IS THE ASSOCIATION BETWEEN INHALED BETA-AGONIST USE AND LIFE-THREATENING ASTHMA BECAUSE OF CONFOUNDING BY SEVERITY

We have previously reported an increasing dose-response relationship b etween the regular use of beta-agonist inhalers and the risk of asthma death and near death among a cohort of 12,301 subjects who had been d ispensed 10 or more prescriptions of asthma drugs from January 1980 to April 1987. That analysis was based solely on information obtained fr om linkable computerized data bases. Such an association might be expl ained in part by the tendency of patients with more severe asthma, tha t is, those at greatest risk for an adverse outcome, to use more beta- agonist medication. To further examine this potential confounding by s everity, we gathered clinical information independently from the field on the 129 case patients and their 655 control patients from the matc hed case-control analysis of 12,301 subjects. In 68% of the control pa tients with a life-threatening episode and 75% of the matched control subjects, we obtained a valid questionnaire from at least one physicia n who had seen the patient during the previous 2 yr. Acceptable inform ation on hospitalizations because of asthma was obtained in 87% of tho se hospitalized. Clinical features associated with an increased risk o f fatal and near-fatal asthma were: a history of loss of consciousness or seizures during a previous asthma attack (odds ratio, 10.2; 95% Cl , 3.9 to 26.7), a history of attacks of asthma precipitated by eating certain foods (odds ratio, 5.1; 95% Cl, 2.4 to 11.1), a clinical score designed to reflect the severity of prior attacks of asthma leading t o hospitalization, and prior respiratory acidosis among those in whom a blood gas determination was recorded. After adjustment for these cli nical markers of asthma severity, there was no significant reduction i n the odds ratio for asthma death and near death per metered-dose inha ler of fenoterol (e.g., odds ratio, 2.5; 95% Cl, 1.7 to 3.8) or albute rol (e.g., odds ratio, 2.0; 95% Cl, 1.5 to 2.7). We conclude that this further attempt at adjusting for confounding by severity did not alte r the relationship between the use of beta-agonist inhalers by subject s outside of hospital and the risk of asthma death and near death.