Lower airway inflammation in infants with cystic fibrosis detected by newborn screening
Lower airway inflammation in infants with cystic fibrosis detected by newborn screening
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DOI：
10.1002/ppul.20294
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发表时间：
2005-12-01
影响因子：
3.1
通讯作者：
Grimwood, K
中科院分区：
文献类型：
--
作者：
Armstrong, DS;Hook, SM;Grimwood, K
关于以囊性纤维化（CF）为特征的下气道炎症是否主要由遗传缺陷引起存在争议。为了确定炎症是否发生在感染之前，我们检查了支气管肺泡灌洗液（BAL）细胞学、细胞因子（白细胞介素(IL)-1 β、IL-4、IL-5、IL-6、IL-8、IL-10和肿瘤坏死因子- α）和游离中性粒细胞弹性酶活性，这些数据来自70名新生儿筛查出的CF（1.5-71个月）儿童和19名慢性哮鸣症对照组（2.0-48个月）。选择CF受试者并将其分类为原始（13岁= 10(5)个菌落形成单位/ml BAL中致病菌）和未感染（15岁，bb - 6个月，无症状，支气管镜检查时未服用抗生素，BAL中无病原体）。为了进一步确定炎症是否在没有感染的情况下发生，对来自38名CF受试者的配对年度BAL样本中的炎症介质进行了测量，并根据BAL是否表现出持续性（n = 6）、获得性（n = 8）、清除（n = 13）或无感染（n = 11）对结果进行了分组。虽然未感染和对照组患者的BAL特征相似，但感染患者的炎症指数升高，包括IL-10升高（P < 0.001）。原始受试者的炎症症状最少。BAL对分析发现，四种感染组在中性粒细胞百分比、IL-8 （P < 0.001）和游离中性粒细胞弹性蛋白酶（P = 0.009）的变化方面存在差异。感染与BAL液中炎症介质升高有关。相比之下，轻微或减轻炎症的迹象，并没有从BAL液中根除感染。我们得出结论，在CF中，感染引发并维持气道炎症。
Controversy exists over whether the lower airway inflammation that characterizes cystic fibrosis (CF) is initiated primarily by the genetic defect. To determine if inflammation precedes infection, we examined bronchoalveolar lavage (BAL) fluid cytology, cytokines (interleukin (IL)-1 beta, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha), and free neutrophil elastase activity from 70 CF (aged 1.5-71 months) children detected by newborn screening and 19 (aged 2.0-48 months) controls with chronic stridor. CF subjects were selected and categorized as pristine (13 aged = 10(5) colony-forming units/ml of pathogenic bacteria in BAL), and uninfected (15 aged > 6 months, asymptomatic, not taking antibiotics at bronchoscopy, and free of pathogens in their BAL). To further resolve if inflammation develops without infection, inflammatory mediators in paired annual BAL samples from 38 CF subjects were measured, and results were grouped according to whether BAL showed persistence (n = 6), acquisition (n = 8), clearance (n = 13), or absence (n = 11) of infection. While pristine, uninfected, and control subjects had similar BAL profiles, infected patients showed elevated inflammatory indices, including increased IL-10 (P < 0.001). Pristine subjects had the fewest signs of inflammation. Analysis of BAL pairs found differences between the four infection groups for changes in neutrophil percentages, IL-8 (P < 0.001), and free neutrophil elastase (P = 0.009). Infection was associated with elevated inflammatory mediators in BAL fluid. In contrast, minimal or reduced signs of inflammation accompanied absence of eradication of infection from BAL fluid. We conclude that in CF, infection initiates and sustains airway inflammation.