A Case-control Study of Asthma Death and Life-threatening Attack: Their Possible Relationship with Prescribed Drug Therapy in Japan

Sales of inhaled β(2)-agonist bronchodilators may be related to the increase in asthma deaths. The aim of this study is to find whether prescribed drug therapy was associated with the increased risk of death from asthma and life-threatening attacks (LTA). The “case” group comprised those under 35 years of age who expired or experienced LTA from January 1994 through December 1996. For each case, an age and sex matched control was selected from asthma patients. Hospital records were reviewed to obtain information on the prescribed drug therapy and clinical asthma severity for the cases and controls. Bivariate analysis with conditional logistic regression models for matched data sets were used to estimate the severity-adjusted odds ratios for each asthma medication. Twenty-four fatal cases and 54 LTA cases were observed. The crude odds ratio of clinical severity (OR=9.33, 95%CI:2.84-30.7) was larger than unity and with statistical significance. After adjusting for clinical severity, the odds ratios computed for all β(2)-agonists delivered by metered dose inhaler (MDI) increased (OR=2.08, 95%CI:0.78-5.50) from that of crude analysis. Among those subjects under 20 years of age, the clinical severity-adjusted odds ratio for the use of all β(2)-agonists by MDI (OR=3.67, 95%CI:0.77-17.5) was higher than that of all subjects. The prescription of β(2)-agonists by MDI increased the risk of asthma death after taking clinical severity into account. Although not statistically significant, our results suggested that β(2)-agonists administered by a MDI might have increased the risk of asthma death and LTA in Japan because the magnitude of the effect was similar to that reported in other countries.