Determinants of Corticosteroid Insensitivity in Smokers With Asthma

Study Overview
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Brief Summary
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Smokers with asthma display a relative insensitivity to inhaled and oral corticosteroids. The causes of this phenomenon are currently unknown. The investigators will perform a number of blood & breathing tests to try to discover the cause/s behind this phenomenon with the aim of producing leads for further investigation and possible new treatments for smokers with asthma.

Detailed Description
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Smokers with asthma display a relative insensitivity to inhaled and oral corticosteroids. The causes of this phenomenon are currently unknown. However research into steroid resistance in severe asthma and the smoking related condition chronic obstructive pulmonary disease (COPD) points to a number of possible causes. We will characterise a group of smokers with asthma and perform a number of investigations and compare the results to ex-smokers and never smokers with asthma with the aim of establishing which previously published steroid resistance phenomena are related to the steroid resistance displayed by smokers with asthma. Results produced from this trial will provide hypothesis generating information leading to future pharmaceutical trials.

Official Title
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Determinants of Corticosteroid Insensitivity in Smokers With Asthma

Conditions
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Asthma, Smoking, Steroid Resistance, Corticosteroid Insensitivity

Intervention / Treatment
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* Drug: oral steroid-dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asthma (defined by either reversibility to bronchodilator or methacholine testing) Asthma duration of 6 months or greater Stable asthma Age 18-60 Treatment with inhaled corticosteroids Smoking history consistent with group smokers with asthma: > or = 5 pack years and currently smoking more than 5 cigarettes per day ex-smokers: smoking ceased > or = two years prior to recruitment, minimum 5 pack year history non-smokers: no smoking history Exclusion Criteria: Presence of medical condition likely to be exacerbated by treatment with oral corticosteroids Treatment with > 2000 mcg beclomethasone (or equivalent) per day Subject requires oral corticosteroids to maintain asthma control Subject requires oral theophylline to maintain asthma control Recent treatment with oral corticosteroids Pregnancy or subject planning to become pregnant

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Smokers with asthma | Drug: oral steroid-dexamethasone<br>* 2 week steroid trial<br>|
| Active Comparator: Group 2<br>Ex-smokers with asthma | Drug: oral steroid-dexamethasone<br>* 2 week steroid trial<br>|
| Active Comparator: Group 3<br>Non-smokers with asthma | Drug: oral steroid-dexamethasone<br>* 2 week steroid trial<br>|
| No Intervention: Group 4<br>Non smokers without asthma | |
| No Intervention: Group 5<br>Smokers without asthma or COPD | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bronchodilator response to oral corticosteroid trial in smokers with asthma vs non smokers and ex-smokers with asthma |  | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Smoking, Steroid Resistance, Corticosteroid insensitivity