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儿童支气管扩张症加重的表型特征与口服抗生素治疗 14 天后症状缓解有关。

Phenotypic Features of Pediatric Bronchiectasis Exacerbations Associated With Symptom Resolution After 14 Days of Oral Antibiotic Treatment.

机构信息

Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, QLD, Australia; Department of Respiratory and Sleep Medicine, Queensland Children's Hospital, Brisbane, QLD, Australia; Department of Paediatrics, Gold Coast Health, Griffith University, Gold Coast, QLD, Australia.

Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, QLD, Australia; NHMRC Centre for Research Excellence in Paediatric Bronchiectasis, Child Health Division, Menzies School of Health Research, Darwin, NT, Australia.

出版信息

Chest. 2023 Dec;164(6):1378-1386. doi: 10.1016/j.chest.2023.07.002. Epub 2023 Jul 10.

Abstract

BACKGROUND

Respiratory exacerbations in children and adolescents with bronchiectasis are treated with antibiotics. However, antibiotics can have variable interindividual effects when treating exacerbations.

RESEARCH QUESTION

Can phenotypic features associated with symptom resolution after a 14-day course of oral antibiotics for a nonsevere exacerbation of bronchiectasis be identified?

STUDY DESIGN AND METHODS

Combining data from two multicenter randomized controlled trials, we identified 217 children with bronchiectasis assigned to at least 14 days of oral antibiotics to treat nonsevere (nonhospitalized) exacerbations. Univariable and then multivariable logistic regression were used to identify factors associated with symptom resolution within 14 days of commencing antibiotics. Identified associations were re-evaluated by mediation analysis.

RESULTS

Of the 217 study participants (52% male patients), 41% were Indigenous (Australian First Nations, New Zealand Māori, or Pacific Islander). The median age was 6.6 years (interquartile range, 4.0-10.1 years). By day 14, symptoms had resolved in 130 children (responders), but persisted in the remaining 87 children (nonresponders). Multivariable analysis found those who were Indigenous (adjusted OR [AOR], 3.59; 95% CI, 1.35-9.54) or showed new abnormal auscultatory findings (AOR, 3.85; 95% CI, 1.56-9.52) were more likely to be responders, whereas those with multiple bronchiectatic lobes at diagnosis (AOR, 0.66; 95% CI, 0.46-0.95) or higher cough scores when starting exacerbation treatment (AOR, 0.55; 95% CI, 0.34-0.90) were more likely to be nonresponders. Detecting a respiratory virus at the beginning of an exacerbation was not associated with antibiotic failure at 14 days.

INTERPRETATION

Children with Indigenous ethnicity, milder bronchiectasis, mild exacerbations (low reported cough scores), or new abnormal auscultatory signs are more likely to respond to appropriate oral antibiotics than those without these features. These patient and exacerbation phenotypes may assist clinical management and development of biomarkers to identify those whose symptoms are more likely to resolve after 14 days of oral antibiotics.

TRIAL REGISTRY

Australian New Zealand Clinical Trials Registry; Nos.: ACTRN12612000011886 and ACTRN12612000010897; URL: https://www.anzctr.org.au.

摘要

背景

支气管扩张症患儿和青少年的呼吸道恶化需要用抗生素治疗。然而,抗生素在治疗恶化时可能会对个体产生不同的影响。

研究问题

能否确定与支气管扩张症非严重恶化(非住院)经 14 天口服抗生素治疗后症状缓解相关的表型特征?

研究设计和方法

我们结合了两项多中心随机对照试验的数据,确定了 217 名接受至少 14 天口服抗生素治疗非严重(非住院)恶化的支气管扩张症儿童。使用单变量和多变量逻辑回归来确定开始使用抗生素后 14 天内症状缓解的相关因素。通过中介分析重新评估已确定的关联。

结果

在 217 名研究参与者中(52%为男性患者),41%为原住民(澳大利亚原住民、新西兰毛利人或太平洋岛民)。中位年龄为 6.6 岁(四分位间距,4.0-10.1 岁)。到第 14 天,130 名儿童(应答者)的症状已缓解,但其余 87 名儿童(无应答者)的症状仍持续存在。多变量分析发现,原住民(调整后的比值比 [OR],3.59;95%CI,1.35-9.54)或出现新的异常听诊发现(OR,3.85;95%CI,1.56-9.52)的患者更有可能成为应答者,而那些在诊断时存在多个支气管扩张肺叶(OR,0.66;95%CI,0.46-0.95)或在开始治疗恶化时咳嗽评分较高(OR,0.55;95%CI,0.34-0.90)的患者更有可能成为无应答者。在恶化开始时检测到呼吸道病毒与 14 天内抗生素治疗失败无关。

解释

具有原住民种族、较轻的支气管扩张症、较轻的恶化(报告的咳嗽评分较低)或新的异常听诊迹象的儿童比没有这些特征的儿童更有可能对适当的口服抗生素产生反应。这些患者和恶化表型可能有助于临床管理和开发生物标志物,以识别那些在口服抗生素治疗 14 天后症状更有可能缓解的患者。

试验注册

澳大利亚和新西兰临床试验注册处;编号:ACTRN12612000011886 和 ACTRN12612000010897;网址:https://www.anzctr.org.au。

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