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Asthma is characterized by chronic airway inflammation and the recruitment of inflammatory cells, typically eosinophils and lymphocytes, into the airway. Although several chemical mediators are released during the inflammatory process of asthma, evidence strongly suggests that the cysteinyl leukotrienes (LT), LTC4, LTD4, and LTE4, play key roles in asthma. The short-term clinical efficacy of an LT receptor antagonist, pranlukast hydrate, in symptomatic patients with asthma who had already been treated with moderate to high doses of inhaled corticosteroids was therefore investigated. Treatment with pranlukast hydrate for 4 weeks significantly improved respiratory function and decreased asthma symptoms, the rescue use of inhaled β2-agonists, the number of peripheral blood eosinophils and serum levels of eosinophil cationic protein. Furthermore, airway inflammation, as evaluated by the percentage of eosinophils in induced sputum and airway responsiveness to histamine, decreased significantly after treatment. There were no significant changes in these parameters in control patients with asthma whose treatment was not changed over 4 weeks. These preliminary results suggest that pranlukast hydrate, an LT receptor antagonist, is an effective agent in the management of asthma in combination with moderate to high doses of inhaled corticosteroids.

Background: Eosinophilic airway inflammation is thought to be associated with airflow limitation and airway hyperresponsiveness. Methods: Spirometry, peak expiratory flow (PEF) measurement, histamine challenge test, and sputum induction with hypertonic saline inhalation were performed in 70 asymptomatic patients with asthma who were treated with bronchodilators or an inhaled corticosteroid (beclomethasone dipropionate, 400–800 µg/day) or both for more than 2 months. The relationships between the sputum eosinophils, respiratory function, and airway responsiveness to histamine were investigated. Results: Induced sputum was obtained from 53 patients. Although significant correlations between sputum eosinophils and forced expiratory volume in 1 s/forced vital capacity × 100% (FEV1%) or maximum expiratory flow at 25% of the forced vital capacity (v̇25) divided by height (v̇25/Ht) were observed, no significant correlations were found between sputum eosinophils and percent predicted PEF (%PEF) or airway responsiveness to histamine. Furthermore, airway responsiveness to histamine was not correlated with FEV1%, v̇25/Ht or %PEF. Conclusion: Single-point measurements of FEV1% and v̇25/Ht but not PEF or airway responsiveness to histamine correlate with the degree of airway inflammation evaluated indirectly with induced sputum.

Recent guidelines for the management of asthma recommend that peak expiratory flow (PEF) should be measured to monitor the level of airflow limitation and to maintain PEF values within the green zone (80–100% of the patient's highest PEF value). Because no studies have evaluated the efficacy of PEF zone management on the basis of patients' physical activity, we studied the appearance of exercise-induced asthma (EIA) using treadmill exercise challenging in asthma patients whose PEF values had been maintained in the green zone for at least 3 months. Exercise-induced asthma was induced in nine of 44 (20.5%) asthma patients. The acetylcholine concentration required to cause a 20% fall in forced expiratory volume in 1s (log PC20) was significantly lower in patients with EIA (2.39±0.21μg/mL) compared with patients without EIA (3.22±0.12μg/mL; P

Rush immunotherapy (RIT) has been shown to be effective in allergic asthma.We investigated the mechanisms of RIT on the basis of cytokine production by T-cell lines and airway inflammation and responsiveness.Subjects were 8 patients with house dust mite-allergic asthma treated with dust mite extract RIT for 6 months and 6 RIT-untreated control patients. IL-5 production by Dermatophagoides farinae -specific T-cell lines, eosinophil percentages, and eosinophil cationic protein (ECP) in induced sputum and airway responsiveness to allergen and histamine were evaluated before and after treatment. Changes in eosinophil percentages and ECP in induced sputum and responsiveness to histamine 24 hours after allergen inhalation were also studied.After 6 months of RIT, percentages of total eosinophils (43. 0% +/- 6.90% to 16.8% +/- 2.48%; P.01), percentages of EG2(+ ) eosinophils (32.6% +/- 6.39% to 19.7% +/- 4.68%; P.01) and ECP (362.7 +/- 125.3 ng/mL to 26.2 +/- 5.15 ng/mL; P.05) decreased in induced sputum, and IL-5 production by T-cell lines decreased (617 +/- 93.2 pg/mL to 200.0 +/- 34.1 pg/mL; P.01). RIT decreased both early- and late-phase bronchoconstriction (early phase: 33.2% +/- 3. 46% to 25.4% +/- 1.42%; P.03; late phase: 16.2% +/- 3.52% to 6.2% +/- 1.96%; P.03) and suppressed increases in the percentages of total (61.8% +/- 4.89% to 42.0% +/- 4.67%; P.01) and EG2-positive eosinophils (55.54% +/- 7.21% to 36.5% +/- 6.43%; P.01) and ECP (685.6 +/- 217.0 ng/mL to 85.4 +/- 23.4 ng/mL; P.05) in induced sputum after allergen inhalation. RIT also decreased airway responsiveness to dust mite (1:303.7 +/- 123.7 wt/vol to 1:65.0 +/- 13.2 wt/vol; P.03) and to histamine before (397.1 +/- 206.9 microgra/mL to 1391.3 +/- 283.3 microgram/mL; P.03) and after allergen inhalation (139.2 +/- 36.5 microgram/mL to 629.1 +/- 196.3 microgram/mL; P.03).RIT decreases airway inflammation and airway hyperresponsiveness before and after bronchial provocation with allergen, possibly by inhibiting both allergen-specific T-cell- and mast cell-dependent pathways. RIT is an effective antiinflammatory treatment in allergic asthma.

It is well known that allergic rhinitis and asthma often coexist in the same patients. Here, we investigated the influence of Japanese cedar pollinosis on the exacerbation of asthma investigated by questionnaire, daily asthma diary, and peak expiratory flow (PEF) monitoring. Furthermore, airway responsiveness to histamine before pollen season was also investigated in some patients. 333 adult patients with asthma were enrolled into the study and 116 patients (34.8%) were suffering from Japanese cedar pollinosis diagnosed by the presence of nasal allergic symptoms during pollen season and high titer of Japanese cedar-specific IgE antibody. Exacerbation of asthma symptoms, including wheezing, dyspnea, cough, and sputum, was detected in 41 of 116 patients (35.3%) during pollen season. Decrease in morning PEF more than 10% compared with the baseline values before pollen season was observed in 13 of 41 patients (11.2% of total asthmatic patients who complicated with Japanese cedar pollinosis). No significant differences in airway responsiveness to histamine and the titer of Japanese cedar-specific IgE antibodies before pollen season were observed between the patients whose asthma exacerbated and the patients whose asthma was not exacerbated. These results suggest that Japanese cedar pollinosis is one of risk factors for asthma in Japanese adult patients with asthma.

Objective: Leukotrienes (LTs) are involved in airway eosinophilic inflammation in patients with asthma. We examined the effects of a cysteinyl LT 1-receptor antagonist, montelukast, on sputum eosinophil levels, and the correlation between sputum eosinophils and bronchodilatation in patients with asthma. Design: Double-blind, randomized, crossover study. Setting: University hospital and private hospital. Patients: Twenty-nine patients with mild-to-moderate asthma. Interventions: Montelukast, 10 mg, and placebo tablet, once daily, each for 4 weeks. Measurements: Sputum eosinophils analyzed using hypertonic saline solution-induced sputum and airway hyperresponsiveness to histamine were evaluated before and after treatment. In addition, morning and evening peak expiratory flow (PEF), asthma symptoms, and peripheral blood eosinophil levels were assessed. Results: The percentage of eosinophils in sputum decreased from 24.6 12.3% at baseline to 15.1 11.8% after montelukast treatment, for a change of 9.5 12.7% (n 20). During placebo administration, the percentage of eosinophils fell from 21.3 12.1% to 21.0 11.5%, resulting in a decrease of 0.3 10.8% (n 20). There was a statistically significant difference in the change in sputum eosinophil levels between these two periods (p < 0.005). The number of peripheral blood eosinophils also significantly decreased after montelukast treatment (314.1 237.6/mL) compared with placebo (413.1 232.1/mL; p < 0.005, n 21). Although morning and evening PEF values were significantly improved from baseline after montelukast treatment (p < 0.01, n 20), asthma symptoms and airway responsiveness to histamine were not significantly altered. Furthermore, there was no significant correlation between the decrease in sputum eosinophils and the increase in PEF. Conclusion: These results suggest that montelukast has anti-inflammatory effects on the airway in patients with asthma, and that its bronchodilatory effect is not solely dependent on a decrease in airway eosinophilia. (CHEST 2002; 121:732–738)

Background: A step-down therapy may be more beneficial for the management of asthma than a step-up therapy. Methods: Eighty-two asthmatic patients with moderate persistent asthma were enrolled in the study and randomized into three groups. One group of patients received 400 µg/day of beclomethasone dipropionate (BDP) for 4 weeks and then 800 µg/day for another 4 weeks (step-up group). The other two groups of patients received 1,200 µg/day of BDP for 4 weeks with or without short-term oral steroid (prednisolone, 0.5 mg/day for 1 week) and then 800 µg/day for another 4 weeks (step-down group). Severe exacerbation of asthma, asthma symptoms, respiratory function and rescue use of inhaled β2-agonists were monitored. If asthma was well controlled, the dose of BDP was decreased every 3 months and if asthma was exacerbated, the dose of BDP was increased until 8 months after the initial treatment. Results: Twenty-two patients during the run-in period, 4 patients in the step-up group, 2 patients in the step-down group treated with a high dose of BDP and no patients in the step-down group with oral steroids during first 4 weeks dropped out because of severe exacerbation of asthma. Although asthma symptoms and respiratory function significantly improved 8 weeks after the therapy in all groups, more significant and prompt improvements of these parameters were observed in patients of the step-down group than in patients of the step-up group after the first 2 weeks of treatment. Furthermore, step-down therapy with short-term oral steroid resulted in the lowest maintenance doses of BDP at 8 months of the three groups. Conclusions: These results suggest that step-down therapy starting with a high dose of inhaled steroid and short-term oral steroid is more effective in gaining prompt control of asthma and reducing the severe exacerbation of asthma and the maintenance dose of inhaled steroids than a step-up therapy starting with a low dose of inhaled steroids in patients with moderate persistent asthma.

Suplatast tosilate (IPD-1151T) is an antiallergic agent that suppresses airway eosinophil infiltration in asthma. We investigated the effects of IPD-1151T on proliferative response and cytokine production by human antigen-specific T cell lines. Purified protein derivatives (PPD)-specific T helper 1 (Th1) cell lines and Dermatophagoides farinae (Der f)-specific T helper 2 (Th2) cell lines were established from patients with asthma sensitized with house dust mite. Stimulation of PPD-specific and Der f-specific T cell lines with relevant antigens resulted in production of mostly interferon (IFN)-gamma and of interleukin (IL)-4 and IL-5, respectively. IPD-1151T did not inhibit the proliferative responses of either the Th1 or Th2 cell line to antigens. Although IPD-1151T did not inhibit IFN-gamma production by PPD-specific Th1 cell lines, it did inhibit IL-4 and IL-5 production by antigen-stimulated Der f-specific Th2 cell lines in a dose-dependent manner. IPD-1151T directly inhibited cytokine production by Der f-specific Th2 cell lines stimulated with immobilized anti-CD3 antibodies. Although IPD-1151T did not inhibit the clonal expansion of memory T cells among PBMCs into PPD-specific Th1 and Th2 cell lines, it did inhibit IL-4 and IL-5 production by Der f-specific Th2 cell lines but not IFN-gamma production by PPD-specific Th1 cell lines. These results suggest that IPD-1151T selectively inhibits Th2-type cytokine production.