Long-term monotherapy with suplatast tosilate in patients with mild atopic asthma: a pilot comparison with low-dose inhaled fluticasone.

BACKGROUND AND OBJECTIVE: Suplatast tosilate is a Th2 cytokine inhibitor that is effective for controlling persistent asthma. However, the long-term efficacy of suplatast is unknown. We compared the clinical efficacy of long-term monotherapy with suplatast tosilate with a low dose of inhaled steroids in patients with mild atopic asthma. METHODS: A total of 32 patients with mild atopic asthma were randomly assigned to receive suplatast (n=15) or fluticasone (n=17). In the suplatast group, 100 mg of suplatast was given orally 3 times a day (total daily dose = 300 mg) for 2 years. In the fluticasone group, 100 pg of fluticasone was inhaled twice a day (total daily dose = 200 tg) for 2 years. RESULTS: In the suplatast group, the improvements in peak expiratory flow (PEF) rate and forced expiratory volume in 1 second (FEV1) and the changes in the symptom diary scale and frequency of beta2 stimulant inhalation were generally similar to those in the fluticasone group, and efficacy was maintained for 2 years. Improvements in inflammatory indices, such as the sputum eosinophil cationic protein (ECP) level and exhaled nitric oxide concentration, were comparable in the suplatast and fluticasone groups. The improvement in airway hyperresponsiveness was also similar in the 2 groups. The peripheral blood eosinophil percent change, serum ECP level, and total IgE antibody titer improved only in the suplatast group. CONCLUSIONS: Long-term treatment with suplatast significantly improved symptoms and inflammatory indices in patients with mild atopic asthma. Along with fluticasone, suplatast is considered a useful drug for the management of mild atopic asthma.

[A couple suffering acute respiratory illness due to waterproofing spray exposure].

The patients were a 28-year-old man and a his 27-year-old wife. The husband smoked a cigarette immediately after using a waterproofing spray, and developed fever, cough, and dyspnea 15 min later. The wife had nausea 2 hours later. Nine hours later, the husband visited a local clinic, and was referred to our hospital because of hypoxemia. In addition, chest CT showed ill-defined areas of increased density, predominantly in the bilateral upper lung fields, with interlobular septal thickening, and he was hospitalized. Although the wife was asymptomatic at the time of examination, she had chest CT findings similar to those of her husband, and was also hospitalized. After admission, the husband received steroid pulse therapy and oxygen inhalation for his symptoms and hypoxemia, with return of arterial blood gas analysis results to normal on the third day. The wife had no symptoms or hypoxemia during her hospital stay. Their chest CT findings improved on the seventh day after admission, and they were discharged. Thus, it appears that the couple suffered from acute respiratory illness due to waterproofing spray exposure, and probably heat degradation products from cigarette smoking caused the husband to have severe symptoms.

[Three cases of spontaneous pneumomediastinum].

We encountered 3 male patients with spontaneous pneumomediastinum. The patients were a 16-year old and a 17-year old and a 24-year old. Predisposing episodes for the development of spontaneous pneumomediastinum could be identified in all 3 patients: throwing a ball during a baseball game in 1, lifting a heavy load during work in 2. However, they were healthy and suddenly developed symptoms in the absence of any underlying disease. The presenting complaint was chest pain in all 3 patients. Chest X-ray films and chest CT images revealed pneumomediastinum. A diagnosis of spontaneous pneumomediastinum was made based on chest X-ray films and chest CT images. After conservative treatment, all 3 patients recovered.

[Clinical evaluation of tulobuterol patch in patients with mild or moderate persistent bronchial asthma-effects of long-term treatment on airway inflammation and hypersensitivity].

The tulobuterol transdermal therapeutic system (TTS) is the world's first commercially available transdermal preparation of tulobuterol, a beta-2 stimulant, that can maintain effective blood tulobuterol levels for 24 hours when applied once daily. In the present study, a total of 36 adult patients with mildly persistent (Step 2) or moderately persistent (Step 3) bronchial asthma 19 who were using inhalational steroids and 17 who were not used tulobuterol TTS for one year and underwent measurement of peak expiratory flow (PEF) once daily. Peripheral eosinophil count, serum eosinophil cationic protein (ECP) level and airway responsiveness (Dmin) were evaluated at 6 months and 1 year after the start of the study. PEF exhibited significant improvements at 6 months and 1 year in patients treated with or without inhalational steroids, while serum ECP was improved significantly only in the patients on inhalational steroids. Patients not using inhalational steroids exhibited no significant exacerbation of Dmin at either 6 months or 1 year: One-year treatment with tulobuterol TTS did not appear to cause tachyphylaxis. The significant improvements in Dmin at 6 months and 1 year in the patients using inhalational steroids suggested that inhalational steroids offer beneficial effects in controlling airway inflammation. Tulobuterol TTS is considered quite beneficial in improving quality of life (QOL) in patients with bronchial asthma because its incidence of adverse effects including palpitations and shivering is significantly lower than those of oral preparations, because of its remarkable improvement of pulmonary function and symptoms of airway obstruction without increasing airway responsiveness even after repeated use, and because it is simple to use and offers excellent clinical efficacy.

[Clinical effects of long-term administration of pranlukast, a leukotriene receptor antagonist, on adult patients with bronchial asthma].

Eighty-one adult patients with bronchial asthma who suffered asthmatic episodes in spite of treatment with 400 mg/day of BDP were placed on pranlukast therapy for 4 weeks. Group I, which showed a 5% or greater increase in PEFR, continued oral pranlukast medication for an additional two years. Those patients who did not show an increase of 5% or greater in PEFR after 4 weeks of pranlukast therapy were instructed to continue the medication for another year. Group II, which exhibited a 5% or greater increase in PEFR after a one-year period continued medication for one more year. Medication was suspended for Group III, which failed to show improvement in PEFR after one year, and the group was placed under observation for the following year. Group I improved significantly in PEFR and exhibited a reduction in the frequency of b2 inhalation, the number of night visits to a medical facility, the amount of steroids inhaled, and the quantity of oral steroids given at regular intervals; and the Group I peripheral eosinophil count, serum ECP level, and FEV1.0 ameliorated. After one year, Group II also showed significant improvement in PEFR and a reduction in both the peripheral eosinophil count and the serum ECP level. This group's PEFR continued to improve after two years. One year after medication was suspended, Group III showed a significant increase in the number of night visits to a medical facility and a rise in the serum ECP level. These findings indicated the efficacy of pranlukast.

Clinical evaluation of leukotriene receptor antagonists in preventing common cold-like symptoms in bronchial asthma patients.

BACKGROUND: We investigated the possibility of preventing common cold-like symptoms as a previously unknown benefit of leukotriene receptor antagonists (LTRAs). METHODS: A total of 279 adult patients with bronchial asthma referred to our hospital between June and December 2004 were retrospectively analyzed. Patients were divided into LTRA treated and untreated groups. Frequency of acute exacerbations and number of visits to emergency rooms and of hospital admissions were analyzed as indicators of frequency of infections and asthma exacerbation over the previous 12 months. RESULTS: Irrespective of inhaled corticosteroid (ICS) use, frequency of infections was significantly lower in the LTRA treated group (0.3 +/- 0.7 times/year) than in the LTRA untreated group (1.6 +/- 4.2 times/year) (P < 0.05), suggesting that LTRA therapy prevents common cold-like symptoms. Frequency of acute exacerbations and number of hospital admissions were significantly lower in the LTRA treated versus LTRA untreated group (0.4 +/- 0.8 versus 2.7 +/- 4.3 times/year and 0.0 +/- 0.2 versus 0.4 +/- 0.7 times/year, respectively; both P < 0.01). When the patients were divided into ICS treated and untreated groups, none of the parameters analyzed differed significantly between the two groups, although all parameters tended to be lower in the ICS treated group. CONCLUSIONS: Adult asthma patients undergoing treatment with LTRAs exhibit lower incidence rates of common cold-like symptoms than those not receiving LTRAs. LTRAs play an important role in reducing the incidence of common cold-like symptoms among asthma patients and in suppressing exacerbation of asthma symptoms possibly associated with these symptoms.

Comparative evaluation of the leukotriene receptor antagonist pranlukast versus the steroid inhalant fluticasone in the therapy of aged patients with mild bronchial asthma.

A comparative study was conducted in elderly subjects with mild bronchial asthma to investigate the clinical usefulness of monotherapy with a leukotriene receptor antagonist in comparison to an inhaled corticosteroid. A total of 41 elderly patients aged 65 years or older with mild bronchial asthma, classified as being in severity step 1 and 2, were randomly assigned to the following two treatment groups: a pranlukast (CAS 103177-37-3, Onon) treatment group of 21 patients and an inhaled corticosteroid treatment group of 20 patients. Patients of the former group received pranlukast 450 mg daily and those of the latter group received fluticasone (CAS 90566-53-3) 200 microg daily for eight weeks. In the reference group, one patient was found to suffer from oral candidiasis 4 weeks after the start of the study. Therefore the evaluation was conducted on the remaining 19 participants. The evaluation parameters examined were obtained by keeping an asthma diary, determinations of PEF (peek expiratory flow), use frequency of beta2 stimulants, changes in symptom scores, and medication compliance. Further, measured before and after therapy were the ratio of peripheral blood eosinophils counts, serum ECP (eosinophils cationic protein), ECP levels induced sputum, and forced expiratory volume in one second (FEV1.0). As a result, in the time-course changes of symptoms scores and morning PEF, swift improvement was noted in the pranlukast group. Further, in the variables such as use frequency of beta2 stimulants, serum ECP levels, ECP levels induced sputum, and FEV1.0, an almost comparable level of improvement to the fluticasone group was demonstrated. From the above results, it was deemed that in elderly patients with mild bronchial asthma classified as steps 1 and 2, the pranlukast monotherapy, with superior medication compliance to inhaled therapy, would produce an equivalent level of clinical efficacy to the monotherapy with inhaled corticosteroid (fluticasone 200 microg daily).

Long-term monotherapy with suplatast tosilate in patients with mild atopic asthma: A pilot comparison with low-dose inhaled fluticasone.

Background and objective: Suplatast tosilate is a Th2 cytokine inhibitor that is effective for controlling persistent asthma. However, the long-term efficacy of suplatast is unknown. We compared the clinical efficacy of long-term monotherapy with suplatast tosilate with a low dose of inhaled steroids in patients with mild atopic asthma. Methods: A total of 32 patients with mild atopic asthma were randomly assigned to receive suplatast (n = 15) or fluticasone (n = 17). In the suplatast group, 100 mg of suplatast was given orally 3 times a day (total daily dose = 300 mg) for 2 years. In the fluticasone group, 100 mg of fluticasone was inhaled twice a day (total daily dose = 200 µg) for 2 years. Results: In the suplatast group, the improvements in peak expiratory flow (PEF) rate and forced expiratory volume in 1 second (FEV1) and the changes in the symptom diary scale and frequency of β2 stimulant inhalation were generally similar to those in the fluticasone group, and efficacy was maintained for 2 years. Improvements in inflammatory indices, such as the sputum eosinophil cationic protein (ECP) level and exhaled nitric oxide concentration, were comparable in the suplatast and fluticasone groups. The improvement in airway hyper-responsiveness was also similar in the 2 groups. The peripheral blood eosinophil percent change, serum ECP level, and total IgE antibody titer improved only in the suplatast group. Conclusions: Long-term treatment with suplatast significantly improved symptoms and inflammatory indices in patients with mild atopic asthma. Along with fluticasone, suplatast is considered a useful drug for the management of mild atopic asthma.

Usefulness of HFA-BDP for adult patients with bronchial asthma: randomized crossover study with fluticasone.

In this randomized crossover study, 22 adult patients with moderate-to-severe persistent bronchial asthma were assigned to one of two groups. Patients in group 1 were administered fluticasone dry powder inhaler (DPI) for 8 weeks followed by a 2-week washout period, then hydrofluoroalkane-beclometasone dipropionate (HFA-BDP) for 8 weeks. After a further 2-week washout, they were again administered fluticasone DPI for 8 weeks. Patients in group 2 were assigned HFA-BDP followed by fluticasone PII and finally HFA-BDP over the same time periods. In both groups, no significant difference was observed in use of beta2-agonists and symptom score between the treatment periods; however, markers of pulmonary function were significantly higher when on HFA-BDP versus fluticasone DPI. Significant increases of morning peak expiratory flow (PEF) (p < 0.01), forced expiratory volume in 1 second (FEV1.0) (p < 0.01), V50 (p < 0.05), and V25 (p < 0.01) were observed at 18 weeks in group 1, whereas there were significant decreases of V50 (p < 0.05) at 18 weeks in group 2. No significant difference was noted in circulating eosinophil count and serum ECP between the 2 treatments; however, ECP in induced sputum and nitric oxide in expired gas were significantly lower (p < 0.05 and < 0.01, respectively) when on HFA-BDP versus fluticasone DPI. HFA-BDP might be delivered to small airways more effectively than fluticasone DPI.

Study on the usefulness of seratrodast in the treatment of chronic pulmonary emphysema.

It has been reported that the biosynthesis of thromboxane A2 (TXA2) is enhanced in platelets in the presence of chronic obstructive pulmonary disease (COPD), and 11-dehydro-TXB2, a urinary metabolite of thromboxane, also increases in blood. In the present study, seratrodast (CAS 112665-43-7, Bronica), a TXA2 receptor antagonist, was administered to 14 patients with chronic pulmonary emphysema in the stable phase for 8 weeks. Respiratory distress was evaluated in the attending physicians' judgments using the Hugh-Jones (H-J) classification, and also by the patients themselves using the Borg scale. Respiratory function tests, including forced vital capacity (FVC), percent of one second forced expiratory volume (FEV1.0%), arterial blood gases during respiration of room air, and peak expiratory flows (PEF) (morning and evening), and measurement of plasma 11-denhydro-TXB2 and TXB2 levels were performed before and 8 weeks after the start of administration, as well as at the time of the start of administration. The results revealed significant improvement of respiratory distress, evaluated on both the H-J classification and the Borg scale, at week 8. Although no significant changes were observed in plasma TXB2 levels, the plasma 11-dehydro-TXB2 level significantly decreased at week 8. Among the respiratory function parameters examined, only FVC was significantly improved. These results indicated that seratrodast is useful for the improvement of respiratory distress in patients with chronic pulmonary emphysema in the stable phase.

Evaluation of the combined effect of pranlukast during high-dose steroid inhalation.

In 40 patients with moderate to severe persistent adult asthma who had been requiring more than 1200 micrograms/day of beclomethasone dipropionate (CAS 5534-09-8, BDP) inhalation, the present study evaluated the combined effects of pranlukast (CAS 103177-37-3, Onon) during highdose steroid inhalation (20 in the pranlukast group and 20 in the control group). In the pranlukast group, 450 mg/day of pranlukast was administered. The course of these patients was monitored for 6 weeks during which the dose of BDP was decreased to 1/2 of the initial dose 2 weeks later and to 1/4 of the initial dose additional 4 weeks later. The dose of BDP was also decreased in the control group. The concomitant use of pranlukast significantly improved asthmatic symptoms and respiratory functions in asthmatic patients receiving high-dose steroid inhalation. Furthermore, the concomitant use of pranlukast significantly inhibited worsening of asthmatic symptoms, respiratory functions and parameters, which are frequently observed when the dose of inhalation steroids is decreased.

Clinical effects of long-term administration of pranlukast, a leukotriene receptor antagonist, on adult patients with bronchial asthma.

Eighty-one adult patients with bronchial asthma who suffered from an unstable peak expiratory flow rate (PEFR) and asthmatic attacks that developed at irregular intervals in spite of inhaling beclometasone dipropionate (CAS 5534-09-8, BDP) in excess of 400 micrograms/day were treated with pranlukast (CAS 103177-37-3, Onon) 450 mg/day for 1 to 2 years and the clinical effects of its long-term administration were studied. The patients were divided into 3 groups: Group I with drug effect seen on peak expiratory flow rate (PEFR) in a short-term; Group II showing long term PEFR improvement; and Group III with no sustained improvement in PEFR. Those in the first two groups continued oral medication for 2 years, while those of the third group withdrew from medication after one year and their clinical course was observed. The evaluation parameters were: PEFR, frequency of beta 2-stimulant inhalation, number of night time visits to health service facilities, quantity of inhalation steroids used, amount of oral steroids used at fixed intervals, peripheral eosinophil count, serum eosinophil cationic protein (ECP) concentration and FEV1.0. In Group I, the frequency of beta 2-stimulant inhalation, number of night time visits to health service facilities, quantity of inhalation steroids used, and the amount of oral steroids used at fixed intervals were reduced; and after two years, the frequency of beta 2-stimulant inhalation and quantity of inhalation steroids used were further reduced. In Group II, reductions were seen in the peripheral eosinophil count and serum ECP level. The asthmatic severity shifted from step 3 to 2 in 12 patients and from step 4 to 3 in 4 patients in Group I; and from step 3 to 2 in 3 patients in Group II. In Group III, an increase in the number of night time visits to health service facilities after the medication was interrupted and a rise in the serum ECP concentration were recognized.