肿瘤坏死因子-α与哮喘及其拮抗剂治疗研究进展

支气管哮喘是呼吸道慢性疾病,发病机制复杂,是由多种炎症细胞及细胞因子参与的气道变态反应性疾病.肿瘤坏死因子-α(TNF-α)作为重要的炎性介质,参与哮喘的发病过程.哮喘时呼吸道上皮细胞、血管内皮细胞释放TNF-α,TNF-α可导致气道高反应和局部炎症,且与气道重建密切相关.研究表明抗TNF药物对哮喘患者气道重塑和重症哮喘有一定治疗作用,能下调血液及呼吸道中TNF-α水平,减低气道炎症反应,为治疗哮喘提供新的思路和方法.     

Acquired upper airway obstruction

Acquired upper airway obstruction is a common cause of respiratory emergencies in children. Most pathologic processes that result in upper airway compromise are a consequence of infection, trauma or aspiration. Today, many of the infectious causes of upper airway obstruction have lost their threat as a result of the progress made in preventing and treating these infections. Prompt recognition and appropriate management of the child presenting with upper airway obstruction remains critical, because certain causes can progress rapidly from a mild to a potentially life-threatening disease state. A correct diagnosis can often be made by history and physical examination, but additional studies may be useful in selected cases. The child's clinical appearance is the most reliable indicator of severity, and measurable signs are of less value. If respiratory failure is imminent, airway protection and endoscopy for definitive diagnosis may have priority over any other therapeutic or diagnostic procedure.     

Approach to a Child with Breathing Difficulty

Breathing difficulty and respiratory distress is the most common cause of admission to the Pediatric Emergency. Respiratory distress presents as altered breathing pattern, forced breathing efforts or obstructed breathing, and chest indrawing; respiratory failure is defined as paCO₂ >50 mmHg (inadequate ventilation) and/or a paO₂ < 60mmHg (inadequate oxygenation). Rapid assessment is aimed to ascertain adequacy of airway patency, breathing, and circulation. Immediate care is directed at (a) restoration of airway patency- by positioning (head tilt –chin lift), cleaning the oropharynx, and/or insertion of oropharyngeal airway; (b) supporting breathing- with high flow oxygen and assisted ventilation (with bag and mask or endotracheal intubation and ventilation), and (c) restoration of circulation- using fluid boluses and inotropes, if necessary. Immediate specific management may require endotracheal intubation/tracheostomy for upper airway obstruction; needle thoracotomy and drainage of pneumothorax; and first dose of antibiotic for febrile children. Thereafter meticulous history, focused physical examination, and specific laboratory/radiological investigations are undertaken to identify the underlying cause. At the end of this, one should be able to categorize the child to one of the following: (a) upper airway obstruction, (b) pneumonia (syndrome of cough, fever and breathing difficulty), (c) lower airway obstruction, (d) slow or irregular breathing without pulmonary signs, and (e) respiratory distress with cardiac findings, to initiate specific treatment. Further respiratory support by Continuous Positive Airways Pressure (CPAP) and mechanical ventilation may be required in some cases. All children with respiratory distress must be monitored for early detection of worsening/complications, assessment of response to therapy and rapid documentation of clinical state.     

The Wheezy Child

ABSTRACT. Wheezing in association with viral respiratory tract infections occurs in 10-20 % of all infants and young children and usually indicates hyperreactive bronchi. Signs of airway hyperreactivity can usually be demonstrated many years after the child has stopped wheezing. This hyperreactivity is partly constitutional, but it may be further aggravated by viral infections in the respiratory tract. Similarly, allergic inflammation or long-term exposure to airway irritants may also cause or aggravate a state of hyperreactivity which may be expressed as a proneness to asthmatic reactions. As viral infections are among the most potent asthma-provoking factors known, the hyperreactivity does not need to be very pronounced before wheezing develops in the infant or young child, with its small-calibred airway. As long as wheezing only occurs sporadically and only in association with viral respiratory tract infections, the prognosis is usually excellent. However, recommendations regarding avoidance of potent allergens and airway irritants in the daily environment should be given to such families. Such advice is especially important for families with a proneness to atopic reactions or if wheezing begins to occur even during infection-free periods     

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??Excessive mucus produced by airway glands and goblet cells can cause airway mucus hypersecretion??long term of mucus secretions can blocking the airway and cause severe airflow limitation and ventilation dysfunction. Meanwhile??excessive mucus can reduce mucociliary clearance and local defense function??and foreign bodies and pathogens may remain in the lungs and airway??leading to recurrent respiratory infections. Airway mucus hypersecretion is closely related to bronchial asthma??bronchiectasis??low respiratory tract infection and other diseases. Airway mucus hypersecretion is an important factor influencing the occurrence??development and prognosis of bronchial asthma??bronchiectasis??lower respiratory tract infection and other diseases??so pediatricians should pay high attention to them.     

Dexmedetomidine for transport of a spontaneously breathing combative child

Interhospital transport presents a challenge for pediatricians, and airway protection is often a significant concern. The severely agitated child without respiratory compromise poses an extremely difficult dilemma, as most sedative agents can cause respiratory depression. Intubation offers definitive control of the airway but is not without risk, especially in an environment where experience and resources for pediatric intubation may be limited. Dexmedetomidine may be used for sedation in certain circumstances for the transport of a child without the need for intubation and mechanical ventilation.     

儿童塑型性支气管炎的常见病因及致病机制

塑型性支气管炎(PB)是一种少见的呼吸道疾病,其特征性改变为支气管内管型形成及由此造成的支气管阻塞,导致呼吸困难乃至呼吸衰竭。儿童PB的常见病因为下呼吸道感染、发绀型先天性心脏病、支气管哮喘及呼吸道变应性疾病,也可见于镰刀型细胞贫血病、珠蛋白生成障碍性贫血、囊性纤维化等。PB的形成有3个主要机制:气道炎症造成气道内黏液分泌大量增多;气道炎症导致呼吸道上皮坏死脱落、黏膜水肿,呼吸道清理能力下降;气道内淋巴液渗漏。但本病病因多样、发病机制复杂,仍需更多的研究来阐明其发病机制。     

Airway infectious disease emergencies

Upper and lower respiratory infections are encountered commonly in the emergency department. Visits resulting from occurrences of respiratory disease account for 10% of all pediatric emergency department visits and 20% of all pediatric hospital admissions. Causes of upper airway infections include croup, epiglottitis, retropharyngeal abscess, cellulitis, pharyngitis, and peritonsillar abscesses. Lower airway viral and bacterial infections cause illnesses such as pneumonia and bronchiolitis. Signs and symptoms of upper and lower airway infections overlap, but the differentiation is important for appropriate treatment of these conditions. This article reviews the varied clinical characteristics of upper and lower airway infections.     

软式支气管镜在儿童呼吸系统疾病中的应用

目的探讨软式支气管镜在儿童呼吸系统疾病中的临床应用价值。方法对80例因呼吸系统疾病住院(包括重症肺炎、肺炎支原体肺炎并肺不张/肺实变/局限性肺气肿、迁延性肺炎、咳喘原因待查、慢性咳嗽查因、喉喘鸣)接受软式支气管镜检查/肺泡灌洗治疗患儿的临床资料进行回顾性分析。结果支气管镜检查发现,80例患儿均有支气管内膜炎症,其中分泌物严重雍塞气道28例。在支气管内膜炎症基础上合并先天性气道发育异常24例,另发现支气管异物3例。咳喘原因待查及喉喘鸣的患儿中,部分患儿存在先天性气道发育异常或支气管异物等病变。27例肺炎支原体肺炎患儿中,分泌物严重雍塞/栓塞气道26例;25例患儿(93%)在肺泡灌洗治疗后2周复查胸部影像学,显示肺部完全或大部分复张。行支气管镜检查的80例患儿中,术中出现严重低氧血症3例,鼻出血1例,肺泡灌洗术中少量出血1例,支气管短暂性痉挛3例,术后发热5例,均经对症处理后好转。结论软式支气管镜在儿童呼吸系统疾病的临床应用是安全可靠的。重症/难治性肺炎支原体肺炎患儿建议早期行软式支气管镜下肺泡灌洗治疗,可改善预后。反复咳喘及持续喉喘鸣患儿均建议积极行软式支气管镜检查,内镜直视下了解咽喉部及气道情况,避免误诊和漏诊。     

22Q11 microdeletion syndrome: cardiorespiratory symptoms and fibrobronchoscopy

The 22q11 deletion syndrome is a frequent contiguous-gene deletion syndrome. This disorder has a broad spectrum of phenotypic manifestations. It includes various syndromes such as DiGeorge syndrome. The most frequent clinical manifestations are congenital cardiac defects, characteristic facies, palate malformations, hypoparathyroidism, immunodeficiency due to thymic hypoplasia, growth retardation, and behavioural and psychiatric problems. Among the symptoms observed, many patients suffer from respiratory insufficiency or failure. The origin is often multifactorial. Structural airway abnormalities are frequently found in this syndrome. In many of these patients the malformation is mild or non-existent, and remains asymptomatic. However, in some cases it can cause a severe respiratory insufficiency, being diagnosed when other disorders are ruled out. These cases illustrate the importance of early visualisation of the airway by fibrobronchoscopy in the management of the patient with 22q11 deletion syndrome who has recurrent respiratory difficulties.     

The wheezy child

Wheezing in association with viral respiratory tract infections occurs in 10-20% of all infants and young children and usually indicates hyperreactive bronchi. Signs of airway hyperreactivity can usually be demonstrated many years after the child has stopped wheezing. This hyperreactivity is partly constitutional, but it may be further aggravated by viral infections in the respiratory tract. Similarly, allergic inflammation or long-term exposure to airway irritants may also cause or aggravate a state of hyperreactivity which may be expressed as a proneness to asthmatic reactions. As viral infections are among the most potent asthma-provoking factors known, the hyperreactivity does not need to be very pronounced before wheezing develops in the infant or young child, with its small-calibred airway. As long as wheezing only occurs sporadically and only in association with viral respiratory tract infections, the prognosis is usually excellent. However, recommendations regarding avoidance of potent allergens and airway irritants in the daily environment should be given to such families. Such advice is especially important for families with a proneness to atopic reactions or if wheezing begins to occur even during infection-free periods.     

Respiratory tract malacia: possible cause of sudden death in infancy and early childhood

AIM: To stress the importance of considering Laryngo-tracheo-bronchomalacia (LTBM) as a cause of death in infancy and early childhood. METHODS: A case of Tracheo-bronchomalacia diagnosed at autopsy is presented, with a short review of the literature. RESULTS: The condition causes functional weakness of the airways due to congenital or acquired abnormalities of airway cartilage. The etiology of the congenital variant is uncertain; the acquired may be caused by localized external pressure. Morphologically, cartilage rings are shorter and softer than normal, causing collapse, especially during forced expirations. The defect can be an isolated finding, but there are a number of associations with other malformations. LTBM may be misdiagnosed as asthma. Symptoms include wheezing, barking cough, frequent respiratory infections and cyanotic episodes. Treatment might be conservative or include surgery, depending on etiology and severity. CONCLUSION: Laryngo-tracheo-bronchomalacia (LTBM) is usually not considered a sufficient cause of death in infancy and early childhood, but airway malacia may be an unrecognized cause of sudden death in infancy and early childhood, and should be considered, especially in cases where there is a history of respiratory distress.     

New interpretation and management of dry lung syndrome: A case report

A premature female infant with life-threatening respiratory distress which was diagnosed as ‘dry lung syndrome’ is reported. The mother had 4 weeks of large volume leakage of the amniotic fluid due to premature rupture of the fetal membranes (PROM) at 23 weeks' gestation. The infant was bom after 27 weeks' gestation (birthweight, 1016 g) and was suffering severe respiratory distress. Although a chest radiogram and gastric juice microbubble test did not prove the possibility of respiratory distress syndrome (RDS), very high ventilator settings did not improve her respiratory disorders. Considering the infant's deteriorating respiratory status and the prolonged leakage of the amniotic fluid, we suspected the presence of pulmonary hypoplasia. Although an attempt at high frequency oscillation (HFO) to rescue this infant had no effect, intratracheal instillation of epinephrine (EP) showed dramatic improvement of her respiratory status. This clinical course showed that the patient did not have pulmonary hypoplasia but might have severe airway obstruction and this airway obstruction may be the major cause of ‘dry lung syndrome’. We postulate that when a newborn with suspected pulmonary hypoplasia is unresponsive to respiratory support, HFO should be administered. If HFO is ineffective in relieving the respiratory distress, one should suspect the presence of airway collapse and administer a bronchodilator such as EP. If the infant improves, a diagnosis of ‘dry lung syndrome’ may be assumed.     

Airwaymanagement bei Kindern in Notfallsituationen

In babies and toddlers, most emergencies that necessitate resuscitation attempts are respiratory in origin. This is in contrast to emergencies in adults, in which circulatory failure with low output is often present, as it is for examplein dysrhthmia following cardiac infarct, and the treatment is fundamentally different from that in a paediatric emergency. In paediatric emergencies correction of the respiratory disturbance is often enough to deal with the acute risk situation. In general, particular attention should be paid to making certain the airway stays open. The airway is smaller in children than in adults. In view of the frequent respiratory infections children are exposed to they are often swollen and can therefore themselves be the actual cause of a life-threatening situation not only when foreign bodies have been aspirated, but also in cases of epiglottitis and pseudocroup. Since a cardiovascular arrest often occurs as the result of respiratory hypoxia in children, its prognosis is serious. In adults the organs are initially still adequately oxygenated when a dysrhythmia occurs or in the presence of other cardiovascular diseases. In children the cardiac arrest comes about as the result of preceding hypoxia of all tissues, so that particularly rapid action is essential. It is the object of any airway management to ensure an adequate oxygen supply and prevention of aspiration, but preparations must also be made for intratracheal administration of emergency medications.     

Clinical practice

Stridor is the sound caused by abnormal air passage during breathing. The cause of stridor can be located anywhere in extrathoracic airway (nose, pharynx, larynx, and trachea) or the intrathoracic airway (tracheobronchial tree). Stridor may be acute (caused by inflammation/infection or foreign body inhalation) or chronic. It may be congenital or acquired. Stridor is a sign from which the underlying cause must be sought; it is not a diagnosis. The role of the pediatrician faced with a child or infant with noisy breathing is: (1) to determine the severity or respiratory compromise and the need for immediate intervention (to prevent respiratory failure); (2) to decide based upon history and clinical examination whether a significant lesion is suspected and, in the latter situation, to refer the child to an ENT surgeon for an upper and lower airway endoscopy; (3) to understand the consequences and management strategies of the underlying lesion and to collaborate with colleagues from related disciplines for follow-up and subsequent management of the child.     

An approach to the diagnosis and treatment of membranous laryngotracheobronchitis in infants and children.

The purpose of this study is to report 18 cases of membranous laryngotracheobronchitis (MLTB) and to review 143 published cases in order to accurately characterize the epidemiology, presentation, clinical course, treatment, and outcome of patients with this disorder. The male:female ratio was 2:1; mean age was four years. Most patients presented with acute onset of respiratory distress with fever, toxicity, and stridor after a prodrome of upper respiratory tract infection lasting a few days. White blood cell counts varied over a wide range, and blood culture results were rarely positive. Respiratory cultures commonly yielded Staphylococcus aureus or Haemophilus influenzae. Diagnosis was usually confirmed by airway radiographs or endoscopy. An artificial airway was required in 83% of patients. Complications included respiratory failure, toxic shock syndrome, anoxic encephalopathy, and death. MLTB is a serious, potentially fatal cause of acute infectious airway obstruction in infants and children that requires an organized approach to diagnosis and management.     

Respiratory support for children in the emergency department

Respiratory support in paediatric emergency settings ranges from oxygen delivery with subnasal oxygen to invasive mechanical ventilation. Recent data suggest that oxygen can cause reperfusion injuries and should be delivered with caution within well‐defined clinical target ranges. Most mild to moderate respiratory distress conditions with an oxygen requirement may benefit from early use of continuous positive airway pressure. High‐flow nasal cannula therapy (HFNC) is an emerging alternative way to support the inspiratory effort combined with oxygen delivery and positive expiratory pressures without the need of complicated equipment or good compliance from the child. Besides a positive pressure support effect, HFNC therapy reduces the physiological dead space with improved CO₂ clearance. A decrease in heart and respiratory rate within the first few hours after initiation of HFNC therapy is likely to identify responders of the treatment. The use of non‐invasive ventilation such as continuous positive airway pressure or the use of bi‐level positive airway pressure ventilation in emergency departments has increased, and it has been recognised that continuous positive airway pressure support for older children with asthma is particularly efficient.     

Congenital airway anomalies

Congenital airway anomalies (CAA) include a variety of conditions that cause respiratory distress in neonates and infants. These malformations occur at various anatomic levels and manifest in a wide spectrum of airway symptoms, with presentation significantly influenced by the level at which obstruction occurs as well as by the severity of obstruction. The prevalence of congenital airway malformations has been estimated to range between 0.2 and 1 in 10,000 live births. The most frequent CAA are laryngomalacia, bilateral vocal cord paralysis, subglottic stenosis, laryngeal webs, subglottic hemangioma, tracheomalacia, congenital tracheal stenosis, laryngotracheal cleft, and tracheal agenesis.     

Congenital upper airway obstruction

Most causes of upper airway obstruction are rare in the neonatal period and during infancy. They may, however, cause major respiratory problems either initially or during the first few weeks of life. It is important to recognise these problems at an early stage so that appropriate measures to overcome airway obstruction can be initiated, thus avoiding significant hypoxia-related complications. Specific treatment includes the use of nasal stents, a nasopharyngeal airway or, in severe cases, tracheostomy. Many such infants have associated feeding problems secondary to the airway obstruction and associated swallowing difficulties, which can lead to recurrent aspiration. The anomalies seen in clinical practice are best classified anatomically. Treatment is aimed at overcoming the mechanical effects of airway obstruction and maximising nutritional input so as to promote growth of the airway and long-term recovery of normal upper airway function.     

儿童气道黏液高分泌的管理

气道黏液通常是呼吸道的第一道防线,是先天免疫的重要组成部分。分泌出现异常时可导致气道黏液高分泌,黏液聚集并阻塞气道,可引起通气功能障碍;同时过量黏液可降低黏液纤毛清除功能和局部防御功能,导致出现反复呼吸道感染。气道黏液高分泌与支气管哮喘、囊性纤维化、支气管扩张、下呼吸道感染等多种疾病密切相关,是影响这些疾病发生、发展及预后的重要因素。临床医生应充分认识到加强儿童气道黏液高分泌管理的重要性,在药物治疗基础上选择合适的物理治疗方法。