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Background: Consensus asthma guidelines recommend antileukotriene agents as alternative therapy to existing anti-inflammatory medications; however, the full therapeutic potential of these medications has not yet been determined., Objective: The purpose of this study was to assess the efficacy and safety of the oral leukotriene receptor antagonist zafirlukast (20 mg twice daily) in subgroups of patients who have asthma with the use of integrated data from four 13-week trials., Methods: The trials had comparable designs, entry criteria, and clinical assessments. Patient subgroups were characterized by demographic and baseline asthma characteristics. Analysis of covariance models were tested for overall treatment effect and for interactions between treatment and subgroup characteristics., Results: Patients with mild-to-moderate asthma (12 to 76 years old) who were treated with albuterol alone were randomized (nZ = 879; nP = 605) and included in subset analyses. Significant overall treatment effects, favoring zafirlukast, were noted for measures of daytime and nighttime symptoms, beta2 -agonist use, and pulmonary function (P <.05). A significant, quantitative, treatment-by-age interaction was noted for beta2 -agonist use (P <. 03), suggesting greater reductions in rescue medication use with increasing patient age. Compared with placebo, similar size and/or direction of response was noted with zafirlukast in the various subgroups, indicating a benefit with zafirlukast regardless of subgroup. Significant treatment-by-strata interactions (P <.05), favoring zafirlukast, were noted for various outcome measures in subgroups with the greatest amount of baseline beta2 -agonist use (>8 puffs/day) and with greater baseline peak flow variability (>/=20%) and baseline airflow obstruction (FEV1 /forced vital capacity ratio, <0.70). The overall treatment failure rate was significantly lower in the zafirlukast group compared with the placebo group (P <.003). No associations were observed between any adverse events and subgroups defined by demographic characteristics., Conclusions: Exploratory subset analyses showed that zafirlukast is similarly efficacious in patients with asthma who have differing demographic characteristics and degrees of subjective symptoms. Additionally, zafirlukast appears to be incrementally beneficial in patients with more moderate disease, defined by a greater requirement for as-needed rescue medication and more abnormal pulmonary function at baseline. Over 13 weeks, zafirlukast was well tolerated and demonstrated a safety profile clinically indistinguishable from placebo.

Objective: The objective of this study was to develop, pretest, and validate a questionnaire to measure quality of life in children with seasonal allergic rhinoconjunctivitis (SAR)., Methods (development Study): Thirty-four children with SAR were enrolled from summer camps, notices in the media, and an allergy clinic (Southern Ontario). After generating a pool of 48 potentially important quality of life items, the children identified the ones that they experienced with their SAR and scored each for bother (1 = a little bothered to 4 = extremely bothered). Items identified most frequently and with the highest bother score were included in the Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ). The PRQLQ was pretested for ease completion and accuracy of understanding., Results (development Study): The PRQLQ has 23 items in five domains (nose symptoms, eye symptoms, practical problems, other symptoms, and activities). Responses are given on a seven-point scale, and children are asked to score their experiences during the previous 7 days., Methods (validation Study): Seventy-five children with symptomatic SAR were enrolled from notices in the media and a pediatric allergy clinic (Austin, Tex.). A single cohort design was used, with children assessed at 0, 1, and 3 weeks. The PRQLQ was administered to the children by a trained interviewer at 1 and 3 weeks. A conventional nasal symptom daily diary was completed for 1 week before each of these clinic visits. Global ratings were completed at the final visit., Results (validation Study): In patients who were stable between clinic visits, the PRQLQ demonstrated good reliability (intraclass correlation coefficient = 0.93). The questionnaire was very responsive to change (p < 0.001) and was able to differentiate between patients who were in a stable clinical state and those whose clinical state changed between visits (p = 0.005). Correlations between the PRQLQ and diary scores were close to predicted and supported both the cross-sectional and longitudinal validity of the PRQLQ., Conclusions: The PRQLQ measures the quality of life impairments important to children with SAR. Children provide reliable and accurate responses, the measurement properties are strong, and the questionnaire can be used with confidence in clinical trials, clinical practice, and surveys.

Background: The use of intranasally administered corticosteroid sprays is an established treatment option for seasonal allergic rhinitis., Methods: In this double-blind, placebo-controlled, multicenter study, 438 patients with moderate to severe symptoms of seasonal allergic rhinitis were treated for 4 weeks with double-strength beclomethasone dipropionate (BDP) aqueous nasal spray (84 micrograms/spray: BDP-ds), once daily; regular-strength BDP (42 micrograms/spray: BDP-rs), twice daily; high-strength BDP (336 micrograms/spray: BDP-hs), once daily; or placebo. BDP-hs was included as a safety comparison group. All treatments were given as two sprays per nostril., Results: Physician-rated nasal symptom scores were significantly improved in all three active treatment groups compared with those of the placebo group within the initial 3 days of treatment. Improvement was maintained throughout the 4-week treatment period. BDP-ds and BDP-rs were equivalent at all time points. The BDP-ds, BDP-rs, and BDP-hs groups had greater numbers of patients with a good or excellent therapeutic response at end point than the placebo group. All treatments were well-tolerated, and no unexpected adverse events were reported. No effects on laboratory evaluations or vital signs were evident for any treatment group., Conclusions: The results of this study show that BDP-ds given once a day and BDP-rs given twice a day in the same total daily dose are comparably safe and effective in the treatment of patients with seasonal allergic rhinitis.

Background: One of the risks associated with the use of oral corticosteroids is suppression of adrenocortical function. Triamcinolone acetonide (TAA) aqueous nasal spray administered once daily (110 micrograms and 220 micrograms) has been shown to reduce allergic rhinitis symptoms., Objective: This multicenter, placebo-controlled, double-blind study determined the effects of TAA aqueous nasal spray, placebo, and oral prednisone on adrenocortical function in patients with allergic rhinitis., Methods: Sixty-four patients received TAA aqueous nasal spray (220 micrograms or 440 micrograms), oral prednisone (10 mg), or placebo once daily for 6 weeks. Adrenocortical function was assessed after cosyntropin stimulation for 6 hours before treatment and after 6 weeks of treatment., Results: There was no statistically significant effect on adrenocortical function in patients who received either dose of TAA aqueous nasal spray compared with placebo. In contrast, prednisone produced statistically significant (p < 0.001) reductions in adrenocortical function compared with placebo; reductions occurred in both the mean 6-hour plasma cortisol levels and mean change in 6-hour plasma cortisol levels from pretreatment., Conclusion: This study demonstrated that, unlike oral prednisone, TAA aqueous nasal spray, in therapeutic doses, did not alter adrenocortical function and was comparable to treatment with placebo in its absence of measurable effects on adrenocortical function.

Background: Few clinical trials have directly compared the efficacy of antihistamines with topical nasal corticosteroids., Objective: The study was performed to compare the efficacy and safety of triamcinolone acetonide nasal spray at a dose of 110 micro g in each nostril once daily with 10 mg of oral astemizole once daily for the treatment of seasonal allergic rhinitis., Methods: A multicenter, double-blind, parallel-group study was conducted in 239 patients who were randomized to receive either triamcinolone acetonide or astemizole. A 5-day, drug-free, lead-in period was followed by 4 weeks of double-blind treatment. One hundred four patients treated with triamcinolone acetonide and 105 patients treated with astemizole could be evaluated., Results: Overall, triamcinolone acetonide was more effective than astemizole in reducing total nasal symptoms, nasal stuffiness, nasal itching, and sneezing (p

This study was designed to determine whether lettuce treated with a commercially available sulfite-containing freshener prepared according to manufacturer's directions could provoke reactions in sulfite-sensitive subjects with asthma (SSAs). Five adult SSAs with stable asthma who had multiple prior reactions to double-blind, placebo-controlled, sulfite-capsule challenges were studied. Each patient ingested, in a double-blind, placebo-controlled fashion, four portions of lettuce (3 oz) pretreated with one of two commercially available, nearly identical vegetable fresheners. One freshener contained sodium bisulfite and was used on one portion of lettuce. The other freshener contained no sulfite and was used on three portions of lettuce. The fresheners were prepared and the lettuce was treated according to label instructions. After baseline spirometry, the SSAs consumed the lettuce samples with the same dressing of their choice, serial spirometry was performed, and a positive reaction was defined as a greater than 20% drop in FEV1 decreased 0% to 7%; mean, 3%. Two of the subjects experienced severe reactions to the sulfite-treated lettuce. One of these reactions was life threatening; the other reaction occurred despite placing only 30% of the usual sulfite dose on the lettuce. This study has demonstrated that sulfite-treated lettuce is capable of provoking bronchospasm in SSAs and suggests that such food is one cause of restaurant-provoked asthma in these individuals.