下呼吸道

第7讲 下呼吸道感染 Lower Respiratory Tract Infections,DEFINITION,Lower respiratory tract infections include infectious processes of the lungs and bronchi, pneumonia, bronchitis, bronchiolitis, and lung abscess.下呼吸道感染是指肺炎、支气管肺炎，支气管炎，毛细支气管炎，肺脓肿的感染过程。,BRONCHITIS,ACUTE BRONCHITIS支气管炎是指气管、支气管树的大范围广义呼吸道感染的一种炎症状态。不包括肺泡炎症。常分为急性或慢性炎症。急性支气管炎可发生在所有年龄段，而慢性支气管炎的主要影响成年人。Bronchitis refers to an inflammatory condition of the large elements of the tracheobronchial tree that is usually associated with a generalized respiratory infection. The inflammatory process does not extend to include the alveoli. The disease entity is frequently classified as either acute or chronic. Acute bronchitis occurs in all ages, whereas chronic bronchitis primarily affects adults.急性支气管炎常发生于冬季，寒冷，潮湿的气候和/或高浓度的刺激性的物质，如空气污染或香烟的烟雾中可能沉淀在气管内引起炎症。Acute bronchitis most commonly occurs during the winter months. Cold, climates and/or the presence of high concentrations of irritating substances such as air pollution or cigarette smoke may precipitate attacks.,Pathophysiology,呼吸道病毒是迄今为止最常见的与急性支气管炎有关的因素。普通感冒病毒，鼻病毒，冠状病毒，下呼吸道病原体，包括流感病毒，腺病毒，呼吸道合胞病毒，占了大多数。肺炎支原体也是一个常见的急性支气管炎病原。其他病原还包括肺炎衣原体、百日咳杆菌菌Respiratory viruses are by far the most common infectious agents associated with acute bronchitis. The common cold viruses, rhinovirus and coronavirus, and lower respiratory tract pathogens, including influenza virus, adenovirus, and respiratory syncytial virus, account for the majority of cases. Mycoplasma pneumoniae also appears to be a frequent cause of acute bronchitis. Other bacterial causes include Chlamydia pneumoniae and Bordetella pertussis.粘膜和支气管分泌物增加，呼吸道上皮细胞从轻度到广泛损伤，可能会影响支气管纤毛功能。此外，增加的支气管分泌物变得粘稠及厚实，进一步削弱黏膜纤毛活动。反复急性呼吸道感染可增加气道高反应性和慢性阻塞性肺疾病。Infection of the trachea and bronchi causes hyperemic and edematous mucous membranes and an increase in bronchial secretions. Destruction of respiratory epithelium can range from mild to extensive and may affect bronchial mucociliary function. In addition, the increase in bronchial secretions, which can become thick and tenacious, further impairs muco-ciliary activity. Recurrent acute respiratory infections may be associated with increased airway hyperreactivity and possibly the pathogenesis of chronic obstructive lung disease.,Clinical Presentation,支气管炎是一种自限性疾病，很少致死。急性支气管炎往往继发于上呼吸道感染。急性支气管炎患者通常没有特异性主诉，主诉主要是如身体不适、头痛、鼻炎，咽痛。Bronchitis is primarily a self-limiting illness and rarely a cause of death.Acute bronchitis usually begins as an upper respiratory infection. The patient typically has nonspecific complaints such as malaise and headache,coryza, and sore throat.咳嗽是急性支气管炎的标志。早期发生，并会持续，不管鼻腔或鼻咽部症状是否缓解。通常情况下，咳嗽最初是无痰的，但随着进展，会产生粘液脓性痰。 Cough is the hallmark of acute bronchitis. It occurs early and will persist despite the resolution of nasal or nasopharyngeal complaints. Frequently, the cough is initially nonproductive but progresses, yielding mucopurulent sputum.胸部检查可能会显示双肺干啰音，呼吸音增粗、湿性罗音。胸部X线片通常是正常的。 Chest examination may reveal rhonchi and coarse, moist rales bilaterally.Chest radiographs, when performed, are usually normal.,一般来说痰细菌培养作用有限，因为采样技术无法避免鼻咽正常菌群。当需要某个特定诊断时，必须做病毒抗原检测。 在长期或严重的情况下， 根据流行病学考虑，应该进行肺炎支原体的培养或血清学诊断及百日咳肺炎的培养或直接荧光抗体检测。Bacterial cultures of expectorated sputum are generally of limited utility because of the inability to avoid normal nasopharyngeal flora by the sampling technique. Viral antigen detection tests can be used when a specific diagnosis is necessary. Cultures or serologic diagnosis of M.pneumoniae and culture or direct fluorescent antibody detection for B.pertussis should be obtained in prolonged or severe cases when epidemiologic considerations would suggest their involvement.,Treatment,急性支气管炎的治疗主要是对症和支持疗法。休息及单独用退热药就足够了。卧床休息和温和的解热镇痛治疗通常有助于减轻嗜睡，全身乏力，发热等症状。应鼓励患者喝水，并可能降低的粘度呼吸道分泌物。The treatment of acute bronchitis is symptomatic and supportive in nature. Reassurance and antipyretics alone are often sufficient. Bedrest and mild analgesic-antipyretic therapy are often helpful in relieving the associated lethargy, malaise, and fever. Patients should be encouraged to drink fluids to prevent dehydration and possibly decrease the viscosity ofrespiratory secretions.阿司匹林或对乙酰氨基酚每4-6小时给药一次（成人650毫克 或儿童10-15mg/kg，成人每日最大剂量为4g，儿童60毫mg/kg） Aspirin or acetaminophen (650 mg in adults or 10 to 15 mg/kg per dose in children with a maximum daily adult dose of 4 g and 60 mg/kg for children) or ibuprofen (200 to 800 mg in adults or 10 mg/kg per dose in children with a maximum daily dose of 3.2 g for adults and 40 mg/kg for children) is administered every 4 to 6 hours.在儿童，应避免首选阿司匹林，因为阿司匹林可能引起瑞夷综合症。 In children, aspirin should be avoided and acetaminophen used as the preferred agent because of the possible association between aspirin use and the development of Reyes syndrome.,雾化吸入有助于稀释支气管分泌物。Mist therapy and/or the use of a vaporizer may further promote the thinning and loosening of respiratory secretions.持续的轻度咳嗽可以用右美沙芬治疗，严重的咳嗽可以选用可待因或类似药物。Persistent, mild cough, which may be bothersome, may be treated with dextromethorphan; more severe coughs may require intermittent codeine or other similar agents.不鼓励对支气管炎常规使用抗菌药，然而别人持续发热及呼吸道症状超过4-6天，应该考虑使用抗菌药。Routine use of antibiotics in the treatment of acute bronchitis is discouraged; however, in patients who exhibit persistent fever or respiratory symptomatology for more than 4 to 6 days, the possibility of a concurrent bacterial infection should be suspected.,如有必要使用抗菌药，应选择直接作用于预期病原菌（如肺炎链球菌、流感嗜血杆菌）或者咽喉部优势菌。When possible, antibiotic therapy is directed toward anticipated respiratory pathogen(s) (i.e., Streptococcus pneumoniae, Haemophilus influenzae) and/or those demonstrating a predominant growth upon throat culture.如果因病史或感冒凝集素阳性（抗体滴度大于或等于1:32），应怀疑感染 肺炎支原体，如果经过培养或血清学检查确认，可用阿奇霉素治疗。此外，对成人可选用喹诺酮类（如左氧氟沙星）。M. pneumoniae, if suspected by history or positive cold agglutinins (titers greater than or equal to 1:32) or if confirmed by culture or serology, may be treated with azithromycin. Also, a fluoroquinolone with activity against these pathogens (levofloxacin) may be used in adults.,在已知的流行病， 如果在病程的早期疑似感染A型流感病毒，金刚烷胺或金刚乙胺可有效地减少相关症状。During known epidemics involving the influenza A virus, amantadine or rimantadine may be effective in minimizing associated symptomatology if administered early in the course of the disease.,CHRONIC BRONCHITIS,Pathophysiology慢性支气管炎是多种因素引起的：如吸烟、职业灰尘烟雾暴露、环境污染及细菌感染。Chronic bronchitis is a result of several contributing factors, including cigarette smoking; exposure to occupational dusts, fumes, and environmental pollution; and bacterial (and possibly viral) infection.在慢性支气管炎，支气管壁增厚和大支气管及细支气管表面分泌粘液的杯状细胞数目显着增加。粘液腺变得肥厚及黏液腺导管扩张。作为这些损害的结果，慢性支气管炎患者在其外围呼吸道有更多的粘液，进一步损害正常肺的防御，造成黏液堵塞较小的气道。In chronic bronchitis, the bronchial wall is thickened and the number of mucus-secreting goblet cells in the surface epithelium of both larger and smaller bronchi is markedly increased. Hypertrophy of the mucus glands and dilatation of the mucus gland ducts are also observed. As a result of these changes, patients with chronic bronchitis have substantially more mucus in their peripheral airways, further impairing normal lung defenses and causing mucus plugging of the smaller airways.炎症继续进展，可以导致残留的小支气管形成疤痕，气道阻塞及支气管壁的变薄Continued progression of this pathology can result in residual scarring of small bronchi, augmenting airway obstruction and the weakening of bronchial walls.,病 因,外因吸烟感染因素理化因素气候过敏因素,内因呼吸道局部防御及免疫功能减低植物神经功能失调,Clinical Presentation,慢支的典型症状是从轻度至“呛烟样”咳嗽，直至严重的持续性有大量浓痰的咳嗽。绝大部分患者晨早会咳出大量的痰液，也有患者整天都咳出大量痰液。痰液颜色呈白色至黄绿色。 The hallmark of chronic bronchitis is cough that may range from a mild “smokers” cough to severe incessant coughing productive of purulent sputum. Expectoration of the largest quantity of sputum usually occurs upon arising in the morning, although many patients expectorate sputum throughout the day. The expectorated sputum is usually tenacious and can vary in color from white to yellow-green.慢支的诊断主要依赖临床表现及病史。只要咳嗽伴痰液每年至少持续3个月，连续2年以上即可确诊为慢支。下表1列出慢支分类及治疗方案。 The diagnosis of chronic bronchitis is based primarily on clinical assessment and history. By definition, any patient who reports coughing up sputum on most days for at least 3 consecutive months each year for 2 consecutive years suffers from chronic bronchitis. Table 43-1 presents a classification and treatment scheme for chronic bronchitis.排除其他肺病，轻中度慢支的体检一般没有明显的表现（见表2）。 With the exception of pulmonary findings, the physical examination of patients with mild to moderate chronic bronchitis is usually unremarkable(Table 43-2).,痰液中中性粒细胞增加提示有持续性的支气管刺激物存在，痰液中嗜酸性粒细胞增加提示有过敏原刺激，痰液细菌培养分离鉴定出的常见细菌：（常用总培养的百分数表示）提示慢支的急性发作。An increased number of polymorphonuclear granulocytes in sputum often suggests continual bronchial irritation, whereas an increased number of eosinophils may suggest an allergic component. The most common bacterial isolates (expressed in percentages of total cultures) identified from sputum culture in patients experiencing an acute exacerbation of chronic bronchitis are as follows:流感嗜血杆菌 a 45% a:产beta-内酰胺酶 卡他莫拉菌 a 30% b:对青霉素耐药肺炎链球菌 b 20%E.coli，肠球菌属、克雷伯杆菌、绿脓杆菌 5%,临床表现,症状咳嗽咳痰喘息或气促,体征早期无异常体征；急性发作期可有散在的干、湿罗音；哮鸣音、肺气肿体征。,经常在胸部听诊听到吸气和呼气罗音，哮鸣音，呼气相轻度延长。敲击心脏浊音区域有回声,正常呼吸声音减弱,杵状指（晚期）,临床分型、分期,分型单纯型喘息型,分期急性发作期 1周慢性迁延期 1月临床缓解期 2月,眼底至少有4耀斑，或者有严重的合并症,Treatment,General Principles 一般原则首先必须评估病人是否有职业/环境毒物、刺激性气体等暴露史、是否吸烟。如果有暴露史，必须减少暴露。 A complete occupational/environmental history for the determination of exposure to noxious, irritating gases, as well as cigarette smoking, must be assessed. Exposure to bronchial irritants should be reduced.减少或者禁止吸烟 Attempts should be made with the patient to reduce or eliminate cigarette smoking.加湿或者雾化吸入有助于稀释浓痰，减少痰液分泌。使用的粘液裂解气雾剂（例如，N-乙酰半胱氨酸;脱氧核糖核酸酶）对中度或重度的慢性阻塞性肺疾病又未接受糖皮质激素吸入治疗的患者有很大的治疗价值。Humidification of inspired air may promote the hydration (liquefaction) of tenacious secretions, allowing for more effective sputum production. The use of mucolytic aerosols (e.g., N-acetylcysteine; deoxyribonuclease) is of questionable therapeutic value. Mucolytics may have the greatest benefit in patients with moderate or severe chronic obstructive pulmonary disease who are not receiving inhaled corticosteroids.体位引流可能有助于促进肺部分泌物的清除。Postural drainage may assist in promoting clearance of pulmonary secretions.,Pharmacologic Therapy,急性发作期口服或者雾化吸入支气管扩张药是有益的。如果有证据显示病人有持续性的气道阻塞，必须考虑改变扩张支气管。Oral or aerosolized bronchodilators (e.g., albuterol aerosol) may be of benefit to some patients during acute pulmonary exacerbations. For patients who consistently demonstrate limitations in airflow, a therapeutic change of bronchodilators should be considered.长期吸入异丙基阿托品可以降低咳嗽频率、咳嗽严重程度及痰液分泌。Long-term inhalation of ipratropium decreases the frequency of cough,severity of cough, and the volume of expectorated sputum.抗菌药是非常重要的治疗药物，但是对其使用存在争议。抗菌药必须对可能的感染病原有效，且不和其他药物发生相互作用，增加病人的依从性。The use of antimicrobials has been controversial, although antibiotics are an important component of treatment. Agents should be selected that are effective against likely pathogens, have the lowest risk of drug interactions, and can be administered in a manner that promotes compliance,选择抗菌药前必须认识到超过30-40%的流感嗜血杆菌，超过95%的肺炎支原体是产-内酰胺酶的，30%的肺炎球菌对青霉素中度耐药。Selection of antibiotics should consider that up to 30% to 40% of H.influenzae and 95% of M. pneumoniae are -lactamase producers, and up to 30% of S. pneumoniae are at least moderately penicillin resistant.抗菌药使用总结见表43-3.在症状缓解期，使用抗菌药治疗剂量的上限为5-7天。Antibiotics commonly used in the treatment of these patients and their respective adult starting doses are outlined in Table 43-3. Duration of symptom-free periods may be enhanced by antibiotic regimens using the upper limit of the recommended daily dose for 5 to 7 days.某些病人的病史提示有些特定的因素会加重病情，如季节变化、冬季，应该提前预防性使用抗菌药。如果2-3年内连续2-3月无明显临床效果，抗菌药预防性治疗无效。 In patients whose history suggests recurrent exacerbations of their disease that might be attributable to certain specific events (i.e., seasonal, winter months), a trial of prophylactic antibiotics might be beneficial. If no clinical improvement is noted over an appropriate period (e.g., 2 to 3 months per year for 2 to 3 years), prophylactic therapy could be discontinued.,BRONCHIOLITIS毛细支气管炎,毛细支气管炎是一种急性病毒性下呼吸道感染，50%患儿发作于1岁以内的新生儿、100%发生于3岁以内。 Bronchiolitis is an acute viral infection of the lower respiratory tract of infants that affects approximately 50% of children during the first year of life and 100% by 3 years.合胞病毒是引起毛细支气管炎的主要病毒，大约占到70%。副流感病毒是第二位病原，细菌性感染作为继发因素只占到很少的部分。Respiratory syncytial virus is the most common cause of bronchiolitis,accounting for up to 70% of all cases. Parainfluenza viruses are the second most common cause. Bacteria serve as secondary pathogens in only a small minority of cases.,Clinical Presentation,出现临床症状之前，有2-8天前驱症状。The most common clinical signs of bronchiolitis are found in Table 43-4.A prodrome suggesting an upper respiratory tract infection, usually lasting from 2 to 8 days, precedes the onset of clinical symptoms.由于摄入量的限制，加上咳嗽、发热、呕吐、腹泻，容易导致脱水。As a result of limited oral intake due to coughing combined with fever,vomiting, and diarrhea, infants are frequently dehydrated.毛细支气管炎诊断主要根据临床表现及病史。在喘息的患儿呼吸道分泌物中的分离病毒病原体确定毛细支气管炎的诊断。The diagnosis of bronchiolitis is based primarily on history and clinical findings. The isolation of a viral pathogen in the respiratory secretions of a wheezing child establishes a presumptive diagnosis of infectious bronchiolitis.,Treatment,属于自限性疾病，除了安抚及解热外，毛细支气管炎一般不需要处理，除非出现了缺氧及脱水。发热的患儿可以给于口服补液、密切观察。Bronchiolitis is a self-limiting illness and usually requires no therapy (other than reassurance and antipyretics) unless the infant is hypoxic or dehydrated. Otherwise healthy infants can be treated for fever, provided generous amounts of oral fluids, and observed closely.严重患者需要吸氧及IV补充液体。 In severely affected children, the mainstays of therapy for bronchiolitis are oxygen therapy and IV fluids.,除了判断患儿发生了支气管痉挛，雾化吸入beta-拟肾上腺素药物是无益的。Aerosolized -adrenergic therapy appears to offer little benefit for the majority of patients but may be useful in the child with a predisposition toward bronchospasm.由于细菌不是主要的病原菌，不需要常规给与抗菌药。但是医生往往在等待培养结果时初始阶段给药空军药物治疗。因为有建议认为毛细管支气管炎往往有可能引起细菌性肺炎。Because bacteria do not represent primary pathogens in the etiology of bronchiolitis, antibiotics should not be routinely administered. However, many clinicians frequently administer antibiotics initially while awaiting culture results because the clinical and radiographic findings in bronchiolitis are often suggestive of a possible bacterial pneumonia.大部分合胞病毒引起的可以考虑利巴韦林治疗（无其他肺病、心血管病或这样严重感染）。需要雾化吸入的设施及专门培训的人员。Ribavirin may be considered for bronchiolitis caused by respiratory syncytial virus in a subset of patients (those with underlying pulmonary or cardiac disease or with severe acute infection). Use of the drug requires special equipment (small-particle aerosol generator) and specifically trained personnel for administration via oxygen hood or mist tent.,PNEUMONIA,PATHOPHYSIOLOGY,病原微生物到达下呼吸道有以下3条路径：和空气颗粒物一起吸入；通过肺部以外感染进入血液；鼻咽部病原菌吸入。Microorganisms gain access to the lower respiratory tract by three routes: they may be inhaled as aerosolized particles; they may enter the lung via the bloodstream from an extrapulmonary site of infection; or aspiration of oropharyngeal contents may occur.病毒感染能够抑制肺部自洁功能，损害肺泡巨噬细胞功能及粘膜纤毛细胞的摆动。导致继发性细菌感染。Lung infections with viruses suppress the bacterial clearing activity of the lung by impairing alveolar macrophage function and mucociliary clearance, thus setting the stage for secondary bacterial pneumonia.大部分健康成人的肺炎由肺炎球菌引起的社区获得性肺炎（75%以上急性肺炎患者），其他病原有肺炎支原体、军团菌、肺炎衣原体等“非典型”致病因子由金黄色葡萄球菌、G-细菌引起的获得性肺炎主要见于老人、特别是养老院的老人，酗酒者及其他有伤害行为的人。The vast majority of pneumonia cases acquired in the community by otherwise healthy adults are due to S. pneumoniae (pneumococcus) (up to 75% of all acute bacterial pneumonias). Other common bacterial causes include M. pneumoniae, Legionella, and C. pneumoniae, which are referred to as “atypical” pathogens. Community-acquired pneumonias caused by Staphylococcus aureus and gram-negative rods are observed primarily in the elderly, especially those residing in nursing homes,and in association with alcoholism and other debilitating conditions.,革兰阴性需氧杆菌和金黄色葡萄球菌是医院获得性肺炎的主要病原体Gram-negative aerobic bacilli and S. aureus are also the leading causativeagents in hospital-acquired pneumonia.口腔及鼻咽部病菌的吸入是引起厌氧菌肺炎的主要病菌Anaerobic bacteria are the most common etiologic agents in pneumonia that follows the gross aspiration of gastric or oropharyngeal contents.儿童阶段的非要主要有病毒引起，特别是合胞病毒、副流感病毒及腺病毒。A组链球菌、金黄色葡萄球菌及肺炎球菌是常见的病原菌。In the pediatric age group, most pneumonias are due to viruses, especially respiratory syncytial virus, parainfluenza, and adenovirus. Pneumococcus is the most common bacterial cause, followed by Group A Streptococcus and S. aureus.,社区获得性肺炎 Community Acquire Pneumonia CAP,一、社区获得性肺炎(CAP)的定义：,社区获得性肺炎是指在医院外罹患的感染性肺实质（含肺泡壁，即广义上的肺间质）炎症，包括具有明确潜伏期的病原体感染而在入院后平均潜伏期内发病的肺炎。,1.CAP的临床诊断依据：,新近出现的咳嗽，咳痰，或原有呼吸道疾病加重,并出现脓性痰；伴或不伴胸痛发热肺实变体征和(或)湿性罗音WBC1010/L或4109/L，伴或不伴核左移胸部X线检查显示片状，斑片状浸润阴影或间质性改变，伴或不伴胸腔积液,以上1-4项中任何一款加第5项，并除外肺结核，肺部肿瘤，非感染性肺间质性疾病，肺水肿，肺不涨，肺栓塞，肺嗜酸性粒细胞润浸症，肺血管炎等，可建立临床诊断。,2.CAP感染的细菌主要是：,肺炎链球菌、流感嗜血杆菌、副流感嗜血杆菌、卡他莫拉氏球菌、支原体、衣原体和其他病原菌,社区呼吸道感染(CARTI)常见致病菌1,其他,卡他10%,流感25%,肺链40%,社区获得性感染常见病原菌,CAP 4重症患者,3.成人CAP患者分类,CAP 3需住院(不需ICU)治疗,CAP 2老年人有/无基础疾病,CAP 1青壮年无基础疾病,4.经验治疗CAP1的初始经验性抗菌治疗,抗菌药物选择大环内酯类青霉素复方磺胺多西环素一代头孢新喹诺酮类（如左氧氟沙星、司帕沙星、莫西沙星等）,常见病原体肺炎链球菌肺炎支原体肺炎衣原体流感嗜血杆菌等,抗菌药物选择二代头孢-内酰胺类/抑制剂或联合大环内酯类新喹诺酮类,常见病原体肺炎链球菌流感嗜血杆菌需氧革兰阴性杆菌金黄色葡萄球菌卡他莫拉菌等,CAP2的初始经验性抗菌治疗,抗菌药物选择 二代头孢单用，或联合 大环内酯类 头孢噻肟或头孢曲松单 用，或联合大环内酯类 新喹诺酮类或新大环内 酯类 青霉素或一代头孢联合 喹诺酮类或氨基糖甙类,常见病原体肺炎链球菌流感嗜血杆菌复合菌(包括厌氧菌)需氧革兰阴性杆菌金黄色葡萄球菌肺炎衣原体呼吸道病毒等,CAP3的初始经验性抗菌治疗