妊娠期支气管哮喘治疗进展

临床研究已证明妊娠期重度及控制不佳的支气管哮喘（简称哮喘）与母亲及胎儿严重并发症相关.对于妊娠期哮喘患者,接受药物治疗比存在哮喘症状和哮喘发作更安全.所有程度的持续妊娠哮喘患者都应当应用吸入糖皮质激素作为控制药物,首选布地奈德.白三烯受体拮抗剂可以缓解支气管痉挛、减轻症状、改善肺功能.长效β2受体激动剂对于正在应用吸入糖皮质激素的患者可作为首选的添加药物.吸入短效β2受体激动剂可以作为缓解药物.对于正在接受维持量或接近维持量治疗,无不良反应、临床疗效好的妊娠哮喘患者可以继续进行变应原免疫治疗.     

特殊类型支气管哮喘的治疗问题——妊娠期支气管哮喘的药物治疗

妊娠期支气管哮喘(哮喘)是哮喘治疗和管理中的一种特殊情况。妊娠期间哮喘的发作不仅危及孕妇,且因母体缺氧而使胎儿产生一系列并发症。妊娠期哮喘患者应首选吸入型糖皮质激素,配合使用β2受体激动剂和茶碱等支气管舒张剂,给予抗炎和平喘的治疗。未良好控制的哮喘对孕妇和胎儿的危害要远远高于哮喘治疗药物对妊娠造成的风险。     

β2受体激动剂在支气管哮喘治疗中的合理应用

β2受体激动剂临床应用较广、种类较多,根据其作用持续时间可分为短效和长效β2受体激动剂,后者又可分为速效和缓慢起效2种。目前慢性持续性支气管哮喘(简称哮喘)的一线治疗药物为吸入型糖皮质激素及吸入型糖皮质激素与长效β2受体激动剂的联合制剂,但β2受体激动剂,尤其是速效吸入剂型可以有效地缓解哮喘的急性症状,仍广泛用于哮喘的急性发作期的治疗。β2受体激动剂在哮喘治疗中强调吸入治疗且必须与糖皮质激素联合应用,或在糖皮质激素治疗的基础上按需应用。吸入型长效β2受体激动剂与吸入型糖皮质激素联合应用是目前控制慢性持续性哮喘的有效治疗方法。β2受体激动剂的主要不良反应为心脏反应、肌肉震颤、低敏感现象和代谢紊乱,应用时应加以注意。     

支气管哮喘的个体治疗

目的 临床医师每天面对的支气管哮喘(简称哮喘)患者复杂多样,如何针对每例患者的具体情况,选择合适的药物种类和剂量,实现哮喘控制目标,是需要解决的问题.方法 对2008年5月至2009年3月北京协和医院呼吸科门诊控制不好的32例哮喘患者在治疗的同时进行2周动态肺量和症状监测,对其中4例进行病例分析和文献复习.结果 例1患者中年女性,咳嗽喘息10余天,夜间症状明显.2周动态肺量监测同时妥洛特罗贴剂2 mg/晚.监测初期第1秒用力呼气容积和最大呼气峰流速明显晨降,随治疗进展第1秒用力呼气容积恢复正常.最大呼气峰流速晨降消失.2周后患者开始了联合吸入肾上腺糖皮质激素和长效β2受体激动剂的治疗.例2老年女性,哮喘10多年,未正规治疗.开始联合吸入肾上腺糖皮质激素和长效β2受体激动剂治疗时,短期加用妥洛特罗贴剂,2周后肺功能基本恢复正常,未出现心血管系统不良反应.例3咳嗽变异性哮喘,吸入肾上腺糖皮质激素气雾剂后咳嗽加重,改妥洛特罗贴剂和复方甲氧那明全身用药,咳嗽很快缓解.2周后开始吸人肾上腺糖皮质激素干粉剂.3个月随访,症状控制.例4长期没有控制好的哮喘,需要寻找合适的治疗方案,联合吸入肾上腺糖皮质激素和长效β2受体激动剂治疗同时短期妥洛特罗贴剂,动态监测2周达到哮喘控制.结论 针对患者具体情况制定个体化的诊疗方案有助于提高哮喘的控制水平.     

妊娠合并支气管哮喘使用激素的临床分析

目的探讨妊娠期合并支气管哮喘使用激素的安全性。方法对确诊的妊娠期合并支气管哮喘患者82例,随机分为两组(患者同意激素治疗的为治疗(A)组,不同意激素治疗的为对照(B)组。对照组(B组)给予吸氧、补液纠正水盐电解质稳乱、吸入β2受体激动剂,有感染的给予抗生素等常规治疗。治疗组(A组)在常规治疗的基础上加用糖皮质激素(据病情轻重及妊娠的分期选择激素的给药方式)。观察患者的症状缓解、母婴的肝肾功能、血糖及动脉血气,并发症的发生,及婴儿的生长发育情况,随访至产后3个月。结果随访81例,治疗组完全症状缓解快,肺功能及动脉血气均明显改善,且均无早产、流产、胎儿畸形、肝肾功能血糖异常情况。仅1例重症哮喘母亲静脉点滴激素后血糖呈一过性偏高,但停药3天后复查血糖恢复正常。对照组完全症状缓解时间偏慢,且有发生早产5例、流产3例。结论妊娠期可使用糖皮质激素(吸入小剂量糖皮质激素或短期静滴小剂量糖皮质激素),控制哮喘发作效果快,且没用药控制的哮喘患者远比药物的不良反应要危险得多。     

长期联合吸入糖皮质激素和β2受体激动剂治疗哮喘疗效观察

目的观察糖皮质激素和β2受体激动剂长期联合吸入治疗哮喘疗效。方法58例哮喘患者随机分为糖皮质激素＋长效β2受体激动剂组和单用糖皮质激素组，观察患者1年内无症状天数、急诊就医次数、治疗开始及第1、2个月后FEV1。结果糖皮质激素＋长效β2受体激动剂组在1年内无症状天数、急诊就医次数、治疗第1、2个月后FEV1均较单用糖皮质激素组有明显差异（P〈0．05）。结论在哮喘长期治疗中糖皮质激素＋长效β2受体激动剂联合吸入治疗较单用糖皮质激素有效，应考虑首选。     

妊娠期支气管哮喘管理中的新认识

妊娠期支气管哮喘(简称哮喘)的发病率在增加.未控制的妊娠期哮喘可以增加胎儿先天性异常的风险.妊娠期哮喘的管理应该包括避免或控制哮喘的诱发因素、个体化的药物治疗、监测肺功能和患者教育.吸入激素是不同程度妊娠期哮喘患者首选的治疗药物.妊娠期间给予哮喘治疗药物对胎儿造成的风险小于妊娠期间出现哮喘症状和哮喘急性发作而对胎儿造成的风险.妊娠期哮喘管理的目标就是保证母亲和胎儿的健康.     

妊娠期支气管哮喘35例临床分析

目的分析妊娠期哮喘急性发作的临床特点,制定合理治疗方案,控制哮喘发作,减少对胎儿的影响。方法对35例妊娠期哮喘急性发作患者的临床资料进行回顾性分析。结果 35例患者症状完全缓解,1例自然流产,34例随访至产后1个月,婴儿和母亲均正常。结论妊娠期哮喘应按病情的轻重,给予恰当治疗;妊娠早期可选用对胎儿较小影响的药物,如头孢类抗生素、β2受体激动剂、糖皮质激素等药物,妊娠中晚期可选用茶碱药物。     

吸入布地奈德/福莫特罗干粉剂与联合吸入两种干粉剂治疗支气管哮喘的疗效和安全性研究

吸入型糖皮质激素（简称激素）和长效β2受体激动剂是目前治疗支气管哮喘（简称哮喘）的常用药物,临床上可单独使用,也经常联合应用.两药可能在细胞、受体和分子水平有协同作用. 联合吸入型激素和长效β2激动剂治疗中、重度持续性哮喘的作用和地位已被充分肯定。但分别使用两种吸入剂治疗，往往导致患者混淆用药，甚至治疗顺从性下降，采用激素和长效β2激动剂的复合吸入制剂治疗，可提高患者使用的方便程度和依从性。     

布地奈德/福莫特罗复合型粉剂小剂量吸入治疗轻度支气管哮喘的临床研究

吸入型糖皮质激素（简称激素）和长效β2受体激动剂是治疗支气管哮喘的常用药物，临床效果肯定，其中代表性药物如布地奈德／福莫特罗和布地奈德吸人剂。近年小剂量吸人剂治疗支气管哮喘在临床上被广泛研究，特别对于轻度支气管哮喘，研究证明使用小剂量的布地奈德吸人剂即可控制轻度支气管哮喘。本研究应用布地奈德／福莫特罗短期内小剂量的复合剂治疗轻度支气管哮喘，取得较好的治疗效果。     

Asthma: Versatile Treatment for a Variable Disease

Objective. This review describes factors contributing to the variable nature of asthma and the versatile treatment strategies required for the clinical management of the disease. Data Sources. A comprehensive review of the literature using MEDLINE was conducted. Study Selection. Included articles were selected for their relevance to variability or severity of asthma. Bibliographies of selected articles served as additional sources of considered publications. Results. Asthma severity can vary substantially among patients and within individual patients because of physiologic, environmental, or behavioral factors. Inhaled corticosteroids are an effective and versatile treatment option for special populations with asthma and for patients with varying degrees of asthma severity. Inhaled corticosteroids are now the preferred treatment for all three severity levels of persistent asthma, especially in young children and pregnant women. Treatment regimens may be adjusted up or adjusted down when appropriate to maintain optimal symptom control and limit potential adverse systemic effects. Conclusions. The clinical management of asthma is challenging given the day-to-day variability of the disease. Variability in pulmonary function and asthma symptoms may be minimized through increased awareness of the factors contributing to asthma variability as well as the effective use of inhaled corticosteroid therapy. Flexible treatment strategies that consider the different severities of asthma and account for variability within individual patients may be particularly useful in improving adherence and patient outcomes.     

Tolerability Profiles of Leukotriene Receptor Antagonists and Long-Acting β2-Adrenoceptor Agonists in Combination with Inhaled Corticosteroids for Treatment of Asthma: A Review

Inhaled corticosteroids, long-acting β₂-adrenoceptor agonists, and leukotriene receptor antagonists are widely used for treatment of asthma. Inhaled corticosteroids are recommended as first-line therapy, whereas long-acting β₂-adrenoceptor agonists and leukotriene receptor antagonists are indicated as add-on therapy in patients not adequately controlled with corticosteroids alone. A number of studies have investigated the efficacy of combinations of these drugs in asthma, but several issues concerning the safety of these treatments are highly debated. This review provides a critical appraisal of the tolerability profiles of long-acting β₂-agonists and leukotriene receptor antagonists used in combination with inhaled corticosteroids for the treatment of asthma.     

Inhaled Corticosteroids versus Leukotriene Antagonists as First-Line Therapy for Asthma

Inhaled corticosteroids are the most effective anti-inflammatory drugs for asthma. Leukotriene receptor antagonists are a new class of anti-inflammatory drugs that have the advantage of oral administration and the potential for better compliance compared with inhaled corticosteroids. This article summarizes evidence from randomized controlled trials, comparing the efficacy and tolerability of inhaled corticosteroids with those of leukotriene receptor antagonists in patients with persistent asthma. The evidence derived from a systematic review of randomized controlled trials confirms that patients treated with inhaled corticosteroids of chlorofluorocarbon-propelled beclomethasone 400 mug/day or fluticasone propionate 200 mug/day have better asthma control than those treated with oral leukotriene receptor antagonists. More specifically, treatment with inhaled corticosteroids is associated with 65% fewer exacerbations requiring systemic corticosteroids, greater improvement in spirometry and symptoms, fewer night-time awakenings and less use of rescue beta(2)-adrenoceptor agonists. This review does not identify any difference in short-term safety between inhaled corticosteroids and leukotriene receptor antagonists. Although adverse effects typically associated with inhaled corticosteroids (such as growth suppression, osteopenia, and adrenal suppression) were not measured, preventing a fair comparison of the safety profile on long-term use.In conclusion, the scientific evidence does not support the substitution of leukotriene receptor antagonists for low doses of inhaled corticosteroids, which should remain first-line therapy for asthma control.     

Managing Asthma in Expectant Mothers

Pregnancy does not appear to have a consistent effect on the frequency or severity of asthma. The most common cause of worsening asthma in pregnancy is likely to be noncompliance with medication. Emphasizing to the patient in advance that fetal well-being is dependent on maternal well-being may help prevent this.In general, well controlled asthma is not associated with a higher risk of adverse pregnancy outcomes. Essential to successful asthma management is patient education that helps to ensure effective medication use, avoidance of triggers, and prompt treatment. This education should include measurement of peak expiratory flow rate and a written asthma action plan. Most of the medications that are used to control asthma in the general population can be safely used in pregnant women. Inhaled beta-adrenoceptor agonists (beta-agonists), cromolyn sodium (sodium cromoglycate), and inhaled and systemic corticosteroids all appear to be very well tolerated by the fetus. Budesonide and beclomethasone should be considered as the preferred inhaled corticosteroids for the treatment of asthma in pregnancy. Use of the leukotriene receptor antagonists zafirlukast and montelukast in pregnancy is probably safe but should be limited to special circumstances, where they are viewed essential for asthma control. Zileuton should not be used in pregnancy.Acute asthma exacerbations in pregnant women should be treated in a similar manner to that in non-pregnant patients. Maternal blood glucose levels should be monitored periodically in pregnant women receiving systemic corticosteroids because of the deleterious effects of hyperglycemia upon embryos and fetuses. During pregnancy, maternal arterial oxygen saturations should be kept above 95% if possible for fetal well-being. Ambulatory oxygenation should be checked prior to discharge to ensure that women do not desaturate with their daily activities.Acute exacerbations of asthma during labor and delivery are rare. Dinoprost, ergometrine, and other ergot derivatives can cause severe bronchospasm, especially when used in combination with general anesthesia, and should be avoided in asthmatic patients. Pregnant women who have been treated with corticosteroids in the past year may require stress-dose corticosteroids during labor and delivery. Most asthma medications, including oral prednisone, are considered compatible with breast-feeding.     

Initial corticosteroid therapy for asthma

PURPOSE OF REVIEW: This review examines the commencement of maintenance pharmacotherapy for asthma: inhaled corticosteroids alone or in combination with long-acting beta2 agonists. RECENT FINDINGS: A systematic review of randomized controlled trials has examined the starting dose of inhaled corticosteroids (high, moderate, low) and the dose regimen (step down versus constant) in asthma. There was no significant difference in key asthma outcomes for step down compared with a constant inhaled corticosteroid dose. There was no significant difference between high or moderate dose inhaled corticosteroid groups (n=11) for morning peak expiratory flow, symptoms and rescue medication use. There may be a benefit from high-dose inhaled corticosteroids for airway hyperresponsiveness. There was a significant improvement in peak expiratory flow and nocturnal symptoms in favour of a moderate inhaled corticosteroid dose compared with low-dose treatment. Long-acting beta2 agonists combined with inhaled corticosteroids as initial asthma therapy has been examined in a systematic review of nine randomized controlled trials. Inhaled corticosteroids combined with long-acting beta2 agonists led to significant improvements in forced expiratory volume in 1 s, morning peak expiratory flow, symptom score and symptom-free days but no difference in exacerbations requiring oral corticosteroids. A randomized controlled trial of patients with uncontrolled asthma found a benefit of escalating doses of salmeterol/fluticasone compared with fluticasone on asthma control. SUMMARY: Initial inhaled corticosteroid therapy should begin with a constant, moderate dose. Initial therapy with long-acting beta2 agonist and inhaled corticosteroids achieves superior improvement in symptoms and lung function, and at a quicker rate than inhaled corticosteroids alone. There is no benefit in terms of reduced exacerbations unless an escalating inhaled corticosteroid dose strategy is used.     

Inhaled steroids for children: effects on growth, bone, and adrenal function.

Inhaled corticosteroids are the first-line therapy for persistent asthma in children. Major safety concerns of long-term inhaled corticosteroid therapy include suppression of adrenal function and impaired growth and bone development. Proper interpretation of inhaled corticosteroid safety requires knowledge of differences among various drug devices. Dosage, type of inhaler device used, patient technique, and characteristics of the individual drug influence systemic effects of inhaled corticosteroids. Systemic side effects can occur when continuous high-dose treatment is required for severe asthma or when prescribed dosage is excessive and compliance is unusually good. Recent studies confirm that benefits of inhaled corticosteroids outweigh potential adverse effects and the risks associated with poorly controlled asthma.     

The Efficacy and Safety of Mometasone Furoate Delivered via a Dry Powder Inhaler for the Treatment of Asthma

Inhaled corticosteroids are the gold standard of daily therapy for effective control of all stages of persistent asthma. For this review of the new inhaled corticosteroid mometasone furoate, a MEDLINE/PubMed search using the terms “mometasone furoate AND asthma” found 57 articles, 17 of which presented data from efficacy and safety studies reviewed herein. In clinical trials, once-daily evening dosing of mometasone furoate delivered via dry powder inhaler (200 or 400 μ g/day) was effective in patients with mild to moderate asthma previously treated with short-acting β₂-agonists alone and in those previously maintained on inhaled corticosteroid therapy. In patients with severe asthma, mometasone furoate 400 μ g twice daily eliminated or reduced the need for oral prednisone while improving lung function, asthma symptoms, and quality of life. Clinical studies have shown that mometasone furoate is generally well tolerated and has minimal systemic activity at recommended doses. In conclusion, mometasone furoate provides primary care and specialty physicians with a safe, effective, and convenient option to meet the challenges of asthma management.     

Tolerability Profiles of Leukotriene Receptor Antagonists and Long-Acting β2-Adrenoceptor Agonists in Combination with Inhaled Corticosteroids for Treatment of Asthma: A Review

Inhaled corticosteroids, long-acting β₂-adrenoceptor agonists, and leukotriene receptor antagonists are widely used for treatment of asthma. Inhaled corticosteroids are recommended as first-line therapy, whereas long-acting β₂-adrenoceptor agonists and leukotriene receptor antagonists are indicated as add-on therapy in patients not adequately controlled with corticosteroids alone. A number of studies have investigated the efficacy of combinations of these drugs in asthma, but several issues concerning the safety of these treatments are highly debated. This review provides a critical appraisal of the tolerability profiles of long-acting β₂-agonists and leukotriene receptor antagonists used in combination with inhaled corticosteroids for the treatment of asthma.     

Effets synergiques et additifs entre les différentes classes d'anti-inflammatoires de l'asthme

Persistent asthma is a chronic airway inflammatory disease that requires treatment with anti-inflammatory drugs. Inhaled corticosteroids are the cornerstone of the treatment of airway inflammation. Clinical studies have shown that asthmatic patients treated with long-acting β₂-agonists and inhaled corticosteroids have more reduced exacerbations than those given higher doses of corticosteroids suggesting synergistic effects on the inflammatory process. The understanding of the molecular modes of action of these two classes of drugs explained part of the enhanced anti-inflammatory activity of the combination therapy. However, the production of cysteinyl-leukotrienes is not well controlled by corticosteroids. Antileukotrienes, by the blockade of the effects of cysteinyl-leukotrienes, exert therefore a complementary antiinflammatory action. In addition, the efficacy of antileukotrienes for the symptomatic treatment of allergic seasonal rhinitis can improve both the quality of life and asthma control in mild to moderate persistent asthmatic patients, with seasonal allergic rhinitis, who are already treated with an antileukotriene as maintenance treatment for their asthma.     

Update on inhaled corticosteroids: safety, compliance, and new delivery systems.

Since the introduction of inhaled beclomethasone, inhaled corticosteroids have revolutionized the treatment of asthma. Inhaled corticosteroids provide the most potent and consistently effective long-term control of asthma. They have become the mainstay of therapy for chronic disease and have been recommended for asthmatics of all severities. During the past two decades, after the introduction of beclomethasone, several new inhaled corticosteroids have been introduced. With more widespread use of these agents, particularly in pediatric patients, concerns about safety have risen. These concerns emanate from the use of higher dose inhaled corticosteroids and higher potency molecules. The side effects of most concern are those that are similar to those associated with systemic corticosteroids. Recently, the U.S. Food and Drug Administration (FDA) issued a class warning of potential growth suppression in some pediatric patients using inhaled corticosteroids. Patient compliance with inhaled corticosteroid therapy is problematic. Some patients think that all inhaled corticosteroid therapy is inherently dangerous because they confuse it with systemic corticosteroid or even anabolic steroid use. Most of the products are available only as metered dose inhalers. Use of these inhalers is difficult and often poorly taught to patients. The two newest inhaled corticosteroids, budesonide and fluticasone, are available as dry powder inhalers with new delivery systems.