PATTERNS OF INCREASING BETA-AGONIST USE AND THE RISK OF FATAL OR NEAR-FATAL ASTHMA

The association between the use of inhaled beta-agonists by metered-dose inhaler and the risk of fatal or near-fatal asthma has been demonstrated. It shows that asthmatics who use one canister of beta-agonist per month more than the number used by other similar asthmatics have twice the risk of fatal or near-fatal asthma. The present investigation assesses the magnitude of this excess risk when an asthmatic increases his/her own monthly use of inhaled beta-agonists over time. From a previous nested case-control study of 129 deaths and near-deaths from asthma (cases) and 655 controls from a cohort of 12,301 asthmatics, the subset using at least 12 inhalers during the 12 month study period was identified (97 cases and 258 controls). A profile score, ranging 0-11, was formed to quantify the patterns of beta-agonist use over time for each subject, covering the entire spectrum extending from decreasing to increasing use. The relative risk was 15.2 (95% confidence interval (CI) 2.4-96.2) per unit increase of the profile score in subjects with a pattern of increasing beta-agonist use (profile score of 6.5 or more), but this relative risk was only 1.5 (95% CI 0.8-2.6) per unit when the profile score was less than 6.5 (non-increasing use). This relative risk was independent of the risk associated with the total quantity of beta-agonist use in the 12 month period, which remained around 1.6 (95% CI 1.3-2.0) per inhaler per month. We conclude that above and beyond the quantity of beta-agonist used during a one year period, a pattern of increasing use of beta-agonist inhalers over that period is a major predictive factor of unfavourable outcomes in asthma. Any trend, over a six month span, of a doubling in the monthly use of beta-agonists, or, alternatively, of an increase by one canister in this monthly use, should be regarded as a serious warning sign of an impending life-threatening attack of asthma.