High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy.
High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy.
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DOI：
10.1161/circulationaha.111.079780
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发表时间：
2012-05-08
期刊：
影响因子：
37.8
通讯作者：
Lo CW
中科院分区：
文献类型：
--
作者：
Nakhleh N;Francis R;Giese RA;Tian X;Li Y;Zariwala MA;Yagi H;Khalifa O;Kureshi S;Chatterjee B;Sabol SL;Swisher M;Connelly PS;Daniels MP;Srinivasan A;Kuehl K;Kravitz N;Burns K;Sami I;Omran H;Barmada M;Olivier K;Chawla KK;Leigh M;Jonas R;Knowles M;Leatherbury L;Lo CW
先天性心脏病(CHD)和异位畸形患者的术后发病率/死亡率较高，部分患者还会出现呼吸道并发症。虽然这一发现通常被归因于CHD，但呼吸道清除和左右模式都需要运动纤毛功能。因此，类似于原发性纤毛运动障碍(PCD)的呼吸道纤毛功能障碍(CD)可能会增加异位患者的呼吸道并发症。我们评估了43例有呼吸道CD异位的CHD患者。使用电视显微镜检查鼻腔组织中的纤毛运动，并测量鼻腔一氧化氮(NNO)；PCD患者的NNO水平通常较低。18例CD以纤毛运动异常和NNO水平低于或接近PCD临界值为特征。6岁的CD患者表现出与PCD相似的呼吸道症状增加。对13例CD异位症患者、12例非CD患者、10例PCD疾病对照组和13例健康对照的所有已知的14个PCD基因进行测序后，每个患者分别产生了0.769、0.417、1.0和0.077个新的变异。1例CD异位症患者的PCD导致DNAI1创始人突变。另一例睫状心动过速患者的DNAH11基因有2个突变，DNAH11是唯一已知的导致睫状心动过速的PCD基因。在PCD患者中，有2例已知PCD导致CCDC39和CCDC40突变。我们的研究表明，有异位倾向的冠心病患者有相当大的风险患CD和增加呼吸道疾病。CD异位症患者PCD基因突变较丰富。未来的研究需要评估CD患者的预先筛查和预防性治疗的潜在益处。
Patients with congenital heart disease (CHD) and heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. Although this finding is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Thus, airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may contribute to increased respiratory complications in heterotaxy patients. We assessed 43 CHD patients with heterotaxy for airway CD. Videomicrocopy was used to examine ciliary motion in nasal tissue, and nasal nitric oxide (nNO) was measured; nNO level is typically low with PCD. Eighteen patients exhibited CD characterized by abnormal ciliary motion and nNO levels below or near the PCD cutoff values. Patients with CD aged >6 years show increased respiratory symptoms similar to those seen in PCD. Sequencing of all 14 known PCD genes in 13 heterotaxy patients with CD, 12 without CD, 10 PCD disease controls, and 13 healthy controls yielded 0.769, 0.417, 1.0, and 0.077 novel variants per patient, respectively. One heterotaxy patient with CD had the PCD causing DNAI1 founder mutation. Another with hyperkinetic ciliary beat had 2 mutations in DNAH11, the only PCD gene known to cause hyperkinetic beat. Among PCD patients, 2 had known PCD causing CCDC39 and CCDC40 mutations. Our studies show that CHD patients with heterotaxy have substantial risk for CD and increased respiratory disease. Heterotaxy patients with CD were enriched for mutations in PCD genes. Future studies are needed to assess the potential benefit of prescreening and prophylactically treating heterotaxy patients for CD.