Division of Pulmonary and Sleep Medicine, Department of Pediatrics.
Children's Core for Biomedical Statistics, Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, Washington; and.
Ann Am Thorac Soc. 2020 Dec;17(12):1590-1598. doi: 10.1513/AnnalsATS.202002-179OC.
Considerable morbidity and disease progression in people with cystic fibrosis (CF) result from pulmonary exacerbations (PExs). PEx guidelines note insufficient evidence to recommend for or against the concomitant use of inhaled and intravenous antibiotics. We hypothesize that the addition of inhaled antibiotics for PEx therapy is associated with improvements in lung function and a longer time to next PEx compared with standard intravenous antibiotics alone. We performed a retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. People with CF were included if they were hospitalized for PEx between 2006 and 2016 and 6 to 21 years of age. Lung function outcomes were assessed by linear mixed effect modeling and generalized estimating equations. The time to next PEx was assessed by Cox proportional hazards regression. To estimate independent causal effects while accounting for indication bias and other confounders, inverse probabilities of treatment weights were calculated based on covariates believed to influence the likelihood of inhaled antibiotic use during PEx treatment. A total of 3,253 children and adolescents contributed 9,040 PEx events for analysis. Inhaled antibiotics were used in 23% of PEx events but were not associated with better pre- to post-PEx percent predicted forced expiratory volume in 1 second responses (mean difference, -1.11%; 95% confidence interval [CI], -1.83 to -0.38; = 0.003), higher odds of returning to lung function baseline (odds ratio, 0.94; 95% CI, 0.82 to 1.07; = 0.34), or longer time to next PEx (hazard ratio, 1.05; 95% CI, 0.99 to 1.12; = 0.098). The addition of inhaled antibiotics to standard intravenous antibiotic PEx treatment was not associated with improved lung function outcomes or a longer time to next PEx.
在囊性纤维化（CF）患者中，相当多的发病率和疾病进展是由肺部恶化（PEx）引起的。PEx 指南指出，没有足够的证据来推荐或反对同时使用吸入和静脉内抗生素。我们假设，与单独使用标准静脉内抗生素相比，在 PEx 治疗中添加吸入抗生素与肺功能的改善和下一次 PEx 的时间延长有关。我们使用 CF 基金会患者注册-Pediatric Health Information System 链接数据集进行了回顾性队列研究。如果患者在 2006 年至 2016 年期间因 PEx 住院，且年龄在 6 至 21 岁之间，则将其纳入研究。通过线性混合效应模型和广义估计方程评估肺功能结果。使用 Cox 比例风险回归评估下一次 PEx 的时间。为了在考虑指示偏差和其他混杂因素的情况下估计独立的因果效应，根据被认为会影响在 PEx 治疗期间使用吸入抗生素的可能性的协变量，计算了治疗的逆概率权重。共有 3253 名儿童和青少年参与了 9040 次 PEx 事件的分析。在 23%的 PEx 事件中使用了吸入抗生素，但与更好的 PEx 前后预测 1 秒用力呼气量的百分比反应（平均差异，-1.11%；95%置信区间 [CI]，-1.83 至 -0.38； = 0.003）、更高的恢复到肺功能基线的可能性（比值比，0.94；95% CI，0.82 至 1.07； = 0.34）或下一次 PEx 的时间更长（风险比，1.05；95% CI，0.99 至 1.12； = 0.098）无关。在标准静脉内抗生素 PEx 治疗中添加吸入抗生素与改善肺功能结果或延长下一次 PEx 的时间无关。
