Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies.
Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies.
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DOI：
10.3389/fped.2017.00135
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发表时间：
2017
影响因子：
2.6
通讯作者：
Santamaria F
中科院分区：
文献类型：
--
作者：
Mirra V;Werner C;Santamaria F
原发性纤毛运动障碍（PCD）是一种孤儿病（MIM 244400），常染色体隐性遗传，以纤毛运动功能障碍为特征。PCD的估计患病率为活产婴儿的1:10 000至1:20 000，但真实患病率可能更高。PCD的特点是慢性上呼吸道和下呼吸道疾病、不孕症/异位妊娠和部位异常，约50%的PCD患者（Kartagener综合征）出现这种情况，这些可能与先天性心脏异常有关。大多数患者报告说，从出生后的第一年开始，他们每天都会出现全年的湿咳或鼻塞。每日湿咳与复发性感染加重相关，可导致慢性化脓性肺病的发展，伴局限性至弥漫性支气管扩张。没有一种诊断测试可以完美地确认PCD。诊断可能具有挑战性，并且依赖于临床数据，鼻一氧化氮水平以及纤毛超微结构和功能分析的结合。辅助试验包括基因分析和纤毛培养标本的重复试验。目前已知的与PCD相关的基因有33个，基因型与超微结构缺陷之间的相关性越来越得到证实。全面的基因检测有望在症状出现之前筛查婴儿，从而提高生存率。最近PCD遗传学的惊人进展设计了一种称为“基因编辑”的新方法来恢复基因功能并使纤毛运动正常化，为PCD的治疗开辟了新的途径。目前，没有随机临床试验的数据来支持任何特定的治疗，因此，管理策略通常是从囊性纤维化推断出来的。治疗的目标是防止病情恶化，减缓肺部疾病的进展。治疗主要包括气道清除操作，主要是雾化高渗盐水和胸部物理治疗，以及及时和积极的抗生素治疗。在专业中心采用多学科方法进行标准化护理，对肺功能和气道生物膜组成进行监测，可能会改善患者的预后。儿科医生、新生儿医生、肺科医生和耳鼻喉外科医生应保持对PCD的高度认识，并在持续的不可逆肺损伤发展之前将患者转诊到专业中心。最近建立的PCD临床中心网络，专注于改善诊断和治疗，有望帮助改善PCD患者的护理和知识。
Primary ciliary dyskinesia (PCD) is an orphan disease (MIM 244400), autosomal recessive inherited, characterized by motile ciliary dysfunction. The estimated prevalence of PCD is 1:10,000 to 1:20,000 live-born children, but true prevalence could be even higher. PCD is characterized by chronic upper and lower respiratory tract disease, infertility/ectopic pregnancy, and situs anomalies, that occur in ≈50% of PCD patients (Kartagener syndrome), and these may be associated with congenital heart abnormalities. Most patients report a daily year-round wet cough or nose congestion starting in the first year of life. Daily wet cough, associated with recurrent infections exacerbations, results in the development of chronic suppurative lung disease, with localized-to-diffuse bronchiectasis. No diagnostic test is perfect for confirming PCD. Diagnosis can be challenging and relies on a combination of clinical data, nasal nitric oxide levels plus cilia ultrastructure and function analysis. Adjunctive tests include genetic analysis and repeated tests in ciliary culture specimens. There are currently 33 known genes associated with PCD and correlations between genotype and ultrastructural defects have been increasingly demonstrated. Comprehensive genetic testing may hopefully screen young infants before symptoms occur, thus improving survival. Recent surprising advances in PCD genetic designed a novel approach called “gene editing” to restore gene function and normalize ciliary motility, opening up new avenues for treating PCD. Currently, there are no data from randomized clinical trials to support any specific treatment, thus, management strategies are usually extrapolated from cystic fibrosis. The goal of treatment is to prevent exacerbations, slowing the progression of lung disease. The therapeutic mainstay includes airway clearance maneuvers mainly with nebulized hypertonic saline and chest physiotherapy, and prompt and aggressive administration of antibiotics. Standardized care at specialized centers using a multidisciplinary approach that imposes surveillance of lung function and of airway biofilm composition likely improves patients’ outcome. Pediatricians, neonatologists, pulmonologists, and ENT surgeons should maintain high awareness of PCD and refer patients to the specialized center before sustained irreversible lung damage develops. The recent creation of a network of PCD clinical centers, focusing on improving diagnosis and treatment, will hopefully help to improve care and knowledge of PCD patients.