Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81.

Abstract

A previous New Zealand case-control study of asthma deaths in the 5-45 year age group during 1981-3 found that prescription of fenoterol (by metered dose inhaler) was associated with an increased risk of death in patients with severe asthma. One major criticism of this study was that drug data for the cases and controls came from different sources. A new case-control design has been used to evaluate the same hypothesis, with a different set of asthma deaths, the same source for drug information being used for both cases and controls. This depended on identifying deaths from asthma during 1977-81 from national mortality records, and ascertaining which patients from those who died had been admitted to a major hospital for asthma during the 12 months before death. The study was confined to this subgroup, which accounted for about 20% of all asthma deaths in the areas served by a major hospital. For each of the eligible patients who died four age matched controls were selected from patients admitted to hospital for asthma during the year that the death occurred who had also had an admission for asthma in the previous 12 months. For the 58 cases and 227 control subjects information on prescribed drugs was collected from the hospital records relating to the previous admission. The odds ratio of asthma death in patients prescribed inhaled fenoterol was 1-99 (95% confidence interval 112-3-55, p = 0 02). As in the previous study, subgroups defined by markers of chronic asthma severity were also considered. The inhaled fenoterol odds ratio was 2-98 (95% CI 1-15-7 70, p = 0 02) in patients prescribed three or more categories of asthma drugs, 3-91 (95% CI 179-8 54, p < 0-01) in patients with a previous admission for asthma in the past 12 months, and 5 83 (95% CI 1-62-21-0, p = 0-01) in patients prescribed oral corticosteroids at the time of admission. In patients with the most severe asthma (defined by a previous admission for asthma during the past 12 months and prescribed oral corticosteroids at time of admission) the inhaled fenoterol odds ratio was 9-82 (95% CI 2-23-43 4, p < 0 01). These findings add further support to the hypothesis that inhaled fenoterol increases the risk of death in patients with severe asthma.

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

“…Many investigations were conducted to elucidate uncertainty about the confounding between severity and fenoterol use [4][5][6][7][8][9][10][11] Opinion is still divided: one is that fenoterol was not associated with severe life-threatening attacks (LTA) after controlling severity 8,10);and the other is that the association between fenoterol and asthma death was significant, but after adjustment for markers of asthma severity was made, there was no difference in the magnitude of the association between fenoterol and asthma death 4-7,9,11) In this paper, we report the results of a case-control study on prescribed drug therapy, severity, and the risk of death from asthma and LTA in Japan.…”

Clinical Characteristics of Asthmatic Patients Prescribed Various β-Agonist Metered-Dose Inhalers at Yamagata University Hospital

“…5) Similar results have also been reported recently for fenoterol MDI. [6][7][8] However, with regard to fenoterol MDI, previous studies showed that this medication did not cause an increase in death from asthma classied according to the severity of patients who were prescribed other b-agonist MDIs. 10) Furthermore, such a relationship has been observed only in Australia.…”

“…3,4) Another problem relates to a potentially higher risk of death from asthma posed by some b-agonists due to the patient's dependency on and excess use of these inhalers, which was initially noted with the regular and excessive use of isoprenaline 5) and later with fenoterol. [6][7][8] In this regard, whether fenoterol MDI increases the risk of death from asthma is still controversial. [9][10][11] Accurate conclusions have not been made; however, proper instructions on the inhalation manoeuvres using bagonist MDIs as well as other useful information on self-management by asthmatics are undoubtedly necessary for reducing deaths from asthma and preventing exacerbation of the disease.…”

A childhood asthma death in a clinical trial: potential indicators of risk

“…However, no studies have been able to satisfactorily compare and contrast the factors in the patients who have died with those of individuals with severe asthma who have not died. Indeed, this has become a major issue in interpreting the data relating to fenoterol usage in the New Zealand studies of asthma deaths during the 1970s [16][17][18], and a subsequent study from Saskatchewan, Canada [19]. There is much dispute about the selection of appropriate comparator populations and the use of statistical adjustment for confounder factors [18].…”