The Effects of Montelukast on Smokers With Asthma

Phase 4

Completed

Interventions: Drug: Fluticasone Propionate
Drug: Montelukast
Drug: Salmeterol

Brief Summary: The purpose of this study is:

1. To compare neutrophilia, eosinophilic inflammatory markers and asthma symptom indices between smokers and non-smokers.

2. To elucidate the mechanism by which cigarette smokers are resistant to corticosteroids.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Asthmatics:

Smokers:

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

Arm && Interventions

Group	Intervention	Description
1	Fluticasone Propionate	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
1	Salmeterol	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
3	Salmeterol	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
4	Montelukast	Non-smoking asthmatic treated with Montelukast only: Montelukast dosage: PO 10 mg QHS for 3 months
2	Montelukast	Asthmatic smoker treated with Montelukast only: Montelukast dosage: PO 10 mg QHS for 3 months
3	Fluticasone Propionate	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

Primary Outcome Measures

Name	Time	Method
Sputum Neutrophil Percentages	24 weeks	Week 24 sputum neutrophil percentages were measured in active treatment groups.

Secondary Outcome Measures

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