Timing of once-a-day theophylline dose to match peak blood level with diurnal variation in severity of asthma.

To test the hypothesis that nighttime and early morning signs and symptoms of air flow obstruction in patients with moderately severe asthma would be better controlled by theophylline given on a once-a-day evening dosing schedule chosen to provide a peak blood level in the early morning than by the traditional twice-a-day dosing schedule designed to maintain levels more constant throughout the 24-hour period, the effects on nocturnal asthma of Uniphyl once a day and Theo-Dur twice a day were studied in 14 patients with moderately severe asthma. Although both regimens were effective, more patients preferred the Uniphyl dosing schedule. Nighttime symptoms were better controlled, without an increase in daytime symptoms or significant side effects. Optimal timing of theophylline dosing is an important consideration in the management of asthma.

Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed allergy.

Although three effective topical treatments for allergic rhinitis are available, little information to assist the clinician in choosing among them has been reported. Therefore, we conducted a randomized clinical trial to compare beclomethasone nasal solution, flunisolide, and cromolyn with placebo in 120 patients with hay fever during the ragweed season of 1984. We found that all three agents were superior to placebo (P less than 0.001) and that the glucocorticoids were more effective than cromolyn (P less than 0.001). Surprisingly, we also found that these intranasal treatments considerably reduced the symptoms of seasonal asthma. Further study of this therapeutic advantage is needed.

Effects of topical nasal treatment on asthma symptoms.

During the ragweed season of 1984 we studied 120 patients with hay fever; 58 had a history of asthma during the ragweed season the year before. They were divided into four treatment groups to receive nasal sprays of placebo, cromolyn sodium, flunisolide, or beclomethasone. In controlling hay fever symptoms all medications were superior to placebo; the glucocorticoids were more effective than was cromolyn sodium. Chest symptoms in the 58 patients with a history of asthma were also relieved by the topical nasal treatment. Various explanations for the beneficial effect of topical nasal treatment in asthma symptoms are conceivable. We consider the most likely to be improvement of nasal airway function. With restoration of the filtering action of the nose, less allergen would penetrate to the intrathoracic airways because of reduction in mouth breathing.

Preseasonal IgE ragweed antibody level as a predictor of response to therapy of ragweed hay fever with intranasal cromolyn sodium solution.

Intranasal administration of a 4% solution of cromolyn sodium for the treatment of ragweed hay fever was tested in an 8-week double-blind matched-pair study involving 66 patients. Patients on active drug received 5.2 mg into each nostril 6 times daily; control patients received a placebo spray. The treated group showed a significant reduction in mouth breathing (p less than 0.001), stuffy nose (p less than 0.002), runny nose (p less than 0.003), and postnasal drip (p less than 0.035). Patients receiving the active drug also reported fewer sneezing episodes (p less than 0.003) and nose blowing episodes (p less than 0.015). One patient using cromolyn solution developed nasal ulceration, tongue swelling, coughing, and wheezing. Other side effects were minimal and occurred with equal frequency in both groups. In the treated group relief of symptoms was most marked in patients with high preseasonal levels of IgE ragweed antibody. Intranasal 4% cromolyn solution appears to be an effective drug for the treatment of ragweed hay fever; measurement of the preseasonal level of IgE ragweed antibody is a useful screening test to identify patients most likely to achieve a maximal beneficial response to treatment.

Allergen-controlled study of intranasal immunotherapy for ragweed hay fever.

Previous studies of intranasal immunotherapy have not included control groups treated with an irrelevant allergen. In the present double-blind study, we tested the effectiveness of intranasal immunotherapy in 20 patients sensitive to both short ragweed (SRW) and orchard grass (OG). Patients sprayed increasing concentrations of either SRW (n = 11) or OG (n = 9) extract intranasally six times per day for 8 wk before the SRW pollination season. The effects of this treatment were determined by analysis of symptom score diaries and clinical examinations during the SRW pollination season. SRW-treated patients received cumulative AgE doses from 3 to 59 micrograms (mean 21); this mean dose was approximately sevenfold less than that used in a previous study from our laboratory. All patients reported immediate hay fever symptoms after use of the nasal spray. Five patients (four SRW- and one OG-treated) reported episodes of mild epistaxis during treatment; no other unexpected side effects were noted. During the treatment period, more SRW-treated patients showed signs of nasal obstruction and edematous nasal mucosa than OG-treated control patients (p less than 0.03). During the SRW pollination season, the SRW-treated patients reported lower mean weekly symptom scores than the OG-treated control patients, but the difference was not statistically significant. Supplemental antihistamine use was significantly higher (p less than 0.016) in the OG-treated control patients during the SRW pollination period. Subjective assessment of treatment efficacy by patients was similar in both treatment groups. We conclude that intranasal immunotherapy was of only marginal benefit in this study.

Preseasonal intranasal immunotherapy with nebulized short ragweed extract.

We determined the effect of preseasonal intranasal short ragweed (SRW) immunotherapy in a double-blind, nonpaired, 20-wk study involving 33 SRW-sensitive patients. Patients were selected on the basis of an elevated IGE serum antibody level, a positive intradermal skin test, and a positive intranasal challenge to SRW antigen. SRW-treated patients sprayed SRW solutions intranasally six times a day for 12 wk preseasonally. Placebo-treated patients used nebulized solutions containing buffer or histamine that were interchanged randomly throughout this period. The SRW-treated group reported more preseasonal symptoms than the placebo-treated group (p less than 0.003); however, during the SRW pollination season, the SRW-treated group reported significantly less sneezing, nasal congestion, rhinorrhea, red/itchy eyes, itchy nose/throat, and cough/wheeze. Supplemental antihistamine usage was similar in both groups. The treatment did not affect serum IgE antibody levels to crude SRW, AgE Ra3, or Ra5 in either group at any time during the study. No significant production of IgG antibody to SRW was seen in either group. One SRW-treated patient developed acute sinusitis after 2 wk of treatment; otherwise no side effects other than symptoms of hay fever were noted. Although intranasal SRW immunotherapy may offer an effective and less costly alternative to parenteral immunotherapy, reduction in hay fever symptoms during the pollination season was achieved at the expense of provoking these symptoms during the preceding weeks.

Detection of antibodies to proteases used in laundry detergents by the radioallergosorbent test.

Two proteases, Esperase and Alcalase, derived from Bacillus licheniformis and B. subtilis, respectively, are used in laundry products. In testing for the prevalence of IgE antibodies to these enzymes in sera among 300 laundry product workers, we experienced two problems in the establishment of a reliable RAST for these antigens. The first problem was the propensity of the allergen, Esperase, to undergo autolysis, suggesting that solid-phase Esperase might also lose reactivity through degradation. Treatment of Esperase with phenylmethylsulfonyl fluoride stabilized the enzyme and permitted the synthesis of a stable solid-phase antigen. The second problem was the finding that sera reactive with Esperase in the RAST were also reactive with Savinase, an enzyme from B. licheniformis to which the workers were not exposed. Immunochemical analyses of the three enzymes with specific rabbit antisera by gel diffusion and by two-site immunoradiometric assay demonstrated that they were not cross contaminated to any appreciable extent. RAST inhibition demonstrated that solid-phase Esperase possessed unique allergenic determinants in that the reactivity of IgE antibodies was inhibited by low concentrations of Esperase and only by very high concentrations of Alcalase and Savinase. In contrast, the reactivity of solid-phase Alcalase was occasionally inhibited equally well by Esperase and Alcalase. Most strikingly, the reaction of IgE antibodies with solid-phase Savinase was always inhibited by comparable quantities of Esperase, Alcalase, and Savinase. Thus, the establishment of the RAST for these proteases appears to require the use of phenylmethylsulfonyl fluoride to retard autolysis, and the results must be interpreted with caution because IgE antibodies in certain sera demonstrate cross-reactivity with Alcalase and Savinase.

Pharmacokinetic properties of sustained-release theophylline (Theolair-SR) in relation to timing of doses after low-fat meals.

Pharmacodynamic and pharmacokinetic properties of sustained-release anyhdrous theophylline (Theolair-SR) were similar when doses were given either immediately after or two hours after low-fat meals in children with moderate asthma requiring daily theophylline maintenance. Asthma and pulmonary function values were maintained and approached values for healthy subjects during both treatment regimens.