Asthma and the beta agonist debate.

The association between the use of inhaled /3 agonists and the risk of death and near death from asthma has previously been reported. It was based on a nested case-control study of 129 cases and 655 control subjects selected from a cohort of 12301 users of asthma drugs followed during the period 1980 through 1987. In this paper, we examine the question of asthma and non-asthma mortality using data from the entire cohort of 12301 asthmatics. There were 46 asthma and 134 non-asthma deaths in this cohort, for which there were 47842 person-years of follow-up. The overall rate of asthma death was 9 6 per 10 000 asthmatics per year. This rate varied significantly according to the use of fenoterol, albuterol, or oral corticosteroids in the prior 12 months and the number of hospitalisations in the prior 2 years. The rate decreased significantly, by 0-6 asthma deaths per 10 000 asthmatics per year over the study period, after controlling for the effect of the four other risk factors. It also increased significantly with the use of all ,B agonists, and more so for fenoterol than for albuterol, although this difference was partly explained by the dose inequivalence of the two drugs. Change-point dose-response curves showed that the risk of asthma death began to escalate drastically at about 1*4 canisters (of 20 000 ug each) per month of inhaled /3 agonist, the recommended limit. For non-asthma death, the overall rate of 28 deaths per 10000 asthmatics per year was not related to the use of inhaled /3 agonists. We conclude that the strong association between the use of inhaled /3 agonists and asthma mortality is confined primarily to the use of these drugs in excess of recommended limits. Non-asthma mortality, including that from cardiovascular causes, is not associated with the use of inhaled /3 agonists. (Am J Respir Crit Care Med 1994;149:604-10)

[1]  A. Tattersfield.  Use of beta 2 agonists in asthma: much ado about nothing? Still cause for concern. , 1994, BMJ.

[2]  W. Spitzer,et al.  Clinical complexity and epidemiologic uncertainty in case-control research. Fenoterol and asthma management. , 1991, Chest.

[3]  N. Pearce,et al.  Confounding by severity does not explain the association between fenoterol and asthma death , 1994, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[4]  N. Pearce,et al.  PRESCRIBED FENOTEROL AND DEATH FROM ASTHMA IN NEW ZEALAND, 1981-83; CASE-CONTROL STUDY , 1989, The Lancet.

[5]  C. Burgess,et al.  The myocardial effects of fenoterol, isoprenaline and salbutamol in normoxic and hypoxic sheep. , 1994, International journal of experimental pathology.

[6]  C. Madden.  Regular inhaled beta-agonist treatment in bronchial asthma , 1991 .

[7]  Stolley Pd.  Asthma mortality. Why the United States was spared an epidemic of deaths due to asthma. , 1972 .

[8]  N. Pearce,et al.  β-Agonist Use and Death from Asthma , 1994 .

[9]  J Crane,et al.  End of the New Zealand asthma mortality epidemic , 1995, The Lancet.

[10]  J Crane,et al.  Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case-control study. , 1991, Thorax.

[11]  J. Morley.  Asthma mortality and inhaled beta agonist therapy. , 1992, Australian and New Zealand journal of medicine.

[12]  B. Lask.  International Consensus Report on Diagnosis and Management of Asthma , 1993, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[13]  A. Buist,et al.  A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. , 1994, American journal of respiratory and critical care medicine.

[14]  A. Buist,et al.  Is the association between inhaled beta-agonist use and life-threatening asthma because of confounding by severity? , 1993, The American review of respiratory disease.

[15]  R. Shanks,et al.  The cardio‐toxicity of isoprenaline during hypoxia , 1969, British journal of pharmacology.

[16]  N. Pearce,et al.  Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81. , 1990, Thorax.

[17]  J. Morley,et al.  Beta-Adrenoceptor Agonists , 1983 .

[18]  D. Dacruz,et al.  Guidelines for management of asthma. , 1990, BMJ.

[19]  S. Kesten,et al.  Regular vs as-needed inhaled salbutamol in asthma control , 1994, The Lancet.

[20]  L. Mansfield,et al.  Comparison of four weeks' treatment with fenoterol and terbutaline aerosols in adult asthmatics. A double-blind crossover study. , 1979, The Journal of allergy and clinical immunology.

[21]  M. Sears,et al.  Regular beta-adrenergic agonists. Evidence, not reassurance, is what is needed. , 1994, Chest.

[22]  M. Lockett.  DANGEROUS EFFECTS OF ISOPRENALINE IN MYOCARDIAL FAILURE. , 1965, Lancet.

[23]  M. Sears,et al.  International trends in asthma mortality: 1970 to 1985. , 1988, Chest.

[24]  R. Westendorp,et al.  Asthma deaths in New Zealand: whodunnit? , 1995, The Lancet.

[25]  P. Stolley.  Asthma mortality. Why the United States was spared an epidemic of deaths due to asthma. , 1972, The American review of respiratory disease.

[26]  Pierre Ernst,et al.  The Use of β-Agonists and the Risk of Death and near Death from Asthma , 1992 .

[27]  N. Pearce,et al.  Albuterol and deaths from asthma in New Zealand from 1969 to 1976: A case‐control study , 1992, Clinical pharmacology and therapeutics.

[28]  The association between beta-agonist use and death from asthma. A meta-analytic integration of case-control studies. , 1993, JAMA.

[29]  B. Mullen,et al.  The Association Between β-Agonist Use and Death From Asthma: A Meta-analytic Integration of Case-Control Studies , 1993 .

[30]  J. Morley.  Beta agonists and asthma mortality: déjà vu , 1992, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.