Montelukast and Nasal Epithelial Cell Inflammatory Responses in Asthma and Rhinitis

Study Overview
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Brief Summary
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The airways of the lung are lined by specialised cells called airway epithelial cells. As well as being at the interface between the lungs and the air we breathe; airway epithelial cell (AEC) function is altered in people with respiratory diseases such as asthma. AEC secrete many mediators that contribute to asthma symptoms and these also contribute to asthmatic inflammation in the lungs. The study of such cells is difficult because of their location deep in the lungs. Nasal airway epithelial cells provide a useful and easily accessible model of model of lower airway cells. This study will examine whether the asthma medication Singulair (montelukast) can inhibit the inflammatory secretions of nasal AEC of asthmatic patents who also have allergic rhinitis compared with patients who have asthma alone. We will also examine if montelukast has differential modulating effects in these two patient groups.

Detailed Description
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Hypothesis The inflammatory secretory profile of nasal airway epithelial cells (NEC) cultured from asthmatics with concomitant allergic rhinitis (AR) will differ from that of NEC from patients with asthma alone. Treatment (in vitro and in vivo) with montelukast may have differential modulating effects in these two patient groups. For the primary objective of this proposal we will use nasal AEC from asthmatics with or without concomitant AR as to ascertain differences in pro-inflammatory cytokine and chemokine production between these two groups and determine whether in vitro treatment with montelukast has a differential modulating effect on NEC secretion. In the secondary pilot study any modulating effects by montelukast on AEC secretion in vitro will be correlated with any in vivo response to montelukast withdrawal. This sub study will provide pilot data indicating whether in vivo response to montelukast can be predicted from in vitro effects on NEC.

Official Title
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The Effect of Montelukast on Inflammatory Responses of Nasal Epithelial Cells Cultured From Patients With Asthma, With and Without Concomitant Allergic Rhinitis

Conditions
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Asthma, Allergic Rhinitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: stable physician confirmed mild/moderate asthma (Steps 1-4 of BTS/SIGN guidelines <10 pack-year smoking histories Currently taking montelukast with a documented clinical history of benefit Exclusion Criteria: Nasal corticosteroid therapy

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| asthmatic patients taking montelukast<br>asthma with or without rhinitis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of montelukast on nasal epithelial cell secretion in vitro. | Nasal AEC will be cultured from 20 patients with asthma and 20 patients with asthma and concomitant allergic rhinitis. Unstimulated, TNFα (a surrogate for viral infection, a well known trigger of exacerbations) or allergen stimulated secretion of IL-6, IL-10, INFgamma TGFbeta, GM-CSF, eotaxin 1 & 2, RANTES and IL-8 by NEC will be measured. The in vitro inhibitory effects of a concentration range (10-6M to 10-10M) of montelukast will be assessed. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of 1-week montelukast withdrawal on clinical scores and pro-inflammatory cytokine output by nasal epithelial cells | The secondary outcome of the study will be to examine the effect of withdrawal montelukast for 1-week on clinical scores and pro-inflammatory cytokine/ chemokine secretion by cultured NEC in montelukast-responsive patients with asthma (20 subjects) and asthma/AR (20 subjects). The clinical scores and NEC secretory responses in these patients following montelukast withdrawal will be compared with the responses generated in the primary study i.e., while taking montelukast. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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montelukast, asthma, allergic rhinitis, nasal epithelial cells, inflammatory mediators