2015芬兰儿童喉炎、哮喘支气管炎、细支管治疗指南.doc

Finnish guidelines for the treatment of laryngitis, wheezing bronchitis and bronchiolitis in children芬兰儿童喉炎、气喘支气管炎、细支气管炎治疗指南Terhi Tapiainen (terhi.tapiainenoulu.fi)1,2, Janne Aittoniemi3, Johanna Immonen4, Heli Jylkka5, Tuula Meinander6, Kirsi Nuolivirta7, Ville Peltola8,Eeva Salo9, Raija Seuri10, Satu-Maaria Walle11, Matti Korppi121. Department of Pediatrics and Adolescence, Oulu University Hospital, Oulu, Finland1.芬兰奥卢大学附属医院儿童和青少年门诊2.PEDEGO Research Unit - Research Unit for Pediatrics, Dermatology, Clinical Genetics, Obstetrics and Gynecology, and Medical Research Center, University of Oulu,Oulu, Finland 2.芬兰奥卢大学PEDEGO（儿科、皮肤科、临床遗传学、妇产科）研究中心和医学研究中心3.Fimlab Laboratories, Tampere, Finland 3.芬兰坦佩雷Fimlab实验室4.Terveystalo Pediatric Clinic, Kuopio, Finland 4.芬兰库奥皮奥Terveystalo儿科诊所5.Department of Pediatrics, University of Tampere, Tampere, Finland,5.芬兰坦佩雷大学儿科系6.Department of Internal Medicine, Tampere University Hospital and the Finnish Medical Society Duodecimo, Tampere, Finland6.芬兰坦佩雷大学附属医院内科门诊和芬兰坦佩雷Duodecimo医学会7.Seineajoki Central Hospital, Seinajoki, Finland7.芬兰Seinaejoki中心医院8.Department of Pediatrics, Turku University Hospital and University of Turku, Turku, Finland8.芬兰图尔库大学及其附属医院儿科门诊9.Department of Pediatrics, Helsinki University Hospital, Helsinki, Finland9.芬兰赫尔辛基大学附属医院儿科门诊10.HUS Imaging, Children0s Hospital, Helsinki University Hospital, Helsinki, Finland10.芬兰赫尔辛基大学附属医院、儿童医院溶血性尿毒综合征成像11.Espoonlahti Health Care Center, Espoo, Finland 11.芬兰埃斯波Espoonlahti卫生保健中心12.Department of Pediatrics, Tampere University Hospital and University of Tampere, Tampere, Finland12.芬兰坦佩雷大学及其附属医院儿科门诊Keywords 关键词Bronchiolitis, Bronchitis, Cough, Laryngitis, Wheezing bronchitis细支气管炎、支气管炎、咳嗽、喉炎、哮喘支气管炎Correspondence T Tapiainen, MD, PhD, Department of Pediatrics,Oulu University Hospital, P.O. Box 23, 90029 Oulu,FinlandTel: +358 8 315 5185 |Fax: +358 8 315 5559 |Email: terhi.tapiainenoulu.fi Received 13 January 2015; revised 22 June 2015;accepted 17 August 2015.DOI:10.1111/apa.13162通信地址：芬兰奥卢大学附属医院儿科医学博士、哲学博士Tapiainen先生邮政编码：23, 90029电话：+358 8 315 5185 |传真：+358 8 315 5559邮箱：terhi.tapiainenoulu.收稿日期：2015.1.13 修订日期：2015.6.22 批准日期：2015.8.17（非专业人士翻译，供参考，孙桂华， QQ:479327458）ABSTRACT 摘要 Evidence-based guidelines are needed to harmonise and improve the diagnostics and treatment of childrens lower respiratory tract infections. Following a professional literature search, an interdisciplinary working group valuated and graded the available evidence an constructed guidelines for treating laryngitis, bronchitis, wheezing bronchitis and bronchiolitis. 需制定循证指南来协调和改善儿童下呼吸道感染的诊断和治疗。根据专业文献研究，交叉学科工作组对现有证据（即喉炎、支气管炎、气喘支气管炎、细支气管炎治疗指南）进行了评价和等级划分。Conclusion: Currently available drugs were not effective in relieving cough symptoms.Salbutamol inhalations could relieve the symptoms of wheezing bronchitis and should be administered via a holding chamber. Nebulised adrenaline or inhaled or oral glucocorticoids did not reduce hospitalisation rates or relieve symptoms in infants with bronchiolitis and should not be routinely used. 结论:目前可用药物不能有效缓解咳嗽症状。舒喘灵喷雾疗法可以缓解哮喘支气管炎的症状,并需通过储药腔来给药。雾化吸入肾上腺素或吸入/口服糖皮质激素并没有降低住院率或缓解婴儿毛细支气管炎症状且不应经常服用。INTRODUCTION 引言Evidence-based clinical practice guidelines for the treatment of lower respiratory tract infections (LRTIs) inchildren were developed in Finland in 20132014. They were devised by an independent interdisciplinaryworking group, established by the Finnish Medical Society Duodecim and the Finnish Pediatric Society, that included paediatric infectious disease specialists, general paediatricians,a clinical microbiologist, a paediatric radiologist and a general practitioner. The scope of the guidelines was the treatment of acute paediatric LRTIs, excluding severe cases requiring hospital admission or intensive care.2013 - 2014年芬兰开发了儿童下呼吸道感染治疗临床实践循证指南，并由芬兰医学会和芬兰儿科学会共同组建的交叉学科工作组对该指南进行修订，交叉学科工作组由儿科传染病专家、普通儿科医生、儿科临床微生物学家、儿科放射科医生和全科医生组成。指南范围包括小儿急性下呼吸道感染治疗，不包括需住院治疗或需重症监护的重症患者。Our professional librarian performed systematic literature searches using selected topics and questions, and then,the group reviewed the literature and evaluated the available evidence. The level of evidence was assessed and marked within guideline statements for the most critical decisions. The following category levels for the evidence were used: level A referred to strong evidence with at least two separate, high-quality studies; level B referred to moderate evidence with at least one high-quality study;and level C referred to weak evidence with at least one satisfactory study. A high-quality study was defined as a study performed in an appropriate population with a strong study design, such as a randomised controlled trial with an appropriate outcome measure. The guideline document was peer-reviewed by 14 experts and clinicians before it was published in the Finnish Current Care Guidelines series in 2014. The process is described in detail on the Current Care Guideline Web pages (www.kaypahoito.fi).由我们专业的图书管理员利用所选标题和问题进行系统文献搜索，然后由交叉工作组对文献进行评审并对现有证据进行评价。指南说明对最重要决定的证据等级进行了评估和划分。证据等级种类如下：A级指有力证据，要求至少有两个独立的高质量研究；B级指中等证据，要求至少有一个高质量研究；C级指弱证据，要求至少有一个令人满意的研究。高质量研究是指对适度人群所开展的带强烈研究设计的研究，如具有适当检测指标的随机受控试验。2014年，在芬兰现行护理指南系列一书发表该篇指南文献前，由14位同行专家和临床医生对该指南进行了评审。详细过程请登录www.kaypahoito.fi，查看网页版现行护理指南。Key Notes 关键词 _ An interdisciplinary working group constructed guidelines to harmonise and improve the treatment of childrens lower respiratory tract infections.通过由交叉学科工作组创建的指南来协调和改善治疗儿童下呼吸道感染的治疗。Our review found that currently available drugs were not effective in relieving cough symptoms, but salbutamol inhalations could relieve the symptoms of wheezing bronchitis通过审查，我们发现目前可用药物不能有效缓解咳嗽症状，但吸入舒喘灵可以缓解哮喘支气管炎症状_ Nebulised adrenaline or inhaled or oral glucocorticoids did not reduce hospitalisation rates or relieve symptoms in infants with bronchiolitis and should not been routinely used.document included approximately 200 references and more than 50 linked supplementary Web pages presenting the systematic literature review for each statement. This formed the first part of the summary document. The second part presented the treatment of pneumonia and pertussis in children (1). The detailed search description by the professional librarian is presented (Tables S1S2).雾化吸入肾上腺素、吸入或口服糖皮质激素并不能降低住院率或缓解婴儿细支气管炎症状，且不应经常服用。该文献所列入的参考资料约200篇，50多个链接补充网页，对每种论述进行了系统地文献评审，并将其作为摘要的第一部分。摘要第二部分讲述了儿童肺炎和百日咳治疗(1)。专业图书馆理员检索详细描述见表S1-S2。 This paper presents the available evidence and the new guidelines for treating laryngitis, wheezing bronchitis and bronchiolitis in children in Finland. The evidence-based statements, which appear in italics in this paper, arepresented and the reasoning behind the recommendations is discussed. Table 1 summarises the recommendations for the use of antimicrobials, glucocorticoids and sympathomimetics. In addition to the presentation of new guidelines,we have discussed relevant new studies published since2014 and explained their effect on the present guidelines. 本篇文章讲述了有关芬兰儿童喉炎、哮喘支气管炎和毛细支气管炎治疗的现有证据和新指南。文章中的循证论述采用斜体字，并对所做建议的背后原因进行了讨论。表1归纳了建议服用的抗菌素、糖皮质激素和拟交感神经药。除指南外，我们还对自2014年以来所发表的相关新研究进行了讨论，并就其对当前指南的影响进行了阐释。AETIOLOGY AND DIAGNOSTICS OF RESPIRATORY VIRUSES 呼吸道病毒病原及其诊断 All known respiratory viruses are capable of causing different LRTIs such as laryngitis, wheezing bronchitis,bronchiolitis or pneumonia. The most important viruses causing LRTIs in children are rhinoviruses, the respiratory syncytial virus (RSV), parainfluenza viruses 14, the adenovirus group and influenza viruses A and B. Some viruses,however, are more likely to cause specific LRTIs (2).Rhinoviruses are particularly associated with wheezing bronchitis, RSV with bronchiolitis in infants and parainfluenza viruses with laryngitis. Accordingly, RSV is the most important virus that causes wheezing in children under one year of age and rhinoviruses are the most important in older children (3). All respiratory viruses are capable of causing febrile infections (2), for instance rhinoviruses are associated with fever in 4050% of children with respiratory tract infections, the parainfluenza virus is associated with fever in 6080% and influenza A in 9095%. The most important recently recognised respiratory viruses are the human metapneumovirus, which is associated with bronchiolitis, and the human bocavirus,which is associated with wheezing bronchitis. Bacteria do not usually cause laryngitis, bronchitis, bronchiolitis or wheezing bronchitis in children. The aetiology of pneumonia is presented in the separate guideline document from the same group (1). 所有已知呼吸道病毒均能导致不同的下呼吸道感染（LRTIs），如喉炎、喘息性支气管炎、细支气管炎或肺炎。导致儿童下呼吸道感染的最重要病毒为鼻病毒、呼吸道合胞病毒(RSV)、副流感病毒1-4、重组腺病毒、A类和B类流感病毒。但有些病毒更有可能会导致特异性下呼吸道感染（2）。鼻病毒尤其与哮喘支气管炎相关，RSV病毒与婴儿细支气管炎相关，副流感病毒则与喉炎相关。相应地，RSV是导致1岁以下儿童哮喘的最重要病毒，而鼻病毒则是导致大龄儿童哮喘的最重要原因（3）。所有呼吸道病毒均能引发热性传染病（2），例如鼻病毒会导致40 - 50%呼吸道感染儿童出现高烧，副流感病毒会导致60 - 80%呼吸道感染儿童出现高烧，A类流感病毒会导致90 - 95%呼吸道感染儿童出现高烧。最近确认的最重要呼吸道病毒是人类偏肺病毒和人类博卡病毒，人类偏肺病毒与细支气管炎有关，而人类博卡病毒则与哮喘支气管炎有关。细菌通常不会引发儿童喉炎、支气管炎、细支气管炎或哮喘支气管炎。肺炎病原请见同组单独指南文献（1）。Testing of influenza A and B virus is recommended to all children with LTRIs during the influenza season if the duration of the acute symptoms is 48 hours (level B).Influenza cannot reliably be diagnosed based on clinical symptoms in children. Antiviral treatment against influenza is effective if the treatment is started within 48 hours of the start of the symptoms (4). However, influenza virus testing may be beneficial for patients admitted to hospital even after 48 hours. Influenza virus testing during an LRTI is likely to decrease antimicrobial consumption (5). 在流感季节，如果急性症状持续时间低于48小时（B级），则建议对所有下呼吸道感染儿童进行A类和B类流感病毒检测。不能根据儿童临床症状对流感进行确诊。如果在症状开始48内即开始治疗，则能有效地进行抗病毒治疗。但即使是在症状开始48后，对入院病人进行流感病毒检测也是有益的。对下呼吸道感染者进行流感病毒检测有可能会降低抗菌消费（5）。Testing of RSV and other respiratory viruses can be performed on children who are admitted to hospital due to an LRTI (level B) (6,7). Respiratory virus testing may decrease the use of antimicrobial treatment after hospitalisation(8). Wheezing bronchitis or bronchiolitis are rarely associated with a bacterial infection of the lower respiratory tract. Nosocomial infections may be decreased with active cohorting of hospitalised patients based on viral testing.Wheezing associated with a rhinovirus infection is a risk factor for later asthma in children (3). The sensitivity of point-of-care antigen tests is lower than that of polymerase chain reaction (PCR) performed in laboratory, but their sensitivity and specificity in detecting influenza viruses and RSV is rather good (9). The accuracy and feasibility of point-of-care tests for other respiratory viruses than influenza viruses and RSV is largely unknown.可对住院治疗的下呼吸道感染（B级）（6，7）儿童进行RSV或其他呼吸道病毒检测。呼吸道病毒检测可减少住院后的抗菌处理。哮喘支气管炎、细支气管炎很少与下呼吸道细菌感染有关。根据病毒检测，可减少住院病人活动集中院内感染。鼻病毒感染引发的哮喘有可能会导致儿童后期哮喘（3），床旁抗原检测敏感度低于实验室聚合酶链反应测试结果，但其流感病毒和RSV敏感性和特异性检测结果相当不错（9）。除流感病毒和RSV病毒外，其他呼吸道病毒的大部分床旁检测精确性和可行性还是未知。LARYNGITIS 喉炎 Laryngitis can be classified into upper respiratory tract or lower respiratory tract infections. Our working group decided to include laryngitis in the present LRTI guideline as laryngeal symptoms are caused by subglottic oedema,dyspnoea is common and laryngitis can be treated with drug inhalations. Typical symptoms of laryngitis are inspiratory wheezing and a barking cough. Bacterial tracheitis is rare,and epiglottitis is very rare in the era of Haemophilus influenzae B immunisation, but they can also cause inspiratory difficulties and should be remembered in the differential diagnostics. The occurrence of laryngitis is highest among children aged six months to three years.These days, children with laryngitis are mainly treated in emergency departments and other outpatient clinics and hospitalisation due to laryngitis is rare. 喉炎可分为上呼吸道感染和下呼吸道感染。由于喉部症状是由声门下水肿引起的，因此我们工作组决定将喉炎纳入当前的LRTI指南。呼吸困难是常见症状，可用药物吸入来治疗喉炎。喉炎典型的症状是吸气哮鸣和犬吠样咳嗽。在接种B型流感嗜血杆菌疫苗的年代，细菌性气管炎是罕见的，而会厌炎则非常罕见，但这两种病也会导致吸气困难，在鉴别诊断中，应记住这两种罕见病。6个月3岁大儿童喉炎发生率最高。目前，由于喉炎属于罕见病，因此患喉炎儿童主要是在急诊科和其他门诊诊所治疗或住院治疗。Mist is not effective in relieving the symptoms of laryngitis (level A) (10,11). In two randomised controlled trials (RCTs), mist administration did not decrease clinically evaluated symptoms of laryngitis. Nebulised racemic adrenaline is effective in relieving the symptoms of laryngitis (level A) (12). The effect is short term and lasts for one to two hours. Nebulised levo-adrenaline, an isomer used in systemic adrenaline products, was used in one small study.There was no statistically significant difference in symptom scores between children receiving nebulised racemic adrenaline and levo-adrenaline, but the sample size of the study was too small to confirm equal efficacy. Oral glucocorticoids are effective in relieving the symptoms of laryngitis (level A) (13). Different doses of glucocorticoids appear to be equally beneficial and oral glucocorticoids as effective as intramuscular glucocorticoids. Possible drug alternatives include a single oral dose of betamethasone 0.250.4 mg/kg (Betapred_, water soluble tablets) or dexamethasone 0.150.6 mg/kg. Nebulised budesonide (2 mg) may provide additional efficacy in children treated with systemic glucocorticoids(14). 雾化并不能有效缓解喉炎症状（A级）（10、11）。在两组随机控制试验中，雾化并不能降低喉炎的临床评估症状。雾化吸入外消旋肾上腺素可有效缓解喉炎（A级）症状（12）。效果持续时间较短，为1-2小时。另一小型研究则采用雾化吸入左旋肾上腺素（全身肾上腺素产品所采用的一种异构体）来治疗儿童喉炎。两组儿童症状等级评分并没有显著的统计差异，但由于进养量太小，因此无法确认等效性。口服糖皮质激素能有效缓解喉炎的症状(A级)(13)。即使糖皮质激素剂量不同，但似乎同样有益，而且口服糖皮质激素和肌内糖皮质激素治疗效果一样。可选备用药品包括单次口服倍他米松0.25-0.4毫克/千克（倍他米松钠水溶性片剂）或地塞米松0.15 -0.6毫克/千克。对于采用全身糖皮质激素治疗的儿童，雾化吸入布地奈德（2毫克）可提高治疗功效(14)。ACUTE BRONCHITIS 急性支气管炎Acute cough in children is usually caused by viral respiratory infections. The duration of cough is usually less thanthree weeks, but in 10% of cases, the cough may continue longer. Antimicrobials are ineffective in treating cough in children. Antitussive drugs (1521) and beta-sympathomimetic agents (18,22) are ineffective in relieving acute cough in children and may cause serious adverse events (level A). This is in line with an earlier statement by the U.S. Food and Drug Administration recommending that antitussives should not be used for infants due to seriousadverse events. Honey may relieve acute nocturnal cough during an LRTI in children older than one year of age (level C) (2326). Dosing of honey in RCTs has ranged from a single dose of a few millilitres to 10 g given orally approximately 30 minutes before sleep in children with an acute viral LRTI. Honey should not be given to infants younger than one year of age due to the risk of infant botulism.Chronic wet cough, which is also called presumed protracted bacterial bronchitis in the literature and lasts for several weeks, is a less frequent condition in children than acute bronchitis. More commonly, a child suffers from recurrent viral LRTIs and is asymptomatic between LRTI episodes. If chronic bacterial bronchitis is suspected in children, other diagnoses such as tuberculosis, foreign body aspiration, cystic fibrosis or primary immunodeficiency should be excluded. Antimicrobial treatment may be effective in treating chronic wet cough in children (level C)(2729). 儿童急性咳嗽通常是由病毒性呼吸道感染引起的。咳嗽持续时间通常不超过三周，但有10%儿童病人咳嗽持续时间会更长。抗菌药物不能有效治疗儿童咳嗽。镇咳药（15-21）和-拟交感神经药物（18-22）不能有效缓解儿童急性咳嗽，且可能会导致严重不良事件发生。对于年龄超过1岁的下呼吸道感染儿童患者（C级）（23-26），在随机控制试验中（RCT），让患急性病毒性下呼吸道感染的儿童在睡前30分钟服用蜂蜜，单次口服剂量为几毫升10克。因存在婴儿型肉毒中毒风险，一岁以下儿童不应服用蜂蜜。与急性支气管炎儿童患者相比，儿童患慢性湿咳（医学文献也称之为假定持久细菌性支气管炎，持续时间为几周）的情况并不常见。更为常见的是儿童复发性病毒性下呼吸道感染，且病发间无临床症状。如儿童患有疑似慢性细菌性支气管炎，则应排除其它诊断，如肺结核、异物吸入、囊性纤维化和原发性免疫缺陷病。抗菌治疗法可有效治疗儿童慢性湿咳（C级）（27-29）。ACUTE WHEEZING UNDER THREE YEARS OF AGE 三岁以下儿童急性哮喘Acute wheezing in children under three years of age covers two clinical conditions, wheezing bronchitis and bronchiolitis, that are different in terms of causative agents, clinical symptoms and outcomes. However, in the literature we examined, both conditions were often included together in the same trials. The term bronchiolitisis used for children under 24 months of age with wheezing in the United States, but in Europe, it is restricted tochildren under 12 months of age experiencing their first wheezing episode. The European definition of bronchiolitis is used in this guideline. However, RSV bronchiolitis during the first months of life differs from rhinovirusinduced wheezing in older infants who are under 12 months of age. In future trials, RSV infection in infants younger than six months of age and rhinovirus-induced wheezing in infants older than six months of age would ideally be assessed separately. 3岁以下儿童急性哮喘包含两种临床状况，即喘息性支气管炎和细支气管炎，就病原体、临床症状和结果而言，这两种状况是不同的。然而在我们检查的文献中，这两种状况通常被纳入相同试验中。在美国，细支气管炎用于2岁以下哮喘儿童患者，而在欧洲细气支管炎则仅限于1岁以下第一次发哮喘的儿童。该指南采用了欧洲细支气管炎定义。但几个月大初生儿RSV细支气管炎与1岁以下较大儿童的鼻病毒哮喘是不同的。在未来试验中，应对6个月以下婴儿RSV感染和6个月以上鼻病毒哮喘分别进行评价。WHEEZING BRONCHITIS 哮喘支气管炎Wheezing bronchitis is most frequently triggered by a rhinovirus and is defined as wheezing in children aged 12 to 36 months during acute respiratory viral infection or repeated wheezing in children aged six to 12 months.Rhinovirus-induced wheezing in children is a clear risk factor for asthma in later childhood (3). The border between repeated episodes of wheezing bronchitis and childhood asthma is sliding. In most cases, children with wheezing grow out of this tendency before school age,but there are no reliable means to assess, early in life, who will stop and who will continue wheezing. Risk factors for recurrent wheezing are passive smoking,parental asthma, atopic disease in the child and wheezing starting when the child is more than 12 months of age.最易引发哮喘支气管炎的是鼻病毒，哮喘支气管炎是指1-3岁儿童因急性呼吸道病毒感染而出现的哮喘，或6-12个月大儿童反复性哮喘。鼻病毒哮喘有可能会导致儿童在童年后期出现哮喘。哮喘支气管炎复发与儿童哮喘间的近似边界正逐渐降低。大多数情况下，儿童在长大至学龄前，出现哮喘的趋势会消失，但没有可靠的方法来评估在童年早期，谁会停止或谁会继续发生哮喘。哮喘复发风险因素包括被动吸烟、父母哮喘、儿童过敏性疾病和儿童哮喘始发时间大于1岁。TREATMENT OF WHEEZING BRONCHITIS 哮喘支气管炎治疗Salbutamol inhalations may relieve the symptoms of wheezing bronchitis (level C) (30). Salbutamol