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We read with interest the recent paper by Dockhornet al comparing the effects of single doses of intravenous and oral montelukast on forced expiratory volume in one second (FEV1) in patients with chronic persistent asthma.1 We agree with the accompanying editorial, that a study of montelukast in acute severe asthma is now warranted.2 Indeed, few published studies have examined the use of leukotriene receptor antagonists in patients with severe persistent asthma.3
There are several good reasons why an intravenous leukotriene receptor antagonist might be effective in acute severe asthma, including evidence that high dose oral steroids do not affect leukotriene synthesis in vivo,4 and that induced sputum cysteinyl leukotriene concentrations are significantly higher in subjects with acute severe asthma than in patients with milder asthma and normal controls which suggests that leukotrienes may be more functionally important in patients with acute severe asthma.5
The question that most clinicians wish to answer is whether adding an intravenous leukotriene receptor antagonist will produce further improvements in patients with acute severe asthma who have already received conventional first line treatment including nebulised high dose salbutamol, ipratropium bromide, and systemic corticosteroids.6 In other words, is an intravenous leukotriene receptor antagonist any better as second line intravenous treatment than aminophylline or salbutamol? The results of such studies are awaited with keen interest. It is behoven upon the pharmaceutical industry to sponsor such studies, asking clinically relevant questions regarding the use of leukotriene receptor antagonists as second line intravenous treatment.
authors' reply We would like to thank Drs Dempsey and Lipworth for their concise thoughts on the topic of the additive effects of antileukotriene drugs in acute asthma.
In chronic asthma antileukotriene drugs have been shown to have additive benefits with β agonists,1-1-1-3corticosteroids,1-4 and theophylline.1-2 Since acute asthmatic episodes are included in the spectrum of the asthmatic response, it is highly likely that antileukotriene drugs will provide at least similar additive effects in this setting.
Adult studies with antileukotrienes in acute asthma in addition to usual treatment will be required. Once safety and efficacy have been demonstrated in adequately controlled trials in adults, paediatric studies or trials with active comparators can be considered.
Conflict of interests: The Asthma & Allergy Research Group have received funding and educational support from the following companies: Astra-Zeneca, GlaxoWellcome, Aventis, Merck, Sharp & Dohme, and Schering-Plough.
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