CHILDHOOD ASTHMA PREVENTION STUDY (CAPS) FOR PACRN

哮喘是儿童期最常见的慢性呼吸道疾病，尽管有更好的诊断和更好的抗炎治疗，但其患病率、发病率和死亡率在全世界范围内呈流行病比例增加。 重组人源化单克隆抗IgE抗体是目前最有前途的免疫调节剂，可用于非特异性调节过敏性哮喘的主要效应分子IgE。抗IgE抗体可降低游离IgE和IgE受体超过95%，改善哮喘症状、肺功能，并减少青少年和成人中重度持续性过敏性哮喘患者的PRN支气管扩张剂使用和皮质类固醇使用。 这里提出了两个项目，每个前瞻性，随机，设盲和安慰剂对照，以评估抗IgE抗体在儿童哮喘一级和二级预防中的有效性和安全性。1号提案或哮喘初级预防将确定抗IgE抗体是否可以预防232名1 - 2岁患有特应性皮炎、食物过敏或过敏性鼻炎和特异性IgE且父母有特应性病史的高危婴儿发生哮喘。 将患者随机分为抗IgE组或安慰剂组，每两个月皮下注射一次抗IgE或安慰剂，并随访哮喘的发展3年。 次要目的包括确定抗IgE与安慰剂相比是否在以下方面存在差异：（1）至少轻度持续性哮喘的发作，（2）通过脉冲振荡测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，以及（5）长期安全性和生长。方案2或二级哮喘预防将在140例5-12岁需要吸入性皮质类固醇（ICS）的中重度持续性过敏性哮喘儿童中确定抗IgE与安慰剂相比减少吸入性皮质类固醇（ICS）需求（类固醇保留）的有效性。 受试者将随机分为抗IgE或安慰剂组，每两个月皮下注射抗IgE或安慰剂一次，持续1年，并分两个阶段进行随访。 在I期或12周维持期，患者将维持其ICS稳定剂量，在II期或40周ICS停药期，受试者将根据方案降低ICS剂量。 将在以下方面比较抗IgE治疗与安慰剂的疗效和安全性：（1）通过电子方式对ICS使用进行真实的实时监测测量的ICS剂量降低（主要目的），（2）哮喘症状评分、药物使用和电子监测的呼气峰流量水平，（3）肺功能和支气管反应性水平，（4）人文和药物经济学指标，（6）皮肤试验反应性和炎症标志物，（7）体细胞生长，和（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.