Short-acting inhaled beta-2-agonists increased the mortality from chronic obstructive pulmonary disease in observational designs

OBJECTIVE: The effect of short-acting inhaled beta(2)-agonists on mortality from chronic obstructive pulmonary disease (COPD) is controversial. Different observational designs were used to investigate about this topic. STUDY DESIGN AND SETTING: A population-based case-control design was performed, by linking automated health databases from the Varese Province of Italy. Deaths of COPD generated from the cohort of 135,871 patients for whom at least one prescription for drugs used to treat COPD had been dispensed between 1997 and 1999 entered into the study as cases. Up to 20 controls were randomly selected for each case from the cohort after matching on gender, age, and date of cohort entry. Risk ratios were estimated using the case-control, case-crossover, and case-time-control approaches. RESULTS: A total of 222 cases and 3022 controls met the inclusion criteria. Odds ratios (and corresponding 95% confidence intervals) corresponding to more than 0.5 defined-daily-doses were 2.6 (1.7, 4.0), 1.9 (1.1, 3.3), 2.1 (1.1, 4.0), and 2.3 (1.2, 4.6) by using crude and adjusted case-control, case-crossover, and case-time-control estimates, respectively. CONCLUSION: Evidence that higher doses of short-acting inhaled beta(2)-agonists are associated with higher mortality from COPD was consistently supplied by three observational approaches.