© 2005 American Thoracic Society
An Own GOAL or a Real Breakthrough?To the Editor:Bateman and colleagues (1) advocate the use of the fluticasone/salmeterol combination for all severities of asthma, to obtain "total control." "Total control" is defined using the GINA goals for optimal control, which are mostly driven by smooth muscle responsive outcome measures, particularly symptoms, rescue use, PEF, and exacerbations. The bias of the study outcomes toward those of airway caliber overlooks the key issue of airway inflammation, the pathologic hallmark of asthma. All outcome measures were based on simple tests of pulmonary function, with no surrogate marker for active inflammatory processes, or airway hyperresponsiveness. It is well known that there is a disconnect between airway inflammation and airway caliber; moreover, significant inflammation may be asymptomatic (2). Despite initial in vitro findings of ligand-independent activation of the corticosteroid receptor by long-acting ß2-agonists (3), this finding has not been substantiated by potentiation of inhaled corticosteroid by long-acting ß2-agonists in vivo (4, 5). If we are to believe that long-term inflammation leads to airway remodeling and fixed airway obstruction, it is important to detect this inflammation, rather than mask it with long-acting bronchodilators; perhaps an inflammatory surrogate should have been included in the trial. As patients in all three strata had a mean FEV1 reversibility to short-acting ß2-agonist of over 26% (a group one does not commonly see in real life), it is predictable that they would also exhibit a good bronchodilator response to a long-acting ß2-agonist, given that they work on the same receptor. It follows that the patient group studied was primed to show an improved response to the fluticasone/salmeterol combination, in terms of airway caliber outcomes. It is worth noting the compliance rate of 89% for both groups compares favorably with recently published data of 18% persistence with inhaled corticosteroid at 1 year (6). Perhaps the message should be that persisting with prescribed inhaled corticosteroid can provide 60% of patients in stratum 2, the majority of real-life patients with asthma, with well-controlled asthma and 28% with totally controlled asthma without the need for more costly therapies. The assertion that there is better compliance with the salmeterol/fluticasone combination, rather than fluticasone alone, was not borne out in this study. We applaud the motives of the study, and would encourage the appropriate use of salmeterol, but only when added to a dose of inhaled corticosteroid that is sufficient to adequately treat the underlying inflammation.
University of Dundee Dundee, United Kingdom FOOTNOTES Conflict of Interest Statement: T.C.F. has received funding from GlaxoSmithKline (GSK) to attend the American Thoracic Society annual meeting in 2004 to the value of £1,000 and has received payment for lectures from GSK in 2004 to the value of £800; B.J.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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