婴幼儿喘息的诊治婴幼儿喘息的诊治. .首次喘息诊断首次喘息诊断 毛细毛细 （病毒感染性喘息）（病毒感染性喘息） 喘支喘支 哮喘首次发作哮喘首次发作 肺肺 炎炎 支气管异物支气管异物 支气管畸形合并感染支气管畸形合并感染. .迁延或持续或反复喘息诊断迁延或持续或反复喘息诊断首次病毒感染性喘息治疗不彻底首次病毒感染性喘息治疗不彻底哮喘哮喘胃食道反流胃食道反流气道畸形气道畸形 ：气管：气管-支气管软化、狭窄支气管软化、狭窄血管发育畸形血管发育畸形: 双主动脉弓等双主动脉弓等肺结核肺结核: 肿大淋巴结压迫气道或支气管结核肿大淋巴结压迫气道或支气管结核支气管异物支气管异物免疫功能缺陷合并气道、肺部反复感染免疫功能缺陷合并气道、肺部反复感染闭塞性细支气管炎闭塞性细支气管炎*持续性细菌性支气管（细支气管）炎持续性细菌性支气管（细支气管）炎*. .气道狭窄气道狭窄 支气管异物支气管异物支气管畸形和血管压迫支气管畸形和血管压迫. .首次病毒感染性喘息治疗不彻底首次病毒感染性喘息治疗不彻底 病毒感染性气道高反应持续病毒感染性气道高反应持续 合并感染合并感染: 肺炎和持续性细菌性支气管炎肺炎和持续性细菌性支气管炎 平喘药物停用后反复平喘药物停用后反复 . .哮喘早期考虑哮喘早期考虑 具有哮喘特征：发作性、可逆性，重复性具有哮喘特征：发作性、可逆性，重复性 喘息病情重：喘息病情重： 家族或个人过敏史家族或个人过敏史 除外其他引起喘息性疾病除外其他引起喘息性疾病. .持续性细菌性支气管炎持续性细菌性支气管炎 很多诊断名词：很多诊断名词： （1）慢性化脓性肺疾病（）慢性化脓性肺疾病（Chronic Suppurative Lung Disease） （2）持续性支气管内膜感染）持续性支气管内膜感染( Persistent Endobrobchial Infections) （3）迁延性支气管炎（）迁延性支气管炎（Protracted Bronchitis） （4）慢性支气管炎（）慢性支气管炎（Chronic Bronchitis）. .临床表现临床表现 发病年龄：发病年龄：2岁以内常见岁以内常见 诱因：急性上下呼吸道感染诱因：急性上下呼吸道感染 表现：持续性湿性咳嗽、喘息表现：持续性湿性咳嗽、喘息 吸气相和呼气相吸气相和呼气相粗痰鸣音粗痰鸣音 而不是典型的喘鸣而不是典型的喘鸣. .影像学表现影像学表现 可以正常可以正常 最常见的异常表现为支气管壁增厚最常见的异常表现为支气管壁增厚 斑片片影斑片片影 可有支气管扩张可有支气管扩张. .支气管镜表现支气管镜表现 传导气道分泌物多，多呈脓性传导气道分泌物多，多呈脓性 粘膜水肿粘膜水肿 气道闭塞气道闭塞 支气管内膜炎支气管内膜炎 肺泡灌洗液细胞学分析，中性粒细胞为主肺泡灌洗液细胞学分析，中性粒细胞为主. .病原学病原学肺炎链球菌、流感嗜血杆菌最常见肺炎链球菌、流感嗜血杆菌最常见 卡他汉菌、其他链球菌卡他汉菌、其他链球菌G- 杆菌杆菌. .并存疾病并存疾病 哮哮 喘喘同时存在哮喘而导致诊断过程复杂化同时存在哮喘而导致诊断过程复杂化. .治 疗 流感嗜血杆菌、肺炎链球菌等治疗流感嗜血杆菌、肺炎链球菌等治疗 疗程疗程3-6周周. . Wheeze in preschool age is associated with pulmonary bacterial infection and resolves after antibiotic therapyBACKGROUND: Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children.METHODOLOGY/PRINCIPAL FINDINGS: Preschool children (n=42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2-16 weeks (n=29). Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts ( 10 colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination.CONCLUSIONS/SIGNIFICANCE: Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy. PLoS One. 2011;6(11):e27913. Epub 2011 Nov 29. .闭塞性细支气管炎闭塞性细支气管炎（Bronchiolitis Obliterans) 北京儿童医院北京儿童医院 赵顺英赵顺英. .定 义 闭塞性细支气管炎（闭塞性细支气管炎（Bronchiolitis obliterans）是与细支气管炎症性损伤相）是与细支气管炎症性损伤相关，导致管腔闭塞的慢性气流阻塞综合关，导致管腔闭塞的慢性气流阻塞综合征。征。 也可发生于支气管也可发生于支气管, 出现闭塞、扩张出现闭塞、扩张 . . 病 因 毒气的吸入 感染 病毒 ：腺病毒 、流感病毒、麻疹病毒 细菌： 金葡菌、 B族溶血性链球菌、 肺炎链球菌 肺炎支原体. . 结缔组织病、组织器官移植： 自身免疫性溶血、骨髓移植、心肺移植、 类风湿性关节炎、渗出性多形性红斑 其它： 支气管肺发育不良（BPD） 先天性心脏病、囊性纤维化 吸入： 异物吸入 胃-食管返流（GER） 药物、肿瘤 特发性 狭窄性为主. .症状 咳嗽、喘息 气促、呼吸困难 运动不耐受、反复呼吸道感染 短暂的症状改善期后加重、持续体征 喘鸣音 “crackles”临床表现. .实验室检查实验室检查 血气分析血气分析 肺功能肺功能 影像学影像学 电子支气管镜检查电子支气管镜检查 肺通气灌注扫描肺通气灌注扫描. .实验室检查肺功能（续实验室检查肺功能（续）用来诊断小气道疾病的方法用来诊断小气道疾病的方法世界心肺移植协会世界心肺移植协会19931993年提议、年提议、20022002年修订年修订BOBO临临 床分级，被广泛用于描述床分级，被广泛用于描述BOBO 可用于可用于BOBO疗效的观察疗效的观察 建议用所测值占预计值的百分数来表示建议用所测值占预计值的百分数来表示. .实验室检查肺功能（续）正常婴儿正常婴儿TBFVTBFV环环BOBO婴儿婴儿TBFVTBFV环环 升枝陡，高峰前移，峰值较高，降枝凹陷潮气流速容量环（TBFV）特点%V-PF25/PFPTEFViVi/kgVeTiRRPF/Ve容量流速. .实验室检查胸片实验室检查胸片 无特异性改变无特异性改变 两肺过度充气两肺过度充气 随病情进展，出现斑片状肺泡浸润影，呈毛玻璃随病情进展，出现斑片状肺泡浸润影，呈毛玻璃 样，边缘不清样，边缘不清 可有单侧透明肺可有单侧透明肺. .实验室检查实验室检查 肺肺CTCT HRCT HRCT征象征象： 马赛克灌注征马赛克灌注征 支气管扩张支气管扩张 支气管壁增厚支气管壁增厚 气体捕捉征气体捕捉征 呼气相呼气相CTCT： 较吸气相较吸气相CTCT能更好地能更好地 显示小气道病变显示小气道病变. .BO的临床诊断(1)(1)急性感染或急性肺损伤后急性感染或急性肺损伤后6 6周以上的反复或持续气促，周以上的反复或持续气促，喘息或咳嗽、喘鸣，对支气管扩张剂无反应；喘息或咳嗽、喘鸣，对支气管扩张剂无反应；(2)(2)临床表现与胸部临床表现与胸部x x线片轻重程度不符，临床床症状重，线片轻重程度不符，临床床症状重，胸部胸部x x线片多为过度通气；线片多为过度通气；(3)(3)肺肺CTCT显示支气管壁增厚，支气管扩张，肺不张，马赛显示支气管壁增厚，支气管扩张，肺不张，马赛克灌注征、小叶中心行结节；克灌注征、小叶中心行结节；(4)(4)肺功能示阻塞性通气功能障碍；肺功能示阻塞性通气功能障碍；(5)(5)胸部胸部x x线片为单侧透明肺线片为单侧透明肺; ;排除其他阻塞性疾病，如哮喘、先天纤毛运动功能障排除其他阻塞性疾病，如哮喘、先天纤毛运动功能障碍、囊性纤维化、异物吸入、先天发育异常、结核、碍、囊性纤维化、异物吸入、先天发育异常、结核、艾滋病和其他免疫功能缺陷等。艾滋病和其他免疫功能缺陷等。. .治疗激素激素大环内酯类大环内酯类孟鲁司特孟鲁司特支气管扩张剂：对有反应的病人支气管扩张剂：对有反应的病人抗生素：合并感染时应用，常感染抗生素：合并感染时应用，常感染. .儿科治疗儿科治疗 激 素（泼尼松） 足量：12mg/kg.d 13个月，必要时冲击。 维持： 1年以上 大环内酯类 小剂量红霉素、阿奇霉素 抗生素：常合并感染，肺炎链球菌多见 避免再次打击很重要！ . .儿科治疗儿科治疗孟鲁司特孟鲁司特 文献报道对文献报道对BO有效有效 主要机制为抑制平滑肌增殖主要机制为抑制平滑肌增殖 为抑制肌成纤维细胞活化为抑制肌成纤维细胞活化 临床使用临床使用. .学龄前期反复喘息表型学龄前期反复喘息表型 发作性喘息发作性喘息(Episodic wheezing ): 不能缓解喘息不能缓解喘息(unremitting wheezing): 未分类喘息未分类喘息: 几周评价治疗反应几周评价治疗反应, 表型评价表型评价 . .学龄前期反复喘息表型学龄前期反复喘息表型 发作性喘息发作性喘息: 诱因通常为病毒诱因通常为病毒,发作间歇期正发作间歇期正常常,常无家族和个人过敏史常无家族和个人过敏史 不能缓解的喘息不能缓解的喘息: 诱因多种诱因多种, 有家族和个人过有家族和个人过敏史敏史. .学龄前期反复喘息表型分类学龄前期反复喘息表型分类Episodic wheezing is defined as wheezing in discrete episodes of 2 to 4 weeks in duration, with the child being well in between episodes. The trigger is usually a viral infection. In unremitting wheezing, the child has distinct episodes of wheezing but between these severe episodes also has intermittent symptoms, such as coughing or wheezing at night or in response to exercise, crying, laughter, mist, or cold air. Viral infections are also the most common causes of these severe episodes, but they may persist in the presence of other triggers, such as passive smoking, allergen exposure, or air pollution. Consequently, this wheezing phenotype has also been termed multitrigger wheezing. The wheezing phenotypes can sometimes be hard to distinguishand can change as children grow older:. .学龄前期反复喘息表型分类学龄前期反复喘息表型分类Episodic wheezing is usually not associated with atopy and rarely progresses to asthma. In contrast, unremitting wheezing in children of preschoolage is often associated with atopic sensitizationas early as the first year of life. children often have allergies to foods such as hens eggs and cows milk. Many of these children have atopic dermatitis or sensitization to indoor allergens, with subsequent development of impaired lung function. By the time they are in school, we call their disease asthma. .学龄前期反复喘息治疗学龄前期反复喘息治疗发作性（病毒诱发性喘息）发作性（病毒诱发性喘息）: 孟鲁司特孟鲁司特不能缓解喘息（多因素有关）：吸入激素不能缓解喘息（多因素有关）：吸入激素（ICS）或）或 孟鲁司特孟鲁司特. . .A simple tool to identify infants at high risk of mild to severe childhood asthma: the persistent asthma predictive scoreJ Asthma. 2011 ;48(10):1015-21 Three parameters independently predicted persistent asthma: family history of asthma, personal atopic dermatitis, and multiple allergen sensitizations. Based on these variables, the PAPS showed 42% sensitivity, 90% specificity, 67% positive predictive value, and 76% negative predictive value for the prediction of persistent asthma. . .Daily or Intermittent Budesonide in Preschool Children with Recurrent WheezingN Engl J Med 2011; 365:1990-2001 BACKGROUND Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy.METHODS We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy.RESULTS The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval CI, 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen.CONCLUSIONS A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. . .气道重塑何时发生气道重塑何时发生? 年幼儿气道炎症作为哮喘起源的根本已经年幼儿气道炎症作为哮喘起源的根本已经受到挑战受到挑战 因为研究发现在幼儿哮喘发病时，气道结因为研究发现在幼儿哮喘发病时，气道结构改变已经存在，但气道炎症相对缺乏构改变已经存在，但气道炎症相对缺乏 . .气道重塑何时发生？气道重塑何时发生？ 在哮喘中观察到的在哮喘中观察到的“气道重塑气道重塑”与胎儿肺与胎儿肺发育时在分支形成期气道的构建类似，异发育时在分支形成期气道的构建类似，异常构建与哮喘发病有关常构建与哮喘发病有关 认为气道重塑为先天性，至少与气道炎症认为气道重塑为先天性，至少与气道炎症平行平行. .儿童哮喘防治重要性儿童哮喘防治重要性儿童哮喘的病理变化处于可逆性功能性儿童哮喘的病理变化处于可逆性功能性改变（量变）阶段，改变（量变）阶段，必须防止发展到不可逆性器质性改变必须防止发展到不可逆性器质性改变 （质变）阶段（质变）阶段对儿童哮喘要抓对儿童哮喘要抓“三早三早”： 关注气道重塑关注气道重塑 早诊断、早治疗、早预防早诊断、早治疗、早预防. . 谢 谢！. .