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We thank Drs. Tai and Ranganathan for their comments on our article (1), and we generally agree with their approach to asthma treatment. Inhaled corticosteroids (ICS) are effective agents for control of asthma symptoms, and should be the first line of therapy for patients who exhibit poor asthma control. Drs. Tai and Ranganathan should not be surprised, however, that ICS are not prescribed for or used by many patients with poorly controlled asthma. Approximately 30 to 50% of patients with persistent asthma are not prescribed ICS, and only about 50% of patients who are prescribed ICS adhere to their therapy (2, 3). In one Australian study, half of the patients who died of asthma were not taking ICS (4). Thus, we hypothesized that a once-daily, oral medication might improve asthma control as an add-on treatment.

We were disappointed that neither low-dose theophylline nor montelukast significantly improved asthma control overall or in the subgroup of patients on ICS. Our subgroup analyses, however, suggested that low-dose theophylline might be an inexpensive and effective treatment for patients with poorly controlled asthma who cannot or will not take ICS, because of cost or fear of adverse effects.

In previous Asthma Clinical Research Center studies, we have found that about one in five patients in the community with poorly controlled asthma uses a long-acting -agonist (LABA) without concomitant ICS. We agree with Drs. Tai and Ranganathan that LABA monotherapy should be discouraged for initial management of persistent asthma. This view is based on evidence that recurrence of symptomatic asthma is more frequent after switching from ICS to LABA monotherapy (5). Although it is a concern, it is not established that LABA monotherapy is associated with increased mortality, or that ICS are protective from such an effect. In the study of Nelson and coworkers, severe asthma morbidity was slightly increased in those taking salmeterol without ICS (0.383 vs. 0.375%), but the majority (7/13) of the salmeterol-treated patients who died of asthma were taking concomitant oral or inhaled corticosteroids (6). Thus, we consider it an unanswered question whether LABA monotherapy in asthma is associated with increased mortality, or whether coprescription of ICS reduces adverse effects of salmeterol versus providing added therapeutic benefit (7).

Charles G. Irvin, David A. Kaminsky, Nicholas R. Anthonisen, Mario Castro, Nicola A. Hanania, Janet T. Holbrook, John J. Lima, Robert A. Wise and for the American Lung Association Asthma Clinical Research Centers

FOOTNOTES

Conflict of Interest Statement: C.G.I. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.A.K. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. N.R.A. has served on advisory boards for GlaxoSmithKline (GSK) and Altana, receiving approximately $2,000 per year for 5 years, and has given 2–3 talks per year over the past 5 years for GSK with an honorarium of $2,500 for each. M.C. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. N.A.H. has been reimbursed by GSK for speaking, as a consultant, and for serving on advisory committees; he also served as a speaker for Merck; he also served on the advisory board for Genentech. J.T.H. served as a consultant to Merck. J.J.L. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.A.W. received consulting fees from AstraZeneca, GSK, Novartis, Pfizer, Sanofi-Aventis, Emphasys, Spiration, and Forest in the past 3 years for research oversight and review committees; he has served on advisory boards or as a consultant for Boehringer Ingelheim, GSK, Hill-Rom, Merck Manual, Otsuka, and Pfizer.

REFERENCES

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