Abstract
摘要:背景:染色體22q11 缺失症候群包括了各式各樣的疾病,包括了DiGeorge 症候群、心臟錐幹及面部異常症候群、Velocardiofacial 症候群等等。在西元1989 年,這些常見的身體缺損伴隨基因的缺失被專家統稱為CATCH 22 症候群,其中包括了心臟異常、臉部異常、胸腺發育不全造成的T 免疫細胞缺損、顎裂及低血鈣症。先天性心臟疾病一直是臨床上最主要的問題。先天性心臟疾病的問題種類繁多,包括了心室中隔缺損、右側動脈弓、法洛氏四重症、主動脈阻斷和肺動脈發育不良。同時,也有一些研究發現此症候群也會有支氣管軟化及口咽喉部的異常。然而卻很少完整的研究報告去探討下呼吸系統包括氣管、支氣管是否有狹窄軟化或氧化侵襲,以及氣管發育長度對於先天性心臟病的孩童手術預後影響及變化。我們在以往的臨床觀察可以發現到,下呼吸道的異常在合併CATCH 22 症候群和先天性心臟病的兒童身上較容易被發現。這些呼吸道異常可能導致病人接受開刀術式,困難移除氣管內管,甚至需要長期呼吸器治療及氣切治療,也導致術後照護的困難度。這些相關的呼吸道問題也許能解釋為什麼法洛式四重症的病童合併有CATCH 22 症候群比一般沒有CATCH 22 症候群的病童預後較差。目標:(1)找出CATCH 22 症候群的病童中,下呼吸道異常的發生率;(2)在不同種類的先天性心臟病的孩童之中,同時是CATCH 22 症候群,其下呼吸道異常的發生率;(3)這些表現在臨床上的意義;(4)最後施行氣管及支氣管動態研究做為進一步前瞻性研究。方法:第一部分:回溯性研究:於1990-2009 間,從本院先天性心臟病資料庫找出先天性心臟病童伴隨外觀診斷為CATCH 22 症候群的案例。收案標準如下:(1) 診斷年紀小於18 歲(2) 外觀診斷是CATCH 22 症候群,包括心臟、臉部、內分泌、免疫方面異常或者是基因檢查確定是CATCH 22 症候群的病童。(3) 病童在開刀前接受過電腦斷層或支氣管鏡檢查確定存在或不存在呼吸道異常。呼吸道的動態大小、軟化程度和支氣管構造將被評估。第二部分:前瞻性研究:確定的病童將會被邀請進入前瞻性研究。(1)基因檢查是藉由multiplex ligation-dependent probe amplification (MLPA)方法來確定診斷。(2)呼吸道氧化侵襲傷害將藉由支氣管肺泡灌洗術取得檢體,監測其中8-isoprostane 的濃度來代表氧化壓力的情形。每年的概述:第一年:病人資料庫的建立和呼吸道系統性的回顧。第二年:病童預後分析和基因體學的確認。第三年:呼吸道病生理的研究統計:透過T 檢定、變異數分析及複迴歸統計方法來評估分析。預期成果:(1)我們將得到關於CATCH 22 症候群病童合併下呼吸道異常的發生率和型式的資料。(2)我們將知道在CATCH 22 症候群病童伴隨不同種類先天性心臟病時,合併下呼吸道異常的關係。(3)我們將獲得在CATCH 22 症候群病童裡,會干擾下呼吸道功能的過程的一些病生理資料。(4)這些資料將對我們將來診治這些病童時,能達到更好的治療品質是非常重要的資訊。可能困難及解決:(1)死亡的病童將沒有辦法由基因檢查確定診斷。因此,嚴格的外觀診斷對於案例收集是必須的。(2)電腦斷層的影像解讀可能會因為影像不清楚而變得困難。病童的呼吸道診斷經由二位專家仍無法判斷時將被排除在研究外。
Abstract: Background: The 22q11.2 deletion syndrome comprises various syndromes that include DiGeorge syndrome,conotruncal anomaly face syndrome, Velocardiofacial syndrome and etc. The common defects associatedwith this deletion are acronymed as CATCH 22 syndrome in 1989: i.e., Cardiac abnormality, Abnormal faces,T cell deficit to thymic hypoplasia, Cleft palate and Hypocalcemia. Congenital heart disease is most of thetime the major clinical problem. The spectrum is wide and may include ventricular septal defect, right-sidedaortic arch, tetralogy of fallot, interruption of aorta and pulmonary hypoplasia. Some previous studies hadalso revealed the coexistence of bronchomalacia and upper airway anomalies in some patients. However, therole of lower airway anomalies had been described. Our previous clinical observation and studies had shownthat lower airway anomalies are relatively common in children with CATCH 22 syndrome and CHD. Theseairways problems may result in the difficulties to extubation in these patients after cardiac surgery. Somechildren even need invasive tracheostomy and home ventilator support. The prognosis of TOF patients withCATCH 22 is worse than that in patients without CATCH 22, which can be attributed in part to the associatedairway problems.Specific Aims: We aim to 1) the incidence of lower airway anomalies in CATCH 22, 2) the incidence oflower airway problems in CATCH 22 patients in each specific CHD diagnosis, 3) the clinical implicationsand 4) finally the bronchial dynamic study as a prospective study extension.Methods: Part I: Retrospective study: Patients with CHD with phenotype diagnosis of CATCH 22 will beidentified from the CHD database of this institution from 1990 to 2009. The inclusion criteria are asfollowing:(1) Age at diagnosis < 18 years old(2) The phenotype of CATCH 22 syndrome, including the cardiac, facial, endocrine, immuneanomalies and the child diagnosed CATCH 22 syndrome by genetic analysis.(3) Patients who had received CT or bronchoscope evaluation before the cardiac operation to ascertainthe presence or absence of airway anomalies. The dynamic size of airway, the extent of malacia andthe anatomy of bronchi will be assessed.Part II. Prospective study: Patients identified will be invited to participate in this prospective study.(1) The genetic analysis by the method of multiplex ligation-dependent probe amplification (MLPA)will be performed to ascertain the diagnosis.(2) Airway oxidative damage will be evaluated by checking the level of 8-isoprostane, a biomarker ofoxidative stress from BAL specimen.Outline of each year:Year 1: Patient database establishment and review of the airway images systemically.Year 2: Outcome analysis and genomic confirmationYear 3:Pathophysiological study of the airwayStatistics: All values will be expressed as mean ± SD, and p < 0.05 will be considered to be statisticalsignificant. The values will be analyzed by student t-test and ANOVA for repeated measures whenappropriate.Predicted outcomes:1. We will have the incidence data and the pattern of lower airway anomalies in CATCH 22 patients.2. We will know the relationship between the lower airway anomalies and each specific CHD inpatients with CATCH 22.3. We will have some information of the pathophysiological process of the disturbed lower airwayfunction in CATCH 22 patients.4. These data will be very important information for us to make management strategy for best qualitycare of these patients.Potential difficulties and solution: 1)Mortality patients will not be able to be confirmed by genetic study.Therefore, strict phenotype diagnosis will be required for case enrollment. 2)CT images interpretation may bedifficult if the images are unclear due to inadequate study quality. Those who the airway diagnosis cannot beascertained by two of our specialties will be excluded from the study.
Keyword(s)
CATCH 22症候群
染色體22q11缺失
先天性心臟疾病
CATCH 22 syndrome
Chromosome 22q11 deletion syndrome
congenital heart disease