The efficacy and safety of single oral doses of the leukotriene D4-receptor antagonist, ICI 204,219, were tested in subjects with acute seasonal allergic rhinitis. Subjects who were enrolled in the double-blind, placebo-controlled trial spent 8 h/d for two consecutive days in a park at the peak of ragweed season (counts > 1,000 grains/m3). Subjects (n = 164) who had sufficient symptoms during a 3-h baseline period on Day 1 were randomized to treatment with 10 (n = 33), 20 (n = 33), 40 (n = 33), or 100 mg (n = 32) of ICI 204,219 or placebo (n = 33). Rhinitis symptoms (nasal congestion, sneezing, rhinorrhea, itchy nose, throat and palate, and eye symptoms) were recorded hourly in the park and three times each evening at home. Blood samples were collected twice daily to determine plasma levels of ICI 204,219. Nasal congestion improved (p < 0.01) most consistently from the evening of Day 1 through Day 2 after treatment with 20- and 40-mg doses of ICI 204,219 versus placebo. Sneezing and rhinorrhea (p < or = 0.05) also improved on Day 2 for subjects who received 20- and 40-mg doses of ICI 204,219 compared with placebo. Mean symptoms scores for the entire day showed that 20 mg of ICI 204,219 was the minimally effective dose in this trial. The onset of action for all treatment groups, including placebo, was within the first 2 h of dosing. No serious adverse events were reported during the trial. ICI 204,219 was well tolerated and relieved symptoms of acute seasonal allergic rhinitis.

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We studied 50 nonsmoking volunteers, ages 18-35 yr, with no past or present history or physical examination findings of asthma, rhinitis, allergic disease, or recent respiratory infections, to evaluate the usefulness of the methacholine bronchoprovocation challenge (MBPC) as a screening test for asthma. All were skin-test-negative to 29 aeroallergens and had base-line pulmonary function values greater than 80% predicted. Fourteen (28%) subjects had a drop in forced expiratory volume in 1 s (FEV1) of 20% or greater at a provocative dose (PD20FEV1) less than or equal to 225 breath units. Moreover, when these subjects were compared with 21 asymptomatic allergic asthmatics, there was significant overlap between the two groups in concentration of methacholine causing this decline in FEV1. A positive MBPC at methacholine concentrations less than or equal to 5 mg/ml was not diagnostic of asthma, and a negative MBPC at methacholine concentrations greater than or equal to 10 mg/ml did not rule out asthma. These data strongly suggest that MBPC should not be used as the sole factor for the diagnosis of clinically significant asthma. A positive MBPC is one indication of the presence of airway hyperresponsiveness and thus is only one of many factors that must be considered in the diagnosis of asthma.