布地奈德粉吸剂对哮喘患者肺功能的影响

目的研究采用布地奈德粉吸剂对哮喘患者肺功能的影响。方法选取成都市第六人民医院2011年12月至2013年1月收治的64例哮喘患者,随机将其分成治疗组与对照组各32例。对照组患者实施抗感染、止咳、吸氧、化痰等综合治疗措施;治疗组患者采用布地奈德粉吸剂进行治疗,每次400μg,每天2次,同时运用适当的茶碱类药物与白三烯调节剂。对两组患者的治疗效果进行观察比较。结果通过治疗两组患者的哮喘症状得到明显改善,治疗组患者的哮喘评分与咳嗽评分明显好于对照组;同时对两组患者的肺功能恢复状况进行比较,治疗组明显好于对照组。结论采用布地奈德粉吸剂进行治疗,可以对患者的哮喘病症进行有效控制,同时对其肺功能具有明显的改善作用,对提升患者的生活质量具有十分重要的意义。     

Successful multidrug treatment of a pediatric patient with severe Churg-Strauss syndrome refractory to prednisolone

Churg-Strauss syndrome (CSS), which is characterized by systemic small-vessel vasculitis of unknown etiology, is associated with a history of asthma. Although reports of CSS occurring in children are limited, effective treatment of pediatric patients with severe CSS remains challenging. A 10-year-old Japanese boy with a 6-month history of asthma treated with a leukotriene modifier, pranlukast, developed high fever, pleural infiltration, and pericarditis that were associated with marked hypereosinophilia (10,350 eosinophils/μl). Owing to his persistent high fever, mononeuritis multiplex, and severe abdominal pain that was refractory to prednisolone, his general condition progressively deteriorated thereafter. Although intravenous high-dose immunoglobulin administration was transiently effective for mononeuritis multiplex, the recurrent high fever and severe abdominal pain remained refractory. An endoscopic study revealed ulcerative lesions of the total colon. In this context, we treated the patient with an aggressive multidrug immunosuppressive regimen consisting of a high-dose methylprednisolone pulse plus short-course intravenous cyclophosphamide pulse therapy, followed by oral tacrolimus combined with prednisolone. After the rescue multidrug treatment, his severe clinical signs dramatically subsided within a short time, and the concomitantly administered prednisolone was successfully tapered without flare. At present, 12 months after the presentation, he is free from CSS signs or therapy-related toxicity except for an occasional mild asthma attack. Although further close observation should be needed to draw a long-term outcome in this patient, we believe that aggressive multidrug immunosuppressive treatment should be considered as an alternative rescue treatment in selected patients with severe CSS, even with pediatric-onset disease, that is refractory to prednisolone.     

变应性肉芽肿性血管炎11例临床分析

【目的】分析变应性肉茅肿性血管炎(CSS)的临床表现．以便提高临床诊断水平【方法】11例确诊CSS患者．分析其既往痛史、临床表现、实验室检查、活检病理及治疗情况【结果】11例患者中发生哮喘10例;10例出现皮肤损伤;分别有1例和2例出现周围神经和中枢神经病变：消化道症状者1例．包括腹痛、腹泻和脓血便：肾脏损害者4例;心脏受累者6例全部病例周围血嗜酸粒细胞(EOS)均增高．有1例活捡病理支持CSS诊断。所有患者均用糖皮质激素和免疫抑制制治疗。【结论】CSS的临床表现多种多样．对于有系统性表现．特别是血嗜酸细胞升高者应提高警惕。     

Where do leukotriene modifiers fit in asthma management?

Effective asthma treatment requires long-term inflammation control. Patient adherence to corticosteroid treatment regimens remains problematic. Leukotriene modifiers, a newer drug class, add to the pharmacologic approaches to asthma management. Here, we review the role of leukotrienes in asthma pathogenesis and appropriate uses for leukotriene modifiers in asthma management.     

Montelukast in guidelines and beyond

In all asthma guidelines, preventive anti-inflammatory treatment is essential in all patients with persistent asthma. Inhaled corticosteroids are the mainstay of treatment in the control of asthma, but other treatments may be used as a monotherapy in patients with mild asthma or as an add-on treatment in those with moderate-to-severe asthma. Leukotriene modifiers are the only validated preventive treatment for all age groups. This review discusses the place of montelukast, a leukotriene receptor antagonist, using guidelines and consensus reports on asthma and rhinitis: the US National Asthma Education and Prevention Program (NAEPP); the British Guideline on the Management of Asthma; the Global Initiative on Asthma (GINA); and Allergic Rhinitis and its Impact on Asthma (ARIA). This review includes new studies that have not yet been considered in guidelines.     

Leukotriene modifiers to prevent aspirin-provoked respiratory reactions in asthmatics

OBJECTIVE: To evaluate the use of leukotriene modifiers in preventing aspirin-provoked respiratory reactions in asthmatics. DATA SOURCES: Clinical literature accessed through MEDLINE (1965-February 2001). Key search terms included aspirin, asthma, leukotriene, and treatment. DATA SYNTHESIS: Aspirin-sensitive asthmatics experience a wide variety of symptoms, ranging from rhinitis to life-threatening bronchospasms, after the ingestion of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs). The relationship between aspirin sensitivity, asthma, and nasal polyps was first reported in 1922. The exact mechanism of these reactions is not clearly understood. Four studies investigated the use of leukotriene modifiers to prevent aspirin-provoked respiratory reactions. The efficacy of these agents ranged from complete inhibition to no blockade. CONCLUSIONS: Patients who experience aspirin-sensitive asthma should be cautious when taking aspirin and NSAIDs, despite treatment with leukotriene inhibitors.     

Montelukast in the prophylaxis of migraine: a potential role for leukotriene modifiers

OBJECTIVE: Clinical observation of a decrease in migraine frequency in patients with comorbid asthma taking montelukast, a specific D4 leukotriene receptor antagonist, or zafirlukast, another leukotriene receptor antagonist, prompted us to explore a possible role for leukotriene modifiers in the treatment of migraine. (A further prompt was a pharmacist colleague's observation that a number of patients on these agents reported a decreased sensitivity to perfume triggers and improvement in migraine.) BACKGROUND: Nonsteroidal anti-inflammatory agents have been used widely in the treatment of migraine. Another class of anti-inflammatory agents, known as leukotriene modifiers, have not been studied to date with regard to their possible role in the treatment of migraine. The name "leukotriene is derived both from the parent molecule, which was originally isolated from leukocytes, and from its three double-bond carbon backbone or triene structure. Both prostaglandins and leukotrienes are derived from the metabolism of arachidonic acid, with prostaglandins coming off the cyclooxygenase pathway and leukotrienes derived via the enzyme 5-lipoxygenase. Both prostaglandins and leukotrienes mediate inflammatory responses. The latter have been studied with regard to their role in the pathophysiology of asthma. METHODS: A prospective, open-label study evaluating the efficacy of montelukast, 10 mg or 20 mg, in the prophylaxis of migraine in 17 patients is presented in this paper. All 17 patients completed the study that consisted of a 2-month baseline run-in period and a 3-month treatment phase. RESULTS: Montelukast was extremely well tolerated, and no adverse events were reported by any of the patients. Fifty-three percent showed a reduction of greater than 50% (P<.025) in the frequency of severe attacks, with 41% showing a reduction of greater than 60%. Responders, including modest responders, rated the drug as excellent. CONCLUSIONS: We conclude, given the limitations of an open-label study design and the small sample size, that montelukast shows potential as an effective, well-tolerated prophylactic agent in migraine. Double-blinded, placebo-controlled studies are warranted. In addition, the leukotrienes, as suggested previously in the literature, may play a role in the pathogenesis of migraine.     

Recurrent panniculitis in a man with asthma receiving treatment with leukotriene-modifying agents

Leukotriene-modifying drugs are novel agents introduced recently to treat asthma. Both 5-lipoxygenase inhibitors, such as zileuton, and leukotriene receptor antagonists, such as zafirlukast and montelukast, have proved effective in the treatment of asthma. To our knowledge, there have been no detailed reports regarding dermatologic manifestations of this class of drugs. This article describes an unusual case of erythema nodosum in a 46-year-old asthmatic man who received 2 different leukotriene modifiers.     

白三烯受体拮抗剂在慢性咳嗽治疗中的临床价值

目的 探讨白三烯受体拮抗剂在慢性咳嗽临床治疗中的意义.方法 选择81例慢性咳嗽患者(根据慢性咳嗽诊断流程诊断),所有患者均符合咳嗽时间≥8周,不吸烟或戒烟4周以上,无服用血管紧张素转换酶抑制剂类药物史,服用者停药观察4周,X线胸片检查未见异常,并除外胃食管反流性咳嗽、除变应性鼻炎的其他上气道咳嗽综合征、支气管内膜结核等其他慢性咳嗽病因.对诊断为咳嗽变异性哮喘、变应性鼻炎、嗜酸粒细胞性支气管炎及感染后咳嗽的患者给予孟鲁司特钠10 mg,每晚1次进行治疗4周并观察疗效.结果 81例入选患者中咳嗽变异性哮喘36例,变应性鼻炎30例,嗜酸粒细胞性支气管炎5例,感染后咳嗽10例.经孟鲁司特钠治疗后,67例患者咳嗽症状临床控制,12例患者显效,2例无效,有效率97.5%(79/81).结论 气道炎症是慢性咳嗽患者常见的病理特征,白三烯受体拮抗剂孟鲁司特钠有显著的抗炎作用,能明显改善咳嗽变异性哮喘、嗜酸粒细胞性支气管炎、感染后咳嗽、变应性鼻炎等慢性咳嗽患者的气道炎症,减轻咳嗽症状,是治疗慢性咳嗽的重要药物.     

Asthma update: Part II. Medical management

The National Asthma Education and Prevention Program recently updated its guidelines for the management of asthma. An evidence-based approach was used to examine several key issues regarding appropriate medical therapy for patients with asthma. The updated guidelines have clarified these issues and should alter the way physicians prescribe asthma medications. Chronic inhaled corticosteroid use is safe in adults and children, and inhaled corticosteroids are recommended as first-line therapy in adults and children with persistent asthma, even if the disease is mild. Other medications, such as cromolyn, theophylline, and leukotriene modifiers, now are considered alternative treatments and should have a more limited role in the management of persistent asthma. The addition of a long-acting beta2 agonist to an inhaled corticosteroid is superior to all other combinations as well as to higher dosages of inhaled corticosteroids alone. Combination therapy with an inhaled corticosteroid and a long-acting beta2 agonist is the preferred treatment for adults and children with moderate to severe asthma. Antibiotic therapy offers no additional benefit in patients with asthma exacerbations.     

Treatment of polyarteritis nodosa and Churg-Strauss syndrome: indications of plasma exchanges

To define the most effective treatment for polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS), we undertook 4 consecutive prospective therapeutic trials including 236 patients and tried to answer several important questions: Should cyclophosphamide (CYC) be given as the first-line treatment? What is the place of plasma exchanges (PE) in the treatment of systemic vasculitis? and does hepatitis B virus (HBV) related PAN require treatment? Our first randomized trial in 71 patients (1981-1983) compared the association of CYC with corticosteroids (CS) and PE to CS and PE, in order to evaluate the efficacy of CYC given as the first-line treatment to control disease activity and subsequent survival of PAN and CSS patients. Between December 1983 and December 1988, we conducted two trials simultaneously: one aimed at patients without HBV markers and the second at patients with HBV markers. In 78 patients without HBV markers, we compared prednisone and PE to prednisone alone as the initial therapeutic regimen. In 33 patients with PAN related to HBV, a new therapeutic strategy was applied as an alternative to long-term steroid and immunosuppressive therapy: short-term steroid therapy and PE were used to control the evolution of PAN and anti-viral therapy was administered to suppress the etiological agent of the vasculitis. In the last protocol including 56 patients and addressed to severe PAN without HBV markers or CSS we have shown that PE did not improve the prognosis and control of the disease. Twelve years after the beginning of the trials on PAN and CSS patients, we think that the therapeutic strategy should be as follows: In PAN without HBV and CSS: prednisone in association with CYC improves the control of the disease despite infectious side effects which may be reduced by better CYC dose adaptation. In PAN related to HBV: The first-line treatment should be the association of anti-viral agents and PE. This treatment was effective and cured a majority of patients within 2 to 3 months; half of them seroconverted. The length of HBV infection before its diagnosis, delay before initiation of treatment and previous immunosuppressive therapy led to a poor seroconversion rate. The role of PE in the treatment of systemic necrotizing vasculitis: PE are obviously useful in PAN related to HBV where immune complex deposition has been demonstrated. When PAN is not related to HBV and in CSS, even in severe cases, there is presently no argument supporting systematic administration of PE at the time of diagnosis.     

Association of asthma therapy and Churg-Strauss syndrome: an analysis of postmarketing surveillance data

BACKGROUND: Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis (AGA), is a rare vasculitis that occurs in patients with bronchial asthma. The nature of the association of CSS with various asthma therapies is unclear. OBJECTIVE: This study investigated the associations of different multidrug asthma therapy regimens and the reporting of AGA (the preferred code for CSS in the coding dictionary for the Adverse Event Reporting System [AERS]) by applying an iterative method of disproportionally analysis to th AERS database maintained by the US Food and Drug Administration. METHODS: The public-release version of the AERS database was used to identify reports of AGA in patients receiving asthma therapy. Reporting of AGA was examined using iterative disproportionality methods in patients receiving > or =1 of the following drug classes: inhaled corticosteroid (ICS), leukotriene receptor antagonist (LTRA), short-acting beta(2)-agonist (SABA), or long-acting beta(2)-agonist (LABA). The Bayesian data-mining algorithm known as the multi-item gamma poisson shrinker was used to determine the relative reporting rates by calculation of the empirical Bayes geometric mean (EBGM) and its 90% CI (EB05 = lower limit and EB95 = upper limit) for each drug. Subset analyses were performed for each drug with different medication combinations to differentiate the relative reporting of AGA for each. RESULTS: A strong association was found between LTRA use and AGA (EBGM = 104.0, EB05 = 95.0, EB95 = 113.8) that persisted with all combinations of therapy studied. AGA was also associated with the ICS, SABA and LABA classes (EBGM values of 27.8, 14.6 and 40.4, respectively). However, the latter associations were mostly dependent on the presence of concurrent LTRA and, to a lesser extemt, oral corticosteroid therapy and became negligible (ie, EB05 < 2) for patients who were not receiving these concurrent treatments. CONCLUSIONS: Differences based on relative reporting were observed in the patterns of association of AGA with LTRA, ICS, and beta(2)-agonist therapies. A strong association between LTRA use and AGA was present regardless of the use of other asthma drugs.     

Immunoglobulin E-mediated airway inflammation is active in most patients with asthma

PURPOSE: To review the role of immunoglobulin E (IgE)-mediated inflammation in the pathogenesis of asthma, limitations of standard therapies, and IgE as a logical target for therapy with omalizumab aimed at attaining asthma symptom control. DATA SOURCES: Review of worldwide scientific literature on the role of IgE-mediated inflammation in patients with asthma, supplemented with a clinical case study. CONCLUSIONS: Clinical trials point to an important role for IgE blocker therapy as an add-on to current therapy to reduce exacerbations and corticosteroid use and to improve quality of life in patients with moderate-to-severe asthma. Omalizumab, a monoclonal antibody that binds IgE, has been shown to be an effective, well-tolerated treatment in these patients. IMPLICATIONS FOR PRACTICE: A significant number of patients with moderate-to-severe asthma do not achieve asthma symptom control, despite adhering to current guidelines-based standards of therapy, including the use of inhaled corticosteroids, beta-agonists, and leukotriene modifiers. None of these therapies directly addresses IgE-mediated inflammation. Therefore, patients with persistent symptoms of moderate-to-severe asthma should be evaluated and considered for therapy with the IgE blocker omalizumab.     

Evidence-based pharmacologic treatment for mild asthma

BACKGROUND: Although mild asthmatics form the majority of asthma sufferers, there is a relative paucity of evidence-based treatment compared with severe asthmatics. OBJECTIVE: We have performed an up-to-date review of the literature on therapy in this group of patients who form an overlooked but important majority. Potential trials were identified through MEDLINE (1965-2007) and Cochrane library (up to February 2007). DISCUSSION: Recent trials have shown that inhaled corticosteroids (ICS) remain the cornerstone of treatment for patients with mild persistent asthma. Early intervention with ICS decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset. ICS are superior to leukotriene receptor antagonists and xanthines for control of asthma and in the improvement of lung functions. The addition of long-acting beta2-agonist may be considered in those with moderately persistent asthma or whom asthma is not well controlled with low doses of ICS.     

Churg-Strauss syndrome in an HCV seropositive patient

Churg-Strauss syndrome was considered rare until leukotriene modifiers were introduced into medical practice in 1996. Since then, an increasing number of reports considering a possible relationship between leukotriene receptor antagonists and the Churg-Strauss syndrome have been published. Hepatitis C virus (HCV) is a blood-borne infection and a major health problem with an increasing prevalence worldwide. Previously, numerous reports suggested a relationship between HCV and certain autoimmune disorders such as cryoglobulinaemia and polyarteritis nodosa. We present a patient with HCV seropositive Churg-Strauss syndrome and a history of systemic corticosteroid and leukotriene receptor antagonist use, and discuss the possible risk factors in the aetiology of Churg-Strauss syndrome.     

Management of acute,severe asthma in children

OBJECTIVE: To briefly present the current options available for the treatment of acute, severe asthma in children, with a special focus on emergency department and inpatient treatment, and to describe newer therapies that may aid treatment in the future. DATA SOURCES AND STUDY SELECTION: A MEDLINE search (1966-May 2001) of the English-language literature pertaining to drug therapy of acute asthma was performed. Key word searches included acute asthma, albuterol, ipratropium, corticosteroids, magnesium, and theophylline. Additional articles from these sources and published national guidelines were identified. Relevant studies pertaining to current therapy of acute asthma in pediatric patients were selected; if there were minimal pediatric data, adult data were included. DATA SYNTHESIS: Asthma is a chronic, inflammatory disorder of the airways. Acute exacerbations can occur and are challenging to manage. Albuterol, ipratropium, and systemic corticosteroids have been shown to be effective in acute asthma exacerbations. Because some patients do not respond to maximal therapy, older therapies such as magnesium and theophylline are being reevaluated. Theophylline may have some therapeutic effect, but given its toxicity profile, it is unclear whether it offers any advantage over maximal beta(2)-agonist therapy. There are only minimal published data evaluating the use of magnesium in pediatrics, and most are small trials or case reports. Newer therapies such as ventilation strategies with heliox and intravenous leukotriene modifiers currently being evaluated may or may not prove to be beneficial in the future. CONCLUSIONS: beta(2)-agonists, ipratropium, and corticosteroids remain the most useful therapeutic agents for acute asthma exacerbations in pediatric patients. However, these agents are not ideal in all patients and, given the existing questions regarding safety and/or efficacy of available alternatives, more effective options are needed.     

哮喘患者白细胞介素13与临床特征、糖皮质激素疗效相关性研究

目的:探讨白介素13(IL-13)对支气管哮喘患者临床特征和糖皮质激素治疗的影响.方法:采用ELIAS分别检测34例发作期哮喘患者(其中14例激素敏感型和10例激素抵抗型口服强的松治疗1周)、18例缓解期患者和30例健康对照者血浆IL-13浓度.结果:52例哮喘患者和30例健康人血浆IL-13质量浓度(65.65±3.38 vs 25.83±3.59)比较,差异有显著性(P＜0.05).发作期(34例)和缓解期(18例)哮喘患者血浆IL-13质量浓度(72.03±3.72 vs 48.67±4.22)比较,差异有显著性(P＜0.05).在34例发作期哮喘患者中,轻、中、重度者其血浆IL-13质量浓度(52.35±2.98 vs 65.12±2.56 vs 76.57±2.36)相互间比较,差异有显著性(P＜0.05).激素敏感型哮喘经强的松治疗1周后血浆IL-13质量浓度较治疗前明显下降(73.03±3.72 vs 55.67±4.22),差异有显著性(P＜0.05);激素抵抗或依赖型哮喘经强的松治疗1周前后血浆IL-13质量浓度比较(70.35±2.98 vs 68.57±2.36),差异无显著性(P＞0.05).结论:血浆IL-13参与哮喘的病理生理过程,可作为判断哮喘患者病变严重程度的指标之一.IL-13参与调节糖皮质激素作用机制.     

Churg-Strauss syndrome occurring 30 years after the onset of ulcerative colitis.

Churg-Strauss syndrome (CSS) is a rare pulmonary and systemic vasculitis associated with asthma, with peripheral blood and/or tissue eosinophilia. We report the case of a 53-year-old woman who was admitted to the hospital with pneumonia and coma secondary to right hemisphere intracerebral hemorrhage. Although she recovered from the pneumonia, she remained comatose and had sinusitis and persisting blood eosinophilia. A muscle biopsy revealed eosinophilic vasculitis. The diagnosis of CSS was made and the patient recovered after being treated with prednisone and cyclophosphamide. This case reports the very rare appearance of CSS 30 years after the first appearance of ulcerative colitis and 27 years after the onset of asthma.