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NEWS: Pat Hagan Four in five asthma deaths may be due to long acting agonists BMJ 2006; 332: 1467-a [Full text]

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Asthma deaths and long acting beta agonists

Dee Mangin, Les Toop, Andrew Herxheimer   (27 June 2006)

Re: Asthma deaths and long acting beta agonists

Davendralingam Sinniah   (29 June 2006)

Asthma deaths and long acting beta agonists 27 June 2006
Dee Mangin, senior lecturer Dept. of General Practice Christchurch School of Medicine, Les Toop, Andrew Herxheimer Send response to journal: Re: Asthma deaths and long acting beta agonists	The excellent analysis by Salpeter et al provides another example where significant safety concerns develop about a medicine after its introduction.(1) This has troubling echoes of rofecoxib and, for those of us old enough to remember, another beta-2 agonist some decades ago.(2) Less is known about newer medicines and it is not surprising that adverse effects may be revealed after introduction.(3,4) What is important is the quality and speed of the response of the national drug regulatory agencies and the pharmaceutical companies to ensure harm is minimised once concerns are raised. Long acting beta agonists (LABAs) such as salmeterol (Serevent® GlaxoSmithKline) and formoterol (Oxis® AstraZeneca, Foradil® Novartis) continue to be actively promoted. Neither patients nor GPs are likely to be aware of the results published in this paper for months, if ever. In New Zealand some LABAs are promoted direct to consumers in television and print advertisements that prompt even those with milder symptoms (using their reliever 3 to 4 times per week) to ask their doctor about a LABA treatment. This analysis is a strong signal for national drug regulatory agencies to increase pharmacovigilance for this group of bronchodilators, to emphasize a precautionary approach to prescribers and to ensure that both patients and prescribers have the information they need to make informed decisions. Here is an ideal opportunity for national drug regulatory agencies to demonstrate that processes put in place after reflections on the COX 2 episode are effective. Perhaps there could be an international competition to judge their effectiveness with two criteria: the wisdom in the substance of their action, and how long they take to say anything at all. 1.Saltpeter SR, Buckley NS, Ormiston TM Salpeter EE. Meta-analysis: effect of long acting beta-agonists on severe asthma exacerbations and asthma related deaths. Annals of Internal Medicine (2006;144;901-12). 2.Crane J, Pearce N, Flatt A, Burgess C, Jackson R, Kwong T, Ball M, Beasley R. Prescribed fenoterol and death from asthma in New Zealand, 1981 -83: Case control study. Lancet. 1989;139:917-22. 3.Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA 2002;287(17):2215-2220. 4.Wood AJJ. The safety of new medicines. The importance of asking the right questions. JAMA 1999;281(18):1753-1754. Competing interests: None declared
Re: Asthma deaths and long acting beta agonists 29 June 2006
Davendralingam Sinniah, Professor of paediatrics Penang Medical College, 4 Jalan Sepoy Lines, 10450 Penang, Malaysia Send response to journal: Re: Re: Asthma deaths and long acting beta agonists	Asthma deaths will continue to occur as long as asthma medications are used irrationally. The underlying pathology in asthma is inflammation and the best anti-inflammatory medications are steroids both oral and inhaled. Short and long acting bronchodilators while causing dilatation of the bronchi through relaxation of the smooth muscles of the bronchi do not by themselves affect the inflammation. In a situation where a asthma sufferer relies only on bronchodilators to relieve his symptoms, the relief will only last as long as the bronchial lumen is kept sufficiently patent through dilatation. But there is a limit to the maximum amount of dilatation that can be achieved. In the event of further progression of the inflammation, the bronchial lumen will become critically narrowed and this would make it even more difficult for inhaled or nebulised bronchodilators to get through to maintain the bronchodilatation that was previously achieved. This may result in sudden loss of bronchodilatation capability in the face of a near total occlusion of the bronchial lumen by inflammation that had progressed resulting in sudden death. What is required is not condemnation of drugs that have a useful place when used rationally, but education of both health care providers and patients on the proper use of asthma medications. B-agonists can kill a lot of people if used irrationally. Competing interests: None declared