Davis Chelsea S, Faino Anna V, Onchiri Frankline, Gibson Ronald L, Merjaneh Lina, Ramsey Bonnie W, Rosenfeld Margaret, Cogen Jonathan D
Division of Pulmonary and Sleep Medicine and.
Core for Biostatistics, Epidemiology, and Analytics in Research, Seattle Children's Research Institute, Seattle, Washington.
Ann Am Thorac Soc. 2023 Jan;20(1):75-82. doi: 10.1513/AnnalsATS.202203-201OC.
Pulmonary exacerbation (PEx) events contribute to lung function decline in people with cystic fibrosis (CF). CF Foundation PEx guidelines note that a short course of systemic corticosteroids may offer benefit without contributing to long-term adverse effects. However, insufficient evidence exists to recommend systemic corticosteroids for PEx treatment. To determine if systemic corticosteroids for the treatment of in-hospital pediatric PEx are associated with improved clinical outcomes compared with treatment without systemic corticosteroids. We conducted a retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System linked database. People with CF were included if hospitalized for a PEx between 2006 and 2018 and were 6-21 years of age. Time to next PEx was assessed by Cox proportional hazards regression. Lung function outcomes were assessed by linear mixed-effect modeling and generalized estimating equations. To address confounding by indication, inverse probability treatment weighting was used. A total of 3,471 people with CF contributed 9,787 PEx for analysis. Systemic corticosteroids were used in 15% of all PEx. In our primary analysis, systemic corticosteroids were not associated with better pre- to post-PEx percent predicted forced expiratory volume in 1 second responses (mean difference, -0.36; 95% confidence interval [CI], -1.14, 0.42; = 0.4) or a higher odds of returning to lung function baseline (odds ratio, 0.97; 95% CI, 0.84-1.12; = 0.7) but were associated with a reduced chance of future PEx requiring intravenous antibiotics (hazard ratio, 0.91; 95% CI, 0.85-0.96; = 0.002). When restricting the analysis to one PEx per person, lung function outcomes remained no different among PEx treated with or without systemic corticosteroids, but, in contrast to our primary analysis, the use of systemic corticosteroids was no longer associated with a reduced chance of having a future PEx requiring intravenous antibiotics (hazard ratio, 0.96; 95% CI, 0.86, 1.07; = 0.42). Systemic corticosteroid treatment for in-hospital pediatric PEx was not associated with improved lung function outcomes. Prospective trials are needed to better evaluate the risks and benefits of systemic corticosteroid use for PEx treatment in children with CF.
肺部加重（PEx）事件会导致囊性纤维化（CF）患者的肺功能下降。囊性纤维化基金会的PEx指南指出，短期全身性皮质类固醇治疗可能有益，且不会产生长期不良影响。然而，目前尚无足够证据推荐使用全身性皮质类固醇治疗PEx。为了确定与不使用全身性皮质类固醇治疗相比，使用全身性皮质类固醇治疗住院儿科PEx是否能改善临床结局。我们使用囊性纤维化基金会患者登记处 - 儿科健康信息系统链接数据库进行了一项回顾性队列研究。纳入2006年至2018年间因PEx住院且年龄在6至21岁的CF患者。通过Cox比例风险回归评估下次PEx的时间。通过线性混合效应模型和广义估计方程评估肺功能结局。为了解决指征性混杂问题，使用了逆概率治疗加权法。共有3471名CF患者贡献了9787次PEx用于分析。所有PEx中有15%使用了全身性皮质类固醇。在我们的主要分析中，全身性皮质类固醇与PEx前后一秒用力呼气量预测值百分比的改善无关（平均差异为-0.36；95%置信区间[CI]为-1.14，0.42；P = 0.4），也与恢复到肺功能基线的较高几率无关（优势比为0.97；95%CI为0.84 - 1.12；P = 0.7），但与未来需要静脉使用抗生素的PEx几率降低有关（风险比为0.91；95%CI为0.85 - 0.96；P = 0.002）。当将分析限制为每人一次PEx时，使用或未使用全身性皮质类固醇治疗的PEx之间肺功能结局仍然没有差异，但与我们的主要分析不同的是，使用全身性皮质类固醇不再与未来需要静脉使用抗生素的PEx几率降低有关（风险比为0.96；95%CI为0.86，1.07；P = 0.42）。住院儿科PEx的全身性皮质类固醇治疗与改善肺功能结局无关。需要进行前瞻性试验以更好地评估在CF儿童中使用全身性皮质类固醇治疗PEx的风险和益处。
