Addition of Transdermal or Inhaled Long-Acting β 2-Agonists in Adult Asthmatic Patients Treated with Inhaled Corticosteroids: Switchover Study from Tulobuterol Patch to Salmeterol Dry Powder Inhaler

Sixty-four patients with persistent asthma receiving 200 to 800 μ g of fluticasone propionate daily were enrolled in this switchover study. The patients applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by inhalation of salmeterol 100 μ g bid for 4 weeks. The mean values for morning and evening peak expiratory flow improved significantly compared with baseline during the 4 weeks of tulobuterol patch treatment. Further improvement was seen on switching to salmeterol treatment, which was significant even in the first week, and continued until the final week of the study. Use of salmeterol alone resulted in a significant increase in the percentage of forced expiratory volume in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can achieve better control in asthmatic patients after switching from using tulobuterol patches.     

Anti-inflammatory activity of salmeterol: down-regulation of cytokine production.

Elevation of intracellular cAMP levels has been shown previously to inhibit cytokine secretion by various cell types in vitro. Since salmeterol is a beta 2-agonist which activates adenylate cyclase, its ability to inhibit cytokine production was evaluated. Though salmeterol, and the related drug albuterol, did not inhibit IL-1 beta production in vitro, both drugs did inhibit tumour necrosis factor-alpha (TNF-alpha) secretion by lipopolysaccharide (LPS)-activated THP-1 cells with similar IC50s of approximately 0.1 microM. This inhibition was effectively reversed by the beta 2-antagonist oxprenolol, indicating that the inhibition was mediated through the beta 2-adrenergic receptor. A strikingly different reactivity profile was seen with T cells. Salmeterol was able to inhibit the activation of both mouse and human T cells, as measured by proliferation and IL-2 secretion in response to anti-CD3 antibody, whereas albuterol was completely inactive in these assays. This T cell inhibition by salmeterol was about 10-fold less potent than that for TNF-alpha production, and was not reversed by a beta 2-antagonist, indicating that a different mechanism was involved in the effect of salmeterol on T cells. Paralleling the TNF-alpha inhibitory activity in vitro, oral dosing of salmeterol and albuterol inhibited LPS-induced increase in murine serum TNF level in vivo, with ED50s of approximately 0.1 mg/kg. This inhibition could be abrogated by dosing orally with the beta-blocker propranolol. The long-acting pharmacological profile of salmeterol was apparent in that it maintained its efficacy for 3 h, while albuterol had a much shorter duration of action. Salmeterol also had some protective effects in the galactosamine/LPS model of endotoxic shock, which is dependent upon TNF-alpha production. Though salmeterol inhibited serum TNF-alpha levels by up to 94% in this assay, it protected less than 50% of the animals from the lethal effects of the LPS/galactosamine mixture. This observation suggests that functional levels of TNF-alpha localized in tissues may not be accurately reflected by serum levels.     

Acute bronchodilatory effect of salmeterol on methacholine-induced bronchoconstriction in childhood asthma

Abstract A review of the literature highlights the need for research, particularly on the acute bronchodilatory effect of salmeterol on bronchoconstriction in the pediatric age group. The present study attempted to evaluate the acute bronchodilatory effect of salmeterol on methacholine-induced bronchoconstriction in childhood asthma and to compare it with the effect of salbutamol. Forty-four asymptomatic children with mild-to-moderate asthma (23 boys and 21 girls; aged7–17 years) were studied. At the beginning, the baseline forced expiratory volume in 1 s (FEV₁) was measured, and the methacholine challenge was performed by doubling the dose to determine PC₂₀ (provocative concentration of inhaled methacholine required to reduce FEV! by 20%). At the same time, the transcutaneous arterial oxygen saturation (S_ao₂) was also measured. Each subject inhaled a single dose of 25 μ salmeterol (n: 23, group I) or 100 μg salbutamol (n: 21, group II) following the Sp₂ measurement. The same measurements (FEV₁, S_ao₂) were repeated 5 and 20 min after the inhalation. After inhalation of salmeterol or salbutamol, the differences between the values of FEV₁ and S_aO₂ after 5 and 20 min were insignificant in both group I and group II (P > 0.05), although there was a significant improvement in both FEV₁ and S_aO₂ after 5 and 20 min (P < 0.005). From these findings it was concluded that salmeterol can be considered as effective as salbutamol on methacholine-induced bronchoconstriction.     

沙美特罗替卡松粉吸入剂治疗50例中、重度儿童哮喘的疗效

目的 :观察沙美特罗替卡松粉吸入剂在儿童中、重度哮喘治疗中的疗效、安全性。方法 :将 80例中、重度哮喘病儿分成沙美特罗替卡松粉吸入剂治疗组 (治疗组 )和氟替卡松治疗组 (对照组 )。治疗组 5 0例 ,5～ 11a给予沙美特罗替卡松粉吸入剂 5 0μg / 10 0 μg·次 - 1(沙美特罗 5 0 μg,氟替卡松10 0 μg) ,bid。 12～ 14a给予沙美特罗替卡松粉吸入剂 5 0 μg/ 2 5 0 μg·次 - 1,bid。氟替卡松治疗组(对照组 ) 30例 ,5～ 11a给予氟替卡松 12 5 μg·次 - 1,bid。 12～ 14a给予氟替卡松 2 5 0 μg·次 1,tid。2组均连用 6mo ,按需使用沙丁胺醇。结果 :2组平均早、晚最大呼气峰流速值 (PEFam ,PEFpm ) ,需使用沙丁胺醇的日数在 8wk内有显著差异 ,自我评价在 4wk内有显著差异 ,症状评分在 3mo内有显著差异。 2组各有 1例咽部不适 ,经处理后缓解。结论 :沙美特罗替卡松粉吸入剂在儿童中、重度哮喘治疗中具良好的有效性、安全性。     

Addition of Transdermal or Inhaled Long-Acting β 2-Agonists in Adult Asthmatic Patients Treated with Inhaled Corticosteroids: Switchover Study from Tulobuterol Patch to Salmeterol Dry Powder Inhaler

Sixty-four patients with persistent asthma receiving 200 to 800 μ g of fluticasone propionate daily were enrolled in this switchover study. The patients applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by inhalation of salmeterol 100 μ g bid for 4 weeks. The mean values for morning and evening peak expiratory flow improved significantly compared with baseline during the 4 weeks of tulobuterol patch treatment. Further improvement was seen on switching to salmeterol treatment, which was significant even in the first week, and continued until the final week of the study. Use of salmeterol alone resulted in a significant increase in the percentage of forced expiratory volume in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can achieve better control in asthmatic patients after switching from using tulobuterol patches.     

沙美特罗替卡松粉剂吸入治疗70岁以上中、重度AECOPD临床疗效观察

目的 观察沙美特罗替卡松粉剂(舒利迭)吸入用于治疗70岁以上中重度慢性阻塞性肺疾病急性加重期(AECOPD)的疗效.方法 将108例70岁以上中、重度AECOPD患者随机分为沙美特罗/替卡松粉剂吸入组、硫酸沙丁胺醇气雾剂吸入组,对两组治疗前后的FEV1、FEV1/FVC、FEV1占预计值百分比及临床症状改善情况进行比较.结果 使用舒利迭组患者在治疗早期肺功能即有明显改善,随着使用时间延长,肺功能改善得到逐渐提高.使用硫酸沙丁胺醇组,治疗初期,临床症状迅速改善,随着治疗时间延长,疗效有所下降,肺功能无明显改善.结论 舒利迭治疗70岁以上中、重度AECOPD,临床改善明显,能持续改善患者的肺功能.     

Inhibition of Basal and Stimulated Release of Endothelin-1 from Guinea Pig Tracheal Epithelial Cells in Culture by Beta 2-adrenoceptor Agonists and Cyclic AMP Enhancers

The effects of cyclic AMP-related compounds and beta adrenoceptor agonists on the basal and lipopolysaccharide (LPS)-stimulated release of endothelin-1 (ET-1) from guinea-pig tracheal epithelial cells (GPTEpCs) in culture were studied. Forskolin (a potent activator of adenylyl cyclase), 8-bromo-cyclic AMP (a cyclic AMP analogue), salbutamol and salmeterol (two beta 2-adrenoceptor agonists), were used to increase cyclic AMP levels. Cultured GPTEpCs released ET-1 continuously over a 24 h incubation period. The values reached 1,938 ± 122 pg/mg of total cell proteins after 24 h. LPS (10 μg/ml) significantly stimulated the release of ET-1 by 1.6- to 1.8-fold, up to 1,262 ± 56 pg/mg total cell proteins after an 8 h incubation period. Compound 8-bromo-cyclic AMP (10⁻⁵, 10⁻⁴ and 10⁻³ M) reduced the basal release of ET-1 from GPTEpCs by up to 31% (P < 0.01) and the LPS stimulated release by up to 42% (P < 0.05), after an 8 h incubation period. Forskolin (10⁻⁶, 10⁻⁵ and 10⁻⁴ M) also inhibited the basal release of ET-1 by up to 28% (P < 0.05) and LPS-stimulated release of ET-1 by up to 50% (P < 0.05), after an 8 h incubation period. At the concentration of 10⁻⁵ M, forskolin increased cyclic AMP levels in GPTEpCs by 17-fold (P < 0.001) in the medium, 15 min after the beginning of the incubation. Salbutamol (10⁻⁸ to 10⁻⁶ M) had no effect on the basal production and release of ET-1 after 8 h. Conversely, this short acting beta 2-adrenoceptor agonist significantly reduced LPS-mediated increase of ET-1 production by up to 55% (P < 0.05) after an 8 h incubation period. Salmeterol (10⁻⁹ M to 10⁻⁵ M) inhibited basal and LPS-stimulated production and release of ET-1 after an 8 h incubation period (between 44 and 51%, P < 0.01). Both salbutamol and salmeterol (10⁻⁶ M) increase cyclic AMP levels by five- and twofold, respectively (P < 0.05). In summary, these observations indicate that beta 2-adrenoceptor agonists or cyclic AMP enhancers can modulate both basal and more markedly, the enhanced production of ET-1 from LPS-activated guinea pig airway EpCs. In addition, these compounds increase cyclic AMP levels in the cells. It is suggested that there is a correlation between cyclic AMP increase and inhibition of ET-1 release by guinea pig airway EpCs. Since ET-1 production was shown to be elevated in asthmatic subjects and in patients suffering from other inflammatory lung disorders, the inhibition of its production by beta adrenoceptor agonists, such as salbutamol and salmeterol, could be added to their therapeutical benefits.     

噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病急性加重期伴呼吸衰竭的临床研究

目的观察噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病(COPD)急性加重期伴呼吸衰竭的临床疗效及安全性。方法将76例COPD急性加重期伴呼吸衰竭患者随机分为对照组38例和试验组38例。对照组予以常规治疗配合呼吸机辅助通气治疗;试验组在对照组治疗的基础上,予以沙美特罗替卡松粉吸入剂每次1吸,bid,吸入治疗+噻托溴铵粉雾剂每次18μg,qd,吸入治疗。2组患者均治疗2周。比较2组患者的临床疗效、动脉血气指标、降钙素原和免疫功能,以及药物不良反应的发生情况。结果治疗后,试验组和对照组的总有效率分别为92.11%(35例/38例)和73.68%(28例/38例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的动脉血氧分压分别为(86.35±7.04)和(77.49±6.85)mm Hg,氧合指数分别为(310.89±29.87)和(281.34±27.53)mm Hg,降钙素原分别为(1.42±0.54)和(1.93±0.61)ng·m L^-1,肿瘤坏死因子-α分别为(275.49±48.62)和(310.05±54.73)ng·L^-1,白细胞介素-8分别为(312.62±75.64)和(389.75±78.76)pg·m L^-1,超敏C-反应蛋白分别为(4.73±2.45)和(8.34±2.53)mg·L^-1,差异均有统计学意义(均P<0.05)。2组患者治疗期间均未发生药物不良反应。结论噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗COPD急性加重期伴呼吸衰竭的临床疗效确切,其能显著降低患者的降钙素原水平,改善患者的血气指标和免疫功能,且安全性较好。     

噻托溴铵联合沙美特罗/氟替卡松对老年支气管哮喘患者肺通气功能的改善

目的：探讨联合吸入噻托溴铵和沙美特罗/氟替卡松对老年支气管哮喘患者肺通气功能的影响。方法：将本院呼吸内科100例确诊为支气管哮喘的患者随机分为吸入噻托溴铵和沙美特罗/氟替卡松治疗组43例,沙美特罗/氟替卡松组29例,噻托溴铵组28例。治疗6个月后,观察治疗疗效、治疗前后肺功能变化及治疗后肺功能改善率。结果：联合吸入噻托溴铵和沙美特罗/氟替卡松组的总有效率为88.4%,明显高于噻托溴铵组的67.9%和沙美特罗/氟替卡松组的72.4%,差异具有统计学意义,P〈0.05。同时联合吸入噻托溴铵和沙美特罗/氟替卡松组的肺功能改善率高于其他两组,改善更显著,差异具有统计学意义。结论：噻托溴铵联合沙美特罗/氟替卡松能明显改善支气管哮喘患者肺通气功能,疗效显著。