LETTERS TO THE EDITOR Risk factors for death from asthma

Guite and colleagues recently attempted to identify risk factors for certain causes of death among patients admitted to hospital with asthma. The data were originally collected for a diVerent purpose, however, and problems of data quality and completeness limit the conclusions that can be drawn from this analysis. The current study is based on follow up of 2242 (68%) of the original cohort of 3292 patients. An expert panel identified 22 patients who died from asthma, 14 from chronic obstructive pulmonary disease (COPD) and other respiratory diseases, and 14 from cardiovascular diseases. In the paper by Guite et al the numbers of cases have changed significantly with 29 deaths from asthma, 21 from COPD, and 21 cardiovascular deaths. Because both papers relied on the same expert panel, these discrepancies raise fundamental questions about the interpretation of this paper. The fact that drugs are prescribed to patients who diVer according to baseline risk poses an extraordinary methodological challenge to any epidemiological study. Guite and colleagues concluded that “ipratropium bromide is associated with increased risk of death from asthma even after adjustment for a range of markers of COPD.” Even after including extra deaths not identified by the expert panel as asthma deaths and controlling for a marker of COPD co-morbidity but for no markers of asthma mortality, the 95% confidence interval for the odds ratio for ipratropium bromide and death from asthma is extremely imprecise (1.2 to 11). Reducing the number of cases to the original 22 asthma deaths identified by the expert panel and controlling for validated markers of asthma mortality would only further degrade the precision of this estimate. Boehringer Ingelheim has marketed ipratropium bromide for 25 years and its impressive safety profile has been firmly established by hundreds of randomised, controlled studies and epidemiological studies evaluating tens of thousands of patients. Limitations of the current data—understandable from the fact that the study was not originally designed to meet this challenge—preclude them from providing a reliable empirical basis for suggesting an adverse eVect of ipratropium.