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Potency, Time Course, and Effect of Aspirin Therapy

J. Woodrow Weiss, MD; Jeffrey M. Drazen, MD; E. Regis McFadden, Jr, MD; Peter Weller, MD; Elias J. Corey, PhD; Robert A. Lewis, MD; K. Frank Austen, MD

JAMA. 1983;249(20):2814-2817.

Abstract
Five normal human subjects inhaled aerosols generated from solutions of leukotriene D (LTD) to determine the bronchoconstrictor potency and the time course of airway obstruction produced by this constituent of slow-reacting substance of anaphylaxis. The dose-effect and time-effect curves were compared with curves similarly generated for the well-characterized airway constrictor histamine. Leukotriene D was, on average, 5,900 times more potent than histamine on a molar basis in producing an identical decrement in maximal expiratory flow rate at 30% of control vital capacity above residual volume. In addition, although LTD had a rapid onset of effect, similar to that of histamine, the airway obstruction produced by LTD was longer lasting, thereby reflecting more closely the response of asthmatic allergic individuals to antigen inhalation. The response of these subjects to inhalation of LTD was not altered by ingestion of aspirin, suggesting that the airway obstruction was not mediated by cyclooxygenase products of arachidonic acid.

(JAMA 1983;249:2814-2817)

Author Affiliations
From the Department of Medicine, Harvard Medical School (Drs Weiss, Drazen, McFadden, Weller, Lewis, and Austen), the Departments of Medicine (Drs Drazen and McFadden) and Rheumatology and Immunology (Drs Lewis and Austen), Brigham and Women's Hospital, the Department of Medicine, Beth Israel Hospital (Drs Weiss and Weller), and the Shipley Institute of Medicine (Dr McFadden), Boston; and the Department of Chemistry, Harvard University, Cambridge, Mass (Dr Corey).

Footnotes
Reprint requests to Seeley G. Mudd Building, Sixth Floor, 250 Longwood Ave, Boston, MA 02115 (Dr Austen).

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