抽象
坏死性肺炎(NP)是社区获得性肺炎,其特征在于通过液化和肺组织的气穴的严重并发症。该present研究描述流行病学,aetiology,管理和以NP在15年period住院患儿的结果。
NP的病例进行回顾性的观察研究是从1990年1月至2005年2月分析临床表现,实验室检查,住院期间和长期随访。
共检出80宗NP个案,检出个案数目由1993-1996年期间的12宗增至2001-2004年期间的40宗。共有69例(86%)胸膜积液,pH值低(平均值7.08),38例(48%)培养阳性肺炎链球菌作为主要生物体。最近,其他生物,最值得注意的是耐甲氧西林金黄色葡萄球菌,出现了。Patients had prolonged hospitalisations (median 12 days). A total of 69 patients required pleural interventions and those receiving chest drainage alone had similar outcomes to those managed surgically. All patients had full clinical resolution within 2 months of presentation.
坏死性肺炎越来越被认为是儿科肺炎的一种并发症。肺炎链球菌仍然是主要的生物,但自2002年以来,不同的细菌已被隔离,病例年龄范围已经扩大。尽管严重疾病,大量的实质损伤和长期住院治疗,长期结果如下坏死性肺炎是优秀的。
儿童社区获得性肺炎的并发症包括胸腔积液,脓胸,肺脓肿,pneumatocele和坏死性肺炎(NP)。NP,也称为空洞性肺炎或cavitatory坏死,已经与不良的临床结果在成人和相关的最初描述的时候,这种并发症被认为是儿童极为罕见。第一个案例系列NP的包括4名儿童是在1994年出版1随后有过几次小报告的病例系列儿童NP的2-6包括流行病学观察最近的一份报告7。
即使NP的诊断可以通过简单的胸部X光被怀疑,致密肺叶实变和胸腔积液的频繁存在可能掩盖适当定义和胸部CT需要一个更明确的诊断(CT)扫描。对于NP放射线标准包括正常肺实质架构的损耗和降低的实质增强的区域的存在,代表液化,即逐渐被多个小空气或流体填充的腔替换1,8。NP的病理生理学表现为大量的肺坏疽、组织液化和坏死9但导致这一巨大损失的确切途径尚未确立。NP的放射性诊断已与这样的病理结果相关10。此前报道都集中在NP所致肺炎链球菌11,尽管其它细菌生物体,包括金黄色葡萄球菌和肺炎支原体,据报道导致NP12,13。NP的病例报告数量增多,正值儿童肺炎的一些研究,这些研究报告与肺炎旁胸腔积液增加复杂性肺炎发病率的趋势14,15。当提及在这些研究中取得的NP,NP的这种变化趋势的相关作用尚未进行分析。
本的目的,回顾性,观察性研究是审查NP的情况下,在儿童医院,波士顿(哈佛大学医学院,波士顿,MA,USA)在15年期间住院儿童,并说明:1)流行病学,致病微生物,并与NP住院患儿的关键临床和实验室特征;2)管理策略和儿童并发症的存在下,用NP;在长期的临床结果与NP儿童和3)报告。
方法
病例选择
在波士顿儿童医院从1990年1月,住院至二月患者中NP的情况下,2005年被确定回顾性使用放射学系的电子数据库。所有病例均通过搜索住院患者,并与诸如“没有证据坏死性肺炎”报道的胸部CT扫描报告术语“坏死”被排除在外鉴定。的所有情况下的CT进行回顾和包括用于分析当CT显示示出包含空气,空气和流体,或流体非增强相反包围增强肺实质没有定义增强轮缘肺实质的多个区域的肺段8。孤立性空化周围有清晰可见的肺边缘的病例被排除,因为这可能代表肺脓肿。
数据采集
采用标准化数据收集表进行回顾性医院图表回顾。随后的分析排除了院内性肺炎和已存在肺部或心脏疾病的患者。对于每个患者,在入院时、入院期间以及随后在机构的任何门诊随访时最初获得的人口统计资料、实验室结果、微生物培养数据和临床信息均被记录。在本研究中,发热日定义为患者体温≥38℃的任何24小时期间。缺氧被定义为任何记录的氧饱和度<90%的脉搏血氧测量,测量在房间空气。这项研究得到了波士顿儿童医院机构审查委员会的批准。
统计方法
人口统计学、临床和实验室变量用标准描述性统计方法汇总。根据临床表现、干预措施和并发症进行组间比较,采用配对t检验(均数报告)、Wilcoxon检验(中位数报告)和卡方检验(比例报告)。双侧p值<0.05为差异有统计学意义。
结果
在15年的研究期间,共发现80例社区获得性NP。在1990-1993年期间没有发现任何病例,发现的病例数随时间从3例·年增加-11993-1996年至14例·年-1在2003-2004年(图1⇓)。
临床表现和放射照相发现
The median age at presentation was 3.6 yrs (interquartile range (IQR) 0.25–19 yrs; table 1⇓)。多数患者无显著既往病史;只有14(18%)患者有哮喘或喘息和九(11%)的报告的历史有复发性中耳炎的报道历史。随着两起案件外,这些孩子们没有已知的潜在免疫性疾病。一个病人有一个已知的潜在免疫缺陷(Schwachman-Diamond综合征)和另一名病人被诊断为与NP呈现随后的慢性肉芽肿病。Figure 2⇓从一个患者表现出代表性的CT图像,4-年生先前健康女性,并且证明在识别NP中使用的射线照相的标准,以及所述时间过程的疾病。
Almost all patients had fever (96%) and cough (84%), with a mean onset of symptoms 9 days prior to the hospitalisation. Other constitutional symptoms such as vomiting, abdominal pain and chest pain were only reported by a minority of patients. A total of 54 (74%) patients received at least one dose of oral antibiotics prior to their hospitalisation. For these patients, the mean duration (range) of pre-admission antibiotics was 3 (0–24) days.
实验室和微生物学特性
The predominant laboratory features (table 2⇓)为白细胞增多(平均白细胞计数18.4×103 cells·μL-1), bandaemia (mean 9%), anaemia (mean serum haemoglobin 10.4 mg·dL-1) and hypoalbuminaemia (mean serum albumin 2.0 mg·dL-1)。X光片上或CT扫描可感知的胸腔积液被视为在69(86%)的患者。Pleural fluid analysis revealed a low pH (mean 7.08), a low glucose (median 10.0 mg·dL-1)和高细胞计数(中位数9600)中性粒细胞占主导地位。Positive microbiological identification was obtained in 38 (48%) cases (fig. 1⇑)。胸膜液培养阳性19例,胸膜液乳胶凝集试验阳性5例。其他病原学诊断是基于阳性血培养或痰培养。入院前接受抗生素治疗与阳性微生物鉴定的减少无关(48与56%;p = 0.5).肺炎链球菌通过培养阳性和五个在18(22%)例(13被确定通过正性胸膜乳胶凝集研究)。乳胶凝集诊断均为阴性胸膜液培养。在整个研究期间,每年肺炎球菌的绝对数量是相似的。对阳性肺炎球菌培养的抗生素敏感性模式的回顾没有发现任何青霉素耐药的肺炎球菌。
自2000年以来,其他病原体的发病率,包括甲氧西林敏感金黄色葡萄球菌,耐甲氧西林金黄色葡萄球菌(MRSA),梭杆菌,铜绿假单胞菌和链球菌属。如S.米勒,增加了。所有的MRSA病例都是在2003年后发现的。
住院期间成果
The median length (IQR 9–17) of hospitalisation was 12 days, ranging from 3–84 days (table 3⇓)。During the hospitalisation, the median duration of fever was 6 days (IQR 3–9) ranging from 1–28 days. There were no statistically significant differences in the median number of febrile days between patients based on antibiotic pre-treatment (5与7 days; p = 0.18) or those presenting with pleural effusion (6与4。5 days; p = 0.24). There were no deaths in the cohort. Different types of antibiotic regimens were used as initial empiric treatment: including penicillins, cephalosporins, vancomycin and clindamycin, and in cases with positive cultures, antibiotic regimens were tailored to specific organism susceptibilities. All patients were treated with prolonged courses of antibiotics (median (range) 27 (3–95) days).
管理病人胸腔积液呈现
在69例出现胸腔积液的患者中,47例(68%)放置了胸管或猪尾导管用于胸腔引流,16例(23%)进行了胸管放置联合手术干预,仅有6例(9%)患者仅进行了胸腔穿刺(表3)⇑)。在那些接受外科手术干预,12(17%)接受胸腔镜手术,三(4%)有一个开放的开胸术和胸膜剥脱术和一(1%)患者具有受影响的实质瓣的楔形切除。The median duration of pleural drainage was 6 days (IQR 5–10, range 1–52 days) and did not differ based on the type of intervention (table 4⇓)。The number of febrile days also did not differ based on the type of intervention (p = 0.65); however, the median length of stay was significantly longer in patients requiring chest drainage only or surgery (14 and 14.5 days, respectively) compared with patients having only a thoracentesis (11 days) or those without pleural effusion (6 days; p = 0.0002).
Of the patients with pleural drainage, 10 (15%) developed a bronchopleural fistula (BPF) defined by persistent air leaks noted in the medical record lasting >24 h. Patients who developed BPF were older (median age 6.0与3。5 yrs; p = 0.06) than patients without BPF. The presence of a BPF was associated with a longer time of pleural drainage (median 14与6 days; p = 0.0007) and a longer length of stay (median 19与13 days; p = 0.01). All of the BPF cases were managed conservatively without operative repair.
长期结果
A total of eight (10%) patients required readmission (six due to persistent fever) within 2 weeks following their initial hospital discharge. Three patients developed a small pneumothorax, none required intervention. Of the total cohort, 64 patients were seen post-discharge in the paediatric pulmonary clinic at the Children’s Hospital (median follow-up time 6 months), all with complete clinical resolution of symptoms reported within 2 months of discharge. Of these, 12 patients had pulmonary function testing (PFT) performed; eight (67%) had normal PFTs, three patients had a mild obstructive defect and one had a mild restrictive defect. Follow-up imaging studies included chest radiographs and, in a few cases, chest CT scans (fig. 3⇓),所有病人在六个月内均有明显改善,肺实质结构接近正常。
讨论
In the present study, 80 paediatric cases of NP presenting over 15 yrs at a single institution have been identified. With the exception of two cases, these children had no significant underlying comorbid conditions, such as immunological disease or a history of prior infections. Their course was associated with significant radiographical evidence of lung damage and prolonged hospitalisations. The detection of NP in children increased over time.肺炎链球菌是最常见的微生物,但也培养了其他致病菌。与empyema的联合是常见的。尽管有显著的短期发病率,但随着时间的推移,临床和放射学分辨率都得到了观察。
NP作为复杂性肺炎的频谱内唯一的实体存在先前已分析了几个小系列的病人1-4,其中最大的一个机构包括17名患者2。采用回顾性病例定义NP基于CT诊断,80例被确定。即使考虑到由于依赖CT诊断而漏报病例的可能性,本丛书仍是迄今为止系统描述的最大的儿科NP病例群。
目前患者的年龄范围和人口学特征与其他已发表的儿童并发肺炎的研究相似14-16。Most children had developed symptoms of fever and cough for ≤1 week prior to their hospitalisation, indicating that the parenchymal damage in NP occurs rapidly. Transition from liquefaction to cavitation within 48 h has been observed通过CT扫描。尽管缺少实验室数据为一些情况下,目前的分析结果的回顾性,的异常实验室检查结果升高,许多患者被发现,白细胞计数和血红蛋白低,已在儿童已有报道与复杂肺炎和NP2,16。在许多患者中发现血清白蛋白水平明显下降,这可能是继发于蛋白质丢失到受影响的肺实质和胸膜液中,也可能是由于蛋白质丢失引起的肠病17。与NP在本研究中,尤其是低pH值相关联的胸膜液特性,也已在其它研究中相关联的具有增加的并发症18-20.。大多数本的患者有持续发烧,鉴于经常无菌文化和主要敏感的生物,本作者认为,对于发烧的原因是没有关系的缺乏细菌消灭的效力,而是存在炎症和组织破坏的致热产品20.。
Over the 15 yrs covered by the present study, an increase in the absolute numbers of NP diagnosed in the Children’s Hospital was observed. The rise is likely due to a combination of increased recognition of NP as a specific entity and heightened detection resulting from utilisation of CT scans in the evaluation of children with complicated pneumonia. There was a consistent increase in CT scans performed at the present authors’ institution starting in the early 1990s and preceding the detection of the first cases of NP. Since CT scans are the standard mode for diagnosis of NP, the increased use of CT would increase detection of NP cases. During the same time period, there was not a similar increase in the number of admissions for pneumonia to the institution. It lends itself to reason, therefore, that the observed increase of NP detection parallels the increases observed in complicated parapneumonic effusions in recent years7,14,15。
随着时间的推移,NP病例的增加也可能是由于病原体谱的变化,这已被假定为一般复杂肺炎增加的潜在原因。肺炎球菌是本研究中检测到的主要微生物,与以往大多数NP报告相似1-4。由于本研究的回顾性分析,这是不可能确定具体的肺炎球菌属。血清型的患者。因此,本作者无法复制由谭执行的分析等。14并在特定菌株的长期变化及其对引进的肺炎球菌疫苗的关系发表评论,作为一个可能的贡献者NP。然而,观察到增加各种在这些患者中的病原体。许多情况下是由其他链球菌属引起的。和葡萄球菌属,已在个别情况下先前报道引起NP21,22。还发现几起案件由梭杆菌属引起的。和铜绿假单胞菌,还没有与儿童NP以前相关的两个菌种。最后,3例被MRSA在2003年造成和2004年MRSA已在童年NP的另一起案件报告被报道23并作为一种新兴的有机体在儿童脓胸15。扩大范围致病微生物的对NP值得进一步研究,本案例42短期和长期结果的整体影响并没有确定微生物的原因。None of the patients with positive culture results had received >3 days of antibiotic pre-treatment. A likely explanation is that the infection triggered a severe inflammation that resulted in the development of NP but the antibiotics given prior to the present intervention were sufficient to sterilise the pleural fluid. However, an important alternative possibility is that the culture negative cases were caused by organisms such as anaerobes, viruses,肺炎支原体或肺炎衣原体,但这并不是本系列常规微生物调查的一部分12,13,24。这样的测试,例如使用PCR病毒或支原体属。检测,可能增加在NP诊断率。
回顾性地对NP管理策略进行严格的评估是不可能的,特别是因为脓胸的频繁共存阻止了这两种情况的分离,并分离了它们各自对整体发病率的贡献的分析。然而,在比较接受外科手术和接受保守的非手术胸腔引流的病人时,并没有观察到胸腔积液引流长度和发热时间的差异。目前的作者提出NP应该被认为是复杂肺炎的一个独特的因素,特别是,它的存在应该被认为是一个独立的复杂的特征,从经常伴随的胸腔积液。NP的诊断需要CT成像,因此,尽管有适当的药物治疗,仍建议对合并肺炎和持续症状的患者进行CT诊断。缺乏对NP的认识,可能导致诊断错误,管理上出现严重错误。基于保守治疗的普遍有利结果,目前的作者不同意手术切除治疗NP是必要的,正如最近的出版物所暗示的那样25-27和所关心的术语的使用,如“患者需要”肺切除术14和“破坏肺”26。这些干预措施的作用需要在NP的前瞻性管理研究中进行评估。
NP患儿发生BPF的风险增加。在先前对9例NP病例的研究中,5例发生了BPF,人们认为这可能是由于毗邻坏死肺的发炎胸膜易碎所致28。All patients who developed BPF in the present series had a chest drain in place for >7 days, raising the possibility that length of chest tube drainage is a risk factor for development of BPF. The present observations are, however, too few for a meaningful analysis.
对患者的长期预后随访看到一直不错。All patients had resolution of clinical symptoms within 2 months of their hospitalisation. Although many children were too young for PFT, the children who had follow-up spirometry had essentially normal results. Performing PFT in these children could aid in further characterising any residual effects of NP over time. Follow-up chest radiographs and, in a few cases, CT scans have shown almost complete normalisation of pulmonary parenchyma within several months of hospitalisation (fig. 3⇑)。总的来说,这种改善模式表明NP对儿童肺部的损害是暂时的。在目前病例中观察到的放射学分辨率证实了早期在较小病例中NP系列的类似报告29。因此,当NP诊断,应当认定为严重,然而,自限性,可逆性病变。
总之,坏死性肺炎,应当确认为儿童社区获得性肺炎的日益检测的并发症,是从胸腔积液和脓胸不同。虽然肺炎球菌属。仍然是最常见的致病细菌病原体,小儿肺炎坏死可以通过各种生物体,包括耐甲氧西林引起的金黄色葡萄球菌。坏死性抗生素肺炎和胸腔引流良好成果胸腔积液结果,并没有迹象表明,手术切除是必要的坏死性肺炎的正确治疗的保守管理。尽管童年坏死性肺炎的短期严重的发病率,长期的临床结果是优秀的用最少的结果后遗症。
支持声明
本研究的一些结果之前已经以摘要的形式在7th儿科肺病学国际会议(第七届CIPP;加拿大蒙特利尔)2006年7月。
利益声明
无声明。
致谢
作者要感谢R.马利和K.麦金托什(既有分工传染病,儿童医院波士顿,哈佛大学医学院,波士顿,MA,USA)的手稿的严格审查。
- 收到2007年8月3日。
- 公认2008年1月10日。
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