Murray Clare S, Woodcock Ashley, Langley Stephen J, Morris Julie, Custovic Adnan
University of Manchester, North West Lung Centre, Wythenshawe Hospital, Manchester M23 9LT, UK.
Lancet. 2006 Aug 26;368(9537):754-62. doi: 10.1016/S0140-6736(06)69285-4.
Wheezing and asthma often begins in early childhood, but it is difficult to predict whether or not a wheezy infant will develop asthma. Some researchers suggest that treatment with inhaled corticosteroids at the first signs of wheezing in childhood could prevent the development of asthma later in life. However, other investigators have reported that although such treatment could help control symptoms, the benefits can disappear within months of stopping treatment. We tested our hypothesis that to prevent loss of lung function and worsening asthma later in childhood, anti-inflammatory treatment needs to be started early in life.
We did a randomised, double-blind, controlled study of inhaled fluticasone propionate 100 mug twice daily in young children who were followed prospectively and randomised after either one prolonged (>1 month) or two medically confirmed wheezy episodes. The dose of study drug was reduced every 3 months to the minimum needed. If the symptoms were not under control by 3 months, open-label fluticasone propionate 100 mug twice daily was added to the treatment. Children were followed-up to 5 years of age, at which point we gave their parents or guardians questionnaires, and measured the children's lung function (specific airways resistance [sR(aw)], forced expiratory volume in 1s [FEV1]) and airway reactivity (eucapnic voluntary hyperventilation [EVH] challenge). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN86717853.
We followed 1073 children prospectively, of whom 333 were eligible, and 200 of these began treatment (130 male, median age 1.2 years [range 0.5-4.9]; 101 placebo, 99 treatment); 173 (85 treatment, 88 placebo) completed the follow-up at age five years. The groups did not differ significantly in the proportion of children with current wheeze, physician-diagnosed asthma or use of asthma medication, lung function, or airway reactivity (percentage change in FEV1, adjusted mean for placebo 5.5% [95% CI -2.5 to 13.4]) vs for treatment 5.0% [-2.2 to 12.2], p=0.87). There were no differences in the results after adjustment for open-label fluticasone propionate, nor between the two groups in the time before the open-label drug was added (estimated hazard ratio 1.12 [95% CI 0.73-1.73], p=0.60), or the proportion needing the open-label drug (43 [42.57%] placebo, 41 [41.41%] treatment).
The early use of inhaled fluticasone propionate for wheezing in preschool children had no effect on the natural history of asthma or wheeze later in childhood, and did not prevent lung function decline or reduce airway reactivity.
喘息和哮喘通常始于幼儿期，但很难预测喘息的婴儿是否会发展为哮喘。一些研究人员认为，在儿童期首次出现喘息迹象时使用吸入性糖皮质激素进行治疗，可能会预防日后哮喘的发生。然而，其他研究人员报告称，尽管这种治疗有助于控制症状，但在停止治疗后的几个月内，益处可能会消失。我们检验了我们的假设，即要预防儿童后期肺功能丧失和哮喘恶化，抗炎治疗需要在生命早期开始。
我们对每日两次吸入100微克丙酸氟替卡松的幼儿进行了一项随机、双盲、对照研究，这些幼儿在经历一次持续时间较长（>1个月）或两次经医学确认的喘息发作后进行前瞻性随访并随机分组。研究药物的剂量每3个月减少至所需的最低剂量。如果3个月内症状未得到控制，则在治疗中添加每日两次100微克的开放标签丙酸氟替卡松。对儿童进行随访至5岁，届时我们向他们的父母或监护人发放问卷，并测量儿童的肺功能（比气道阻力[sR(aw)]、第1秒用力呼气容积[FEV1]）和气道反应性（等二氧化碳通气过度[EVH]激发试验）。本研究已注册为国际标准随机对照试验，编号为ISRCTN86717853。
我们前瞻性地随访了1073名儿童，其中333名符合条件，其中200名开始治疗（130名男性，中位年龄1.2岁[范围0.5 - 4.9岁]；101名接受安慰剂治疗，99名接受治疗）；173名（85名接受治疗，88名接受安慰剂治疗）在5岁时完成随访。两组在当前喘息、医生诊断的哮喘或使用哮喘药物的儿童比例、肺功能或气道反应性方面无显著差异（FEV1的百分比变化，安慰剂调整后均值为5.5%[95%CI -2.5至13.4]），治疗组为5.0%[-2.2至12.2]，p = 0.87）。在对开放标签丙酸氟替卡松进行调整后，结果无差异，两组在添加开放标签药物之前的时间（估计风险比1.12[95%CI 0.73 - 1.73]，p = 0.60）或需要开放标签药物的比例（43名[42.57%]安慰剂组，41名[41.41%]治疗组）方面也无差异。
学龄前儿童喘息时早期使用吸入性丙酸氟替卡松对儿童后期哮喘或喘息的自然病程没有影响，也不能预防肺功能下降或降低气道反应性。
