Leukotriene receptor antagonists in the treatment of allergic rhinitis.

OBJECTIVE: To review the literature examining the clinical use of leukotriene receptor antagonists in the treatment of allergic rhinitis. DATA SOURCES: Biomedical literature accessed through MEDLINE (1990-November 2000) and Current Contents (week 35 of 1999 to week 48 of 2000). Key terms included leukotriene antagonists, montelukast, zafirlukast, and rhinitis (allergic). DATA SYNTHESIS: Preliminary evidence on the clinical use of either montelukast or zafirlukast as monotherapy is equivocal, with one study noting benefit and another noting lack of benefit in symptom amelioration. A third study suggests that these agents may have a role in further modifying allergic rhinitis symptoms when used in combination with standard treatments. CONCLUSIONS: Future large-scale studies should assess the efficacy of these agents in the treatment of allergic rhinitis, in particular, to identify subsets of patients likely to derive the most benefit. Available data suggest it is reasonable and safe to add these agents to standard therapy if symptomatology remains unresolved.     

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.     

Acute phase reactants in allergic airway disease

Acute phase reactants have been implicated for their involvement as proinflammatory molecules in various inflammatory diseases. However, little is known regarding their role in the allergic airway disease. The aim of the present study was to examine the blood concentrations of three acute-phase proteins, namely C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen in patients with allergic rhinitis and asthma. Three study groups include: non-smoker allergic rhinitis (n = 50), non-smoker asthma (n = 20), and non-allergic, non-smoker healthy control subjects (n = 20). Patients who have had recent upper or lower respiratory tract infection and trauma, any rheumatological illnesses, malignancy or obesity were excluded. Blood samples were obtained from all the patients and control subjects and were analyzed for serum CRP, SAA and plasma fibrinogen. The mean CRP and fibrinogen values in the rhinitis and asthma groups were not significantly different when compared to the control group. However, the mean SAA levels of both groups were found to be significantly higher than those of the control group (p = 0.002 for rhinitis, p = 0.02 for asthma). There was no significant correlation between the FEV(1) values and the levels of the serum markers. This study demonstrates that acute phase reactant SAA rises in patients with allergic rhinitis and patients with asthma. We therefore suggest that SAA may have a role in the inflammatory airway disease.     

孟鲁司特联用布地奈德吸入防治儿童哮喘合并变应性鼻炎

目的：观察在吸入糖皮质激素（布地奈德）的基础上联合应用白三烯受体拮抗剂（孟鲁司特）对儿童哮喘伴变应性鼻炎的防治作用。方法：74例轻、中度支气管哮喘伴变应性鼻炎患儿随机分为治疗组和对照组各37例，进行3个月的治疗，观察组吸入布地奈德每天400μg，一个月后减至每天200μg，治疗组在此基础上加用孟鲁司特每天5mg。记录患儿的哮喘症状评分、变应性鼻炎症状评分、按需吸入β2受体激动剂的次数及测定气道反应性。结果：治疗后两组患儿的哮喘症状评分、变应性鼻炎症状评分及气道高反应性均明显改善。治疗组治疗后夜间哮喘症状评分及变应性鼻炎症状评分为0分及（0.30±0.36）分，对照组治疗后夜间哮喘症状评分及变应性鼻炎症状评分为（0.41±0.36）分及（1.29±0.54）分，两组比较差异有显著意义（P〈0.01）；按需吸入β2受体激动剂的次数治疗组为（1.84±0.04）喷，对照组为（2.97±0.03）喷，两组比较差异有显著性（P〈0.05）。结论：在吸入糖皮质激素的基础上联合应用白三烯受体拮抗剂可显著提高对儿童哮喘伴变应性鼻炎的疗效。     

Atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense pruritus and frequent relapsing courses. It occurs mostly in patients who have a personal or family history of other atopic conditions, such as asthma or allergic rhinitis. The prevalence of AD is high, particularly in children, with rapidly increasing numbers in the past few decades. The chronicity of this disease, along with its relapsing nature, presents treatment and management challenges for clinicians and frustration for patients and their families.     

Management of patients with asthma and allergic rhinitis

This article discusses the pathophysiology and management of patients with allergic rhinitis. The author relates the condition to asthma, which is often experienced by those with allergic rhinitis.     

Atopic dermatitis

Atopic dermatitis (AD) is an eczematous, highly pruritic chronic inflammatory skin disease. It usually begins early in life and often occurs in people with a personal or family history of asthma and allergic rhinitis. The prevalence is high, especially in children,and it has been rising in recent decades, in parallel with asthma prevalence. Although AD is often described as an "allergic" dis-ease, allergic causation is difficult to document, and AD is increasingly viewed as a skin disease that predisposes to allergies. This interpretation, based on clinical, epidemiologic, and animal stu-dies, may greatly influence our approach to therapy and prevention of atopic diseases in the coming years.     

The use of anti-IgE in the treatment of allergic asthma

Allergic sensitization plays a significant role in the development of asthma in many patients. IgE-mediated immune responses play a central role in the pathogenesis of this condition. The development of a treatment that interrupts this pathway is particularly desirable to prevent downstream events. Large-scale trials in patients ranging in age from 6 to 76 years have shown that omalizumab therapy is safe and effective in the treatment of severe allergic asthma. This is particularly true in patients who experience poor disease control despite high doses of inhaled steroids or need oral steroids for control of their disease. These patients are at risk for severe exacerbations despite recommended therapy, and anti-IgE therapy has proved to reduce these episodes. Early aggressive therapy of asthma is needed for maximum control in all age groups. Despite the efficacy of inhaled steroids there is a reluctance to use these agents, especially in younger children. Because of these concerns a long-acting treatment is especially desirable. Because of imperfect effort or technique limiting inhaled medications, introduction of an effective agent that could be administered parenterally at long intervals also is very important. Allergic rhinitis is a co-existing problem in many patients with allergic asthma. Immunotherapy trials have suggested that early intervention with immunotherapy and allergic rhinitis patients may actually prevent the development of asthma. Early treatment of patients with anti-IgE may also have benefits, particularly in those who have concomitant allergic rhinitis in addition to allergic asthma. Although omalizumab has not yet received Food and Drug Administration approval in the United States, it shows great promise in the management of patients requiring high doses of inhaled or oral corticosteroids for control of their disease and to prevent exacerbations of asthma in such patients. Reductions in high doses of inhaled or oral corticosteroids may prevent long-term complications of these treatments.     

Review of recent results of montelukast use as a monotherapy in children with mild asthma

Background: Asthma is a chronic disease with a heterogeneous phenotype that is often associated with allergic sensitization in childhood. The earliest definable form of asthma is mild (intermittent or persistent), a severity level that may be characteristic of a majority of children with asthma. Several asthma controllers are indicated for use in children. International guidelines recommend the use of inhaled corticosteroids as the preferred controller therapy in mild persistent asthma. Objective: This article reviewed recent results from randomized, double-blind studies of children with mild asthma treated with montelukast, a leukotriene receptor antagonist that is approved for the treatment of asthma and allergic rhinitis in children and adults. Methods: A literature search of MEDLINE was conducted to gather relevant, English-language articles using search terms such as randomized controlled studies, double-blind studies, montelukast, leukotriene receptor antagonist, pediatric asthma, mild asthma, exercise-induced asthma, and bronchoconstriction. Recent articles (since 1998) that described the use of montelukast as a monotherapy were chosen for this review. Results: Releevant studies included a 48-week, placebo-controlled study of 2- to 5-year-old mild intermittent asthmatics (N = 549); a 12-week, placebo-controlled study of 2- to 5-year-old mild persistent asthmatics (N = 689); an analysis of a mild persistent asthmatic cohort (N = 138) from an 8-week, placebo-controlled study of 6- to 14-year-old asthmatics; a 12-month study comparing montelukast with fluticasone in 6- to 14-year-old mild persistent asthmatics (N = 949); and 3 placebo-controlled studies in children with exercise-induced asthma (N = 123). The results from these studies, encompassing end points measuring lung function and symptoms, found that montelukast provided effective and beneficial asthma control to children aged 2 to 14 years with mild asthma. Conclusion: The evidence suggests that montelukast is an effective monotherapy controller in children with mild asthma.     

Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model

Airways inflammation is thought to play a central role in the pathogenesis of asthma. However, the precise role that individual inflammatory cells and mediators play in the development of airways hyperreactivity and the morphological changes of the lung during allergic pulmonary inflammation is unknown. In this investigation we have used a mouse model of allergic pulmonary inflammation and interleukin (IL) 5-deficient mice to establish the essential role of this cytokine and eosinophils in the initiation of aeroallergen-induced lung damage and the development of airways hyperreactivity. Sensitization and aerosol challenge of mice with ovalbumin results in airways eosinophilia and extensive lung damage analogous to that seen in asthma. Aeroallergen-challenged mice also display airways hyperreactivity to beta-methacholine. In IL-5-deficient mice, the eosinophilia, lung damage, and airways hyperreactivity normally resulting from aeroallergen challenge were abolished. Reconstitution of IL-5 production with recombinant vaccinia viruses engineered to express this factor completely restored aeroallergen-induced eosinophilia and airways dysfunction. These results indicate that IL-5 and eosinophils are central mediators in the pathogenesis of allergic lung disease.     

New insights into atopic dermatitis

Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. The clinical phenotype that characterizes atopic dermatitis is the product of interactions between susceptibility genes, the environment, defective skin barrier function, and immunologic responses. This review summarizes recent progress in our understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies.     

Correlations of health-related quality of life questionnaire results in asthma and allergic rhinitis: effects of a leukotriene receptor antagonist

Bronchial asthma and allergic rhinitis frequently coexist. This study investigated correlations of health-related quality of life (QOL) questionnaires for these diseases, assessing whether the selective leukotriene receptor antagonist (LTRA), pranlukast, had additional benefits to overall asthma control when there was concomitant allergic rhinitis. Patients with asthma-associated allergic rhinitis were randomly allocated to either LTRA(+) (n = 21, treated for 3 months with pranlukast), or LTRA(-) (n = 8, no pranlukast). At study start and at 3 months, pulmonary function was evaluated and QOL assessments were made using the Asthma Health Questionnaire-Japan (AHQ-Japan) and the Japan Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ). Total scores were significantly correlated both before and after therapy. After 3 months' therapy, pulmonary function and total AHQ-Japan and JRQLQ scores significantly improved in the LTRA(+) group, but not in the LTRA(-) group. A significant correlation between change at 3 months in the AHQ-Japan and JRQLQ scores from baseline values was seen in the LTRA(+) group. LTRA therapy improved allergic rhinitis symptoms, asthma symptoms and pulmonary function.     

Does rhinitis lead to asthma? Evidence for the one-airway hypothesis

The link between upper airway disease (allergic rhinitis) and lower airway disease (asthma) has long been of interest to physicians. Recently, extensive research has established that epidemiologic and therapeutic links exist between allergic rhinitis and asthma. Other recent evidence has provided a better understanding of the pathophysiologic interrelationship between allergic rhinitis and asthma. Such information has had an impact on the management of these disorders, including treatment and prophylaxis.     

Current and emerging biologic therapies for allergic rhinitis and chronic rhinosinusitis

ABSTRACT

Introduction: Allergic rhinitis and chronic rhinosinusitis, with and without nasal polyps, are the most common chronic inflammatory diseases of the upper airways. They both cause relevant respiratory symptoms and a substantial detriment to patients’ quality of life, mainly in uncontrolled and severe patients.

Areas covered: This review aims to present the most recent evidence on current and emerging biologic therapies for allergic rhinitis and chronic rhinosinusitis and discuss their potential implementation in clinical practice. To select relevant literature for inclusion in this review, we conducted a literature search using the PubMed database, using terms ‘biologics OR biological agents’, ‘allergic rhinitis’ and ‘chronic rhinosinusitis’. The literature review was performed for publication years 2009–2019, restricting the articles to humans and English language publications.

Expert opinion: Biological therapies represent a potential step forward in providing individualized care for all patients with uncontrolled severe upper airway diseases. Biologics recently showed promising results for the treatment of severe uncontrolled allergic rhinitis and chronic rhinosinusitis with nasal polyps with or without associated asthma. Endotyping inflammatory pathways and identifying related biomarkers remain the major challenge for positioning biologics in the care pathway of chronic respiratory diseases.     

Use of intranasal cromolyn sodium for allergic rhinitis

Allergic rhinitis affects 10% to 20% of Americans. It frequently coexists with other conditions, such as allergic conjunctivitis, sinusitis, and asthma, and is associated with impaired occupational function and performance in school, decreased quality of life, and increased health care costs. An efficacious agent with minimal adverse effects and a lack of drug interactions is needed to help simplify treatment of allergic rhinitis, especially in patients with comorbidities. Controlled studies of intranasal cromolyn sodium therapy for patients with seasonal and perennial allergic rhinitis are reviewed, and appropriate candidates for treatment with this agent are discussed. Cromolyn inhibits the degranulation of sensitized mast cells, thereby blocking the release of inflammatory and allergic mediators. It reduces symptoms of allergic rhinitis, and, when used prophylactically, cromolyn can prevent symptoms from occurring. Controlled studies comparing cromolyn with placebo, intranasal corticosteroids, and antihistamines have shown the efficacy of cromolyn in relieving rhinitis symptoms. In addition, because cromolyn is poorly absorbed systemically, it is well tolerated and not associated with drug interactions. Intranasal cromolyn has an excellent safety record, is available as an over-the-counter medication, and has been proved to be efficacious in patients with allergic rhinitis.     

Inflammatory mechanisms and treatment of obstructive airway diseases with neutrophilic bronchitis

Obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major global health issues. Although considered as distinct diseases, airway inflammation is a key underlying pathophysiological process in asthma, COPD and bronchiectasis. Persistent neutrophilic airway inflammation (neutrophilic bronchitis) occurs with innate immune activation and is a feature of each of these airway diseases. Little is known about the mechanisms leading to neutrophilic bronchitis and few treatments are effective in reducing neutrophil accumulation in the airways.There is a similar pattern of inflammatory mediator release and toll like receptor 2 expression in asthma, COPD and bronchiectasis. We propose the existence of an active amplification mechanism, an effector arm of the innate immune system, involving toll like receptor 2, operating in persistent neutrophilic bronchitis.Neutrophil persistence in the airways can occur through a number of mechanisms such as impaired apoptosis, efferocytosis and mucus hypersecretion, all of which are impaired in airways disease. Impairment of neutrophil clearance results in a reduced ability to respond to bacterial infection. Persistent activation of airway neutrophils may result in the persistent activation of the innate immune system resulting in further airway insult.Current therapies are limited for the treatment of neutrophilic bronchitis; possible treatments being investigated include theophylline, statins, antagonists of pro-inflammatory cytokines and macrolide antibiotics. Macrolides have shown great promise in their ability to reduce airway inflammation, and can reduce airway neutrophils, levels of CXCL8 and neutrophil proteases in the airways. Studies also show improvements in quality of life and exacerbation rates in airways diseases.     

Anti-IgE in allergic asthma and rhinitis: an update

Allergic asthma and rhinitis imposes a huge burden in terms of treatment costs, productivity loss and hospital admissions. IgE plays a significant role in the manifestation of these conditions and the identification of a monoclonal antibody that binds to IgE provides clinicians another therapeutic strategy in the management of these conditions. Blocking the effects of IgE by omalizumab, a recombinant humanised monoclonal antibody that selectively binds to IgE has been shown to be a useful adjunct in the treatment of allergic asthma and rhinitis. Omalizumab is effective as a steroid reducing agent in patients with severe asthma and is successful in decreasing asthma exacerbations. Omalizumab was well tolerated in clinical trials, however, the potential long-term side effects need careful monitoring. The high cost of the molecule could make this a therapeutic option in a small proportion of patients in whom there is a large unmet need.     

Anti-IgE in allergic asthma and rhinitis: an update

Allergic asthma and rhinitis imposes a huge burden in terms of treatment costs, productivity loss and hospital admissions. IgE plays a significant role in the manifestation of these conditions and the identification of a monoclonal antibody that binds to IgE provides clinicians another therapeutic strategy in the management of these conditions. Blocking the effects of IgE by omalizumab, a recombinant humanized monoclonal antibody that selectively binds to IgE has been shown to be a useful adjunct in the treatment of allergic asthma and rhinitis. Omalizumab is effective as a steroid reducing agent in patients with severe asthma and is successful in decreasing asthma exacerbations. Omalizumab was well tolerated in clinical trials, however, the potential long-term side effects need careful monitoring. The high cost of the molecule could make this a therapeutic option in a small proportion of patients in whom there is a large unmet need.     

南京地区支气管哮喘患者合并过敏性鼻炎的现状及其临床表现相关性

背景:过敏性鼻炎和支气管哮喘均为呼吸道炎性疾病,它们常并存于同一患者。目的:了解南京地区支气管哮喘患者中过敏性鼻炎的发生率,并分析过敏性鼻炎与支气管哮喘在临床表现方面的相关性。设计:问卷调查。单位:解放军南京军区南京总医院耳鼻咽喉-头颈外科及呼吸内科。对象:纳入2001-02/2005-04解放军南京军区南京总医院确诊为支气管哮喘的患者134例,男73例,女61例;年龄3～72岁。参照全球哮喘防治创议(Global initiative for asthma,GINA)方案进行哮喘严重程度分级;过敏性鼻炎的诊断标准参照1997-11"海口会议"的修订标准;所有患者均同意参与问卷调查。方法:通过问卷调查,详细了解134例支气管哮喘患者中患支气管哮喘、过敏性鼻炎患者的年龄、症状分型及严重程度、治疗状况、家族史等临床资料。应用统计学描述和两个独立样本的t检验,并计算支气管哮喘合并过敏性鼻炎的发生率,比较支气管哮喘和过敏性鼻炎患者的年龄、发病年龄及病程的差异有无显著性。应用Spearman等级相关分析进行两者严重程度相关性分析。主要观察指标:支气管哮喘患者中过敏性鼻炎的发生率,以及过敏性鼻炎与支气管哮喘在临床表现方面的相关性。结果:支气管哮喘患者134例中82例(61.2%,82/134)并发过敏性鼻炎,其中男45例,女37例。此82例患者中,哮喘严重程度一级(轻度间歇)56例,二级(轻度持续)21例,三级(中度持续)4例,四级(重度持续)1例。其过敏性鼻炎分型,间歇性65例,持续性17例;按严重程度分级,轻度63例,中-重度19例。过敏性鼻炎与支气管哮喘严重程度呈明显正相关(r=0.689,P<0.01)。结论:南京地区支气管哮喘合并过敏性鼻炎的发生率较高;过敏性鼻炎与支气管哮喘严重程度具有高度相关性。