Aspirin-induced asthma (AIA) is characterized by the overproduction of cysteinyl leukotrienes (cys-LTs). The A to C transversion in the promoter region of the leukotriene C4 synthase (LTC4S) gene is proposed to be associated with the development of AIA. Kawagishi et al (p 936) investigated the frequency of the polymorphism in a Japanese population and its association with clinical characteristics and cys-LT production. Genotyping of LTC4S gene promoter was performed in 60 patients with AIA, 100 patients with aspirin-tolerant asthma (ATA), and 110 control subjects. The frequency of variant C allele was significantly higher in the AIA patients (q = 0.192) than in the ATA patients (q = 0.110; P = .042). Variant C allelic carriers developed asthma at a significantly younger age (31.8 ± 2.9 years [mean ± SEM]) than wild-type A homozygotes (41.3 ± 2.2 years; P = .007). Basal levels of LTE4 and the increment of urinary LTE4 on venous aspirin challenge did not show the difference between wild-type A homozygotes and variant C allelic carriers. There was no relationship between the polymorphism and the LTC4S activity in peripheral eosinophils, though LTC4S activities were significantly higher in AIA patients than in ATA patients. LTC4S promoter polymorphism does not affect cys-LT production but might be associated with the development of AIA. Leukotriene-receptor antagonists, with or without the addition of a nonsedating antihistamine, have been suggested as treatment for seasonal allergic rhinitis. In this issue of the Journal, Pullerits and coworkers (p 949) compare a leukotriene receptor antagonist, either alone or in combination with a nonsedating antihistamine, with both an active (fluticasone) and an inactive (placebo) comparator. Sixty-two patients with grass pollen-induced allergic rhinitis received montelukast 10 mg/day, montelukast 10 mg/day combined with loratadine 10 mg/day, fluticasone propionate 200 μg/day, or placebo. In addition to symptom-medication scores, patients underwent nasal biopsies before and at the peak of the grass pollen season. Daytime and nighttime symptom scores for the 4 regimens are shown in the Figure. The grass pollen season induced a significant increase in the number of EG2+ eosinophils in both epithelium and subepithelium in patients treated with placebo, montelukast, or montelukast plus loratadine. No such increase was observed in patients treated with fluticasone. The authors conclude that fluticasone propionate is more effective than the combination of montelukast and loratadine in reducing pollen-induced rhinitis symptoms and nasal mucosal eosinophilic inflammation. Therefore, treatment with glucocorticoids rather than the combination of an antihistamine and an antileukotriene should be the cornerstone of treatment in seasonal allergic rhinitis. Genetic factors of allergic diseases, including bronchial asthma, are heterogenous. A variant of the IL-13 gene, in which arginine residue at amino acid 110 is replaced with glutamine, is genetically associated with bronchial asthma, a high level of IgE, or atopic dermatitis. It has attracted great interest, because IL-13 is pivotal in the pathogenesis of bronchial asthma, and TH2 cytokine genes (including IL-13) are clustered in 5q31-33, showing linkage to bronchial asthma. However, the function of the variant remained an open question. Arima et al (p 980) generated 2 types of recombinant IL-13 proteins and analyzed the functional properties of the variant. It showed a lower affinity with the IL-13 receptor α2 chain, a decoy receptor, whereas it did not affect the affinity with the IL-13 receptor α1 chain. The variant also demonstrated an enhanced stability in vitro and in vivo. These properties of the variant might cause upregulation of local and systemic IL-13 concentration, explaining the functional mechanism of the variant as a genetic factor in bronchial asthma and giving us a clue as to how to remodel IL-13 receptor for developing a therapeutic agent. Mild eosinophilic airway inflammation and bronchial hyperresponsiveness—ie, mild asthma—have been shown to affect a high proportion of endurance athletes. The persistence of airway inflammation, bronchial hyperresponsiveness, and asthma in this population are not known, however, inasmuch as follow-up studies on athletes' asthma have not been performed. Helenius et al (p 962) prospectively followed 42 elite swimmers for 5 years. Sixteen swimmers had continued their competitive careers during follow-up (active swimmers); the other 26 had stopped competing (past swimmers). All of the swimmers completed questionnaires and underwent resting spirometry, histamine challenge testing, and skin prick tests at baseline and at follow-up. Twenty-nine swimmers also gave induced sputum samples on both occasions. Mild eosinophilic and lymphocytic airway inflammation was increased among active swimmers, and occurrence of asthma increased significantly during follow-up. In past swimmers, bronchial hyperresponsiveness and asthma attenuated or even disappeared. Eosinophilic airway inflammation tended to decrease during follow-up in the past swimmers. In conclusion, symptoms indicating mild asthma might result from high swimming activity and are partly reversible. Cysteinyl leukotrienes (cysLTs)—LTC4 LTD4, and LTE4—have many well-recognized actions as paracrine inflammatory mediators pertinent to asthma and other forms of allergic disorders. These leukotrienes can cause bronchoconstriction, mucous hypersecretion, increased microvascular permeability, bronchial hyperresponsiveness, and eosinophil infiltration. Indeed, therapeutic agents that block the formation or action of cysLTs are used in the management of asthma. In this issue of the Journal, Bandeira-Melo et al (p 975) demonstrate that cysLTs are also capable of activating additional functional responses of eosinophils germane to allergic inflammation. Using human eosinophils derived in vitro from IL-3- and IL-5-stimulated cord blood progenitors embedded in EliCell preparations (a novel technique for detection of cytokine secretion), the authors studied the ability of cysLTs to induce the extracellular secretion of the prototypical TH2 cytokine IL-4, which is stored preformed within eosinophil-specific granules. The investigators found that cysLTs can induce the secretion of IL-4 from cord blood-derived human eosinophils. LTC4, LTD4, and LTE4, acting via Gi protein-coupled, cysLT receptors, stimulated the rapid, nonexocytotic release of preformed IL-4. Inasmuch as eosinophils are major sources of cysLTs, the effectiveness of the therapeutic agents targeting cysLTs' synthesis or receptor activation might have activities broader than simply blocking the paracrine-mediator activities of cysLTs. Liposomes, small phospholipid vesicles, have been reported to act as immunologic adjuvants as well as to produce a depot effect after subcutaneous injection. In this issue of the Journal, Basomba and coworkers (p 943) report the results of a 1-year double-blind, placebo-controlled study of immunotherapy with a vaccine consisting of Dermatophagoides pteronyssinus extracts encapsulated in liposomes. Injections included a 7-week build-up followed by monthly maintenance injections that contained 3.2 μg of Der p 1. Fifty patients with mild to moderate asthma completed the 1-year study. Ninety percent of the patients in the active group achieved the projected maintenance dose. Patients in the active group reported an increase in “healthy days” to 65%; this compared with 18% in the placebo-treated patients. Actively treated patients also had significantly greater reduction in immediate and late-phase skin tests and bronchial allergen challenge results. Serum-specific IgE levels showed only an initial transient increase, whereas specific IgG rose progressively in the actively treated group. The authors conclude that their study shows that specific allergy vaccination with liposome-entrapped D pteronyssinus is highly effective, safe, and well tolerated. Furthermore, the method allows simplification of the dosing schedule in comparison with conventional treatments without an increase in side effects. Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthmaJournal of Allergy and Clinical ImmunologyVol. 109Issue 6PreviewBackground: The A to C transversion in the promoter region of the gene encoding leukotriene C4 synthase (LTC4S) is proposed to be associated with the development of aspirin-induced asthma (AIA). Objective: We investigated the frequency of the polymorphism in Japanese population and its association with clinical characteristics and cysteinyl leukotriene production. Methods: Genotyping of LTC4S gene promoter was performed on 60 patients with AIA, 100 patients with aspirin-tolerant asthma (ATA), and 110 control subjects. Full-Text PDF Comparison of a nasal glucocorticoid, antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitisJournal of Allergy and Clinical ImmunologyVol. 109Issue 6PreviewBackground: Allergic rhinitis requires active intervention for symptom relief. A combination of antileukotriene and antihis-tamine drugs has been suggested to provide additive treatment benefits for patients with allergic rhinitis. Objective: We evaluated how such a combination treatment would affect symptoms and local mucosal eosinophilia in comparison with a nasal glucocorticoid. Methods: In a double-blind, randomized study 62 patients with grass pollen-induced allergic rhinitis received a nasal glucocorticoid (fluticasone propionate aqueous nasal spray [FPANS], 200 μg/d), an antileukotriene (montelukast, 10 mg/d), a combination of montelukast with an antihistamine (loratadine, 10 mg/d), or placebo throughout the season. Full-Text PDF Upregulation of IL-13 concentration in vivo by the IL13 variant associated with bronchial asthmaJournal of Allergy and Clinical ImmunologyVol. 109Issue 6PreviewBackground: A substantial body of evidence exists to support the pivotal role of IL-13 in the pathogenesis of bronchial asthma. We recently found that a variant of the IL13 gene (Arg110Gln) is genetically associated with bronchial asthma, which is concordant with animal experiments using IL-13 in the development of asthma. Objective: To address whether the Gln110 variant of IL13 influences IL-13 function, contributing to the pathogenesis of bronchial asthma, we studied the functional properties of the variant. Full-Text PDF Effect of continuing or finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma: A 5-year prospective follow-up study of 42 highly trained swimmersJournal of Allergy and Clinical ImmunologyVol. 109Issue 6PreviewBackground: Mild eosinophilic airway inflammation and bronchial hyperresponsiveness-ie, mild asthma-have been shown to affect a high proportion of endurance athletes. The persistence of airway inflammation, bronchial hyperresponsiveness, and asthma in this population is not known, however, inasmuch as follow-up studies of athletes' asthma have not been performed. Objective: The purpose of this study was to investigate effect of finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma. Full-Text PDF Cysteinyl leukotrienes induce IL-4 release from cord blood–derived human eosinophilsJournal of Allergy and Clinical ImmunologyVol. 109Issue 6PreviewBackground: Eosinophils contain preformed stores of IL-4 within their cytoplasmic granules, but physiologic stimuli to release IL-4 from eosinophils are not yet defined. Objective: We evaluated whether cysteinyl leukotrienes (CysLTs) could elicit IL-4 release from eosinophils. Methods: We used a dual-antibody capture and detection assay (EliCell) for IL-4 release and used eosinophils differentiated in vitro from human cord blood-derived progenitors. Results: Leukotriene (LT) C4, LTD4, and LTE4 each elicited the rapid, vesicular transport-mediated, dose- and time-dependent release of IL-4 from eosinophils. Full-Text PDF Allergen vaccination with a liposome-encapsulated extract of Dermatophagoides pteronyssinus : A randomized, double-blind, placebo-controlled trial in asthmatic patientsJournal of Allergy and Clinical ImmunologyVol. 109Issue 6PreviewBackground: Liposomes are potent immunologic adjuvants and have been proposed as allergen carriers in allergy vaccination. Objective: We sought to investigate the efficacy and safety of vaccination with Dermatophagoides pteronyssinus encapsulated in liposomes. Methods: We conducted a double-blind, placebo-controlled study. Fifty-five asthmatic patients sensitized to mites were randomly assigned vaccination with D pteronyssinus extract encapsulated in liposomes or empty liposomes for a period of 12 months. Full-Text PDF