The Effects of Montelukast on Smokers With Asthma

Study Overview
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Brief Summary
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The purpose of this study is: To compare neutrophilia, eosinophilic inflammatory markers and asthma symptom indices between smokers and non-smokers. To elucidate the mechanism by which cigarette smokers are resistant to corticosteroids.

Detailed Description
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Many smokers have insufficient control of their symptoms due to inefficacy of ICS in this subpopulation of asthmatics. Cigarette smoking has been shown to stimulate production of cysLTs. CysLTs could activate production of IL-8 for neutrophilia as well as cause eosinophilia in the airway of asthmatics. LTRAs are felt to be less efficacious than ICS in smokers with asthma. However, LTRA's unique mechanism of action could be particularly efficacious in preventing worsening symptoms and lung function for smokers with asthma. Given this, along with the fact that ICS are less effective in smokers, targeting cysLT could lead to significant clinical benefits for asthmatic smokers. Data from this study may possibly serve as crucial data for the significant clinical benefits for asthmatic smokers and determination of the mechanism of corticosteroid resistance in smokers with asthma.

Official Title
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The Effects of Montelukast on Sputum Cells and Inflammatory Markers in Smokers With Asthma

Conditions
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Asthmatic Smokers, Non-asthmatic Smokers

Intervention / Treatment
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* Drug: Fluticasone Propionate
* Drug: Montelukast
* Drug: Salmeterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asthmatics: clinical history of asthma for at least 1 year with evidence of reversible airway obstruction, two documented FEV1 between 60-85%, PC20 < 4mg/ml by methacholine challenge test and average baseline β-agonist use of 2 puffs/day Smokers: smoke 1/2 to 2 packs a day with a smoking history of 5-30 pack years Non-smokers: Non-smokers will have either never smoked or have stopped smoking cigarettes over 5 years ago Exclusion Criteria: positive HCG (for females) have a respiratory tract infection or need oral corticosteroids within the preceding 6 weeks history of COPD or respiratory disorder other than asthma history of psychiatric illness allergy to fluticasone propionate, salmeterol, montelukast or any of their components significant, unstable medical condition other than asthma history of life-threatening asthma exacerbation requiring intubation and mechanical ventilation in the last ten years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months | Drug: Fluticasone Propionate<br>* DPI 250 mcg BID for 3 weeks<br>* Other names: inhaled corticosteroid;Drug: Salmeterol<br>* DPI 50mg BID for 3 weeks<br>* Other names: long-acting beta-agonist;|
| Experimental: 2<br>Asthmatic smoker treated with Montelukast only: Montelukast dosage: PO 10 mg QHS for 3 months | Drug: Montelukast<br>* PO 10 mg QHS for 3 weeks<br>* Other names: leukotriene receptor antagonist;|
| Active Comparator: 3<br>Non-smoking asthmatics treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months | Drug: Fluticasone Propionate<br>* DPI 250 mcg BID for 3 weeks<br>* Other names: inhaled corticosteroid;Drug: Salmeterol<br>* DPI 50mg BID for 3 weeks<br>* Other names: long-acting beta-agonist;|
| Active Comparator: 4<br>Non-smoking asthmatic treated with Montelukast only: Montelukast dosage: PO 10 mg QHS for 3 months | Drug: Montelukast<br>* PO 10 mg QHS for 3 weeks<br>* Other names: leukotriene receptor antagonist;|
| No Intervention: 5<br>Normal controls | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum Neutrophil Percentages | Week 24 sputum neutrophil percentages were measured in active treatment groups. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum Eosinophil Percentages | Secondary endpoints of inflammatory markers (sputum eosinophil percentages at 24 weeks) were measured in active treatment groups | 24 weeks | 
| Sputum IL-8 Levels | Week 24 sputum IL-8 levels in active treatment groups | 24 weeks | 
| Sputum GM-CSF Levels | Week 24 sputum GM-CSF levels in active treatment groups were measured. | 24 weeks | 
| Sputum IFN-gamma/IL-5 Ratios | Week 24 sputum IFN-gamma/IL-5 ratios were determined in active treatment groups. | 24 weeks | 
| Sputum Eotaxin Levels | Week 24 sputum eotaxin levels in active treatment groups were measured. | 24 weeks | 
| Sputum RANTES Levels | Week 24 sputum RANTES levels in active treatment groups were measured. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthmatics, smokers, inhaled corticosteroids, leukotriene receptor antagonists