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More on Life-Threatening Asthma and Salmeterol
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     To the Editor: Weinberger and Abu-Hasan (Aug. 24 issue)1 report severe asthma in two patients receiving inhaled corticosteroids and salmeterol. Each actuation of the salmeterol inhaler also delivers xinafoate, which according to the package insert has "no apparent pharmacological activity." However, at a molecular level, xinafoate is similar to compounds such as plicatic acid that are known to cause asthma.

    Among the more than 250 known causes2 of occupational asthma are organic compounds of low molecular weight with bifunctional reactivity composed of at least two basic, hydroxyl, carboxyl, sulfonyl, isocyanate, or similar reactive groups.3 Xinafoate has a molecular mass of 188 daltons and features a carboxyl group with an adjacent hydroxyl group.

    A logistic regression–based prediction model4 assigns xinafoate an asthma hazard index of 0.73, which has a corresponding rating of "undoubtedly hazardous." Recurrent exposure to xinafoate through the use of a salmeterol inhaler may cause more severe asthma in some patients and deserves further investigation.

    Matthew C. Lawyer, M.D., J.D.

    Rollins School of Public Health, Emory University

    Atlanta, GA 30322

    mlawyer@sph.emory.edu

    References

    Weinberger M, Abu-Hasan M. Life-threatening asthma during treatment with salmeterol. N Engl J Med 2006;355:852-853.

    Chan-Yeung M, Malo J-L. Occupational asthma. N Engl J Med 1995;333:107-112.

    Jarvis J, Seed MJ, Elton R, Sawyer L, Agius R. Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds. Occup Environ Med 2005;62:243-250.

    Chemical Asthma Hazard Assessment Program. (Accessed October 26, 2006, at http://homepages.ed.ac.uk/jjarvis/research/hazassess/hazassess.html.)