Department of Paediatrics, University of Auckland, , Auckland, New Zealand.
Thorax. 2013 Jul;68(7):643-51. doi: 10.1136/thoraxjnl-2012-202342. Epub 2013 Jan 23.
Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years.
Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry.
168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospital-managed exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient -0.39, 95% CI -0.74 to -0.05).
Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group.
新生儿筛查可在不可逆性肺损伤发生前，于幼儿期尝试囊性纤维化（CF）的新疗法。由于呼吸恶化是潜在的试验结果变量，我们确定了学龄前 CF 患儿的恶化发生率、持续时间和临床特征；并确定了它们是否与 5 岁时的生长、肺结构和功能有关。
在澳大利亚囊性纤维化支气管肺泡灌洗试验中，前瞻性地记录了筛查后入组的患儿的呼吸恶化情况，直至 5 岁。所有参与者都接受了临床评估、胸部 CT 扫描和肺功能检查。
168 名儿童（88 名男孩）经历了 2080 次恶化，平均每人每年恶化 3.66 次；80.1%为社区管理，19.9%需要住院治疗。恶化率平均每年增加 9%（95%CI 4%至 14%；p<0.001）。恶化率因部位而异（p<0.001），接受 12 个月预防性抗生素治疗的儿童恶化率降低 26%（95%CI 12%至 38%）。前 2 年恶化率与 1 秒用力呼气量 z 评分降低有关。有过住院管理的恶化史与胸部 CT 扫描中的支气管扩张症（OR 2.67，95%CI 1.13 至 6.31）和 5 岁时的体重 z 评分较低有关（系数-0.39，95%CI-0.74 至-0.05）。
幼儿期的呼吸恶化是 CF 肺部疾病进展的标志物，也是该年龄段新疗法的潜在试验结果指标。
