法莫着丁活动性十二指肠溃疡的疗效比较

法莫替丁(famotidine)是一种含有脒丙基噻唑环的长效强力 H_2受体阻滞剂,作用较西米替丁强20～160倍,较雷尼替丁强3～20倍;抑制分泌的作用时间也较西米替丁和雷尼替丁长,服用法莫替丁10mg之后,其抑制分泌作用可持续12h 以上。现已证实法莫替丁是一种安全可靠的新型长效 H_2受体阻滞剂.方法本文以双盲随机安慰剂对照的方法,对384例活动性十二指肠溃疡进行对照研究。全部患者均经内窥镜确诊,溃疡直径为0.5～2.5cm.随机分为4组:第1组,早晨服安慰剂一次,睡前服法莫替丁     

重组甘精胰岛素联合阿卡波糖治疗老年2型糖尿病临床观察

甘精胰岛素是第一个模拟人生理基础胰岛素分泌的长效人胰岛素类似物.作用平稳。血药浓度无峰值,能有效、平稳地降低血糖[1-2]。注射时间灵活,低血糖(尤其是夜间低血糖)发生率低[3]。阿卡波糖通过竞争性抑制α-葡     

生长抑素对上消化道出血的治疗作用

生长抑素是一种环状多肽类激素 ,广泛存在于人类的胃肠道及中枢神经系统 ,其中胃肠道含量占 70 %。生长抑素主要作用为抑制生长激素和胃肠激素的分泌 ,抑制消化液的分泌及胃肠运动。生长抑素作为临床用药 ,目前主要有两种 :一是生长抑素长效类似物生长抑素 8肽 (善得定 ,奥曲肽     

胰高血糖素样肽1的胰腺外作用研究进展

胰高血糖素样肽1(GLP-1)是体内重要的肠肽激素,在调节体内葡萄糖稳态中起重要作用.它通过促进胰岛素分泌、抑制胰高血糖素产生以及减慢餐后胃排空降低血糖.在胰腺外组织它也可通过调节葡萄糖代谢来参与全身血糖的调节.一方面通过激活磷脂酰肌醇3激酶、蛋白激酶B、蛋白激酶C、1型蛋白磷酸酶和丝裂原活化蛋白酶等增加糖原合酶a活性,促进糖原合成和糖利用.另一方面,在脂肪组织直接促进葡萄糖利用或增强胰岛素对葡萄糖的利用.此外,GLP-1还具有其它生物学作用包括舒张血管、保护血管内皮功能并激活垂体前叶激素分泌等.exendin-4是GLP-1的长效类似物,具有比GLP-1更持久的生物学活性和更强的降血糖作用,是一种治疗2型糖尿病的新型药物.     

脱氢表雄酮抗动脉粥样硬化机制的研究进展

随衰老而降低的脱氢表雄酮具有抗动脉粥样硬化作用.它可能具有调脂作用、抑制血管平滑肌细胞增殖作用、抗血小板聚集、抑制胶原和胶原基因表达、抑制从单核细胞分泌的白细胞介素6、对抗高胰岛素血症、提高细胞钙离子反应和血管松弛性而起抗动脉粥样硬化作用.     

胰高糖素样肽-1及其类似物和二肽酰肽酶-Ⅳ抑制剂对胰岛功能的保护作用

胰岛β细胞功能受损是2型糖尿病发病的中心环节.随着病程的进展,多种机制参与导致β细胞功能进行性下降.胰高糖素样肽-1(GLP-1)是由肠道内分泌细胞L细胞分泌的肠促胰岛素,可以葡萄糖依赖性地增加胰岛素分泌、促进胰岛β细胞再生并抑制胰高糖素分泌.长效GLP-1类似物和二肽酰肽酶(DPP)-Ⅳ抑制剂能够减少内源性GLP-1在体内降解,从而更有效地保护胰岛β细胞功能,对于糖尿病的防治具有重要意义.     

胰升糖素样肽-1的研究进展

胰升糖素样肽-1(GLP-1)是由肠道内分泌L细胞分泌的肠促胰岛素,具有促进胰岛素分泌、胰岛细胞生长、增殖和分化并抑制胰岛β细胞凋亡等多种作用,可用来预防和治疗糖尿病,辅助进行胰岛细胞移植,且不引起体重增加和低血糖。但GLP-1可很快被二肽基肽酶Ⅳ降解,限制了其临床应用。目前对长效的GLP-1类似物、二肽基肽酶Ⅳ抑制剂和GLP-1基因治疗的研究已成为热点。     

白细胞介素Ⅰ的胃肠道生物学效应

白细胞介素Ⅰ(IL-Ⅰ)具有细胞保护功能,可防止乙醇等所致的冒粘膜损害;具有抑制胃分泌作用,可通过中枢、局部使胃液、胃酸分泌减少,因此有抗溃疡作用。此外,还有抑制胃排空,抑制摄食行为等作用。提示IL-Ⅰ在一些胃肠疾病的发生发展中可能起重要作用。     

关于应用基础胰岛素控制空腹高血糖的问题

空腹高血糖发生原因主要有:(1)基础胰岛素分泌和敏感性减低;(2)黎明现象;(3) Somogyi反应。睡前皮下注射中效胰岛素(NPH)或长效甘精胰岛素(Glargine)可改善空腹高血糖,消除后半夜高血糖抑制胰岛素分泌和胰岛素敏感性的“糖毒”作用。现报告1例空腹高血糖的诊治情况如下。患     

性激素对脂肪细胞瘦素和脂联素分泌的影响

目的 观察性激素对前脂肪细胞增殖与分化及脂肪细胞瘦素脂联素分泌的影响.方法 原代培养人大网膜前脂肪细胞,观察其增殖、分化过程.性激素作用前脂肪细胞增殖和分化过程,检测瘦素、脂联素分泌及mRNA水平.结果 成功地培养出人大网膜前脂肪细胞.雌二醇促进前脂肪细胞增殖(0.823±0.059对0.276±0.032,P＜0.05)、抑制分化(P＜0.05);睾酮对前脂肪细胞增殖无明显作用,但抑制分化(P＜0.05).前脂肪细胞增殖及分化期均分泌瘦素.雌二醇促进瘦素分泌,而睾酮抑制(均P＜0.05).脂联素仅在分化期分泌,且性激素抑制其分泌.雌二醇促进瘦素mRNA表达但抑制脂联素mRNA表达;睾酮抑制瘦素、脂联素mRNA表达(均P＜0.05).结论 雌二醇促进脂肪细胞瘦素分泌及mRNA表达,抑制脂联素分泌及mRNA表达;睾酮抑制二者分泌及mRNA表达.     

规律吸入噻托溴铵对慢性阻塞性肺疾病稳定期患者的长期疗效

噻托溴铵是一种长效的吸入型支气管扩张剂,通过选择性地拮抗M3受体发挥作用,吸入一次,疗效可维持24 h以上.目前已有的临床证据表明,规律使用该药对中、重度慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)具有良好疗效,除了改善肺功能参数外,它在改善呼吸困难、生活质量、减少急性加重次数和住院次数方面要优于安慰剂、异丙托溴胺和长效β2受体激动剂.本品用药方便,安全性好,可作为一线和基础药物长期用于稳定期COPD患者.噻托溴铵的远期疗效及其与其他药物联合治疗的作用还有待进一步研究.     

Tiotropium Bromide

Tiotropium bromide (Spiriva) is a long-acting anticholinergic bronchodilator that maintains bronchodilation for at least 24 hours, allowing once-daily administration. The active moiety is the tiotropium cation (tiotropium); tiotropium bromide 22.5 micrograms is equivalent to 18 micrograms of tiotropium cation. Greater improvements in lung function from baseline (primary endpoint mean trough FEV(1)) were observed with inhaled tiotropium 18 micrograms once daily than with placebo in 6-month and 1-year randomized, double-blind trials in patients with COPD. Tiotropium improved lung function (trough FEV(1) response) more effectively than ipratropium bromide (ipratropium) 40 micrograms four times daily in 1-year clinical trials, and was at least as effective as salmeterol 50 micrograms 12-hourly in 6-month trials. Preliminary data suggest that tiotropium alone or in combination with once-daily formoterol has a greater bronchodilator effect than twice-daily formoterol in patients with COPD. Improvements in patients' perception of health-related quality of life (HR-QOL) or dyspnea were greater with tiotropium than with placebo or ipratropium, and were similar to those with salmeterol. Reductions in the frequency and severity of acute exacerbations and in the use of rescue medication were also greater with tiotropium than with ipratropium or placebo. There was no evidence of tachyphylaxis with tiotropium during 1-year clinical trials. Inhaled tiotropium was generally well tolerated in clinical trials. Apart from dry mouth, the type and incidence of adverse events with tiotropium were similar to those with ipratropium, salmeterol or placebo in patients with COPD. In conclusion, inhaled tiotropium 18 micrograms once daily improved lung function, dyspnea, and HR-QOL, and decreased the incidence of acute COPD exacerbations and the use of rescue medication relative to placebo or ipratropium in clinical trials in patients with COPD. Tiotropium was at least as effective as salmeterol in terms of bronchodilator efficacy and improvements in dyspnea or HR-QOL. With the exception of dry mouth, the tolerability profile of tiotropium was similar to that with placebo, ipratropium, or salmeterol. Consequently, inhaled tiotropium is likely to be a valuable option for first-line, long-term maintenance therapy in the management of bronchoconstriction in patients with symptomatic COPD. Tiotropium bromide has a quaternary ammonium structure and acts as an anticholinergic bronchodilator; the active moiety is the tiotropium cation (tiotropium). A 22.5 micrograms dose of tiotropium bromide provides 18 micrograms of tiotropium. Orally inhaled tiotropium bromide antagonizes the muscarinic M(1), M(2), and M(3) receptors located in airway smooth muscle, reversing vagally mediated bronchoconstriction. Receptor binding assays and in vitro tests indicate that tiotropium bromide is kinetically selective for M(1) and M(3) receptors over the M(2) receptor, unlike ipratropium bromide, which is nonselective. Animal and in vitro studies showed that tiotropium bromide was more potent ( approximate, equals 20-fold) than ipratropium bromide in displacing [(3)H]N-methylscopolamine (NMS) from muscarinic receptors, and had a more sustained protective effect (>70% inhibition) against NMS binding. Tiotropium bromide was a more potent inhibitor of bronchial contraction than atropine ( approximate, equals 23-fold), and had a slower onset and markedly longer duration of action than atropine or an equipotent dose of ipratropium bromide. Aerosol particle penetration is improved with tiotropium, without delaying mucus clearance from the lungs. Tiotropium 4.5-36 micrograms once daily for 4 weeks increased mean trough and average FEV(1) and FVC and mean PEFR values from baseline compared with placebo, with no evidence of tachyphylaxis. Improvements in trough FEV(1) from baseline with tiotropium 4.5-36 micrograms were not dose dependent. Based on a lack of dose response, the optimal once-daily tiotropium dosage is 18 micrograms. Steady-state trough FEV(1) values are achieved within 48 hours of commencing tiotrochodilation (for >/=24 hours) and an attenuation of the nocturnal decline in FEV(1) that were unaffected by timing of the daily tiotropium dose were seen in randomized, double-blind, placebo-controlled studies in patients with stable COPD. The drug improved static and dynamic lung hyperinflation (evidenced by reduced trapped air volume and increased tidal volume and end-of-exercise inspiratory capacity), and improved exertional dyspnea (during activities of daily living and exertion) and exercise tolerance compared with placebo in randomized, double-blind studies. In patients with stable COPD, improved sleep-related oxygen desaturation that was unaffected by the timing of the daily dose was seen with tiotropium but not with placebo. Clinically significant treatment-related disorders of conduction or rhythm, or changes in heart rate were not observed with tiotropium in this patient group. Mean maximal plasma concentrations (C(max)) were observed within 5 minutes of inhalation of a single dose of tiotropium 18 micrograms in patients with COPD. Plasma drug levels declined to minimum concentrations (C(min)) within 1 hour of treatment in healthy volunteers. Mean steady-state C(max) concentrations (16 ng/L) were achieved after 2-3 weeks of once-daily inhaled tiotropium 18 micrograms in elderly patients with COPD; tiotropium does not appear to accumulate once steady-state has been achieved.The estimated absolute bioavailability of tiotropium at steady state in healthy volunteers was approximately 20-25%, and approximately 72% of the drug is bound to plasma proteins. Excretion of tiotropium is predominantly renal (through active secretion by the kidneys), although in vitro studies suggest that cytochrome P450 (CYP) oxidation (possibly involving CYP2D6 and CYP3A4 enzymes) may have a minor role. In patients with COPD, renal excretion of the unchanged drug at 24 hours (Ae(24)) was approximately 7%. The mean plasma elimination half-life after single or multiple doses in healthy volunteers and elderly patients with COPD was approximately 5-6 days. The renal clearance and urinary excretion of tiotropium decrease with increasing age; however, these changes are not considered to be clinically significant. Because of altered steady-state C(max), C(min), area under the concentration-time curve, and Ae(24) values, caution is required with tiotropium administration in patients with moderate-to-severe renal impairment. The pharmacokinetics of tiotropium in patients with severe renal or hepatic impairment have not been studied. Tiotropium does not interact with drugs such as cimetidine or ranitidine, which are also eliminated by active renal secretion. Orally inhaled tiotropium bromide has been evaluated as a bronchodilator for the management of patients with COPD in randomized, double-blind 6-month and 1-year trials, and in several shorter studies. In clinical trials, COPD was diagnosed according to the American Thoracic Society guidelines. The bronchodilator effect was expressed as the trough FEV(1) response (the mean change in FEV(1) from baseline measured 1 hour prior to and immediately before a scheduled dose), and was the primary endpoint in all but two clinical trials. The bronchodilator effect with tiotropium 18 micrograms once daily was superior to that with placebo in several well designed trials in patients with COPD. Moreover, greater improvements in mean peak and average FEV(1) responses occurred with tiotropium but not with placebo. Mean trough, peak, and average FVC responses, and weekly mean morning and evening PEFR values were also improved to a greater extent with tiotropium than with placebo. Tiotropium demonstrated a greater bronchodilator effect than ipratropium bromide (hereafter referred to as ipratropium when used at approved dosages) 40 micrograms four times daily in two 1-year trials in patients with COPD. Mean peak and average FEV(1), mean trough FVC responses, and weekly mean morning and evening PEFR values were also increased to a greater extent with tiotropium than with ipratropium. In one of the two 6-month trials that compared the efficacy of tiotropium with that of inhaled salmeterol 50 micrograms twice daily, greater improvements from baseline in mean trough, peak, and average FEV(1) and FVC responses were seen with tiotropium than with salmeterol. Increases in weekly mean evening, but not morning, PEFR values were generally greater with tiotropium than salmeterol. In the second trial, improvement in the primary endpoint (mean trough FEV(1) response from baseline) with tiotropium or salmeterol was similar, although peak and average responses were superior with tiotropium. Preliminary results from a 6-week crossover study in patients with COPD suggested that tiotropium alone or in combination with once-daily formoterol improved mean trough and average FEV(1) and trough FVC values from baseline to a greater extent than twice-daily formoterol. More patients achieved a clinically important improvement (increase of >/=1 unit) in the transitional dyspnea index focal score (a measure of dyspnea-related impairment) with tiotropium than with placebo in the 1-year trials. Tiotropium was superior to ipratropium in 1-year trials, and was at least as effective as salmeterol in 6-month trials, in achieving a clinically important improvement in focal scores. Tiotropium recipients experienced fewer COPD exacerbations than placebo or ipratropium recipients and had fewer and shorter COPD-related hospitalizations compared with placebo recipients. Unlike salmeterol, tiotropium lengthened the time to onset of the first exacerbation and decreased the number of exacerbations compared with placebo in two 6-month trials. Similar proportions of tiotropium, salmeterol, and placebo recipients required COPD-related hospitalizations. (ABSTRACT TRUNCATED)     

Therapie der stabilen COPD

Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a systemic disease, especially at advanced disease stages. The very different COPD phenotypes require an individualized therapeutic approach. Bronchodilators remain the basis of long-term therapy. Long-acting ß2-agonists and the long-acting anticholinergic tiotropium led to a further improvement in the management of COPD. Inhaled corticosteroids prevent frequent exacerbations in patients with more severe disease. At GOLD stages III and IV more patients will need evaluation and therapy of conditions such as chronic respiratory failure, myopathy, cardiovascular disease, osteoporosis, depression, and nutritional deficits.     

The role of tiotropium in the management of asthma

Asthma is a chronic respiratory disease characterized by reversible airway obstruction that is secondary to an allergic inflammation and excessive smooth muscle contraction. Cholinergic signals were known to contribute significantly to the pathophysiology of asthma. However, the use of anti-cholinergic agents in asthma has been justified only in acute asthma exacerbations, until tiotropium bromide, a long-acting anti-cholinergic agent was introduced. Recent reports showing a promising role of tiotropium in the treatment of asthma have aroused interest of the use of anti-cholinergic agent for the management of asthma. This report describes pharmacological characteristics, potential effects on inflammatory cells, and the current status of tiotropium in the treatment of asthma.     

NVA237, a long-acting muscarinic antagonist, as an emerging therapy for chronic obstructive pulmonary disease

Bronchodilation with a long-acting muscarinic antagonist (LAMA) or long-acting β(2)-agonist is central to the management of chronic obstructive pulmonary disease (COPD). Tiotropium, the first LAMA available for use in COPD, has been shown to be an effective bronchodilator and is generally safe and well tolerated. However, tiotropium has limitations that include a high incidence of dry mouth, slow onset of action and, in some studies, a part of the patient population did not achieve clinically significant bronchodilation. It also remains unclear whether tiotropium reduces progressive deterioration of lung function in patients with COPD. An ideal LAMA would provide clinically meaningful bronchodilation, deliver symptom relief, prevent disease progression, improve exercise tolerance and health status, prevent and treat complications and exacerbations and reduce mortality risk. A 24-h duration of action, rapid onset of action and a good safety and tolerability profile are also desirable. The once-daily LAMA, NVA237 (glycopyrronium bromide), may meet some of these characteristics. NVA237 has high selectivity for the muscarinic type-3 (M(3)) receptor which might potentially result in a higher therapeutic index than tiotropium, which is less selective for M(3). Phase II studies showed that NVA237 once daily provides clinically significant 24-h bronchodilation with a rapid onset of action and a favourable safety and tolerability profile. Phase III studies are ongoing that will assess the long-term safety and efficacy of NVA237.     

Eletrocardiographic monitoring in COPD patients receiving tiotropium

Tiotropium is a once-daily, inhaled anticholinergic for the treatment of chronic obstructive pulmonary disease that acts as a prolonged antagonist of the M3-receptor. To ascertain whether electrophysiologic effects can be detected following tiotropium treatment in patients with chronic obstructive pulmonary disease, serial electrocardiograms were incorporated into multiple placebo-controlled clinical trials including long-term (6 and 12-month) trials with tiotropium 18 mcg daily (n=2,128) and a 4-week dose-ranging study with tiotropium up to 36 mcg daily (n= 169). In addition, 24-hour electrocardiographic (Holter) monitoring was performed as part of a 6-week, placebo-controlled trial with tiotropium 18 mcg daily (n= 121). Electrocardiograms were performed before and up to 6 times during treatment in the 12-month trials, and before and at the end of treatment in the 6-month trials. For both the 12 and 6-month trials, electrocardiograms were recorded as adverse events if significant changes occurred, and were retrospectively sent for centralized analysis. During the 6-week trial, Holter monitoring was performed prior to the first dose and following 6 weeks of treatment. In all of these trials, no significant differences were observed in any of the electrocardiogram or Holter outcome parameters compared to placebo. Specifically, there was no clinically relevant difference in heart rate, atrio-ventricular conduction or the occurrence of ventricular or supraventricular arrhythmias. In conclusion, tiotropium was not associated with any signs of cardiac safety concerns as defined by electrocardiographic evaluations in placebo-controlled clinical trials.     

The pharmacodynamic effects of single inhaled doses of formoterol, tiotropium and their combination in patients with COPD

The aim of this double-blind, double-dummy, cross-over, randomized, pilot study was to compare the acute bronchodilator efficacy of a single dose of formoterol with that of tiotropium in patients with stable chronic obstructive pulmonary disease (COPD). Because the potential of tiotropium for additive effects is yet unknown, the acute effects of adding this anticholinergic agent to formoterol were also explored. A total of 20 outpatients with stable COPD were enrolled. Single doses of 12 microg formoterol, 18 microg tiotropium, and 12 microg formoterol+18 microg tiotropium were given. Serial measurements of FEV1 were performed over 24 h. Formoterol, either alone or in combination with tiotropium, elicited a significantly faster onset of action and showed a trend for a greater maximum bronchodilation than tiotropium alone. At 24 h, mean FEV1 continued to be significantly higher than pre-dosing value following tiotropium and formoterol+tiotropium. These findings indicate that formoterol and tiotropium have different profiles that make both agents attractive alternatives in the treatment of stable COPD. Since tiotropium ensures prolonged bronchodilation, whereas formoterol adds fast onset and a greater peak effect, the two drugs appear complementary.     

A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease.

Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.     

Long-term treatment benefits with tiotropium in COPD patients with and without short-term bronchodilator responses

OBJECTIVES: To determine whether long-term symptomatic improvement occurs in COPD patients with maintenance bronchodilator therapy despite a nonsignificant short-term improvement in FEV(1) following bronchodilator inhalation obtained at a single time point. METHODS: Data obtained during two identical 1-year, placebo-controlled trials of tiotropium, 18 micro g once daily, were analyzed retrospectively to determine the associations of long-term improvements in lung function and patient health status with short-term improvements in FEV(1), as measured on the first day of treatment. Based on the presence or absence of a short-term improvement in FEV(1) of > or = 12% and > or = 200 mL, respectively, patients who had been treated with tiotropium were characterized as being responsive to tiotropium (TIO-R) or poorly responsive to tiotropium (TIO-PR). RESULTS: Baseline characteristics were similar other than baseline FEV(1), which was higher in the TIO-R group than in both the TIO-PR and placebo groups (p < 0.05). Baseline FEV(1) was 1.08 L in the TIO-R group (n = 263), 0.95 L in the TIO-PR (n = 255), and 0.99 L in the placebo group (n = 328). The mean (+/- SD) morning predose FEV(1) at 1 year significantly (p < 0.001) improved in patients in both of the tiotropium treatment subgroups (TIO-R group, 212 +/- 17 mL; TIO-PR group, 94 +/- 17 mL) relative to those treated with placebo. Statistically significant improvements in both tiotropium-treated groups also were noted over 1 year for dyspnea (p < 0.001), as assessed by the transition dyspnea index (TDI) [TIO-R group, 1.36 +/- 0.23 L; TIO-PR group, 0.86 +/- 0.23 L] relative to the placebo group. Patient health status assessed by the St. George Respiratory Questionnaire (SGRQ) showed statistically significant improvements over placebo for the TIO-R and TIO-PR groups (-3.96 +/- 0.99 and -3.05 +/- 1.00 L, respectively; p < 0.005). There was a significant correlation of the first-dose short-term FEV(1) response to the end-of-trial trough response (r = 0.43), but there was only a weak correlation to TDI focal score (r = 0.17) or SGRQ total score (r= -0.12). CONCLUSIONS: Tiotropium was effective in the treatment of patients with COPD, irrespective of the presence or absence of a short-term response on the first day of treatment. The short-term bronchodilator response should not be used as a definitive criterion for prescribing long-term treatment with inhaled bronchodilators.     

Bronchodilator response to formoterol after regular tiotropium or to tiotropium after regular formoterol in COPD patients

We conducted a randomized, crossover trial with tiotropium 18 microg once daily (group A), and formoterol 12 microg twice daily (group B) over a 5-day period for each drug, with a 10-day washout, in 20 COPD patients. At the end of each period, patients inhaled both drugs separated by 180 min in alternate sequence (group A: tiotropium 18 microg+formoterol 12 microg; group B: formoterol 12 microg+tiotropium 18 microg). FEV1 and FVC were measured at baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. FEV1 and FVC further improved after crossover with both sequences. The mean maximal change in FEV1 over baseline was 0.226 L (0.154-0.298) after tiotropium+formoterol and 0.228 L (0.165-0.291) after formoterol+tiotropium; the mean maximal change in FEV1 over pre-inhalation the second drug value was 0.081 L (0.029-0.133) after tiotropium+formoterol and 0.054 L (0.016-0.092) after formoterol+tiotropium. The mean maximal change in FVC over baseline was 0.519 L (0.361-0.676) after tiotropium+formoterol and 0.495 L (0.307-0.683) after formoterol+tiotropium; the mean maximal change in FVC over pre-inhalation of the second drug value was 0.159 L (0.048-0.270) after tiotropium+formoterol and 0.175 L (0.083-0.266) after formoterol+tiotropium. The FEV1 AUCs(0-360 min) were 62.70 (45.67-79.74) after tiotropium+formoterol and 69.20 (50.84-87.57) after formoterol+tiotropium, the FEV1 AUCs(0-180 min) were 24.70 (18.19-31.21) after tiotropium+formoterol and 29.74 (21.02-38.46) after formoterol+tiotropium, whereas the FEV1 AUCs(180-360 min) were 15.70 (10.88-20.52) after tiotropium+formoterol and 11.71 (7.21-16.21) after formoterol+tiotropium. Differences between the two treatments were not statistically significant (P>0.05). The addition of second different long-acting bronchodilator to a regularly administered long-acting bronchodilator seems to be to patient's advantage.