Potential for long-acting muscarinic antagonists in chronic obstructive pulmonary disease

Importance of the field: The prevention and relief of symptoms by regular use of bronchodilators is central to the pharmacological management of chronic obstructive pulmonary disease (COPD).

Areas covered in this review: The aim of this article is to review the effects of inhaled muscarinic antagonists in the treatment of stable COPD.

What the reader will gain: An update of the clinical studies performed with the long-acting inhaled muscarinic antagonist (LAMA) tiotropium bromide in patients with COPD is given. In recent years, combinations of a LAMA and a long-acting inhaled beta2-agonist (LABA), and ‘triple therapy’ consisting of a LAMA, a LABA, and an inhaled steroid are being developed. Issues of safety of inhaled anticholinergics in COPD are discussed and a short overview of new LAMAs being developed for COPD is given.

Take home messages: The importance of anticholinergic drug treatment in COPD was largely advanced by the development of the first LAMA, tiotropium bromide. The vast experience obtained with tiotropium bromide has paved the way for new LAMAs such as aclidinium bromide and glycopyrrolate (NVA-237).     

Safety and pharmacological profile of tiotropium bromide

Background: Chronic obstructive pulmonary disease (COPD) is associated with progressive airflow obstruction and is characterized by a high risk of morbidity and mortality. With early detection and treatment, the natural history of this disease may be improved. So far, bronchodilator therapy is the most important treatment for COPD. Tiotropium is a bronchodilator of recent introduction. Objective: To discuss the clinical data on the safety and efficacy of tiotropium, a very long-acting antimuscarinic drug, available at present. Methods: The Cochrane trial database, Medline, Embase, were searched systematically, and ～ 20 respiratory journals and conference abstracts were searched manually. Language of publication was limited to English. included tiotropium, COPD, anticholinergic, safety and adverse events. Conclusion: A large body of evidence is available at present on the safety and efficacy of tiotropium in COPD, with dry mouth being the most common adverse event. Reviews of serious adverse event data in the literature have reported that tiotropium is safe and that the incidence of these events is the same as with placebo. Tiotropium is a convenient treatment for COPD with a good clinical efficacy and safety profile.     

长、短效抗胆碱能药物对轻中度稳定期COPD患者的疗效比较

目的:比较异丙托溴铵气雾剂、噻托溴铵干粉剂治疗轻、中度稳定期慢性阻塞性肺疾病(COPD)患者的疗效。方法:采用随机、单盲、平行对照试验设计,将42例稳定期COPD患者,随机分为噻托溴铵组(每次18μg,qd,吸入)和异丙托溴铵组(每次40μg,qid,吸入),2组疗程均为12周。结果:治疗6周末,2组间肺功能比较差异无统计学意义(P>0.05);治疗12周末,噻托溴铵组第1秒用力肺活量(FEV1)、吸气峰流速(PEF)明显改善,与异丙托溴铵组比较,差异有统计学意义(P<0.05);噻托溴铵组症状评分、机体状况评分及精神状态评分均较异丙托溴铵组显著下降(P<0.05)。结论:噻托溴铵较异丙托溴铵更能改善轻、中度稳定期COPD患者的肺功能,并提高患者的生活质量。     

Tiotropium bromide

Tiotropium bromide is a new long-lasting anticholinergic drug which, like ipratropium bromide, is a quaternary ammonium derivative. It binds with high affinity to muscarinic receptors but dissociates very slowly from M₁- and M₃-muscarinic receptors. Pharmacology studies have demonstrated a prolonged protective effect against cholinergic agonists and cholinergic nerve stimulation in animal and human airways. In Phase II studies single inhaled doses of tiotropium bromide have a bronchodilator and bronchoprotective effect in asthmatic and chronic obstructive pulmonary disease (COPD) patients of over 24 h. In Phase III studies, once daily inhaled tiotropium is an effective bronchodilator in COPD patients, giving great improvement in lung function and reduction in symptoms than ipratropium bromide given four times daily. The drug is well-tolerated and the only side effect of note is dryness of the mouth which occurs in approximately 10% of patients. Since, anticholinergics are the bronchodilators of choice in COPD it is likely that tiotropium bromide will become the most widely used bronchodilator for COPD patients in the future.     

Tiotropium bromide,a new,once-daily inhaled anticholinergic bronchodilator for chronic-obstructive pulmonary disease

Tiotropium bromide is a quaternary ammonium compound structurally related to ipratropium and has recently been approved in the US for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic-obstructive pulmonary disease (COPD). It is available in a dry powder form, where 18 mg of the drug is inhaled once-daily through a device, the HandiHaler^®. The potency and long duration of effect of this anticholinergic bronchodilator result primarily from a prolonged blockade of the M₁ and M₃ muscarinic receptors in the airways and a relatively more rapid dissociation from the M₂ receptor (which provides inhibitory feedback). Multiple studies of up to a duration of 1 year have demonstrated its effectiveness as a bronchodilator for COPD, with a trough increase (measured ～ 24 h after administration of the drug) in forced expiratory volume in 1 s of ～ 0.12 l and a peak increase of ～ 0.25 l. Tiotropium inhalation also leads to a significant reduction in static lung volumes in hyperinflated patients with COPD; this probably contributes to the reduction in dyspnoea that is associated with long-term use of this maintenance bronchodilator. Regular use of the drug was associated with clinically meaningful increases in the Transitional Dyspnoea Index, which indicate reductions in dyspnoea associated with daily activities. Improvement in the respiratory-specific health status questionnaire, the St George’s Respiratory Questionnaire component and total scores was also documented. Finally, pooled data from two 1-year studies and two 6-month studies documented 20 and 28% reductions in the number of exacerbations per patient per year. Side effects have been relatively minimal, with dry mouth the most common symptom, ranging 6 – 16% of patients and rarely leading to discontinuation of the study drug. Limited comparisons of efficacy with other bronchodilators are available. Once-daily tiotropium has been demonstrated to be clearly superior to ipratropium four times daily as a bronchodilator for COPD. Combined results from two studies comparing once-daily tiotropium to twice-daily inhalation of standard doses of salmeterol, indicate a magnitude of the bronchodilator response similar in the two drugs early in the study. However, by 6 months, the bronchodilator effect of tiotropium was somewhat greater than that of the long-acting β-agonist. Preliminary data suggest that combining tiotropium with long-acting β-agonists may produce additional bronchodilator action in COPD.     

Once-daily glycopyrronium bromide (Seebri Breezhaler®) for the treatment of chronic obstructive pulmonary disease (COPD)

Introduction: Long-acting bronchodilators are the mainstay of pharmacological therapy for patients with chronic obstructive pulmonary disease (COPD). The choice of optimal bronchodilator therapy for COPD is increasingly difficult for clinicians as new treatments are marketed.Areas covered: Inhaled glycopyrronium bromide (Seebri Breezhaler®) is a well-tolerated long-acting anti-muscarinic agent (LAMA) with a fast onset of action. In patients with moderate to severe COPD, glycopyrronium bromide has clinically important effects on level of FEV₁, use of relief medication, day-time dyspnea scores, and probably also on health status. Furthermore, glycopyrronium bromide also has beneficial effects on dynamic hyperinflation and, probably by that, exercise tolerance. Glycopyrronium bromide has been shown to reduce the rate of exacerbations in patients with moderate to severe COPD, although as a secondary outcome only. Expert opinion: Once-daily inhaled glycopyrronium bromide has positive impact on important COPD outcomes, comparable to the effects of other marketed LAMAs. Once-daily administration may improve adherence, and glycopyrronium bromide has the potential for a role in the future management of COPD similar to that of other long-acting anti-muscarinic agents, including tiotropium. Studies of glycopyrronium bromide with exacerbation rate as the primary outcome of interest is needed.     

Tiotropium therapy and mortality risk in COPD patients: the most severe,the most protected?

Importance of the field: Tiotropium bromidum is an inhaled long acting anticholinergic used as first line monotherapy in stable COPD due to its beneficial effects on the lung function, respiratory symptoms, quality of life or disease morbidity. However there is limited data on its effects on mortality.

Areas covered in this review: The results of the UPLIFT (Understanding Potential Long-Term Impacts on Function with Tiotropium) study evaluating the effects of 4 year therapy with tiotropium on above mentioned outcomes including mortality.

What the reader will gain: Tiotropium demonstrated an uniform beneficial effect on mortality risk reduction but subset analyses yielded relevant results as well.

Take home message: On long-term basis tiotropium therapy can reduce mortality rate overall and can exert such protective effects in various subsets such as patients with very severe COPD.     

Tiotropium bromide inhalation powder: a review of its use in the management of chronic obstructive pulmonary disease

The anticholinergic agent tiotropium bromide (Spiriva?) is a long-acting bronchodilator that is indicated for the treatment of chronic obstructive pulmonary disease (COPD). This article reviews the clinical efficacy and tolerability of tiotropium bromide inhalation powder, administered using the HandiHaler? device, in patients with COPD, as well as reviewing its pharmacological properties and the results of pharmacoeconomic analyses. Shorter-term placebo-controlled trials in patients with COPD demonstrated significantly higher trough forced expiratory volume in 1 second (FEV(1)) responses with tiotropium bromide than with placebo, confirming it has a duration of action of ≥24 hours and is suitable for once-daily administration. Lung function improved to a greater extent with tiotropium bromide than with ipratropium bromide or, in most instances, salmeterol. Indacaterol was shown to be noninferior to tiotropium bromide in terms of the trough FEV(1) response. The large, 4-year UPLIFT? trial did not show a significant reduction in the annual rate of decline in FEV(1) with tiotropium bromide versus placebo in patients with COPD, although subgroup analyses demonstrated a significantly lower rate of decline with tiotropium bromide than with placebo in some patient groups (e.g. patients with moderate COPD, patients aged ≥50 years, patients not receiving maintenance therapy at baseline). Tiotropium bromide prevented exacerbations in patients with COPD, with a significantly lower exacerbation rate and a significantly longer time to first exacerbation seen with tiotropium bromide than with placebo or salmeterol. Exacerbation rates did not significantly differ between patients receiving tiotropium bromide and those receiving salmeterol/fluticasone propionate. Tiotropium bromide also had beneficial effects on health-related quality of life (HR-QOL) and other endpoints, such as dyspnoea and rescue medication use. Combination therapy with tiotropium bromide plus formoterol with or without budesonide improved lung function to a significantly greater extent than tiotropium bromide alone in patients with COPD. In addition, exacerbation rates were lower and HR-QOL was improved with tiotropium bromide plus budesonide/formoterol versus tiotropium bromide alone. Although the addition of salmeterol/fluticasone propionate to tiotropium bromide did not reduce the COPD exacerbation rate, it did improve lung function and HR-QOL. Tiotropium bromide inhalation powder is generally well tolerated in patients with COPD, with anticholinergic adverse events (e.g. dry mouth, constipation, gastrointestinal obstruction, dysuria) among the most commonly reported adverse events. The UPLIFT? trial showed no significant difference between tiotropium bromide and placebo recipients in the risk of stroke, and the risk of serious cardiac adverse events (including congestive heart failure and myocardial infarction) was significantly lower with tiotropium bromide than with placebo. The absence of a detrimental effect on cardiovascular outcomes was supported by the results of a meta-analysis and pooled analyses. In addition, on-treatment mortality was lower with tiotropium bromide than with placebo in the UPLIFT? trial. Pooled analyses showed significantly lower cardiovascular mortality with tiotropium bromide than with placebo, with a meta-analysis demonstrating no significant difference between patients receiving tiotropium bromide and controls in cardiovascular mortality. Results of modelled pharmacoeconomic analyses conducted from a healthcare payer perspective in several developed countries suggest that tiotropium bromide is a cost-effective option in patients with COPD. In conclusion, tiotropium bromide inhalation powder is a useful option for the maintenance treatment of patients with COPD.     

Tiotropium: an inhaled anticholinergic for chronic obstructive pulmonary disease.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, dosage and administration, and formulary considerations of tiotropium are discussed. SUMMARY: Tiotropium, a long-acting inhaled anticholinergic, recently received approval from the Food and Drug Administration for the management of chronic obstructive pulmonary disease (COPD). In patients with COPD, increased parasympathetic nervous system activity leads to bronchoconstriction and mucus secretion. Tiotropium induces relaxation of the airway smooth muscle, as does ipratropium, but differs in receptor association and dissociation rates, allowing for once-daily administration. After inhalation, tiotropium reaches maximal plasma concentrations within five minutes, but clinical improvements in forced expiratory volume in one second (FEV(1)) are maintained over 24 hours. Clinical trials of tiotropium with placebo, ipratropium, and salmeterol have demonstrated the efficacy of tiotropium in improving FEV(1) and forced vital capacity values and health-related quality of life. The most commonly observed adverse effect is dry mouth. No increase in adverse effects was observed when tiotropium was administered concomitantly with other drugs for COPD, including sympathomimetic bronchodilators and oral and inhaled corticosteroids. The combination of tiotropium and other anticholinergics has not been studied and is not recommended. The recommended dosage of tiotropium is the inhalation of an 18-mug capsule with a HandiHaler breath-actuated inhalation device once daily. CONCLUSION: Tiotropium appears to be at least as effective as currently available alternatives in the treatment of patients with COPD who require daily bronchodilator treatment. Its simplified dosing and tolerable adverse-effect profile can potentially lead to enhanced patient compliance.     

Tiotropium bromide: a novel once-daily anticholinergic bronchodilator for the treatment of COPD

Tiotropium bromide (Spiriva, BA679BR, Boehringer Ingelheim) is a novel inhaled, long-acting anticholinergic bronchodilator that is employed as a once-daily maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). Like ipratropium bromide, tiotropium bromide is a quaternary ammonium derivative that binds to muscarinic receptors. However, although tiotropium binds with high affinity to muscarinic receptors of M1-, M2- and M3-subtypes, it dissociates very slowly from M1- and M3-receptors but more rapidly from M2-receptors, thereby giving it a unique kinetic selectivity. To date, the short-acting anticholinergic agents ipratropium and oxitropium bromide have been extensively employed as bronchodilator therapy for patients with COPD. Indeed, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy emphasises the role of bronchodilators in symptomatic management of all stages of COPD. It is encouraging that tiotropium given once daily from a dry powder inhaler at 18 g has been shown to cause greater improvement in lung function and reduction in symptoms than ipratropium bromide given four times daily. Furthermore, clinical studies over a 1-year period have demonstrated that tiotropium has impressive and maintained effects on lung function, symptoms and health-related quality of life, and may also reduce exacerbations. In a recent large scale comparative study over 6 months, tiotropium has been shown to cause superior bronchodilation and symptomatic improvement when compared to twice daily salmeterol in COPD. The only significant reported adverse event is dry mouth, which is found in approximately 10%-15% of subjects, but this is reversible and rarely causes discontinuation of therapy. Based on these promising features, it is likely that tiotropium used alone or in combination with other bronchodilators will emerge as first-line maintenance treatment for patients with airway obstruction due to COPD.     

Tiotropium bromide

Tiotropium bromide is a new long-lasting anticholinergic drug which, like ipratropium bromide, is a quaternary ammonium derivative. It binds with high affinity to muscarinic receptors but dissociates very slowly from M(1)- and M(3)-muscarinic receptors. Pharmacology studies have demonstrated a prolonged protective effect against cholinergic agonists and cholinergic nerve stimulation in animal and human airways. In Phase II studies single inhaled doses of tiotropium bromide have a bronchodilator and bronchoprotective effect in asthmatic and chronic obstructive pulmonary disease (COPD) patients of over 24 h. In Phase III studies, once daily inhaled tiotropium is an effective bronchodilator in COPD patients, giving great improvement in lung function and reduction in symptoms than ipratropium bromide given four times daily. The drug is well-tolerated and the only side effect of note is dryness of the mouth which occurs in approximately 10% of patients. Since, anticholinergics are the bronchodilators of choice in COPD it is likely that tiotropium bromide will become the most widely used bronchodilator for COPD patients in the future.     

Olodaterol + tiotropium bromide for the treatment of chronic obstructive pulmonary disease

A solid scientific rationale and an increasing body of clinical evidence for combining a β₂-agonist with an antimuscarinic agent in COPD fully support the opinion that patients not controlled by a single bronchodilator should be given two bronchodilators with different mechanisms of action. Tiotropium is an established choice for the management of patients with stable COPD, and olodaterol is a new effective and safe once-daily long-acting β2-agonist. The parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The large ongoing TOviTO Phase III trial program is documenting the efficacy and safety of olodaterol/tiotropium fixed dose combination delivered via the Respimat Soft Mist Inhaler as maintenance therapy in patients with moderate to very severe COPD. However, we must still know whether this fixed-dose combination will affect exacerbations and hospitalizations, and ultimately death, and also the precise estimates of its relative cardiovascular safety.     

Tiotropium bromide, a new, once-daily inhaled anticholinergic bronchodilator for chronic-obstructive pulmonary disease

Tiotropium bromide is a quaternary ammonium compound structurally related to ipratropium and has recently been approved in the US for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic-obstructive pulmonary disease (COPD). It is available in a dry powder form, where 18 microg [corrected] of the drug is inhaled once-daily through a device, the HandiHaler). The potency and long duration of effect of this anticholinergic bronchodilator result primarily from a prolonged blockade of the M1 and M3 muscarinic receptors in the airways and a relatively more rapid dissociation from the M2 receptor (which provides inhibitory feedback). Multiple studies of up to a duration of 1 year have demonstrated its effectiveness as a bronchodilator for COPD, with a trough increase (measured approximately 24 h after administration of the drug) in forced expiratory volume in 1 s of approximately 0.12 l and a peak increase of approximately 0.25 l. Tiotropium inhalation also leads to a significant reduction in static lung volumes in hyperinflated patients with COPD; this probably contributes to the reduction in dyspnoea that is associated with long-term use of this maintenance bronchodilator. Regular use of the drug was associated with clinically meaningful increases in the Transitional Dyspnoea Index, which indicate reductions in dyspnoea associated with daily activities. Improvement in the respiratory-specific health status questionnaire, the St George's Respiratory Questionnaire component and total scores was also documented. Finally, pooled data from two 1-year studies and two 6-month studies documented 20 and 28% reductions in the number of exacerbations per patient per year. Side effects have been relatively minimal, with dry mouth the most common symptom, ranging 6 - 16% of patients and rarely leading to discontinuation of the study drug. Limited comparisons of efficacy with other bronchodilators are available. Once-daily tiotropium has been demonstrated to be clearly superior to ipratropium four times daily as a bronchodilator for COPD. Combined results from two studies comparing once-daily tiotropium to twice-daily inhalation of standard doses of salmeterol, indicate a magnitude of the bronchodilator response similar in the two drugs early in the study. However, by 6 months, the bronchodilator effect of tiotropium was somewhat greater than that of the long-acting beta-agonist. Preliminary data suggest that combining tiotropium with long-acting beta-agonists may produce additional bronchodilator action in COPD.     

Tiotropium for chronic obstructive pulmonary disease

In 2001, we concluded that patients with symptoms of stable chronic obstructive pulmonary disease (COPD) inadequately controlled by an 'as-required' inhaled short-acting beta 2 agonist can be helped by regular use of an inhaled antimuscarinic bronchodilator or a long-acting beta 2 agonist. Since then, a new antimuscarinic drug [symbol: see text] tiotropium bromide (Spiriva--Pfizer/Boehringer Ingelheim) has been licensed as a once-daily bronchodilator for maintenance treatment of COPD in people aged 18 years or over. Here, we review the evidence for efficacy of tiotropium and discuss its role in the maintenance treatment of COPD.     

Tiotropium for the treatment of asthma: a drug safety evaluation

ABSTRACT

Introduction: Tiotropium, a once-daily long-acting anticholinergic bronchodilator, has recently been approved for use in the treatment of asthma in a number of countries, including the EU and the USA, and was incorporated into the 2015 update of the Global Initiative for Asthma treatment guidelines. Here we review safety data from published clinical trials to help inform the use of tiotropium in the treatment of patients with asthma.

Areas covered: Safety data from recently published clinical trials, which compared tiotropium with placebo or an active control, were reviewed. Trials included children, adolescents, and adults across severities of symptomatic asthma, and assessed tiotropium delivered via the Respimat and HandiHaler devices.

Expert opinion: Based on the reviewed scientific evidence, tiotropium is a safe and well-tolerated long-acting anticholinergic bronchodilator for use in the treatment of asthma. In the trials assessed, the safety of tiotropium was found to be comparable with that of placebo and alternative therapeutic options, including a doubling in the dose of inhaled corticosteroids and the long-acting β₂-agonist salmeterol.     

Healthcare costs with tiotropium plus usual care versus usual care alone following 1 year of treatment in patients with chronic obstructive pulmonary disorder (COPD)

BACKGROUND: Healthcare costs for chronic obstructive pulmonary disease (COPD) have continued to increase with the increasing prevalence of the disease. New interventions that can reduce the medical costs of COPD are needed. Tiotropium bromide, a once-daily inhaled anticholinergic, has been evaluated in patients with COPD enrolled in two 1-year randomised, double-blind, placebo-controlled (usual care) trials which showed the drug reduced exacerbations and improved spirometry, dyspnoea, and health status. OBJECTIVE: To retrospectively assess the direct costs of medical care for COPD in a US healthcare setting for patients treated with tiotropium in addition to usual care compared with usual care alone over a 1-year timeframe. The study was based on resource utilisation in the two previously described trials. METHODS: Resource utilisation and clinical data were prospectively collected for the two 1-year, randomised, double-blind trials of tiotropium plus usual care versus usual care alone (placebo) in 921 patients with COPD. Usual care was defined as any medication for COPD used prior to the trial except anticholinergics and long-acting beta-adrenoceptor agonists. Medical care resource utilisation was recorded at every scheduled visit in each trial. Mean total costs were calculated retrospectively by combining the resources utilised with the appropriate unit costs (1999 US dollars), excluding study drug (tiotropium) costs. RESULTS: Compared with usual care, patients receiving tiotropium in addition to usual care had significantly fewer COPD exacerbations (20% decrease), hospitalisations (44% reduction) and hospital days (50% reduction). Utilisation of resources other than hospitalisation did not differ between study groups. As a consequence, patients receiving tiotropium had significantly lower mean per- patient costs of hospitalisation compared with patients receiving usual care alone (tiotropium US 1,738 dollars +/- US 259 dollars; placebo US 2,793 dollars +/- US 453 dollars). The mean difference in the cost of hospitalisation (resulting from all causes, including COPD) between treatment groups was -US 1,056 dollars (95% CI -US 2,078 dollars, -US 34 dollars), and the difference in total healthcare costs (excluding study drug acquisition cost) was -US 1,043 dollars (95% CI -US 2,136 dollars, US 48 dollars) in favour of tiotropium. The cost of hospital admissions accounted for 48% of the total direct medical costs in this trial. CONCLUSIONS: As hospitalisation is a large contributor to the cost of COPD, the addition of tiotropium to usual care therapy may have the potential to reduce the economic burden of COPD in a US healthcare setting. However, as our study did not consider the acquisition cost of tiotropium, further economic evaluation including this cost is needed to address whether tiotropium is cost saving compared with usual care (placebo).     

抗胆碱药物在哮喘治疗中的地位

作为支气管扩张药,抗胆碱药物在治疗阻塞性气道疾病(包括哮喘和慢性阻塞性肺疾病)方面有重要地位。本文就短效和长效抗胆碱药物治疗哮喘的有效性和不良反应进行综述。异丙托溴铵和速效β受体激动药合用可有效控制不同年龄哮喘的急性发作。噻托溴铵是长效支气管扩张药,它与M1、M2、M3受体竞争结合,与异丙托溴铵相比噻托溴铵从M1、M3胆碱能受体复合物上解离的速度要比从M2胆碱能受体复合物上解离的速度慢。噻托溴铵能减少Th2细胞因子和气道炎症,降低气道重塑和气道高反应性。噻托溴铵与吸入激素联合用药能有效控制未完全缓解的哮喘患者的症状并改善其肺功能。吸入抗胆碱药物不易吸收入血,因而全身不良反应小。     

Anticholinergic drugs in the therapy of obstructive airway diseases

The anticholinergic effects from botanical preparations of the deadly nightshade family have been used for hundreds of years for the treatment of obstructive airway diseases. Nowadays, derivatives of the plant alkaloids with quaternary ammonium structure, ipratropium bromide and tiotropium bromide, are used, which retain the bronchodilator properties of the parent compounds but are much safer since they are poorly absorbed across biologic membranes. They are the bronchodilators of choice in the management of chronic obstructive pulmonary disease (COPD). However, ipratropium is considered a second-line agent in the treatment of asthma as the bronchodilatory effects seen with ipratropium are less than those seen with beta-adrenergic drugs. Tiotropium is only approved for use in COPD. Though, a recent study provides some evidence that this agent may be an alternative to long-acting beta agonists as an add-on therapy to inhaled glucocorticoids for asthma.     

噻托溴铵干预对慢性阻塞性肺疾病大鼠气道重塑和MMP-9表达的影响

目的观察噻托溴铵早期干预对慢性阻塞性肺疾病(COPD)大鼠模型气道重塑及基质金属蛋白酶(MMP)-9的表达变化。方法Wistar大鼠随机分为3组:健康对照组(A组),COPD模型组(B组),噻托溴铵干预组(C组),采用熏烟并气管内注入脂多糖的方法建立COPD模型,C组于早期给予噻托溴铵雾化干预。观察肺组织病理形态学变化,图像分析测量小气道管壁和平滑肌厚度,采用免疫组织化学法测MMP-9蛋白。结果与B组相比,C组大鼠肺组织气道重塑病理变化减轻,MMP-9降低。结论噻托溴铵对COPD气道重塑有抑制作用,可降低MMP-9表达。