© 2005 American Thoracic Society
Montelukast for Viral Respiratory Infection–induced Exacerbations of AsthmaFrom the Authors:We would like to thank Dr. Weinberger for identifying some aspects of the PREVIA study that may need further clarification. The first issue raised concerns about the fact that there was no change in the treatment course of oral corticosteroids. As mentioned in the article, the protocol for worsening asthma standardized the use of oral corticosteroids for predefined periods of time even if symptoms resolved earlier. Therefore, no conclusions can be drawn on the use of oral corticosteroids from this study (1). The second issue raised relates to whether the patients really had intermittent asthma. As detailed in the article, the majority of patients probably had intermittent asthma rather than mild persistent asthma. Although patients could have had symptoms for up to 4 days during the 2 weeks of the run-in period, the severity of symptoms had to be very low (i.e., no symptoms > 1.0 out of an average daily score of 4 for the daytime symptom questions, 0–5 range). Because patients had to be asymptomatic in a typical week in the 3 months before the run-in period and also could not use ß-agonists between episodes, they all had a history of being free of symptoms for extended periods of time. In addition, as part of the study design, no preventive therapy could be used, except for montelukast (or placebo), during the 12-month trial. The genuinely intermittent nature of the patient population is illustrated in Figure 2 of the article, which shows a mean severity score of 0.4 of 20 during the month before and after the first episode. We may add a word of caution on overinterpreting asthma categories since patients often move in and out of such categories over time; yet, to the extent possible, we are confident that the study population predominantly represents intermittent asthma. Dr. Weinberger highlights that our study population had fewer exacerbations compared with those in the studies of Doull and coworkers and Wilson and coworkers (see References 2 and 3 of Dr. Weinberger's letter.) The most obvious explanations would include different seasonal viral load, different populations, different exposures to viruses, different age groups, and more severe underlying asthma in the former two trials. For example, the study by Doull and associates was conducted in the United Kingdom during the winter (virus) season (September to March) to cover the maximum wheezing episodes. Our study was conducted on five continents over 12 months, including summer periods. We studied preschool children 2–5 years of age, whereas those studied by Doull and colleagues were 7–9 years of age. It is hardly justified to expect similar exacerbation rates under such different circumstances. Finally, Dr. Weinberger suggests that the study would have been cleaner had we excluded children with risk factors for persistent asthma. However, the treatment effect was found to be independent of such risk factors, showing that risk factors for persistent asthma should not be confused with factors predicting response to treatment. Our study therefore convincingly documents a treatment effect of montelukast in preschool children with intermittent asthma typically driven by viral infections.
Copenhagen University Hospital, Gentofte, Copenhagen, Denmark FOOTNOTES Conflict of Interest Statement: H.B. has, within the last 3 years, received honoraria for lectures and attendance at pediatric advisory boards for Aerocrine, Altana, AstraZeneca, GlaxoSmithKline (GSK), and Merck and holds no stock options in the pharmaceutical industry in the respiratory field, and owns a world patent for an inhaler device but received no royalty; and the COPSAC clinical research unit has in the last 3 years received research grants from the following industry partners in increasing order: Aerocrine, Merck, GSK, and AstraZeneca. REFERENCES
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