先天性中枢性低通气综合征5例临床研究

目的 研究先天性中枢性低通气综合征(CCHS)的临床特征,提高对CCHS的认识,以便早期诊断和治疗.方法 分析2002年8月至2006年6月收治的反复撤离呼吸机失败的5例患儿临床资料,经过仔细观察及相关检查,除外可导致低通气的心、肺、神经肌肉功能障碍原发病,结合相关文献,对照cCHS诊断标准.结果 5例患儿均有CCHS的典型临床特征:清醒时有足够的通气,睡眠时呼吸频率减慢,通气不足伴高碳酸血症,常需机械通气,对低通气所致的高碳酸血症与低氧血症无呼吸增快及觉醒反应.第1例在早期未能引起足够的重视,明确诊断较晚,提示CCHS的临床特征不易认识可致漏诊.结论 对于持续存在的睡眠状态通气不足及高碳酸血症,无心、肺、神经肌肉功能障碍的原发病可解释时,应考虑CCHS,采取措施尽早明确诊断,进行有效的干预.     

疑难病研究——我国首例先天性中枢性低通气综合征的诊治

报道我国首例先天性中枢性低通气综合症 (CCHS)患儿临床诊治情况。患儿胎龄 36周 ,生后第 1天即发病 ,整个临床过程表现为低通气并致高碳酸血症及低氧血症 ,经机械通气后血气迅速恢复正常 ,撤机或降低呼吸机参数后又出现异常血气 ,导致撤机困难。住院第 6天后发现患儿于醒觉期自主呼吸活动增强 ,睡眠期呼吸活动减弱且无呼吸增快 ,并伴体温波动 ,心律失常及胸骨上窝轻度吸气性凹陷 ,参照国外相关文献 ,最后确诊为CCHS ,并以机械通气治疗至住院第 1 4天家属放弃。     

先天性中枢性低通气综合征1例并文献复习

目的 提高对先天性中枢性低通气综合征(CCHS)的临床和基因特征的认识。方法 总结分析1例CCHS患儿的临床表现、诊断和基因检测结果,并进行文献复习。结果 男,7月龄。以肺部感染、撤机困难入院。入院肺部感染基本控制撤机后,患儿睡眠状态下出现呼吸浅慢,再次予机械通气,模式为双水平正压通气。患儿觉醒时呼吸活跃,入睡后依赖呼吸机,自主呼吸减慢,潮气量减小,出现CO2储留。同时相关辅助检查排除了原发心、肺、脑、神经肌肉及代谢性疾病,临床诊断为CCHS。取患儿及其父母静脉血行PHOX2B基因序列检测,显示患儿PHOX2B第3外显子存在突变（基因型为20/25）,其父母未检出突变,确诊为CCHS。患儿随访至11月龄,呼吸和循环情况尚平稳。结论 CCHS以觉醒时有充足通气,睡眠状态下通气不足为主要表现,行PHOX2B基因突变分析可确诊CCHS。     

先天性中枢性低通气综合征6例病例系列报告

正1病例资料回顾性收集2017年3月至2021年2月在浙江大学医学院附属儿童医院(我院)住院确诊的6例先天性中枢性低通气综合征(CCHS)病例。CCHS诊断符合以下标准[1,2]:(1)存在肺泡低通气(低氧血症及高碳酸血症),并排除心肺及神经肌肉原发疾病;(2)基因检测证实存在PHOX2B基因突变。     

以肺动脉高压为首发表现的先天性中枢性低通气综合征临床特征和基因分析

目的探讨先天性中枢性低通气综合征(CCHS)的临床和基因变异特征。方法分析1例首发表现为不明原因肺动脉高压的CCHS患儿的临床资料,并总结国内外文献中CCHS病例的临床特点、致病机制和基因变异情况。结果11月龄女婴,主要表现为浮肿、尿少、低血压、嗜睡、发绀、抽搐及颅内压增高。B型脑利钠肽、丙氨酸氨基转移酶升高,凝血酶原时间延长。颅脑磁共振示右侧额叶出血;超声心动图示中重度肺动脉高压。靶向捕获二代测序未发现可能的致病基因。采用Sanger法验证示患儿PHOX 2 B基因第3外显子存在多聚丙氨酸重复扩展变异,基因型为20/25。患儿入院后采用无创通气,睡眠时呼吸浅慢、微弱,伴血氧下降;血气分析提示二氧化碳潴留。随后改用夜间无创通气、降肺压药物治疗。复查肺动脉压力明显下降,生命体征稳定。随访至24月龄,夜间只需较低压力水平的无创通气,生长发育无异常。结论对于不明原因的肺动脉高压伴撤机困难患儿,需警惕CCHS。疑诊者应尽早针对CCHS相关基因进行靶向捕获二代测序及PHOX 2 B基因Sanger法验证。早期给予无创通气有望改善预后。     

先天性中枢性低通气综合征的研究进展

先天性中枢性低通气综合征（congenital central hypoventilation syndrome,CCHS）,也称Ondine＇s curse,是一类自出生即存在的呼吸自主控制障碍。由于机体对高碳酸血症和低氧血症的敏感性降低或缺失,从而导致通气反馈控制障碍,临床表现为新生儿期发生的觉醒状态下通气充足,而睡眠时出现严重的、甚至致命性的肺泡低通气,需要机械通气支持;严重病例睡眠和觉醒状态都需要通气支持。[第一段]     

先天性中枢性低通气综合征研究现状

先天性中枢性低通气综合征（congenital central hypoventilation syndrome，CCHS）又称Ondine＇s curse（翁氏困扰）是指呼吸中枢化学感受器的原发性缺陷，对二氧化碳敏感性降低，自主呼吸控制衰竭，造成肺通气减少，导致高碳酸血症、低氧血症及一系列临床症状的综合征。CCHS患儿可伴发先天性巨结肠症（hirschspmng disease）、原发性神经嵴肿瘤（神经母细胞瘤、神经节瘤及成神经节细胞瘤），     

机械通气不当致低碳酸血症68例

目的 探讨过快纠正高碳酸血症致低碳酸血症的危害。方法 对我院应用呼吸机治疗287例患儿的临床资料进行回顾性分析。结果 287例中由于在出现高碳酸血症后过度通气导致低碳酸血症者68例，其中男57例，女ll例。从高碳酸血症至低碳酸血症的时间为2～72h，平均23．93h。进行影像学随访22例，颅内出血加重15例，与出现高碳酸血症而未出现低碳酸血症患儿比较，两组有统计学差异(χ^2＝10．74P＜0．01)，血钙检查结果两组无统计学差异(χ^2＝1．77P＞0．05)。结论 在应用机械通气过程中应避免低碳酸血症的发生，在儿科应用可容许性高碳酸血症策略是可行的，出现低碳酸血症对机体确有一定危害。     

早产极低出生体质量儿撤机后两种鼻塞式辅助通气方式的临床疗效比较

目的 比较在呼吸机撤机后的早产儿中应用鼻塞式同步间歇指令通气(nSIMV)和鼻塞式持续气道正压通气(nCPAP)的临床疗效.方法 52例需要使用气管插管、SIMV通气的早产儿,出生体质量<1 500 g,孕周<34周,当呼吸机参数降至FiO2<0.4,频率<20次/min,给予氨茶碱负荷量后拔除气管插管.患儿随机分为nSIMV组和nCPAP组.观察记录患儿撤机后72 h的临床情况.结果 两组患儿出生孕周、出生体质量、气管插管上机时间比较差异均无显著性(P>0.05).nSIMV组与nCPAP组比较,撤机失败率低、严重呼吸暂停较少、高碳酸血症和低氧血症发生率低,组间比较差异均有显著性(P<0.05).喂养不耐受、坏死性小肠结肠炎、呼吸机相关性肺炎、败血症、支气管肺发育不良和住院时间的组间比较差异无显著性(P>0.05).结论 nSIMV能更有效地对早产极低出生体质量儿撤机后进行呼吸支持.这一无创辅助通气方式将有更广阔的应用前景.     

儿童睡眠呼吸暂停低通气综合征及无创正压通气治疗的研究进展

儿童睡眠呼吸暂停低通气综合征在流行病学、病因学、诊断、临床表现、病理生理及治疗方面与成人有很大差异，大多数患儿手术切除扁桃体及／或腺样体效果良好，但仍有部分患儿需家庭无创机械通气治疗。本文就儿童睡眠呼吸暂停低通气综合征及应用无创通气治疗的研究进展进行综述。     

Congenital central hypoventilation syndrome: not just another rare disorder

Congenital central hypoventilation syndrome (CCHS) is a rare syndrome, present from birth, and is defined as the failure of automatic control of breathing. Patients have absent or negligible ventilatory sensitivity to hypercapnia and hypoxaemia during sleep and wakefulness. Therefore, especially while asleep, children with CCHS experience progressive hypercapnia and hypoxaemia. They lack arousal responses and sensations of dyspnoea to the endogenous challenges of isolated hypercapnia and hypoxaemia and to the combined stimulus of hypercapnia and hypoxaemia. Patients with CCHS do not exhibit signs of respiratory distress when challenged with hypercarbia or hypoxia. The diagnosis is one of exclusion, ruling out any primary pulmonary, cardiac, metabolic or neurologic cause for central hypoventilation. CCHS is associated with other manifestations of autonomic nervous system dysfunction, including Hirschsprung's disease. All patients with CCHS require lifelong ventilatory support during sleep but some will be able to maintain adequate ventilation without assistance while awake once past infancy. However, some CCHS patients require ventilatory support for 24h/day. Modalities of home mechanical-assisted ventilation include positive pressure ventilation via tracheostomy, non-invasive positive pressure ventilation (bi-level ventilation), negative pressure ventilation and diaphragmatic pacers. Supplemental oxygen alone is inadequate treatment. With early diagnosis and adequate ventilatory support, these children can have good outcomes and lead productive lives.     

Congenital central hypoventilation syndrome in children

Congenital central hypoventilation syndrome (CCHS) is a rare, lifelong condition wherein control of breathing is abnormal and patients present with symptoms of alveolar hypoventilation. The severity of hypoventilation varies and although most patients present in the neonatal period, late onset cases have been reported. In 2003, it was discovered that mutations in the PHOX2B gene were responsible for CCHS. This gene also plays a role in neural crest cell migration, and many patients present with symptoms of autonomic dysfunction in addition to hypoventilation. The pathophysiology responsible for hypoventilation remains unclear although a unifying hypothesis is that the abnormality is located in areas of the brain involved in integration of chemoreceptor afferent pathways for ventilation. The goal of treatment for CCHS is to ensure adequate ventilation during wakefulness and sleep. A variety of ventilation modalities are available including positive pressure ventilation via tracheostomy, non-invasive ventilation via nasal mask, and diaphragmatic pacing. With close monitoring and support, children with CCHS can be expected to function well in society and have a good quality of life.     

Congenital central hypoventilation syndrome in a full-term baby presenting with repeated extubation failure

Congenital central hypoventilation syndrome (CCHS) is a rare condition. The main characteristic is respiratory insufficiency during sleep. Patients who have CCHS need varying degrees of ventilation support during sleep, or even all day long, according to its severity. We report a term baby with repeated extubation failure, CCHS and Hirschsprung's disease diagnosed at 1 month of age. This patient was discharged at 5 months old with a home ventilator and reached normal developmental milestones.     

Hypercapneic arousal responses in children with congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is generally thought to be due to insensitivity of the central chemoreceptors to carbon dioxide. Children with CCHS have absent ventilatory responses to both hypercapnea and hypoxia, suggesting either abnormal central and peripheral chemoreceptor function or abnormal central integration of chemoreceptor input. Because ventilatory and arousal responses to respiratory stimuli are distinct from each other, if children with CCHS have complete chemoreceptor dysfunction, one would predict that both ventilatory and arousal responses to respiratory stimuli would be abnormal. However, if they have abnormal central integration of chemoreceptor input for ventilation, they may still arouse to respiratory stimuli despite the absence of a ventilatory response. Hypercapneic arousal responses were tested in eight children with CCHS, aged 5.8 +/- 1.2 (SEM) years, and seven healthy control subjects, aged 4.4 +/- 1.1 years. Children were studied during sleep while normal ventilation was maintained using their home ventilators. Hypercapneic challenges were performed by rapidly increasing the inspired carbon dioxide tension to 60 mm Hg and maintaining this level until the child aroused or for a maximum of 3 minutes. Of children with CCHS, 87.5% aroused to hypercapnea, compared with 100% of control children. There was no significant difference in arousal between children with CCHS and normal control subjects. It is concluded that most children with CCHS arouse to hypercapnea, indicating the presence of some central chemoreceptor function. It is speculated that because these children do respond to hypercapnea, the most probable mechanism for CCHS is a brainstem lesion in the area where input from both chemoreceptors is integrated.     

Congenital central hypoventilation syndrome and the PHOX2B gene mutation

Congenital central hypoventilation syndrome (CCHS) is a rare syndrome of dysfunction of the autonomic nervous system characterized by a decreased response to hypercarbia. It is a disorder in which affected individuals fail to breathe during sleep despite progressive hypercapnia and hypoxia. Infants simply fall asleep and quit breathing. They are found by their parents or caregivers blue and lifeless. CCHS is an autosomal dominant disease. It has been linked with tumors of neural crest origin, segmental aganglionosis of the colon, and diffuse autonomic dysregulation but can occur alone. Discovery of the genetic link between the paired-like homeobox 2B (PHOX2B) genetic mutations and CCHS represents a breakthrough in the diagnosis of CCHS, association of mutated alleles with disease severity, and clues to the pathophysiology responsible for the disorder. Early genetic screening and intervention can provide the families of these infants with hope for achieving a normal life.     

Epidemiologic survey of patients with congenital central hypoventilation syndrome in Japan

Background: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by hypoventilation during sleep. This study discusses the first epidemiologic survey of patients with CCHS in Japan. Methods: The first survey was conducted between September and December 2006 and involved 507 registered institutes for pediatric training in Japan. The second survey was conducted between January and April 2007 and involved only those institutes that confirmed diagnosis of CCHS in the first survey or reported on CCHS at a conference during the preceding decade. Results: Thirty‐seven patients with CCHS were reported from 23 hospitals. Patient characteristics were as follows: 18 were male, 19 were female; and age range 4 months to 34 years. Diagnosis was based on clinical symptoms in 37/37 patients; blood gas analysis in 25/37; ventilatory response to inhaled CO₂ in 14/37; and genetic analysis (paired‐like homeobox gene 2B) in 11/37. Complications included Hirschsprung's disease in 13/37 and central nervous system disorders in 15/37. Prognoses were as follows: 3/37 died in hospital, 1/37 remained in hospital, 33/37 were on home mechanical ventilation (died 4/33, survived 29/33), and 0/37 were cured. Ventilation methods included tracheostomy (21/37), use of a nasal mask (9/37), use of a facemask (5/37), and diaphragmatic pacing (1/37). Conclusions: There is currently no consensus on the most appropriate methods for diagnosing and treating patients with CCHS in Japan. More CCHS‐related data need to be collected in the near future in order to enable appropriate diagnosis and management of patients with CCHS.     

Temporal trends of cardiac and respiratory responses to ventilatory challenges in congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome (CCHS) patients exhibit respiratory deficits to ventilatory challenges, diminished breathing drive during sleep, and reduction of respiratory-related heart rate variation, but at least partially preserved peripheral chemoreception. We hypothesized that integration of afferent activity with respiratory motor output is deficient in CCHS, rather than chemoreceptor failure, and that examination of trends in heart and breathing rates and variabilities following ventilatory challenges may clarify the deficient mechanisms. Twelve children with CCHS and 12 age- and gender-matched control cases were subjected to hyperoxic hypercapnic, poikylocapnic hypoxic, and hyperoxic challenges while supine. Heart and respiratory rates and variabilities during 60-s baseline and 120-s challenge periods were assessed. Hypoxia and hypercapnia enhanced breathing rate in control subjects; in CCHS cases, the rise differed during hypercapnia and did not occur to hypoxia. Hyperoxia showed initial transient patterns in breathing rate that differed between groups. A heart rate increase to hypoxia and late decline to hyperoxia were muted in CCHS patients. In hypercapnia, heart rate followed similar rising patterns in both groups. Overall CCHS heart rate variability was lower in baseline and challenge periods, principally due to diminished respiratory-related variation, especially during hypercapnia. No heart rate variability group differences emerged in hypoxia, and only a late increase for CCHS cases developed in hyperoxia. The findings indicate retention of aspects of chemoreceptor sensitivity in CCHS cases. The heart rate alterations to ventilatory challenges suggest specific compensatory responses of a slower nature remain intact in CCHS, whereas other rapidly changing components are deficient.