled beclomethasone in the treatment of asthma. Am J Respir Crit Care Med 1999;160:
Phipatanakul W, Greene C, Downes SJ et al. Montelukast improves asthma control in asthmatic children maintained on inhaled corticosteroids. Ann Allergy Asthma Immunol 2003;91:49-54.
Vaquerizo MJ, Casan P, Castillo J et al. Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma. Thorax 2003;58:
Price DB, Hernandez D, Magyar P et al. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax 2003;58:
Bjermer L, Bisgaard H, Bousquet J et al. A one-year comparative trial of montelukast and fluticasone vs salmeterol and fluticasone in protecting against asthma exacerbations in adult patients. BMJ 2003;327:
National Institutes of Health, National Heart, Lung, and Blood Institute. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. NIH Publication Number Revised 2002.
Rabe KF, Vermeire PA, Soriano JB, Maier WC. Clinical management of asthma in 1999: The Asthma Insights and Reality in Europe (AIRE) study. Eur Respir J 2000;16:
Price D, Ryan D, Pearce L, Bride F. The AIR study: Asthma in real life. Asthma J 1999;4:74-78.
Milgrom H, Bender B, Ackerson L et al. Non-compliance and treatment failure in children with asthma. J Allergy Clin Immunol 1996;98:
Kelloway JS, Wyatt RA, Adlis SA. Comparison of patients’ compliance with prescribed oral and inhaled asthma medications. Arch Intern Med 1994;154:
Williams B, Noonan G, Reiss TF et al. Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older. Clin Exp Allergy 2001;31:
Bender B, Milgrom H, Rand C et al. Psychological factors associated with medication nonadherence in asthmatic children. J Asthma 1998;35:
Maspero JF, Duenas-Meza E, Volovitz B et al. Oral montelukast vs 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 to therapy. Curr Med Res Opin 2001;17:
Cochrane MG, Bala MV, Downs KE et al. Inhaled corticosteroids for asthma therapy: Patient compliance, devices, and inhalation technique. Chest 2000;117:
Leynaert B, Neukirch F, Demoly P et al. Epidemiologic evidence for asthma and rhinitis comorbidity. J Allergy Clin Immunol 2000;106(Suppl 5):S201-S205.
Malonne H, Lachman A, Van den Brande P. Impact of montelukast on symptoms of mild-to-moderate persistent asthma and exercise-induced asthma: Results of the ASTHMA survey. Curr Med Res Opin 2002;18:
Volovitz B, Tabachnik E, Nussinovitch M et al. Montelukast, a leukotriene receptor antagonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma. J Allergy Clin Immunol 1999;104:
Csoma Z, Kharitonov SA, Balint B et al. Increased leukotrienes in exhaled breath condensate in childhood asthma. Am J Respir Crit Care Review 2002;166:
Claesson HE, Dahlen SE. Asthma and leukotrienes: Antileukotrienes as novel anti-asthmatic drugs. J Intern Med 1999;245:
Henderson WR Jr. Role of leukotrienes in asthma. Ann Allergy 1994;72:
Diamant Z, Sampson AP. Anti-inflammatory mechanisms of leukotriene modulators. Clin Exp Allergy 1999;29:
References
See notes page for references.

22. Before prescribing, please consult the manufacturers’ prescribing information.
Merck does not recommend the use of any product in any different manner than as described in the prescribing information.
Before prescribing, please consult the manufacturers’ prescribing information.
Merck does not recommend the use of any product in any different manner than as described in the prescribing information.
Copyright © 2003 Merck & Co., Inc., Whitehouse Station, NJ, USA.
All rights reserved SGA 2003-W-6734-SS Printed in USA
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Copyright © 2003 Merck & Co., Inc., Whitehouse Station, NJ, USA.
All rights reserved SGA 2003-W-6734-SS Printed in USA
VISIT US ON THE WORLD WIDE WEB AT