Determinants of Corticosteroid Insensitivity in Smokers With Asthma

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.

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