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The place of nebulised inhaled corticosteroids in the treatment of patients with asthma is difficult to assess, but Dr J M Hill's editorial in Thorax 1 was inaccurate and below accepted standards for a major medical journal.
Nebulised fluticasone is frequently referred to, yet all the studies referenced2-4 have only been published as abstracts (sponsored by the manufacturers of fluticasone) in supplements to journals. There are insufficient details for these papers to be properly scrutinised. They have not been subject to proper peer review and should have no place as the sole references for a new treatment for asthma in the editorial of a major medical journal.
Dr Hill states that “it is clear from a number of studies that fluticasone is twice as potent as budesonide at a mg for mg dose” but references this with a study which compares fluticasone with beclomethasone5 and not budesonide.
This is clearly incorrect. She forgets that different inhaling devices influence potency ratios. Thus, fluticasone in a Diskhaler may be equipotent with budesonide in a Turbohaler6 and fluticasone in a metered dose inhaler may be equipotent with beclomethasone in the newer, smaller particle, CFC free inhaler (Qvar).7
As far as nebulised steroids are concerned, she seems unaware that even different nebuliser systems may affect the amount delivered to the lung by a factor of four or more.8 Is this not important to mention? Also, the respirable fraction of nebulised steroid depends on the physical properties of the steroid molecule. For example, beclomethasone might be equipotent with budesonide in metered dose inhalers, but beclomethasone solution nebulises poorly and has been withdrawn from use. So, what is the potency ratio between nebulised fluticasone and budesonide? The answer is unknown, simply because there are no comparative studies. Yet Dr Hill confidently assumes a 1:2 potency ratio when giving the costs of each treatment—and fluticasone appears to be one half the price of budesonide.
Finally, any article, editorial or otherwise—and especially one that makes unfavourable comparisons between drugs—should be accompanied by a declaration of competing interests. There is nothing wrong with having a competing interest but readers need to know. Dr Hill should have stated these interests (if any) in the same detail as reported recently in a review article on asthma drugs in theBMJ.9
References
author's reply The author thanks Dr Todd for his constructive comments on her review article.1-1
There are few published randomised controlled trials of nebulised fluticasone or budesonide in the treatment of asthma. Despite this, these agents are being actively marketed by the pharmaceutical industry so it is vital that the debate about the place of these agents in the treatment of asthma should begin. The author therefore thinks that it is justifiable to review what evidence is available, accepting its limitations in abstract form.
The author apologises for incorrectly quoting a paper comparing the potency of budesonide and fluticasone. The correct reference is cited below.1-2 However, the author had presumed that the readers of Thorax would be well aware that data comparing different inhaled corticosteroids apply only to the type of inhaler used in any comparison, and that this basic principle did not require explanation.
Dr Todd's comments about different nebuliser systems and drug solubility are well taken. However, this was a short review of the available clinical evidence for the use of nebulised corticosteroids in the treatment of patients with asthma. It was not possible to, nor did I, review nebuliser pharmacokinetics and, as Dr Todd states, there are no comparative studies of the potency ratio of nebulised budesonide and fluticasone.
Finally, neither Dr Hill nor her spouse has shares in any pharmaceutical company manufacturing asthma treatments. She has received payment from GlaxoWellcome, Boehringer, Bayer, Abbott Laboratories and Astra for presentations/lectures and for attending meetings in the last three years.
Footnotes
Conflict of interests: neither Dr Todd nor his spouse have shares in any pharmaceutical company. He has received payment from Astra, Boehringer, 3M, Forest Laboratories (USA), GlaxoWellcome, MSD and Zeneca for presentations/lectures in the past five years. He has only received payment for research from GlaxoWellcome (fluticasone).