CHILDHOOD ASTHMA PREVENTION STUDY (CAPS) FOR PACRN

哮喘是儿童最常见的慢性呼吸道疾病，尽管诊断和抗炎治疗有所改善，但全世界的患病率、发病率和死亡率仍在以流行病的比例上升。重组人源化单克隆抗IgE是目前最有希望非特异性调节过敏性哮喘主要效应分子IgE的免疫调节剂。抗IgE可使游离IgE和IgE受体减少95%以上，改善哮喘症状和肺功能，并减少青少年和成人中度至重度持续性过敏性哮喘患者使用prn支气管扩张剂和皮质类固醇。本文提出了两个项目，分别为前瞻性、随机、隐蔽性和安慰剂对照，以评估抗ige在儿童一级和二级哮喘预防中的有效性和安全性。建议1或初级哮喘预防将确定抗IgE是否可以预防232例1至2岁患有特应性皮炎、食物过敏或变应性鼻炎、特异性IgE和父母有特应性史的高危婴儿哮喘的发展。患者将被随机分为抗ige组或安慰剂组，每个月皮下注射抗ige组或安慰剂组，随访3年观察哮喘的发展情况。次要目标包括确定抗ige与安慰剂相比在以下方面是否存在差异：(1)至少轻度持续性哮喘的发作，(2)由脉冲振荡确定的肺阻抗和支气管反应性，(3)皮肤试验反应性和炎症标志物，(4)对特应性疾病的影响，(5)长期安全性和生长。建议2或二级哮喘预防将确定与安慰剂相比，抗ige减少吸入皮质类固醇（ICS）需求（类固醇节约）的有效性，140名5-12岁的中度至重度持续性过敏性哮喘需要ICS的儿童。受试者将随机分为抗ige组或安慰剂组，每两个月皮下注射抗ige组或安慰剂1年，并分为两个阶段进行随访。在I期或12周辅助期，患者将维持其稳定的ICS剂量，在II期或40周的ICS停药期，受试者将根据方案减少ICS剂量。反IgE治疗的有效性和安全性与安慰剂相比,将减少的(1)ICS剂量测量的实时监测ICS使用电子(主要目的),(2)哮喘症状评分、药物使用、和呼气流量峰值水平电子设备监控,(3)和支气管肺功能响应性水平,人文和pharmacoeconomic措施,(4)(6)皮肤测试反应和炎症标记物,(7)体增长,(8)不良事件。

Asthma is the most common chronic respiratory disease of childhood with prevalence, morbidity and mortality increasing in epidemic proportions throughout the world despite better diagnosis and improved anti-inflammatory treatment. Recombinant humanized monoclonal anti-IgE is the most promising immunomodulatory agent available today to non-specifically modulate IgE, the major effector molecule in allergic asthma. Anti-IgE reduces free IgE and IgE receptors more than 95 percent, improves asthma symptoms, lung function, and reduces prn bronchodilator use and corticosteroid use in moderate to severe persistent allergic asthma in adolescents and adults. Proposed here are two projects, each prospective, randomized, masked, and placebo-controlled, to evaluate the effectiveness and safety of anti-IgE in primary and secondary asthma prevention in children. Proposal number 1 or primary asthma prevention will determine whether anti-IgE can prevent the development of asthma in 232 high-risk infants 1 to 2 years of age with atopic dermatitis, food allergy, or allergic rhinitis and specific IgE and a parental history of atopy. Patients will be randomized into anti-IgE or placebo groups, given bimonthly subcutaneous injections of anti-IgE or placebo, and followed for the development of asthma for 3 years. Secondary objectives include determination if anti-IgE compared to placebo differ with respect to (1) the onset of at least mild persistent asthma, (2) lung impedance and bronchial responsiveness determined by impulse oscillation, (3) skin test reactivity and markers of inflammation, (4) effect on atopic disorders, and (5) long-term safety and growth. Proposal number 2 or secondary asthma prevention will determine the effectiveness of anti-IgE compared to placebo to reduce inhaled corticosteroid (ICS) requirements (steroid sparing) in 140 children 5-12 years of age with moderate to severe persistent allergic asthma requiring ICS. Subjects will be randomized into anti-IgE or placebo groups, given bimonthly subcutaneous injections of anti-IgE or placebo for 1 year, and followed in two phases. During Phase I or the 12-week adjunctive phase, patients will maintain their stable dose of ICS, and during Phase II or the 40-week ICS withdrawal phase, subjects will have their ICS reduced according to protocol. The efficacy and safety of anti- IgE therapy versus placebo will be compared in terms of (1) the reduction in ICS dose measured by real time monitoring of ICS use electronically (primary aim), (2) asthma symptom scores, medication use, and peak expiratory flow levels monitored electronically, (3) levels of lung function and bronchial responsiveness, (4) humanistic and pharmacoeconomic measures, (6) skin test reactivity and markers of inflammation, (7) somatic growth, and (8) adverse events.