CHILDHOOD ASTHMA PREVENTION STUDY (CAPS) FOR PACRN

哮喘是儿童最常见的慢性呼吸道疾病，尽管有更好的诊断和更好的抗炎治疗，但在世界各地，哮喘的患病率、发病率和死亡率仍在以流行的比例增加。重组人源化抗IgE单抗是目前最有前景的非特异性免疫调节剂，可用于非特异性调节过敏性哮喘的主要效应分子IgE。在青少年和成人中，抗-IgE可使游离的IgE和IgE受体减少95%以上，改善哮喘症状和肺功能，并减少PRN支气管扩张剂和皮质类固醇的使用。这里提出了两个项目，每个项目都是前瞻性的、随机的、掩蔽的和安慰剂对照的，以评估抗IgE在儿童哮喘一级和二级预防中的有效性和安全性。建议1或初级哮喘预防将决定抗-IgE能否防止232名患有特应性皮炎、食物过敏或过敏性鼻炎、特异性IgE和父母有特应性过敏症病史的1-2岁高危婴儿发生哮喘。患者将被随机分为抗IgE组或安慰剂组，每两个月皮下注射一次抗IgE或安慰剂，并跟踪观察哮喘的发展情况，为期3年。次要目标包括确定抗-IgE与安慰剂在以下方面是否不同：(1)至少轻度持续性哮喘的发病，(2)由脉冲振荡确定的肺阻抗和支气管反应性，(3)皮试反应性和炎症标志物，(4)对特应性疾病的影响，以及(5)长期安全性和成长性。建议2或哮喘二级预防将确定与安慰剂相比，在140名5-12岁患有中度至重度持续性过敏性哮喘需要吸入性皮质类固醇(ICS)的儿童中，抗IgE与安慰剂相比是否有效。受试者将被随机分为抗-IgE组或安慰剂组，每两个月皮下注射一次抗-IgE或安慰剂，为期一年，随后分两个阶段进行。在第一阶段或12周的辅助阶段，患者将保持稳定的ICS剂量，在第二阶段或40周的ICS停药阶段，受试者将按方案减少ICS。抗-IgE疗法与安慰剂的有效性和安全性将从以下方面进行比较：(1)通过对ICS使用进行电子实时监测来衡量ICS剂量的减少(主要目的)，(2)通过电子监测哮喘症状评分、用药情况和最大呼气流速水平，(3)肺功能和支气管反应性水平，(4)人文和药物经济学措施，(6)皮试反应性和炎症标志物，(7)体格生长和(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.